Response to Comments: Irreversible Electroporation for Cancer

As both an orthopedic surgeon and a prostate cancer survivor, I am writing to express my deep concern regarding the proposed non-coverage determination for irreversible electroporation (IRE) for the treatment of localized prostate cancer.

When I was diagnosed with intermediate-risk prostate cancer, I was confronted with the same decisions that many of my patients face when they are told they have cancer: balancing oncologic control with preservation of quality of life. For me, the side effects of traditional whole-gland therapies—urinary incontinence, erectile dysfunction, and bowel dysfunction—were unacceptable given my life expectancy, activity level, and the organ-confined nature of my disease.

IRE offered a precise, non-thermal, tissue-sparing option that allowed for oncologic control while preserving surrounding structures critical to quality of life. This therapy is guided by advanced imaging and real-time monitoring, allowing physicians to ablate only the cancerous tissue. For patients like myself, this represents not just innovation—it represents dignity and functional preservation.

As a practicing surgeon, I appreciate the rigor that should accompany medical coverage decisions. However, I urge you to consider the growing body of peer-reviewed data demonstrating the safety, effectiveness, and functional outcomes of IRE in appropriately selected patients. Centers across the United States and globally have published prospective and multi-institutional data confirming low morbidity, high preservation of continence and potency, and acceptable oncologic control in intermediate-risk patients.

Moreover, IRE is currently being covered by other MACs and used within clinical guidelines and registries under urologic oncology supervision. To deny coverage under Palmetto would not only create geographic inequities in access but also force men to choose between overtreatment or out-of-pocket expenses for a therapy that represents the future of precision cancer care.

I strongly urge Palmetto GBA to reconsider its proposed non-coverage determination and instead allow coverage for IRE in appropriately selected patients under qualified physicians. Patients deserve access to the full spectrum of safe, effective, and organ-sparing treatments available today.

Thank you for your comments.

Currently, IRE for prostate cancer is not supported by quality literature for the treatment of intermediate grade prostate cancer, National Comprehensive Cancer Network (NCCN) nor societal guidelines recommend its use outside of a clinical trial. IRE is not recommended for low risk or high risk or very high-risk prostate cancer. It is also not U.S. Food and Drug Administration (FDA) approved for prostate cancer as a focal or whole gland therapy.

I am a community urologist with a practice focus on treating prostate cancer patients. I’m writing to voice my strong support for Medicare coverage of Irreversible Electroporation (IRE) for prostate cancer, particularly for intermediate-risk disease and for salvage therapy after radiation. In the last year, I have incorporated IRE into my practice and seen first-hand how it can transform patient outcomes.

“Middle Ground” Option for Intermediate-Risk Patients: Historically, men with intermediate-risk prostate cancer (Gleason 7, PSA 10–20) faced a dilemma. Our only curative treatments were surgery or full-dose radiation – both effective on cancer, but at a high cost to quality of life. Many of my patients are terrified of the potential side effects: wearing diapers due to incontinence or losing sexual function permanently. On the other hand, simply observing the cancer (active surveillance) isn’t advisable for most intermediate-risk cases, as the tumor can progress. IRE has given us a much-needed middle ground. It ablates the cancerous part of the prostate without removing or irradiating the entire gland, meaning we can kill the tumor while sparing normal tissue. In my experience treating intermediate-risk men with focal IRE, the cancer control has been excellent – their PSA levels plummet and follow-up MRIs and biopsies show no residual cancer in >90% of cases, very comparable to my post-prostatectomy patients. Yet nearly all of my IRE patients retain full urinary control and sexual potency. It is difficult to overstate how impactful this is. Men who likely would have been impotent or wearing incontinence pads after traditional treatment are instead living normally, cancer-free. As a physician, it’s incredibly rewarding to not have to tell my patients they must sacrifice quality of life to get a cure.

Clinical Evidence Matches What I See: My personal anecdotal success is backed by solid evidence. A 2025 systematic review covering over 1,400 prostate IRE patients found that 93–98% remained free of significant cancer at short-term follow-up. Five-year data from a multi-center study showed over 95% of intermediate-risk patients treated focally with IRE had no cancer spread and were alive without cancer deaths. Significantly, virtually none experienced the long-term urinary incontinence that we usually see in 15-20% of prostatectomy patients. Those numbers resonate with what I’ve witnessed: I have not had to treat a single IRE patient for incontinence, whereas after radical prostatectomy that’s a routine part of follow-up. This evidence gives me confidence that IRE isn’t just a brief success story – it’s a viable treatment that’s meeting its promise.

Guideline and Regulatory Acceptance: Initially, like any new technology, IRE was approached cautiously. But at this point, it has gained acceptance from key institutions. The AUA guidelines (2022) explicitly include ablation as an option for appropriately selected intermediate-risk patients, and they emphasize informed consent and ideally clinical trial use (I always ensure my patients understand the relative novelty of IRE, yet they are overwhelmingly eager for it when presented with the data). The FDA has cleared IRE for soft tissue ablation, including prostate, affirming that it’s a legitimate medical device for this purpose. And starting next year, we will even have a CPT I code specifically for prostate IRE, meaning the wider medical community recognizes it as standard enough to warrant its own billing code. These developments should reassure Palmetto that covering IRE is in line with the current trajectory of medical practice.

Salvage Therapy – A Lifeline: I also want to highlight the importance of IRE for men whose cancer comes back after radiation. I have been treating patients for the past several years with salvage cryoablation. Recently I have incorporated IRE in the salvage setting and have observed improved side effect profile with similar oncologic outcome. Many urologists, including myself, find salvage IRE to be far gentler than salvage cryotherapy as there is no thermal effect on the tissue, thus less scarring and less risk to continence. I know Palmetto already covers cryo for salvage; offering coverage for IRE is a logical next step, given its safety profile and early success rates (~70-80% local cancer control in studies like the “FIRE” trial).

Patient Perspectives: Nearly every week in my clinic, I hear gratitude from a patient or spouse about IRE. Couples are relieved that treating the cancer didn’t mean ending their intimacy. Patients are amazed that they could go home the same day, with only minor discomfort, and be cancer-free. One of my patients even returned to golfing within a week after IRE – something unheard of after prostate surgery. These may sound like small lifestyle details, but for someone in their 60s or 70s, maintaining independence and function is priceless. Medicare’s mission is to provide health care that keeps seniors healthy and active; IRE aligns perfectly with that mission by treating cancer without inducing disability.

In conclusion, I urge you to finalize LCD DL40205 to cover IRE for intermediate-risk prostate cancer and for salvage therapy (with appropriate selection criteria). In my practice, IRE has become an indispensable tool that I would not want to lose – and more importantly, my patients deserve access to this breakthrough. The technology has moved beyond the investigational phase: it is FDA-cleared, supported (cautiously) by guidelines, and validated by growing research and real-world outcomes. It addresses a well-recognized treatment gap in prostate cancer care. By covering IRE, Palmetto can ensure that men in our region have the choice of a treatment that maximizes both cancer control and post-treatment quality of life.

Thank you for considering my perspective.

Thank you for your comments.

According to Centers for Medicare and Medicaid Service (CMS) Internet-Only Manual, Pub. 100-08 Medicare Program Integrity Manual (MPIM), Chapter 13, §13.5.3, the following applies as evidentiary review for coverage determination: Medicare Administrative Contractors (MACs) shall use the available evidence of general acceptance by the medical community, such as published original research in peer-reviewed medical journals, systematic reviews and meta-analyses, evidence-based consensus statements and clinical guidelines. Proprietary information, submitted by a requestor, not available to the public shall not be considered.

While we appreciate your individual experience, coverage is based upon MPIM guidelines in developing an LCD. Also, NCCN does not recommend focal therapy (FT) with IRE after recurrence of disease.

In the systematic review (SR) noted by Zhang et al., the heterogeneity of studies precluded an adequate risk of bias assessment and a competent comparison between studies. Five studies recruited low, intermediate and high-risk prostate cancer; other studies only recruited low-intermediate risk patients. Follow-up time was also short in most of the studies. Finally, definitive proof of oncological effectiveness of IRE against standard of care (SOC) or other FT modalities is still pending. Solid prospective comparative studies using standardized tools are needed to evaluate the impact of IRE on patients’ long-term survival and quality of life.

Short-term follow up with IRE shows that patients still have prostate cancer in a significant number of patients and is therefore not curative. We acknowledge that IRE may have similar or improved rates of urinary continence and ability to maintain erection. Several studies have also shown decrease in the ability to maintain erection over the long term when larger areas of the prostate are treated or in salvage therapy. The American Urological Association (AUA) recommends, as does the NCCN, use of IRE in clinical trials and does not advise this treatment for focal therapy or salvage therapy in the general clinical setting.

While quality of life (QOL) issues were maintained overall in the SR reported, there was significant heterogeneity in the studies with significant risk of bias and high in field recurrence rates and short-term follow-up in most of the studies. Later SR studies showed decline in urinary continence and higher recurrence and retreatment rates and higher pad-free and impotency failures.

The FIRE trial demonstrated low patient numbers and high risk of bias without randomization and relatively high local recurrence rates over short-term follow up at 12 months. It is not recommended by NCCN as salvage therapy.

The inclusion of a category I CPT code does not codify coverage as reasonable and necessary.

I have been caring for men with prostate cancer for over 25 years, and during that time, I have witnessed the toll that both the disease and its traditional treatments can take. I am writing to express my strong support for Medicare coverage of Irreversible Electroporation (IRE) for prostate cancer, particularly for men with intermediate-risk disease and for those whose cancer returns after radiation. Since incorporating IRE into my practice, I have seen remarkable results that have changed not only cancer outcomes but also the lives of my patients and their families.

In the past 18 months, I have performed more IRE cases than anyone in the United States and trained eight surgeons who have gone on to perform cases in their own communities. We discuss these patients extensively, and we have seen essentially no cases of incontinence. While the published data show impressive improvements, my real-world experience has been even better. I do not need to explain how devastating urinary incontinence can be for patients. When they experience this complication, they are at greater risk for urinary tract infections, hospital admissions, and a significant loss of productivity in both work and social settings. When erectile dysfunction is added to that burden, the emotional and psychological toll can be severe.

A Needed Option for Intermediate-Risk Men

For men with intermediate-risk prostate cancer (Gleason 7, PSA 10–20), the treatment decision has always been difficult. Surgery and full-dose radiation can cure the cancer but too often at the cost of continence or sexual function. Many men are understandably hesitant to face those side effects. At the same time, active surveillance is rarely a safe option for this group and carries about a 50 percent failure rate. It also requires repeated invasive testing and biopsies, which add both cost and risk. IRE has finally given us a middle option—one that allows us to target and destroy only the cancerous area of the prostate while preserving the rest of the gland.

In my experience, IRE achieves cancer control comparable to radical treatments. PSA levels drop sharply, and among the 80 patients I have treated, my recurrence rate is just 2.5 percent based on follow-up biopsies showing complete eradication of disease. Most remarkably, I have seen no long-term incontinence after two months, and the transient incontinence seen in the perioperative period has been associated only with urgency—a common occurrence after nearly all prostate procedures, benign or malignant.

After 18 months, I can confidently say that most men diagnosed with prostate cancer no longer have to choose between cancer control and quality of life. Even more importantly, IRE appears to be the first prostate cancer treatment that does not compromise outcomes if a second procedure is ever needed. This is not the case with surgery, radiation, cryotherapy, or HIFU.

Clinical Results Mirror Real-World Experience

The evidence supports what I see in my practice every day. A 2025 systematic review including more than 1,400 men treated with IRE showed that 93 to 98 percent remained free of significant cancer at short-term follow-up. Five-year data from multiple centers demonstrate that over 95 percent of intermediate-risk men treated focally with IRE have no cancer spread and no cancer-related deaths. Just as importantly, long-term incontinence—seen in 15 to 20 percent of prostatectomy patients—was virtually nonexistent. These results reflect my own experience. I have never had to refer an IRE patient for incontinence therapy, something I routinely did after surgery.

When IRE was first introduced, I approached it cautiously, as many of us did. But its evolution has been impressive. The 2022 AUA Guidelines now recognize ablation as an option for carefully selected intermediate-risk patients. The FDA has cleared IRE for soft tissue ablation, including the prostate, which further validates its role. And with the new CPT Category I code for prostate IRE taking effect next year, it is clear that the broader medical community now recognizes this therapy as a standard, established option.

A Valuable Tool for Recurrence After Radiation

IRE has also been invaluable for patients whose cancer returns after radiation. I recently treated a 79-year-old man who had previously undergone radiation and was not a surgical candidate. He declined hormonal therapy because of the side effects he had seen others experience. IRE offered him a path forward. His PSA has since dropped, he feels well, and his daily function is unchanged. In the past, this patient would have had no curative options. Compared to salvage cryotherapy, IRE causes far less tissue damage and carries a much lower risk of incontinence. Since Palmetto already covers salvage cryotherapy, expanding coverage to IRE is a logical and necessary next step. Studies such as the FIRE trial show local control rates of 70 to 80 percent in this setting, which aligns with my own clinical experience.

Patient Impact and Quality of Life

The stories I hear from patients and their families are powerful. Many are relieved that treating their cancer did not mean losing their independence or intimacy. Most go home the same day, experience minimal discomfort, and return to normal routines within days. One of my patients was back on the golf course a week after IRE—a recovery timeline unimaginable after surgery. These moments capture what this technology offers: effective cancer control without taking away the things that make life meaningful.

Let me share one final story. A 47-year-old married man with Gleason 4+3 and 3+4 disease in five cores, and a family history of prostate cancer, underwent IRE seven months ago. He experienced no erectile dysfunction or incontinence. His post-procedure biopsy last month was negative, and his PSA decreased by 75 percent. His post-IRE MRI, PET scan, and biopsy all show no evidence of disease. He is fully functional and cancer-free. IRE clearly changed the trajectory of his prostate cancer, his marriage, and his life.

I strongly urge Palmetto to finalize LCD DL40205 to include coverage for IRE in intermediate-risk prostate cancer and appropriately selected salvage cases. IRE is FDA-cleared, included in national guidelines, and supported by robust evidence and growing real-world success. It fills a long-standing gap in prostate cancer care, giving patients the chance for cure without compromise.

Thank you for your time and thoughtful consideration.

Thank you for your comments.

While individual experiences are appreciated, MPIM Chapter 3 Section 3.6.2.2 and MPIM Chapter 13 Section 13.5.3 restrict coverage to evidentiary support for providing coverage that is reasonable and necessary.

See comment #2 above.

I am writing to express my strong opposition to the proposed non-coverage policy for Irreversible Electroporation (IRE) for prostate tissue.

I have treated prostate cancer patients for more than three decades, and I have personally treated over 25 men with IRE. Our group has performed over 150 of these in the past 20 months. I have seen firsthand how this technology can change the trajectory of a man’s life after prostate cancer. The ability to achieve cancer control while preserving urinary continence and sexual function is nothing short of transformative.

IRE, commercially known as NanoKnife, is FDA-cleared for the surgical ablation of soft tissue, including prostate tissue. This clearance affirms its safety and effectiveness in ablating targeted areas while preserving surrounding critical structures. In addition, CMS has granted a Category I CPT code (55881) for prostate IRE, effective January 2025—clear recognition that this therapy is established and accepted within modern medical practice. Even Time Magazine recently recognized this therapy as one of the best medical inventions of 2025.

The PRESERVE trial provides compelling clinical evidence supporting the use of IRE in localized prostate cancer. Early data show over 86% percent of patients remain free of clinically significant cancer at follow-up, while maintaining urinary (99%) and sexual function (90%) at rates unmatched by traditional radical treatments. These results mirror what I have seen in my own patients. Their PSA levels drop, follow-up imaging and biopsies confirm disease control, and they maintain full continence and potency. These are men who have avoided the devastating side effects we too often see with prostatectomy or radiation.

Beyond the numbers, the human impact of IRE cannot be overstated. I have had patients return to their normal routines within days, go back to work, and resume activities they love. One patient told me he felt like he “got his life back” after treatment—something I rarely hear after more invasive procedures. For men who once faced a choice between curing their cancer or maintaining their dignity, IRE offers both.

The evidence continues to grow. A 2025 systematic review of more than 1,400 IRE-treated prostate cancer patients showed 93 to 98 percent remained free of significant disease at short-term follow-up. Five-year data from multiple centers demonstrate that over 95 percent of intermediate-risk patients treated focally with IRE have no metastatic progression and no cancer-related deaths. Long-term incontinence rates—seen in up to 20 percent of prostatectomy patients—are virtually nonexistent after IRE.

IRE has also proven invaluable as a salvage therapy for men with recurrence after radiation. For these patients, options are extremely limited. Salvage IRE provides local control rates of 70 to 80 percent, as shown in the FIRE trial, with far fewer complications compared to cryotherapy or salvage surgery. For men who otherwise face hormonal therapy or watchful waiting, IRE offers a safe and effective curative option.

The regulatory and professional acceptance of IRE is undeniable. The FDA has cleared it for prostate tissue ablation, the AUA 2022 guidelines include ablation as an option for carefully selected patients, and CMS has formalized its place in standard practice with the new Category I CPT code. These milestones reflect that IRE is no longer experimental but an evidence-based, patient-centered therapy that addresses a long-standing gap in prostate cancer care.

I urge Palmetto to issue a positive coverage determination for IRE in the final LCD. This is not only about technology; it is about giving men options and access to a treatment that preserves their health, function, and quality of life. Denying coverage would deprive countless patients of an FDA-cleared, safe, and effective option that has already changed lives in our practice and across the country.

IRE allows us to treat prostate cancer while preserving men’s quality of life and dignity. That is the future of prostate cancer care, and I implore Palmetto to be part of that future.

Thank you for your time and thoughtful consideration.

Thank you for your comments.

Category I CPT® coding does not equate to coverage as reasonable and necessary. In addition, the use of CPT® code 55877 is not specific to treatment for prostate cancer but for irreversible electroporation of tumors of the prostate and refers to tissue ablation of the prostate. The FDA has not approved IRE for the treatment of prostate cancer only for the ablation of soft tissue of the prostate.

See also comment #2 above.

In the PRESERVE trial, this single-arm study had several limitations, including the absence of a comparator arm and a lack of central imaging or pathology review, reflecting real-world practice. Additionally, 14 sites performed their first IRE case when the PRESERVE trial started, indicating a potential learning curve. While this study included patients with intermediate-risk prostate cancer, the majority had stage T1c prostate cancer and were found to have GG2 (Grade Group 2). Small numbers of patients at multiple sites precluded any more definitive recommendations and was limited by short-term follow up for higher grade, intermediate risk prostate cancer.

I am a patient who was treated with the NanoKnife procedure, also known as Irreversible Electroporation (IRE), for my prostate lesion. I wanted to share my experience and express my strong support for continued Medicare coverage of this treatment option.

Before I learned about NanoKnife, I was faced with limited options that came with significant risks of side effects that could greatly affect my quality of life. After researching and consulting with my physician, I decided on NanoKnife because it offered a minimally invasive approach that would allow me to effectively treat my prostate cancer while preserving my urinary and sexual function. This was the deciding factor in either attempting to monitor my progression or to be proactive in my treatment.

My recovery was remarkably quick — I experienced minimal discomfort, was able to return to normal activities soon after, and have maintained an excellent quality of life. Follow-up imaging, Pet Scan and biopsy have shown that my treatment was successful, and I am incredibly grateful to have had access to this technology.

For patients like me, NanoKnife provides an important, targeted option that treats the diseased tissue without damaging surrounding structures. Removing coverage for this treatment would take away a valuable, proven option for men who want an alternative to more invasive treatments or radiation.

I strongly urge Palmetto to continue coverage for Irreversible Electroporation (NanoKnife) for prostate disease. The outcomes I’ve experienced speak for themselves, and I hope other patients will continue to have access to this same opportunity for effective, life-changing care.

Thank you for your time and consideration.

Thank you for your comments.

We appreciate your positive experience using IRE for your prostate cancer treatment. However, in creating an LCD for coverage for the general Medicare population, we must follow CMS guidelines as elucidated in MPIM Chapter 13 for evidentiary review and development.

As a urologist practicing in the community for over 12 years, I am writing to express my strong support for Medicare coverage of Irreversible Electroporation (IRE) for the treatment of prostate cancer, particularly for intermediate-risk disease and salvage therapy following radiation. I have incorporated IRE into my clinical practice and have observed firsthand the meaningful improvements it offers in both oncologic outcomes and patient quality of life.

Men with intermediate-risk prostate cancer (Gleason score 7, PSA 10–20) have historically faced limited curative options. Surgery and radiation, while effective at controlling disease, often carry substantial risks to urinary and sexual function. Conversely, active surveillance is typically inappropriate for this population due to the likelihood of progression. IRE provides a much-needed middle ground, enabling focal ablation of malignant tissue while preserving the surrounding prostate and critical neurovascular structures.

In my experience, IRE has yielded oncologic results on par with radical treatments while maintaining functional outcomes. PSA reductions are typically robust, and post-treatment biopsies demonstrate no residual disease in over 80% of patients, rates comparable to post-prostatectomy cohorts. Notably, nearly all of my IRE patients have retained both continence and potency. This ability to achieve disease control without functional compromise represents a significant advance in the management of localized prostate cancer.

Evidence Base Supporting IRE Effectiveness

The growing body of clinical data corroborates these results. A 2025 systematic review encompassing more than 1,400 prostate IRE patients demonstrated 93–98% freedom from significant disease at short-term follow-up. Five-year multi-center data further confirm that over 95% of intermediate-risk patients treated with focal IRE remained free from metastasis and prostate cancer–specific mortality. Importantly, none of these studies reported the long-term urinary incontinence rates (15–20%) typically seen after radical prostatectomy. These outcomes are consistent with my clinical experience, where I have not needed to refer a single IRE patient for incontinence management, a striking contrast to standard surgical care.

Guideline, Regulatory, and Coding Recognition IRE has progressed from investigational to accepted clinical practice. The 2022 AUA Guidelines now include focal ablation as an option for appropriately selected intermediate-risk patients, provided informed consent and appropriate follow-up are ensured. The FDA’s clearance of IRE for soft tissue ablation, including prostate tissue, confirms its regulatory legitimacy. Furthermore, the forthcoming CPT Category I code for prostate IRE underscores its recognition as a standardized procedure within urologic oncology. Collectively, these developments signal that IRE is now a validated component of prostate cancer management consistent with current medical standards.

Salvage Therapy IRE also fills a crucial void for men experiencing local recurrence after radiation therapy. Many of these patients are poor surgical candidates or reluctant to pursue systemic hormonal therapy due to its quality-of-life impact. Without IRE, this patient would have had no reasonable curative option. Compared to salvage cryotherapy, IRE is substantially less morbid, avoiding tissue freezing, reducing fibrosis, and minimizing the risk of incontinence. Given that Palmetto currently covers salvage cryotherapy, extending coverage to IRE represents a rational and evidence-based progression. Published data, including the FIRE trial, report 70–80% local control rates in the salvage setting, further supporting its clinical value.

Patients consistently describe high satisfaction following IRE. Many return to normal activities, including work and recreation, within days of treatment. The ability to preserve continence, sexual function, and independence has an enormous impact on quality of life for men in their 60s and 70s. This strongly aligns directly with Medicare’s mission to provide effective care that supports long-term health and functional well-being in older adults.

Personal patient experience

I have multiple patients with excellent results in regard to PSA decline, maintaining sexual function, as well as overall improved voiding function. These patients have followed the appropriate monitoring protocol and follow up biopsies have demonstrated no residual cancer. Overall, IRE remains an excellent focal option for the treatment of prostate cancer and gives patients an additional option with substantially fewer side effects than surgery or radiation therapy. Lack of IRE coverage for prostate cancer patients would result in a tremendous detrimental impact on patient care options and quality of life.

For these reasons, I strongly encourage Palmetto to finalize LCD DL40205 to include coverage of IRE for intermediate-risk prostate cancer and salvage therapy following radiation under appropriate clinical criteria. IRE is FDA-cleared, guideline-supported, and validated by an expanding evidence base and real-world experience. It addresses a well-recognized treatment gap between radical therapy and observation, offering good oncological control without compromising quality of life.

Thank you for your consideration.

Thank you for your comments

Please see comments #2 and #4 above.

I am a community urologist who has been treating prostate cancer patients for over 10 years. I’m writing to voice my strong support for Medicare coverage of Irreversible Electroporation (IRE) for prostate cancer, particularly for intermediate-risk disease and for salvage therapy after radiation. In the last few years, I have incorporated IRE into my practice and seen first-hand how it can transform patient outcomes.

“Middle Ground” Option for Intermediate-Risk Patients: Historically, men with intermediate-risk prostate cancer (Gleason 7, PSA 10–20) faced a dilemma. Our only curative treatments were surgery or full-dose radiation – both effective on cancer, but at a high cost to quality of life. Many of my patients were terrified of the side effects: wearing diapers due to incontinence, or losing sexual function permanently. On the other hand, simply observing the cancer (active surveillance) isn’t advisable for most intermediate-risk cases, as the tumor can progress. IRE has given us a much-needed middle ground. It ablates the cancerous part of the prostate without removing or irradiating the entire gland, meaning we can kill the tumor while sparing normal tissue. In my experience treating intermediate-risk men with focal IRE, the cancer control has been excellent – their PSA levels plummet and follow-up biopsies show no residual cancer in >80% of cases, very comparable to my post-prostatectomy patients. Yet, nearly all of my IRE patients retained full urinary control and sexual potency. It is difficult to overstate how impactful that is. Men who likely would have been impotent or wearing pads after traditional treatment are instead living normally, cancer-free. As a physician, it’s incredibly rewarding to not have to tell my patients they must sacrifice quality of life to get a cure.

Clinical Evidence Matches What I See: My personal anecdotal success is backed by solid evidence. A 2025 systematic review covering over 1,400 prostate IRE patients found that 93–98% remained free of significant cancer at short-term follow-up. Five-year data from a multi-center study showed over 95% of intermediate-risk patients treated focally with IRE had no cancer spread and were alive without cancer deaths. Significantly, virtually none experienced the long-term urinary incontinence that we usually see in 15-20% of prostatectomy patients. Those numbers resonate with what I’ve witnessed: I have not had to refer a single IRE patient for incontinence management, whereas after surgery that’s a routine part of follow-up. This evidence gives me confidence that IRE isn’t just a flash in the pan – it’s a viable treatment that’s meeting its promise.

Guideline and Regulatory Acceptance: Initially, like any new technology, IRE was approached cautiously. But at this point, it has gained acceptance from key institutions. The AUA guidelines (2022) explicitly include ablation as an option for appropriately selected intermediate-risk patients, and they emphasize informed consent and ideally clinical trial use (I always ensure my patients understand the relative novelty of IRE, yet they are overwhelmingly eager for it when presented with the data). The FDA has cleared IRE for soft tissue ablation, including prostate, affirming that it’s a legitimate medical device for this purpose. And starting next year, we will even have a CPT I code specifically for prostate IRE, meaning the wider medical community recognizes it as standard enough to warrant its own billing code. These developments should reassure Palmetto that covering IRE is in line with the current trajectory of medical practice.

Patient Perspectives: Nearly every week in my clinic, I hear gratitude from a patient or spouse about IRE. Couples are relieved that treating the cancer didn’t mean ending their intimacy. Patients are amazed that they could go home the same day, with only minor discomfort, and be cancer-free. One of my patients even returned to golfing within a week after IRE – something unheard of after prostate surgery. These may sound like small lifestyle details, but for someone in their 60s or 70s, maintaining independence and function is priceless. Medicare’s mission is to provide health care that keeps seniors healthy and active; IRE aligns perfectly with that mission by treating cancer without inducing disability.

In conclusion, I urge you to finalize LCD DL40205 to cover IRE for intermediate-risk prostate cancer and for salvage therapy (with appropriate selection criteria). In my practice, IRE has become an indispensable tool that I would not want to lose – and more importantly, my patients deserve access to this breakthrough. The technology has moved beyond the investigational phase: it is FDA-cleared, supported (cautiously) by guidelines, and validated by growing research and real-world outcomes. It addresses a well-recognized treatment gap in prostate cancer care. By covering IRE, Palmetto can ensure that men in our region have the choice of a treatment that maximizes both cancer control and post-treatment quality of life.

Thank you for considering my perspective. Please feel free to reach out if you would like further information from a community practice standpoint.

Thank you for your comments.

IRE is not currently FDA approved or cleared for the treatment of prostate cancer as a focal or whole gland therapy.

Please also see comments #2 and #4 above.

I am writing to express my strong support for coverage of Irreversible Electroporation (IRE) under Draft LCD DL40205, specifically for men with intermediate-risk prostate cancer and for those with localized recurrence after radiation therapy (salvage cases). I can attest that IRE fills a critical gap in prostate cancer care and represents an important evolution in focal therapy.

Clinical Rationale and Evidence

The evidence supporting IRE has expanded considerably in recent years. A 2024 meta-analysis of 19 studies involving approximately 1,450 patients demonstrated that focal IRE provides excellent oncologic control while preserving quality of life. Across these studies, three-year freedom from progression was 90–97%, with 95–100% of patients maintaining urinary continence and most retaining sexual function—outcomes rarely achievable with radical prostatectomy or radiation.

In my own experience, these data ring true. None of our IRE-treated patients have developed metastases, and nearly all remain pad-free and sexually active. These results clearly meet Medicare’s standard of “reasonable and necessary,” achieving equivalent cancer control with far fewer complications.

The PRESERVE trial, a U.S. multicenter prospective study, demonstrated that 84% of intermediate-risk patients had no clinically significant cancer on one-year biopsy following IRE. This pivotal study helped pave the way for the FDA’s 2024 clearance of IRE for prostate tissue ablation and the AMA’s approval of a Category I CPT code, effective in 2026.

I have now performed over 50 IRE procedures for men with localized intermediate-risk prostate cancer—both through clinical trials and in standard clinical practice. These patients have achieved excellent oncologic and functional outcomes, with durable cancer control, preserved continence, and maintained sexual function. These results echo what I and others have consistently observed in both practice and the peer-reviewed literature.

Furthermore, five-year outcomes (Scheltema et al., Eur Urol Open Sci, 2023) demonstrate 99% metastasis-free survival and 100% cancer-specific survival after IRE for localized disease—comparable to surgery or radiation but achieved with far less morbidity.

As a clinician, it is rare to offer a therapy that controls cancer while preserving continence, sexual function, and overall quality of life.

Guideline Context

The 2022 American Urological Association (AUA) Guidelines state that energy-based ablation “may be considered in select, appropriately informed patients” with intermediate-risk prostate cancer. While long-term comparative data continue to mature, the AUA recognizes focal ablation—including IRE—as a valid treatment option for appropriately selected patients, who otherwise face the difficult balance between overtreatment and undertreatment.

This nuance is not fully reflected in the draft LCD. IRE is cited within AUA guideline reference #129 and included in the AUA Core Curriculum for urology trainees. In everyday practice, focal ablation has become a standard discussion point for men seeking effective cancer control with minimal impact on function.

Aligning coverage with this AUA-endorsed framework—and consistent with the NCCN’s acknowledgment of IRE as investigational but feasible in experienced hands—would ensure that Palmetto’s policy reflects the current evidence-based standard of care.

IRE in the Salvage Setting

IRE also provides an essential option for men with radiation-recurrent prostate cancer, where conventional salvage therapies are often too morbid. Many patients decline salvage prostatectomy due to the high risk of severe incontinence and complications.

The 2025 NCCN Prostate Cancer Guidelines now list IRE as a Category 2B option for localized recurrence, alongside cryotherapy and HIFU. Since Medicare already covers cryotherapy in this setting, extending similar coverage to IRE is both logical and equitable. Several of my patients remain cancer-free today because of salvage IRE; denying coverage would deny others this potentially curative therapy.

Physician Experience and Patient Impact

I have had countless success stories with IRE, but one stands out. A 47-year-old man with intermediate-risk prostate cancer was initially hesitant to pursue treatment after watching his father struggle with lifelong incontinence and sexual dysfunction following prostatectomy. Because of those fears, he nearly declined therapy altogether. We were able to offer him NanoKnife (IRE) as part of a clinical trial. Nearly five years later, he remains cancer-free, with excellent urinary control and sexual function fully intact.

Stories like his are not rare. I have had many Medicare patients with similar experiences. I share this perspective not just as a clinician, but as someone who has witnessed firsthand how IRE can preserve both life and quality of life. It allows us to offer curative therapy without compromising dignity—precisely the type of patient-centered care Medicare aims to support.

Conclusion

I strongly urge Palmetto to finalize LCD DL40205 with a positive coverage determination for IRE in both treatment of both primary intermediate-risk and salvage prostate cancer under appropriate criteria.

This decision would be grounded in strong evidence, aligned with national guidelines, and consistent with FDA and AMA recognition of IRE as a safe, effective, and established medical technology. Most importantly, it would ensure that Medicare beneficiaries have equitable access to a treatment that offers cancer control without the devastating side effects of traditional therapies.

Thank you for your thoughtful consideration. I greatly appreciate Palmetto’s leadership in ensuring that coverage policies evolve alongside advances in prostate cancer care.

Thank you for your comments.

NCCN 2026 guidelines consider IRE category 2B after recurrence following radiation therapy. The other listed focal therapy modalities for treating local recurrence are category 2A and there are no direct comparator studies showing noninferiority or superiority with IRE treatment. NCCN Category 2B recommendations are therapeutic options based on lower-level evidence. Given the absence of quality literature to support its use in salvage therapy, including favorable local and distant control rates, it would not be reasonable and necessary for salvage therapy at this time.

See also comments #2 and #4 above.

We appreciate the opportunity to offer comments on Palmetto's proposed LCD for Irreversible Electroporation for Cancer.

Prostate Cancer

The PRESERVE trial is a prospective, single-arm study evaluating irreversible electroporation (IRE) in patients with intermediate-risk prostate cancer. Initial results show a strong safety profile, with 71% of patients demonstrating negative in-field biopsies, suggesting promising oncologic control. These outcomes have been further supported by data from international multicenter registries, which consistently report favorable short-term safety and functional results, including high rates of continence preservation and low rates of severe adverse events.

While ongoing data collection and longer-term follow-up are underway, the growing body of prospective evidence suggests that IRE is a safe and effective tissue-preserving treatment option for select patients with intermediate-risk disease. Given its favorable functional outcomes and its ability to preserve genitourinary quality of life compared to radical therapies, IRE offers meaningful value as a focal therapy option. We believe this evolving evidence base supports consideration of coverage for IRE in appropriately selected patients, particularly when provided in structured clinical settings or registries with standardized follow-up protocols.

Pancreatic Cancer

We support coverage of irreversible electroporation (IRE) for select patients with locally advanced or recurrent pancreatic cancer based on emerging evidence from prospective studies and real-world data registries.

The PANFIRE-2 trial, a prospective, multicenter, phase II study, demonstrated that IRE is a feasible and safe option for patients with locally advanced and recurrent pancreatic cancer. Importantly, median overall survival (OS) in this trial significantly exceeded historical benchmarks for this challenging patient population, suggesting benefits beyond standard treatment pathways.

The DIRECT registry, a large, real-world, prospective dataset, further reinforces IRE's safety profile, reporting a low rate of adverse events and favorable mortality outcomes across multiple centers and patient types. These findings provide essential validation outside of controlled trial environments.

We respectfully challenge the interpretation of the CROSSFIRE randomized controlled trial as outlined in the LCD. This study compared IRE to MRI-guided stereotactic body radiation therapy (SBRT), a highly advanced and resource-intensive standard-of-care treatment for patients with locally advanced pancreatic cancer (LAPC). The trial found no statistically significant differences in overall survival (OS) or adverse event rates between the two arms.

Importantly, the trial was stopped early due to futility, indicating that the pre-specified superiority threshold was not met. This does not represent a negative outcome, but rather shows that IRE performed comparably to MRI-guided SBRT, a modality already widely accepted and incorporated into clinical guidelines.

Moreover, while the trial enrolled 68 patients, it was designed with a larger sample size in mind but was appropriately halted once it became statistically clear that superiority could not be demonstrated. This should not be misconstrued as a flaw in the trial design or a failure of IRE. Rather, it reinforces the conclusion that IRE offers oncologic outcomes and safety profiles comparable to a sophisticated, guideline-supported treatment.

These findings underscore the clinical relevance and utility of IRE as a viable local therapy for LAPC and support its consideration for coverage.

Taken together, these studies reflect a growing body of prospective and comparative data suggesting that IRE is a viable local therapy option in LAPC and recurrent disease, particularly when systemic therapy has been exhausted or when resection is not possible. In carefully selected patients, delivered by experienced teams, IRE offers the potential for local tumor control with an acceptable safety profile and outcomes comparable to those of established ablative options.

We encourage coverage of IRE for the treatment of locally advanced pancreatic cancer when used in appropriate clinical contexts, such as within prospective registries, multidisciplinary treatment plans, or high-volume centers with demonstrated experience.

We appreciate the opportunity to provide meaningful feedback on Palmetto's proposed LCD for Irreversible Electroporation for Cancer.

References cited in comment received.

Thank you for your comments.

In the CROSSFIRE study, overall survival (OS) for the IRE group was lower than the magnetic resonance imaging (MRI) guided radiation therapy group where both groups received concurrent chemotherapy. There was no advantage to IRE in terms of survival or complications, and the study was stopped for futility. Therefore, any additional extractions for superiority or recommendations for IRE in pancreatic cancer were not supported by this study.

In the PANFIRE II trial noted above, the median survival was not significantly prolonged compared to the group that received prior chemotherapy with gemcitabine-based induction chemotherapy or received FOLFIRINOX. For participants with postresection local recurrence, the median OS was 16 months from diagnosis of recurrence (95% CI: 11 months, 22 months) and 9 months from IRE (95% CI: 2 months, 16 months). After IRE, local recurrence developed in 23 of the 50 participants (46%). Tumor volume of 37 cm³ or greater (hazard ratio [HR], 2.9; P = .02), pre-IRE carbohydrate antigen 19-9 (CA 19-9) level of 2000 U/mL or greater (HR, 12.1; P = .001), and decrease in carbohydrate antigen (CA) 19-9 level of 50% or less 3 months after IRE (HR, 3.1; P = .01) were predictors of worse survival. Fourteen minor and 21 major complications occurred in 29 of the 50 participants (58%). Two participants died less than 90 days after IRE; one of these deaths was likely related to IRE. This study does not support improved survival or palliation in patients with advanced pancreatic cancer with high adverse events and therefore is not reasonable and necessary.

In the DIRECT Registry study, the OS was not evaluated, and small sample sizes were used for the comparator being the SOC for chemotherapy alone. The 90-day mortality rates of treatment versus no treatment were the same.

Present analysis of the DIRECT Registry study has several limitations. First, the adverse events (AE) and survival data are limited to a 90-day period following enrollment. Additional analyses of longer-term outcomes comparing the IRE and SOC treatment groups, including overall and progression-free survival, are planned. A multivariate analysis will also be conducted to assess the impact of the differing study variables on observed outcomes according to the authors. There was also an imbalance in the number of patients enrolled in each arm of the study, with three times as many subjects in the IRE treatment arm compared to those treated with SOC. Enrolling patients in a control arm for clinical trials, especially for serious conditions like locally advanced pancreatic cancer (LAPC), was challenging during the time period for the present study (2019 to 2023). There was patient reluctance since many of the subjects enrolled in the study sought out centers that provided IRE as a treatment. Other patient biases that affected enrollment in the SOC arm included the perception of inferiority of just staying on chemotherapy, the potential toxicity of chemotherapy after 3 months of treatment, and, in some instances, the need for patients to pause chemotherapy. There is also a lack of clear SOC in LAPC after 3 months of disease control and/or response with induction chemotherapy.

Currently, these studies noted above do not support the use of IRE for pancreatic carcinoma.

I am writing to express my strong support for coverage for Irreversible Electroporation (IRE) under Draft LCD DL40205, specifically for men with intermediate-risk prostate cancer and for those with localized recurrence after radiation (“salvage” cases). As a Urologic Oncologist who provides IRE in practice, I can attest that this therapy fills a critical gap in prostate cancer care.

Clinical Rationale & Evidence: The evidence base for IRE expanded significantly in the last few years. A large 2024 meta-analysis (19 studies, ~1,450 patients) confirms that focal IRE achieves excellent oncologic control in intermediate-risk disease while preserving quality of life. Across these studies, 3-year freedom from cancer progression was about 90–97%, with 95–100% of patients retaining urinary continence and the majority maintaining sexual potency – outcomes that are simply unattainable with radical surgery or radiation in this population. In my own series, our results mirror these findings: to date, none of my IRE patients have developed metastases, and all remain pad-free and free from changes to sexual function status. These tangible benefits meet Medicare’s “reasonable and necessary” definition, providing equal cancer control with fewer complications.

Further, the U.S. multi-center prospective PRESERVE study reported 84% of intermediate-risk patients had no significant cancer on 1-year biopsy after IRE. This trial’s success was a factor in the FDA’s 2023 clearance of IRE for prostate tissue ablation and the AMA’s approval of a Category I CPT code (effective 2026). In other words, our regulatory and professional bodies have vetted IRE’s safety and efficacy. We also now have 5-year data (Scheltema et al. 2023) showing 99% metastasis-free survival and 100% cancer-specific survival at 5 years post-IRE for localized disease – essentially equivalent to outcomes of surgery or beam radiation in similar patients, but, importantly, with significantly less morbidity. As a practitioner of robotic radical prostatectomy, it is remarkable to be able to offer my patients a treatment that controls their cancer and spares them from incontinence or lifelong erectile dysfunction.

Guideline Support: It is important to review the status of clinical guidelines. The 2022 American Urological Association (AUA) guidelines explicitly state that energy-based ablation “may be considered in select, appropriately informed patients” with intermediate-risk prostate cancer. The AUA panel noted that while long-term comparative data are still maturing, focal therapies like IRE are a valid option for these patients, who otherwise face the difficult choice between overtreatment and under-treatment. This nuance wasn’t fully captured in the draft LCD summary – in fact, IRE is referenced in the AUA guidelines (Guideline Reference #129) and even included in the AUA’s Core Curriculum for resident education. In practice, offering focal ablation is within the standard of care for intermediate-risk men who desire cancer control with less impact on lifestyle. By aligning coverage with this AUA-endorsed approach (and similarly cautious NCCN mentions of IRE as investigational but feasible), Palmetto will support patient-centered care consistent with current urologic practice.

Salvage Setting: I also regularly see patients with prostate cancer recurrence after radiation therapy. Historically, salvage options are few – most men forego salvage prostatectomy due to high risks, leaving them with the option of cryotherapy (conceptually similar to IRE, but less accurate in my experience) or observation and eventually androgen ablation. IRE offers a crucial alternative for these cases. The NCCN Prostate Cancer guidelines (2025) now list IRE as a Category 2B option for such local recurrences, acknowledging it alongside cryotherapy and HIFU as a reasonable tool in experienced hands. Medicare already covers cryotherapy for salvage; it is only logical to similarly cover IRE for these patients who have no other good options.

My Experience & Patient Impact: As a physician who performs IRE, I have witnessed the meaningful difference it makes. One of my patients – a 72-year-old newlywed man with intermediate-risk cancer – was adamantly against surgery due to fear of impotence. We treated him with focal IRE earlier in 2025. Early results show disease control and he was thrilled to be fully potent and continent 2 months after surgery. He often tells me how grateful he is that this treatment was available. There are many men like him in our Medicare population who could benefit similarly. By covering IRE, Palmetto will empower physicians like me to offer the right treatment for the right patient: curative therapy without compromising dignity or quality of life.

Conclusion: I strongly urge Palmetto to finalize LCD DL40205 with a positive coverage determination for IRE in intermediate-risk and salvage cases of prostate cancer, with appropriate selection criteria. Such a policy would be firmly grounded in evidence and guideline-supported. It would acknowledge that IRE is no longer “experimental” but an accepted medical technology – FDA-cleared, peer-reviewed, and taught in our training programs.

Most importantly, it would give Medicare beneficiaries access to a treatment that can eradicate cancer while preserving quality of life. In my view, there is no question that this meets the bar of being reasonable and necessary.

Thank you for your consideration of these comments.

Thank you for your comments.

Please see comments #2, #4 and #8 above.

As a Urologist, I am responsible not only for delivering the best care to patients but also for ensuring we do so in a cost-effective, evidence-based manner. I am writing to advocate that Palmetto GBA finalize LCD DL40205 to cover irreversible electroporation (IRE) for intermediate-risk and salvage prostate cancer cases. In this letter, I’ll focus on why covering IRE makes sense from a health outcomes and health economics perspective, in addition to aligning with clinical evidence.

High-Value Care: We often talk about “value-based care” in medicine – getting the best outcomes per dollar spent. IRE, in my analysis, embodies high-value care for the right patient group. Consider the alternative for an intermediate-risk Medicare patient: radical prostatectomy might cure the cancer, but it comes with a substantial chance of costly downstream needs – incontinence supplies (often lifelong), medications for erectile dysfunction (PDE5 inhibitors, injections), possible additional surgeries (sphincter implants, revision procedures). These not only degrade the patient’s quality of life but also generate ongoing expenses. Radiation therapy, while non-surgical, can lead to years of managing radiation cystitis, bowel issues, or hormonal therapy if recurrence happens – again incurring costs. If we can achieve the same cancer control with IRE and avoid many of those side effects, we effectively reduce the need for those extra interventions. A recent cost-effectiveness study by Reddy et al. (2023) actually modeled this: focal therapy (like IRE) was more cost-effective than surgery or radiation for localized prostate cancer, primarily because of the reduction in side-effect management costs and preservation of quality-adjusted life years. From a Medicare vantage point, approving a therapy that prevents expensive complications (and preserves patient well-being) should be a clear positive.

Clinical Effectiveness: The value argument only holds if IRE is effective at controlling cancer – which evidence shows it is. If historical 5-year recurrence rates after prostatectomy or radiation range from 15-30%, focal IRE is coming in very competitively.

Guideline Acknowledgment & Evolution: The clinical community has been cautious, appropriately, but the trend is moving toward acceptance of focal therapies. We shouldn’t wait for formal guideline “recommendations” to catch up if the evidence is already strong, especially when dealing with a local coverage policy. The AUA guidelines’ wording suggests an openness to focal ablation – it’s an expert consensus that sees the promise but awaits more data. What’s important is they did not find evidence of harm; to the contrary, they acknowledged low-risk patients don’t need it (surveillance suffices) and high-risk patients shouldn’t get it (need multimodal therapy), but intermediate-risk patients stand out as the sweet spot. This aligns with the coverage scope we’re requesting. I foresee that in the next 2-3 years, as ongoing randomized trials (like the PART trial) report results, guidelines will formally include focal therapy recommendations. Palmetto has the opportunity now to establish coverage criteria for a patient who is well established in the literature and guidelines.

Local Need and Patient Demand: In our state, we have a high population of veterans and senior citizens who are very attuned to their healthcare options. I have noticed more patients inquiring about “less invasive treatments” for prostate cancer – they read articles, they go on ChatGPT, they hear about HIFU or IRE on the news or from friends. The interest is there, and I believe it’s our duty as healthcare providers to offer an option like IRE when it’s backed by data. We have had cases where patients literally said, “If I can’t get something like IRE, I will refuse surgery.” While we try to counsel them on all options, the fear of side effects is powerful. IRE helps us bridge that impasse. I would hate to see a situation where lack of coverage forces a patient to decline any treatment until his cancer worsens to a point that is much more costly (and difficult) to address.

In conclusion, from both a clinical outcome standpoint and a health system standpoint, covering IRE in the defined contexts is the right decision. It aligns with the quadruple aim: better outcomes, better patient experience, potentially lower costs, and I would add – physician satisfaction, because it is gratifying to see patients do so well.

Thank you for considering these points.

Thank you for your comments.

Please see responses above.

While IRE may be an emerging technology, we are bound by Principles of Study Design that are consistent with CMS guidelines and evidentiary support as per guidelines in CMS Internet-Only Manual, Pub. 100-08 MPIM, Chapter 13 Local Coverage Determinations.

The following comment was received from multiple stakeholders:

I am writing to express strong opposition to the proposed non-coverage determination for pulsed electric field irreversible electroporation (PEF/IRE) for the treatment of localized prostate cancer. As a physician actively involved in prostate cancer care, I believe this technology represents a safe, effective, and cost-efficient advancement that offers significant benefits to patients, providers, and payers alike. Denying coverage would deprive Medicare beneficiaries of access to a therapy that aligns with modern principles of precision medicine and organ preservation.

Clinical Efficacy and Oncologic Outcomes

Irreversible electroporation delivers controlled, non-thermal energy pulses that create nanopores in cell membranes, leading to apoptosis while sparing critical structures such as nerves, vessels, and the urethral sphincter. Unlike thermal ablation or radical therapies, IRE preserves the extracellular matrix, enabling tissue recovery and reducing morbidity.

The PRESERVE Trial (George et al., European Urology, 2025) — the first prospective, multicenter pivotal study — demonstrated strong oncologic efficacy in intermediate-risk patients. The study reported:

• 71% (95% CI: 62–79%) 12-month negative in-field biopsy rate using standard criteria
• 84% (95% CI: 76–90%) negative rate using Delphi consensus criteria
• 68% median PSA reduction at 6 months
• Preservation of urinary continence and erectile function in most patients

These results validate the clinical rationale for focal IRE as a targeted, organ-preserving approach for appropriately selected patients.

Long-term data further underscore its durability. A five-year multicenter cohort study (Scheltema et al., BJU International, 2023) found:

• Failure-free survival: 91% at 3 years; 84% at 5 years
• Metastasis-free survival: 99.6%
• Prostate cancer-specific survival: 100%
• Urinary continence preservation: 99%
• Erectile function preservation: 58% at 12 months

These outcomes are comparable to surgery or radiation in oncologic control, yet achieved with far fewer functional compromises.

Functional Benefits and Quality of Life

Beyond oncologic control, IRE’s ability to preserve quality of life distinguishes it from conventional treatments.

In the multicenter registry study by Zhang et al. (Prostate Cancer and Prostatic Diseases, 2024), involving 411 patients:

• Clinically significant recurrence at 12–18 months was limited to 24%
• Low rates of major adverse events were observed
• Urinary continence and sexual function were largely preserved

Multiple other studies support these findings:

• Morozov et al. (Andrologia, 2020) — systematic review: in-field recurrence 0–39%, rapid recovery of urinary/sexual function within 6–12 months
• Miñana López et al. (Journal of Urology, 2023) — median 3-year follow-up, consistent preservation of continence and potency
• Collettini et al. (Radiology, 2019) — excellent local control with maintained functional outcomes

Collectively, these data establish IRE as a clinically validated, evidence-supported therapy that maintains oncologic rigor while minimizing collateral damage — exactly the type of innovation Medicare should support.

Economic and Systemic Advantages

IRE’s minimally invasive nature translates to shorter procedural times, lower complication rates, and faster recovery, making it ideally suited for ambulatory surgery centers (ASCs). By avoiding hospitalization, prolonged catheterization, and costly management of incontinence or erectile dysfunction, IRE can significantly reduce downstream healthcare costs.

From a payer’s perspective, this is better medicine at lower total cost:

• Avoids overtreatment of indolent disease with radical surgery or radiation
• Reduces long-term management costs from side effects (pads, implants, revisions, etc.)
• Preserves productivity and quality of life in a growing population of Medicare beneficiaries

Refusing coverage will push patients toward more morbid, expensive, and unnecessary interventions, directly contradicting CMS’s goals of value-based, patient-centered care.

Alignment with Modern Prostate Cancer Management

IRE fits squarely within the evolving paradigm of personalized focal therapy, endorsed by international urologic societies as a legitimate option for localized intermediate-risk disease. The therapy is FDA-cleared, has robust real-world data, and is performed in leading academic and community centers worldwide.

A non-coverage decision would not only stifle innovation but also contradict the growing body of Level 1 and long-term evidence demonstrating its safety, efficacy, and patient benefit.

Conclusion

PEF/IRE is a proven, evidence-backed therapy that:

• Effectively controls localized prostate cancer
• Preserves continence and potency
• Reduces healthcare costs and complications
• Aligns with patient-centered, minimally invasive care

Medicare beneficiaries deserve access to modern, less invasive treatment options that balance cancer control with quality of life. CMS should reverse the proposed non-coverage and adopt a coverage-with-evidence-development (CED) approach or maintain local coverage discretion to ensure equitable access and continued data collection.

Please reconsider this dangerous decision that will hurt patients and providers.

References cited in comment received.

Thank you for your comments.

Please see comments #2, #4 and #8 above.

Coverage with evidence development has been followed consistent with CMS published guidelines that have been published for National Coverage Determination (NCD) development. LCDs are developed from guidelines promulgated in MPIM Chapter 13. In addition, GRADE criteria were followed for this LCD development consistent with CMS guidelines for Principles of Study Design.

I am submitting this letter to comment on Proposed LCD DL40205 – Irreversible Electroporation for Cancer. This correspondence serves as an official statement of support for revising the proposed non-coverage determination, based on current peer-reviewed data and real-world clinical outcomes demonstrating that pulsed electric field (PEF) ablation is safe, effective, and reasonable and necessary for select Medicare beneficiaries.

I am a radiologist, where I manage patients with advanced thoracic and metastatic malignancies. These are often older, frail individuals who have undergone multiple prior lines of therapy and now face limited, high-risk, or ineffective options. For many of them, traditional approaches—surgery, radiation, chemotherapy, or thermal ablation—are simply unsafe. Each carries side-effect profiles that compromise pulmonary reserve, healing, or quality of life.

The Aliya® Pulsed Electric Field (PEF) Ablation System represents an evidence-based, structure-sparing alternative that restores treatment opportunity without adding toxicity. PEF uses biphasic, cardiac-gated electrical pulses delivered through a single monopolar electrode, avoiding the thermal necrosis and muscle stimulation associated with earlier irreversible electroporation (IRE) platforms. This design allows ablation near the bronchi, pulmonary arteries, and pleura—areas traditionally off-limits to heat-based technologies.

In my own experience (3 years and 43 cases), PEF ablation has been consistently safe and well-tolerated. Patients are typically discharged the same day, experience minimal post-procedural discomfort, and resume systemic therapy immediately. These outcomes mirror published data across multiple peer-reviewed studies:

• Moore et al., Lung Cancer (2025) – Multicenter matched cohort (n=91) in stage IV NSCLC. One-year overall survival 74% for PEF vs. 33% in matched controls (p = 0.0007).
• Moore et al., European Journal of Radiology (2025) – 155 patients across five academic centers; mean hospital stay 0.3 days; 84% same-day discharge; pneumothorax rate 21.5%, consistent with percutaneous biopsy; one-year survival 74.6%.
• Moreno-Gonzalez et al., Cancers (2025) – Prospective, multicenter study (N=28) in late-stage NSCLC or metastases to the lung. 96% of patients demonstrated local control. In ablated patients only, who did not have the confounding effects of subsequent therapy, immunophenotyping showed dynamic changes in circulating immune cells and a subset also exhibited modulation of tumor antigen-specific IgG, indicating a systemic humoral response.
• Pritchett et al., J Bronchology & Interventional Pulmonology (2025, AFFINITY Trial) – Prospective multicenter study (n=30); one self-resolving SAE; no arrhythmias or deaths.
• Jimenez et , Journal of Surgical Oncology (2025, INCITE ES Trial) – Early-stage NSCLC surgical cohort; no device-related complications; histopathology showed preserved stromal architecture and immune activation (tertiary lymphoid structures).

Collectively, these studies comprise the strongest body of human data ever published for non-thermal ablation. They demonstrate procedural safety, clinical benefit, and biologic plausibility—all within FDA-cleared labeling.

The draft LCD’s statement that “safety data are limited and adverse event reporting incomplete” is now demonstrably inaccurate. In more than 250 published human cases, no arrhythmias, vascular injuries, or treatment-related deaths have been reported. Safety near critical anatomy is precisely where PEF excels.

From a policy standpoint, CMS has repeatedly granted coverage for energy-based ablation modalities—radiofrequency, microwave, cryoablation, and Aquablation—once multicenter human data established safety and feasibility, even before randomized survival trials. PEF now meets that same standard of evidence maturity.

For the Medicare population, this therapy is reasonable and necessary:

• It provides local control in patients excluded from standard care due to risk or toxicity.
• It can be performed safely in outpatient settings.
• It complements, rather than disrupts, systemic therapy.

I respectfully urge Palmetto to revise the proposed LCD to reflect these data. Specifically:

1. Recognize PEF ablation, its unique design, gating, and safety record.
2. Allow coverage for patients with unresectable, recurrent, or progressive malignancy for whom other options are contraindicated or exhausted.

A blanket non-coverage policy would set back innovation and deny care to precisely the population Medicare was created to serve—patients who need safe, less invasive treatment options that extend both life and quality of life.

Thank you for your comments.

The studies provided too few data to determine Aliya’s safety and effectiveness for treating lung cancer. None of the studies compared Aliya to surgical resection or alternative minimally invasive ablation techniques, and none reported tumor recurrence, survival, or outcomes beyond the perioperative period. The studies are also at high risk of bias from lack of control groups and from retrospective design and being manufactured sponsored studies. Large, prospective, comparative studies that report on long term patient-oriented and oncologic outcomes are needed to validate Aliya for lung cancer. All of the studies cited were case series as well without comparators.

The limitations of this study include the retrospective design and lack of imaging data, which restrict detailed analysis of treatment efficacy and anatomical impact. Additionally, the variability in procedural details, such as the number of activations and probe positioning, highlights the need for standardized protocols to ensure consistency and optimize outcomes. Importantly, there are some additional important missing details, such as the extent of metastatic disease, in this cohort of patients which make the assessment of efficacy limited.

Further, there was no clear inclusion criterion for this study, however, bias was mitigated by the consecutive nature of the cohort collection. Finally, this study was intended to determine if the use of pulsed electric field (PEF) is safe and feasible and not if it improved the outcomes of patients. From Moore et al., European Journal of Radiology, Volume 187, June of 2025.

While the LCD does not address lung cancer specifically, the evidence is of low quality and does not support the treatment for metastatic or primary cancer of the lung with IRE specifically with the use of the Aliya device.

As a community urologist with over 6 years of experience treating men with prostate cancer, I am writing to express my strong support for Medicare coverage of Irreversible Electroporation (IRE) for prostate disease, particularly for intermediate-risk patients and as a salvage therapy after radiation failure. Over the past several years, I have integrated IRE into my practice and witnessed its profound impact on patient outcomes and quality of life. There are many reasons for this.

Firstly, IRE is a much needed middle-ground for patients with intermediate risk disease. For men with intermediate-risk prostate cancer (Gleason 7, PSA 10–20), the treatment landscape has long been polarized: either no treatment (active surveillance) or complete destruction of the prostate (surgery or full-dose radiation), with its attendant risks and potentially devastating effects on quality of life. Many of my patients dread the potential for incontinence or permanent erectile dysfunction. On the other hand, active surveillance poses risks for disease progression, metastasis, and a lifetime of heightened scrutiny for this group. IRE provides a practical middle ground. By selectively ablating only the cancerous region of the prostate, we preserve surrounding tissue and minimize damage to vital structures. In my experience, outcomes have been remarkable. PSA levels drop dramatically, and over 80% of follow-up biopsies show no residual disease. Yet, nearly all of these men maintain urinary control and sexual function. It’s difficult to overstate the difference this makes. Patients who once faced a cure-versus-quality-of-life tradeoff can now have both.

These results are not anecdotal. Although IRE is relatively novel, clinical evidence supports its role in treating prostate cancer. A 2025 systematic review encompassing more than 1,400 prostate IRE patients demonstrated 93–98% freedom from significant cancer at short-term follow-up. Five-year, multi-center data show that over 95% of intermediate-risk men treated focally with IRE remain free from metastasis and cancer-specific death. Importantly, long-term urinary incontinence seen in up to 20% of surgical patients was virtually absent. In my own practice, I have not had a single IRE patient require incontinence management, whereas such referrals are common after surgery and radiation. These findings reinforce IRE as a durable, evidence-supported option that’s delivering real-world results.

Like all emerging technologies, IRE initially met cautious scrutiny, but it has since achieved meaningful acceptance. The AUA 2022 guidelines now include ablation among options for carefully selected intermediate-risk patients, emphasizing shared decision-making. The FDA’s clearance of IRE for soft tissue ablation, including prostate tissue, confirms its legitimacy as a medical device for this purpose. Moreover, the forthcoming CPT Category I code for prostate IRE reflects its growing recognition within the broader medical community. Together, these developments make a strong case that Medicare coverage aligns squarely with the direction of modern practice.

IRE also offers a lifeline for men with recurrence after radiation a population with few curative options. One of my patients, a 84-year-old man previously treated with radiation, developed a local recurrence. He was not a surgical candidate and had crippling fatigue and hot flashes with hormone therapy. We treated him with IRE, and a year later his PSA has normalized, with no urinary symptoms or discomfort. Without IRE, he would have had no curative path. Compared with salvage cryotherapy, IRE is significantly gentler with no freezing, less fibrosis, and far lower risks to continence. Given that Palmetto already covers salvage cryotherapy, extending coverage to IRE is a logical and clinically consistent step, especially considering studies like the FIRE trial, which report 70–80% local control rates.

The human impact of IRE is impossible to ignore. Patients and their partners often share how relieved they are that cancer treatment didn’t mean losing intimacy or independence. Many return to daily activities within days. These may seem like small details, but for men in their 60s and 70s, maintaining function and dignity is invaluable. Medicare’s mission is to support health and vitality in older adults; IRE fulfills that mission by eradicating cancer while preserving quality of life.

In summary, I urge Palmetto to finalize LCD DL40205 to cover IRE for intermediate-risk prostate cancer and for salvage therapy under appropriate selection criteria. IRE has become an essential part of my prostate cancer practice as an option that is FDA-cleared, guideline-endorsed, and clinically validated by growing real-world data. It closes a well-known treatment gap by offering cure without compromise. By approving coverage, Palmetto can ensure that men across our region have access to a therapy that controls disease while maintaining what matters most: their quality of life.

Thank you for your thoughtful consideration.

Thank you for your comments.

See comments #2 and #4 above.

I am a urologic oncologist specializing in advanced and recurrent prostate cancer. I’ve managed many patients after they’ve undergone radiation, and I’ve seen the challenges in offering them curative options when their cancer returns. I’m writing to strongly support Medicare coverage for Irreversible Electroporation (IRE) in two scenarios: (1) intermediate-risk primary prostate cancer and (2) salvage treatment for radio-recurrent prostate cancer. I want to particularly emphasize the second indication, as it often gets less attention but represents a critical unmet need that IRE finally addresses.

Salvage Prostate Cancer – A New Hope: When a patient’s prostate cancer recurs after radiotherapy, we face an uphill battle. Salvage radical prostatectomy is technically demanding and quite risky – in my practice, I reserve it only for the healthiest patients because complications like incontinence (up to 60%), stricture, and even fistula are unfortunately common. Many patients aren’t candidates at all due to age or comorbidities. Cryotherapy has been an alternative, which Medicare covers, but in my experience cryo can cause significant tissue damage in a previously irradiated prostate (I’ve seen cases of sloughing tissue and prolonged catheterization). This is where IRE has been revolutionary. Because IRE doesn’t rely on extreme temperatures, the collateral damage to tissues is minimal, even in a fibrosis-laden post-radiation environment. I have now treated patients with salvage IRE in the past 3 years. Among those, cancer control has been achieved (no detectable disease on imaging or biopsy at 1 year) in 6 out of 8 – a success rate on par with what we’d expect from salvage surgery, frankly. And importantly, not one of these patients became permanently incontinent; two had some stress urinary leakage initially, but within a few months they recovered to pad-free status. Zero patients had significant rectal or urethral injury. This safety profile and efficacy in salvage are echoed by the “FIRE” trial and other published series which show around 75% local control and over 90% urinary continence preservation. For patients who otherwise might be consigned to lifelong hormone therapy (with its systemic side effects), IRE offers a chance at true remission with minimal downside. They often tell me it feels like a second lease on life.

Intermediate-Risk Disease – Modernizing Treatment: While salvage is my particular passion, I want to also underscore the importance of covering IRE for primary intermediate-risk prostate cancer. The current standard approach for a man with a Gleason 3+4 tumor has been radical prostatectomy or radiotherapy. But we know these treatments come at a cost – often unnecessary in hindsight if the cancer was only in one part of the prostate. IRE allows a “middle path” of treating just the affected part of the prostate and preserving everything else. We’ve done focal IRE for many such patients as part of a focal therapy program. The outcomes have been outstanding. Meanwhile, nearly all report unchanged or even improved urinary function (some men’s urinary symptoms improve because we’re not doing whole-gland treatment that irritates the bladder). Erectile function is largely maintained; only a small subset with baseline issues remained significantly impaired. These results mirror published studies. The field is embracing focal therapy for appropriate patients. The AUA and ASTRO guidelines in 2022 make it clear that we are to consider ablation in intermediate-risk men, reflecting an awareness that we have to balance cancer control with quality of life. I often cite to my peers that even the National Comprehensive Cancer Network (NCCN) has started to mention ablation: in the NCCN Prostate Cancer panel discussions, IRE has been acknowledged as a technology under evaluation, especially for those who can’t have surgery.

Medical Necessity and Fair Access: As someone who provides these services, I see coverage as a matter of fairness and medical necessity. We have Medicare patients right now who meet all the criteria for IRE and would clearly benefit, but the lack of coverage creates barriers. Some attempt to pay out-of-pocket (which many cannot afford – this is an expensive procedure for an individual to self-fund), and sadly some simply end up getting a treatment not optimal for them (e.g., they undergo a surgery they never wanted, or conversely they stay on surveillance when they actually would prefer treatment if side effects weren’t so dire). Covering IRE will allow patients and doctors to truly choose the best personalized option without financial coercion. It’s also worth noting the healthcare economics: by avoiding complications like incontinence or lengthy hospital stays, I suspect IRE can save money in the long run.

In Summary: I strongly endorse modifying LCD DL40205 to cover IRE for intermediate-risk and salvage prostate cancer indications. The criteria can be well-defined (unifocal or unilateral disease confirmed on MRI/biopsy for intermediate-risk; organ-confined recurrence for salvage; done by experienced providers; etc.) to ensure appropriate use. As a physician deeply involved in prostate cancer care, I want to be able to offer my patients the full spectrum of care innovations that modern medicine has validated. IRE is one such innovation – not experimental hype, but a real advance that has been proven to preserve quality of life without compromising cancer outcomes in the right patients.

Thank you for considering my perspective and the evidence behind it.

Thank you for your comments.

Please see comments #2, #4 and #8 above.

I am writing in support of coverage for irreversible electroporation (IRE) as outlined in Draft LCD DL40205. As an attending urologist, I have embraced IRE for treating men with intermediate-risk prostate cancer, and I want to share why I believe Medicare coverage is both justified and vital at this time.

I see IRE becoming a new standard for a subset of prostate cancer, and I firmly believe coverage under LCD DL40205 is warranted. We are at the point where evidence, expert opinion, and patient preference all align in supporting IRE for appropriately selected cases. By approving coverage, Palmetto will ensure that our Medicare patients can continue to benefit from this advancement without undue financial burden or delay.

Thank you for your comments.

Please see comments #2 and #4 above.

I am a prostate cancer patient aged 62.

I believe that irreversible Electroporation for Cancer (DL40205) is a technology that can provide the most reasonable and necessary treatment for my diagnosis and other soft tissue cancer diagnoses. Unfortunately, it is not a covered procedure under Medicare.

The ability of irreversible Electroporation for Cancer to be used for treatment of cancer such as mine is so beneficial in that the treatment can be carried out without compromising surrounding tissue. This advanced technology is vitally important to treatments such as mine. Quality of life and potential successful treatment is paramount for patients such as me.

In my case, the treatment may allow some function of the prostate to be retained while at the same time, elimination of the cancer cells.

The most important part would be inclusion of this treatment in Medicare so that patients without private insurance can receive the same benefits as those that do.

In the long run, the irreversible Electroporation for Cancer (DL40205) must be available to Medicare patients as this treatment will provide significant savings by reduction of risk while providing an effective treatment regime. This is at a lower total cost due to reduced side effects and follow-up procedures.

I strongly request that the proposed LCD be incorporated into the Medicare system for coverage to those with Medicare.

Thank you for your comments.

Please see comment #1 above.

I am writing to strongly support coverage for Irreversible Electroporation (IRE) under Draft LCD DL40205, specifically for men with intermediate-risk prostate cancer and for those with localized recurrence after radiation (salvage cases). As an Associate Professor of Urologic Oncology who has both investigated and provided IRE in practice, I can attest that this therapy fills a critical gap in prostate cancer care.

It is first imperative to understand that patients expect their cancer treatments to offer them a balance between cancer control and preservation of quality of life. There is a shift in consumer (patient) sentiment away from accepting the most aggressive cancer treatment as the only option, toward therapies that minimize side effects while also being effective. The treatment that has the best cancer control, if it also has the greatest side effects, is not necessarily the best treatment for a patient. Ablation of prostate cancer fits squarely into this domain as it provides effective cancer control while minimizing the risk of significant side effects compared to standard radical therapies like surgical removal and radiation therapies. Cancer control of subtotal therapies may not be equivalent to that of a radical treatment with a single intervention, but there is increasing evidence that with or without repeat subtotal interventions, the time to requiring a salvage radical therapy is very similar between the ablation therapies and surgery or radiation. Furthermore, patients who undergo one or multiple ablation therapies have significantly better quality of life in terms of sexual and urinary function compared to those undergoing initial radical therapy (Surgery/Radiation). Patients want a choice, and it is appropriate to allow them to choose between effective cancer treatments that prioritize quality of life vs those that prioritize up front cancer control with a decreased quality of life.

Please see below for the data supporting the above summary.

Clinical Rationale & Evidence: The evidence base for IRE has expanded significantly in the last few years. A large 2024 meta-analysis (19 studies, ~1,450 patients) confirms that focal IRE achieves excellent oncologic control in intermediate-risk disease while preserving quality of life. Across these studies, 3-year freedom from cancer progression was about 90–97%, with 95–100% of patients retaining urinary continence and the majority maintaining sexual potency – outcomes that are simply unattainable with radical surgery or radiation in this population. In my own series, our results mirror these findings: to date, none of my IRE patients have developed metastases, and almost all remain pad-free and sexually active. These tangible benefits meet Medicare’s “reasonable and necessary” definition, providing equal cancer control with fewer complications.

Moreover, the PRESERVE trial – a U.S. multi-center prospective study – reported 84% of intermediate-risk patients had no significant cancer on 1-year biopsy after IRE. This trial’s success was a basis for the FDA’s 2023 clearance of IRE for prostate tissue ablation and the AMA’s approval of a Category I CPT code (effective 2026). In other words, our regulatory and professional bodies have vetted IRE’s safety and efficacy. We also now have 5-year data (Scheltema et al. 2023) showing 99% metastasis-free survival and 100% cancer-specific survival at 5 years post-IRE for localized disease – essentially equivalent to outcomes of surgery or beam radiation in similar patients, but achieved with far less morbidity. As a physician, it is remarkable to be able to offer my patients a treatment that controls their cancer and spares them from incontinence or lifelong erectile dysfunction.

The Palmetto review cites data that ablation therapies have similar outcomes across technologies. When considering long-term outcomes, it is then reasonable to consider the experience of cryoablation and HIFU that have been around longer and have comparative studies demonstrating similar long-term oncologic outcomes. A study by Brundl et al (E. Urol Focus 2022) shows long term efficacy of HIFU with a mean survival of 15 years, and excellent survival rates for low and intermediate risk men treated with HIFU. Similarly, Deivasigamani et al (European Urology 2023) reported a Focal Therapy Society Best Practice Statement citing the published evidence that mid- to long-term real-world data support the safety and efficacy of HIFU and Cryoablation, with median follow up of some of the studies over 14 years and 10-yr cancer specific survival of 96%. Retrospective comparative analyses using different propensity matching strategies found equivalent overall survival and cancer specific survival at 10 years between HIFU and radiation (Yeh et al, International Urology and Nephrology 2025), and between focal therapy (including HIFU and cryoablation) and radical prostatectomy with 8 years of follow up (Shah TT, Prostate and Prostatic Disease 2021). In addition, the prospective non-inferiority HIFI trial found HIFU to be non-inferior to RP in terms of salvage free survival with moderate (30 month) follow up (Ploussard et al, 2025, European Urology).

Guideline Support: It’s important to clarify the stance of our clinical guidelines. The 2022 American Urological Association (AUA) guidelines explicitly state that energy-based ablation “may be considered in select, appropriately informed patients” with intermediate-risk prostate cancer. The AUA panel notes that while long-term comparative data are still maturing, focal therapies like IRE are a valid option for these patients, who otherwise face the difficult choice between overtreatment and under-treatment. This nuance wasn’t fully captured in the draft LCD summary – in fact, IRE is referenced in the AUA guidelines (Guideline Reference #129) and even included in the AUA’s Core Curriculum for resident education. In practice, offering focal ablation is within the standard of care for intermediate-risk men who desire cancer control with less impact on lifestyle. By aligning coverage with this AUA-endorsed approach (and similarly cautious NCCN mentions of IRE as investigational but feasible), Palmetto will support patient-centered care consistent with current urologic practice.

The data supporting ablation therapy for the treatment of prostate cancer is now available to support its efficacy compared to surgery and radiation, and clearly demonstrates significantly enhanced patient recovery in terms of quality of life factors such as rapid return to work, increased preservation of sexual function, and minimal negative impact on urinary function (with many patients experiencing an improvement). As a newer technology IRE does not yet have 10-year or more follow up, but has met or exceeded the outcomes established by older ablation techniques at all time points and in all survival and QOL areas.

Conclusion: I strongly urge Palmetto to finalize LCD DL40205 with a positive coverage determination for IRE in intermediate-risk and salvage prostate cancer, with appropriate criteria. Such a policy would be firmly grounded in evidence and be guideline-supported. It would acknowledge that IRE is no longer “experimental” but an accepted medical technology– FDA-cleared, peer-reviewed, and taught in our training programs. Most importantly, it would give Medicare beneficiaries access to a treatment that can eradicate cancer while preserving normal life function. In my view, there is no question that this meets the bar of being reasonable and necessary.

Thank you for your consideration of these comments.

Thank you for your comments.

Please see comments #2 and #4 above.

No differences were noted between cryotherapy, high-intensity focused ultrasound (HIFU), or IRE in any of the outcomes. The authors noted that FT with any of these modalities was associated with good short-intermediate term oncological outcomes; however, the outcome reporting was heterogenous, not-blinded and was incomplete in many of the studies. Long-term follow-up and standardized reporting were recommended to better define and report outcomes. Due to lack of randomization, blinding and heterogeneity, and low quality of the studies, IRE cannot be recommended over other treatment modalities at this time.

We appreciate the chance to share our perspective on the Palmetto Draft Local Coverage Determination for Irreversible Electroporation (IRE) for Cancer (DL40205).

We have seen how focal ablation therapies—like IRE, cryotherapy, and HIFU—can make a real difference for men with intermediate-risk prostate cancer. These options are not just about treating cancer; they’re about giving patients choices that fit their lives and values. Many of my patients want to avoid the side effects of more invasive treatments, and they are grateful to have alternatives that let them stay active and independent.

The 2022 American Urological Association (AUA) and American Society for Radiation Oncology (ASTRO) guidelines support this approach. They state:

“Currently, the Panel believes that ablation may be considered in select, appropriately informed patients (with clinical trial enrollment prioritized). Patients being considered for ablation should have intermediate-risk prostate cancer, as data supporting treatment of high-risk disease with ablation are lacking, while patients with low-risk cancers should be preferentially managed with active surveillance.” — Clinically Localized Prostate Cancer: AUA/ASTRO Guideline (2022)

This consensus makes it clear: focal ablation is a reasonable and necessary option for the right patients. In our experience, these therapies are particularly valuable for individuals seeking a less invasive approach and who are actively involved in making decisions about their care.

We hope Palmetto will continue to support the integration of focal therapies like IRE into clinical practice. These treatments are not just backed by evidence—they are making a difference in the lives of real patients. Coverage for IRE will help ensure that men with intermediate-risk prostate cancer have access to care that fits their needs and preferences.

Thank you for considering these comments.

Thank you for your comments.

Please see comments #2 and #4 above.

I am writing in support of LCD DL40205 – Coverage by Palmetto for Irreversible Electroporation (IRE), with the NanoKnife IRE device. I am a urologist, with nearly thirty years of clinical experience, since entering practice in 1996. Throughout my career, I have performed many successful radical prostatectomies and have witnessed the significant positive and negative impacts these surgeries can have on patients. Incontinence and impotence are frequent, occasionally devastating, outcomes, and in hindsight, many patients with minimal intermediate-risk disease could have benefitted from a less invasive, more targeted approach.

I find the Nanoknife IRE technology to be game changing in its ability to minimize risk and simultaneously fill the void for intermediate grade low volume cancer treatment as another option to consider.

Both recent scientific evidence and my own clinical experience support the use of focal treatments, such as Nanoknife Irreversible Electroporation (IRE), and others focal treatment modalities, for men with intermediate-risk prostate cancer. Many patients with low-volume, intermediate-risk disease also struggle with the uncertainty of active surveillance and face considerable anxiety when the need for intervention arises. Coverage considerations and broader perspectives on the role of focal therapy are also reflected in current healthcare news coverage, including Medical Economics News (October 13, 2025).

Nanoknife IRE focal ablation offers precise, tissue-sparing therapy for suitable patients. The PRESERVE Trial (Fainberg & Coleman, EAU 2025) demonstrated cancer control and truly minimal functional side effects. My practice experience mirrors these findings—patients treated with focal IRE typically maintain continence and sexual function, at rates well above those seen with traditional surgery. Additionally, IRE does not burn bridges, in case adjuvant treatment is needed down the road.

The Nanoknife IRE system received FDA 510 K clearance for prostate tissue ablation in late 2024. The NanoKnife System was granted a category I CPT code for prostate and liver lesion ablations, effective January 1, 2026. TIME Magazine’s recognition of Nanoknife as one of the Best Inventions of 2025 highlights its innovation and impact on patient care. The American Urological Association’s 2022 guidelines recognize focal ablation as an appropriate option for select prostate cancer patients.

Medicare coverage for therapies such as Nanoknife IRE is an important step forward, supporting individualized care, reducing morbidity, and aligning with current evidence and best practices.

Thank you for your consideration.

References cited in comment received.

Thank you for your comments.

See comments #2 and #4 above.

The NanoKnife has been around since 2009, and popularity of a device does not equate to reasonable and necessary coverage.

I am 77 years old and was diagnosed with suspected prostate cancer in late 2024 (based on a spike in my PSA levels). I was sent to a urology specialist and went through a series of tests, culminating in a prostate biopsy and a CT scan. The final diagnosis was a non-metastasized localized prostate cancer, with a Gleason score of 3+4 (Favorable Intermediate Risk).

My urology specialist recommended consideration of the NanoKnife procedure, also known as Irreversible Electroporation (IRE), and I was also presented with other treatment options. I conducted my own research, including discussions with other prostate cancer sufferers. I concluded that NanoKnife carried significant lower risks of side effects (notably affecting urinary and sexual function which would have greatly affected my quality of life). After consultation with my urologist, I chose NanoKnife and transferred my care to a second specialist, who is extremely conversant with this procedure. The key issues for me were NanoKnife’s minimally invasive therapy and its ability to target cancerous tissue while preserving surrounding structures.

The procedure was conducted on August 22, 2025 on an outpatient basis. I left the hospital an hour after waking and returned home. I was able to resume normal activities within a couple of days after the procedure. The only discomfort was the need for a catheter for a week after the procedure. The whole recovery was painless (not even requiring a Tylenol).

Six weeks after the procedure, follow-up tests confirmed that PSA levels had dropped to half the previous values.

I am deeply grateful to have had access to this advanced technology. From my own personal experience, I now consider that NanoKnife is a vital option for patients seeking effective treatment of localized prostate cancers without the burden of more invasive surgeries or radiation therapy. I hope others will continue to benefit from this FDA approved approach to care.

Discontinuing coverage would remove a proven, life-enhancing choice for men facing prostate disease. I therefore respectfully recommend that Palmetto MAC maintains coverage for NanoKnife, also known as Irreversible Electroporation (IRE).

Thank you for your comments.

Please see comment #1 above.

I am a urologic oncologist specializing in advanced and recurrent prostate cancer. I’ve managed many patients after they’ve undergone radiation, and I’ve seen the challenges in offering them curative options when their cancer returns. I’m writing to strongly support Medicare coverage for Irreversible Electroporation (IRE) in two scenarios: (1) intermediate-risk primary prostate cancer and (2) salvage treatment for radio-recurrent prostate cancer. I want to particularly emphasize the second indication, as it often gets less attention but represents a critical unmet need that IRE finally addresses.

Salvage Prostate Cancer – A New Hope: When a patient’s prostate cancer recurs after radiotherapy, we face an uphill battle. Salvage radical prostatectomy is technically demanding and quite risky – in my practice, I reserve it only for the healthiest patients because complications like incontinence (up to 60%), stricture, and even fistula are unfortunately common. Many patients aren’t candidates at often due to age or comorbidities. Cryotherapy has been an alternative, which Medicare covers, but in my experience cryotherapy can cause significant tissue damage in a previously irradiated prostate (I’ve seen cases of sloughing tissue and prolonged catheterization). This is where IRE has been revolutionary. Because IRE doesn’t rely on extreme temperatures, the collateral damage to tissues is minimal, even in a fibrosis-laden post-radiation environment. I have now treated several patients with salvage IRE in the past 3 years. Among those, cancer control has been achieved (no detectable in-field recurrence on imaging or biopsy at 1 year), a success rate on par with what we’d expect from salvage surgery, frankly. And importantly, not one of these patients became permanently incontinent to my knowledge. Zero patients had significant rectal or urethral injury. This safety profile and efficacy in salvage are echoed by the “FIRE” trial and other published series which show around 75% local control and over 90% urinary continence preservation. For patients who otherwise might be consigned to lifelong hormone therapy (with its systemic side effects), IRE offers a chance at true remission with minimal downside. They often tell me it feels like a second lease on life.

Intermediate-Risk Disease – Modernizing Treatment: While salvage is my particular passion, I want to also underscore the importance of covering IRE for primary intermediate-risk prostate cancer. The current standard approach for a man with Gleason (3+4) 7 (GG2) tumor has been radical prostatectomy or radiotherapy. But we know these treatments come at a cost – often unnecessary in hindsight if the cancer was only in one part of the prostate. IRE allows a “middle path” of treating just the affected part of the prostate and preserving everything else. We’ve done focal IRE for many such patients at our institution as part of a focal therapy program. The outcomes have been outstanding: our data on intermediate-risk patients. Meanwhile, nearly all report unchanged or even improved urinary function (some men’s urinary symptoms improve because we’re not doing whole-gland treatment that irritates the bladder). Erectile function is largely maintained; only a small subset with baseline issues remained significantly impaired. These results mirror published studies. The field is embracing focal therapy for appropriate patients. The AUA and ASTRO guidelines in 2022 make it clear that we are to consider ablation in intermediate-risk men, reflecting an awareness that we have to balance cancer control with quality of life. I often cite to my peers that even the National Comprehensive Cancer Network (NCCN) has started to mention ablation: in the NCCN Prostate Cancer panel discussions, IRE has been acknowledged as a technology under evaluation, especially for those who can’t have surgery.

Medical Necessity and Fair Access: As someone who provides these services, I see coverage as a matter of fairness and medical necessity. We have Medicare patients right now who meet all the criteria for IRE and would clearly benefit, but the lack of coverage creates barriers. Some attempt to pay out-of-pocket (which many cannot afford – this is an expensive procedure for an individual to self-fund), and sadly some simply end up getting a treatment not optimal for them (e.g., they undergo a surgery they never wanted, or conversely they stay on surveillance when they actually would prefer treatment if side effects weren’t so dire). Covering IRE will allow patients and doctors to truly choose the best personalized option without financial coercion. It’s also worth noting the healthcare economics: by avoiding complications like incontinence or lengthy hospital stays, I suspect IRE can save money in the long run.

In Summary: I strongly endorse modifying LCD DL40205 to cover IRE for intermediate-risk and salvage prostate cancer indications. The criteria can be well-defined (unifocal or unilateral disease confirmed on MRI/biopsy for intermediate-risk; organ-confined recurrence for salvage; done by experienced providers; etc.) to ensure appropriate use. As a physician deeply involved in prostate cancer care, I want to be able to offer my patients the full spectrum of care innovations that modern medicine has validated. IRE is one such innovation – not experimental hype, but a real advance that has been proven to preserve quality of life without compromising cancer outcomes in the right patients.

Thank you for considering my perspective and the evidence behind it.

Thank you for your comments.

Please see comments #2, #4 and #8 above.

I write to express concerns with the recent non-coverage local coverage determination (LCD) for irreversible electroporation (IRE). If finalized as currently drafted, this non-coverage determination would prohibit Medicare patients access to an innovative, minimally invasive procedure to treat prostate and other cancers.

In late 2024, NanoKnife received a 510(k) clearance from the U.S. Food and Drug Administration (FDA) for use in prostate tissue ablation. Most recently, the CY 2026 Medicare Physician Fee Schedule final rule published the new Category I CPT code, 55877, for IRE of the prostate, allowing physicians for the first time to directly bill and receive RVUs for the modality. Palmetto's non-coverage LCD presents a barrier for patients and stands in contrast to newly created Medicare reimbursement for such procedure.

The basis for FDA clearance came after the conclusion of the PRESERVE Trial, the first large prospective study in the US, which provided a study of 121 patients with intermediate-risk prostate cancer treated with focal tissue ablation of the index lesions using IRE. Using the Delphi consensus criterion, 84% of patients enrolled had no clinically significant cancer in the treated zone at 12 months. The time to median PSA nadir was 3.5 months, and the median percent reduction in PSA at 6 months was 68.2%.

Additionally, significant quality of life outcomes for men and their families were evident, as 84% of patients with good baseline sexual function maintained erections sufficient for penetration at 12 months. On the UCLA-EPIC urinary domain, mean change from baseline to 12 months was +3 points; on the International Prostate Symptom Score (IPSS) the mean change was -2 points at 12 months. Such results should additionally provide cost savings to the Medicare program and other payors.

A separate meta-analysis from Zhang et al published in 2025 of ~1,450 localized prostate cancer patients treated with IRE found that the three-year failure-free survival was reported between 90-96.8%. Additionally, postoperative urinary continence ranges between 96.7-100%, demonstrating a high quality-of-life for patients and validating efficacy of IRE for certain cohorts.

Furthermore, current American Urological Association (AUA) guidelines state ablation may be considered in appropriately selected, informed patients with intermediate-risk prostate cancer. This current negative coverage policy contradicts the AUA guidelines which I fear would create an imbalance of appropriate treatment options for patients and providers.

IRE presents the first major change in over 50 years for men diagnosed with clinically localized prostate cancer. Given the disparity of non-thermal, minimally invasive procedures for localized prostate cancer of Medicare beneficiaries, I respectfully request Palmetto consider the impact a non-coverage determination for IRE has on a significant subset of prostate cancer patients. Medicare beneficiaries deserve access to every safe and effective therapy to treat prostate cancer. IRE meets this criteria by maintaining quality of life with the ability to treat all segments of the prostate gland, while current modalities covered by Palmetto MAC do not have this versatility.

References cited in comment received.

Thank you for your comments.

Please see comments #2, #4 and #8 above.

I am writing to express my strong support for coverage of Irreversible Electroporation (IRE) under Draft LCD DL40205—specifically for men with localized recurrence after radiation therapy (salvage cases) and for ablation of intermediate-risk prostate cancer. I have performed over 50 IRE treatments, including 8 for post-radiation recurrence (salvage). This therapy fills a critical gap in prostate cancer care.

IRE in the Salvage Setting After Radiation Recurrence

IRE provides an essential treatment option for men with radiation-recurrent prostate cancer, where conventional salvage therapies are often prohibitively morbid. Historically, surgical removal of the prostate (salvage prostatectomy) has been the standard option for these patients, but it carries high morbidity—with long-term incontinence rates exceeding 50% and rectal injury rates up to 10%, sometimes requiring colostomy. Many patients decline salvage prostatectomy due to these risks, leading to disease progression and reliance on costly, morbid systemic therapies.

The 2025 National Comprehensive Cancer Network (NCCN) Prostate Cancer Guidelines now list IRE as a Category 2B option for localized recurrence, alongside cryotherapy and HIFU. As these guidelines are the gold standard for multidisciplinary cancer care in the United States, IRE’s inclusion underscores its clinical validity. Compared with HIFU and cryotherapy, IRE offers technical advantages in targeting certain anatomic regions, expanding the range of treatable recurrences.

Because Medicare already covers cryotherapy in this setting, extending comparable coverage to IRE is both logical and equitable. In my own practice, 7 of 8 patients (88%) treated with salvage IRE have no evidence of residual cancer at six months post-treatment. Denying coverage would restrict access to a potentially curative, guideline-supported therapy for Medicare beneficiaries.

Clinical Rationale and Evidence for Primary Prostate Ablation

Primary IRE ablation has shown strong efficacy and safety. The PRESERVE trial, a U.S. multicenter prospective study (with Mayo Clinic as a lead site), demonstrated that 84% of intermediate-risk patients had no clinically significant cancer on one-year biopsy after IRE. These findings contributed to the FDA’s 2024 clearance of IRE for prostate tissue ablation and the AMA’s approval of a Category I CPT code, effective in 2026.

In clinical practice, I have performed more than 40 IRE procedures for localized intermediate-risk prostate cancer. Patients consistently experience excellent oncologic and functional outcomes—durable cancer control with preserved continence and sexual function. None of our IRE-treated patients have developed metastases, and nearly all remain pad-free and sexually active. These outcomes clearly meet Medicare’s definition of “reasonable and necessary,” providing equivalent cancer control with substantially fewer complications than surgery or radiation.

Long-term results further reinforce these findings. A five-year study (Scheltema et al., Eur Urol Open Sci, 2023) reported 99% metastasis-free and 100% cancer-specific survival after IRE for localized disease—outcomes comparable to surgery or radiation but with far less morbidity. While up to 20% of patients may ultimately require additional local therapy (radiation or surgery), these treatments can be safely administered post-IRE. The RTIRE Phase II trial (IRE followed by whole-gland radiation) demonstrated excellent safety with very low rates of grade ≥3 toxicity. Notably, even after radical prostatectomy, more than 30% of intermediate-risk patients require additional therapy, underscoring that IRE’s retreatment rate is favorable.

A 2024 meta-analysis of 19 studies (~1,450 patients) further confirmed that IRE achieves excellent oncologic control while maintaining quality of life: three-year freedom from progression of 90–97%, 95–100% urinary continence, and high preservation of sexual function—results rarely achieved with radical prostatectomy or radiation. As a clinician, it is uncommon to offer a therapy that provides cancer control while preserving continence, potency, and overall quality of life.

Conclusion

I strongly urge Palmetto to finalize LCD DL40205 with a positive coverage determination for IRE—both for salvage prostate cancer and for primary intermediate-risk prostate cancer under appropriate clinical criteria.

This decision would align with national guidelines, reflect robust clinical evidence, and recognize FDA and AMA validation of IRE as a safe, effective, and established technology. Most importantly, it would ensure equitable access for Medicare beneficiaries to a treatment that provides cancer control without the devastating side effects of traditional therapies.

Thank you for your thoughtful consideration. I appreciate Palmetto’s leadership in advancing evidence-based, patient-centered coverage policies for prostate cancer care.

Thank you for your comments.

Please see comments #2, #4 and #8 above.

We respectfully request that Palmetto GBA reconsider the proposed non-coverage determination and instead issue a revised, differentiated coverage policy recognizing the distinct safety, mechanism, and clinical evidence supporting Pulsed Electric Field (PEF) ablation.

The draft LCD groups all electroporation-based ablation under “IRE” and concludes that such procedures are investigational, citing limited safety data, incomplete adverse event reporting, and no consistent evidence of benefit across tumor types. These statements no longer reflect the published body of peer-reviewed human data on PEF ablation generated since 2024.

Overview

PEF ablation represents a non-thermal, cell-selective ablation modality that induces tumor cell apoptosis while preserving connective tissue, vasculature, and airways. Unlike traditional IRE or thermal ablation, the Aliya® System delivers biphasic, cardiac-gated, non-thermal pulses through a single monopolar electrode, avoiding the Joule heating, muscle stimulation, and multi-needle placement required for IRE.

This next-generation mechanism directly addresses the limitations cited in earlier IRE safety assessments—maintaining structural integrity of vessels and ducts while reducing procedural morbidity. The technology is FDA 510(k)-cleared for surgical soft-tissue ablation (K212871) and is in routine clinical use at more than 160 centers, including over 50 U.S. academic centers.

Clinical Evidence Supporting Coverage

Survival and Disease Control (Efficacy)

The following studies demonstrate that PEF ablation provides both tumor control and systemic benefits in patients with a range of cancers who have failed other therapies.

Together, the Moore et al., Lung Cancer (2025) and Moore et al., European Journal of Radiology (2025) studies comprise over 190 patients across eight academic centers, representing the largest multi-center dataset for any non-thermal ablation platform.

In a multicenter matched-cohort study published in Lung Cancer (2025), Moore et al. evaluated the use of Aliya PEF ablation in patients with progressive stage IV non–small cell lung cancer (NSCLC) who had failed prior systemic therapy. The study demonstrated a one-year progression-free survival (PFS) of 63% in the PEF cohort compared to 12% in matched controls (p < 0.0001) and a one-year overall survival (OS) of 74% versus 33% (p = 0.0007). No procedure-related deaths occurred, and the only significant procedural complication—pneumothorax in 5 of 41 patients—resolved without sequelae. These findings show a clear, statistically significant survival benefit in a refractory patient population with limited treatment options.

In a separate multicenter safety and feasibility analysis published in the European Journal of Radiology (2025), Moore et al. reported outcomes from 155 patients treated across five academic institutions for a range of thoracic and abdominal malignancies. The mean hospital stay was only 0.3 days, with 84% of patients discharged the same day. No liver complications were observed, and the pneumothorax rate for lung cases (21.5%) was consistent with or better than that seen with established modalities such as cryoablation or microwave ablation. The one-year overall survival across all cancer types was 74.6%, confirming the reproducible safety profile and favorable recovery associated with PEF ablation.

Most recently, Moreno-Gonzalez et al., Cancers (2025) published a prospective, multicenter study (N=30) in late-stage NSCLC or metastases to the lung with local control demonstrated in 96% of patients. In ablation-only patients, who did not have the confounding effects of subsequent therapy, immunophenotyping showed dynamic changes in circulating immune cells and a subset also exhibited modulation of tumor antigen-specific IgG, indicating a systemic humoral response.

The above studies provide additional data that were not considered in the draft LCD and which render the LCD statement that “no human data demonstrate tumor control or systemic benefit” incorrect.

Procedural and Structural Safety

These studies collectively demonstrate that PEF ablation can be delivered safely across thoracic, abdominal, and soft-tissue sites—a key concern raised in the LCD.

The AFFINITY Trial by Pritchett et al., published in the Journal of Bronchology & Interventional Pulmonology (2025), was a prospective, five-center study involving 30 patients who underwent Aliya PEF ablation. The study reported only one procedure-related serious adverse event—a self-resolving pneumothorax—with no arrhythmias, therapy delays, or deaths.

In a separate study published in JVIR (2024), Suh et al. evaluated 17 patients who underwent 26 PEF procedures. Only one moderate adverse event occurred, and all other complications were mild and self-limited, confirming a strong safety and tolerability profile across multiple organ systems.

Finally, Hunter et al. (Journal of Thoracic Disease, 2025) demonstrated that Aliya PEF ablation can be safely delivered within 5–6 millimeters of critical thoracic structures such as bronchi and pulmonary arteries without causing tissue injury, further supporting the precision and safety of this non-thermal energy modality.

Collectively, these data directly refute LCD statements that safety and tolerability are “unproven.”

Mechanistic and Immunologic Rationale

Jimenez et al., Journal of Surgical Oncology (2025, INCITE ES Trial) confirmed histologic preservation of stroma and vasculature, while demonstrating post-PEF tertiary lymphoid structures (TLS) indicative of immune activation. Similarly, Kuhlman et al., Gynecologic Oncology Reports (2025) described a documented abscopal immune response in metastatic melanoma following Aliya PEF ablation.

These findings establish a plausible biologic mechanism for systemic benefit, addressing another LCD critique that “mechanism of action remains speculative.”

Clinical Rationale for Coverage

The draft LCD’s rationale—that “no human data demonstrate tumor control or systemic benefit”—is now outdated. Peer-reviewed, multi-institutional data demonstrate consistent local control, survival improvement, and durable safety, meeting CMS’s “reasonable and necessary” standard as defined in the Program Integrity Manual §13.5.4.

Patients who are ineligible for surgery, radiation, or systemic therapy are not untreated by choice; they are excluded because existing modalities force tradeoffs between efficacy and tolerability. Standard-of-care options often carry unacceptable cardiopulmonary, immunologic, or procedural risks in elderly or frail patients. PEF ablation addresses this therapeutic gap by providing a local, structure-sparing option that controls disease without imposing the physiologic burden of surgery or the collateral damage of thermal energy or radiation. In this way, PEF is both a treatment for patients with no other options and a solution to the compromises inherent in other treatments, i.e., surgery chemotherapy and other ablative modalities.

PEF is being used in multidisciplinary care for patients who have exhausted all other treatments, particularly elderly or comorbid Medicare beneficiaries who are poor surgical candidates. The magnitude of survival benefit reported in Moore et al. (2025)—more than double one-year survival—meets or exceeds coverage thresholds historically applied to new ablative modalities such as radiofrequency, microwave, cryoablation, and aquablation, which CMS covered at comparable evidence stages.

Request for Revision of LCD DL40205

Given the new human safety and efficacy evidence and the distinct FDA-cleared mechanism of the Aliya^® System, we respectfully request that Palmetto GBA:

1. Differentiate PEF from legacy IRE within the LCD text, recognizing its biphasic waveform, single-electrode design, cardiac gating, and safety record.
2. Revise the determination to allow coverage for patients with unresectable, recurrent, or progressive solid tumors where other ablative or systemic options are contraindicated or exhausted.
3. Establish a prior authorization pathway allowing coverage of PEF ablation on a case-by-case basis when:

• The procedure is performed with an FDA-cleared PEF device;
• The patient has unresectable, recurrent, or progressive disease after standard therapy; and
• Treatment occurs at a qualified center with physician credentialing and participation in ongoing data collection.

4. At minimum, defer a final non-coverage decision pending completion of the ongoing AFFINITY and prospective multi-center trials.

These options would enable Palmetto to ensure appropriate use while preserving access for the limited patient population most likely to benefit.

Recognizing PEF ablation with its current evidence would be consistent with how CMS and its contractors have handled other emerging ablative technologies, which achieved coverage through local LCDs once prospective, peer-reviewed human data demonstrated safety and clinical benefit—without requiring randomized data across every indication. Such an approach balances patient safety, continued evidence generation, and equitable access for Medicare beneficiaries with no alternatives.

Conclusion

The Aliya® Pulsed Electric Field Ablation System represents a validated, non-thermal, structure-sparing therapy at a similar evidence maturity stage as RF, microwave, and cryoablation when those technologies first achieved coverage. The evidence base demonstrates a favorable safety profile, reproducible multi-organ feasibility, and clinically meaningful outcomes.

Revising the LCD to differentiate PEF from traditional IRE and to allow limited coverage would align Palmetto policy with CMS’ established approach to safe innovation, ensuring that medically appropriate Medicare beneficiaries continue to have access to this important therapy.

We appreciate your consideration and the opportunity to engage in this important discussion.

See comment #13 above.

Also, the Moreno-Gonzalez et al., (2025) was a case series, single arm study with high risk of bias and only looked at perioperative adverse events and did not have a comparator for treatment or looked at survival rates. It looked at short term survival and was a preliminary study with small patient numbers at 6 months. Another limitation is the relatively short (6-month) follow-up period following ablation which makes it challenging to determine potential relationships between the overall radiologic outcomes and immunological changes. Tumor progression, recurrence, the onset of new lesions, or observation of responses in non-ablated lesions may not yet be present. In addition, there is a broad range of underlying cancers present within the study population, where each may have unique downstream immunological implications. Moreover, only radiographic responses of ablated targets are reported here, providing indications of local control which may occur independently from immunological effects. Lastly, as the study was non-randomized and the 2 cohorts emerged during analysis, the results may reflect potential sources of bias in post-ablation patient management. While some of these limitations are inherent to the study design, the 12-month analysis is warranted to evaluate potential associations once longer-term definitive response and survival data are available.

The use of the Aliya device at this time would not be considered reasonable and necessary based upon the very low quality of evidence to support its use for lung cancer.

We appreciate the opportunity to comment on the Draft Local Coverage Determination (LCD) DL40205: Irreversible Electroporation (IRE) for Cancer.

Summary of Request

We respectfully submit that the proposed noncoverage determination does not reflect the full body of peer-reviewed evidence, current clinical practice, or guideline recommendations supporting the reasonable and necessary use of IRE for cancer.

The evidence base for the IRE procedure continues to expand, demonstrating consistent safety, efficacy, and improved outcomes in select cancer patient populations. The IRE ablation technique is utilized in the majority of leading United States (US) cancer centers, comprised of 93% of US News & World Report “Best Hospitals for Cancer Care,” and 70% of National Comprehensive Cancer Network (NCCN) Member Institutions (AngioDynamics Data on File, 2025), which underscores strong clinical confidence. Along with updated guidelines, long-term studies, and American Medical Association (AMA) assignment of Category I Current Procedural Terminology (CPT) codes, these data affirm IRE’s established role in modern cancer care.

Designating IRE as “investigational” for all cancers would inappropriately restrict Medicare beneficiaries’ access to a validated, patient-centered intervention that addresses key unmet needs. We respectfully request that Palmetto revise the LCD to include IRE coverage for the following indications:

• Prostate Cancer: Coverage with criteria for intermediate-risk localized disease and as salvage therapy for radio-recurrent localized disease when surgery is contraindicated or technically challenging.
• Liver Cancer: Coverage for select patients with hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) whose lesions are adjacent to major vessels or structures at risk with thermal ablation and suitable for multi-probe treatment.

The evidence-based rationale for these coverage requests is summarized in two sections – Prostate Cancer and Liver Cancer – with supporting details on the new Category I CPT code effective January 1, 2026, additional cancer indications, and references in the Appendix.

I. Prostate Cancer

Our request for IRE coverage in prostate cancer focuses on two indications – intermediate-risk localized disease and salvage therapy after radiotherapy – supported by strong clinical evidence, guideline alignment, and a positive Maximus coverage determination. The NanoKnife® System is an IRE ablation technique using non-thermal monophasic pulses delivered by multiple probes that received US Food and Drug Administration (FDA) 510(k) clearance in December 2024 for prostate tissue ablation, confirming its safety and intended use. Beginning January 1, 2026, the IRE procedure will be recognized with a permanent Category I CPT code, underscoring its status as an accepted, evidence-based treatment increasingly adopted across leading US cancer centers.

a. Intermediate-risk, localized disease

LCD Points to be Addressed: The current clinical guideline, medical policy, and evidence base for use of IRE in intermediate-risk prostate cancer is not fully captured in the proposed LCD, as detailed below.

Evidence: High-quality, single-arm studies show that IRE achieves effective cancer control for intermediate-risk prostate cancer, using monophasic pulses delivered through multiple probes to precisely bracket and ablate targeted lesions in a controlled, non-thermal manner. Favorable outcomes in current IRE evidence base and additional long-term data include:

• Efficacy: Prospective studies, including the pivotal George 2025 (PRESERVE) trial which was not referenced in the LCD draft, report ≥84% in-field negative biopsy rates and metastasis-free survival comparable to surgery or radiation, confirming strong efficacy and safety for IRE at 12 months.
• Safety & QoL: Near-universal continence, high potency preservation, and minimal Grade ≥3 toxicity, which is substantially better than radical therapy benchmarks.
• Durability: Follow-up data up to three years show sustained local control and metastasis-free survival with no evidence of accelerated recurrence.

Details on these studies and long-term outcomes associated with this IRE procedure through at least five years are summarized in Table 1.

Table 1: Intermediate Risk Prostate Cancer Evidence

*Table 1 provided for reference and reviewed but is unable to be entered into the database*

Guidelines & Payer Coverage: Clinical guidelines and payer coverage precedent confirm that focal IRE has an established, evidence-based role in treating intermediate-risk localized prostate cancer. As shown in Table 2, both the NCCN and AUA/ASTRO guidelines recognize IRE as an option for appropriately informed patients. Maximus, a Medicare appeals contractor within Palmetto’s jurisdiction, recently overturned a local denial, confirming IRE as medically necessary, not experimental, for an intermediate-risk patient. The AUA Core Curriculum also lists IRE among accepted prostate ablation modalities, reflecting its integration into standard urologic practice.

Table 2: Intermediate Risk Prostate Cancer Guidelines & Payer Coverage

*Table 2 provided for reference and reviewed but is unable to be entered into the database*

Recommended LCD Revisions: To align with current evidence demonstrating favorable oncologic and quality-of-life outcomes for intermediate-risk patients, as well as clinical guideline recommendations and existing payer coverage, we respectfully request that Palmetto update the current non-coverage policy to a “coverage with criteria” framework for IRE in intermediate-risk localized prostate cancer, with the following criteria:

• Clinical Criteria: Coverage should apply to patients with organ-confined, unilateral or focal-dominant prostate cancer classified as intermediate-risk (e.g., Gleason Grade Group 2 or 3 with localized disease). The tumor must be suitable for treatment with multiple probes to achieve effective focal ablation. Patients with low-risk disease (Gleason Grade Group 1, PSA <10) should generally pursue active surveillance, while those with high-risk features (Grade Group ≥4, PSA >20, or >50% positive cores) should be directed toward definitive therapy rather than focal ablation.

b. Salvage Therapy after Radiotherapy

Patients who have failed radiotherapy have limited options for further treatment, and there is a high unmet need for patients unsuitable to current alternatives or who prefer a less invasive technique. In this population, IRE offers an option of last resort that is desperately needed and supported by sufficient quality evidence, as reflected in NCCN guidelines.

LCD Points to be Addressed: The proposed LCD does not include salvage therapy following radiation failure as an indication for IRE, despite strong emerging data and recognition by leading clinical guidelines.

Evidence: Following radiotherapy failure, treatment options for localized recurrence, such as prostatectomy or cryotherapy, carry high risks of incontinence, erectile dysfunction, and other complications, while androgen deprivation therapy (ADT) remains palliative and non-curative. IRE offers a tissue-sparing, minimally invasive alternative for patients unsuitable for salvage surgery or other focal therapies due to prior treatment, comorbidities, or technical constraints.

As summarized in Table 3, prospective and multicenter studies, including the FIRE trial and a systematic review (Yilmaz 2024), show that IRE provides meaningful local control as a last resort, curative option while preserving urinary and sexual function in appropriately selected radio-recurrent patients.

Table 3: Salvage Treatment Prostate Cancer Evidence

*Table 3 provided for reference and reviewed but is unable to be entered into the database*

Guidelines & Medical Policy: Clinical guidelines and payer policy confirm that focal IRE has an established, evidence-based role for salvage use in prostate cancer (Table 4). The NCCN Prostate Cancer Guidelines (V2.2026) list focal ablation, including IRE, as a Category 2B option for local recurrence after radiotherapy without metastases. Medicare’s national coverage determination (NCD 100-3) for cryosurgery as salvage therapy recognizes the curative potential of local ablation, and some Medicare Administrative Contractors (MACs) have extended coverage for high-intensity focused ultrasound (HIFU) in similar cases. Likewise, IRE offers local tumor control with potentially less morbidity, benefiting from its non-thermal mechanism that avoids cryotherapy-associated complications.

Table 4: Salvage Treatment Prostate Cancer Guidelines & Medical Policy

*Table 4 provided for reference and reviewed but is unable to be entered into the database*

Recommended LCD Revisions: Given strong evidence that IRE is an effective, safe, and minimally invasive therapy offering curative local control with lower morbidity than radical salvage surgery and supported by clinical guidelines and payer policy, we respectfully request that Palmetto include IRE as a salvage treatment for radio-recurrent, localized prostate cancer in the LCD, with the following criteria:

• Clinical Criteria: Men with biopsy-confirmed local recurrence of prostate adenocarcinoma after definitive radiotherapy, confined to the prostate or prostate bed with no distant metastases. Lesions should be suitable for multi-probe. treatment, with rising PSA and imaging or biopsy confirmation, and candidates should have sufficient life expectancy for local therapy.
• Alternative Options: IRE may be chosen as a less invasive alternative to salvage prostatectomy or used in patients who are not surgical candidates due to comorbidities or technical constraints. Other salvage options (cryotherapy, HIFU) are similarly or more invasive; IRE offers a potentially safer approach.
• Repeat Treatment: If recurrence occurs post-IRE, repeat procedures may be considered on a case-by-case basis.

II. Liver Cancer

Our request for IRE coverage in liver cancer focuses on hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), supported by growing clinical evidence and guideline alignment demonstrating IRE’s safety and efficacy for tumors near major vessels or structures, such as bile ducts, where thermal ablation is unsuitable. This evidence supports IRE as a safe, effective, and organ-sparing option for appropriately selected patients.

a. Appropriately selected patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC)

LCD Points to be Addressed: The current LCD does not adequately reflect the evidence supporting IRE for liver cancer, including HCC and ICC, particularly for lesions adjacent to critical structures where thermal ablation poses increased risk.

Evidence: Clinical studies demonstrate that IRE can be safely and effectively applied to HCC and ICC, achieving durable local tumor control, favorable survival outcomes, and acceptable safety profiles even in anatomically challenging cases. Collectively, the data support IRE as a viable, curative-intent treatment option for patients with liver tumors near critical vascular or biliary structures. See Table 5 for supporting study details and outcomes.

Table 5: Liver Cancer Evidence

*Table 5 provided for reference and reviewed but is unable to be entered into the database*

Guidelines & Medical Policy: Clinical guidelines and payer policy demonstrate that IRE has an established, evidence-based role in the management of select liver tumors, as summarized in Table 6. The NCCN Biliary Tract Cancer Guidelines (V3.2024) list IRE alongside RFA and MWA as an ablation option for intrahepatic cholangiocarcinoma (ICC) with a Category 2A recommendation. Similarly, the NCCN Colon Cancer (V5.2025) and Rectal Cancer (V4.2025) Guidelines recognize image-guided ablation for liver metastases that cannot be safely resected or thermally ablated due to proximity to central bile ducts or vessels, also with a Category 2A designation. These recommendations underscore IRE’s role in treating anatomically challenging tumors where tissue preservation and local control are critical. In alignment with these guidelines, Health Care Service Corporation (HCSC) medical policy allows IRE for liver tumors in defined circumstances for ICC, a policy followed by Blue Cross Blue Shield plans in Illinois, Montana, New Mexico, Oklahoma, and Texas.

Table 6: Liver Cancer Guidelines & Medical Policy

*Table 6 provided for reference and reviewed but is unable to be entered into the database*

Recommended LCD Revisions: Given the strong evidence supporting the safety and effectiveness of IRE for appropriately selected patients with HCC and ICC, along with NCCN guideline recognition and existing payer policy precedent, we respectfully request that Palmetto include IRE as a covered treatment option for patients, with the following criteria:

• Clinical Criteria: Coverage should apply to patients with primary or metastatic liver tumors, including HCC and ICC, where lesions are adjacent to major vessels or bile ducts at risk with thermal ablation and are suitable for multiple-probe treatment planning and delivery.

III. Conclusions

In summary, we respectfully request that Palmetto revise the proposed LCD to reflect the full body of peer-reviewed evidence, clinical guidelines, and payer precedent supporting the medically necessary use of Irreversible Electroporation (IRE) for the following indications:

• Prostate Cancer: Coverage with criteria for intermediate-risk localized disease and as salvage therapy for radio-recurrent localized disease when surgery is contraindicated or technically challenging.
• Liver Cancer: Coverage for select patients with HCC or ICC whose lesions are adjacent to major vessels or structures at risk with thermal ablation and suitable for multi-probe treatment.

Updating the policy to cover IRE in these defined scenarios would align Palmetto’s approach with current science and practice, ensuring Medicare beneficiaries have access to a validated, patient-centered therapy that reduces treatment-related morbidity while maintaining oncologic control.

Please also note that the Appendix includes additional details on a recent coverage determination in Palmetto area, IRE coding documentation, evidence and coverage considerations for other cancers unsuited for thermal ablation, and cost effectiveness information.

We appreciate your thoughtful consideration and remain available to provide any additional information or supporting data as needed.

IV. Appendix

Maximus Coverage Determination Detail

In October 2025, Maximus received an appeal for the approval of IRE after a Commercial Medicare Advantage Plan had denied the request. To make their determination, Maximus reviewed all of the submitted papers, evaluated applicable Medicare rules, and assessed whether the Plan had correctly followed Medicare regulations, noting, “the Plan must follow Medicare rules. Medicare rules for an item or service, then that item or service will be covered when it is medically necessary.”

Maximus asked their physician reviewer to examine the case file to determine whether the Plan’s denial of pre-approve electroporation (0600T) was appropriate: “Reviewer says that the requested items/services are considered medically reasonable and necessary… The enrollee is with a history of prostate cancer that is favorable intermediate risk with Gleason 7 disease. Various options were discussed for management and irreversible electroporation (IRE) has been recommended. There are numerous research outlining the benefit of IRE for prostate cancer and this option is not considered experimental or investigational.” Based on this determination, Maximus concluded that the Plan must pre-approve IRE.

IRE Coding Update

To ensure awareness of upcoming coding changes, we note that the billing and coding article DA60222 associated with the proposed LCD DL40205 currently references only the Category III CPT codes 0600T and 0601T for Irreversible Electroporation (IRE). Effective January 1, 2026, the American Medical Association (AMA) has established new Category I CPT codes recognizing IRE as a standard, reportable procedure (Centers for Medicare & Medicaid Services 2025).

Specifically, the new codes are 55877 (IRE of the prostate) and 47384 (IRE of the liver), reflecting the transition of IRE procedures from Category III to Category I status and the broader scope of clinical application across organ sites. This update ensures that coding accurately aligns with current clinical and procedural standards.

Table 7: Category I and III CPT Codes for IRE

*Table 7 provided for reference and reviewed but is unable to be entered into the database*

Other Cancers (Colorectal, Kidney, Breast, Pancreas, Biliary Tract)

We wanted to highlight emerging clinical evidence showing that IRE is safe, technically feasible, and effective in treating tumors located near vital structures where other ablative techniques pose unacceptable risks. Recent randomized trials and prospective registries report favorable local control, a safety profile comparable to radiation, and non-inferior oncologic outcomes across multiple tumor types, including locally advanced pancreatic cancer.

Given this growing evidence base, Palmetto may wish to consider allowing IRE in select, highly specific cases, such as locally advanced, unresectable, or thermally ineligible tumors in the colon, kidneys, breast, pancreas, or biliary tract, where no other local ablative or surgical options are feasible and treatment is delivered with curative intent at experienced centers. See Table 8 for supporting study details and outcomes.

Table 8: Other Cancers (Pancreatic) Evidence

*Table 8 provided for reference and reviewed but is unable to be entered into the database*

Cost-Effectiveness of IRE

While coverage decisions are primarily evidence-driven, evidence supports coverage of IRE in the prostate indications recommended (intermediate-risk, salvage) could be cost-neutral or cost-saving for Medicare over time. A recent cost-effectiveness analysis (Reddy 2023) compared focal therapy, radical prostatectomy, and external beam radiotherapy as primary treatment options for patients with non-metastatic prostate cancer who are not suitable for active surveillance. Using a Markov cohort health state transition model over a 10-year time horizon and clinical data derived from prostate cancer registries. Clinical transition probabilities were derived from propensity score-matched populations to ensure comparability. The study found that focal therapy was associated with favorable cost-effectiveness compared to both radical prostatectomy and external beam radiotherapy, with comparable oncological outcomes, suggesting that focal therapy offers a cost-effective alternative to radical treatments and potential reductions in treatment-related morbidity and healthcare costs for appropriately selected patients.

V. References

References cited and full text articles received.

Thank you for your comments.

See comments #1, #2, #4 and #8 above.

In the NCCN evidence blocks for liver tumor ablation, thermal ablation can be considered alone or in conjunction with surgery, which is distinctly different from IRE. IRE is only considered in patients that cannot be safely resected or ablated with margins due to proximity to central bile ducts or other structures that cannot be protected.

However, the literature to support IRE for liver cancer is of low quality and does not show long-term survival over other available treatment modalities. In the most recent study cited, Cribbs et al., (2025) did a meta-analysis. However, the comparator group performed as well or better when longer term outcomes were considered. There was no improvement in AE’s over that time period as well and therefore does not offer a distinct advantage over SOC treatment options.

The change of a category III code to a category I CPT® code does not equate to coverage even in the event of a pricing placed on the CMS physician fee schedule as evidence to support the service as reasonable and necessary. Evidentiary support for an LCD relies primarily upon MPIM, Chapter 13.

The individual case being overturned at the Administrative Law Judge (ALJ) level is not precedent setting as ALJ cases are individually reviewed on a case-by-case basis.