Approximately 50 percent of men at age 50, and up to 80 percent at age 80, have LUTS/BPH (1). In 2015, it was estimated that 12.2 million men were actively managed for LUTS/BPH; accounting for almost 25% of a urology practice (2). An aging population means the impact of LUTS/BPH will only increase. BPH develops primarily in the periurethral or transitional zone of the prostate (normally only 5% of prostate volume), and its pathogenesis remains incompletely understood. The natural history is variable; about one-third will ultimately require treatment, one-third remain stable, and one-third have some spontaneous regression of symptoms.
The array of therapeutic options includes conservative approaches (watchful waiting), pharmacotherapy, and a burgeoning variety of surgical options (transurethral prostate resection or ablation). The need for surgical intervention is generally based upon the adequacy of medical therapy, the development of complications, and patient preference, rather than any specific urological parameter (3). The American Urologic Association/International Prostate Symptom Score (AUA/IPSS) (assessing for both storage (frequency, nocturia, urgency), and voiding (weak urinary stream, hesitancy, intermittence, incomplete emptying) symptoms, is useful for quantifying and monitoring BPH symptoms. Symptoms (individually ranked 0-5) are classified as mild (total score 0-7), moderate (total score 8-19), or severe (total score 20-35). Surgery is usually reserved for those with moderate to severe symptoms despite medical management (insufficient efficacy and tolerability, including drug side effects involving sexual dysfunction) (4).
Transurethral resection of the prostate (TURP) has been the standard-of-care for decades. However, despite technical refinements that have improved safety, the procedure is still associated with a perioperative morbidity rate of 20% and long-term complications like ejaculatory dysfunction (EjD) (65%), erectile dysfunction (ED) (10%), urethral strictures (7%), urinary tract infection (4%), bleeding requiring transfusion (2%), urinary incontinence (2%) and a retreatment rate of 6% (5). EjD has a significant negative impact on quality-of-life (QoL), including on fertility, considering the relatively early onset of BPH.
In recent years, an alphabet soup of minimally invasive treatment options have emerged with the main goal to be equally effective to TURP but with a more favorable safety and convenience profile. Ideally, this includes the rapid and durable relief of LUTS without compromise of sexual function, under local anesthesia in an ambulatory setting, with a short convalescence (6). Increasingly, a balance between symptomatic improvement in LUTS and preservation of sexual function is expected (7). The most apt comparators to water vapor thermal therapy include transurethral needle ablation (TUNA), and transurethral microwave thermotherapy (TUMT), both minimally invasive thermal ablative techniques.
Transurethral needle ablation (TUNA)
TUNA delivers radiofrequency energy to the prostate via needles inserted transurethrally into the prostatic parenchyma. The energy induces coagulation necrosis in the prostatic transition zone resulting in prostate volume reduction and LUTS reduction. There may also be a poorly understood neuromodulatory effect (8).
Detailed comparisons between TUNA and other treatments can be found in two comprehensive, systematic reviews and meta-analyses (9,10). Improvements in urodynamic and symptom score parameters are generally inferior to TURP but TUNA is considered an alternative for men who are poor candidates for surgery, particularly men who require anticoagulation, but also for those who wish to undergo a procedure with fewer lower urinary and sexual side effects than TURP.
Transurethral microwave therapy (TUMT)
TUMT of the prostate works by emitting microwave radiation through an intra-urethral antenna in order to deliver heat into the prostate. Tissue is destroyed by being heated at temperatures above cytotoxic thresholds (> 45°C) (coagulation necrosis). It is thought that the heat generated by TUMT also causes apoptosis and denervation of alpha-receptors, thereby decreasing the smooth muscle tone of the prostatic urethra (8).
A Cochrane systematic review of all available randomized controlled trials (RCTs) on TUMT shows roughly similar therapeutic efficacy to TUNA (11).
Water vapor thermal therapy
Water vapor thermal therapy uses convective water vapor energy to ablate prostatic tissue. The Rezum system for delivering water vapor thermal therapy received FDA 510(k) clearance in 2015 to treat LUTS/BPH in men ≥ 50 years old with a prostate volume 30-80cc, and includes treatment of hyperplasia of the central prostate zone and median lobe (12).
This technology uses radiofrequency current to generate “wet” thermal energy in the form of water vapor (steam). Using a TUNA approach, the steam is injected into the hyperplastic prostate, passing through the tissue interstices and disrupting cell membranes to effect rapid cell death and necrosis. Unlike conductive thermal ablation (TUNA, TUMT), steam convection at a physical phase change boundary best realizes a “prescribed temperature boundary condition”, effectively precluding a temperature gradient beyond the targeted prostate (usually the transition zone) (13). This was confirmed by histologic and imaging studies using gadolinium enhanced MRI (14,15). According to the manufacturer, water vapor thermal therapy requires “fewer joules per gram of tissue, ~1/6–1/23, to produce cell necrosis in prostate tissue compared to TUNA and TUMT, respectively (16).”
A prospective, open-label, multicenter, pilot study reported the 1- and 2-year outcomes of 65 men with IPSS defined moderate (32.3%) to severe (67.7%) LUTS (overall mean IPSS: 21.6; Qmax: 7.9 mL/s; prostate volume (PV) 48.6 cc) (17,18). Clinically and statistically significant improvements in urinary symptoms were evident as early as one month after treatment and optimal at 3–12 months. The maximum IPSS improvement (-13.4) occurred at 3 months (N=62) and gradually decreased (-12.1) at 24 months (N=43); both were significantly different from baseline (p<.001). The maximum Qmax improvement (4.7 mL/s) occurred at 3 months (N=61) and decreased to (3.7 mL/s) at 24 months (N=39); both were significantly different from baseline (p<.001). Prostate volume was reported significantly decreased at all time points (p≤0.001). Adverse events were reported to be transient and mild to moderate, primarily related to endoscopic instrumentation. No clinically significant changes in sexual function were reported.
A retrospective study analyzed 131 consecutive patients with moderate (53.1%) to severe (46.9%) LUTS treated with water vapor thermal therapy by seven urologists in a large group-community practice (19). While patient demographics were similar to the pilot study, some notable differences included older mean age (70.9 years), broader range of prostate volumes (mean 45.1 [12.9-183] cc), and higher post-void residual (PVR) volumes (mean 216.8 [0-2,000] mL, and three in retention. The maximum IPSS improvement (-10.1, -47.2%) occurred at 3-6 months (N=115) and decreased (-9.4, -45.2%) at 12 months (N=87); both were significantly different from baseline (p<.0001). The maximum Qmax improvement (3.0 mL/s, 75.3%) occurred at 3-6 months (N=38) but was markedly decreased (1.5 mL/s, 51.4%) at 12 months (N=7); only the 3-6 month value was significantly different from baseline (p=0.0388). PVR was significantly decreased at all time points. The safety profile was similar to the pilot study.
The single level 1 study of water vapor thermal therapy is a multicenter RCT involving 197 men ≥50 years old with an IPPS ≥13, Qmax ≤15 mL/s, and PV 30-80 cc, randomized to thermal therapy with Rezum System or control (2:1) (20-22). Rigid cystoscopy with simulated active treatment sound effects served as the control procedure. The primary end point was the IPSS at 3 months. Both IPSS and Qmax (but not PVR) were significantly improved relative to sham at 3 months (p<0.0001). After the 3-month blinded comparison, 53 of 61 control subjects enrolled in a separate crossover active treatment study. The original active treatment group was followed annually for 3 years. The maximum IPSS improvement (-12.2, -54%) occurred at 6 months (N=129) and decreased (-11.0, -50%) at 36 months (N=97); both were significantly different from baseline (p<.0001). The greatest Qmax improvement (6.4 mL/s, 69%) occurred at 3 months (N=125) and decreased markedly (3.5 mL/s, 39%) by 36 months (N=80); both were significantly different from baseline (p<.0001). The surgical retreatment rate was 4.4 percent (6/135) over three years (open prostatectomy (1), plasma-button transurethral vaporization (3), water vapor thermal therapy re-treatment (2)). Subjects with a median lobe or central zone hyperplasia achieved similar significant relief of symptoms. Sexually active subjects had no negative changes in the International Index of Erectile Function (IIEF-15) and Male Sexual Health Questionnaire for Ejaculatory Dysfunction (MSHQ-EjD) function scores throughout 3 years of follow-up. Adverse events reported were infrequent and of short duration. The most common were dysuria (16.9%), hematuria (11.8%), frequency and urgency (5.9%), acute urinary retention (3.7%), and suspected urinary tract infection (3.7%); all were treated routinely or resolved without treatment within 3 weeks. There were no late occurring related adverse events. Four year results were reassuring, with IPSS relatively stable (-10.1, -46.7%, N=90), and Qmax improved (4.2 mL/s, 49.5%, N=81) (33). The surgical retreatment rate was unchanged at 4.4%.
A retrospective analysis of 38 catheter-dependent men with complete urinary retention treated with water vapor thermal therapy found that 70.3% voided spontaneously and were catheter free a median of 26 days (range 4-65) post procedure (34). Adverse events were infrequent, mild, and resolved quickly. The authors conclude: “As a minimally invasive surgical procedure it represents an alternative for treatment of catheter-dependent urinary retention in elderly and frail patients who are at anesthesia risk for invasive surgical approaches to relieve retention.”
The table below compares the mid-term (3-4 -year) results of water vapor thermal therapy with traditional comparators (the subjective IPSS and objective Qmax are the almost universal primary outcome measures).
Mid-term Thermal Ablation Results vs. Traditional Comparators
|Water vapor thermal therapy (33)
|*3 month data; **F/U time varies, ***Zlotta 4-5 yr. data