SUPERSEDED Local Coverage Determination (LCD)

Luteinizing Hormone-Releasing Hormone (LHRH) Analogs

L39387

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Superseded
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Document Note

Note History

Contractor Information

LCD Information

Document Information

Source LCD ID
N/A
LCD ID
L39387
Original ICD-9 LCD ID
Not Applicable
LCD Title
Luteinizing Hormone-Releasing Hormone (LHRH) Analogs
Proposed LCD in Comment Period
N/A
Source Proposed LCD
DL39387
Original Effective Date
For services performed on or after 02/19/2023
Revision Effective Date
N/A
Revision Ending Date
01/17/2024
Retirement Date
N/A
Notice Period Start Date
01/05/2023
Notice Period End Date
02/18/2023
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Issue

Issue Description

This LCD outlines coverage for this service with specific details under Coverage Indications, Limitations and/or Medical Necessity.

Issue - Explanation of Change Between Proposed LCD and Final LCD

Under Coverage Indications, Limitations and/or Medical Necessity added "palliative treatment of advanced prostate cancer" for Leuprolide Acetate, Goserelin implant and Triptorelin. Additionally, clarification was provided for Goserelin implant as it pertains to use in combination with flutamide. NCCN Clinical Practice Guidelines in Oncology® have been added and are cited. Palliative treatment of advanced prostate cancer has been removed from coverage for Histrelin acetate implant. Under Bibliography added #13-17.

CMS National Coverage Policy

Title XVIII of the Social Security Act, §1862(a)(1)(A) allows coverage and payment for only those services that are considered to be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.

Title XVIII of the Social Security Act, §1862(a)(7) states Medicare will not cover any services or procedures associated with routine physical checkups.

CMS Internet Only Manual, Publication 100-08, Medicare Program Integrity Manual, Chapter 13, §13.5.4 Reasonable and Necessary Provision in an LCD.

CMS Internet Only Manual, Publication 100-02, Medicare Benefit Policy Manual, Chapter 15 Covered Medical and Other Health Services, §§50.3 Incident-to Requirements and 50.4.1 Approved Use Of Drug.

Coverage Guidance

Coverage Indications, Limitations, and/or Medical Necessity

Luteinizing Hormone-Releasing Hormone (LHRH) Analogs are synthetic analogs of the naturally occurring gonadotropin releasing hormone (GnRH) with greater potency than the naturally occurring hormone, that when given inhibits pituitary gonadotropin secretion and suppresses testicular and ovarian steroidogenesis.

Leuprolide Acetate (Lupron Depot), Goserelin (Zoladex®), Triptorelin pamoate (Trelstar®), Histrelin acetate (Vantas®) are synthetic LHRH agonist, analogs of the naturally occurring gonadotropin-releasing hormone (GnRH), and Leuprolide mesylate (Camcevi®). They will be covered for Food and Drug Administration (FDA) approved indications. The dose and frequency of administration should be consistent with the FDA approved labeling.

Covered Indications

Leuprolide Acetate is covered for endometriosis, uterine fibroids, advanced prostate cancer, head and neck cancer (salivary gland tumors), ovarian cancer/fallopian tube cancer/primary peritoneal cancer, premenopausal breast cancer, male breast cancer, central precocious puberty (CPP) and palliative treatment of advanced prostate cancer.1 Leuprolide mesylate is covered for advanced prostate cancer.12 The NCCN Clinical Practice Guidelines in Oncology for Breast Cancer® 14, The NCCN Clinical Practice Guidelines in Oncology for Head and Neck Cancers® 15, The NCCN Clinical Practice Guidelines in Oncology for Ovarian Cancer®16, and The NCCN Clinical Practice Guidelines in Oncology for Prostate Cancer®17 are referenced for recommendations for coverage across each of these disease settings.

Goserelin implant is covered for locally confined prostate cancer in combination with flutamide, for stage T2b-T4 (Stage B2-C) flutamide is recommended only with radiation in this disease setting. Goserelin implant is covered for advanced breast cancer in premenopausal and perimenopausal women, endometriosis, to thin the endometrial lining of the uterus prior to endometrial ablation for dysfunctional uterine bleeding, and palliative treatment of advanced prostate cancer.2 The NCCN Clinical Practice Guidelines in Oncology for Breast Cancer®, is cited to nationally recognized guidelines to accommodate specific clinical scenarios.14 The NCCN Clinical Practice Guidelines in Oncology for Prostate Cancer® is cited to nationally recognized guidelines to accommodate specific clinical scenarios for “advanced prostate cancer”.17

Triptorelin pamoate is covered for palliative treatment of advanced prostate cancer.3 The NCCN Clinical Practice Guidelines in Oncology for Prostate Cancer® is cited to nationally recognized guidelines to accommodate specific clinical scenarios for “advanced prostate cancer”.17

Histrelin acetate implant is covered for CPP.

Note: The NCCN Clinical Practice Guidelines in Oncology for Prostate Cancer® is cited to nationally recognized guidelines to accommodate specific clinical scenarios for “advanced prostate cancer”.17

Limitations

Services that are not reasonable and necessary cannot be covered by Medicare in the following:

  1. The dose and frequency of administration is not consistent with the FDA approved labeling. Doses and frequencies that exceed the FDA recommended dosage/frequency as per the prescribing information, are considered not reasonable and necessary and not covered by Medicare.
  2. It is contraindicated to administer these products if you have experienced any type of allergic reaction to these drugs or to any of its ingredients.
Summary of Evidence

Lawrence et al (2020) conducted a systemic review to create the AUA/ASTRO/SUO Guideline to aid clinicians in the management of patients with advanced prostate cancer. Clinicians should offer ADT (Androgen deprivation therapy) with either luteinizing hormone-releasing hormone (LHRH) agonists or antagonists or surgical castration in patients with mHSPC (metastatic hormone sensitive prostate cancer) (Strong Recommendation; Evidence Level: Grade B). The use of primary ADT for the management of mHSPC has been the SOC since its discovery by Huggins and colleagues in the 1940’s.5

Conn et al (1991) review article reports the use of GnRH agonist analogues therapy to induce biochemical castration. The suppression of the normal pituitary-gonadal function is sought because physiologic levels of secretion of gonadal steroids which exacerbate an underlying medical condition, such as endometriosis, uterine fibroids, or prostate cancer.6

Guzick D et al (2011) conducted a prospective, randomized, double-blind controlled trial to compare the efficacy of leuprolide and continuous oral contraceptives in the treatment of endometriosis associated pain. The major findings of this trial is that both treatment arms provided a significant reduction in pain from baseline and there was no significant difference in the extent of pain relief between the two treatment regimens. The strengths of this clinical trial include its study design (randomized, double-blind prospective, multicenter) and the choice of contemporary medical regimens currently in widespread clinical use in the United States. The greatest weakness of the study is its limited sample size, a direct result of significant challenges in subject recruitment.7

Kendzierski et al (2018) assessed the efficacy of leuprolide depot in combination with an aromatase inhibitor delivered monthly compared to once every 3 months in premenopausal women with estrogen receptor positive-breast cancer in a single center retrospective study. The SOFT/TEXT trials solidified GnRH agonists as a definitive option in adjuvant therapy for premenopausal women with ER-positive breast cancer. They concluded leuprolide acetate depot administered every 3 months is as efficacious and tolerable as a monthly injection in combination with an aromatase inhibitor for premenopausal patients with hormone receptor positive breast cancer. The study’s retrospective design comes with inherent limitations. Our patient population was small, and we describe a single institution experience not a larger randomized, multicenter trial of adjuvant hormone therapy in breast cancer patients.9

Hassett et al (2020) convened an expert panel to develop clinical practice guideline recommendations based on a systematic review of the medical literature. To date, approaches to treating men with breast cancer have been extrapolated largely from research conducted in women with breast cancer. Guideline development involved a formal consensus process. The ASCO guideline offers recommendations on several key aspects of the management of male breast cancer.10

Francis et al (2018) reported the updated results from the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT). They concluded that among premenopausal women with breast cancer, the addition of ovarian suppression to tamoxifen resulted in significantly higher 8-year rates of both disease free and overall survival than tamoxifen alone. The use of exemestane plus ovarian suppression resulted in even higher rates of freedom from recurrence.11

Analysis of Evidence (Rationale for Determination)

The analysis of evidence reviewed for LHRH analogs included the AUA/ASTRO/SUO Guideline, a prospective, randomized, double-blind controlled trial, a retrospective study, and the ASCO Guideline.

The AUA/ASTRO/SUO Guideline has a strong recommendation for the use of primary ADT for the management of mHSPC.5 The article by Conn reports the use of GNRH agonist analogues therapy to suppress the normal pituitary gonadal function in medical conditions such as endometriosis, uterine fibroids, prostate cancer.6 Kendzierski stated that the SOFT/TEXT trials solidified GnRH agonists as a definitive option in adjuvant therapy for premenopausal women with ER-positive breast cancer.9

Proposed Process Information

Synopsis of Changes
Changes Fields Changed
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Associated Information
Sources of Information
Bibliography
Open Meetings
Meeting Date Meeting States Meeting Information
N/A
Contractor Advisory Committee (CAC) Meetings
Meeting Date Meeting States Meeting Information
N/A
MAC Meeting Information URLs
N/A
Proposed LCD Posting Date
Comment Period Start Date
Comment Period End Date
Reason for Proposed LCD
Requestor Information
This request was MAC initiated.
Requestor Name Requestor Letter
View Letter
N/A
Contact for Comments on Proposed LCD

Coding Information

Bill Type Codes

Code Description
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Revenue Codes

Code Description
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CPT/HCPCS Codes

Group 1

Group 1 Paragraph

N/A

Group 1 Codes

N/A

N/A

ICD-10-CM Codes that Support Medical Necessity

Group 1

Group 1 Paragraph:

N/A

Group 1 Codes:

N/A

N/A

ICD-10-CM Codes that DO NOT Support Medical Necessity

Group 1

Group 1 Paragraph:

N/A

Group 1 Codes:

N/A

N/A

Additional ICD-10 Information

General Information

Associated Information

Services performed for any given diagnosis must meet all of the indications and limitations stated in this LCD, the general requirements for medical necessity as stated in CMS payment policy manuals, any and all existing CMS national coverage determinations, and all Medicare payment rules.

The patient’s medical record must contain documentation that fully supports the medical necessity for services included within this LCD (“Coverage Indications, Limitations and/or Medical Necessity”).

The documentation must include the following:

  1. All documentation must be maintained in the patient's medical record and made available to the contractor upon request.
  2. The recommended dosages for specific FDA indications must be consistent with the FDA approved labeling and must be clearly documented.
Sources of Information

L33685 Luteinizing Hormone-Releasing Hormone (LHRH) Analogs

L34822 Luteinizing Hormone-Releasing Hormone (LHRH) Analogs

Bibliography
  1. U.S. Food and Drug Administration (FDA). Lupron Depot (leuprolide acetate) prescribing information. Accessed 11/28/22.
  2. U.S. Food and Drug Administration (FDA). Zoladex® (goserelin acetate implant) prescribing information. Accessed 11/28/22.
  3. U.S. Food and Drug Administration (FDA). Trelstar® (triptorelin pamoate) prescribing information. Accessed 11/28/22.
  4. Virgo KS, Rumble RB, deWit R, et al. Initial management of noncastrate advanced, recurrent, or metastatic prostate cancer: ASCO Guideline Update. J Clin Oncol. 2021;39(11):1274-1305.
  5. Lowrance WT, Breau RH, Chou R, et al. Advanced prostate cancer: AUA/ASTRO/SUO guideline part 1. J Urol. 2021;205(1):14- 21.
  6. Conn PM, and Crowley WF. Gonadotropin-releasing hormone and its analogues. N Engl J Med. 1991;324(2):93-103.
  7. Guzick DS, Huang LS, Broadman BA, Nealon M, Hornstein MD. Randomized trial of leuprolide versus continuous oral contraceptives in the treatment of endometriosis – associated pelvic pain. Fertil Steril. 2011;95(5):1568-1573.
  8. Brown J, Pan A, Hart RJ. Gonadotrophin-releasing hormone analogues for pain associated with endometriosis. Cochrane Database of Systemic Reviews. 2010;12:1-105.
  9. Kendzierski D, Schneider BP and Kiel PJ. Efficacy of different leuprolide administration schedules in premenopausal breast cancer: A retrospective review. Clinical Breast Cancer. 2018;18(5):e939-42.
  10. Hassett MJ, Somerfield MR, Giordano SH. Management of male breast cancer: ASCO guideline summary. JCO Oncology Practice. 2020;16(8):e839-e843.
  11. Francis PA, Pagani O, Fleming GF, et al. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 2018;379(2):122-137.
  12. Shore N, Mincik I, DeGuenther M, et al. A phase 3, open-label, multicenter study of a 6-month pre-mixed depot formulation of leuprolide mesylate in advanced prostate cancer patients. World J Urol. 2020;38(1):111-119.
  13. U.S. Food and Drug Administration (FDA).Camcevi® prescribing information. Accessed 11/28/22.
  14. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Breast Cancer. Accessed 11/28/22.
  15. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Head and Neck Cancers. Accessed 11/28/22.
  16. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Ovarian Cancer. Accessed 11/28/22.
  17. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Prostate Cancer. Accessed 11/28/22.

Revision History Information

Revision History Date Revision History Number Revision History Explanation Reasons for Change
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Associated Documents

Attachments
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Related National Coverage Documents
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Public Versions
Updated On Effective Dates Status
01/10/2024 01/18/2024 - N/A Currently in Effect View
12/29/2022 02/19/2023 - 01/17/2024 Superseded You are here

Keywords

  • Luteinizing Hormone
  • LHRH

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