Subject:
Radiation Therapy for Endometrial Cancer
Description:
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IMPORTANT NOTE:
The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
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Over the past several decades, methods to plan and deliver radiation therapy have evolved in ways that permit more precise targeting of tumors with complex geometries. Earlier methods involved two-dimensional treatment planning based on flat images, and radiation beams with cross-sections of uniform intensity that were sequentially aimed at the tumor along 2 or 3 intersecting axes. These methods were collectively termed conventional external beam radiation therapy (EBRT).
Subsequent enhancement evolved using 3-dimensional images, usually from computed tomography (CT) scans, to delineate the tumor, its boundaries with adjacent normal tissue, and organs at risk for radiation damage. Radiation oncologists used these images, displayed from a "beam's-eye-view", to shape each of several beams (e.g., with compensators, blocks, or wedges) to conform to the patient's tumor geometry perpendicular to the beam's axis. Computer algorithms were developed to estimate cumulative radiation dose delivered to each volume of interest by summing the contribution from each shaped beam. Methods also were developed to position the patient and the radiation portal reproducibly for each fraction, and immobilize the patient, thus maintaining consistent beam axes across treatment sessions. However, "forward" planning used a trial and error process to select treatment parameters (the number of beams and the intensity, shape, and incident axis of each beam). The planner/radiotherapist modified one or more parameters and recalculated dose distributions, if analysis predicted underdosing for part of the tumor or overdosing of nearby normal tissue. Furthermore, since beams had uniform cross-sectional intensity wherever they bypassed shaping devices, it was difficult to match certain geometries (e.g., concave surfaces). Collectively, these methods are termed 3-dimensional conformal radiation therapy (3D-CRT).
Other methods were subsequently developed to permit beam delivery with non-uniform cross-sectional intensity. This often relies on a device (multi-leaf collimator, MLC) situated between the beam source and patient that moves along an arc around the patient. As it moves, a computer varies aperture size independently and continuously for each leaf. Thus, MLCs divide beams into narrow "beamlets", with intensities that range from zero to 100% of the incident beam. Beams may remain on as MLCs move around the patient (dynamic MLC), or they may be off during movement and turned on once the MLC reaches prespecified positions ("step and shoot" technique). Another method of delivering radiation beam uses a small radiation portal emitting a single narrow beam that moves spirally around the patient, with intensity varying as it moved. This method, also known as tomotherapy or helical tomotherapy, is described as the use of a linear accelerator inside a large "donut" that spirals around the body while the patient laid on the table during treatment. Each method (MLC-based or tomotherapy) is coupled to a computer algorithm for "inverse" treatment planning. The planner/radiotherapist delineates the target on each slice of a CT scan, and specifies that target's prescribed radiation dose, acceptable limits of dose heterogeneity within the target volume, adjacent normal tissue volumes to avoid, and acceptable dose limits within the normal tissues. Based on these parameters and a digitally-reconstructed radiographic image of the tumor and surrounding tissues and organs at risk, computer software optimizes the location and shape of beam ports, and beam and beamlet intensities, to achieve the treatment plan's goals. Collectively, these methods are termed intensity-modulated radiation therapy (IMRT).
According to ECRI Institute, there are two different approaches to image-guided radiation therapy that are in current use: pre-treatment imaging and real-time guidance. IMRT is an example of a method that uses pre-treatment imaging to prepare a treatment plan. In contrast, real-time guidance utilizes real-time imaging (at the time of treatment) to guide treatment. It provides real-time, online images of the radiation target area from a computed tomography (CT) scanner before, during, and after therapy. Patient positioning, radiation field alignment, and collimator positioning can be verified and adjusted before and during irradiation. This approach should, in theory, provide more accurate radiation delivery than conventional IMRT. Organ motion, day-to-day variations in tumor position, and differences in patient positioning in each treatment session could be taken into account with real-time imaging.
Policy:
(NOTE: This policy only applies to adult members. It does not apply to pediatric members.
For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
Treatment options in fully a surgically staged individual:
I. Postoperative brachytherapy alone is considered medically necessary for any of the following:
A. Stage IA without adverse risk factors (G2, G3)
B. Stage IA with adverse risk factors (G1, G2, G3)
C. Stage IB (G1, G2, G3)
D. Stage II (G1, G2)
II. Pelvic external beam radiation therapy with or without brachytherapy considered is medically necessary for either of the following:
A. Medically inoperable
B. Postoperative for any of the following:
1. Stage IB (G3)
2. Stage II (G1, G2, G3)
3. Stage IIIA, Stage IIIB, and Stage IIIC
4. Stage IVA
III. Radiation therapy to the primary tumor is considered medically necessary for any of the following:
A. Local only recurrence with no evidence of metastatic disease
B. Palliative treatment of symptoms such as pain or bleeding
DOSE and TECHNIQUE
I. External Beam Radiation Therapy
A. A dose of 45 to 50 Gy using a 3D conformal technique is considered medically necessary for definitive treatment. In the post-hysterectomy setting, the use of IMRT is considered medically necessary.
B. A dose greater than 50 Gy may be necessary in the following scenarios:
1. When a boost is planned for positive lymph node(s), positive surgical margins and/or gross residual disease
C. Palliation/Recurrence:
1. Pelvic external beam photon radiation therapy alone or combined with brachytherapy may be considered based on the clinical presentation.
2. In the non-curative setting and where symptoms are present, palliative external beam photon radiation therapy may be appropriate. In this scenario, treatment is typically delivered with Complex or three-dimensional conformal radiation therapy (3DCRT), up to 4 gantry angles, 1 phase, and up to 15 fractions.
3. When salvage radiotherapy is attempted for recurrence, treatment is typically 3DCRT, up to 4 gantry angles, and up to 35 fractions. Two phases may be appropriate, and the use of brachytherapy may be appropriate.
II. Brachytherapy
A. Preoperative Stage II with gross disease:
1. External beam photon radiation therapy and intrauterine brachytherapy
2. Up to a total dose of 75 to 80 Gy Low Dose Rate (LDR) equivalent
B. Postoperative:
1. HDR Brachytherapy should be initiated as soon as the vaginal cuff has healed or no later than 12 weeks following surgery
2. Brachytherapy using a vaginal cylinder is generally limited to the upper vagina with the dose prescribed at the vaginal surface or to a depth of 0.5 cm
a. In conjunction with external beam radiation, regimens of 4 to 6 Gy for 2 to 3 fractions to the vaginal mucosa is recommended
b. When delivered as sole therapy, regimens of 7 Gy for 3 fractions or 5.5 Gy x 4 fractions prescribed to a depth of 0.5 cm from the vaginal surface or 6 Gy for 5 fractions prescribed to the vaginal surface are recommended
C. Palliation/Recurrence: Brachytherapy alone or as combined treatment may be considered based on the clinical presentation for recurrent disease or palliation of symptoms.
III. Electronic brachytherapy is considered investigational.
Medicare Coverage:
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for Three-dimensional (3D) Conformal Radiation Therapy (3DCRT) or brachytherapy. Therefore, Medicare Advantage Products will follow the Horizon Policy for these services.
Novitas Solutions, Inc, the Local Medicare Carrier for jurisdiction JL, has issued a determination for Intensity-Modulated Radiation Therapy (IMRT). For additional information and eligibility for IMRT, refer to Local Coverage Determination (LCD): Intensity Modulated Radiation Therapy (IMRT) (L36711) and Local Coverage Article: Billing and Coding: Intensity Modulated Radiation Therapy (IMRT) (A56725). Available at: https://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=36711&ver=18&name=314*1&UpdatePeriod=749&bc=AAAAEAAAAAAAAA%3d%3d&.
[INFORMATIONAL NOTE:
Within the United States in 2018, 63,230 new cases of uterine malignancy are projected, resulting in projected 11,350 deaths. Uterine cancers represent the most common female genital tract malignancy. Endometrioid (tumors resembling the lining of the uterus; adenocarcinomas) are the most prevalent subtype. Papillary serous carcinoma, clear cell carcinoma and uterine sarcoma are not covered under this guideline.
The staging definitions used in the creation of the treatment criteria may be found in the 8th Edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual. The treatment options for treatment of cancer of the endometrium are defined by stage of disease, grade of the cancer, completeness of surgical staging and the presence of adverse risk factors. Complete surgical staging is defined as total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO), peritoneal lavage for cytology, dissection of pelvic and para-aortic lymph nodes and careful inspection and palpation of abdominal organs including but not limited to diaphragm, liver, peritoneal surfaces of the abdomen, pelvis, bowel and omentum. Adverse risk factors include advancing age, lymphovascular extension, tumor size, lower uterine involvement classified as cervical glandular involvement (newly classified as Stage I). For cases that are not completely surgically staged, radiologic imaging plays an important role in selecting a treatment strategy.
For surgically staged Stage IA with or without adverse risk factors, all individuals regardless of pathologic grading may be observed as per NCCN Guidelines®. Observation may also be employed for individuals with Stage IB G1 and G2 disease without risk factors. Should treatment rather than observation be decided upon for these same groups, radiation techniques are stratified in the preceding guideline statements. With more advanced clinical state and/or radiological presentations, more extended external beam photon radiation fields with or without brachytherapy may be medically necessary.
In advanced disease, the increased utilization of adjuvant chemotherapy has called into question the magnitude of the added benefit of adjuvant radiation therapy. We are awaiting the results of some recent trials that may help to answer some of these questions. Gynecologic Oncology Group (GOG) trial 249 randomized high risk early-stage patients to pelvic external beam photon radiation therapy or intravaginal external beam photon radiation therapy and chemotherapy. GOG 258 is comparing surgical Stage III or IVA patients to concurrent tumor directed external beam photon beam radiation therapy/chemotherapy to chemotherapy alone and PORTEC-3 is comparing concurrent pelvic external beam photon radiation therapy/chemotherapy to pelvic external beam photon beam radiation therapy alone in high risk surgical Stage IB-III patients. The early-stage endometrial cancer study by Aalders et al. (1980) updated by Onsrud, et al. (2013) of 568 patients with a median follow up of 20.5 years suggested no statistical difference in overall survival (OS) between women treated with vaginal brachytherapy alone versus those treated with vaginal brachytherapy and external beam radiation. Patients younger than age 60 who received external beam treatment did not have a survival benefit but did suffer an increased risk of secondary cancers with subsequent increased mortality.
For all other stages and those with positive radiologic imaging, surgical restaging or pathologic confirmation of more advanced disease is recommended (image directed biopsy). Individuals then enter the fully surgically staged treatment recommendations with their newly assigned stage.
The American Brachytherapy society published “The American Brachytherapy Society Consensus Statement for Electronic Brachytherapy” to serve as a guideline for the appropriate use of electronic brachytherapy (Tom et al., 2019). In the consensus statement, the authors note concerns in extrapolating data from traditional brachytherapy techniques to electronic brachytherapy regarding “clinical outcomes, toxicity profiles, and indications.” There is limited clinical data available on the use of electronic brachytherapy in vaginal cuff brachytherapy. The consensus statement notes that there is “paucity of data with respect to utilizing EB (electronic brachytherapy) for gynecologic cancers. It is not recommended that EB be used to deliver vaginal cuff brachytherapy outside of a clinical trial.”]
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Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
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Index:
Radiation Therapy for Endometrial Cancer
Radiation Treatment of Endometrial Cancer
Endometrial Cancer, Radiation Treatment of
Uterine Cancer, Radiation Treatment of
References:
1. Aalders J, Abeler V, Kolstad P, et al. Postoperative external irradiation and prognostic parameters in stage I endometrial carcinoma: clinical and histiopathologic study of 540 patients. Obstet Gynecol. 1980 Oct;56(4):419-427.
2. American Cancer Society: Cancer Facts and Figures 2015. Atlanta, Ga. American Cancer Society, 2014. Last medical review: 2/10/16. Last revised 1/4/18.
3. The AJCC Cancer Staging Manual 8th Ed. Chicago, IL. Springer. 2018. Part XII Female Reproductive Organs, Chapter 53. Corpus Uteri – Carcinoma and Carcinosarcoma, 669-678.
4. ASTRO 2014 Choosing Wisely® List.
5. Carboplatin and paclitaxel with or without cisplatin and radiation therapy in treating patients with stage I, stage II, stage III, or stage IVA endometrial cancer. Gynecologic Oncology Group and National Cancer Institute. Last updated posted January 10, 2018.
6. Corn BW, Lanciano RM, Greven KM, et al. Impact of improved irradiation technique, age, and lymph node sampling on the severe complication rate of surgically staged endometrial cancer patients: a multivariate analysis. J Clin Oncol. 1994; 12(3):510–515.
7. Cozad SC. Stage II adenocarcinoma of the endometrium: adjuvant radiotherapy and recurrence patterns. Int J Radiat Oncol Biol Phys. 2008 May 1; 71(1): 205-212.
8. Creutzberg CL, van Putten WLJ, Wárlám-Rodenhuis CC, et al. Outcome of high-risk stage IC, grade 3, compared with Stage I endometrial carcinoma patients: the postoperative radiation therapy in endometrial carcinoma trial. J. Clinical Oncology. 2004 Apr 1; 22(7): 1234-1241.
9. Gallagher MJ, Brereton HD, Rostock RA, et al. A prospective study of treatment techniques to minimize the volume of pelvic small bowel with reduction of acute and late effects associated with pelvic irradiation. Int J Radiat Oncol Biol Phys. 1986; 12(9):1565–1573.
10. Jhingran A, Winter K, Portelance L, et al. A phase II study of intensity modulated radiation therapy to the pelvis for postoperative patients with endometrial carcinoma: Radiation Therapy Oncology Group Trial 0418. Int J Radiat Oncol Biol Phys. 2012 Sep 1; 84(1):e23-e8.
11. Lin LL, Grigsby PW, Powell MA, et al. Definitive radiotherapy in the management of isolated vaginal recurrences of endometrial cancer. Int J Radiat Oncol Biol Phys. 2005 Oct 1; 63(2): 500-504.
12. Nag S, Erickson B, Parikh S, et al. The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the endometrium. Int J Radiat Oncol Biol Phys. 2000 Oct 1; 48(3):779-790.
13. Nakayama K, Nagai Y, Ishikawa M, et al. Concomitant postoperative radiation and chemotherapy following surgery was associated with improved overall survival in patients with FIGO Stages III and IV endometrial cancer. Int J Clin Oncol. 2010 Oct; 15(5): 440-446
14. National Comprehensive Cancer Network (NCCN) Guidelines® Version 5.2019 – December 23, 2019. Uterine Neoplasms. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Uterine Neoplasms. Version 5.2019. ©2019 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of the NCCN®. To view the most recent and complete version of the NCCN Guidelines®, go online to NCCN.org.
15. Onsrud M, Cvancaraova M, Hellebust, et al. Long-term outcomes after pelvic radiation for early stage endometrial early-stage endometrial cancer. J Clin Oncol. 2013 Nov 1;31(31):3951-3956.
16. Pelvic radiation therapy or vaginal implant radiation therapy, paclitaxel, and carboplatin in treating patients with high-risk stage I or Stage II endometrial cancer. Gynecologic Oncology Group and National Cancer Institute. Last verified February 2012.
17. Randomized Trial of Radiation Therapy With or Without Chemotherapy for Endometrial Cancer Leiden University Medical Center. Last update posted February 28, 2018.
18. Scholten AN, van Putten WLJ, Beerman H, et al. Postoperative radiotherapy for stage 1 endometrial carcinoma: long-term outcome of the randomized PORTEC trial with central pathology review. Int J Radiat Oncol Biol Phys. 2005 Nov 1; 63(3) 834-838.
19. Shih KK, Milgrom SA, Abu-Rustum NR, et al. Postoperative pelvic intensity-modulated radiotherapy in high risk endometrial cancer. Gynecol Oncol. 2013 Mar; 128(3):535-539.
20. Siddiqui F, Ibrahim DR, Aref I, et al. Clinical outcome of pathologic Stage IIA endometrial adenocarcinoma after intravaginal brachytherapy alone. Brachytherapy. 2009 Oct-Dec; 8(4): 396-400.
21. Small Jr. W, Erickson B, Kwakwa F. American Brachytherapy Society survey regarding practice patterns of postoperative irradiation for endometrial cancer: current status of vaginal brachytherapy. Int J Radiat Oncol Biol Phys. 2005 Dec 1; 63(5):1502-1507.
22. Solhjem NC, Petersen IA, Haddock MG. Vaginal brachytherapy alone is sufficient adjuvant treatment of surgical stage I endometrial cancer. Int J Radiat Oncol Biol Phys. 2005 August 1; 62(5): 1379-1384.
23. Small W, Beriwal S, Demanes DJ. American Brachytherapy Society consensus guidelines for adjuvant vaginal cuff brachytherapy after hysterectomy. Brachytherapy. 2012; 11:58-67.
24. Tom MC, Hepel JT et al. The American Brachytherapy Society consensus statement for electronic brachytherapy. Brachytherapy. 18 (2019) 292-298.
Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)
CPT*
HCPCS
* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.
The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy
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