307 Form

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Medical Policy Saturation Biopsy for Diagnosis, Staging and Management of Prostate Cancer Table of Contents • Policy: Commercial • Coding Information
• Information Pertaining to All Policies
• Policy: Medicare • Description
• References
• Authorization Information • Policy History

Policy Number: 307

BCBSA Reference Number: 7.01.121 (For Plan internal use only) NCD/LCD: N/A Related Policies
Cryoablation of Prostate Cancer, #149 Policy Commercial Members: Managed Care (HMO and POS), PPO, and Indemnity
Medicare HMO BlueSM and Medicare PPO BlueSM Members

Saturation biopsy is considered INVESTIGATIONAL in the diagnosis, staging, and management of prostate cancer.

Prior Authorization Information
Inpatient • For services described in this policy, precertification/preauthorization IS REQUIRED for all products if the procedure is performed inpatient.
Outpatient • For services described in this policy, see below for products where prior authorization might be required if the procedure is performed outpatient.

Outpatient Commercial Managed Care (HMO and POS) This is not a covered service. Commercial PPO and Indemnity This is not a covered service. Medicare HMO BlueSM This is not a covered service. Medicare PPO BlueSM This is not a covered service.

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CPT Codes / HCPCS Codes / ICD Codes Inclusion or exclusion of a code does not constitute or imply member coverage or provider reimbursement. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage as it applies to an individual member.

Providers should report all services using the most up-to-date industry-standard procedure, revenue, and diagnosis codes, including modifiers where applicable.

The following codes are included below for informational purposes only; this is not an all-inclusive list. The following CPT codes is considered investigational for Commercial Members: Managed Care (HMO and POS), PPO, Indemnity, Medicare HMO Blue and Medicare PPO Blue: CPT Codes CPT codes: Code Description 55706 Biopsies, prostate, needle, transperineal, stereotactic template guided saturation sampling, including imaging guidance

The following HCPCS code is considered investigational when submitted with the CPT code above for Commercial Members: Managed Care (HMO and POS), PPO, Indemnity, Medicare HMO Blue and Medicare PPO Blue:

HCPCS Codes HCPCS codes: Code Description G0416 Surgical pathology, gross and microscopic examinations, for prostate needle biopsy, any method

Description Prostate Cancer Prostate cancer is common and is the second leading cause of cancer-related deaths in men in the U.S. Diagnosis The diagnosis of prostate cancer is made by biopsy of the prostate gland. The approach to biopsy has changed over time, especially with the advent of prostate-specific antigen screening programs that identify cancer in prostates that are normal to palpation and to transrectal ultrasound. For patients with an elevated prostate-specific antigen level but with a normal biopsy, questions exist about subsequent evaluation, because repeat biopsy specimens may be positive for cancer in a substantial percentage of patients. In the early 1990s, use of sextant biopsies involving 6 random, evenly distributed biopsies became the standard approach to diagnose prostate cancer. In the late 1990s, as studies showed high false-negative rates for this strategy (missed cancers), approaches were developed to increase the total number of biopsies and to change the location of the biopsies. While there is disagreement about the optimal strategy, most would agree that initial prostate biopsy strategies should include at least 10 to 14 cores. Additional concerns have been raised about drawing conclusions about the stage (grade) of prostate cancer based on limited biopsy specimens. Use of multiple biopsies has also been discussed as an approach to identify tumors that may be eligible for subtotal cryoablation therapy. At present, many practitioners use a 12- to 14-core "extended" biopsy strategy for patients undergoing initial biopsy. This extended biopsy is done in an office setting and allows for more extensive sampling of the lateral peripheral zone; a sampling of the lateral horn might increase the cancer detection rate by approximately 25%.1,

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Another approach to increasing the number of biopsy tissue cores is "saturation" biopsy. In general, saturation biopsy is considered as more than 20 cores taken from the prostate, with an improved sampling of the anterior zones of the gland, which may be undersampled in standard peripheral zone biopsy strategies and might lead to missed cancers. Saturation biopsy might be performed transrectally or transperineally; the transperineal approach is generally performed as a stereotactic template-guided procedure with general anesthesia. Surveillance In addition to the diagnosis of prostate cancer, some have suggested that saturation biopsy could be a part of active surveillance (a treatment approach that involves surveillance with prostate-specific antigen, digital rectal exam, and routine prostate biopsies in men whose cancers are small and expected to behave indolently). Saturation biopsy has the potential to identify tumor grade more accurately than standard biopsy. Summary Description Saturation biopsy of the prostate, in which more cores are obtained than by standard biopsy protocol, has been proposed in the diagnosis (for initial or repeat biopsy), staging, and management of individuals with prostate cancer. Summary of Evidence For individuals who have suspected prostate cancer who receive initial saturation biopsy, the evidence includes randomized controlled trials (RCTs), observational studies, and systematic reviews. Relevant outcomes are overall survival (OS), disease-specific survival, test accuracy, and treatment-related morbidity. A 2013 systematic review found higher rates of cancer detection with saturation biopsy than with extended biopsy overall, but, in the subgroup of men with prostate-specific antigen (PSA) levels less than 10 ng/mL, the degree of difference was small and possibly not clinically significant. Health outcomes (eg, survival rate) were not reported. Although several studies were published after the systematic review, none showed that initial saturation biopsy improved the detection of clinically significant cancers and none reported progression or survival outcomes. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome. For individuals who have suspected prostate cancer who receive repeat saturation biopsy, the evidence includes observational studies and a systematic review. Relevant outcomes are OS, disease-specific survival, test accuracy, and treatment-related morbidity. Several studies have compared saturation with standard prostate biopsies in the repeat biopsy setting and have found significantly higher detection rates with saturation biopsy. However, at least 1 study found that about one-third of the positive findings with saturation biopsy were clinically insignificant cancers. Moreover, studies of saturation biopsy as the repeat prostate biopsy strategy focused on cancer detection rates and did not report health outcomes (eg, progression or survival). Evidence is lacking as to whether saturation biopsy leads to improved health outcomes, including the possibility of detecting clinically insignificant cancers, which could lead to unnecessary treatment. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have prostate cancer and are candidates for active surveillance who receive saturation biopsy, the evidence includes 2 nonrandomized comparative studies. Relevant outcomes are OS, disease-specific survival, test accuracy, and treatment-related morbidity. Both studies retrospectively compared standard biopsy with saturation biopsy for selecting patients for active surveillance; neither found that saturation biopsy improved the ability to select patients. In 1 study, biopsy method was not a significant predictor of upstaging and, in the other study, biopsy method was not significantly associated with selecting patients with a high Gleason score. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome. Policy History Date Action

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9/2025 Annual policy review. Policy updated with literature review through May 15, 2025; no references added. Policy statement unchanged.
9/2024 Annual policy review. Description, summary, and references updated. Policy statements unchanged. 10/2023 Clarified coding information. 8/2023 Annual policy review. Description, summary, and references updated. Policy statements unchanged. 9/2022 Annual policy review. Description, summary, and references updated. Policy statements unchanged. 9/2020 Annual policy review. Description, summary, and references updated. Policy statements unchanged. 9/2019 Annual policy review. Description, summary, and references updated. Policy statements unchanged. 9/2018 Annual policy review. Description, summary, and references updated. Policy statements unchanged. 8/2017 Annual policy review. New references added. 9/2016 Annual policy review. Policy title changed to Saturation Biopsy for Diagnosis, Staging, and Management of Prostate Cancer. References added. 9/1/2016 2/2016 Clarified coding information. 5/2015 Annual policy review. New references added. 1/2015 Clarified coding information. 4/2014 Annual policy review. Investigational indications clarified. Effective 4/1/2014. 11/2011-4/2012 Medical policy ICD 10 remediation: Formatting, editing and coding updates.
No changes to policy statements.
9/2011 Reviewed - Medical Policy Group – Urology, Obstetrics and Gynecology. No changes to policy statements. 7/2011 Reviewed - Medical Policy Group – Hematology and Oncology. No changes to policy statements. 1/19/2011 New policy effective 1/19/2011 describing ongoing non-coverage. Information Pertaining to All Blue Cross Blue Shield Medical Policies Click on any of the following terms to access the relevant information: Medical Policy Terms of Use Managed Care Guidelines Indemnity/PPO Guidelines Clinical Exception Process Medical Technology Assessment Guidelines

References

1. Zaytoun OM, Jones JS. Prostate cancer detection after a negative prostate biopsy: lessons learnt in the Cleveland Clinic experience. Int J Urol. Aug 2011; 18(8): 557-68. PMID 21692866
2. Jiang X, Zhu S, Feng G, et al. Is an initial saturation prostate biopsy scheme better than an extended scheme for detection of prostate cancer? A systematic review and meta-analysis. Eur Urol. Jun 2013; 63(6): 1031-9. PMID 23414775
3. Xue J, Qin Z, Cai H, et al. Comparison between transrectal and transperineal prostate biopsy for detection of prostate cancer: a meta-analysis and trial sequential analysis. Oncotarget. Apr 04 2017; 8(14): 23322-23336. PMID 28177897
4. Li YH, Elshafei A, Li J, et al. Transrectal saturation technique may improve cancer detection as an initial prostate biopsy strategy in men with prostate-specific antigen 10 ng/ml. Eur Urol. Jun 2014; 65(6): 1178-83. PMID 23768632

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5. Li YH, Elshafei A, Li J, et al. Potential benefit of transrectal saturation prostate biopsy as an initial biopsy strategy: decreased likelihood of finding significant cancer on future biopsy. Urology. Apr 2014; 83(4): 714-8. PMID 24680442
6. Eichler K, Hempel S, Wilby J, et al. Diagnostic value of systematic biopsy methods in the investigation of prostate cancer: a systematic review. J Urol. May 2006; 175(5): 1605-12. PMID 16600713
7. Mabjeesh NJ, Lidawi G, Chen J, et al. High detection rate of significant prostate tumours in anterior zones using transperineal ultrasound-guided template saturation biopsy. BJU Int. Oct 2012; 110(7): 993-7. PMID 22394668
8. Lee MC, Moussa AS, Zaytoun O, et al. Using a saturation biopsy scheme increases cancer detection during repeat biopsy in men with high-grade prostatic intra-epithelial neoplasia. Urology. Nov 2011; 78(5): 1115-9. PMID 22054382
9. Zaytoun OM, Moussa AS, Gao T, et al. Office based transrectal saturation biopsy improves prostate cancer detection compared to extended biopsy in the repeat biopsy population. J Urol. Sep 2011; 186(3): 850-4. PMID 21788047
10. Linder BJ, Frank I, Umbreit EC, et al. Standard and saturation transrectal prostate biopsy techniques are equally accurate among prostate cancer active surveillance candidates. Int J Urol. Sep 2013; 20(9): 860-4. PMID 23278942
11. Quintana L, Ward A, Gerrin SJ, et al. Gleason Misclassification Rate Is Independent of Number of Biopsy Cores in Systematic Biopsy. Urology. May 2016; 91: 143-9. PMID 26944351
12. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer Early Detection. Version 1.2025 https://www.nccn.org/professionals/physician_gls/pdf/prostate_detection.pdf. Accessed May 14,
14. National Comprehensive Cancer Network. Prostate Cancer (v.2.2025). https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf. Accessed May 15, 2025.
15. U.S. Preventive Services Task Force (USPSTF). Final Recommendation Statement: Prostate Cancer: Screening. 2018 May; https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/pro state- cancer-screening1. Accessed May 14, 2025.