Latest Review Date: July 2024

Category: Surgery                                                                 

POLICY:

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

For saturation biopsy using magnetic resonance imaging, refer to medical policy #615: Magnetic Resonance Imaging (MRI) Targeted Biopsy of the Prostate

DESCRIPTION OF PROCEDURE OR SERVICE:

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.

Prostate Cancer

Prostate cancer is common and is the second leading cause of cancer-related deaths in men in the United States. 

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 PSA (prostate-specific antigen) screening programs that identify cancer in prostates that are normal to palpation and to trans-rectal ultrasound.  For patients with an elevated PSA-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%.

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 under-sampled 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.

KEY POINTS:

The most recent literature review was updated through May 22, 2024.

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 (e.g., 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 overall survival, 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 one 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 (e.g., progression or survival). The 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 two nonrandomized comparative studies. Relevant outcomes are overall survival, 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 one 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.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network Guidelines

The National Comprehensive Cancer Network (NCCN) guidelines (v.2.2024) on early detection of prostate cancer state that despite emerging evidence, the panel does not recommend a saturation biopsy strategy for all individuals with previous negative biopsies given the benefits seen for magnetic resonance imaging (MRI) and MRI-targeted biopsy in this patient population. The emerging evidence cited included 1 prospective nonrandomized study (Zaytoun et al 2011) and uncontrolled observational studies published between 2006 and 2013.

NCCN guidelines on prostate cancer treatment (v.4.2024) do not mention saturation biopsy.

U.S. Preventive Services Task Force Recommendations

The U.S. Preventive Services Task Force (2018) recommendations on prostate cancer screening did not address saturation biopsy. This topic is currently being updated.

KEY WORDS:

Biopsy, Prostate, Saturation, prostate cancer, Prostate mapping, saturation sampling of the prostate, stereotactic template guided saturation sampling, transperineal

APPROVED BY GOVERNING BODIES:

Saturation biopsy is a surgical procedure and, as such, is not subject to regulation by the U.S. Food and Drug Administration.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP: Special benefit consideration may apply.  Refer to member’s benefit plan.

CURRENT CODING: 

CPT Codes:

HCPCS:

REFERENCES:

1. American Urological Association. Early Detection of Prostate Cancer: AUA Guideline. 2013; www.auanet.org/common/pdf/education/clincal-guidance/Prostate-Cancer-Detection.pdf. 
2. Ayres BE, Montgomery BS, Barber NJ et al. The role of transperineal template prostate biopsies in restaging men with prostate cancer managed by active surveillance. BJU Int 2012; 109(8):1170-6.
3. Giulianelli R, Brunori S, Gentile BC et al. Saturation biopsy technique increase the capacity to diagnose adenocarcinoma of prostate in patients with PSA < 10 ng/ml, after a first negative biopsy. Arch Ital Urol Androl 2011; 83(3):154-9.
4. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
5. 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.
6. 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.
7. 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.
8. 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):714-718.
9. 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):860-864.
10. 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.
11. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer Early Detection. Version 2.2024 www.nccn.org/professionals/physician_gls/pdf/prostate_detection.pdf. 
12. National Comprehensive Cancer Network. Prostate Cancer (v.4.2024). www.nccn.org/professionals/physician_gls/pdf/prostate.pdf.
13. Pepe P, Aragona F. Morbidity after transperineal prostate biopsy in 3000 patients undergoing 12 vs 18 vs more than 24 needle cores. Urology. Jun 2013; 81(6):1142-1146.
14. Pepe P, Pennisi M. Erectile dysfunction in 1050 men following extended (18 cores) vs saturation (28 cores) vs saturation plus MRI-targeted prostate biopsy (32 cores). Int J Impot Res. Jan-Feb 2016; 28(1):1-3.
15. Quintana L, Ward A, Gerrin SJ, et al. Gleason misclassification rate is independent of number of biopsy cores in systematic biopsy. Urology. May 2016; 91:143-149.
16. U.S. Preventive Services Task Force (USPSTF). Archived: Prostate Cancer Screening. 2012 May; www.uspreventiveservicestaskforce.org/Page/Document/updatesummaryfinal /prostate-cancer-screening. 
17. U.S. Preventive Services Task Force (USPSTF). Final Recommendation Statement: Prostate Cancer: Screening. 2018 May; www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/prostate-cancer-screening1. 
18. 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.
19. 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.
20. 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.

POLICY HISTORY:

Medical Policy Group, December 2009 (3)

Medical Policy Administration Committee, January 2010

Available for comment January 26-March 11, 2010

Medical Policy Group October 2010 (3)

Medical Policy Group, October 2011(1): Update to Key Points and References related to MPP update; no change in policy statement

Medical Policy Panel, October 2012

Medical Policy Group, November 2012 (1): 2012 Updates to Key Points and References

Medical Policy Group, November 2012: Added 2013 HCPCS Code updates

Medical Policy Panel February 2014

Medical Policy Group February 2014 (4): Removed section from policy statement that specified what constitutes a saturation biopsy. Updated Key Points and References.

Medical Policy Panel, March 2015

Medical Policy Group, March 2015 (4): Updates to Key Points Coding, and References. Added previous coding section to include codes G0417 – G 0419.  No change to policy statement.

Medical Policy Panel, July 2016

Medical Policy Group, July 2016 (4): Updates to Policy Title, Description, Key Points, Key Words and References.  No change to policy statement.

Medical Policy Panel, July 2017

Medical Policy Group, July 2017 (4): Updates to Key Points and References. No change to policy statement.

Medical Policy Group, August 2017 (4): Added statement under policy section to refer to MP# 615 for saturation biopsy using MRI guidance.

Medical Policy Panel, July 2018

Medical Policy Group, July 2018 (4): Updates to Key Points, Approved by Governing Bodies, and References. No change to policy statement.  Removed Previous Coding Section including codes G0417 – G0419.  Codes deleted 12/31/14.

Medical Policy Panel, July 2019

Medical Policy Group, July 2019 (4): Updates to Key Points and References. No change to policy statement.

Medical Policy Panel, July 2020

Medical Policy Group, July 2020 (5): Updates to Key Points, Practice Guidelines and Position Statements, and References. No change to Policy Statement.

Medical Policy Panel, July 2021

Medical Policy Group, July 2021 (5): Updates to Description, Key Points, Practice Guidelines and Position Statements, and References. Policy statement updated to remove “not medically necessary,” no change to policy intent.

Medical Policy Panel, July 2022

Medical Policy Group, July 2022 (5): Updates to Key Points, Practice Guidelines and Position Statements, and References. No change to Policy Statement.

Medical Policy Panel, July 2023

Medical Policy Group, July 2023 (11): Updates to Key Points, Benefit Application and References. No change to Policy Statement.

Medical Policy Panel, July 2024

Medical Policy Group, July 2024 (11): Updates to Description, Key Points, and References. No change to Policy Statement.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.