Latest Review Date: October 2024

Category: Surgery                                                       ​​​​

POLICY:

I.  Saturation biopsy of the prostate may be considered medically necessary when ALL of the following criteria are met:

• At least TWO prior extended (12 – 14 core) transrectal prostate biopsies that are negative for invasive cancer; AND
• ONE OR MORE of the following:
  • An elevated prostate specific antigen (PSA) that is persistently rising; OR
  • Histologic evidence of atypia on prior prostate biopsy; OR
  • Histologic findings of high-grade prostatic intraepithelial neoplasia (PIN) on prior biopsy.

II.  Saturation biopsy of the prostate is considered investigational for all other indications, including but not limited to surveillance of patients with prostate cancer, due to the lack of clinical evidence demonstrating an impact on improved health outcomes.

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 patients with prostate cancer.

The diagnosis of prostate cancer is made by biopsy of the prostate gland. The approach to biopsy has changed over time. Earlier methods, usually involving 6 random, evenly distributed biopsies, showed high rates of missed cancers. 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 a wider zone which appears to increase the cancer detection rate.

Another approach to increase 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 improved sampling of the zones of the gland which may be under sampled in standard biopsy strategies and might lead to missed cancers. Saturation biopsy might be performed transrectally or transperineally. The transperineal approach is usually performed as a minimally invasive surgical procedure which makes use of a three-dimensional coordinate (stereotactic) template-guided system to locate the various biopsy targets under general anesthesia.

KEY POINTS:

Summary of Evidence

Clinical studies showing improved initial detection of prostate cancer using saturation biopsy compared to the use of extended biopsies are lacking. Available published evidence does not show that this technology improves the detection of clinically significant cancers. The use of saturation biopsy as a repeat biopsy after prior negative biopsies in men with persistent clinical suspicion of prostate cancer appears to increase the detection rate of cancer. Available published evidence suggests that by using this technology, clinically significant cancer could be detected earlier. Therefore, saturation biopsy of the prostate may be considered medically necessary when certain criteria are met. For patients with prostate disease, available evidence does not support the use of saturation biopsy for active surveillance.

Prostate cancer is the second leading cause of death from malignancy in American men. The primary goal during pretreatment evaluation of prostate cancer is disease detection, localization, establishing disease extent, and evaluating aggressiveness. Prostate cancer is typically diagnosed by elevated serum prostate-specific antigen level or abnormal digital rectal examination. Initial tissue diagnosis is commonly obtained by transrectal ultrasound-guided biopsy or MRI-targeted biopsy, which has recently been established as standard of care for detecting, localizing, and assessing local extent of prostate cancer. If clinical suspicion of cancer persists despite initial negative biopsies, the use saturation biopsy has been suggested due to an improved sampling of the gland.

Initial Saturation Biopsy

Studies on saturation biopsy as the initial prostate biopsy strategy are summarized in a systematic review published by Jiang et al in 2013. Eight studies (total n=11,997 participants) met eligibility criteria (i.e., compared 2 biopsy strategies on initial biopsy). Two of the studies were randomized controlled trials (RCTs), one study used a paired design, and 5 studies were nonrandomized trials. Overall, prostate cancer was diagnosed in 2,328 (42.4%) of 5,486 men who underwent saturation biopsy compared with 2,562 (39.3%) of 6,511 men who had extended biopsy. The detection rate was statistically significantly higher in the saturation biopsy group (risk difference [RD], 0.004; 95% confidence interval [CI], 0.01 to 0.008; p=0.002). Subgroup analysis found that the difference in detection rates between saturation and extended biopsy strategies was limited to the subgroup of men with prostate-specific antigen (PSA) levels less than 10 ng/ml. Within this group, prostate cancer was diagnosed in 998 (38%) of 2,597 men who had saturation biopsies and in 1,135 (34%) of 3,322 men with extended biopsies (RD=0.04; 95% CI, 0.01 to 0.07; p=0.002). Limitations of this review include lack of differentiation between detection of lower and higher risk prostate cancers. In addition, differences in health outcomes (e.g., progression-free survival, overall survival) were not reported.

In 2017, Xue et al published a related meta-analysis evaluating the literature comparing transrectal and transperineal biopsy approaches for the detection of prostate cancer. Overall, this meta-analysis included a total of 4,280 patients randomly divided between transrectal and transperitonal approaches. Prostate biopsies included sextant (usually 6 random, evenly distributed biopsies), extensive, and saturation biopsy procedures. In an analysis stratified by the number of biopsy cores, there was no significant difference in the prostate cancer detection rate with the transrectal strategy or the transperineal biopsy strategy in studies using extended biopsy (odds ratio, 1.14; 95% CI, 0.89 to 1.45) or studies using saturation biopsy (odds ratio, 1.11; 95% CI, 0.92 to 1.34).

Repeat Saturation Biopsy

In 2006, Eichler et al published a large systematic review of cancer detection rates and complications of various prostate biopsy strategies in men scheduled for biopsy. They pooled data that compared various extended biopsy schemes for 87 studies involving 20,698 patients. Reviewers concluded that prostate biopsy schemes consisting of 12 cores that add laterally directed cores to the standard sextant scheme seem to have the right balance between the cancer detection rate and adverse events, and that taking more than 12 cores added no significant benefit.

In 2011, Zaytoun et al reported the results of a prospective, nonrandomized comparative study of extended biopsy versus office-based transrectal saturation biopsy in a repeat biopsy population. After an initially negative biopsy, 1,056 men underwent a repeat 12- to 14-core biopsy (n=393) or a 20- to 24-core repeat biopsy (n=663) at the discretion of the attending urologist’s practice pattern. Indications for second biopsy included a previous suspicious pathologic finding and/or clinical indications such as abnormal digital rectal exam, persistently increased PSA level, and PSA level increasing more than 0.75 ng/mL annually. Prostate cancer was detected in 29.8% (n=315) of repeat biopsies. The saturation biopsy group had a detection rate of 32.7% versus 24.9% in the extended biopsy group (p=0.008). Of the 315 positive biopsies, 119 (37.8%) revealed clinically insignificant cancer (defined as Gleason score <7, total of ≤3 positive cores, and maximum of <50% of cancer in any positive core). There was a trend toward increased clinically insignificant cancer detection for saturation biopsy (40.1%) versus extended biopsy (32.6%; p=0.02).

In 2015, Isbarn et al published a non-systematic review comparing standard vs saturation schemes in initial and repeat prostate biopsy. Results indicated that on initial prostate biopsy, there is growing evidence that a saturation scheme is associated with higher cancer detection rate compared to a standard one in men with lower PSA levels (<10 ng/ml), larger prostates (>40cc), or lower PSA density values (<0.25 ng/ml/cc). However, these cut-offs are not uniform and differ among studies. On repeat biopsy, cancer detection rate is likewise higher with saturation protocols. Estimates of insignificant prostate cancers vary widely due to differing definitions of insignificant disease. Very extensive sampling is associated with high rate of acute urinary retention, whereas other severe adverse events, such as sepsis, appear not to occur more frequently with saturation schemes.

Active Surveillance

Use of saturation biopsy has been proposed to improve health outcomes by better identifying patients with prostate cancer who are appropriate candidates for surveillance. Traditionally, Gleason score is the criterion used to select men at an increased risk of biochemical recurrence and prostate cancer mortality.

In 2013, Linder et al reviewed data on 500 consecutive patients who underwent standard template prostate biopsy (12 cores) or saturation biopsy (at least 18 cores) before radical prostatectomy. They identified 218 patients who would have been candidates for active surveillance. Criteria were a Gleason score no greater than 6, clinical stage T1 or T2a, PSA level <10 ng/mL, and involvement of no more than 33% of cores. Among these 218 patients, 124 had undergone standard biopsy and 94 underwent saturation biopsy. In a multivariate analysis, biopsy method was not a significant predictor of upstaging on analysis of pathologic findings (p=0.26). In addition, the 5-year biochemical failure-free survival rates (defined as PSA level of at least 0.4 ng/mL) did not differ significantly between groups: rates were 97% for standard biopsy and 95% for saturation biopsy (p=0.11). The reviewers concluded that in men with prostate cancer, standard and saturation transrectal prostate biopsies techniques are equally predictive of candidates for active surveillance.

In 2016, Quintana et al compared 12-core biopsy and saturation biopsy (18-33 cores; median, 20 cores) in 375 patients to determine the Gleason score accurately. The authors stated that patients with Gleason scores of 4 or higher were generally not considered candidates for active surveillance. Gleason score was confirmed by pathologic analysis of prostate specimens. For detecting a high Gleason grade (i.e., ≥4), there were no statistically significant differences in the sensitivity, specificity, negative predictive value, or positive predictive value of 12-core versus saturation biopsies. On multivariate analysis, prebiopsy PSA and clinical T stage independently predicted Gleason upgrading; saturation biopsy was not a significant predictor. The areas under the receiver operating characteristic curve were 0.82 for saturation biopsy and 0.84 for 12-core biopsy (p-value not reported).

Practice Guidelines and Position Statements

In 2023, the American College of Radiology (ACR) published a 2022 update to their appropriateness criteria for pretreatment detection, surveillance, and staging of prostate cancer. The expert panel states the following:

In patients with clinically suspected prostate cancer who have had 1 negative standard TRUS-guided systematic biopsy, a second TRUS-guided systematic biopsy will be positive in 15% to 20% of cases, and so a second repeat biopsy in this setting is reasonable. The yield from additional systematic biopsies after a second biopsy falls off rapidly, with reported positive rates of 8% to 17% for the third biopsy and 7% to 12% for the fourth, suggesting alternative approaches such as MRI-targeted biopsy or saturation biopsy may be more useful in this specific setting of patients with 2 or more negative TRUS-guided systematic biopsies and persistent clinical suspicion for prostate cancer.

In 2015, the American Urological Association (AUA) published a quality improvement white paper addressing optimal techniques of prostate biopsy. The authors conclude that although increasing the number of biopsy cores has led to increased prostate cancer detection rates, many cancers diagnosed on extended sampling are small, low grade, and indolent. Although increasing the number of cores can help detect indolent disease, this strategy can still miss clinically significant or potentially lethal cancers. It is proposed that optimal biopsy strategy includes an adequate number of cores to provide confidence in a negative finding while limiting the number of cores and pathologic specimens sufficiently to avoid over-detection and cost escalation.

National Comprehensive Cancer Network (NCCN) guidelines 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 at this time given the benefits seen for 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 do not address saturation biopsy.

BENEFIT APPLICATION:

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

ITS: Covered if covered by the Participating Home Plan

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

CURRENT CODING:

CPT Codes:

HCPCS:

REFERENCES:

1. 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. 2006;175(5):1605-1612.

2. Expert Panel on Urological Imaging, Akin O, Woo S, Turkbey B, et al. ACR Appropriateness Criteria® pretreatment detection, surveillance, and staging of prostate cancer: 2022 update. J Am Coll Radiol, 2023;20(5):S187-S210.

3. Isbarn H, et al. Systematic ultrasound-guided saturation and template bipsy of the prostate: indications and advantages of extended sampling. Arch Esp Urol. 2015;68(3):296-306.

4. 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. 2013;63(6):1031-1039.

5. 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. 2013;20(9):860-864.

6. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Prostate Cancer. Version 4.2024. Available at: www.nccn.org/guidelines/category_1.

7. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Prostate Cancer Early Detection. Version 2.2024. Available at: www.nccn.org/guidelines/category_2.

8. Quintana L, Ward A, Gerrin SJ, et al. Gleason misclassification rate is independent of number of biopsy cores in systematic biopsy. Urology. 2016; 91:143-149.

9. Taneja SS, Bjurlin MA, Carter HB, et al. American Urological Association/ Optimal techniques of prostate biopsy and specimen handling. Advancing Urology. 2015.

10. 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. 2017;8(14):23322-23336.

11. 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. 2011;186(3):850-854.

POLICY HISTORY

Reviewed and posted July 1, 2021. 

​​​February 2022: Annual review completed. No change to policy intent.

March 2023: Update to Current Coding section to remove CPT code 55700. No change to policy intent.

February 2024: Annual review completed. No change to policy intent.

October 2024: Updates include Key points added and References added. No change to policy intent.

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.