Medical Policies - Surgery


Saturation Biopsy for Diagnosis, Staging and Management of Prostate Cancer, Including Comprehensive 3D Mapping with Biopsy

Number:SUR717.015

Effective Date:10-15-2018

Coverage:

*CAREFULLY CHECK STATE REGULATIONS AND/OR THE MEMBER CONTRACT*

Saturation biopsy or comprehensive 3D (three-dimensional) mapping with biopsy of the prostate may be considered medically necessary for men with a prior non-diagnostic transrectal ultrasound guided biopsy and one or more of the following:

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; OR

Findings of a palpable lesion on digital rectal examination (DRE).

Saturation biopsy or comprehensive 3D mapping with biopsy of the prostate is considered experimental, investigational and/or unproven for all other indications.

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 patients with prostate cancer. Saturation biopsy is meant to describe more than 12 specimens being obtained from the prostate through the rectum under ultrasound guidance. Saturation biopsy is typically done in the operating room under general or spinal anesthesia. The number of specimens obtained, and the location from which they were taken, is subjective in technique. The medical community believes there is a distinct difference between the term saturation biopsy and comprehensive 3D (three-dimensional, 3-dimensional) mapping biopsy.

Background

Prostate cancer is a common cancer 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 the biopsy of the prostate gland. The approach to biopsy has changed over time, especially with the advent of prostate-specific antigen (PSA) screening programs that identify cancer in prostates that are normal to palpation (digital rectal exam [DRE]) and to transrectal 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 diagnosis 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; sampling of the lateral horn might increase the cancer detection rate by approximately 25%. (1)

Another approach to increase the number of biopsy tissue cores is the use of “saturation” biopsy. In general, saturation biopsy is considered as more than 20 cores taken from the prostate, with 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.

Comprehensive 3D mapping prostate biopsy, while also performed under general or spinal anesthesia, is comprehensive and objective. Under transrectal ultrasound imaging, the prostate is positioned on the perineal template grid using the X and Y coordinates corresponding to the template grid. Biopsies are taken from the prostate according to the template coordinates and systematically recorded for the pathologist to identify the exact location from which they were obtained from the prostate gland. The number of specimens obtained is dependent on the size of the prostate gland. Typically, 1 biopsy sample is taken for every 1.25 gram of prostate volume.

Surveillance

In addition to diagnosis of prostate cancer, some have suggested that saturation biopsy could be a part of active surveillance (a treatment approach for men with prostate cancer that involves surveillance with PSA, DRE, 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.

Regulatory Status

Saturation biopsy is a surgical procedure and, as such, is not subject to regulation by the U.S. Food and Drug Administration (FDA). The ClariCore™ Biopsy System (Precision Biopsy, Aurora, CO) has not been approved by the FDA. The needle in the ClariCore™ Handpiece contains a single optical fiber that transmits light of different wavelengths to illuminate the tissue to enable rapid spectral analysis. Spectral analysis, in turn, may help determine if the tissue is normal or possibly suspicious. This could reduce the need for tissue samples and related pathology of normal tissue. This system can be used during the saturation biopsy procedure.

Rationale:

This policy was created in 2013 and has been updated regularly with scientific literature reviews, most recently through October 10, 2017. The following is a summary of the key literature.

Assessment of a diagnostic technology typically focuses on 3 categories of evidence:

1. Its technical performance (test-retest reliability or interrater reliability);

2. Diagnostic accuracy (sensitivity, specificity, and positive and negative predictive value) in relevant populations of patients; and

3. Clinical utility demonstrating that the diagnostic information can be used to improve patient outcomes.

Additionally, in reviewing the evidence on saturation biopsy, it is important to note that most studies report diagnostic yields (i.e., finding cancer) and/or changes in tumor stage/grade. However, more studies that link the use of saturation biopsy to improved health outcomes are needed. In addition, the preferred study design is a comparative study examining various biopsy techniques rather than case series of patients undergoing saturation biopsy.

Initial Biopsy

Technical Performance

Discussion of technical performance is irrelevant because saturation biopsy is a surgical procedure that is a variation on standard biopsy.

Diagnostic Accuracy

The literature of diagnostic accuracy consists of studies reporting prostate cancer detection rates or diagnostic yields as a primary outcome. These data are summarized in a 2013 systematic review by Jiang et al. on the utility of an initial transrectal saturation biopsy compared with an extended biopsy strategy. (2) 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 used a paired design, and 5 were nonrandomized trials. Overall, prostate cancer was diagnosed in 2328 (42.4%) of 5486 men who underwent saturation biopsy compared with 2562 (39.3%) of 6511 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). When only the higher quality studies were analyzed (i.e., the RCTs and prospective paired design), the detection rate remained statistically significantly higher for saturation biopsy (RD=0.03; 95% CI, 0.01 to 0.05; p=0.01). 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 2597 men who had saturation biopsies and in 1135 (34%) of 3322 men with extended biopsies (RD=0.04; 95% CI, 0.01 to 0.07; p=0.002). Although the subgroup analyses included individual risk factors such as PSA level, they did not differentiate between detection of lower and higher risk prostate cancers. In addition, differences in health outcomes (e.g., progression-free survival [PFS], overall survival [OS]) were not reported.

A related meta-analysis was published Xue et al. in 2017. (3) Reviewers evaluated the literature comparing transrectal and transperineal biopsy approaches for the detection of prostate cancer. 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).

A 2014 retrospective nonrandomized study by Li et al. reviewed data on 438 men who received an initial saturation biopsy and 3338 men who had an initial extended prostate biopsy. (4) In an analysis stratified by PSA levels, there was a statistically significantly higher rate of prostate cancer detection using a saturation biopsy strategy in men with a PSA level less than 10 ng/mL. Detection rates among men with a PSA level less than 4 ng/mL were 47.1% (40/85) with saturation biopsy and 32.8% (288/878) with extended biopsy (p=0.008). Rates among men with PSA levels between 4 ng/mL and 9.9 ng/mL were 50.9% (144/283) with saturation biopsy and 42.9% (867/2022) with extended biopsy (p=0.011). There was no statistically significant difference in detection rates between groups when PSA levels were greater than 10 ng/mL. Detection rates at PSA levels greater than 10/ng/mL were 60% (42/70) with saturation biopsy and 61% (267/438) with extended biopsy (p=0.879).

A related 2014 study by Li et al. evaluated the potential benefit of saturation biopsy as the initial prostate biopsy strategy by examining the yield of repeat saturation biopsy in men with initial negative findings by either saturation or extended prostate biopsy. (5) A total of 561 men were included in the study; the initial strategy was saturation biopsy in 81 men and extended biopsy in 480 men. In all cases, saturation biopsy was used for the first repeat biopsy. The overall prostate cancer detection rates were 19.8% in the group with initial saturation biopsy and 34.8% in the group with initial extended biopsy (p=0.008). Low-risk prostate cancer was defined using the Epstein criteria (i.e., Gleason score ≤6, PSA density of ≤0.15 g/mL per gram, <3 positive cores, and >50% cancer involvement in a single core). The number of intermediate- and/or high-risk prostate cancers (i.e., not low-risk) identified at first repeat biopsy was 4 (4.9%) of 81 in the initial saturation biopsy group and 85 (17.3%) of 490 in the initial extended biopsy group (p=0.048). The statistically significantly lower prostate cancer detection rate among men who initially underwent saturation biopsy would suggest that initial saturation biopsy might be less likely to miss prostate cancer than extended biopsy, and, in this study, prostate cancer diagnosed by repeat saturation after negative initial saturation biopsy was more likely to be clinically insignificant. However, the study indirectly evaluated the initial biopsy, and the number of events in men who underwent an initial saturation biopsy was relatively small.

Clinical Utility

No direct evidence from studies comparing the impact of saturation biopsy with standard biopsy for patient management decisions or health outcomes in patients with suspected prostate cancer was identified. Indirect evidence of clinical utility rests on clinical validity. Because the evidence is insufficient to demonstrate the detection of clinically significant cancers with saturation biopsy, no inferences can be made about clinical utility.

Subsection Summary: Initial Biopsy

Studies on saturation biopsy as the initial prostate biopsy strategy were summarized in a 2013 systematic review of 8 studies (2 were RCTs). The prostate cancer detection rate was significantly higher in men with saturation biopsy than in men with standard biopsy. In a subgroup analysis, the systematic review found that the higher detection rate was limited to men with PSA levels less than 10 ng/mL. Health outcomes (e.g., survival rate) were not reported. Although several studies were published after the systematic review, none showed that initial saturation biopsy detected more clinically significant cancers (substantially equivalent) and none reported progression or survival outcomes.

Repeat Biopsy

Technical Performance

Discussion of technical performance is irrelevant because saturation biopsy is a surgical procedure that is a variation on standard biopsy.

Diagnostic Accuracy

In 2006, Eichler et al. published a systematic review of cancer detection rates and complications of various prostate biopsy strategies. (6) They pooled data that compared various extended biopsy schemes for 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.

Representative studies of saturation biopsy in repeat prostate biopsies follow; these studies focused on cancer detection rates and did not report health outcomes (e.g., OS, PFS):

Mabjeesh et al. (2012) reported on a high-risk group of men with at least 2 previous negative transrectal biopsies who then underwent transperineal template-guided saturation biopsy. (7) Prostate cancer was detected in 24 (26%) of the 92 patients, predominantly in the anterior zones. A median of 30 cores was taken in the saturation biopsies. Gleason scores of 7 or higher were detected in 11 (46%) of the diagnosed men. Most tumors (83.3%) were found in the anterior zones of the gland, with a significantly higher number of positive cores than in the posterior zones (mean, 4.9 versus 1.5, p=0.015).

Lee et al. (2011) evaluated the role of transrectal saturation biopsy for cancer detection in men with high-grade prostatic intraepithelial neoplasia (HGPIN) diagnosed by extended biopsy. (8) From 1999 to 2009, 314 men had at least 1 or more repeat biopsies due to the presence of exclusive HGPIN (without any other pathologic finding) in a previous extended biopsy. They were divided into 2 groups according to the initial follow-up biopsy scheme; 178 men were followed using a second standard extended biopsy scheme, and 136 were followed using the saturation biopsy scheme. In the standard repeat biopsy group, 35 (19.7%) of 178 men had cancer on initial repeat biopsy. In the saturation biopsy group, 42 (30.9%) of 136 had cancer on initial repeat biopsy (overall, p=0.04). Multivariate analysis demonstrated that the biopsy scheme on repeat biopsy was an independent predictor of prostate cancer detection (odds ratio, 1.85; 95% CI, 1.03 to 3.29), exclusive of age, PSA level, days from initial biopsy, digital rectal exam status, and multifocal prostatic epithelial neoplasia. Pathologic findings on repeat biopsies demonstrated similar Gleason scores, regardless of biopsy technique: a Gleason score of 6 was present in 74.3% and 73.1% of specimens in the standard and saturation schemes, respectively. The presence of a Gleason score of 8 or higher was 8.6% and 9.5%, respectively.

Zaytoun et al. (2011) reported the results of a prospective, nonrandomized comparative study of extended biopsy versus office-based transrectal saturation biopsy in a repeat biopsy population. (9) After an initially negative biopsy, 1056 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).

Clinical Utility

No direct evidence from studies comparing the impact of saturation biopsy with standard biopsy for patient management decisions or health outcomes in patients with suspected prostate cancer was identified. Indirect evidence of clinical utility rests on clinical validity. Because the evidence is insufficient to demonstrate the detection of clinically significant cancers with saturation biopsy, no inferences can be made about clinical utility.

Subsection Summary: Repeat Biopsy

Several studies have compared saturation and 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.

Localized Disease

There also are discussions of using saturation biopsy as a technique to identify a localized area of prostate cancer that could be treated with subtotal cryoablation. However, given the limited data on the efficacy of this treatment approach, using saturation biopsy to determine if localized disease is present would be considered experimental, investigational and/or unproven without prior negative biopsies or additional key diagnostic features of prostate cancer.

Active Surveillance

Technical Performance

Discussion of technical performance is irrelevant because saturation biopsy is a surgical procedure that is a variation on standard biopsy.

Diagnostic Accuracy

Several studies have evaluated the accuracy of saturation biopsy for identifying patients who might be suitable candidates for active surveillance. 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. (10) 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 less than 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 standard biopsy and saturation biopsy are equally effective for identifying 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. (11) 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. 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).

Clinical Utility

No direct evidence from studies comparing the impact of saturation biopsy with standard biopsy for patient management decisions or health outcomes in patients with prostate cancer being considered for active surveillance was identified. Indirect evidence of clinical utility rests on clinical validity. Because the evidence is insufficient to demonstrate that saturation biopsy improves the identification of tumor grade, no inferences can be made about clinical utility.

Review and Other Articles Focused on Comprehensive 3D (Three-Dimensional) Mapping and Biopsy

Several additional studies, review and other articles were evaluated focusing on 3D mapping with biopsy during this medical policy update. The following table is an outcome summary of those articles.

Table 1. Published Outcome Summaries of 3D Mapping with Biopsy of Prostate

Author and Study Title

Journal and Publication M/Y

Summary

Moran et al.,

Re-biopsy of the prostate using a stereotactic transperineal technique

(12)

The Journal of Urology (2006 October)

180 consecutive patients with increasing total PSA and one benign transrectal prostate biopsy revealed 68 patients with adenocarcinoma. This was 38% of the patients with a confirmed diagnosis with only the one prior biopsy.

Moran et al., stereotactic transperineal prostate biopsy

(13)

The Journal of Urology (2009 February)

747 consecutive patients (some of which may have been a part of the 2006 study above) with increasing total PSA and one benign transrectal prostate biopsy, revealed 291 patients with adenocarcinoma. This was a slight increase to 39%, 1% over the 2006 study.

Nafie et al.,

Transperineal template prostate biopsies in men with raised PSA despite two previous sets of negative TRUS-guided prostate biopsies

(14)

World Journal of Urology (2014 August)

Retrospective review of 122 patients revealed 71 patients confirmed prostate cancer (58%).

Ahmed et al.,

Characterizing clinically significant prostate cancer using template prostate mapping biopsy

(15)

Journal of Urology (2011 August)

500 patients had transperineal biopsies following high PSA only. Parameters of the sampling size of biopsies were studied.

Taira et al.,

Performance of transperineal template-guided mapping biopsy in detecting prostate cancer in the initial and repeat biopsy setting

(16)

Prostate Cancer and Prostate Disease (2010 March)

373 consecutive patients studied following one prior negative biopsy. Cancer detection in initial biopsy was 75.9%, In all, 55.5% of the cancers detected were Gleason score of > or = 7.

Contarato et al.,

Final pathology in patients undergoing radical prostatectomy: a correlation study between stereotactic transperineal prostate biopsy and radical prostectomy

(17)

Presentation to the American Society of Therapeutic Radiation Oncology (ASTRO) Annual Meeting (2010 October)

1452 consecutive patients with rising total PSA and having a minimum of one prior benign transrectal biopsy underwent a transperineal biopsy. Of those patients, 73% had a correlation of the transperineal biopsy results to the pathology obtained from the radical prostatectomy.

Ayres et al.,

The role of transperineal template prostate biopsies in restaging men with prostate cancer managed by active surveillance

(18)

BJU International (2012 April)

101 patients in active surveillance underwent restaging biopsies. 34% had more significant prostate cancer when compared to transrectal biopsies.

Nam et al.,

Increasing hospital admission rates for urological complications after transrectal ultrasound guided prostate biopsy

(19)

The Journal of Urology (2013 January)

75,190 patients had transrectal biopsy to confirm prostate cancer, of which 33, 508 (44.6%) were. The hospital admission rate for complications within 30 days following the biopsy was 1.9% for those without cancer. The abstract did not cite for those with cancer. The majority of admissions were for infection.

Pepe et al.,

Prostate biopsy: results and advantages of the transperineal approach—twenty-year experience of a single center

(20)

World Journal of Urology (2014 April)

4000 patients had transperineal biopsy of prostate following suspicious digital exam or increasing PSA. Results indicated that a higher number of significant cancer diagnosis was found in the anterior zone biopsies (15% of the cases).

Grummet et al.,

Sepsis and ‘superbugs’: should we favor the transperineal over the transrectal approach for prostate biopsy

(21)

BJU International (2014 September)

Retrospective review of pooled data for 245 transperineal biopsies. The rate of readmission following procedure was zero. The study cites that literature shows the rate of sepsis however is rising and is as high as 5%. The data reviewed in this study showed zero for sepsis readmissions.

Barqawi et al.,

The role of 3-dimensional mapping biopsy in decision making for treatment of apparent early stage prostate cancer

(22)

The Journal of Urology (2011 July)

180 cases were prospectively reviewed. The authors found that using 3D mapping enabled a number of patients (44) with low-risk disease to elect for surveillance rather than a more active course of treatment.

Numao et al.,

Characteristics and clinical significance of prostate cancer missed by initial transrectal 12-core biopsy

(23)

BJU International (2012 March)

715 patients with high PSA or abnormal digital exam had either a transrectal or transperineal biopsy. The authors concluded transrectal biopsies were probably low-grade and low-volume disease, whereas initial transperineal has a small, but definite risk of missing anterior significant cancers.

Table Key:

3D: three dimensional;

M/Y; month and year;

PSA: prostate-specific antigen;

TRUS: transrectal ultrasound.

Improving Correlation between Biopsy and Operative Stage

Similarly, data are lacking on a potential use of saturation biopsy to assist in more accurately assessing tumor grade/stage when the treatment regimen is determined through biopsy rather than through surgical removal of the prostate. Evaluation of such an approach would require either a randomized trial or determining treatment plans for a group of patients based on use of varying numbers of their biopsy specimens.

Subsection Summary: Review and Other Articles Focused on Comprehensive 3D Mapping and Biopsy

These studies confirm the utility and favorable outcomes of comprehensive 3D mapping and biopsy in select patients to accurately sample nonpalpable lesions within the prostate and unexplained rising total PSA results. Complications from this type of prostate sampling have been minimized with estimated blood levels below 5 mL, nominal post-biopsy pain, and reduced urinary retention episodes. Confirmed higher rate of clinically significant prostate cancer diagnosis, particularly in the anterior zone, was achieved, enabling comprehensive 3D mapping with biopsy as a technique for requiring more aggressive therapy or elect surveillance.

Clinical Input Received through Physician Specialty Societies and Academic Medical Centers

The Blue Cross Blue Shield Association (BCBSA) received input from physician specialty societies and academic medical centers in 2014. While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

In response to requests, input was received through 3 physician specialty societies and 3 academic medical centers while this policy was under review in 2014. There were 5 responses from 1 specialty society, 4 responses from another, and 1 from the third for a total of 10 specialty society responses. Most reviewers stated that saturation biopsy is considered investigational and did not think that saturation biopsy in patients with 2 prior negative biopsies and persistently rising PSA level is considered medically necessary. Clinicians proposed various options that could be used in the situation of prior negative biopsies and a rising PSA: there was no consensus on the best alternative approach. Suggestions included magnetic resonance imaging (MRI) with transrectal ultrasound, multiparametric MRI, and 3D pelvic MRI. There was near consensus that there is insufficient evidence to support use of any of these techniques in the situation being considered.

Ongoing and Unpublished Clinical Trials

A search of ClinicalTrials.gov in June 2017 did not identify any ongoing or unpublished trials that would likely influence this review.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN) Guidelines

NCCN guidelines (v1.2014) on prostate cancer early detection state that, for high-risk men with negative transrectal ultrasound?guided biopsies, consideration can be given to a saturation biopsy strategy and/or use of multiparametric magnetic resonance imaging followed by an appropriate biopsy strategy given imaging results. (24)

American Urological Association (AUA) Guidelines

The 2015 AUA guideline on the early detection of prostate cancer does mention saturation biopsy in their Quality Improvement Summit Proceedings Paper, “Optimal Techniques of Prostate Biopsy and Specimen Handling”. (25) Their conclusion, “The differences in populations studied makes comparing the results from the studies of protocols involving different numbers of cores challenging. Patient age, serum PSA [prostate-specific antigen], ethnicity, and family history all influence CDR [cancer detection rate] for any biopsy strategy. What can be concluded from the literature is that increasing core number increases CDR and sextant biopsy results in an unacceptably high likelihood of false-negative results, leading to under-detection of clinically significant cancers. Increasing core numbers using saturation techniques might identify cancers missed on extended core sampling but this strategy also increases the risk of over-detection of indolent cancers without significantly improving CDR or pathology concordance.

U.S. Preventive Services Task Force (USPSTF) Recommendations

The 2012 USPSTF recommendation for prostate cancer screening does not address saturation biopsy. (26) As of June 2017, an update is in process.

National Institute for Clinical Excellence (NICE) Guidance

NICE guidance from the 2014 on “Prostate Cancer: Diagnosis and Treatment” does not provide a specific recommendation, but does discuss options available when the initial TRUS biopsy is negative, “The optimal course of action in men who are still suspected of having prostate cancer following a negative initial TRUS [transrectal ultrasound] biopsy is not well defined. The following may be considered review of initial biopsy, repeat TRUS biopsy, mpMRI [multiparametric magnetic resonance imaging], extended/saturation TRUS biopsy, 3D [three-dimensional] ultrasound plus biopsy, template biopsy, contrast enhanced ultrasound plus biopsy, and/or elastography plus biopsy.” (27)

Summary of Evidence

Studies showing improved initial detection of prostate cancer using saturation biopsy compared to the use of extended biopsies are lacking. 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, particularly in the anterior zones. It is possible that by using this technique, clinically significant cancer could be detected earlier. Comprehensive 3D mapping with biopsy has been utilized as well for detecting clinical significant cancer allowing more aggressive therapy or watchful waiting depended on the biopsy results. Therefore, saturation biopsy or comprehensive 3D mapping with biopsy of the prostate may be considered medically necessary for individuals meeting appropriate selection criteria.

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

Saturation biopsy is generally considered to be obtaining more than 20 biopsy tissue cores from the prostate in a systematic manner; it is occasionally defined as obtaining more than 18 biopsy tissue cores. CPT code (effective in 2009) 55706 may be utilized for this service.

The procedure may be also reported with CPT code 55700 when it is performed without stereotactic template guidance. Ultrasound guidance may be the method utilized, which would be reported using CPT code 76942.

Category III code 0443T reflects a biopsy system (ClariCore™) that is not approved by the U.S. Food and Drug Administration and can be used during the saturation biopsy procedure.

As of 1/1/2015, the following HCPCS codes were deleted – G0417, G0418, and G0419. HCPCS code G0416 was revised by removing the number of specimens (10-20) from the description. Although not specific to saturation biopsies, G0416 may be used to report this procedure as multiple specimens are obtained. This code may be used to report the pathology services or the biopsy services.

CODING:

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

55700, 55706, 0443T

HCPCS Codes

G0416

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual


Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does not have a national Medicare coverage position. Coverage may be subject to local carrier discretion.

A national coverage position for Medicare may have been developed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.

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 4, 2017; 8(14):23322-36. 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

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. 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):860-864. 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. Moran BJ, Braccioforte MH, Conterato DJ. Re-biopsy of the prostate using stereotactic transperineal technique. J Urol. Oct 2006; 176:1376-81. PMID 16952636

13. Moran BJ and MH Braccioforte. Stereotactic transperineal prostate biopsy. J Urol. Feb 2008; 73:386-8. PMID 19027936

14. Nafie S, Pal RP, Dormer JP, et al. Transperineal template prostate biopsies in men with raised PSA despite two previous sets of negative TRUS-guided prostate biopsies. World J Urol. Aug 2014; 32(4):971-5. Epub 2013 Dec 14. PMID 24337167

15. Ahmed HU, Hu Y, Carter T, et al. Characterizing clinically significant prostate cancer using template prostate mapping biopsy. J Urol. Aug 2011; 186(2):458-64. Epub 2011 June 15. PMID 21679984

16. Taira AV, Merrick GS, Galbreath RW, et al. Performance of transperineal template-guided mapping biopsy in detecting prostate cancer in the initial and repeat biopsy setting. Prostate Cancer Prostatic Dis. Mar 2010; 13(1):71-7. Epub 2009 Sep 29. PMID 19786982

17. Conterato DJ, Braccioforte MH, Moran BJ. Final Pathology in Patients Undergoing Radical Prostatectomy: A Correlation Study Between Stereotactic Transperineal Prostate Biopsy and Radical Prostatectomy. Paper presented at American Society of Therapeutic Radiation Oncology (ASTRO) Annual Meeting, October 2010, San Diego, California.

18. 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 .Apr 2012; 109(8):1170-6. Epub 2011 Aug 19. PMID 21854535

19. Nam RK, Saskin R, Lee Y, et al. Increasing hospital admission rates for urological complications after transrectal ultrasound guided prostate biopsy. J Urol. Jan 2013; 189(1Suppl); S12-7; discussion S17-8. PMID 23234616

20. Pepe P, Aragona F. Prostate biopsy: results and advantages of the transperineal approach-twenty-year experience of a single center. World J Urol. Apr 2014; 32 92 0; 373-7. Epub 2013 Jun 7. PMID 23743734

21. Grummet JP, Weerakoon M, Huang S, et al. Sepsis and ‘superbugs’: should we favor the transperineal over the transrectal approach for prostate biopsy? BJU Int. Sep 2014; 114(3):384-8. Epub 2014 Feb 19. PMID 24612341

22. Barqawi AB, Rove KO, Gholizadeh S, et al. The role of 3-dimensional mapping biopsy in decision making for treatment of apparent early stage prostate cancer. J Urol. Jul 2011; 186(1):80-5. Epub 2011 May 14. PMID 21571335

23. Numao N, Kawakami S, Sakura M, et al. Characteristics and clinical significance of prostate cancers missed by initial transrectal 12-core biopsy. BJU Int. Mar 2012; 109(5):665-71. Epub 2011 Sep 21. PMID 21939488

24. NCCN – Clinical Practice Guidelines in Oncology: Prostate Cancer Early Detection (V2, 2017) National Comprehensive Cancer Network. Available at <http://www.nccn.org> (accessed on 2017 October 10).

25. AUA – Optimal Techniques of Prostate Biopsy and Specimen Handling: AUA Quality Improvement Summit Proceedings Paper (2014). American Urological Association. Available at <http://www.auanet.org> (accessed on 2017 October 10).

26. USPSTF – Prostate Cancer Screening. U.S. Preventive Services Task Force. Available at <http://www.uspreventiveservicestaskforce.org (accessed on 2017 October 10).

27. NICE – Prostate Cancer: Diagnosis and Treatment 175 (2014). National Institute for Health and Clinical Excellence. Available at <http://www.nice.org.uk> (accessed on 2017 October 10).

28. ClairCore™ Biopsy System – Product information. Aurora, Colorado: Precision Biopsy (2015). Available at <http://www.precisionbiopsy.com> (accessed on 2017 October 18).

29. Saturation Biopsy for Diagnosis and Staging of Prostate Cancer. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2017 July) Surgery: 7.01.121.

Policy History:

Date Reason
10/15/2018 Reviewed. No changes.
12/15/2017 Document updated with literature review. Coverage unchanged. Title changed from: Saturation Biopsy for Diagnosis and Staging of Prostate Cancer, Including Comprehensive 3D Mapping with Biopsy, with “Management” added to policy title.
11/1/2016 Reviewed. No changes.
12/1/2015 Document updated with literature review. Requirement for two biopsies before considering saturation biopsy as medically necessary was removed from the coverage position. The lead in medically necessary coverage statement was changed to the following, “Saturation biopsy or comprehensive 3D mapping with biopsy of the prostate may be considered medically necessary for men with a prior non-diagnostic transrectal ultrasound guided biopsy and one or more of the following.” The following indication was added to the medically necessary criterion, “Findings of a palpable lesion on digital rectal examination (DRE).” The following was added to the experimental, investigational and/or unproven coverage statement, “comprehensive 3D mapping with biopsy.” Title changed from Saturation Biopsy for Diagnosis and Staging of Prostate Cancer.
7/1/2014 The following was added to Coverage: NOTE: For DNA Specimen Provenance Assignment (DSPA) Testing (e.g., Know Error® System) of tissue specimens, including but not limited to prostate or breast cancer specimens, see MED208.001 Genetic Tests (Miscellaneous).
11/15/2013 New medical document. Saturation biopsy of the prostate may be considered medically necessary when criteria are met.

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