Description of Procedure or Service

Prostate cancer is characterized by a malignancy of the small walnut shaped gland that produces seminal fluid in males which ranges clinically from a microscopic, well-differentiated tumor that may never be clinically significant to an aggressive, high-grade cancer (Kantoff, Taplin, & Smith, 2017).

***Note: This Medical Policy is complex and technical. For questions concerning the technical language and/or specific clinical indications for its use, please consult your physician.

Policy

BCBSNC will provide coverage for prostate biopsy when it is determined to be medically necessary because the medical criteria and guidelines shown below are met.

Benefits Application

This medical policy relates only to the services or supplies described herein. Please refer to the Member's Benefit Booklet for availability of benefits. Member's benefits may vary according to benefit design; therefore member benefit language should be reviewed before applying the terms of this medical policy.

When prostate biopsy is covered

Prostate biopsy involving 12 core extended sampling* (see Note 1 below) is considered medically necessary in the initial diagnosis of prostate cancer as a follow up to abnormal PSA results, presence of a palpable nodule on digital rectal examination, or suspicious radiologic findings.

*Note 1: One vial per sextant, with no more than two core samples per vial.

When prostate biopsy is not covered

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

Policy Guidelines

Prostate cancer is the most common cancer in American men and the second leading cause of death in men aged 65 years or older (Balducci, Pow-Sang, Friedland, & Diaz, 1997; Tabayoyong & Abouassaly, 2015) with an estimated 161,000 cases and 26,700 deaths in the US in 2017 (Siegel, Miller, & Jemal, 2017). About 1 man in 6 will be diagnosed with prostate cancer during his lifetime (Kantoff et al., 2017).

Many cases of prostate cancer do not become clinically evident, as indicated in autopsy series, where prostate cancer is detected in approximately 30 percent of men age 55 and approximately 60 percent of men by age 80 (Bell, Del Mar, Wright, Dickinson, & Glasziou, 2015). These data suggest that prostate cancer often grows so slowly that most men die of other causes before the disease becomes clinically advanced (Hoffman, 2017).

Prostate cancer survival is related to many factors, especially the extent of tumor at the time of diagnosis. The five-year relative survival among men with cancer confined to the prostate (localized) or with just regional spread is 100 percent, compared with 29.3 percent among those diagnosed with distant metastases (Hoffman, 2017).

Findings on digital rectal examination including the presence of nodules, induration, or asymmetry or elevated prostate specific antigen (PSA) levels indicate the need for prostate biopsy. Although generally considered safe, prostate biopsy is an invasive procedure and recommendations for its use are limited to a subset of patients. Screening the general population for prostate cancer remains a controversial issue, since improved patient outcomes have not been demonstrated (Andriole et al., 2009; Hoffman, 2017; NCCN, 2017; Schroder et al., 2009).

Multiple sampling schemes have been developed in an effort to improve the accuracy of prostate biopsy in the detection of cancer. Systematic prostate sampling is performed and augmented by additional sampling of any abnormal areas found on ultrasound or rectal examination (Gosselaar et al., 2008). Originally during transrectal ultrasound (TRUS)-guided biopsy, a six-core, or sextant biopsy technique, was commonly employed taking one sample each from the apex, base, and mid-prostate on each side (Hodge, McNeal, Terris, & Stamey, 1989). However, this method misses approximately 30 percent of clinically significant cancers (Babaian et al., 2000; Epstein, Walsh, Sauvageot, & Carter, 1997; Norberg et al., 1997; Roehl, Antenor, & Catalona, 2002), and has been replaced by extended core biopsy which obtains five to seven evenly-distributed specimens from each side, sampling more extensively from the lateral aspects of the prostate (Babaian et al., 2000; Eskicorapci et al., 2004; Ukimura et al., 2013; Uno, Nakano, Ehara, & Deguchi, 2008). Systematic reviews have found that and schemes with 12 core samples that took additional laterally directed cores detected 31 percent more cancers compared with a six-core approach increasing number of cores were significantly associated with increased detection of prostate cancer (Eichler et al., 2006; Hoffman, 2017).

Saturation biopsy involves extensive sampling of the prostate, obtaining up to 24 core samples. Saturation biopsy is not appropriate for initial screening as it does not provide increased cancer detection when used for first-time biopsy but may provide increased sensitivity when repeat biopsies are performed and should be considered after two negative TRUS-biopsies (Li et al., 2014; Sajadi, Kim, Terris, Brown, & Lewis, 2007; Zaytoun, Moussa, Gao, Fareed, & Jones, 2011). Saturation biopsy detects prostate cancer in 22 to 33 percent of patients undergoing repeat biopsy (Pepe & Aragona, 2007; Stewart, Leibovich, Weaver, & Lieber, 2001), but is associated with a higher incidence of complications (Hoffman, 2017).

Magnetic Resonance (MR) imaging, which provides superior resolution to ultrasound (Ward et al., 2012), can also be used to guide biopsy (Hoeks et al., 2011; Pinto et al., 2011). Kasivisvanathan et al (2018) found that in a randomized study of 500 men, the use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously.

Clinical Validity and Utility

Benway and Andriole (2017) stated that “saturation biopsy detects prostate cancer in 22 to 33 percent of patients undergoing repeat biopsy but is associated with a higher incidence of complications.” The authors further stated that saturation biopsy does not provide increased cancer detection when used for first-time biopsy and is not appropriate for initial screening. However, it provides increased sensitivity when repeat biopsies are performed and should be performed after a second negative TRUS-biopsy in the patient for whom clinical suspicion for prostate cancer remains high.

Thompson et al (2015) studied whether saturation or transperineal biopsy altered oncological outcomes, compared with standard transrectal biopsy. They conducted a retrospective analysis of prospectively collected data from two cohorts with localised prostate cancer (1998-2012) undergoing active surveillance for low-risk prostate cancer. Outcomes were compared for standard vs saturation biopsy as well as transrectal vs transperineal biopsy. The authors concluded that “saturation biopsy increased progression to treatment on AS; longer follow-up is needed to determine if this represents beneficial earlier detection of significant disease or overtreatment. Transperineal biopsy reduced the likelihood of unfavourable disease at RP, possibly due to earlier detection of anterior tumours (Thompson et al., 2015).”

Zaytoun et al (2011) “compared saturation and extended repeat biopsy protocols after initially negative biopsy.” They found that “Saturation biopsy detected almost a third more cancers (32.7% vs 24.9%, p=0.0075). In patients with a benign initial biopsy saturation biopsy achieved significantly greater prostate cancer detection (33.3% vs 25.6%, p=0.027). For previous atypical small acinar proliferation and/or high grade prostatic intraepithelial neoplasia there was a trend toward higher prostate cancer detection rate in the saturation group but it did not attain statistical significance (31.2% vs 23.3%, p=0.13). Of 315 positive biopsies 119 (37.8%) revealed clinically insignificant cancer (40.1% vs 32.6%, p=0.2).” The authors concluded that: “Compared to extended biopsy, office based saturation biopsy significantly increases cancer detection on repeat biopsy. The potential for increased detection of clinically insignificant cancer should be weighed against missing significant cases.”

The PROMIS study (Brown et al., 2018) assessed the ability of multi-parametric MRI (mpMRI) to identify men who can safely avoid unnecessary biopsy, the ability of the mpMRI-based pathway to improve the rate of detection of clinically significant (CS) cancer compared with TRUS-guided biopsy and estimated the cost-effectiveness of a mpMRI-based diagnostic pathway in 740 men. They found that “For CS cancer, TRUS-guided biopsy showed a sensitivity of 48% (95% CI 42% to 55%), specificity of 96% (95% CI 94% to 98%), PPV of 90% (95% CI 83% to 94%) and NPV of 74% (95% CI 69% to 78%). The sensitivity of mpMRI was 93% (95% CI 88% to 96%), specificity was 41% (95% CI 36% to 46%), PPV was 51% (95% CI 46% to 56%) and NPV was 89% (95% CI 83% to 94%). A negative mpMRI scan was recorded for 158 men (27%). Of these, 17 were found to have CS cancer on TPM-biopsy. Economic evaluation - the most cost-effective strategy involved testing all men with mpMRI, followed by MRI-guided TRUS-guided biopsy in those patients with suspected CS cancer, followed by rebiopsy if CS cancer was not detected.”

State and Federal Regulations, as applicable

The FDA has cleared devices including needles, reagents, instrumentation, and imaging systems for use in prostate biopsy[MO1].

Guidelines and Recommendations

The American Urological Association (AUA)

The AUA published a paper (2015) on Optimal Techniques of Prostate Biopsy and Specimen Handling which recommended: “12-core systematic sampling methodology that incorporates apical and far-lateral cores in the template distribution. The results of our literature review suggest that collecting more than 12 cores or sampling the transition zone offer no benefit for initial diagnostic biopsies. However, such approaches might be useful for resampling following a negative biopsy”

The AUA/ASTRO/SUO published guidelines (Sanda et al., 2017) which state

“28. Localized prostate cancer patients who elect active surveillance should have accurate disease staging including systematic biopsy with ultrasound or MRI-guided imaging. (Clinical Principle)”

National Comprehensive Cancer Network (NCCN)

NCCN Guidelines (NCCN, 2018) stated that “systemic prostate biopsy under TRUS guidance is the recommended technique for prostate biopsy.” It recommends the use of an extended pattern at least 12 core biopsies as it has been validated and results in enhances cancer detection compared to sextant biopsy schemes.

Anterior directed biopsy is not supported in routine biopsy. However, this can be added to an extended biopsy protocol in a repeat biopsy if PSA is persistently elevated”. “At present the panel does not recommend the use of advanced biopsy techniques or specific imaging other than TRUS for initial biopsy, although they can be considered in the repeat biopsy setting.”

“Overall the panel believes that the data for the use of MRI and MRI targeted biopsies in the initial biopsy setting are insufficient, as yet, to recommend them over standard, US-guided biopsies in this setting at this time. However, data showing that the use of MRI may reduce unnecessary biopsies, lower detection of clinically insignificant disease, and better identify high risk cancer are accumulating. MRI and MRI targeted biopsy can be considered in the setting of repeat biopsy”

“A negative biopsy does not preclude a diagnosis of prostate cancer on subsequent biopsy. If clinical suspicion of cancer persists after a negative biopsy, consideration can be given to saturation biopsy strategies and/or the use of multiparametric MRI followed by an appropriate targeted biopsy technique based on the result.”

“Based on emerging evidence, the panel believes that a saturation biopsy strategy can be considered for very high-risk men with previous negative biopsies”

American College of Radiology

The ACR (Coakley et al., 2017) rated TRUS guided biopsy a 9, and MRI targeted prostate biopsy a 7 in the most recent ACR Appropriateness Criteria for Prostate cancer Pretreatment detection, surveillance and staging for clinically suspected prostate cancer with no prior biopsy. A rating of 7, 8 or 9 are usually appropriate. MRI targeted biopsy was rated an 8 and repeat TRUS biopsy rated a 7 in clinically suspected prostate cancer, prior negative TRUS biopsy as well as Clinically established low risk prostate cancer for active surveillance.

They note that “Overall, the clinical paradigm for prostate cancer diagnosis is rapidly moving towards MRI-targeted transrectal biopsy, based on substantial evidence from several centers (notably the National Institutes of Health; New York University [NYU]; University of California, Los Angeles [UCLA]; and Nijmegen) that this approach can transform baseline cancer evaluation when compared with traditional systematic biopsy, with fewer false negatives, better tumor characterization, improved tumor localization, and better treatment stratification, especially stratification to lower-risk cohorts that may be appropriate for active surveillance or focal therapy”

American Cancer Society

The American Cancer Society published guidelines (Wolf et al., 2010) which state

• A PSA level of 4.0 ng/mL or greater historically has been used to recommend referral for further evaluation or biopsy, which remains a reasonable approach for men at average risk for prostate cancer.
• For PSA levels between 2.5 ng/mL and 4.0 ng/mL, health care providers should consider an individualized risk assessment that incorporates other risk factors for prostate cancer, particularly for high‐grade cancer, that may be used to recommend a biopsy. Factors that increase the risk of prostate cancer include African American race, family history of prostate cancer, increasing age, and abnormal DRE. A previous negative biopsy lowers the risk. Methods are available that merge this information to achieve an estimate of a man's overall risk of prostate cancer and, more specifically, of his risk of high‐grade prostate cancer

US Preventive Services Task Force (USPSTF, 2018) Within the 2018

USPSTF recommendation statement regarding prostate screening, they state, “Men with a positive PSA test result may undergo a transrectal ultrasound-guided core-needle biopsy of the prostate to diagnose prostate cancer… Although protocols vary, active surveillance usually includes regular, repeated PSA testing and often repeated digital rectal examination and prostate biopsy, with potential for exposure to repeated harms from biopsies.”

Billing/Coding/Physician Documentation Information

This policy may apply to the following codes. Inclusion of a code in this section does not guarantee that it will be reimbursed. For further information on reimbursement guidelines, please see Administrative Policies on the Blue Cross Blue Shield of North Carolina web site at www.bcbsnc.com. They are listed in the Category Search on the Medical Policy search page.

Applicable service codes: 88305, G0416

BCBSNC may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful, but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included.

Scientific Background and Reference Sources

Andriole, G. L., Crawford, E. D., Grubb, R. L., 3rd, Buys, S. S., Chia, D., Church, T. R., . . .
Berg, C. D. (2009). Mortality results from a randomized prostate-cancer screening trial. N Engl J
Med, 360(13), 1310-1319. doi:10.1056/NEJMoa0810696

Babaian, R. J., Toi, A., Kamoi, K., Troncoso, P., Sweet, J., Evans, R., . . . Chen, M. (2000). A comparative analysis of sextant and an extended 11-core multisite directed biopsy strategy. J Urol, 163(1), 152-157.

Balducci, L., Pow-Sang, J., Friedland, J., & Diaz, J. I. (1997). Prostate cancer. Clin Geriatr Med, 13(2), 283-306.

Bell, K. J., Del Mar, C., Wright, G., Dickinson, J., & Glasziou, P. (2015). Prevalence of incidental prostate cancer: A systematic review of autopsy studies. Int J Cancer, 137(7), 1749-1757. doi:10.1002/ijc.29538

Brown, L. C., Ahmed, H. U., Faria, R., El-Shater Bosaily, A., Gabe, R., Kaplan, R. S., . . .
Emberton, M. (2018). Multiparametric MRI to improve detection of prostate cancer compared with transrectal ultrasound-guided prostate biopsy alone: the PROMIS study. Health Technol Assess, 22(39), 1-176. doi:10.3310/hta22390

Coakley, F. V., Oto, A., Alexander, L. F., Allen, B. C., Davis, B. J., Froemming, A. T., . . .
Eberhardt, S. C. (2017). ACR Appropriateness Criteria((R)) Prostate Cancer-Pretreatment Detection, Surveillance, and Staging. J Am Coll Radiol, 14(5s), S245-s257. doi:10.1016/j.jacr.2017.02.026

Eichler, K., Hempel, S., Wilby, J., Myers, L., Bachmann, L. M., & Kleijnen, J. (2006). Diagnostic value of systematic biopsy methods in the investigation of prostate cancer: a systematic review. J Urol, 175(5), 1605-1612. doi:10.1016/s0022-5347(05)00957-2

Epstein, J. I., Walsh, P. C., Sauvageot, J., & Carter, H. B. (1997). Use of repeat sextant and transition zone biopsies for assessing extent of prostate cancer. J Urol, 158(5), 1886-1890.

Eskicorapci, S. Y., Baydar, D. E., Akbal, C., Sofikerim, M., Gunay, M., Ekici, S., & Ozen, H.(2004). An extended 10-core transrectal ultrasonography guided prostate biopsy protocol improves the detection of prostate cancer. Eur Urol, 45(4), 444-448; discussion 448-449. doi:10.1016/j.eururo.2003.11.024

Gosselaar, C., Roobol, M. J., Roemeling, S., Wolters, T., van Leenders, G. J., & Schroder, F. H. (2008). The value of an additional hypoechoic lesion-directed biopsy core for detecting prostate cancer. BJU Int, 101(6), 685-690. doi:10.1111/j.1464-410X.2007.07309.x

Hodge, K. K., McNeal, J. E., Terris, M. K., & Stamey, T. A. (1989). Random systematic versus directed ultrasound guided transrectal core biopsies of the prostate. J Urol, 142(1), 71-74; discussion 74-75.

Hoeks, C. M., Barentsz, J. O., Hambrock, T., Yakar, D., Somford, D. M., Heijmink, S. W., . . .
Futterer, J. J. (2011). Prostate cancer: multiparametric MR imaging for detection, localization, and staging. Radiology, 261(1), 46-66. doi:10.1148/radiol.11091822

Hoffman, R. (2017). Screening for prostate cancer - UpToDate. In J. Melin (Ed.), UpToDate. Waltham. MA. Retrieved from https://www.uptodate.com/contents/screening-for-prostatecancer?source=see_link#H30.

Kantoff, P., Taplin, M.-E., & Smith, J. (2017). Clinical presentation and diagnosis of prostate cancer - UpToDate. In M. Ross (Ed.), UpToDate. Waltham. MA. Retrieved from https://www.uptodate.com/contents/clinical-presentation-and-diagnosis-of-prostatecancer?source=search_result&search=prostate%20cancer&selectedTitle=2~150#H74636058.

Kasivisvanathan, V., Rannikko, A. S., Borghi, M., Panebianco, V., Mynderse, L. A., Vaarala, M. H., . . . Moore, C. M. (2018). MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis. N Engl J Med, 378(19), 1767-1777. doi:10.1056/NEJMoa1801993

Li, Y. H., Elshafei, A., Li, J., Hatem, A., Zippe, C. D., Fareed, K., & Jones, J. S. (2014). Potential benefit of transrectal saturation prostate biopsy as an initial biopsy strategy: decreased likelihood of finding significant cancer on future biopsy. Urology, 83(4), 714-718. doi:10.1016/j.urology.2013.12.029

NCCN. (2017). NCCN Clinical Practice Guidelines in Oncology. NCCN Clinical Practice Guidelines in Oncology. Retrieved from https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf

NCCN. (2018). NCCN Clinical Practice Guidelines in Oncology; Prostate Cancer Early Detection v2.2018. https://www.nccn.org/professionals/physician_gls/default.aspx

Norberg, M., Egevad, L., Holmberg, L., Sparen, P., Norlen, B. J., & Busch, C. (1997). The sextant protocol for ultrasound-guided core biopsies of the prostate underestimates the presence of cancer. Urology, 50(4), 562-566. doi:10.1016/s0090-4295(97)00306-3

Pepe, P., & Aragona, F. (2007). Saturation prostate needle biopsy and prostate cancer detection at initial and repeat evaluation. Urology, 70(6), 1131-1135. doi:10.1016/j.urology.2007.07.068

Pinto, P. A., Chung, P. H., Rastinehad, A. R., Baccala, A. A., Jr., Kruecker, J., Benjamin, C. J., . . . Wood, B. J. (2011). Magnetic resonance imaging/ultrasound fusion guided prostate biopsy improves cancer detection following transrectal ultrasound biopsy and correlates with multiparametric magnetic resonance imaging. J Urol, 186(4), 1281-1285. doi:10.1016/j.juro.2011.05.078

Roehl, K. A., Antenor, J. A., & Catalona, W. J. (2002). Serial biopsy results in prostate cancer screening study. J Urol, 167(6), 2435-2439.

Sajadi, K. P., Kim, T., Terris, M. K., Brown, J. A., & Lewis, R. W. (2007). High yield of saturation prostate biopsy for patients with previous negative biopsies and small prostates. Urology, 70(4), 691-695. doi:10.1016/j.urology.2007.05.017

Samir S. Taneja, M. C., Marc A. Bjurlin, DO, H. Ballentine Carter, MD, Michael S. Cookson, MD, MMHC, Leonard G. Gomella, MD, FACS, David F. Penson, MD, MPH, Paul Schellhammer, MD, Steven Schlossberg MD, MBA, Dean Troyer, MD,. (2015). American Urological Association - Optimal Techniques of Prostate Biopsy and Specimen Handling. http://www.auanet.org/guidelines/prostate-biopsy-and-specimen-handling

Sanda, M. G., Cadeddu, J. A., Kirkby, E., Chen, R. C., Crispino, T., Fontanarosa, J., . . . Treadwell, J. R. (2017). Clinically Localized Prostate Cancer: AUA/ASTRO/SUO Guideline. Part I: Risk Stratification, Shared Decision Making, and Care Options. J Urol. doi:10.1016/j.juro.2017.11.095

Schroder, F. H., Hugosson, J., Roobol, M. J., Tammela, T. L., Ciatto, S., Nelen, V., . . . Auvinen, A. (2009). Screening and prostate-cancer mortality in a randomized European study. N Engl J Med, 360(13), 1320-1328. doi:10.1056/NEJMoa0810084

Siegel, R. L., Miller, K. D., & Jemal, A. (2017). Cancer Statistics, 2017. CA Cancer J Clin, 67(1), 7-30. doi:10.3322/caac.21387

Stewart, C. S., Leibovich, B. C., Weaver, A. L., & Lieber, M. M. (2001). Prostate cancer diagnosis using a saturation needle biopsy technique after previous negative sextant biopsies. J Urol, 166(1), 86-91; discussion 91-82.

Tabayoyong, W., & Abouassaly, R. (2015). Prostate Cancer Screening and the Associated Controversy. Surg Clin North Am, 95(5), 1023-1039. doi:10.1016/j.suc.2015.05.001

Thompson, J. E., Hayen, A., Landau, A., Haynes, A. M., Kalapara, A., Ischia, J., . . . Stricker, P. D. (2015). Medium-term oncological outcomes for extended vs saturation biopsy and transrectal vs transperineal biopsy in active surveillance for prostate cancer. BJU Int, 115(6), 884-891. doi:10.1111/bju.12858

Ukimura, O., Coleman, J. A., de la Taille, A., Emberton, M., Epstein, J. I., Freedland, S. J., . . . Jones, J. S. (2013). Contemporary role of systematic prostate biopsies: indications, techniques, and implications for patient care. Eur Urol, 63(2), 214-230. doi:10.1016/j.eururo.2012.09.033

Uno, H., Nakano, M., Ehara, H., & Deguchi, T. (2008). Indications for extended 14-core transrectal ultrasound-guided prostate biopsy. Urology, 71(1), 23-27. doi:10.1016/j.urology.2007.09.020

USPSTF. (2018). Screening for prostate cancer: US Preventive Services Task Force recommendation statement. JAMA, 319(18), 1901-1913. doi:10.1001/jama.2018.3710

Ward, A. D., Crukley, C., McKenzie, C. A., Montreuil, J., Gibson, E., Romagnoli, C., . . . Fenster, A. (2012). Prostate: registration of digital histopathologic images to in vivo MR images acquired by using endorectal receive coil. Radiology, 263(3), 856-864. doi:10.1148/radiol.12102294

Wolf, A. M., Wender, R. C., Etzioni, R. B., Thompson, I. M., D'Amico, A. V., Volk, R. J., . . . Smith, R. A. (2010). American Cancer Society guideline for the early detection of prostate cancer: update 2010. CA Cancer J Clin, 60(2), 70-98. doi:10.3322/caac.20066

Zaytoun, O. M., Moussa, A. S., Gao, T., Fareed, K., & Jones, J. S. (2011). Office based transrectal saturation biopsy improves prostate cancer detection compared to extended biopsy in the repeat biopsy population. J Urol, 186(3), 850-854. doi:10.1016/j.juro.2011.04.069

Policy Implementation/Update Information

1/1/19 New policy developed. BCBSNC will provide coverage for prostate biopsy when it is determined to be medically necessary because the medical criteria and guidelines are met. Medical Director review 1/1/2019. Policy noticed 1/1/2019 for effective date 4/1/2019. (sk)