Prostate Biopsy Specimen Analysis AHS – G2007

Policy Guidelines

Prostate cancer is the most common cancer in American individuals with a prostate and the second leading cause of death in individuals with a prostate who are 65 years of age or older with an estimated 299,010 new cases and 35,250 deaths in the US in 2024 (Society,2024). About 11% of individuals with a prostate will be diagnosed with prostate cancer during their lifetime (Taplin & Smith, 2024).

Many cases of prostate cancer do not become clinically evident, as indicated in autopsy series of individuals with a prostate, prostate cancer is detected in approximately 30% of these individuals at age 55 and approximately 60% of these individuals by age 80 (Bell et al., 2015). These data suggest that prostate cancer often grows so slowly that most affected individuals die of other causes before the disease becomes clinically advanced. Prostate cancer survival is related to many factors, especially the extent of tumor at the time of diagnosis. The five-year relative survival among individuals with cancer confined to the prostate (localized) or with just regional spread is 100%, compared with 31% among those diagnosed with distant metastases (Hoffman & Preston, 2024).

Findings on digital rectal examination (DRE) including the presence of nodules, induration, or asymmetry or elevated prostate specific antigen (PSA) levels indicate the need for prostate biopsy. Although 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 (Hoffman & Preston,2024). Screening may reduce the risk of distant-stage prostate cancer. The European Randomized Study of Screening for Prostate Cancer (ERSPC) enrolled 162,243 individuals with a prostate ages 50 to 69 years. The cumulative incidence rate of metastatic disease in the regular screening group was 0.67 percent compared to the control group of 0.86 percent. The absolute risk reduction of metastatic disease was 3.1 per 1000 individuals randomized (Hoffman & Preston, 2024).

Multiple sampling schemes have been developed 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). During transrectal ultrasound (TRUS)-guided biopsy, a six-core, or sextant biopsy technique, takes one sample each from the apex, base, and mid-prostate on each side (Hodge et al., 1989). However, this method may miss approximately 30% of clinically significant cancers 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 (Benway & Andriole, 2021). A meta-analysis by Eichler et al. (2006) found that schemes with 12 core samples that took additional laterally directed cores detected 31% more cancers compared with a six-core approach, with increasing number of cores significantly associated with increased detection of prostate cancer (Eichler et al., 2006). This biopsy method has been used to obtain up to 18 cores for evaluation (Benway & Andriole, 2021).

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 can be considered after one or more negative TRUS-biopsies. Saturation biopsy detects prostate cancer in approximately 22% to 33% of patients undergoing repeat biopsy, but it is associated with a higher incidence of complications (Benway & Andriole, 2021).

Complications may occur with biopsy. Firstly, the samples from a biopsy may be inadequate to make a diagnosis; the cores obtained may not be of high enough quality or more cores may be needed. Other findings such as an abnormal but nonmalignant histology may warrant a repeat biopsy. Clinical complications such as inflammation, bleeding, infection, and urinary obstruction are also possible (Benway & Andriole, 2021). Pepe and Aragona (2007) estimated the rate of clinical complication after a transperineal biopsy to be as high as 40% (Pepe & Aragona, 2007).

Clinical Utility and Validity

Thompson et al. (2015) studied whether saturation or transperineal biopsy altered oncological outcomes as compared with standard transrectal biopsy. In total, 650 individuals with a prostate were analyzed, and saturation biopsy was associated with “increased objective biopsy progression requiring treatment” on both the Kaplan-Meier analysis and multivariate Cox analysis. A logistic regression analysis of 179 individuals undergoing a radical prostatectomy (RP) found that transperineal biopsy was associated with lower likelihood of “unfavourable” RP pathology. 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 over-treatment. 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.” The study included 1,056 individuals with a prostate- 393 of these individuals underwent a 1,214 core biopsy (“extended”) and 663 of these individuals underwent a 20-24 core biopsy (“saturated”). Overall, prostate cancer was detected in 315 patients, but saturated biopsy detected a third more cancers and identified more cancers in a benign initial biopsy. In total,119 biopsies identified clinically “insignificant” cancer. The authors concluded, “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” (Zaytoun et al., 2011).

The Prostate Magnetic resonance Imaging Study (PROMIS) study (Brown et al., 2018) assessed the ability of multi-parametric MRI (mpMRI) to identify individuals with a prostate who could safely avoid an “unnecessary biopsy” and compared mpMRI to TRUS-guided biopsy. A TPMbiopsy was included for comparison, and 576 individuals with a prostate underwent all three tests. Clinically significant (CS) cancer was defined as “a Gleason score of ≥ 4 + 3 and/or cancer core length of ≥ 6 mm”. For CS cancer, TRUS-guided biopsy showed a sensitivity of 48%, specificity of 96%, PPV of 90%, and NPV of 74%. The sensitivity of mpMRI was 93%, specificity was 41%, PPV was 51%, and NPV was 89%. A negative mpMRI scan was recorded for 158 individuals with a prostate (27%). Of these, 17 were found to have CS cancer on TPMbiopsy. The authors also found that the most cost-effective strategy involved testing all individuals with a prostate 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” (Brown et al., 2018).

Sidana et al.(2018) compared the yield of MRI fusion biopsy (FBx) to 12-core TRUS biopsy (SBx) in patients with prior negative biopsies. The study included 779 patients, and a total of 346 cancers were detected with 239 of 346 considered clinically significant. FBx diagnosed a total of 205 patients with SBx diagnosing an additional 34 patients. FBx identified high proportions of clinically significant cancers over all amounts of prior negative biopsies. The authors stated that “SBx added a relatively small diagnostic value to FBx for detecting CS disease” and concluded that “repeat SBx alone in patients with multiple prior negative biopsies will be hindered by lower yield and FBx should be utilized concurrently in these patients” (Sidana et al., 2018).

Pepe et al. (2018) investigated the diagnostic accuracies for clinically significant prostate cancer, multiparametric magnetic resonance imaging (MRI) and transperineal saturation prostate biopsy. Lesions with PI-RADS (Prostate Imaging Reporting and Data System) scores of three or higher were subjected to additional targeted fusion prostate biopsy. A total of 1,032 patients were included, with 372 deemed to have T1c prostate cancer. Further, 272 of these cases were considered “clinically significant.” Saturation biopsy missed 12 of 272 clinically significant cancers, and targeted fusion prostate biopsy with the score cutoff of three missed 44 cases. However, the authors noted that using multiparametric MRI in combination with a score cutoff of 3 in PI-RADS would have prevented 49.3% of biopsies, and a score cut-off of 4 would have prevented 73.6% of biopsies, although the score cutoff of 4 missed 108 of 272 clinically significant cases. The authors concluded that multiparametric MRI could “significantly reduce the number of unnecessary repeat prostate biopsies in about 50% of cases in which a PI-RADS score of 3 or greater is used” (Pepe et al., 2018).

Pepe et al. (2020) investigated the number of cores (combined with multiparametric MRI [mpMRI]) needed to diagnose all clinically significant cases of prostate cancer (csPCa) in individuals with a prostate who were subject to transperineal saturation biopsy (SPBx; 30 cores). The study included 875 patients and stage1 prostate cancer was found in 306 of these patients, with 222 of these classified as clinically significant. The initial 20 needle cores obtained from SPBx identified all 222 cases of clinically significant prostate cancer, although it missed 84 of 129 indolent cases. Overall, the “diagnostic accuracy, sensitivity, and specificity [were] equal to 83.1%, 100%, and 65.1%, respectively.” The authors concluded that in individuals with a prostate who were “subject to mpMRI and/or TPBx, a maximum of 20 systematic transperineal needle cores detected all cases of csPCa and minimized the diagnosis of indolent cancers” (Pepe et al., 2020).

Klotz et al. (2021) investigated magnetic resonance imaging (MRI) with targeted biopsy against TRUS-guided biopsy to determine whether MRI with a targeted biopsy was as effective in detecting a grade 2 or greater prostate cancer. In total, 453 individuals underwent tests and were randomized to receive TRUS biopsy or MRI-TB. Cancers of grade 2 or greater (GG2) were identified in 67 of 225 individuals (30%) who underwent TRUS biopsy vs 79 of 227 (35%) allocated to MRI-TB. The authors concluded that “magnetic resonance imaging followed by selected targeted biopsy is noninferior to initial systemic biopsy in [individuals] at risk for prostate cancer in detecting GG2 or greater cancers” (Klotz et al., 2021).

Lokeshwar et al. (2022) studied the clinical utility of mpMRI guided prostate biopsy. The study started with a retrospective analysis of 415 individuals with low-risk prostate cancer that was being managed with active surveillance. Then, 125 participants were selected based on having a mpMRI visible index lesions score of 2 or 3 according to PI-RADS version 2. Clinically significant prostate cancer, defined as Gleason grade group of at least 2, was found in 22 of 125 patients (17.6%). The authors found that the only significant variable that could predict detection was “higher PSAD.” The authors conclude that “integration of PSAD may be a useful adjunctive tool in identifying patients at highest risk for upgrade despite favorable imaging findings” (Lokeshwar et al., 2022).

State and Federal Regulations, as applicable

The FDA has cleared numerous devices including needles, reagents, instrumentation, and imaging systems for use in prostate biopsy. Many labs have developed specific tests that they must validate and perform in house. These laboratory-developed tests (LDTs) are regulated by the Centers for Medicare and Medicaid (CMS) as high-complexity tests under the Clinical Laboratory Improvement Amendments of 1988 (CLIA ’88). LDTs are ot approved or cleared by the U. S. Food and Drug Administration; however, FDA clearance or approval is not currently required for clinical use.

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” (Samir et al., 2015).

The AUA/American Society for Radiation Oncology (ASTRO)/Society of Urologic Oncology (SUO) published guidelines (Sanda et al., 2018) which state:

• “Localized prostate cancer patients who elect active surveillance should have accurate disease staging including systematic biopsy with ultrasound or MRI-guided imaging.”
• “Localized prostate cancer patients undergoing active surveillance should be encouraged to have a confirmatory biopsy within the initial two years and surveillance biopsies thereafter.”

In 2018, the American Society of Clinical Oncology (ASCO) endorsed the above 2017 AUA/ASTRO/SUO joint guideline, with only a minor disagreement on two cryosurgery recommendations (Bekelman et al., 2018).

In 2020, The American Urological Association and the Society of Abdominal Radiology Prostate Disease Focus Panel published a guideline (Bjurlin et al., 2020) on standard operating procedures for multiparametric magnetic resonance imaging in the diagnosis, staging, and management of prostate cancer. The guideline states:

• “mpMRI of the prostate allows for risk stratification of individualsat risk for prostate cancer including its ability to predict cancer aggressiveness prior to biopsy.”
• “The performance of prostate mpMRI in indivdiuals with no prior biopsy is now supported by randomized clinical trials, while its use in individualswith a prior negative biopsy continues to be endorsed by consensus statements and national guidelines” (Bjurlin et al., 2020).

In 2023, the AUA and SUO released guidelines on early detection of prostate cancer (Wei et al., 2023). They recommend the following regarding prostate biopsies.

In terms of PSA screening:

• “For people with a newly elevated PSA, clinicians should repeat the PSA prior to a secondary biomarker, imaging, or biopsy.”
• “For people undergoing prostate cancer screening, clinicians should not use PSA velocity as the sole indication for a secondary biomarker, imaging, or biopsy.”
• “Clinicians and patients may use validated risk calculators to inform the SDM process regarding prostate biopsy.”
• “When the risk of clinically significant prostate cancer is sufficiently low based on available clinical, laboratory, and imaging data, clinicians and patients may forgo near-term prostate biopsy.”

In terms of initial biopsy:

• “Clinicians should inform patients undergoing a prostate biopsy that there is a risk of identifying a cancer with a sufficiently low risk of mortality that could safely be monitored with active surveillance (AS) rather than treated.” 
• “Clinicians may use magnetic resonance imaging (MRI) prior to initial biopsy to increase the detection of Grade Group (GG) 2+ prostate cancer.”
• “For biopsy-naïve patients who have a suspicious lesion on MRI, clinicians should perform targeted biopsies of the suspicious lesion and may also perform a systematic template biopsy. “
• “For patients with both an absence of suspicious findings on MRI and an elevated risk for GG2+ prostate cancer, clinicians should proceed with a systematic biopsy.”
• “Clinicians may use adjunctive urine or serum markers when further risk stratification would influence the decision regarding whether to proceed with biopsy.”
• “For patients with a PSA > 50 ng/mL and no clinical concerns for infection or other cause for increased PSA (e.g., recent prostate instrumentation), clinicians may omit a prostate biopsy in cases where biopsy poses significant risk or where the need for prostate cancer treatment is urgent (e.g., impending spinal cord compression).”

In terms of repeat biopsy:

• Clinicians should communicate with patients following biopsy to review biopsy results, reassess risk of undetected or future development of GG2+ disease, and mutually decide whether to discontinue screening, continue screening, or perform adjunctive testing for early reassessment of risk.” 
• “Clinicians should not discontinue prostate cancer screening based solely on a negative prostate biopsy.”
• “After a negative biopsy, clinicians should not solely use a PSA threshold to decide whether to repeat the biopsy.”
• “If the clinician and patient decide to continue screening after a negative biopsy, clinicians should re-evaluate the patient within the normal screening interval (two to four years) or sooner, depending on risk of clinically significant prostate cancer and life expectancy.”
• “At the time of re-evaluation after negative biopsy, clinicians should use a risk assessment tool that incorporates the protective effect of prior negative biopsy.”
• “After a negative initial biopsy in patients with low probability for harboring GG2+ prostate cancer, clinicians should not reflexively perform biomarker testing.”
• “After a negative biopsy, clinicians may use blood, urine, or tissue-based biomarkers selectively for further risk stratification if results are likely to influence the decision regarding repeat biopsy or otherwise substantively change the patient’s management.”
• “In patients with focal (one core) high-grade prostatic intraepithelial neoplasia (HGPIN) on biopsy, clinicians should not perform immediate repeat biopsy.” 
• “In patients undergoing repeat biopsy with no prior prostate MRI, clinicians should obtain a prostate MRI prior to biopsy.”
• “In patients with indications for a repeat biopsy who do not have a suspicious lesion on MRI, clinicians may proceed with a systematic biopsy.”
• “In patients undergoing repeat biopsy and who have a suspicious lesion on MRI, clinicians should perform targeted biopsies of the suspicious lesion and may also perform a systematic template biopsy.”

In terms of biopsy technique:

• “Clinicians may use software registration of MRI and ultrasound images during fusion biopsy, when available.”
• “Clinicians should obtain at least two needle biopsy cores per target in patients with suspicious prostate lesion(s) on MRI.”
• “Clinicians may use either a transrectal or transperineal biopsy route when performing a biopsy.”

National Comprehensive Cancer Network (NCCN)

The NCCN Guidelines on Early Detection for Prostate Cancer state that “image-guided biopsy with targeting (preferred) or without targeting of lesions seen on pre-biopsy MRI 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 enhanced cancer detection compared to sextant biopsy schemes. Moreover, the NCCN states,

• “Anteriorly 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.”
• “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 the use of multiparametric MRI followed by an appropriate targeted biopsy technique based on the results.”
• Despite this emerging evidence, the panel does not recommend a saturation biopsy strategy for all individuals with a prostate with “previous negative biopsies at this time given the benefits seen for MRI and MRI-targeted biopsy in this patient population.”
• “After one or more negative image-guided biopsies, individuals who are considered at high risk (e.g. those with persistently elevated or rising PSA) can be considered for MRI followed by targeted biopsy based on several studies showing improved detection of clinically significant prostate cancer in this setting.” The NCCN notes that targeted biopsy techniques include “cognitive or visual targeting, TRUS-MRI fusion platforms, and direct in-bore magnetic resonance-guided biopsy.
• “Overall, the panel believes that the data for the use of MRI and MRI-targeted biopsies in the initial biopsy setting are increasingly compelling. However, studies using both targeted and systematic sampling routinely demonstrate higher yield of clinically significant cancer with the combined approach and improved sensitivity. Therefore, a combination of systematic and targeted procedures is preferred when MRI-targeting capabilities are available, at least at initial biopsy”(NCCN,2024b).

The NCCN also addressed prostate biopsy in their Prostate Cancer guideline. The NCCN remarks that repeat prostate biopsy (and/or repeat multiparametric MRI) no more often than every 12 months unless clinically indicated (such as PSA increase) can be considered for active surveillance for patients with over 10 years life expectancy. (NCCN, 2024a).

American College of Radiology (ACR)

The ACR 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” (Coakley et al., 2017). The 2023 ACR update reconfirmed the above recommendations (Akin et al., 2023).

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” (Coakley et al., 2017).

The 2023 ACR update also added that “the clinical paradigm for prostate cancer diagnosis undoubtedly is rapidly moving toward MRI-targeted biopsies, based on abundant evidence that this can improve pretreatment evaluation of prostate cancer in many aspects, such as MRItargeted biopsies are more concordant with radical prostatectomy in determining Gleason score; better selected candidates for active surveillance; and improved risk stratification” (Akin et al., 2023).

American Cancer Society (ACS)

The ACS 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 [individuals]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.”

According to the ACS, an update to the guidelines for prostate cancer was initiated in 2019 (Smith et al., 2019).

United States Preventive Services Task Force

Within the 2018 USPSTF recommendation statement regarding prostate screening, they state that for individuals with a prostate, “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” (USPSTF, 2018).

European Society for Medical Oncology (ESMO)

The ESMO includes recommendations for prostate biopsies:

“Transperineal biopsies are recommended, rather than transrectal ultrasound (TRUS)- guided biopsies.” ESMO further noted that “Targeted transperineal biopsies, in comparison with systematic transrectal biopsies, result in an increased detection rate of clinically significant prostate cancer, a decreased detection rate of clinically insignificant prostate cancer, and fewer adverse events.”

When multiparametric MRI is positive (defined as [PI-RADS] ≥3), ESMO recommends performing a targeted (systematic or non-systematic) biopsy. However, when multiparametric MRI is negative (PI-RADS ≤2) and clinical suspicion of cancer is low, the biopsy can be omitted (Parker et al., 2020).

European Association of Urology

The EAU’s recommendations on prostate biopsy include the following: 

• Perform MRI before prostate biopsy in individuals with suspected organ confined disease.
• The follow-up strategy during active surveillance should be based on serial digital rectal examination (at least once yearly), prostate-specific antigen (at least once, every six months) and repeated biopsy.
• “Perform magnetic resonance imaging (MRI) and repeat biopsy if PSA is rising (PSA- doubling time < 3 years).”
• For asymptomatic individuals with a prostate with a “PSA level between 3 and ps.Go20ng/mL and a normal DRE, use one of the following tools for biopsy indication: risk-calculator, provided it is correctly calibrated to the population prevalence; [OR] magnetic resonance imaging of the prostate” (EAU, 2024).

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, 55706

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 su

Scientific Background and Reference Sources

Akin, O., Woo, S., Oto, A., Allen, B. C., Avery, R., Barker, S. J., Gerena, M., Halpern, D. J., Gettle, L. M., & Rosenthal, S. A. (2023). ACR Appropriateness Criteria® Pretreatment Detection, Surveillance, and Staging of Prostate Cancer: 2022 Update. Journal of the American College of Radiology, 20(5), S187-S210. https://acsearch.acr.org/docs/69371/Narrative/

Bekelman, J. E., Rumble, R. B., Chen, R. C., Pisansky, T. M., Finelli, A., Feifer, A., Nguyen, P. L., Loblaw, D. A., Tagawa, S. T., Gillessen, S., Morgan, T. M., Liu, G., Vapiwala, N., Haluschak, J. J., Stephenson, A., Touijer, K., Kungel, T., & Freedland, S. J. (2018). Clinically Localized Prostate Cancer: ASCO Clinical Practice Guideline Endorsement of an American Urological Association/American Society for Radiation Oncology/Society of Urologic Oncology Guideline. Journal of Clinical Oncology, 36(32), 3251-3258. https://doi.org/10.1200/JCO.18.00606

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. https://doi.org/10.1002/ijc.29538

Benway, B., & Andriole, G. (2021). Prostate biopsy. https://www.uptodate.com/contents/prostate-biopsy

Bjurlin, M. A., Carroll, P. R., Eggener, S., Fulgham, P. F., Margolis, D. J., Pinto, P. A., Rosenkrantz, A. B., Rubenstein, J. N., Rukstalis, D. B., Taneja, S. S., & Turkbey, B. (2020). Update of the Standard Operating Procedure on the Use of Multiparametric Magnetic Resonance Imaging for the Diagnosis, Staging and Management of Prostate Cancer. J Urol, 203(4), 706-712. https://doi.org/10.1097/ju.0000000000000617

Brown, L. C., Ahmed, H. U., Faria, R., El-Shater Bosaily, A., Gabe, R., Kaplan, R. S., Parmar, M., Collaco-Moraes, Y., Ward, K., Hindley, R. G., Freeman, A., Kirkham, A., Oldroyd, R., Parker, C., Bott, S., Burns-Cox, N., Dudderidge, T., Ghei, M., Henderson, A., . . . 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. https://doi.org/10.3310/hta22390

Coakley, F. V., Oto, A., Alexander, L. F., Allen, B. C., Davis, B. J., Froemming, A. T., Fulgham, P. F., Hosseinzadeh, K., Porter, C., Sahni, V. A., Schuster, D. M., Showalter, T. N., Venkatesan, A. M., Verma, S., Wang, C. L., Remer, E. M., & Eberhardt, S. C. (2017). ACR Appropriateness Criteria((R)) Prostate Cancer-Pretreatment Detection, Surveillance, and Staging. J Am Coll Radiol, 14(5s), S245-s257. https://doi.org/10.1016/j.jacr.2017.02.026

EAU. (2024). Prostate Cancer. https://d56bochluxqnz.cloudfront.net/documents/fullguideline/EAU-EANM-ESTRO-ESUR-ISUP-SIOG-Guidelines-on-Prostate-Cancer-2024_2024- 04-09-132035_ypmy_2024-04-16-122605_lqpk.pdf

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. https://doi.org/10.1016/s0022-5347(05)00957-2

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. https://doi.org/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.

Hoffman, R., ., & Preston, M. (2024, June 3, 2024). Screening for prostate cancer. https://www.uptodate.com/contents/screening-for-prostatecancer?search=prostate%20cancer&source=search_result&selectedTitle=6~150&usage_type=def ault&display_rank=5

Klotz, L., Chin, J., Black, P. C., Finelli, A., Anidjar, M., Bladou, F., Mercado, A., Levental, M., Ghai, S., Chang, S. D., Milot, L., Patel, C., Kassam, Z., Moore, C., Kasivisvanathan, V., Loblaw, A., Kebabdjian, M., Earle, C. C., Pond, G. R., & Haider, M. A. (2021). Comparison of Multiparametric Magnetic Resonance Imaging-Targeted Biopsy With Systematic Transrectal Ultrasonography Biopsy for Biopsy-Naive Men at Risk for Prostate Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol, 7(4), 534-542. https://doi.org/10.1001/jamaoncol.2020.7589

Lokeshwar, S. D., Nguyen, J., Rahman, S. N., Khajir, G., Ho, R., Ghabili, K., Leapman, M. S., Weinreb, J. C., & Sprenkle, P. C. (2022). Clinical utility of MR/ultrasound fusion-guided biopsy in patients with lower suspicion lesions on active surveillance for low-risk prostate cancer. Urol Oncol, 40(9), 407.e421-407.e427. https://doi.org/10.1016/j.urolonc.2022.06.005

NCCN. (2024a, May 17, 2024). NCCN Clinical Practice Guidelines in Oncology; Prostate Cancer. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf

NCCN. (2024b, March 6, 2024). NCCN Clinical Practice Guidelines in Oncology; Prostate Cancer Early Detection. NCCN. https://www.nccn.org/professionals/physician_gls/pdf/prostate_detection.pdf

Parker, C., Castro, E., Fizazi, K., Heidenreich, A., Ost, P., Procopio, G., Tombal, B., & Gillessen, S. (2020). Prostate Cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. https://doi.org/10.1016/j.annonc.2020.06.011 Pepe, P., & Aragona, F. (2007). Saturation prostate needle biopsy and prostate cancer detection at initial and repeat evaluation. Urology, 70(6), 1131-1135. https://doi.org/10.1016/j.urology.2007.07.068

Pepe, P., Garufi, A., Priolo, G. D., Galia, A., Fraggetta, F., & Pennisi, M. (2018). Is it Time to Perform Only Magnetic Resonance Imaging Targeted Cores? Our Experience with 1,032 Men Who Underwent Prostate Biopsy. J Urol, 200(4), 774-778. https://doi.org/10.1016/j.juro.2018.04.061

Pepe, P., Pennisi, M., & Fraggetta, F. (2020). How Many Cores Should be Obtained During Saturation Biopsy in the Era of Multiparametric Magnetic Resonance? Experience in 875 Patients Submitted to Repeat Prostate Biopsy. Urology, 137, 133-137. https://doi.org/10.1016/j.urology.2019.11.016

Samir, S., ., Bjurlin, D., H. , Carter, M., & S. Cookson, M., 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 https://www.auanet.org/guidelines-and-quality/quality-andmeasurement/quality-improvement/clinical-consensus-statement-and-quality-improvement-issuebrief-(ccs-and-qiib)/prostate-biopsy-and-specimen-handling

Sanda, M. G., Cadeddu, J. A., Kirkby, E., Chen, R. C., Crispino, T., Fontanarosa, J., Freedland, S. J., Greene, K., Klotz, L. H., Makarov, D. V., Nelson, J. B., Rodrigues, G., Sandler, H. M., Taplin, M. E., & Treadwell, J. R. (2018). Clinically Localized Prostate Cancer: AUA/ASTRO/SUO Guideline. Part II: Recommended Approaches and Details of Specific Care Options. J Urol, 199(4), 990-997. https://doi.org/10.1016/j.juro.2018.01.002

Sidana, A., Watson, M. J., George, A. K., Rastinehad, A. R., Vourganti, S., Rais-Bahrami, S., Muthigi, A., Maruf, M., Gordetsky, J. B., Nix, J. W., Merino, M. J., Turkbey, B., Choyke, P. L., Wood, B. J., & Pinto, P. A. (2018). Fusion prostate biopsy outperforms 12-core systematic prostate biopsy in patients with prior negative systematic biopsy: A multi-institutional analysis. Urol Oncol, 36(7), 341.e341-341.e347. https://doi.org/10.1016/j.urolonc.2018.04.002

Smith, R. A., Andrews, K. S., Brooks, D., Fedewa, S. A., Manassaram-Baptiste, D., Saslow, D., & Wender, R. C. (2019). Cancer screening in the United States, 2019: A review of current American Cancer Society guidelines and current issues in cancer screening. CA: A Cancer Journal for Clinicians, 69(3), 184-210. https://doi.org/10.3322/caac.21557

Society, A. C. (2024, January 19, 2024). Key Statistics for Prostate Cancer. https://www.cancer.org/cancer/types/prostate-cancer/about/key-statistics.html

Taplin, M.-E., & Smith, J. (2024, March 22, 2024). Clinical presentation and diagnosis of prostate cancer - UpToDate. https://www.uptodate.com/contents/clinical-presentation-anddiagnosis-of-prostate-cancer

Thompson, J. E., Hayen, A., Landau, A., Haynes, A. M., Kalapara, A., Ischia, J., Matthews, J., Frydenberg, M., & 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. https://doi.org/10.1111/bju.12858

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

Wei, J. T., Barocas, D., Carlsson, S., Coakley, F., Eggener, S., Etzioni, R., Fine, S. W., Han, M., Kim, S. K., Kirkby, E., Konety, B. R., Miner, M., Moses, K., Nissenberg, M. G., Pinto, P. A., Salami, S. S., Souter, L., Thompson, I. M., & Lin, D. W. (2023). Early Detection of Prostate Cancer: AUA/SUO Guideline Part II: Considerations for a Prostate Biopsy. J Urol, 101097ju0000000000003492. https://doi.org/10.1097/ju.0000000000003492

Wolf, A. M., Wender, R. C., Etzioni, R. B., Thompson, I. M., D'Amico, A. V., Volk, R. J., Brooks, D. D., Dash, C., Guessous, I., Andrews, K., DeSantis, C., & 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. https://doi.org/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. https://doi.org/10.1016/j.juro.2011.04.069

Policy Implementation/Update Information

For Policy Titled: Prostate Biopsies

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)

10/29/19 Wording in the Policy, When Covered, and/or Not Covered section(s) changed from Medical Necessity to Reimbursement language, where needed. (gm)

12/10/19 Specialty Matched Consultant Advisory Panel review 11/20/2019. Reviewed by Avalon 3rd Quarter CAB. No change in overall intent of policy. (sk)

11/10/20 Reviewed by Avalon 3rd Quarter CAB. Description section updated. Regulatory section updated. When Not Covered section updated with addition of reimbursement language. Policy Guidelines section updated. Scientific Background/References updated. (sk)

5/18/21 Specialty Matched Consultant Advisory Panel review 11/18/2020. (sk)

11/16/21 Reviewed by Avalon 3rd Quarter CAB. Policy Guidelines section updated. References updated. (sk)

2/8/22 Specialty Matched Consultant Advisory Panel review 11/17/2021. (sk)

12/13/22 Reviewed by Avalon 3rd Quarter CAB. Related Policies updated. Table of Terminology added. “Reimbursement is allowed for followup biopsy (excluding prostate saturation biopsy) when the clinical suspicion of prostate cancer remains in an individual for whom an initial biopsy was negative for prostate cancer” added to When Covered section. Policy Guidelines updated. References updated. (sk)

For Policy Titled: Prostate Biopsy Specimen Analysis

12/5/23 Reviewed by Avalon 3rd Quarter CAB. Policy Title change to “Prostate Biopsy Specimen Analysis”. For clarity the words “pathological examination of tissue obtained from a” where added before prostate biopsy in the When covered and Not Covered sections. No changes to coverage criteria. Policy Guidelines and References updated. Medical Director review 11/2023. (rp)

12/17/24 Reviewed by Avalon 3rd Quarter CAB. Related Policies updated. Policy Guidelines and References updated. No changes to coverage criteria. Medical Director review 11/2024. (rp)