Waisman Malaret AJ, Chang P, Newcomb L et al: Effect of diagnostic biopsy practice location on grade/volume reclassification in active surveillance for prostate cancer: a multicenter analysis from the Canary PASS cohort. Urol Pract 2021; 8: 576.

During prostate cancer (PCa) active surveillance (AS), after the diagnostic (Dx) biopsy (Bx), a confirmatory biopsy (Bx1) is recommended within 1 to 2 years according to the AUA/ASTRO/SUO 2017 guidelines.¹ Some investigators have suggested that when urologists encounter patients who are referred with biopsies performed outside their institutions, they consider immediate repeat biopsy.^2,3 Other retrospective and single institutional studies have suggested that having a biopsy performed in the community predicted both volume and grade-related reclassification.^4,5 We analyzed the Canary Prostate Cancer Active Surveillance (PASS) cohort to determine if patients who had DxBx at an off-site practice were at higher risk for reclassification than those having the DxBx at a PASS site.⁶

Participants were prospectively enrolled at 10 academic institutions. We included patients with Gleason score 6 at DxBx, <34% positive biopsy cores and a Bx1 at a PASS site <2 years after diagnosis. We dichotomized our population based on DxBx location (on-PASS site vs off-PASS site) and used multivariable logistic regression to evaluate association with reclassification at Bx1 after controlling for possible confounders. We also compared rates of definitive PCa treatment by DxBx location.

Out of 1,648 participants in PASS, 906 met the eligibility criteria. Of 519 men who had off-site DxBx 102 (19.7%) had grade/volume reclassification, compared to 72 (18.6%) of 399 patients who had on-site DxBx. After controlling for potential confounders, location of DxBx was not associated with grade/volume reclassification (OR 0.68 [95% CI 0.28-1.48], p=0.251). Uropathological rereview occurred in approximately half (52%) of patients with an off-site DxBx and was not associated with grade reclassification. Participants with an off-site DxBx were more likely to elect definitive treatment than participants with an on-site DxBx (17% [range 14%-20%] vs 14% [10%-17%] within 1 year after Bx1; p <0.01).⁶

In our prospective evaluation of active surveillance patients across 10 academic institutions, the clinical setting where the biopsy was performed was not associated with a difference in grade/volume reclassification on confirmatory biopsy. Moreover, if only grade reclassification was considered, location was still not associated with reclassification at confirmatory biopsy. To our knowledge, ours is the first multicenter study evaluating the reclassification rate as a function of biopsy location.

The PASS study, due to its multi-institutional design, involves many diagnosing urologists, making it generalizable to patients presenting with PCa to diverse practice settings. Therefore, treating physicians can feel comfortable continuing with a standard surveillance protocol regardless of where the initial biopsy was performed, avoiding unnecessary procedures, possible complications and extra costs.

The fact that we found no significant difference in reclassification rate according to the DxBx location likely suggests increased standardization of prostate biopsy techniques and pathology practice across sites, so differences are not as profound as previously reported. The AUA recommends 12-core systematic sampling for maximal detection of significant cancer and to decrease detection of nonsignificant cancer.⁷

Other possible factors for increased consistency in biopsy grading include recent updates of guidelines and templates unanimously embraced by the pathology community,⁸ and the increased utilization of specialized genitourinary pathologists, thus resulting in fewer discrepancies compared to a review by a nongenitourinary pathologists.

Interestingly, patients were treated at a slightly higher rate if they had an original off-site diagnostic biopsy as compared to patients diagnosed at a PASS site (17% vs 14%). Although we did not collect information regarding reasoning for treatment choices, large variations exist between urology practices regarding the number of men who are offered AS,⁹ and likewise it is possible that significant variations in counseling practices for AS patients exist. It is also possible that payer mixes and/or financial burden differ among those patients traveling for a second opinion, influencing treatment decisions. These factors are not measured in the PASS database but are clearly important aspects for future study.

We decided to exclude patients who had magnetic resonance imaging (MRI) studies and/or MRI-guided biopsies. Although the use of MRI is becoming more commonplace, prostate MRI expertise is not widespread, nor is it standard of care, and thus our results remain important in the current paradigm of AS protocols.¹⁰

About half of our pathology reports were reread by genitourinary pathology teams at the respective PASS sites, which did not affect the overall reclassification rate, further suggesting that in our contemporary cohort, the outside pathology results did not influence reclassification rates. Although pathology guidelines may minimize this bias, only a central pathology review would completely eliminate this effect, and central pathology review of biopsies is an ongoing effort within the Canary program.

In conclusion, this evaluation of a large multicenter AS cohort suggests that diagnostic biopsy practice location was not associated with significant differences in grade/volume reclassification on confirmatory biopsy at academic institutions and should not impact confirmatory biopsy schedules.⁶