Introduction and objective
Although PCa misclassification and progression during active surveillance (AS) have been well defined for men with low risk Prostate Cancer (PCa), the definition of adverse outcomes for men with grade group 2 PCa diagnosed at mp-MRI targeted biopsy and eligible for AS is currently unknown. This is key since any AS program applied to intermediate-risk disease should be based on accurate definitions on the optimal triggers for treatment. This would in turn reduce the rates of overtreatment even in this setting.
Methods
Overall, 1,070 patients with ISUP grade group 2 PCa eligible for AS according to the PRIAS criteria diagnosed with MRI-targeted biopsy and treated with RP between 2015 and 2020 at 7 centers were evaluated. As per PRIAS criteria, the percentage of positive cores was ≤50%, where multiple positive cores from the same lesion on mpMRI counted for one positive core. Patients were stratified in: 1) organ-confined and pathological ISUP grade group 1-2; 2) organ-confined disease and ISUP grade group 3; and 3) non-organ-confined disease, grade group ≥4, or nodal invasion. Biochemical recurrence (BCR) was defined as 2 consecutive prostate-specific antigen (PSA) ≥0.2 ng/ml. Kaplan-Meier curves assessed time to BCR. Multivariable Cox regression analyses tested the association between pathologic features and BCR. Multivariable logistic regression analyses identified the predictors of being reclassified in group 3.
Results
Overall, 23 (2.1%), 562 (52.5%) and 485 (45.3%) patients were classified in group 1, 2 and 3 according to pathologic characteristics. Median follow-up was 21 months. The 3-year BCR-free survival rate was 95.5 vs. 93.8 vs. 85.8% in group 1 vs. 2 vs. 3 (p=0.5 between group 1 and 2, all p<0.001 for comparisons between groups 1 and 2 vs. 3). At multivariable analyses, group 3 was associated with increased risk of BCR (HR: 2.3; 95%CI: 1.4-3.8; p<0.001) compared to groups 1 and 2. The maximum diameter of the index lesion at mpMRI represented the only predictor of being reclassified in group 3 (OR: 1.05; 95%CI 1.02-1.07; p<0.001) after adjusting for the PI-RADS and total PSA.
Conclusions
Among selected intermediate-risk patients eligible for AS following MRI-targeted biopsy, only men with ISUP grade group ≥4 or non-organ-confined disease were at increased risk of BCR after surgery. These features represent the real misclassification in this setting. MRI-targeted biopsy allows for the reliable identification of grade group 2 AS candidates who are less likely to have misclassification at RP.