Application of canary histology classifier in prostate biopsies for risk stratification.

412 Background: Nguyen et al recently proposed an outcome-based radical prostatectomy (RP) histologic classifier (PMID 38828674, “Canary histology risk group”), combining all high-risk carcinoma histology patterns into “unfavorable histology,” versus absence as “favorable histology.” We examine whether this classifier, with additional stratification of favorable, is applicable to prostate biopsies for risk stratification. Methods: Archival databases of one single institution were searched for patients with long term clinical follow-up after RP and available prostate biopsy slides. Most recent biopsies underwent blinded re-review. Canary risk group was assigned based on highest risk patterns in any core. Unfavorable histology encompasses all Gleason pattern 5, large cribriform/intraductal carcinoma (>0.25 mm), anastomosing cords of carcinoma, grade 3 stromogenic carcinoma, and complex intraluminal papillary architecture. To capture patterns potentially predictive of unsampled unfavorable histology, “biopsy borderline” combines small cribriform/glomeruloid (≤0.25 mm), simple glomerulations, predominance of extensive poorly formed glands, equivocal small anastomosing cords, grade 2 stromal response, and epithelial complexity associated with mucin (beyond mucinous fibroplasia). “Biopsy favorable” is defined as void of any unfavorable or biopsy borderline histology. Biopsy and RP Gleason Grade Group (GG), pT stage, and pN stage were recorded from original reports. Biochemical recurrence (BCR) was defined as consecutive PSA of ≥0.2 ng/mL 8 weeks after RP or receipt of salvage treatment. RP stage and GG were analyzed using chi-square. BCR-free survival was analyzed using Kaplan-Meier curve. Results: 360 patients were identified (median, IQR): Age at diagnosis 61 years (56, 66), PSA at diagnosis 5.38 ng/mL (4.2, 7.6), post-RP follow-up 9 years, (7, 12). The patients were classified as histologically unfavorable (n=63; 17.8%), biopsy borderline (n=92; 25.6%), and biopsy favorable (n=205; 56.9%). The three-tiered classification is significantly associated with earlier BCR (log-rank p-value <.01), RP GG (<.01), pT stage (<.01), and pN stage (<.01) (Table). Conclusions: Unfavorable histology on biopsy was associated with highest risk of BCR after RP, compared to “biopsy borderline” and “biopsy favorable” groups. This proof-of-principle study demonstrates the three-tiered histology-based classifier could be applicable in biopsies for risk stratification. Canary Histology Risk Group N (%) GG3+ at RP pT3a at RP pT3b at RP pN1 BCR event within 7 years of RP Unfavorable 63 (18%) 46 (73%) 30 (48%) 11 (17%) 11 (17%) 53 (84%) Biopsy Borderline 92 (26%) 21 (23%) 32 (35%) 5 (5%) 1 (1%) 60 (63%) Biopsy Favorable 205 (57%) 22 (11%) 69 (34%) 3 (1%) 0 (0%) 110 (54%) All patients 360 (100%) 89 (25%) 131 (36%) 19 (5%) 12 (3%) 223 (62%)