ObjectivesThere is a recent paradigm shift to extend robot-assisted radical prostatectomy (RARP) to very senior prostate cancer (PCa) patients based on biological fitness, comorbidities, and clinical PCa assessment that approximates the true risk of progression. Thus, we aimed to assess misclassification rates between clinical vs. pathological PCa burden.Materials and MethodsWe compared senior patients with PCa ≥75 y (n = 847), who were propensity score matched with younger patients <75 y (n = 3,388) in a 1:4 ratio. Matching was based on the number of biopsy cores, prostate volume, and preoperative Cancer of the Prostate Risk Assessment (CAPRA) risk groups score. Multivariable logistic regression models (LRMs) predicted surgical CAPRA (CAPRA-S) upgrade, which was defined as a higher risk of the CAPRA-S in the presence of lower-risk preoperative CAPRA score. LRM incorporated the same variables as propensity score matching. Moreover, patients were categorized as low-, intermediate-, and high-risk, preoperative and according to their CAPRA and CAPRA-S scores.ResultsSurgical CAPRA risk strata significantly differed between the groups. Greater proportions of unfavorable intermediate risk (39 vs. 32%) or high risk (30 vs. 28%; p < 0.001) were observed. These proportions are driven by greater proportions of International Society of Urological Pathology (ISUP) Gleason Grade Group 4 or 5 (33 vs. 26%; p = 0.001) and pathological tumor stage (≥T3a 54 vs. 45%; p < 0.001). Increasing age was identified as an independent predictor of CAPRA-S-based upgrade (age odds ratio [OR] 1.028 95% CI 1.02–1.037; p < 0.001).ConclusionApproximately every second senior patient has a misclassification in (i.e., any up or downgrade) and each 4.5th senior patient specifically has an upgrade in his final pathology that directly translates to an unfavorable PCa prognosis. It is imperative to take such substantial misclassification rates into account for this sensitive PCa demographic of senior men. Future prospective studies are warranted to further optimize PCa workflow and diagnostics, such as to incorporate modern imaging, molecular profiling and implement these into biopsy strategies to identify true PCa burden.