Clinically Meaningful Upstaging and Upgrading in Favorable Intermediate-Risk Radical Prostatectomy Patients

In NCCN favorable intermediate-risk (FIR) prostate cancer (PCa) patients treated with radical prostatectomy (RP), we tested the effect of upstaging and upgrading on cancer-specific mortality (CSM).

Within the SEER database (2010-2021), upstaging (≥pT3a or pN1) and upgrading (ISUP ≥3) rates in FIR RP patients were tabulated. Kaplan-Meier (KM) plots and multivariable Cox-regression models (CRMs) were fitted.

In 9,037 FIR RP PCa patients, 1,136 (12.6%) exhibited upstaging, 1,341 (14.8%) upgrading, and 377 (4.2%) both vs. 6,937 (76.8%) that did not. Of all upstaged patients, 812 (71.5%) harbored pT3a vs. 324 (28.5%) ≥pT3b/pN1 stage. Of all upgraded patients, 1,077 (80.3%) harbored ISUP 3 vs. 264 (19.7%) ISUP ≥4. Of all upstaged and upgraded patients, 46 (12.2%) exhibited both ≥pT3b/pN1 and ISUP ≥4. Ten-year CSM-free rates in upstaged (96.0%), upgraded (95.9%) and combined upstaged and upgraded (91.0%) patients were significantly lower (P < .001) than others (98.9%). Significantly lower 10-year CSM-free rates were recorded in ≥pT3b/pN1-only (91.9%), ISUP ≥4-only (94.6%), and combined ≥pT3b/pN1 and ISUP ≥4 (85.3%) patients (all P < .05). In multivariable CRMs, upstaging (HR: 3.8), upgrading (HR: 3.5) as well as both upstaging and upgrading (HR: 8.3), independently increased CSM. Specific upstaging to ≥pT3b/pN1-only, upgrading to ISUP ≥4-only, and both upgrading and upstaging independently increased CSM by 3.5-, 6.7-, and 26-fold, respectively.

Of all FIR RP patients, the vast majority is neither upstaged nor upgraded. Those with ≥pT3b/pN1 upstaging, ISUP ≥4 upgrading, or both are at high, higher, and extremely elevated risk of CSM, respectively, and thus require special considerations.