Beyond PSA90: Deep PSA response predicts outcomes in nonmetastatic CRPC

To evaluate whether deeper prostate-specific antigen (PSA) decline adds prognostic information beyond the conventional 90% decline benchmark (PSA90) in nonmetastatic castration-resistant prostate cancer (nmCRPC).

We retrospectively evaluated 349 patients with nmCRPC treated with first-line androgen receptor signalling inhibitors (ARSIs) at 16 Japanese institutions. To reduce immortal time bias, we used a 6-month landmark cohort (n = 263). Patients were grouped by maximum PSA decline within 6 months: <90% (Group A), 90% to 96% (Group B), and >96% (Group C). The primary endpoint was progression-free survival (PFS). Multivariable Cox models and restricted cubic spline analysis assessed the association between PSA decline and PFS. Exploratory multivariable logistic regression evaluated predictors of >96% PSA decline.

Compared with Group A, Group C had lower progression risk (adjusted hazard ratio [aHR] 0.22, 95% confidence interval [CI] 0.13-0.38; P < 0.001), and Group B also had lower risk (aHR 0.39, 95% CI: 0.19-0.79; P = 0.010). Spline analysis showed a continuous decrease in risk beyond the 90% threshold with no clear evidence of a plateau within the observed range. Higher baseline PSA independently predicted worse PFS (aHR 1.39, 95% CI: 1.12-1.72; P = 0.002). No baseline clinical factor significantly predicted achievement of >96% PSA decline in exploratory analysis.

In nmCRPC treated with first-line ARSI, deeper PSA response was continuously associated with improved PFS. An exploratory >96% PSA decline identified a subgroup with particularly favorable outcomes, but external validation is required.