Abstract
<title>Abstract</title> <p> Background Radiographic progression (rPD) at castration-resistant prostate cancer (CRPC) diagnosis remains poorly characterized in real-world settings. We assessed its prognostic impact and the clinical features of patients with rPD in real-world de novo metastatic castration-sensitive prostate cancer (mCSPC). Methods We retrospectively analyzed 330 patients with de novo mCSPC who progressed to CRPC from two multi-institutional cohorts: a conventional androgen deprivation therapy or combined androgen blockade (ADT/CAB) cohort ( <italic>n</italic> = 272) and an upfront intensification cohort ( <italic>n</italic> = 58). At CRPC diagnosis, patients were categorized as having prostate-specific antigen (PSA)-only progression or PSA + rPD. Post-CRPC overall survival (OS) was evaluated using Kaplan–Meier and Cox proportional hazards models, while rPD-associated characteristics were examined using logistic regression. Results Across both cohorts, patients with PSA + rPD had significantly shorter post-CRPC OS than those with PSA-only progression (ADT/CAB: 21 vs. 44 months, <italic>P</italic> < 0.001; upfront: 14 vs. 24 months, <italic>P</italic> = 0.008). Univariate Cox regression confirmed the adverse prognostic impact of rPD (hazard ratios 2.25 [95% CI 1.53–3.29] and 2.49 [95% CI 1.22–5.07]). Lower baseline PSA was significantly associated with rPD in the upfront cohort (odds ratio [OR] 0.30, 95% CI 0.12–0.75, <italic>P</italic> = 0.010), with a non-significant trend in the ADT/CAB cohort (OR 0.71, 95% CI 0.47–1.06, <italic>P</italic> = 0.092). Conclusion Radiographic progression at CRPC transition predicts poor post-CRPC survival in real-world mCSPC patients, regardless of initial treatment. Lower baseline PSA may identify patients at increased risk of rPD, supporting careful radiographic monitoring at CRPC transition. </p>