Miszczyk, Marcin

Objectives To evaluate biochemical recurrence‐free survival (BRFS) and metastasis‐free survival (MFS) as potential intermediate clinical endpoints (ICEs) for overall survival (OS) in patients undergoing salvage radical prostatectomy (sRP). Patients and Methods Evaluable patients were selected from a retrospective dataset, resulting in a cohort of 879 patients with recurrent, non‐metastatic, hormone‐sensitive prostate cancer treated with sRP at 13 centres. ICE surrogacy was evaluated using a two‐stage approach: (i) at the individual‐patient level by fitting Clayton copula models and estimating Kendall's ( >0.7 indicating a strong association) and (ii) at the centre level, by fitting weighted linear regression of 5‐year OS on 3‐year BRFS and MFS. Results The two‐step analysis included 759 patients for BRFS (366 events) and 476 for MFS (137 events), with median follow‐up of 37 months (95% confidence interval [CI] 36–42 months) and 34 months (95% CI 31–37 months), respectively. At the individual‐patient level, MFS showed a strong association with OS (Kendall's 0.85, 95% CI 0.82–0.88), which was not observed for BRFS (Kendall's 0.63, 95% CI 0.56–0.69). At the centre level, neither 3‐year BRFS ( R 2 = 0.15; slope = 0.34, P = 0.2) nor 3‐year MFS ( R 2 = 0.21; slope = 0.26, P = 0.14) predicted 5‐year OS with sufficient explanatory power. Limitations include the fact that centre‐level analysis was based on single‐arm associations rather than on treatment‐effect surrogacy across arms, and retrospective data collection. Conclusions The BRFS should not be used as a surrogate endpoint in the sRP setting. MFS requires further validation in future prospective studies to confirm its association with OS. Patient‐reported outcomes, such as quality‐of‐life and treatment‐related toxicity, should be considered in parallel with OS.

Purpose: To evaluate the impact of PSMA PET versus conventional imaging for staging, and the effect of dose escalation (DE) to metastatic lymph nodes in cN1 prostate cancer patients treated with EBRT and ADT. Methods: A retrospective multicenter analysis included 197 propensity score-matched patients (77 staged with PSMA PET, 120 with conventional imaging) treated with EBRT and ADT, with or without DE to lymph node metastases. Matching criteria were T stage, nodal involvement, imaging modality, Gleason score, and ADT duration. Primary endpoint was metastasis-free survival (MFS); secondary endpoints included overall survival (OS), locoregional control (LRC), and toxicity. Results: Median follow-up was 42 months (IQR: 25–59). Median EQD2 (alpha/beta=1.5) to elective nodes was 46 Gy, and to metastatic nodes, 66 Gy (PSMA PET) and 63 Gy (conventional imaging). The 3-year MFS was 80.5% (95% CI: 71.3–90.8%) for PSMA PET and 77.2% (95% CI: 69.5–85.8%) for conventional imaging; 5-year MFS was 59.3% versus 65.8% ( P =0.57). OS at 5 years was 82.2% (PSMA PET) and 77.4% (conventional imaging) ( P =0.72). On multivariable analysis, ISUP grade group 3–5 predicted earlier metastasis (HR: 4.03, 95% CI: 1.61–10.06; P =0.003); higher prostate dose (EQD2 ≥113 Gy) improved MFS (HR: 0.53, 95% CI: 0.30–0.95; P =0.033); long-term ADT (≥24 mo) improved OS (HR: 0.38, 95% CI: 0.19–0.78; P =0.009). No significant difference in toxicity was observed between groups. Conclusions: PSMA PET staging and nodal dose escalation >60 Gy were safe but did not improve MFS, OS, or LRC. ISUP grade group 3–5 and higher prostate dose significantly influenced outcomes.