Tilki, Derya

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.

Importance Patients with recurrent prostate cancer after previous radiotherapy typically have poor survival. Those with recurrences prostate confined might be suitable for salvage focal therapy (sFT) or salvage radical prostatectomy (sRP). sFT may offer good cancer control with comparatively less toxic effects, but outcomes beyond 5 years have not been reported, and no study has compared sFT to sRP. Objective To compare cancer control and perioperative complications among patients after sFT vs sRP. Design, Setting, and Participants In this international, multicenter cohort study of matched comparison data, patients undergoing sFT were derived from the prospective UK HIFU (high-intensity focused ultrasound) Evaluation and Treatment and International Cryotherapy Evaluation registries (9 centers; 2006-2024) and the prospective UK Focal Recurrent Assessment and Salvage Treatment cohort study (6 centers; 2014-2018). Patients undergoing sRP were derived from an international retrospective registry (12 centers in 8 countries; 2000-2021). Patients with biopsy-confirmed, localized recurrent prostate cancer postradiotherapy, either external beam radiotherapy, brachytherapy, or both, were included. Data were analyzed from March to July 2025. Exposures sFT using HIFU or cryotherapy vs sRP. Main Outcomes and Measures The primary outcome was cancer-specific survival up to 10 years. Secondary outcomes were overall survival, any perioperative complications (Clavien-Dindo grades 1-5), and major perioperative complications (Clavien-Dindo grades 3-5). Comparisons were made on matched patients following 1:1 cardinality matching within individual multiply-imputed datasets. Matching variables used were radiotherapeutic treatment, years between primary and salvage treatments, European Association of Urology recurrence risk group, and presalvage age, prostate-specific antigen, prostate volume, grade group, T stage, and androgen-deprivation therapy use. Results A total of 923 patients were eligible for matching (419 undergoing sFT and 504 undergoing sRP). Of the patients undergoing sFT, 325 (77.6%) underwent HIFU and the remainder cryotherapy, with 241 (57.5%) treated with quadrant ablation. Of patients treated with sRP, 376 (74.6%) underwent open surgery and the remainder robot-assisted surgery. For sFT vs sRP, 10-year cancer-specific survival was 92% (95% CI, 86%-98%) vs 99% (95% CI, 97%-100%), with no statistically significant difference (restricted mean time lost, −0.09 years; 95% CI, −0.22 to 0.03 years; P = .15; subdistribution hazard ratio, 0.45; 95% CI, 0.05-4.00; P = .47). There was no statistically significant difference in 10-year overall survival (restricted mean survival time, −0.13 years; 95% CI, −0.86 to 0.60 years; P = .72). Undergoing sRP was associated with statistically significant higher odds of any complication (adjusted odds ratio, 24.20; 95% CI, 12.94-45.27; P < .001) and major complication (adjusted odds ratio, 9.31; 95% CI, 3.42-25.36; P < .001). Conclusions and Relevance In this cohort study, sFT and sRP were effective for treating localized radiorecurrent prostate cancer, while sFT was associated with fewer perioperative complications. sFT may provide a favorable therapeutic ratio for many patients with localized radiorecurrent prostate cancer.

Background: Lymph node invasion (LNI) represents a poor prognostic factor after primary radical prostatectomy (RP) for prostate cancer (PCa). However, the impact of LNI on oncologic outcomes in salvage radical prostatectomy (SRP) patients is unknown. Objective: To investigate the impact of lymph node dissection (LND) and pathological lymph node status (pNX vs. pN0 vs. pN1) on long-term oncologic outcomes of SRP patients. Patients and methods: Patients who underwent SRP for recurrent PCa between 2000 and 2021 were identified from 12 high-volume centers. Kaplan–Meier analyses and multivariable Cox regression models were used. Endpoints were biochemical recurrence (BCR), overall survival (OS), and cancer-specific survival (CSS). Results: Of 853 SRP patients, 87% (n = 727) underwent LND, and 21% (n = 151) harbored LNI. The median follow-up was 27 months. The mean number of removed lymph nodes was 13 in the LND cohort. At 72 months after SRP, BCR-free survival was 54% vs. 47% vs. 7.2% for patients with pNX vs. pN0 vs. pN1 (p < 0.001), respectively. At 120 months after SRP, OS rates were 89% vs. 81% vs. 41% (p < 0.001), and CSS rates were 94% vs. 96% vs. 82% (p = 0.02) for patients with pNX vs. pN0 vs. pN1, respectively. In multivariable Cox regression analyses, pN1 status was independently associated with BCR (HR: 1.77, p < 0.001) and death (HR: 2.89, p < 0.001). Conclusions: In SRP patients, LNI represents an independent poor prognostic factor. However, the oncologic benefit of LND in SRP remains debatable. These findings underline the need for a cautious LND indication in SRP patients as well as strict postoperative monitoring of SRP patients with LNI.

AbstractObjectiveTo evaluate the relationship between pre‐operative PSA value, 68Ga‐prostate‐specific‐membrane‐antigen (PSMA) PET performance and oncologic outcomes after salvage lymph node dissection (sLND) for biochemical recurrent prostate cancer (PCa).Patients and methodsThe study included 164 patients diagnosed with ≤2 pelvic lymph‐node recurrence(s) of PCa documented on 68Ga‐PSMA PET scan and treated with pelvic ± retroperitoneal sLND at 11 high‐volume centres between 2012 and 2019. Pathologic findings were correlated to PSA values at time of sLND, categorized in early (<0.5 ng/ml), low (0.5–0.99 ng/ml), moderate (1–1.5 ng/ml) and high (>1.5 ng/ml). Clinical recurrence (CR)‐free survival after sLND was calculated using multivariable analyses and plotted over pre‐operative PSA value.ResultsMedian [interquartile range (IQR)] PSA at sLND was 1.1 (0.6, 2.0) ng/ml, and 131 (80%) patients had one positive spot at PET scan. All patients received pelvic sLND, whereas 91 (55%) men received also retroperitoneal dissection. Median (IQR) number of node removed was 15 (6, 28). The rate of positive pathology increased as a function of pre‐operative PSA value, with highest rates for patients with pre‐operative PSA > 1.5 ng/ml (pelvic‐only sLNDs: 84%; pelvic + retroperitoneal sLNDs: 90%). After sLND, PSA ≤ 0.3 ng/ml was detected in 67 (41%) men. On multivariable analyses, pre‐operative PSA was associated with PSA response (p < 0.0001). There were 51 CRs after sLND. After adjusting for confounders, we found a significant, non‐linear relationship between PSA level at sLND and the 12‐month CR‐free survival (p < 0.0001), with the highest probability of freedom from CR for patients who received sLND at PSA level ≥1 ng/ml.ConclusionsIn case of PET‐detected nodal recurrences amenable to sLND, salvage surgery was associated with the highest short‐term oncologic outcomes when performed in men with PSA ≥ 1 ng/ml. Awaiting confirmatory data from prospective trials, these findings may help physicians to optimize the timing for 68Ga‐PSMA PET in biochemical recurrent PCa.