BJU international · 2026
Intermediate clinical endpoints as surrogates for overall survival after salvage prostatectomy.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Roessler Navid, Nowicka Zuzanna, Miszczyk Marcin, Calleris Giorgio, Dematteis Alessandro, Vetterlein Malte W, Albisinni Simone, Van Der Poel Henk G, Cathcart Paul, Cacciamani Giovanni E, Gill Inderbir S, Persad Raj A, Joniau Steven, Sanchez-Salas Rafael, Smith Joseph A, Karnes Robert Jeffrey, Ahmed Mohamed E, Rajwa Pawel, Tilki Derya, Shariat Shahrokh F, Gontero Paolo, Marra Giancarlo, Young Academic Urologists Prostate Cancer Working Party
Аннотация
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 τ ( τ >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 τ 0.85, 95% CI 0.82-0.88), which was not observed for BRFS (Kendall's τ 0.63, 95% CI 0.56-0.69). At the centre level, neither 3-year BRFS (R2 = 0.15; slope = 0.34, P = 0.2) nor 3-year MFS (R2 = 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.
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 τ ( τ >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 τ 0.85, 95% CI 0.82-0.88), which was not observed for BRFS (Kendall's τ 0.63, 95% CI 0.56-0.69). At the centre level, neither 3-year BRFS (R2 = 0.15; slope = 0.34, P = 0.2) nor 3-year MFS (R2 = 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.