2026-04-13T03:02:44Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/106692025-10-24T10:16:01Zcom_2072_378070com_2072_378040col_2072_378092
RECERCAT
author
Roy, Soumyajit
author
Romero, Tahmineh
author
Michalski, Jeff
author
Feng, Felix
author
Efstathiou, Jason
author
Michel, Bolla
author
Maldonado Pijoan, Javier
2025-10-24T10:16:01Z
2025-10-24T10:16:01Z
2023-11-28T12:50:54Z2023-11-28T12:50:54Z2023-11-10
http://hdl.handle.net/11351/10669
Biochemical recurrence; Radiotherapy; Prostate adenocarcinomaRecurrència bioquímica; Radioteràpia; Adenocarcinoma de pròstataRecurrencia bioquímica; Radioterapia; Adenocarcinoma de próstataPURPOSE
The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods.
MATERIALS AND METHODS
Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed.
RESULTS
Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendall's tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively.
CONCLUSION
BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.Supported by Cancer Research UK Radiation Research Centre of Excellence at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research (grant A28724) (A.C.T.); Cancer Research UK Programme Grant (C33589/A28284)(A.C.T.); NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research (A.C.T.); grant P50CA09213 from the Prostate Cancer National Institutes of Health Specialized Programs of Research Excellence (A.U.K.); grant PC210066 from the Department of Defense (A.U.K.), the Prostate Cancer Foundation, and the American Society for Radiation Oncology (A.U.K.); and funding from the Chapgier, Bershad, De Silva, and McCarrick Families (A.U.K.).
Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
Pròstata - Càncer - Radioteràpia
Adenocarcinoma
Antigen prostàtic específic
DISEASES::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms
DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma
CHEMICALS AND DRUGS::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Endopeptidases::Serine Endopeptidases::Kallikreins::Prostate-Specific Antigen
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Radiotherapy
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales masculinos::neoplasias de la próstata
ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias glandulares y epiteliales::carcinoma::adenocarcinoma
COMPUESTOS QUÍMICOS Y DROGAS::enzimas y coenzimas::enzimas::hidrolasas::péptido hidrolasas::endopeptidasas::serina endopeptidasas::calicreínas::antígeno prostático específico
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::radioterapia
Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion