Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate.
Date
2023-11-10ICR Author
Author
Roy, S
Romero, T
Michalski, JM
Feng, FY
Efstathiou, JA
Lawton, CAF
Bolla, M
Maingon, P
de Reijke, T
Joseph, D
Ong, WL
Sydes, MR
Dearnaley, DP
Tree, AC
Carrier, N
Nabid, A
Souhami, L
Incrocci, L
Heemsbergen, WD
Pos, FJ
Zapatero, A
Guerrero, A
Alvarez, A
San-Segundo, CG
Maldonado, X
Reiter, RE
Rettig, MB
Nickols, NG
Steinberg, ML
Valle, LF
Ma, TM
Farrell, MJ
Neilsen, BK
Juarez, JE
Deng, J
Vangala, S
Avril, N
Jia, AY
Zaorsky, NG
Sun, Y
Spratt, D
Kishan, AU
Meta-Analysis of Randomized Trials in Cancer of the Prostate (MARCAP) Consortium Investigators,
Type
Journal Article
Metadata
Show full item recordAbstract
PURPOSE: 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.
Collections
Subject
Male
Humans
Prostate
Prostatic Neoplasms
Androgen Antagonists
Prostate-Specific Antigen
Adenocarcinoma
Research team
Clinic Acad RT Dearnaley
Language
eng
Date accepted
2023-07-12
License start date
2023-11-10
Citation
Journal of Clinical Oncology, 2023, 41 (32), pp. 5005 - 5014
Publisher
LIPPINCOTT WILLIAMS & WILKINS
Except where otherwise noted, this item's license is described
as
http://creativecommons.org/licenses/by/4.0/
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