TY - JOUR
T1 - Biochemical Recurrence Surrogacy for Clinical Outcomes after Radiotherapy for Adenocarcinoma of the Prostate
AU - Roy, Soumyajit
AU - Romero, Tahmineh
AU - Michalski, Jeff M.
AU - Feng, Felix Y.
AU - Efstathiou, Jason A.
AU - Lawton, Colleen A.F.
AU - Bolla, Michel
AU - Maingon, Philippe
AU - De Reijke, Theo
AU - Joseph, David
AU - Ong, Wee Loon
AU - Sydes, Matthew R.
AU - Dearnaley, David P.
AU - Tree, Alison C.
AU - Carrier, Nathalie
AU - Nabid, Abdenour
AU - Souhami, Luis
AU - Incrocci, Luca
AU - Heemsbergen, Wilma D.
AU - Pos, Floris J.
AU - Zapatero, Almudena
AU - Guerrero, Araceli
AU - Alvarez, Ana
AU - San-Segundo, Carmen Gonzalez
AU - Maldonado, Xavier
AU - Reiter, Robert E.
AU - Rettig, Matthew B.
AU - Nickols, Nicholas G.
AU - Steinberg, Michael L.
AU - Valle, Luca F.
AU - Ma, T. Martin
AU - Farrell, Matthew J.
AU - Neilsen, Beth K.
AU - Juarez, Jesus E.
AU - Deng, Jie
AU - Vangala, Sitaram
AU - Avril, Norbert
AU - Jia, Angela Y.
AU - Zaorsky, Nicholas G.
AU - Sun, Yilun
AU - Spratt, Daniel
AU - Kishan, Amar U.
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2023/11/10
Y1 - 2023/11/10
N2 - PURPOSEThe 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 METHODSIndividual 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.RESULTSOverall, 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.CONCLUSIONBCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.
AB - PURPOSEThe 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 METHODSIndividual 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.RESULTSOverall, 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.CONCLUSIONBCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.
UR - http://www.scopus.com/inward/record.url?scp=85173494659&partnerID=8YFLogxK
U2 - 10.1200/JCO.23.00617
DO - 10.1200/JCO.23.00617
M3 - Article
C2 - 37639648
AN - SCOPUS:85173494659
SN - 0732-183X
VL - 41
SP - 5005
EP - 5014
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 32
ER -