The following is a summary of “Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate,” published in the November 2023 issue of Oncology by Roy, et al.
For a study, researchers sought to address the ongoing controversy surrounding the surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer. The investigation utilized diverse surrogacy analytic methods to scrutinize the relationship between BCR and OS, particularly in radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation.
The study incorporated individual patient data from 11 trials exploring radiotherapy dose escalation, ADT use, and ADT prolongation. 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. Two primary outcomes were considered: biochemical recurrence-free survival (BCRFS) and time to BCR (TTBCR). BCRFS denoted the time from random assignment to BCR or any death, while TTBCR represented the time from random assignment to BCR or cancer-specific deaths, with censoring for noncancer-related deaths.
A total of 10,741 patients were included in the analysis. Dose escalation, the addition of short-term androgen deprivation therapy (ADT), and prolongation of ADT duration significantly improved biochemical recurrence (BCR), with hazard ratios (HR) of 0.71 (95% CI, 0.63 to 0.79), 0.53 (95% CI, 0.48 to 0.59), and 0.54 (95% CI, 0.48 to 0.61), respectively. The addition of short-term ADT (HR, 0.91; 95% CI, 0.84 to 0.99) and prolongation of ADT (HR, 0.86; 95% CI, 0.78 to 0.94) significantly improved overall survival (OS), while 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 treatment 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 HR, 1.00; 95% CI, 0.90 to 1.12, respectively). The patient-level correlation (Kendall’s tau) for biochemical recurrence-free survival (BCRFS) and OS ranged between 0.59 and 0.69, and for time to BCR (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.
Despite the prognostic nature of BCRFS and TTBCR, they did not fully meet surrogacy criteria. The correlation strength increased when considering noncancer-related deaths as events. The findings underscored the intricacies of using BCR as a surrogate endpoint for OS in localized prostate cancer.