Biochemical recurrence (BCR) occurs in almost one-third of men with localized prostate cancer who have been treated with prostatectomy or radiation therapy. Utilizing BCR as a replacement measurement for overall survival (OS) in patients with localized prostate cancer is a controversial topic. Researchers from the University of California, Los Angeles, employed various surrogacy analytic methods to evaluate the efficacy of utilizing BCR in place of OS and found that BCR may not necessarily improve a patient’s long-term OS.
A total of 10,741 patients were included in the study, which analyzed patient data from 11 different trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation. BCR-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.
Dose escalation, addition of short-term ADT, and prolongation of ADT duration were found to significantly improve BCR (hazard ratio [HR], 0.71 [95% CI, 0.63-0.79]; HR, 0.53 [95% CI, 0.48-0.59]; and HR, 0.54 [95% CI, 0.48-0.61], respectively).
The addition of short-term ADT (HR, 0.91; 95% CI, 0.84-0.99) and prolongation of ADT (HR, 0.86; 95% CI, 0.78-0.94) also significantly improved OS, while dose escalation did not (HR, 0.98; 95% CI, 0.87-1.11).
BCR at 48 months was associated with inferior OS in all 3 groups (HR, 2.46 [95% CI, 2.08-2.92]; HR, 1.51 [95% CI, 1.35-1.70]; and HR, 2.31 [95% CI, 2.04-2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96-1.27]; HR, 0.96 [95% CI, 0.87-1.06]; and HR, 1.00 [95% CI, 0.90-1.12], respectively).
The patient-level correlation for BCRFS and OS ranged between 0.59 and 0.69, and between 0.23 and 0.41 for TTBCR and OS. 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.
BCRFS and TTBCR were found to be acceptable prognostic factors, but while BCR was associated with a higher risk of death, it did not meet the criteria needed to be a reliable surrogate end point for OS.