Is Biochemical Recurrence a Surrogate for Overall Survival in Localized Prostate Cancer?

By: Joshua D. Madera, MD
Posted: Friday, September 22, 2023

Efforts to elucidate the role of biochemical recurrence as a marker of overall survival in patients with prostate carcinoma revealed that biochemical recurrence–free survival and time to biochemical recurrence are prognostic, according to the results of a study including 11 randomized controlled trials published in the Journal of Clinical Oncology. However, these prognostic markers failed to satisfy all surrogacy criteria required to be considered a reliable endpoint for overall survival, explained Amar U. Kishan, MD, of the University of California, Los Angeles, and colleagues.

“Only data from specifically designed prospective trials can provide further clarity on the potential surrogacy of biochemical recurrence for such patients. At this point, metastasis-free survival is a more appropriate endpoint for prospective clinical trials investigating strategies related to radiation therapy in localized prostate cancer,” the study authors concluded.

A total of 10,741 patients with adenocarcinoma of the prostate were retrospectively reviewed from 11 clinical trials that assessed the use of androgen-deprivation therapy (ADT), ADT prolongation, and radiotherapy dose escalation. The Prentice criteria and the two-stage meta-analytic approach were used to evaluate for surrogacy candidacy. Biochemical recurrence–free survival was defined as the time from random assignment to the presence of biochemical recurrence or death, and time to biochemical recurrence was defined as the time from random assignment to biochemical recurrence or a cancer-specific death.

Rates of biochemical recurrence were significantly improved with the use of dose escalation (hazard ratio [HR] = 0.71), short-term ADT (HR = 0.53), and prolongation of ADT (HR = 0.54). In addition, patients’ overall survival was improved with short-term ADT (HR = 0.91) and prolongation of ADT (HR = 0.86), but dose escalation did not significantly improve survival rates. No significant benefit of treatment on overall survival was identified after adjusting for the rate of biochemical recurrence at the 48-month interval across all treatment groups.

Disclosure: For full disclosures of the study authors, visit ascopubs.org.

Journal of Clinical Oncology