Impact of biochemical failure classification on clinical outcome: A secondary analysis of radiation therapy oncology group 9202 and 9413

BACKGROUND: Biochemical failure (BF) after radiation therapy is defined on the basis of a rising prostate-specific antigen (PSA) level (A1 failure) or any event that prompts the initiation of salvage androgen-deprivation therapy without PSA failure (A2). It was hypothesized that A2 failure may have a different prognosis. METHODS: Data for 2799 eligible patients from Radiation Therapy Oncology Group (RTOG) 9202 and RTOG 9413 were analyzed. BF was defined according to the 1997 American Society for Therapeutic Radiology and Oncology consensus definition as A1 for PSA failure or as A2 for the start of salvage hormone therapy before 3 consecutive PSA rises. RESULTS: Rates of all-cause mortality (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.5-2.0; P<.0001) and distant metastasis (DM; HR, 1.6; 95% CI, 1.3-2.0; P<.0001) were greater with A2 failure. The 5-year overall survival (OS) rates were 88.2% and 74.6% for A1 and A2, respectively (P<.0001), and the DM rates were 15.7% and 29.0%, respectively (P<.0001). The DM rate was greater at 5 years for A2 patients with DM as the first sign of failure versus patients with other A2 failures (87.3% vs 11.7%, P<.001), and this also correlated with worse OS at 5 years: 81.1% for A2 failure without DM and 52.8% with DM (P<.001). After the removal of patients with DM, the difference between A1 and A2 BF persisted for OS (P5.002) but not for DM (P5.16) CONCLUSIONS: These results suggest that patients with rising PSA levels alone have less risk than those with A2 failures; although DM was the largest contributor of adverse risk to A2 failure, it did not account for all excess risk in A2 failure.