Scrutiny of the astro consensus definition of biochemical failure in irradiated prostate cancer patients demonstrates its usefulness and robustness

Purpose: The goals of this study are: (I) to establish the robustness of th e Fox Chase Cancer Center (FCCC) and the American Society for Therapeutic R adiology and Oncology (ASTRO) consensus definitions of failure by comparing biochemical estimates under various modifications of the censoring and fai lure time components to their respective unaltered definitions; (2) to isol ate the source of variation between the two definitions of failure; and (3) to describe the hazard of failure over time for each definition. Methods: Between May 1989 and May 1997, 670 men were treated at Fox Chase C ancer Center for localized prostate cancer using three-dimensional conforma l radiation therapy (3DCRT), These men were stratified into three groups fo r analysis: 111 men treated with adjuvant hormones; 204 men treated with ra diation therapy alone and presenting with more favorable prognosis tumor ch aracteristics; 255 men treated with radiation therapy alone and presenting with less favorable prognosis tumor characteristics. For each group, bioche mical failure was estimated and compared using the FCCC and ASTRO definitio ns of failure. The robustness of each definition was evaluated by comparing estimates under the definition as stated to those under various modificati ons of the censoring and failure components. Analyses were also performed w hile excluding slow-progressing patients. To isolate the source of variatio n between the two failure definitions, estimates were compared for patients with agreement in failure status. Estimates of biochemical failure, and th us hazard rates, were made using Kaplan-Meier methodology, Results: ASTRO biochemical failure estimates were higher than the FCCC fail ure estimates in the first 5 years post-treatment, Beyond 5 Sears, ASTRO es timates level off, while the FCCC failure estimates continued to increase, These failure patterns were similar in all patient groups; however, patient s treated with adjuvant hormones had a much higher risk of failure immediat ely following treatment under the ASTRO definition, Modifying the censoring pattern had little effect on failure estimates in any patient group, regar dless of definition used. The exclusion of patients with slow prostate-spec ific antigen (PSA) doubling time did not result in biochemical estimates th at differed significantly from those for all patients. The analysis of pati ents with agreement in failure status continued to demonstrate significant differences in estimates between the two definitions, and thus differences may be attributed to the specification of time to failure. For all patient groups, hazard rates were dependent upon failure definition: under the FCCC failure definition, patients were at constant risk of failure over the obs ervation period; under the ASTRO failure definition, patients were at risk of failure during the first 4 Sears following treatment, and then at low ri sk of failure beyond 5 years. Conclusions: Both FCCC and ASTRO failure definitions were robust to modific ations in censoring and the inclusion of patients with long doubling times. The,ASTRO failure definition was robust to specifying the time to failure at first rise, as opposed to midway between nadir and first rise. Similarit ies in estimates for all patients versus patients with agreeing failure sta tus suggest that differences in failure definition lie in the specification of time to failure. The ASTRO definition of failure is more appropriate be cause it does not impose an empirical failure marker but is based on the in itiation of biochemical rise, The use of the ASTRO consensus definition dem onstrated little risk of biochemical failure 4 years beyond treatment, The ASTRO failure definition should be adopted in all research involving bioche mical failure analysis of men treated with radiation therapy. (C) 2000 Else vier Science Inc.