The importance of adequate follow-up in defining treatment success after external beam irradiation for prostate cancer

Purpose: We reviewed our institution's experience treating patients with lo calized prostate cancer with external beam radiation therapy (RT) to determ ine how differences in the length of follow-up affect the determination of treatment outcome using the American Society for Therapeutic Radiology and Oncology (ASTRO) Consensus Panel Definition of biochemical failure (BF). Methods and Materials: From January 1987 through December 1997, 1109 patien ts with localized prostate cancer were treated with definitive external bea m RT at William Beaumont Hospital, Royal Oak, Michigan. All patients receiv ed external beam RT to a median total prostate dose of 66.6 Gy (range: 59.4 -70.4 Gy). A total of 1096 patients (99%) had sufficient prostate-specific antigen (PSA) follow-up to determine their biochemical status. To test the impact of differences in follow-up on the calculation of BF, 389 patients w ith at least 5 years of PSA follow-up were selected as the reference group for the initial analysis. BF was then retrospectively determined using the Consensus Panel definition at yearly intervals, ignoring the remainder of e ach patient's follow-up. The median follow-up for this group of patients wa s 6.6 years (range: 5.0-11.6 years). In a second analysis, patient cohorts were randomly selected with varying median PSA follow-up intervals in order to more accurately represent a population whose follow-up is distributed c ontinuously over a defined range. Seven cohorts were randomly selected with 200 patients in each cohort. Cohorts were individually identified such tha t half of the patients (100) had 2 years or less follow-up than the stated time point for analysis and half (100) had up to 2 years more follow-up tha n the time point chosen for analysis. For example, in the cohort with a med ian follow-up of 3 years, 100 patients with a PSA follow-up from 1 to 3 yea rs were randomly selected, and 100 patients with a follow-up from 3 to 5 ye ars were randomly selected, thus generating a median follow-up of 3 years f or this cohort (range: 1 to 5 years). This process was repeated five times for five random samples of seven cohorts each. Biochemical failure was calc ulated according to the Consensus Panel definition. Results: In the first analysis, significantly different rates of biochemica l control (varying by 6-21%) were calculated for the same actuarial year ch osen for analysis depending only upon the length of follow-up used. For exa mple, the 3-year actuarial rate of biochemical control (BC) varied from 71% when calculated with 3 years of follow-up versus 50.4% with 7 years (p < 0 .01). These differences in actuarial rates of BC were observed in all subse ts of patients analyzed (e.g., PSA < 10, Gleason less than or equal to 6, n = 132,p < 0.001; PSA < 10, Gleason greater than or equal to 7, n = 33, p = 0.03; PSA greater than or equal to 10, Gleason less than or equal to 6, n = 109, p < 0.001; and PSA greater than or equal to 10, Gleason greater than or equal to 7, n = 72, p = 0.002). The absolute magnitude of the differenc e in actuarial rates of BC was greatest during years 2 (range 18-30%), 3 (r ange 16-25%), and 4 (range 15-24%) after treatment. In the second analysis using median PSA follow-ups las defined above), statistically significant d ifferences in actuarial rates of BC were again observed. For example, the 3 -year actuarial rate of BC varied from 74.8% with a median follow-up of 2 y ears versus 49.2% with a median follow-up of 6 years. These dramatic differ ences in BC were still observed beyond 5 years. Conclusion: When the ASTRO Consensus Panel definition of BF is used to calc ulate treatment success with external beam RT for prostate cancer, adequate follow-up is critical. Depending upon the length of time after treatment, significantly different rates of BC (varying by 15% to 30%) can be calculat ed for the same time interval chosen for analysis. These results suggest th at data should only be reported if the length of follow-up extends at least beyond the time point at which actuarial results are examined for the majo rity of patients. (C) 1999 Elsevier Science Inc.