CHANGES IN BIOCHEMICAL DISEASE-FREE SURVIVAL RATES AS A RESULT OF ADOPTION OF THE CONSENSUS CONFERENCE DEFINITION IN PATIENTS WITH CLINICALLY LOCALIZED PROSTATE-CANCER TREATED WITH EXTERNAL-BEAM RADIOTHERAPY

Purpose: The optimal definition of biochemical recurrence of prostate cancer after definitive radiotherapy remains elusive. Different instit utions have developed their own definitions, and a consensus conferenc e (CC) sponsored by the American Society for Therapeutic Radiology and Oncology has recently proposed another definition. This study compare s the definition previously used at our institution with the definitio n proposed by the CC. Methods: Two hundred and eight patients were tre ated for localized prostate cancer with conformal external-beam radiot herapy between 1989-1993 at our institution and followed for at least 24 months. Patients were categorized as failures according to our inst itutional definition and the CC definition. Our definition (CPMC) requ ired two increases in serum prostate specific antigen (PSA) over at le ast a 3-month period with a final value of at least 1 ng/ml or a singl e value resulting in clinical intervention. The CC definition required three consecutive increases in PSA. This was modified to also conside r those patients with one or two increases leading to clinical interve ntion as failures. Differences in the failure rates between the two de finitions were evaluated and factors influencing these differences wer e explored. In an additional analysis, CC was modified such that patie nts with one or two PSA increases were censored at the time of the PSA prior to the increases (CC-II), rather than at the last PSA (CC). The median follow-up time was 31 months. Results: There were 36 fewer fai lures according to CC (n = 96) compared with CPMC (n = 132) (p < 0.001 ). Twenty cases called failures by CPMC subsequently had a decrease in PSA (''false failures''). The other 16 patients have had two increase s in PSA, but are awaiting their next follow-up visit to obtain a thir d PSA (''pending failures''). Analysis of factors predicting ''pending failures'' showed Gleason score to be the sole predictor of this chan ge in status in multivariate analysis (p = 0.03) with patients with lo wer-grade tumors being more likely to change status (Gleason 2-6: 15% vs. Gleason 7-10: 1%). On the other hand, ''false failures,'' compared to true failures, had a lower mean PSA nadir (1.7 ng/ml vs. 7.0 ng/ml , p < 0.001) and significantly smaller mean increases in PSA (1st incr ease: 0.6 ng/ml vs. 3.4 ng/ml, p = 0.006; 2nd increase: 0.4 ng/ml vs. 4.8 ng/ml, p = 0.002). In 85% (17 of 20) of these patients, at least o ne of the increases was less than or equal to 0.3 ng/ml compared with 44% (42 of 96) of the true failures (p = 0.0008). CC-II resulted in a small decrease in BDFS rates compared with CC, but did not affect the overall difference between CC and CPMC. A modified definition that def ines failure as two consecutive increases in PSA over 3 months, with a final value greater than 1.0 ng/ml and each increase being at least 0 .3 ng/ml, or three consecutive increases would result in a ''false'' f ailure rate of only 3% (3 of 99) and identify 56% (54 of 96) of the tr ue failures after only two PSA increases. Conclusion: The CPMC definit ion of two PSA increases can falsely identify patients as failures, pa rticularly if the increases in PSA are small (i.e., less than or equal to 0.3 ng/ml). The CC definition requiring three increases in PSA can falsely identify patients as disease-free when the time to failure is long relative to the follow-up time. We propose a that a definition t hat combines aspects of both definitions (two consecutive increases in PSA over 3 months, with a final value greater than 1.0 ng/ml and each increase being at least 0.3 ng/ml, or three consecutive increases) ma y be a better definition of biochemical failure. (C) 1998 Elsevier Sci ence Inc.