The correlation of serial prostate specific antigen measurements with clinical outcome after external beam radiation therapy of patients for prostatecarcinoma

BACKGROUND. The authors analyzed retrospectively their institution's experi ence in treating patients with localized prostate carcinoma with external b eam radiation therapy (EBRT) to determine the correlation of various bioche mical failure (BF) definitions with clinical failure and cause specific sur vival (CSS). METHODS. Between January 1987 and December 1997, 1094 patients with clinica l T1-T3N0M0 prostate carcinoma were treated with definitive EBRT alone at W illiam Beaumont Hospital, Royal Oak, Michigan. All patients received EBRT a lone (no adjuvant hormones) to a median total prostate dose of 66.6 grays ( Gy) (range, 59.4-70.4 Gy). Multiple BF definitions were tested for their co rrelation with clinical failure and cause specific death (CSD = 1-CSS). All BF definitions were tested for sensitivity, specificity, and accuracy of p redicting subsequent clinical failure and CSD. Positive and negative predic tive values were calculated in the form of 10-year actuarial clinical failu re and CSD rates. Analyses were performed on all 1094 patients as well as f or those 727 patients who had at least 5 post-RT prostate specific antigen (PSA) level measurements and who did not receive hormonal therapy for post- RT PSA elevations. The median PSA follow-up was 4.0 years for the entire po pulation and 4.5 years for those 727 patients included in the second analys is. RESULTS. In the entire population, 167 patients (15%) experienced clinical failure corresponding to 5- and 10-year actuarial rates of 16% and 34%, res pectively. The correlation of various BF definitions with outcome was calcu lated in those 727 patients who did not receive hormonal therapy. For these patients, BF (as defined by the American Society for Therapeutic Radiology and Oncology Consensus Panel) yielded a 73% sensitivity, 76% specificity, and 75% overall accuracy for predicting clinical failure and a 74% sensitiv ity, 69% specificity, and 69% overall accuracy for predicting CSD. The 10-y ear clinical failure rate for those 251 patients demonstrating 3 consecutiv e PSA rises (BF) was 64% versus 14% for those patients who did not meet the se criteria (biochemically controlled [BC]). As expected, definitions requi ring only two rises were more sensitive but less specific in predicting cli nical failure than those definitions requiring three or four rises. Because there were dramatically more clinically controlled patients (85%) than cli nical failures (15%), the overall accuracy for each definition more closely approximated its specificity. The definitions classifying BF as a postnadi r increase of greater than or equal to 3 or greater than or equal to 4 ng/m L above the nadir yielded the highest accuracies of 87% and 88%, respective ly. In addition, these definitions also appeared to provide the greatest se paration in clinical failure rates between BC and BF patients, an absolute difference of 77% and 76%, respectively. CONCLUSIONS. The correlation between BF and clinical failure and CSD varies markedly depending on the BF definition used. Definitions incorporating a fixed baseline (the nadir level) and the postnadir PSA profile may have bet ter correlation with clinical failure than definitions using the nadir only or a specific number of consecutive rises in which a variable baseline "re sets" after a PSA decrease. Cancer 2000;88:2305-18. (C) 2000 American Cance r Society.