Radiotherapy for localized prostate carcinoma. The correlation of pretreatment prostate specific antigen and nadir prostate specific antigen with outcome as assessed by systematic biopsy and serum prostate specific antigen.

Abstract

The objective of this study was to correlate the failure pattern of localized prostate carcinoma after radiotherapy (RT) with pretreatment (preTx) PSA and post-RT nadir PSA, using systematic biopsies and serum PSA in the assessment of outcome. From January 1990 to February 1994, 207 patients treated with external beam RT were followed prospectively with systematic transrectal ultrasound-guided biopsies and measurements of serum PSA levels. Three hundred forty-three biopsies were performed, with 4-7 samples taken per session. The distribution of T classification was as follows: 19 patients had T1b, 15 had T1c, 34 had T2a, 79 had T2b/c, 53 had T3, and 7 had T4. Median follow-up was 36 months (range, 12-70 months). Failures were categorized as biochemical (chemF) (PSA > 2.0 ng/mL and > 1 ng/ mL over nadir), local (LF) (positive biopsy and PSA > 2), and distant (DF). The Cox proportional hazards model was used for multivariate analysis (MVA). Overall, failures were seen in 68 of 207 patients: 20 LF, 24 DF, 7 LF + DF, and 17 chemF. In univariate analysis, failures correlated significantly with preTx PSA, post-RT nadir PSA, T classification, and Gleason's score (GS). The total failure rate was 12% for T1b, T1c, and T2a; 39% for T2b and T2c; and 60% for T3 and T4 (P < 0.0001). By evaluation with preTx PSA, at 36 months the total failure rate was 3% for preTx PSA < or = 5 ng/mL 16% for 5.1-10 ng/mL, 32% for 10.1-15 ng/mL, 42% for 15.1-20 ng/mL, 63% for 20.1-50 ng/mL, and 88% for > 50 ng/mL (P < 0.0001). By evaluation with post-RT nadir PSA, at 36 months the total failure rate was 4% for nadir PSA < or = 0.5 ng/ mL, 26% for 0.6-1 ng/mL, 33% for 1.1-2 ng/mL, and 92% for > 2 ng/mL (P < 0.0001). In MVA, nadir PSA (P < 0.0001) and T classification (P < 0.0005) were independent predictors for any failure. LF occurred in 13% of patients (27 of 207). For these 27 patients, the categorization of T classification was: T1b/T1c/T2a, 7%; T2b/T2c, 16%; and T3/T4, 15% (P = not significant). In MVA, only nadir PSA (P = 0.0004) predicted for LF. DF occurred in 15% of patients (31 of 207). In MVA, nadir PSA (P < 0.0001) and T classification (P < 0.0001) predicted for DF, with pretreatment PSA of borderline significance (P < 0.05). To assess preTx predictors of outcome, post-RT nadir PSA was removed from the model. PreTx PSA then became the dominant variable to predict any failure (P < 0.0001), LF (P = 0.05), chemF (P = 0.0001), and DF (P < 0.003), while T classification also predicted for any failure (P = 0.03), chemF (P = 0.05), and DF (P < 0.0001). Systematic prostate biopsies, performed as part of the rigorous followup of prostate carcinoma after RT, define the patterns of failure and confirm the prognostic value of preTx PSA, post-RT nadir PSA, and T classification. Prior to treatment, preTx PSA is the overwhelming independent predictor of failure, but it is surpassed by post-RT nadir PSA when this is added to the model.