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Objective: To assess the utility of the nested reverse transcription-polymerase chain reaction (RT-PCR) method for measuring prostate specific membrane antigen (PSM) and prostate specific antigen (PSA) in predicting serum PSA recurrence after radical prostatectomy. Patients and methods: Nested RT-PCRs for PSM and PSA were used in 40 patients who subsequently underwent radical prostatectomy. The accuracy of the RT-PCR assays in predicting PSA failure was compared with those for the preoperative serum PSA level, Gleason score and final pathological staging. The patients were monitored using a PSA assay (Tandem-R, Hybritech, San Diego, CA) at 3 weeks after radical prostatectomy and every 2 months thereafter. Biochemical recurrence was defined as a serum PSA level of ≥0.4 ng/mL. Results: Statistical analysis indicated that the nested RT-PCR assay for PSM was the most accurate preoperative predictor of potential surgical failure (PCR-PSM, P<0.001; PCR-PSA, P=0.018; serum PSA level, P=0.149; Gleason score P=0.388, by Fisher’s exact probability test). Biochemical recurrence was evaluated in relation to these methods during a mean (range) follow-up of 16.7 (6–35) months. Of the 40 patients, eight (20%, one with organ-confined cancer and seven with extraprostatic extension of cancer) developed biochemical recurrence. The Kaplan–Meier recurrence-free actuarial probability curves differed significantly between patients with positive and those with negative results for the preoperative nested RT-PCR for PSM (P<0.01, generalized Wilcoxon’s test). The nested RT-PCR for PSA, preoperative serum PSA value and Gleason score were not significant predictors of biochemical recurrence (P=0.16, 0.12 and 0.24, respectively). Conclusions: The nested RT-PCR for PSM was the best preoperative predictor of biochemical recurrence among the factors examined. [ABSTRACT FROM AUTHOR]