ENHANCED REVERSE-TRANSCRIPTASE POLYMERASE CHAIN-REACTION FOR PROSTATE-SPECIFIC ANTIGEN AS AN INDICATOR OF TRUE PATHOLOGICAL STAGE IN PATIENTS WITH PROSTATE-CANCER

Background. As up to 50% of all patients with prostate cancer who have undergone radical prostatectomy are found to be understaged subsequen t to surgery, a more sensitive early staging modality currently is nee ded. A molecular assay that detects prostate specific antigen (PSA)-sy nthesizing cells in the peripheral circulation of patients with prosta te cancer is described. Methods. An enhanced reverse-transcriptase pol ymerase chain reaction (RT-PCR) assay specific for PSA mRNA was perfor med on RNA extracted from blood drawn from 94 patients before radical prostatectomy. Surgical specimens were examined to determine the exten t of tumor spread. The assay was compared with imaging modalities, dig ital rectal examination, and serum PSA level as predictors of patholog y. Additionally, patients were monitored postoperatively by serum PSA level to determine any potential correlation between patient RT-PCR sc ores and subsequent tumor recurrence. Results. Postoperative pathology revealed that 36 of the 94 patients had extraprostatic disease at the time of surgery. Enhanced RT-PCR identified 26 of these patients from preoperative blood specimens (72% sensitivity). The test was negative for 51 of the 58 patients with organ-confined disease (88% specificit y). An odds ratio analysis showed that no other preoperative staging m odality was related more strongly to extraprostatic or organ-confined disease. Follow-up PSA determinations revealed that RT-PCR positive pa tients were at higher risk for a recurrence. At 6 months after surgery , the rates for an increased PSA were 19 and 2% for RT-PCR-positive an d -negative patients, respectively. Conclusions. The data from this fo llow-up study continue to support the utility of enhanced RT-PCR as an early staging modality for radical prostatectomy candidates.