BACKGROUND We examined the utility for prostate cancer staging of nested reverse transcription polymerase chain reaction (RT-PCR) using either prostate specific antigen (PSA) or prostate specific membrane antigen (PSM) as primer. METHODS LNCaP cells were used for the in vitro quantification of RT-PCR. RT-PCR was performed on the peripheral blood of 105 control subjects and 63 patients with prostate cancer (32 who eventually underwent radical prostatectomy and 31 with clinical stage D2 cancer). RESULTS The nested RT-PCR for the PSA and PSM primers was able to detect 1 LNCaP cell per 10(6) leukemia (K562) cells. None of the control subjects was found positive for the presence of prostate cancer cells by nested RT-PCR. In the 32-patient surgery group, the results of nested RT-PCR were significantly correlated with the pathologic stage of the cancer when using PSM primers (P=2.00 x 10(-3) by Kendall's correlation test) but not when using PSA primers (P=0.06). Extraprostatic extension was significantly more closely correlated with positive PSM nested RT-PCR results (P=0.012 by Fisher's exact probability test) than with positive results of PSA, nested RT-PCR, digital rectal examination, CT imaging, level of serum PSA or Gleason score. In the untreated stage D2 patients, the positive result rate of PSM nested RT-PCR was significantly higher than that of PSA nested RT-PCR (P=0.025 by McNemar test). CONCLUSIONS Nested RT-PCR using PSM primers appears to predict the prostate cancer stage more accurately than does nested RT-PCR using PSA primers or conventional clinical staging modalities.