DETECTION OF CIRCULATING TUMOR-CELLS IN PATIENTS WITH LOCALIZED AND METASTATIC PROSTATIC-CARCINOMA - CLINICAL IMPLICATIONS

Purpose: To determine the frequency with which prostate-specific antig en (PSA)-positive cells can be detected in the peripheral blood of pat ients with prostatic cancer in different stages and with different sen sitivities to hormonal therapy. Patients and Methods: Peripheral blood from 107 men with prostatic cancer and 27 non-prostate cancer control s was analyzed for PSA mRNA using reverse-transcriptase polymerase cha in reaction (RT-PCR) and Southern blotting. Results: The lower limit o f detection was one PSA-producing cell diluted into 1 x 10(6) blood mo nonuclear cells. The test detected PSA mRNA in four of 25 patients (16 %) with clinically organ-confined (T1-2) disease, three of 10 (30%) wi th T3-4 or N+ tumors, and 25 of 72 (35%) with distant metastases. None of the control samples were positive. An increase in positivity was o bserved with increasing PSA levels. Within the subgroup of patients wi th distant metastases, positivity was observed in six of 16 patients ( 38%) with normal or undetectable PSA levels after hormonal therapy and , overall, in 37% of patients (21 of 57) with androgen-independent dis ease. Conclusion: AN RT-PCR-based assay for PSA mRNA can detect circul ating cells in the peripheral blood of patients with prostatic cancer. The frequency of positivity increases with tumor stage. A unique obse rvation was the detection of cells in patients with no measurable PSA on hormonal therapy. This suggests that continued seeding of distant s ites may still be occurring in these patients, despite seemingly succe ssful therapy. The relationship between continued seeding, disease pro gression, and survival will require further study.