Proliferation of prostate cancer cells in the bone marrow predicts recurrence in patients with localized prostate cancer

BACKGROUND. Reverse-transcription polymerase chain reaction (RT-PCR) amplification of prostate specific antigen (PSA) mRNA has been used to detect the presence of prostate cancer cells in the peripheral blood and bone marrow of patients with clinically localized disease. Some studies have demonstrated a correlation between detection of PSA-mRNA and disease recurrence. However, many RT-PCR-positive patients remain disease-free. We propose that phenotypic characterization of individual micrometastatic cells may provide more prognostic information than mere detection of such cells. METHODS. We studied 58 patients undergoing radical prostatectomy for clinically localized disease whose bone marrow had been found to contain PSA-mRNA by RT-PCR. Immunohistochemical detection and phenotypic characterization of micrometastatic cells was performed using a two-color technique: cytokeratin antibody for detection and the MIB-1 antibody for proliferation. The clinical endpoint was disease recurrence. RESULTS. One or more micrometastatic cells were proliferating in 36.2% of the patients; the disease-free survival rate was 76.2% in this group. In contrast, in the patients with nonproliferating cells, 97.3% remained disease-free (P = 0.025). Multivariate analysis demonstrated that the presence of proliferating cells was the only preoperative variable that correlated with disease-free survival (P = 0.05). CONCLUSIONS. Determination of the phenotype of individual micrometastatic cells can contribute prognostic information above and beyond the mere determination of their presence or absence. Phenotypic characterization of individual micrometastatic cells may ultimately be used to select patients for systemic therapy given either alone or in combination with local therapy. (C) 2001 Wiley-Liss, Inc.