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) amplif ication 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 demonstrat ed a correlation between detection of PSA-mRNA and disease recurrence. Howe ver, many RT-PCR-positive patients remain disease-free. We propose that phe notypic characterization of individual micrometastatic cells may provide mo re prognostic information than mere detection of such cells. METHODS. We studied 58 patients undergoing radical prostatectomy for clinic ally localized disease whose bone marrow had been found to contain PSA-mRNA by RT-PCR. Immunohistochemical detection and phenotypic characterization o f micrometastatic cells was performed using a two-color technique: cytokera tin antibody for detection and the MIB-1 antibody for proliferation. The cl inical endpoint was disease recurrence. RESULTS. One or more micrometastatic cells were proliferating in 36.2% of t he patients; the disease-free survival rate was 76.2% in this group. In con trast, in the patients with nonproliferating cells, 97.3% remained disease- free (P = 0.025). Multivariate analysis demonstrated that the presence of p roliferating cells was the only preoperative variable that correlated with disease-free survival (P = 0.05). CONCLUSIONS. Determination of the phenotype of individual micrometastatic c ells can contribute prognostic information above and beyond the mere determ ination of their presence or absence. Phenotypic characterization of indivi dual micrometastatic cells may ultimately be used to select patients for sy stemic therapy given either alone or in combination with local therapy. (C) 2001 Wiley-Liss, Inc.