Cell proliferation in prostate cancer patients with lymph node metastasis:A marker for progression

The biological aggressiveness of lymph node-positive prostate cancer is clo sely linked to cancer volume in nodal metastases, We evaluated MIB-1 (Ki-67 ) labeling index and bcl-2 expression in primary cancer and matched nodal m etastases from 138 node-positive patients treated with radical prostatectom y and bilateral pelvic lymphadenectomy between 1987 and 1992 at the Mayo Cl inic. One hundred twenty-eight patients (93%) received androgen deprivation therapy within 90 days after radical prostatectomy, Mean patient age was 6 6 years (range, 51-78), The median follow-up was 6.7 years (range, 0.03-11) , MIB-1 (Ki-67) labeling index was determined by digital image analysis, an d nodal cancer volume was determined by the grid method. Systemic progressi on, defined as the presence of distant metastasis documented by biopsy or r adiographic examination, was used as an outcome end point in the Cox propor tional hazard models. MIB-1 labeling index in nodal metastases was predicti ve of systemic progression-free survival (P = 0.001), The 8-year systemic p rogression-free survival was 100% for those with MIB-1 labeling index < 3.5 % com pared with 78% for those with MIB-1 labeling index greater than or eq ual to 7.8%, MIB-1 labeling index correlated with Gleason score, DNA ploidy , and nodal cancer volume (P < 0.001, 0.04, and < 0.001, respectively). Aft er controlling for nodal cancer volume, MIB-1 labeling index remained signi ficant in predicting systemic progression-free survival (P = 0.047), bcl-2 expression in the primary cancer and lymph node metastasis was associated w ith systemic progression-free survival in univariate analysis (P = 0.027 an d 0.048, respectively) but was not significant after adjusting for nodal ca ncer volume (P = 0.52 and 0.17, respectively). Our data indicate that asses sment of cell proliferation In nodal metastasis is predictive of clinical o utcome in prostate cancer patients with regional lymph node metastasis.