Impact of pretreatment factors, biopsy Gleason grade volume indices and post-treatment nadir PSA on overall survival in patients with metastatic prostate cancer treated with step-up hormonal therapy.

BACKGROUND: In the era when various treatment agents for advanced-stage prostate cancer are available, it is important to investigate overall survival for metastatic prostate cancer treated with step-up hormonal treatment as a reference against new treatment regimens, including antitumor agents and/or new hormonal derivatives, and it is desirable to explore pretreatment, biopsy-related and post-treatment prognostic factors to establish tailor-made treatment strategies.

METHODS: Between 1992 and 2002, 94 patients were diagnosed with prostate cancer with distant metastases in our facility. Various pretreatment clinical findings including serum PSA, testosterone, alkaline phosphatase (ALP), digital rectal examination (DRE) and extension of disease score were investigated for predicting outcomes in step-up hormonal treatment. We also investigated the impact of pathological findings including Gleason grading, tumor volume indices, various Gleason grade 5 volume indices in biopsy specimens, and post-treatment PSA nadir following step-up hormonal treatment on overall survival.

RESULTS: The 3- and 5-year overall survival was 72.4% and 62.5%, respectively. According to univariate analyses, patients with PSA ≤ 100 ng ml(-1), ALP <440 IU l(-1), T1c to T3 on DRE, extension of disease (EOD) score 0-3, no Gleason grade 5 cancer in biopsy specimens or less such cancer and good response at any stage of hormonal therapy had significantly better overall survival than did patients with alternative status. A multivariate Cox proportional hazard model revealed that PSA nadir after first-line hormonal treatment, PSA nadir after second-line treatment and Gleason grade 5 volume index were independent prognostic factors.

CONCLUSIONS: Even in very advanced prostate cancer, local pathological indices, a Gleason grade 5 volume index in particular, could differentiate patients with better prognosis from worse prognosis. Step-up hormonal therapy including luteinizing hormone-releasing hormone agonist, estrogen derivatives and steroid hormones may be valuable in patients with metastatic prostate cancer, especially in good responders at any stage of hormonal therapy.