Impact of Previous Local Treatment for Prostate Cancer on Subsequent Metastatic Disease

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Abstract
Metastatic prostate cancer, which is the precursor of most deaths from the disease, is treated most commonly with hormonal therapy. Generally the primary tumor is never treated. Due to evidence that controlling other primary neoplasms affects patient survival we examined the impact of radical prostatectomy and radiotherapy on the outcome in patients with metastatic prostate cancer in the context of a randomized clinical trial. Southwest Oncology Group Study 8894 randomized 1,286 men with metastatic prostate cancer to orchiectomy and placebo or orchiectomy and flutamide. We performed proportional hazards analysis of variables previously identified to have a significant impact on survival. In this analysis we determined the impact of previous radical prostatectomy or radiotherapy on survival. Previous radical prostatectomy in patients with metastatic prostate cancer was associated with a statistically significant decrease in the risk of death (hazard ratio 0.77, 95% confidence interval 0.53 to 0.89) relative to those who did not undergo earlier prostatectomy. Conversely previous radiotherapy was associated with a greater risk of death in those who had previously undergone prostatectomy and those who received no definitive earlier therapy. It must be stressed that this intriguing observation was a secondary analysis of a phase III study. Nevertheless, it raises the question of whether control of the primary tumor impacts the ultimate outcome in patients with advanced prostate cancer. The suggestion of the role of radical prostatectomy in locally advanced prostate cancer, the now established role of extirpative therapy for renal cell carcinoma and the suggestion of this phenomenon in ovarian carcinoma should prompt further evaluation of this finding in other data sets. It may provide new opportunities for clinical trials.