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High-Risk Localized Prostate Cancer: A Case for Early Chemotherapy

Martin Gleave, W. Kevin Kelly

From the Department of Surgery, University of British Columbia Director, Clinical Research, The Prostate Centre, Vancouver General Hospital Vancouver, British Columbia, Canada; and Yale University, Yale Cancer Center, New Haven, CT

Address reprint requests to Martin Gleave, FRCSC, FACS, Department of Surgery, University of British Columbia, D-9, 2733 Heather St, Vancouver, BC, Canada V5Z 3J5; e-mail: gleave{at}interchange.ubc.ca.

High-risk tumors exhibit a more aggressive natural history and have higher positive margin and recurrence rates after radical prostatectomy or radiotherapy alone, where unimodality therapy likely represents undertreatment. Hence, the therapeutic ratio (patients who actually realize a survival benefit from a therapeutic intervention) may, therefore, be greater in high-risk disease if its natural history can be altered by multimodality therapy. It is, thus, important to investigate therapies that optimize complete extirpation of all cancer cells and reduce the incidence of positive surgical margins and disease recurrence. Neoadjuvant therapy extends the logic of early adjuvant therapy further by applying systemic therapy earlier in the course of the disease before definitive locoregional therapy. In prostate cancer, outcomes have not been improved significantly when neoadjuvant hormone therapy is used before surgery; although outcomes are improved when androgen ablation is combined with radiotherapy, many patients remain at risk for systemic recurrence. With recent data confirming improved survival data with docetaxel chemotherapy in metastatic disease, future trials are now focusing on earlier combinations of chemohormonal or biologic therapies in high-risk patients.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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