Neoadjuvant therapy before radical prostatectomy in high-risk localized prostate cancer: defining appropriate endpoints.
High-risk localized prostate cancer remains a vexing problem for clinicians. Definitive local treatments such as surgery and radiation therapy cure only a minority of these patients. As a result, efforts are being made to reduce the risk of recurrence by using chemotherapy and new agents before, during or after definitive local therapy. Neoadjuvant androgen deprivation therapy has yielded disappointing results when combined with surgery. Chemotherapy in the management of localized disease is evolving, and preliminary studies are just now being completed. Although these agents have established activity and acceptable toxicity in the hormone-refractory setting, more extensive use of them in patients with androgen-dependent disease will require data from randomized studies to determine overall efficacy. New molecular-targeted therapies are promising and hold the greatest hope that outcomes in early disease may be improved with early use of systemic therapy. The neoadjuvant surgical model also has promise in assessing the activity of new drugs, because it provides a means to determine molecular effects of specific agents, along with standard pathologic and clinical parameters of efficacy.
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William K
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Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. william_oh@dfci.harvard.edu
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D000728:Androgens; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000145:classification / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers; D017024:Chemotherapy, Adjuvant; D004961:Estramustine / Q000008:administration & dosage; D005485:Flutamide / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D020360:Neoadjuvant Therapy; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D010166:Palliative Care; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012306:Risk
D000726:Androgen Antagonists; D000728:Androgens; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D015415:Biomarkers; D004961:Estramustine; D005485:Flutamide; D016729:Leuprolide