Adjunctive therapy for men with high risk localized and locally advanced prostate cancer: targeting disseminated tumor cells.
OBJECTIVE
Our research into the pathophysiology of micrometastatic dissemination and cancer recurrence has resulted in the initiation of a clinical trial for men with clinically localized and locally advanced disease.


METHODS
We describe the development of this trial, which exploits anti-angiogenesis therapy, and delineate how our understanding of prostate cancer metastasis influenced its design.


RESULTS
Prostate cancer is a heterogeneous disease. Although many men can be cured with local therapy, a large majority with clinically localized disease will experience a relapse usually at a distant site. This result is most likely due to micrometastatic dissemination early in the disease process. Therefore, successful contemporary treatment of many men with prostate cancer should include a combination of local and systemic therapies. Fortunately, cellular, molecular and genetic features that may predict which men are most in need of this therapeutic approach are being identified and characterized. This insight not only supports the rationale for a combination therapeutic approach to prostate cancer management, but will help identify the pathways and agents that provide the most promising targets for intervention.


CONCLUSIONS
Despite advances in prevention and early detection, refinements in surgical technique, and improvements in radiation and systemic therapies, the ability to cure all men with prostate cancer remains unattainable. The continuing challenge is the successful eradication of recurrent and metastatic disease.
Sokoloff
Mitchell H
MH
Department of Surgery, Section of Urology, Cancer Research Center and Program in Cancer Biology, University of Chicago, Chicago, Illinois, USA. sokoloff@ohsu.edu
Rinker-Schaeffer
Carrie W
CW
Chung
Leland W K
LW
Brendler
Charles B
CB
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D002777:Cholestanols / Q000627:therapeutic use; D018450:Disease Progression; D006801:Humans; D016729:Leuprolide / Q000627:therapeutic use; D008297:Male; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000503:physiopathology* / Q000628:therapy; D009389:Neovascularization, Pathologic; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*
D020533:Angiogenesis Inhibitors; D018931:Antineoplastic Agents, Hormonal; D002777:Cholestanols; D016729:Leuprolide; C079655:squalamine