Treatment of locally advanced prostate cancer: Is chemotherapy the next step?

Purpose: Management of locally advanced prostate cancer remains controversial. Various single and combination modality approaches have been advocated, but an accepted standard of care remains undefined. The purpose of this review is to define the current knowledge in managing locally advanced prostate cancer and to propose new treatment approaches based on current knowledge. Materials and Methods: A MEDLINE search to detect all relevant articles on the management of locally advanced prostate cancer was performed. A review of the staging, natural history, and prognosis of this disease was also performed. Results: The lack of a clearly defined treatment approach to patients with locally advanced prostate cancer stems from multiple factors, including ambiguities in clinical staging, inadequate knowledge of the natural history of the cancer, and a dearth of comparative randomized trials evaluating efficacy of different therapies. Single modality treatment, including radical prostatectomy (RP) or external-beam radiotherapy alone, is associated with high rates of failure. The use of adjuvant hormonal ablation therapy in combination with external-beam radiotherapy has shown improvement in progression-free and overall survival, although similar improvements have not been clearly demonstrated for surgical patients treated with hormonal therapy. New advances in chemotherapy for hormone-refractory prostate cancer suggest that response rates may be as high as 50% or more, and current trials are evaluating the addition of chemotherapy to hormonal ablation in either surgery or radiation therapy in locally advanced prostate cancer. Conclusion: Optimal management of locally advanced prostate cancer remains undefined. Standard treatment options include RP, external-beam radiotherapy, or hormonal ablation therapy, alone or in combination. New approaches being tested include improved methods for delivering radiation or combining hormonal ablation with surgery or radiation. It is possible that other forms of systemic therapy, including chemotherapy, may become important components of multimodality treatment. Clinical trials designed to test this hypothesis are ongoing.