Management Strategies for Locally Advanced Prostate Cancer

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Locally advanced prostate cancer represents a subpopulation of prostate cancer diagnosed in patients who are either untouched by screening efforts or whose disease has an unusually rapidly progressive natural history. The diagnostic work-up for the locally advanced patient is distinct from that of early stage disease in several respects in that it is related principally to ruling out metastases. The typical metastatic work-up consists of a serum alkaline phosphatase, bone scan, CT of the abdomen/pelvis, and chest x-ray. Once metastatic disease has been ruled out, individual components of the management of locally advanced prostate cancer patients may include surgery (palliative or curative), external beam radiation therapy (with photons or particles) or brachytherapy (with low-dose rate/permanent or high-dose rate/temporary radiation sources), and hormone therapy. Unlike in early stage disease, observation/watchful waiting is typically not a treatment option in locally advanced prostate cancer. Of the curative local control modalities, the one most commonly used, and the one which has emerged as the clinical standard, is photon external beam radiotherapy (EBRT). Numerous randomised studies have shown that androgen ablation has an established role in conjunction with radiotherapy for locally advanced disease--the current standard of care is thus photon EBRT plus neoadjuvant and adjuvant androgen ablation. Long-term androgen ablation appears to be better than short-term ablation, even when hormone complications are considered. EBRT is typically delivered to the prostate, seminal vesicles and pelvic lymph nodes, although in some circumstances local fields to the prostate and seminal vesicles may be adequate. New treatment planning and delivery techniques, such as intensity-modulated radiotherapy and organ motion tracking, are being developed to reduce the morbidity of radiotherapy while permitting a higher delivered dose. Further work is necessary to determine the precise sequencing and duration of hormone therapy in conjunction with radiotherapy and the optimum radiotherapy treatment volume. Additional work is also needed to determine the precise groups benefiting from other local control modalities such as surgery and brachytherapy. Finally, novel investigational strategies such as chemotherapy and gene therapy are being applied in an attempt to improve outcomes of locally advanced prostate cancer patients.