The potential advantages of neoadjuvant androgen deprivation include decreased prostatic size, reduced vasculature, and reduced incidence of positive margins. The potential disadvantages are the side effects of hormonal medication, cost, tissue reaction, treatment 'delay,' and progression of androgen-independent clones. Many theories have been postulated to explain the observed reduction in the incidence of positive margins with neoadjuvant hormonal treatment. It is possible that the reduced prostate size and the frequently found periprostatic tissue reaction facilitate dissection, allowing better cancer clearance. It is possible, however, that the fibrosis may also increase the surgical difficulty, which critics argue may increase the risk of a positive margin. It is difficult to conceive of a research methodology that could resolve this issue. The occurrence of tumor cell death is likely a more significant explanation for the improved results. Whether tumor cells beyond the prostatic capsule are consistently affected to pathologically downstage the disease is unknown. The careful pathologic assessment in the, randomized trials discussed previously suggests that pathologic downstaging is not as common as earlier reports have suggested. Difficulty in interpreting pathologic specimens after neoadjuvant treatment must be considered. At this point, neoadjuvant hormonal treatment prior to surgery would appear appropriate for those patients at high risk of having a positive surgical margin. Specifically, this includes clinical stage T2b, PSA elevation greater than 10 to 20 ng/ml., and a high Gleason score on the prostatic biopsy. Research to date suggests that neoadjuvant hormonal therapy prior to radical prostatectomy has a significant effect in reducing the incidence of positive surgical margins. The treatment is well tolerated with minimal side effects. Whether this will translate into improved disease- free survival remains to be determined. Fortunately, the randomized trials have been completed and follow up data will be forthcoming.
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