Neoadjuvant therapy prior to radiotherapy for clinically localized prostate cancer.

The optimal treatment for many unresectable solid tumors involves the combined use of chemotherapy and radiation. Retrospective and prospective randomized trials demonstrating a reduction in failure rates when neoadjuvant androgen suppression is combined with radiotherapy suggest that this is also likely to be true for prostate cancer. The absence of overlapping toxicities, the high response rates to androgen suppression, and the ease with which the prostate is included in radiotherapy portals makes the prostate an ideal site for chemoradiation. Since radiation and hormonally mediated apoptosis appear to be induced by different mechanisms their interaction may well be synergistic. Volumetric changes induced by hormonal suppression facilitate radioactive implantation in the prostate in men with large glands. This neoadjuvant approach also reduces the amount of normal tissue to be irradiated when used prior to 3-dimensional conformal radiotherapy while allowing higher doses to the tumor. It may be particularly important to use antiandrogens to block the 'intraprostatic flare' that may result from the testosterone surge induced by luteinizing hormone-releasing hormone in patients undergoing neoadjuvant (short course) androgen suppression. Men who are at particularly 'high risk' for biochemical failure when treated with radiotherapy alone should probably receive a 'longer' course of complete neoadjuvant and possibly adjuvant hormonal blockade, but the optimal duration and sequence of androgen suppression remain to be defined.