European urology
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Review Comparative Study
Innovative approaches to the hormonal treatment of advanced prostate cancer.
Androgen ablation therapy is the treatment of choice for the palliation of patients with advanced prostate cancer. In addition to palliation, maximal androgen ablation (MAA), with a combination of medical or surgical castration and an antiandrogen, has been shown to increase the survival of patients with metastatic prostate cancer in at least three large well-conducted trials. A subgroup analysis of these trials has suggested that patients, particularly those with low volumes of metastatic disease, fared much better when treated with MAA than with castration alone. ⋯ This method reduces the total time of exposure to castrate levels of androgen and, although prostate-specific antigen levels rise during the second phase of therapy suggesting tumor growth, proponents of this cycling method suggest that this should prolong the time to androgen independence of the tumor. Early results with both methods suggest that the time to progression is long and side effects are minimized as compared to MAA. Large scale trials will be needed to determine the exact risks and benefits of these novel methods of androgen ablation.
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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. ⋯ 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.
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Bone metastases that develop in patients with advanced prostate cancer often cause deep, unremitting pain. Palliative options for the control of this pain include analgesic support, cytotoxic chemotherapy and external-beam radiotherapy. In addition to external irradiation, interest in intravenously injected radioisotopes that are preferentially localized to bone has been mounting. ⋯ In the large, randomized Trans Canada study in which Metastron or placebo was given to patients as an adjunct to local field irradiation, those patients treated with Metastron had a significantly reduced intake of analgesics. Furthermore, progression of pain, as measured either by sites of new pain or by the requirement for further palliative radiotherapy, demonstrated statistically significant differences in favour of Metastron. There is thus increasing evidence of a useful role for Metastron in the treatment of prostate cancer metastatic to bone.