Strategies for improving the outcome of patients with poor prognosis prostate cancers

We can identify groups of patients with a poor outcome when treated with radiation therapy alone. Patterns of failure indicate the problem in these patients, including both excessive local regional failure and metastatic disease. The latter is probably present in 30-60% of these patients at the time of treatment but is not detectable by present diagnostic means. There is a clear dose response for 4-year biochemical and clinical freedom from failure and dose is an independent variable on multivariate analysis. The relative ineffectiveness of conventional dose level radiation (<70 Gy) vs 76 Gy is clearly demonstrated. If possible, despite the technological requirements of 3D conformal treatment technique (3 DCRT), future trials of adjuvant treatments should be combined with radiation-delivering doses of 75-80 Gy by 3 DCRT. The reduction in the later morbidity associated with 3 DCRT is impressive and on its own justifies adopting this technology. Adjuvant androgen deprivation with radiation in prostate cancer was originally thought to perhaps be similar to the addition of tamoxifen to breast cancer management with an opportunity for eliminating micro-metastasis. It appears that this result may have been achieved in prostate cancer, but the magnitude of effect (17%) is much more than one would expect and this trial needs to be confirmed. It is worth noting from both a cost and morbidity viewpoint that LHRH agonist used alone with radiation is the only adjuvant hormone manipulation associated with a survival advantage. The addition of androgen blockers with their cost, GI, liver and other toxicities has yet to be proven in the adjuvant setting. (orig./MG)