Expectant management with selective delayed intervention for favorable risk prostate cancer

Management options for favorable risk prostate cancer are diverse, varying from a conservative approach (expectant management) to definitive treatment (radical prostatectomy or radiotherapy.) Several studies have suggested that expectant management provides similar 10-year survival rates and quality-adjusted life years compared with radical prostatectomy or radiotherapy. Expectant management alone clearly deprives some patients with potentially curable life-threatening disease of the opportunity for curative therapy. However, every series of conservative management contains a substantial subset of long-term survivors, particularly in the group with favorable clinical parameters. We have conducted a clinical study to evaluate a novel approach in which the choice between a definitive therapy and conservative policy is determined by the rate of PSA increase or the development of early, rapid clinical and/or histologic progression. This strategy, which has never been previously evaluated, offers the powerful attraction of individualizing therapy according to the biological behavior of the cancer. This would mean that patients with slowly growing malignancy would be spared the side effects of radical treatment, while those with more rapidly progressive cancer would still benefit from curative therapy. Doubling time varied widely. In this series of 200 patients, neither grade, stage, nor baseline PSA predicted the PSA doubling time. Thirty-three percent of patients had a PSA doubling time (T(D)) > 10 years. Doubling time appears to be a useful tool to guide treatment intervention for patients managed initially with expectant management. A doubling time of less than 2 years appears to identify patients at high risk for local progression in spite of otherwise favorable prognostic factors. Fifteen to 20% of patients will fall into this category. The remainder have a high chance of remaining free of recurrence and progression for many years. Watchful waiting is clearly appropriate for patients who are elderly, have significant co-morbidity, and have favorable clinical parameters. The use of co-morbidity indices like the Index of Co-existent Disease (ICED) facilitate the identification of patients whose life-expectancy is diminished relative to the natural history of their prostate cancer. The likelihood of a prostate cancer death in these patients is low. Furthermore, many healthy patients fall into a grey zone where the benefits of treatment are unclear. In these patients, a policy of close monitoring with selective intervention for the 15-20% who progress rapidly is appealing. This approach is currently the focus of several clinical trials.