Prostate cancer, Incidence, management and outcomes

The incidence of prostate carcinoma in the US now appears to be declining slightly, as a consequence of removal of prevalent cases from the population by screening. Screening for serum prostate-specific antigen (PSA) levels has been improved by the use of PSA transformations including PSA density, PSA velocity and age-specific PSA reference ranges. The ratio of free to total PSA may increase the specificity of single serum PSA evaluations without decreasing its sensitivity for the diagnosis of prostate cancer. Despite the proliferation of risk assessment tools and nomograms, the optimal therapy for localised disease remains controversial, and the usefulness of radical prostatectomy or radiation therapy (either external beam or brachytherapy) has not been tested prospectively against watchful waiting. However, watchful waiting is probably more appropriate for men whose life expectancy is less than 10 to 15 years and/or who have low grade tumours. In patients with metastatic disease, androgen deprivation remains the mainstay of treatment. Whether or not the addition of an antiandrogen prolongs survival remains controversial. Intermittent androgen deprivation appears to be one means of avoiding continuous androgen deprivation and possibly decreasing adverse effects, although its efficacy remains to be proven. For patients whose disease progresses after combined androgen blockade, withdrawal of antiandrogen is now considered mandatory. Tremendous heterogeneity exists among patients who progress after antiandrogen withdrawal, so that patients previously considered resistant to hormones may in fact retain some hormonal sensitivity to second- or third-line hormone therapy. For patients with hormone-refractory prostate cancer, a variety of options exist, including the use of estramustine combinations, suramin, mitoxantrone and doxorubicin combinations. Despite these options, there is presently no standard of care, and clinical trials should receive priority. Palliative interventions, including the use of corticosteroids, radiopharmaceuticals and external beam radiation therapy, should not be overlooked.