Localized prostate cancer: quality of life meets Whitmore's legacy.

Dr. Willet Whitmore, the father of urologic oncology, is perhaps best remembered for his question: “For a patient with prostate cancer, if treatment for cure is necessary, is it possible? If possible, is it necessary? ” This question crystallized the dilemma of decision making for patients and physicians and, in the third decade of prostate-specific antigen (PSA) screening, is now even more pertinent and pressing than ever. In this issue, Potosky et al. (1) contribute to the growing evidence of substantial and long-lasting side effects from prostate cancer treatment. Five years after treatment, 80% of radical prostatectomy and 64% of external beam radiotherapy patients were impotent, 29% of radical prostatectomy and 4% of external beam radiotherapy patients were using pads for urinary incontinence, and 20% of radical prostatectomy and 29% of external beam radiotherapy patients had bowel urgency. How many men would accept these risks if they knew that often, definitive treatment will not affect the risk of prostate cancer death? Clinicians and researchers must now acknowledge that we have good evidence of treatment outcomes but poor evidence of treatment benefit. We cannot yet gauge benefit because we cannot identify the specific man for whom treatment is both necessary and sufficient. There are at least two, if not three, groups of patients with localized prostate cancer. The two groups that unequivocally exist are men with a tumor that will never cause them morbidity or mortality during their lifetime (2–4) and men with a tumor that will progress and cause symptoms or death despite treatment (5,6). It is generally hoped that there is also a third group—men who avoid morbidity and mortality by early detection (7,8). Each year, approximately 200 000 men in the United States and their physicians will struggle with the question of what to do about their diagnosis of prostate cancer. This situation reflects the inadequacy of current prognostic measures for prostate cancer, including stage, PSA level, and tumor grade. Studies of watchful waiting consistently demonstrate that some men with one or more risk factors for aggressive disease have prolonged disease-free survival and that some men with seemingly indolent disease progress and die from the disease. If we do not then know whom to treat, what can we say about prostate cancer screening with the PSA test? The Prostate Cancer Prevention Trial obtained prostate biopsy samples from 2950 men with PSA levels of less than 4.0 ng/mL and normal digital rectal examinations. Of these men with a heretofore-considered “normal” PSA level, 15% had prostate cancer; of these, 15% had high-grade disease (9). Considering that more than 92% of U.S. men screened have a PSA level of less than 4.0 ng/mL, these data suggest that most prostate cancer is present in men with PSA levels less than 4.0 ng/mL. If we choose to find these tumors, we are woefully ill-equipped to make treatment decisions. It is currently not possible to predict whether a low-grade tumor detected in a man with low PSA levels poses a true health risk. However, in our risk-averse and litigious society, which generally treats disease for the worst-case scenario, a substantial proportion of physicians will recommend—and men will choose—definitive treatment. The study of Potosky et al. has provided powerful evidence about the long-term morbidity of prostate cancer treatment. As such, it is a clarion call for a focused, long-term investment at the national level to address seminal questions regarding prostate cancer detection and treatment. First and foremost, we need the results of well-designed and wellexecuted screening trials. Second, trials need to be designed that will indicate whether treatment provides long-term benefits to men with early-stage prostate cancer. Third, we need to develop better ways to identify those men for whom the benefits of treatment outweigh the harms. To this end, a large national cohort study of men with prostate cancer should be designed and implemented that includes a repository of biological specimens that will help in characterizing the hallmarks of biologically consequential disease. Such a study could also collect information on behavior that may affect prostate cancer outcome, as well as quality of life information to help men and their physicians make truly informed treatment decisions. It is now time to regroup, develop a national strategy, and invest in the future. It is possible that, with such an investment, within two decades we can achieve the goal of a screening test in an individual man that identifies a cancer that will cause him harm, at a stage when it can be cured, and that specifies treatment that will cure the disease while optimizing quality of life.