UC San Francisco UC San Francisco Previously Published Works Title Active surveillance for prostate cancer : Progress and promise

Widespread prostate-specific antigen (PSA) –based screening and aggressive treatment of prostate cancer have reduced mortality rates substantially, but both remain controversial in large part because of high rates of overdiagnosis and overtreatment of otherwise indolent tumors. Active surveillance—or close monitoring of PSA levels combined with periodic imaging and repeat biopsies—is gaining acceptance as an alternative initial management strategy for men with low-risk prostate cancer. In reported series, rates of progression to active treatment with intermediate-term follow-up have ranged from 14% to 41%, and likelihood of subsequent cure with surgery or radiation does not seem to be compromised by an initial trial of surveillance. Two related challenges to broader acceptance of surveillance are better characterization at time of diagnosis of the risk of progression (including likelihood that given tumor may have been undersampled by diagnostic biopsy) and validation of optimal end points once surveillance begins. Both are subjects of intense ongoing investigation, with emerging biomarkers and novel imaging tests expected to facilitate decision making substantially. Recent reports have suggested active surveillance can be a cost-effective approach and preserve quality of life, but these questions must be assessed more definitively in prospective cohorts. Ultimately, by minimizing the harms of overtreating low-risk prostate cancer, active surveillance may help settle the controversy surrounding prostate cancer screening and management. J Clin Oncol 29:3669-3676. © 2011 by American Society of Clinical Oncology RATIONALE FOR SURVEILLANCE Although prostate cancer kills more men annually in the United States than any malignancy except lung cancer, a substantial majority of men diagnosed ultimately die as a result of other causes. Indeed, many prostate cancers would never cause any impairment to quality or quantity of life if undetected and are thus said to be overdiagnosed. In the era of prostate-specific antigen (PSA) – based screening, the percentage of prostate cancers overdiagnosed has recently been estimated, based on data from large screening trials, to be as high as 23% to 67%, depending on the specific definitions of overdiagnosis assessed. In contemporary practice in the United States, diagnosis tends to lead to treatment; thus, as the proportion of prostate cancers diagnosed with low-risk characteristics has grown, overdiagnosis has been associated with high rates of overtreatment. Despite randomized controlled trials demonstrating survival benefits for prostate cancer screening among men with good life expectancy, the harms of detection, primarily those related to overtreatment, underlie the negative opinions on screening promulgated by the US Preventive Services Task Force and others. Although the new recommendation by the American Urological Association to begin screening at age 40 years for most men might be expected to identify a higher proportion of lethal tumors at an earlier, curable stage, it will likely be associated with risks of further overdiagnosis of indolent tumors among men at even younger ages. Therefore, treatment must be applied selectively, and the timing and intensity of treatment should reflect disease and patient characteristics. An emerging consensus now supports deferring treatment initially for a growing proportion of men diagnosed with low-risk (ie, low volume, stage, and grade) prostate cancer. Under the management strategy of active surveillance, men are observed carefully with serial PSA assessments, repeat biopsies, and other tests intended to identify early signs of progression. The term active surveillance has supplanted watchful waiting, but the two are not synonymous. The latter term generally applied to older men with significant comorbidity; they were advised to defer treatment unless symptoms developed, at which point palliative androgen deprivation could be offered. Active surveillance, on the other hand, rests on the presumptions that the lead time from diagnosis to clinical progression is usually long for JOURNAL OF CLINICAL ONCOLOGY R E V I E W A R T I C L E VOLUME 29 NUMBER 27 SEPTEMBER 2