Effective Management of Localized Prostate Cancer: First, Do No Harm.

The diagnosis of prostate cancer (PCa) is a difficult reality, regardless of age, health status, or disease risk, and management decisions for localized disease are complex because of the paucity of evidence comparing various treatment options. In a 2008 review, ‘‘Comparative Effectiveness and Harms of Treatments for Clinically Localized Prostate Cancer,’’ prepared for the US Agency for Healthcare Research and Quality, the panel concluded that the ‘‘assessment of the comparative effectiveness and harms of localized prostate cancer treatments is difficult because of limitations in the evidence’’ [1]. The results of the recent randomized trial comparing observation and definitive treatment in men with localized PCa (Prostate Cancer Intervention Versus Observation Trial [PIVOT]) have further complicated management decisions [2]. However, recommendations for treatment of localized PCa should be individualized to patient characteristics, including health status, life expectancy, and treatment preference. In a shared-decision model, prognosis and life expectancy are difficult concepts for physicians and patients. Importantly, physician estimates of healthadjusted life expectancy are imprecise [3]. In the PIVOT trial, patients were enrolled if their life expectancy was estimated to be>10 yr; however, 48.4% and 47% of patients in the surgery and observation groups, respectively, died at 12 yr, and only 7.1% of deaths were attributed to PCa. Life expectancy estimations are a key component of treatment decisions for localized PCa, as shown by the inclusion of a 10-yr life expectancy benchmark in the recommendations of the American Urological Association [4] and the National Comprehensive Cancer Network guidelines [5]. Chronological age is a standard tool used to estimate life expectancy because it is readily available for physicians. However, comorbidity has a significant impact on health status and treatment tolerance. Identifying comorbidity and health status in a patient enables physicians to individualize treatment recommendations based on biologic age. Importantly, the association between age and comorbidity with cancer diagnosis is well established, and an estimated 68% of patients diagnosed with cancer have comorbidity. The frequency of comorbidity is increased in elderly and African American patients [6], thus many comorbidity assessment tools have been developed and validated in clinical practice. The Charlson comorbidity index is one of the most wellknown validated tools and predicts 1-yr mortality for hospitalized patients [7]. In addition, it has been shown to be a significant independent predictor of survival in patients with clinically localized PCa [8]. The validity of any comorbidity prognostic tool assumes an accurate assessment of comorbidity severity. In this issue of European Urology, Nepple and colleagues evaluate the impact of treatment on prostate cancer mortality (PCM) and overall mortality (OM) in men with localized PCa [9]. In this retrospective multi-institutional observational study, the authors focus on improving the accuracy of their comparisons among treatment options and mitigating the impact of medical comorbidity by restricting their analysis to men with no documented comorbidities. The authors studied a group of healthy men diagnosed with localized PCa who would benefit most from effective treatment. In men without recorded medical comorbidity, external-beam radiation therapy (ERBT) was EU RO P E AN URO L OG Y 6 4 ( 2 0 1 3 ) 3 7 9 – 3 8 0