Does delaying prostate cancer treatment miss the window of curability

Prostate cancer screening has been shown to reduce metastasis and disease-specific mortality, although these gains are offset to varying degrees by treatment-related decrements in quality of life (QoL) [1]. Despite advances in standard treatment and the advent of several new therapeutic modalities, the potential for side effects remains. An alternative option is observational management, including traditional watchful waiting as well as contemporary active surveillance (AS) protocols. According to theNational Institutes of Health Consensus Statement, AS is designed to delay curative treatment until it is warranted based on defined indicators of disease progression [2]. How often does AS fulfill this objective, and what is the risk that the window of curability will be missed? In the current issue, van den Bergh et al. published the results of a systematic review of the impact of treatment delay on prostate cancer oncologic outcomes [3]. They identified 17 retrospective studies addressing this issue in 34 517 patients diagnosed from 1981 to 2009. Unfortunately, there was substantial heterogeneity among the studies in criteria and/or reason for delayed treatment as well as in statistical methodology and outcome measurements (from pathology to survival). Seven studies suggested no significant impact of treatment delay of 2.1 yr on outcome, and an additional four studies showed no difference in outcome after multivariable adjustment. Conversely, four studies showed more adverse pathology or biochemical progression with longer treatment delay. Finally, two studies actually showed less upstaging in men undergoing delayed treatment, although this was considered likely due to bias. The authors concluded that most studies failed to reject the null hypothesis (no difference in outcomes between immediate vs delayed treatment) but had limited power [3]. An important consideration is that this review strictly evaluated oncologic outcomes and did not evaluate QoL. Although AS is often suggested as a way to avoid or delay treatment-related side effects, more data are needed on the potential morbidity of surveillance itself. Perhaps most significant, repeated prostate biopsies increase the cumulative risk of experiencing a serious infectious complication requiring hospitalization [4]. Biopsies also frequently lead to bleeding and can exacerbate lower urinary tract symptoms, although both of these sequelae are usually minor and transient [5]. More recent data have raised the concern that serial prostate biopsies may be associated with an increased risk of erectile dysfunction [6] or worse functional outcomes after subsequent radical prostatectomy [7]. Moving forward, ongoing improvements in biomarkers and imaging may help to reduce reliance on serial prostate biopsies during AS and thus potentially reduce morbidity. Less invasive tests such as the Prostate Health Index and magnetic resonance imaging have recently been shown to predict disease reclassification during surveillance [8,9]. Even so, delaying curative treatment may still affect QoL in other ways such as anxiety and depression [10]. The results by van den Bergh et al. are generally encouraging and suggest that delays ranging from a few months to a few years are unlikely to negatively affect short-term oncologic outcomes for low-risk patients [3]. However, the overall quality of the available evidence was low. More data are needed on the long-term consequences of deferring treatment, particularly for young men with life expectancy of >15 to 20 yr. This group also has the best oncologic and functional outcomes with immediate definitive treatment, so correspondingly, the balance of benefits and risks differs from that of older men with significant E U RO P E AN URO L OG Y 6 4 ( 2 0 1 3 ) 2 1 6 – 2 1 8