Active Surveillance for Low-Risk Prostate Cancer-An Evolving International Standard of Care.

In 2016, active surveillance has finally become standard of care for low-risk prostate cancer in the United States. Recent articles from prospective, community-based registries have shown uptake of active surveillance skyrocketing to 40% to 50% for low-risk disease in the current decade, up from rates that historically rarely exceeded 10%. 1,2 A growing body of evidence indicates that active surveillance can preserve quality of life without posing substantial shortto intermediate-term oncologic risk. Based on this evidence, a recent guideline endorsed by the American Society of Clinical Oncology (ASCO) now clearly states that surveillance is not merely an option for men with low-risk disease but rather is the preferred alternative for any clinically localized, Gleason 3 + 3 cancer.3 From this perspective, given that most men with low-risk tumors who undergo any therapeutic intervention face substantial likelihoods of overtreatment, active surveillance rates for low-risk disease are still too low in the United States. In the current study by Loeb et al,4 the authors provide an updated analysis of active surveillance and watchful waiting rates for low-risk disease in Sweden, where active surveillance has long been a standard approach and an important aspect of early detection efforts.5 The authors report that the combined use of active surveillance and watchful waiting rose from 50% in 2009 to 79% in 2014.4 The National Prostate Cancer Register (NPCR) is enviable for its completeness and linkages to other national data sources, yielding better accuracy than comparable national tumor registries in the United States or most other countries. Direct reporting of treatments, moreover, prevents mislabeling the simple absence of active treatment as “active surveillance” or “watchful waiting. ” Across various academic cohorts, substantial variation exists in eligibility criteria for active surveillance. The definition of “very-low-risk” prostate cancer used by Loeb et al4 requires not only low-grade, low-stage disease, but also low prostate specific antigen density, and minimal tumor volume on biopsy. This definition is essentially a modification of the National Comprehensive Cancer Network very-low-risk definition, which in turn recapitulates the Johns Hopkins University criteria for active surveillance.6 None of these definitions has ever been validated as optimal for selecting men for surveillance, and in fact they are almost certainly overly restrictive. Recognizing of course that many men with low-risk disease who start on surveillance will ultimately receive treatment—but that the window of opportunity for cure is typically measurable at least in years—the ASCO guideline includes no mention of supplemental criteria such as tumor volume in its recommendation for eligibility. In fact, if there should be a role for sub-stratifying the traditional low-risk group in the setting of conservative management, it may be to identify some men eligible for less active surveillance—or for watchful waiting. Men with low-risk prostate cancer who are older or otherwise have limited life expectancy face a negligible risk of cancer mortality and in many cases should not need to undergo serial biopsies and the other frequent testing that defines active surveillance. The Swedish data are therefore surprising in demonstrating a steady drop in use of watchful waiting—by nearly twothirds (32% to 12%) for men 70 years or older with very-lowrisk disease and drops in older men with higher-risk disease too. These data may reflect some change over time in the way clinicians report their management decisions to NPCR, but if on the other hand surveillance intensity is rising for these men at lowest risk of prostate cancer mortality, then this may be a trend in the wrong direction. By the one indicator of surveillance intensity reported in the study—repeat prostate biopsy— surveillance in Sweden tends to be quite lax, with only 31% and 26% of men younger than 70 years, and far fewer men older than 70 years, undergoing biopsy in the first and second year, respectively. The fact that these respective rates were 8% and 13% even for men on watchful waiting suggests some inconsistency in definitions and/or clinicians’ understanding of these terms. Particularly given changes in pathology grading practices over the years, active surveillance is increasingly recognized as a safe alternative for carefully selected men with lowvolume, Gleason 3 + 4 tumors, as reflected in the ASCO guideline.3 This recommendation is based on findings from academic cohorts supporting the intermediate-term oncologic safety of active surveillance,7 but remains relatively uncommon in the United States. Broader use of advanced imaging and genomic testing may identify more men with Gleason 3 + 4 tumors eligible for surveillance. The data reported by Loeb et al4 data suggest that for men with these tumors, active surveillance rates have been relatively low, and essentially constant, over the observation period. Conversely, for men older than 70 years with CAPRA scores as high as 7—indicating high-risk tumors with multiple adverse features—rates of watchful waiting were surprisingly high, indicating possible undertreatment among these men who face substantial risks of cancer-specific mortality in the absence of local treatment.8 Sweden naturally differs from the United States in many ways in terms of both prostate cancer epidemiology and health care delivery. Nonetheless, the observed rate of nearly 80% initial active surveillance or watchful waiting for low-risk prostate cancer is likely a goal to which we should aspire on both sides of the Atlantic. Of course, many men starting on surveillance will ultimately need treatment, but these decisions can Related article Active Surveillance for Low Risk Prostate Cancer Invited Commentary