More Judicious Use of Expectant Management for Localized Prostate Cancer during the Last 2 Decades.

PurposeUrologists have been criticized for overtreating men with low risk prostate cancer and for passively observing older men with higher risk disease. Proponents of active surveillance for low risk disease and critics of watchful waiting for higher risk disease have advocated for more judicious use of observation. Thus, we compared 2 population based cohorts to determine how expectant management has evolved during the last 2 decades.Materials and methodsA total of 5,871 men with localized prostate cancer were enrolled in the PCOS (Prostate Cancer Outcomes Study) or the CEASAR (Comparative Effectiveness Analysis of Surgery and Radiation) study. We compared the use of definitive treatment vs expectant management (watchful waiting or active surveillance) across cohorts, focusing on the influence of disease risk, age and comorbidities.ResultsUse of watchful waiting or active surveillance was similar in PCOS and CEASAR (14% in each). Compared to the PCOS, more men in the CEASAR study with low risk disease selected watchful waiting or active surveillance (25% vs 15%, respectively), whereas fewer men with intermediate (7% vs 14%) and high risk (3% vs 10%) disease chose watchful waiting or active surveillance (p <0.001 for each). The association of disease risk with watchful waiting or active surveillance was significantly larger in CEASAR than in PCOS (OR 7.3, 95% CI 3.4 to 15.7). Older age was associated with watchful waiting or active surveillance in both cohorts but there was no association between comorbidity and watchful waiting or active surveillance in the CEASAR study.ConclusionsUse of watchful waiting or active surveillance was more aligned with disease risk in CEASAR compared to PCOS, suggesting there has been a pivot from watchful waiting to active surveillance. While older men were more likely to be observed, comorbidity had little, if any, influence

Optimal Trial Design for Studying Urinary Markers in Bladder Cancer: A Collaborative Review

Urine-based tumor markers are not routinely used in the diagnosis and surveillance of bladder cancer. The main limitation of urinary markers has been a lack of clarity regarding clinical benefit. To review the indications for urinary marker use, barriers to marker utilization, and clinical trial designs for markers available for detection (hematuria populations) and surveillance (bladder cancer populations). The study aim was to facilitate an optimal trial design that could change clinical practice. A PubMed search was conducted on February 17, 2018, using the MeSH search terms “Urinary Bladder Neoplasms” [Mesh] AND “Biomarkers” [Mesh] AND “Urine” [Mesh] yielded 127 articles, of which only two also fulfilled the search term “Randomized Controlled Trial” [Publication Type]. Neither of these two articles examined clinical outcomes for patients but rather focused on the performance characteristics of the urinary marker. For the search terms “Hematuria” [Mesh] AND “Randomized Controlled Trial” [Publication Type] AND “Urinary Bladder Neoplasms” [Mesh] yielded 12 articles, none of which used randomization with the outcome of interest being a clinical endpoint. Several potential designs for urinary marker trials were developed for detection and surveillance of bladder cancer. A marker-based approach compared to usual care for evaluation of hematuria in a primary care setting could reduce unnecessary cystoscopy in patients with low risk and expedite care in patients with higher risk. For bladder cancer surveillance, marker-based approaches could reduce cystoscopy for patients with low-grade disease and potentially improve detection for patients with high risk. Urinary markers are not currently routinely used owing to the absence of level 1 evidence supporting incorporation of urinary markers into protocols for detection or surveillance of bladder cancer. This review provides practical designs for studies that could demonstrate superiority of marker-based approaches over current clinical care. The sample sizes required for these studies are no greater than many of those accrued for previous urinary marker studies, but the proposed trial concepts require planning and a willingness to risk failure of the marker to demonstrate the desired benefits. In this review we discuss current limitations in the use of urinary markers for detection and surveillance of bladder cancer. We identify potential studies that could demonstrate a clinical benefit of the use of markers in improving detection of bladder cancer by reducing evaluation of patients unlikely to have cancer or expediting identification of cancer. For surveillance, a marker trial could improve identification of bladder cancer or reduce cystoscopy in patients with low risk. Urinary markers are not routinely used for detection or surveillance of bladder cancer. This review provides practical designs for studies that could demonstrate superiority of marker-based approaches over current care