Today, the majority of men with newly diagnosed prostate cancer will present with low-risk features of the disease. Because prostate cancer often takes an insidious course, it is debated whether the majority of these men require radical treatment and the accompanying derangement of quality of life domains imposed by surgery, radiation, and hormonal therapy. Investigators have identified various selection criteria for "insignificant disease," or that which can be monitored for disease progression while safely delaying radical treatment. In addition to the ideal definition of low risk, a lack of randomized trials comparing the various options for treatment in this group of men poses a great challenge for urologists. Early outcomes from active surveillance cohorts support its use in carefully selected men with low-risk disease features, but frequent monitoring is required. Patient selection and disease monitoring methods will require refinement that will likely be accomplished through the increased use of biomarkers and specialized imaging techniques.
Biomarkers ; Cohort Studies ; Disease Management ; Disease Progression ; Humans ; Male ; Patient Selection ; Prostate ; Prostatic Neoplasms ; Quality of Life ; Research Personnel

Purpose: Contemporary treatment strategies for localized prostate cancer (PCa) have been evolved over time. However, there is little data regarding survival outcomes based on initial treatment by risk group in this new era. This study aims to evaluate survival outcomes among men who underwent observation, radiotherapy, or radical prostatectomy for localized PCa using a population-based cohort. Materials and Methods: The Surveillance, Epidemiology, and End Results (SEER) prostate with watchful waiting dataset (2010–2016) was used. We included men diagnosed with localized PCa and clinical stage T1c-2cN0M0. Other inclusion criteria were age 50–79 years, prostate-specific antigen (PSA) ≤50 ng/mL, and initial treatment with observation (active surveillance/watchful waiting), radiotherapy, or radical prostatectomy. PCa risk was assessed using the D’Amico classification. The primary endpoint was overall survival. Secondary endpoints included PCa-specific survival. Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazard regression and competing risk analysis were performed to assess outcomes. Results: After IPTW-adjusting, pseudo-population comprised 521,656 men (observation: 170,428, radiotherapy: 175,628, radical prostatectomy: 175,600) at a median 36.5 month follow-up. Observation demonstrated the lowest 5-year overall survival rate (91.6%) after IPTW-adjusting in comparison to radiotherapy (92.4%) and radical prostatectomy (96.1%, p<0.001). Men who underwent radical prostatectomy had the lowest cumulative PCa-specific and all-cause mortality (p<0.001). Compared to observation, radiotherapy (sub-distribution hazard ratio [sHR], 0.89; 95% CI, 0.81–0.97; p=0.012) and radical prostatectomy (sHR, 0.46; 95% CI, 0.41–0.52; p<.001) had a lower risk of PCa-specific mortality in competing risk analysis after adjustment for all other factors and other-cause death. Conclusions Intermediate-term mortality risk in men with localized PCa were lower with active treatments compared to observation-especially for intermediate- and high-risk disease. However, observation represents a safe management strategy in men within the low-risk group.