The changing face of surgically treated low-risk prostate cancer (PCa): A national cancer database (NCDB) analysis

Introduction & Objectives: The last decade witnessed an increasing adoption of active surveillance (AS)as a treatment option in low-risk PCa patients. However, low-risk patients who don\u27t fulfill the AS criteria still receive some form of local treatment, such as radical prostatectomy (RP)or radiotherapy. We tested the hypothesis that these individuals harbor a higher burden of tumor in comparison to their historic counterparts. Materials & Methods: We identified 164215 clinically low-risk PCa patients (PSA ≤10 ng/ml, biopsy Gleason score ≤6, and clinical T1-T2a stage)who were treated with RP, radiotherapy, or Observation, between 2010 and 2015, within the NCDB. Patients were stratified based on treatment type, and regression analysis was used to evaluate changes in PSA values, percentage of positive cores (%PCores), and life expectancy (LE)overtime. To analyze pathological data, we focused on RP patients and used regression analysis to test changes in the rate of upgrading (pathological Gleason ≥3+4), upstaging (pathological ≥T3a stage), and positive surgical margins overtime, after adjusting to all available covariates. Results: Median (Interquartile range [IQR])PSA, %PCores, and LE were 5.25 (4.1-6.4)ng/mL, 25% (12.5-41.67%), and, 20.75 (15.68-24.63)years respectively. Among these, the %PCores changed significantly overtime among the different treatment groups. Specifically, between 2010 and 2015, mean %PCores increased from 31.33 to 32.44% in RP, 29.25 to 30.70% in radiotherapy, and decreased from 24.78 to 20.41% in AS patients (p\u3c0.0001). On pathological data analysis, more contemporary RP patients (year 2015)showed higher rates of upgrading (54.45% vs 41.62%, P\u3c.0001), upstaging (11.62% vs 9.03%, P\u3c.0001), and positive surgical margins (18.08% vs 15.67%, P\u3c.0001)than their more historic counterparts (year 2010). These findings were confirmed on multivariable analysis. Conclusions: Our findings show that contemporary low-risk PCa patients treated surgically harbor more aggressive disease than historic patients. This is an important observation that should be considered when planning surgery in these individuals, and when using pre-operative prediction models based on historic data. Several factors could have resulted in these changes, such as the increased utilization of AS, and the recommendation against PSA screening, among others