Identifying intermediate-risk candidates for active surveillance of prostate cancer

Although already established for very-low and low-risk (LR) prostate cancer (PCa), controversy remains around offering active surveillance (AS) to men with intermediate-risk (IR) PCa. As IR represents a broad spectrum of disease biology, there is a critical need to define eligibility criteria that will enable both patient and physician to accept AS as the best balance of competing risks. In this study, we aimed to identify predictors of progression to enable optimal patient selection.

In our AS cohort, men were assigned to risk categories according to the National Comprehensive Cancer Network (NCCN favorable and NCCN unfavorable) and the CAPRA classifications. Clinical, biochemical and pathological characteristics, progression to definitive invasive treatment, and pathologic progression on follow-up biopsies were compared among these groups. A multivariate Cox regression model was used to identify independent predictors of progression on AS.

AS was the initial management option for 651 men, including 144 with IR PCa. During the median follow-up of 4.5 years (range: 0.6-19.1), 259 patients (39.7%) underwent definitive treatment. Further, 5- and 10-year predicted rates of intervention for IR patients were 50% and 66%, respectively. Treatment rates were no different between the NCCN LR and NCCN IR groups, but were higher in CAPRA IR compared to CAPRA LR groups (P = 0.025). NCCN unfavorable IR patients had a twofold increased risk of definitive intervention compared to favorable IR (hazard ratio [HR] = 2.07; 95% CI: 1.17-3.65; P = 0.01). In the entire cohort, the percentage of biopsy cores positive (continuous variable; P = 0.006) and ISUP grade 2 or higher on initial biopsy (P = 0.027) were independent predictors of cessation of AS on multivariate analysis. In the intermediate group, only the percentage of positive biopsy cores was an independent predictor (P = 0.021) of AS cessation. Only 1 IR patient developed metastatic disease (0.7%). Actuarial overall survival at 5 and 10 years was 98.6% and 94.1%, respectively. There were 2 PCa deaths at 18.7 and 19.1 years of follow-up.

In all AS, increasing percentage of core involvement and presence of Gleason pattern 4 are predictors of increased risk of progression. For IR patients, the NCCN favorable criteria and CAPRA score predict those more likely to remain on AS.