Age at prostate cancer (PCa) diagnosis has been positively associated with PCa-specific mortality, and for men on active surveillance (AS), a higher risk of biopsy grade reclassification (BGR) to Gleason score ≥3+4 (grade group [GG]≥2); however, the association between age and BGR to an aggressive phenotype (Gleason score ≥4+3 [GG≥3]) has not been explored.

From 1995-2016, 1625 men aged 41-81y with NCCN very-low (68%) or low (32%) risk PCa were followed on AS. We determined rates of BGR to GG≥3. Competing risk analysis was used to evaluate the association between age at enrollment and risk of BGR. Additionally, in men who underwent radical prostatectomy (RP) after BGR, we assessed rates of RP grade reclassification (RPGR; i.e. RP GG>biopsy GG).

The 5-year incidence of BGR to GG≥3 was 4%, 7% and 14% in men <60y, 60-69y and ≥70y, respectively (p<0.001). In univariate analysis, older age was associated with BGR to GG≥3 (HR=2.43 per 10-year increase, p<0.001). In multivariable analysis adjusting for year of diagnosis, race, PSA density and cancer volume at diagnosis, older age remained associated with BGR to GG≥3 (HR=2.19 per 10-year increase; p<0.001). In men who underwent RP after BGR, older men had higher rates of RPGR (p<0.05).

For men on AS, older age at time of diagnosis was positively associated with BGR to GG≥3, and RPGR. These observations imply that for many older men, AS (as opposed to watchful waiting) remains a more appropriate management strategy.