Normal preoperative endogenous testosterone levels predict prostate cancer progression in elderly patients after...

The impact of senior age on prostate cancer (PCa) oncological outcomes following radical prostatectomy (RP) is controversial, and further clinical factors could help stratifying risk categories in these patients.

We tested the association between endogenous testosterone (ET) and risk of PCa progression in elderly patients treated with RP.

Data from PCa patients treated with RP at a single tertiary referral center, between November 2014 and December 2019 with available follow-up, were retrospectively evaluated.

Preoperative ET (classified as normal if >350 ng/dl) was measured for each patient. Patients were divided according to a cut-off age of 70 years. Unfavorable pathology consisted of International Society of Urologic Pathology (ISUP) grade group >2, seminal vesicle, and pelvic lymph node invasion. Cox regression models tested the association between clinical/pathological tumor features and risk of PCa progression in each age subgroup.

Of 651 included patients, 190 (29.2%) were elderly. Abnormal ET levels were detected in 195 (30.0%) cases. Compared with their younger counterparts, elderly patients were more likely to have pathological ISUP grade group >2 (49.0% versus 63.2%). Disease progression occurred in 108 (16.6%) cases with no statistically significant difference between age subgroups. Among the elderly, clinically progressing patients were more likely to have normal ET levels (77.4% versus 67.9%) and unfavorable tumor grades (90.3% versus 57.9%) than patients who did not progress. In multivariable Cox regression models, normal ET [hazard ratio (HR) = 3.29; 95% confidence interval (CI) = 1.27-8.55; p = 0.014] and pathological ISUP grade group >2 (HR = 5.62; 95% CI = 1.60-19.79; p = 0.007) were independent predictors of PCa progression. On clinical multivariable models, elderly patients were more likely to progress for normal ET levels (HR = 3.42; 95% CI = 1.34-8.70; p = 0.010), independently by belonging to high-risk category. Elderly patients with normal ET progressed more rapidly than those with abnormal ET.

In elderly patients, normal preoperative ET independently predicted PCa progression. Elderly patients with normal ET progressed more rapidly than controls, suggesting that longer exposure time to high-grade tumors could adversely impact sequential cancer mutations, where normal ET is not anymore protective on disease progression.