Does Age-Related Immune Impairment Reduce BCG Treatment Response in Non-Muscle Invasive Bladder Cancer? - Expert Commentary
A recent study's retrospective analysis of 473 patients with NMIBC treated with adequate BCG examined this question. Adequate BCG was defined as at least 5 of 6 induction instillations plus either ≥2 of 3 maintenance or ≥2 of 6 reinduction instillations. Patients were stratified as age ≤70 years (232 patients, 49%) and >70 years (241 patients, 51%). Primary outcomes were high-grade recurrence (HGR) and progression to muscle-invasive disease or distant metastasis. Secondary outcomes included overall mortality and cancer-specific mortality (CSM). The cohorts showed no significant differences in sex, race, tobacco use, or tumor characteristics. Median follow-up was 58 months (IQR 27-103), differing between age groups (68 months for ≤70 vs 52 months for >70, p=0.03). HGR occurred in 107 patients (50%) aged ≤70 and 91 patients (35.1%) aged >70. Progression occurred in 22 patients (10.3%) aged ≤70 and 20 patients (7.7%) aged >70. Overall mortality was significantly higher in the >70 cohort (p<0.01). There was no statistically significant difference in cancer-specific mortality. Fine-Gray competing risk analysis accounting for non-bladder cancer death showed age >70 was not significantly associated with increased HGR (HR 0.77; 95% CI 0.59-1.02, p=0.06), progression (HR 1.17; 95% CI 0.62-2.18, p=0.63), or CSM (HR 1.12; 95% CI 0.42-2.95, p=0.82). Multivariable regression confirmed these findings, with age >70 showing an inverse association with HGR (HR 0.85; 95% CI 0.51-1.19, p=0.34) and no significant impact on progression (HR 1.13; 95% CI 0.40-1.86, p=0.74). When analyzed as a continuous variable, age remained non-predictive of HGR (p=0.78) or progression (p=0.64).
Data on re-TURBT rates and postoperative chemotherapy use were unavailable, though these likely did not differ by age. Study limitations include its retrospective design, long study period spanning changing treatment paradigms, and potential underreporting of mortality events due to patient loss to follow-up.
These findings suggest reconsidering whether BCG treatment decisions should be influenced by age alone, as immune competence required for BCG efficacy appears preserved in older patients. A deeper understanding of the biology of immune impairment with age, as it relates to BCG response, would inform these considerations.
Written by: Bishoy M. Faltas, MD, Chief Research Officer, Englander Institute for Precision Medicine, Gellert Family - John P. Leonard, MD, Research Scholar, Associate Professor of Medicine, Cell and Developmental Biology, Weill Cornell Medicine, New York- Presbyterian Hospital, NY
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