Impact of age on the effectiveness of intravesical Bacillus Calmette‑Guérin and gemcitabine/docetaxel in treatment-naïve high-risk non‑muscle‑invasive bladder cancer.

内容摘要

Intravesical Bacillus Calmette&#x2011;Gu&#xe9;rin (BCG) has long been the standard therapy for high&#x2011;risk non&#x2011;muscle&#x2011;invasive bladder cancer (HR&#x2011;NMIBC), yet treatment response may vary with age. Sequential intravesical gemcitabine/docetaxel (Gem/Doce) has emerged as a well&#x2011;tolerated and effective alternative, particularly during periods of BCG shortage, contributing to its increasing global adoption. However, the influence of age on oncologic outcomes with either regimen remains unclear, with prior studies reporting heterogeneous results, especially within BCG&#x2011;treated cohorts. This study evaluated the impact of age on the effectiveness of intravesical BCG and Gem/Doce in treatment&#x2011;na&#xef;ve patients with HR&#x2011;NMIBC. We retrospectively reviewed data on treatment na&#xef;ve HR-NMIBC patients treated with BCG or sequential Gem/Doce from 2011-2024. The BCG cohort received a 6&#x2011;week induction course followed by maintenance at 3, 9, and 15 months. Gem/Doce consisted of six weekly induction instillations, followed by monthly maintenance for up to 24 months in patients who responded to induction. Age groups were defined as <60, 60-69, 70-79, and &#x2265;80 years. Recurrence&#x2011;free survival (RFS) and high&#x2011;grade RFS (HG&#x2011;RFS) were estimated using Kaplan-Meier analysis, and age&#x2011;related recurrence risk was evaluated using univariate Cox regression. A total of 401 patients were included (BCG =192; Gem/Doce =209), with median follow-up of 84 months [interquartile range (IQR), 54-127 months] and 44 months (IQR, 28-62 months), respectively. Age was not significantly associated with RFS or HG-RFS in either cohort (BCG: for RFS, continuous age P=0.13 and categorical age P=0.15; for HG&#x2011;RFS, continuous age P=0.07 and categorical age P=0.12; Gem/Doce: for RFS, continuous age P=0.62 and categorical age P=0.44; for HG&#x2011;RFS, continuous age P=0.51 and categorical age P=0.68). In the BCG cohort, descriptive analyses showed a progressive decline in RFS and HG-RFS with advancing age, particularly among patients &#x2265;70 years, who demonstrated lower 12- and 24-month outcomes (e.g., 24-month RFS: 64% for <60 years vs. 58% for 70-79 years and 59% for &#x2265;80 years). In contrast, age&#x2011;related differences in the Gem/Doce cohort were smaller and primarily evident during early follow&#x2011;up (12 months); patients aged 70-79 and &#x2265;80 years maintained stable outcomes at later time points (24 and 36 months) and did not exhibit lower outcomes (e.g., 24-month RFS: 73% for <60 years vs. 80% for 70-79 years and 76% for &#x2265;80 years). Age was not a statistically significant predictor of HG&#x2011;RFS following either BCG or Gem/Doce therapy when controlling for known clinicopathologic risk factors. Although not statistically significant, a trend toward lower recurrence outcomes in older BCG&#x2011;treated patients was observed and warrants further investigation.