Sequential intravesical gemcitabine/docetaxel provides a durable remission in recurrent high-risk NMIBC following BCG therapy

• Published in: Urologic oncology 2023-11, Vol.41 (11), p.458.e1-458.e7
• Main Authors: Yim, Kendrick, Melnick, Kevin, Mott, Sarah L., Carvalho, Filipe L.F., Zafar, Affan, Clinton, Timothy N., Mossanen, Matthew, Steele, Graeme S., Hirsch, Michelle, Rizzo, Natalie, Wu, Chin-Lee, Mouw, Kent W., Wszolek, Matthew, Salari, Keyan, Feldman, Adam, Kibel, Adam S., O'Donnell, Michael A., Preston, Mark A.
• Format: Article
• Language: English
• Subjects: Aged; BCG; BCG Vaccine - therapeutic use; Bladder cancer; Docetaxel - therapeutic use; Gemcitabine; Humans; Intravesical therapy; Neoplasm Recurrence, Local - drug therapy; Non-Muscle Invasive Bladder Neoplasms; Nonmuscle invasive bladder cancer; Outcomes; Prospective Studies; Retrospective Studies; Urinary Bladder Neoplasms
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2023.06.018

•Half of patients who receive BCG for NMIBC will develop disease recurrence.•Intravesical gemcitabine/docetaxel appears to be well tolerated with minimal delay in treatment schedule.•High-grade RFS at 12 and 24 months was 65% and 49%, respectively.•Gem/doce helped delay cystectomy (median 15 months) with minimal increased risk of progression to muscle invasive disease.•Patients with BCG refractory disease were more likely to develop HG recurrence when compared to patients with BCG relapsing disease. Bacillus Calmette–Guerin (BCG) is the standard of care for high-risk nonmuscle invasive bladder cancer (NMIBC), but half of patients develop disease recurrence. Intravesical regimens for BCG unresponsive NMIBC are limited. We report the safety, efficacy, and differential response of sequential gemcitabine/docetaxel (gem/doce) depending on BCG failure classification. Multi-institutional retrospective analysis of patients treated with induction intravesical gem/doce (≥5/6 instillations) for recurrent high-risk NMIBC after BCG therapy from May 2018 to December 2021. Maintenance therapy was provided to those without high-grade (HG) recurrence on surveillance cystoscopy. Kaplan–Meier curves and Cox regression analyses were utilized to assess survival and risk factors for disease recurrence. Our cohort included 102 patients with BCG-unresponsive NMIBC. Median age was 72 years and median follow-up was 18 months. Six-, 12-, and 24-month high-grade recurrence-free survival was 78%, 65%, and 49%, respectively. Twenty patients underwent radical cystectomy (median 15.5 months from induction). Six patients progressed to muscle invasive disease. Fifty-seven percent of patients experienced mild/moderate adverse effects (AE), but only 6.9% experienced a delay in treatment schedule. Most common AE were urinary frequency/urgency (41%) and dysuria (21%). Patients with BCG refractory disease were more likely to develop HG recurrence when compared to patients with BCG relapsing disease (HR 2.14; 95% CI 1.02–4.49). In patients with recurrence after BCG therapy, sequential intravesical gem/doce is an effective and well-tolerated alternative to early cystectomy. Patients with BCG relapsing disease are more likely to respond to additional intravesical gem/doce. Further investigation with a prospective trial is imperative.