Comparison of Sequential Intravesical Gemcitabine and Docetaxel vs Bacillus Calmette-Guérin for the Treatment of Patients With High-Risk Non–Muscle-Invasive Bladder Cancer

Abstract

ImportanceDue to the ongoing bacillus Calmette-Guérin (BCG) shortage, sequential intravesical gemcitabine and docetaxel has been increasingly used as first-line therapy for high-risk non–muscle-invasive bladder cancer (NMIBC). However, data directly comparing these 2 therapies are lacking.ObjectiveTo compare the outcomes of patients with high-risk NMIBC treated with gemcitabine and docetaxel vs BCG.Design, Setting, and ParticipantsThis retrospective cohort study was conducted from January 1, 2011, to December 31, 2021. The median (IQR) duration of follow-up was 23 (12-33) months for patients receiving gemcitabine and docetaxel and 49 (27-79) months for patients receiving BCG. All patients were treated at the University of Iowa tertiary care center. A total of 312 patients with high-risk treatment-naive NMIBC were included; 174 patients were treated with BCG therapy and 138 were treated with gemcitabine and docetaxel therapy.ExposuresAfter undergoing complete transurethral resection of bladder tumor, patients received either sequential intravesical gemcitabine, 1 g, and docetaxel, 37.5 mg, or 1 vial of BCG. Induction treatments were administered once per week for 6 weeks. Maintenance regimens were initiated if the patient was disease free at the first follow-up visit.Main Outcomes and MeasuresThe primary outcome was high-grade recurrence-free survival (RFS). Survival probabilities were estimated using the Kaplan-Meier method. Cox regression models were used to evaluate the association of covariates with outcomes. Adverse events were reported using the Common Terminology Criteria for Adverse Events, version 5.ResultsAmong 312 patients, the median (IQR) age was 73 (66-79) years; 255 patients (81.7%) were male and 292 (93.6%) were White. Baseline clinicopathological characteristics such as sex, smoking status, and pretreatment tumor pathology were similar between treatment groups. High-grade RFS estimates were 76% (95% CI, 69%-82%) at 6 months, 71% (95% CI, 64%-78%) at 12 months, and 69% (95% CI, 62%-76%) at 24 months in the BCG group and 92% (95% CI, 86%-95%) at 6 months, 85% (95% CI, 78%-91%) at 12 months, and 81% (95% CI, 72%-87%) at 24 months in the gemcitabine and docetaxel group. Multivariable Cox regression analyses controlled for age, sex, treatment year, and presence of carcinoma in situ revealed that treatment with gemcitabine and docetaxel was associated with better high-grade RFS (hazard ratio, 0.57; 95% CI, 0.33-0.97; P = .04) and RFS (hazard ratio, 0.56; 95% CI, 0.34-0.92; P = .02) than treatment with BCG. Induction therapy for BCG was associated with greater treatment discontinuation than induction therapy for gemcitabine and docetaxel (9.2% vs 2.9%; P = .02).Conclusions and RelevanceIn this cohort study, gemcitabine and docetaxel therapy was associated with less high-grade disease recurrence and treatment discontinuation than BCG therapy. These findings suggest that, while awaiting results from an ongoing randomized clinical trial during the current BCG shortage, use of gemcitabine and docetaxel can be considered for recommendation in updated practice guidelines.

Alternative instillation techniques of sequential intravesical gemcitabine and docetaxel for non‐muscle‐invasive bladder cancer

“…To achieve this goal, it is crucial to understand the most common complications associated with RARC to allow surgeons to take action to prevent their occurrence. To the best of our knowledge, only a few studies have evaluated the type of complications that may occur after RARC with intracorporeal neobladder, and the generalizability of their results is limited [1][2][3][4][5]. Previous studies have reported complications from small single-institution or single-surgeon series of patients who underwent RARC with either extracorporeal or intracorporeal neobladder, or did not use standardized criteria to report complications [6].…”

Novel immunotherapeutic options for BCG‐unresponsive high‐risk non‐muscle‐invasive bladder cancer

“…However, recent studies are demonstrating promising outcomes with the combination of two chemotherapeutic agents (gemcitabine and docetaxel) in the treatment of HR-NMIBC. 19,20 In a retrospective review, McElree et al 21 found 84% 2-year high-grade recurrence free survival (HG-RFS) using gemcitabine and docetaxel for BCG-naïve HR-NMIBC. Further long-term, retrospective analysis in a BCG-unresponsive cohort found a 75% 5-year bladder preservation rate, a 91% 5-year cancer-specific survival (CSS) rate, a 75% cystectomy free survival and, a 30% 5-year HG-RFS.…”

“…Several randomized controlled trials (RCTs) have shown that intravesical BCG therapy that includes an induction course of 6 weekly instillations and a maintenance course every 3–6 months for over 1–3 years is superior to TURBT alone 12‐16 or TURBT followed by intravesical induction chemotherapy 15,17,18 in terms of recurrence and progression prevention in NMIBC patients. However, recent studies are demonstrating promising outcomes with the combination of two chemotherapeutic agents (gemcitabine and docetaxel) in the treatment of HR‐NMIBC 19,20 . In a retrospective review, McElree et al 21 .…”

Nonrisk-adapted Sequential Intravesical Gemcitabine and Docetaxel for Nonmuscle-invasive Bladder Cancer: The Time Is Now

“…8 To perform a direct comparison with BCG, we recently published a retrospective report of 312 patients with newly diagnosed high-risk NMIBC, of whom 138 received Gem/Doce and 174 received BCG. 9 Patients who received Gem/Doce were older (median age 74 vs 71 years, P [ .002), but all clinicopathological features were similar between treatment groups. Gem/ Doce yielded superior 2-year HG-RFS compared to BCG (81% vs 69%), with no impact of clinicopathological features on recurrence on multivariable analysis.…”