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- Title
Effect of Intravesical Instillation of Gemcitabine vs Saline Immediately Following Resection of Suspected Low-Grade Non-Muscle-Invasive Bladder Cancer on Tumor Recurrence: SWOG S0337 Randomized Clinical Trial.
- Authors
Messing, Edward M.; Tangen, Catherine M.; Lerner, Seth P.; Sahasrabudhe, Deepak M.; Koppie, Theresa M.; Wood, David P.; Mack, Philip C.; Svatek, Robert S.; Evans, Christopher P.; Hafez, Khaled S.; Culkin, Daniel J.; Brand, Timothy C.; Karsh, Lawrence I.; Holzbeierlein, Jeffrey M.; Wilson, Shandra S.; Wu, Guan; Plets, Melissa; Vogelzang, Nicholas J.; Thompson, Ian M.; Wood, David P Jr
- Abstract
<bold>Importance: </bold>Low-grade non-muscle-invasive urothelial cancer frequently recurs after excision by transurethral resection of bladder tumor (TURBT).<bold>Objective: </bold>To determine whether immediate post-TURBT intravesical instillation of gemcitabine reduces recurrence of suspected low-grade non-muscle-invasive urothelial cancer compared with saline.<bold>Design, Setting, and Participants: </bold>Randomized double-blind clinical trial conducted at 23 US centers. Patients with suspected low-grade non-muscle-invasive urothelial cancer based on cystoscopic appearance without any high-grade or without more than 2 low-grade urothelial cancer episodes within 18 months before index TURBT were enrolled between January 23, 2008, and August 14, 2012, and followed up every 3 months with cystoscopy and cytology for 2 years and then semiannually for 2 years. Patients were monitored for tumor recurrence, progression to muscle invasion, survival, and toxic effects. The final date of follow-up was August 14, 2016.<bold>Interventions: </bold>Participants were randomly assigned to receive intravesical instillation of gemcitabine (2 g in 100 mL of saline) (n = 201) or saline (100 mL) (n = 205) for 1 hour immediately following TURBT.<bold>Main Outcomes and Measures: </bold>The primary outcome was time to recurrence of cancer. Secondary end points were time to muscle invasion and death due to any cause.<bold>Results: </bold>Among 406 randomized eligible patients (median age, 66 years; 84.7% men), 383 completed the trial. In the intention-to-treat analysis, 67 of 201 patients (4-year estimate, 35%) in the gemcitabine group and 91 of 205 patients (4-year estimate, 47%) in the saline group had cancer recurrence within 4.0 years (hazard ratio, 0.66; 95% CI, 0.48-0.90; P<.001 by 1-sided log-rank test for time to recurrence). Among the 215 patients with low-grade non-muscle-invasive urothelial cancer who underwent TURBT and drug instillation, 34 of 102 patients (4-year estimate, 34%) in the gemcitabine group and 59 of 113 patients (4-year estimate, 54%) in the saline group had cancer recurrence (hazard ratio, 0.53; 95% CI, 0.35-0.81; P = .001 by 1-sided log-rank test for time to recurrence). Fifteen patients had tumors that progressed to muscle invasion (5 in the gemcitabine group and 10 in the saline group; P = .22 by 1-sided log-rank test) and 42 died of any cause (17 in the gemcitabine group and 25 in the saline group; P = .12 by 1-sided log-rank test). There were no grade 4 or 5 adverse events and no significant differences in adverse events of grade 3 or lower.<bold>Conclusions and Relevance: </bold>Among patients with suspected low-grade non-muscle-invasive urothelial cancer, immediate postresection intravesical instillation of gemcitabine, compared with instillation of saline, significantly reduced the risk of recurrence over a median of 4.0 years. These findings support using this therapy, but further research is needed to compare gemcitabine with other intravesical agents.<bold>Trial Registration: </bold>clinicaltrials.gov Identifier: NCT00445601.
- Subjects
BLADDER cancer treatment; TUMOR surgery; CANCER chemotherapy; UROTHELIUM; CANCER relapse; BLADDER tumors; CANCER; ANTIMETABOLITES; ANTINEOPLASTIC agents; CANCER invasiveness; COMPARATIVE studies; EPITHELIUM; LONGITUDINAL method; RESEARCH methodology; MEDICAL cooperation; RESEARCH; RESEARCH funding; SALT; STATISTICAL sampling; EVALUATION research; RANDOMIZED controlled trials; DISEASE incidence; BLIND experiment; PAPILLARY carcinoma; INTRAVESICAL administration; DEOXYCYTIDINE; PREVENTION
- Publication
JAMA: Journal of the American Medical Association, 2018, Vol 319, Issue 18, p1880
- ISSN
0098-7484
- Publication type
journal article
- DOI
10.1001/jama.2018.4657