PracticeUpdate: Oncology - Winter 2018

EDITOR’S PICKS 16

Intravesical Instillation of Gemcitabine vs Saline After Resection of Suspected Low- Grade Non-Muscle Invasive Bladder Cancer JAMA: The Journal of the American Medical Association Take-home message • In this randomized clinical trial of 406 patients with suspected low-grade non- muscle invasive urothelial cancer, the authors compared intravesical instillation of gemcitabine with saline to determine recurrence rates. They found that gemcitabine greatly reduced the risk of recurrence over a median of 4 years (recurrence rate: gemcitabine, 35%; saline, 47%; HR 0.66). • Intravesical gemcitabine immediately following tumor excision reduced the risk of recurrence in patients with suspected low-grade non-muscle invasive urothelial cancer.

" Although gemcitabine and mitomycin C have not been compared head to head, given the overall low utilization of mitomycin C in the perioperative setting, this study may provide urologists with a more user-friendly agent in the post-TURBT setting. " DESIGN, SETTING, AND PARTICIPANTS 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 can- cer 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. Abstract IMPORTANCE Low-grade non–muscle-invasive urothelial cancer frequently recurs after xcision by transurethral resection of bladder tumor (TURBT). OBJECTIVE To determine whether immediate post-TURBT intravesical instillation of gem- citabine reduces recurrence of suspected low-grade non–muscle-invasive urothelial can- cer compared with saline.

COMMENT By Thomas J Guzzo MD, MPH I n this study, Messing et al report the results from the SWOG S0337 randomized trial of immediate post-TURBT intravesical instillation of gemcitabine vs saline in patients with presumed low-grade non-muscle invasive bladder cancer. This was a randomized, double-blind multi-institutional trial with the primary outcome of time to tumor recurrence. A total of 406 patients were randomized. In the intention-to- treat analysis, 67 of 201 patients (4-year estimate, 35%) in the gemcitabine arm and 91 of 205 patients (4-year estimate, 47%) in the saline arm had a recurrence (HR, 0.66; 95% CI, 0.48–0.90). For the patients who ultimately proved to have low-grade disease on final pathology, 34 of 102 (4-year estimate, 34%) in the gemcitabine arm and 59 of 113 patients (4-year estimate, 54%) in the saline arm had a recurrence (HR 0.53; 95% CI 0.35–0.81). Immediate instillation of gemcitabine was well-tolerated, with no grade 4 or 5 adverse events. Currently, perioperative mitomycin C instillation is considered the stand- ard of care in this setting; however, the widespread adoption of this practice in the US has been marginal. Reasons for the low penetrance of perioperative

mitomycin C use in this setting is likely multifactorial, including high cost and cli- nician fear of significant toxicity. Although low-grade, noninvasive bladder tumors rarely progress and present minimal lethal potential, they are a significant cost burden to the healthcare system, neces- sitating frequent endoscopic surveillance and retreatments for additional recur- rences. Additionally, recurrent tumors increase patient anxiety and decrease quality of life even when they are non– life threating events. This study supports a cheaper and poten- tially less toxic alternative to perioperative mitomycin C instillation for patients with low-grade, non-muscle invasive bladder cancer. Although gemcitabine and mito- mycin C have not been compared head to head, given the overall low utilization of mitomycin C in the perioperative set- ting, this study may provide urologists with a more user-friendly agent in the post-TURBT setting.

Dr. Guzzo is Chief of Urology and Associate Program Director at the University of Pennsylvania in Philadelphia, Pennsylvania.

PRACTICEUPDATE ONCOLOGY