Single Gemcitabine Instillation Can Reduce Urothelial Cancer Recurrence

An intravesical instillation of gemcitabine immediately following transurethral resection of bladder tumor (TURBT) reduced the risk of recurrence compared with a saline instillation in patients with suspected low-grade non–muscle-invasive urothelial cancer, according to a new randomized study.

“About 75% of bladder cancers are non–muscle invasive at diagnosis and the majority are histologically low grade. Because these tumors often recur after initial resection, monitoring requires frequent cystoscopic examinations, and tumor recurrences usually are treated by repeat TURBT,” wrote study authors led by Edward M. Messing, MD, of the University of Rochester in New York.

The new study tested whether a single intravesical instillation of gemcitabine immediately after TURBT could help prevent frequent recurrences. A total of 406 patients were randomized, and 383 completed the trial; all patients had suspected low-grade non–muscle-invasive urothelial cancer without any high-grade urothelial cancer episodes or without more than 2 low-grade episodes within the previous 18 months. They received either a gemcitabine instillation or a saline instillation for 1 hour immediately following the TURBT procedure. Results were published in JAMA.

On an intention-to-treat analysis, 67 gemcitabine patients (35%) and 91 saline patients (47%) experienced a recurrence within the 4-year follow-up period, for a hazard ratio (HR) of 0.66 (95% CI, 0.48–0.90; P < .001). Among the 215 patients found to have low-grade non–muscle-invasive urothelial cancer, 34% of the gemcitabine patients and 54% of the saline patients had a recurrence, for an HR of 0.53 (95% CI, 0.35–0.81; P = .001).

A total of 15 patients had progression to muscle-invasive cancer, including 5 in the gemcitabine group and 10 in the saline group, for an HR of 0.51 (95% CI, 0.17–1.49; P = .11). Forty-two patients died of any cause during the study, including 17 in the gemcitabine group and 25 in the saline group, for an HR of 0.68 (95% CI, 0.37–1.27; P = .12).

There were no grade 4 or 5 toxicities in the study, and grade 3 adverse events occurred at a similar rate between the gemcitabine (2.4%) and saline (3.4%) groups. Grade 1–2 events also showed few differences between the groups.

“These findings support using this therapy, but further research is needed to compare gemcitabine with other intravesical agents,” the authors concluded.

In an accompanying editorial, authors including Matthew E. Nielsen, MD, MS, of the University of North Carolina at Chapel Hill, wrote that the results are potentially practice-changing, though more work is needed to bring it into more common use. “Given the potential benefit of these findings,” they wrote, “it will be important to educate and mobilize patients with bladder cancer, physicians, advocacy organizations, and health system leaders to facilitate diffusion of this simple, safe, effective, and affordable innovation in the treatment of bladder cancer.”