Edward M. Messing
Flushing the bladder with gemcitabine rather than saline immediately after surgery significantly reduced the risk for recurrence of suspected low-grade nonmuscle-invasive urothelial cancer, according to study data published in JAMA.
The practice is already widely used in Canada and throughout Europe.
“The real importance of this study is that we now have a readily available drug that’s fairly inexpensive, well-tolerated and effective,” Edward M. Messing, MD, professor of urology and professor of oncology and pathology at the University of Rochester School of Medicine and Dentistry, said in a press release. “One of the biggest issues with low-grade bladder cancer is that it frequently returns. I know some patients who have to undergo four surgeries a year, and if we can cut down on these recurrences, we will save a lot of people a lot of pain, money and time lost to recovery.”
Messing and colleagues performed a randomized, double-blind phase 3 clinical trial at 23 centers in the U.S. The researchers randomly assigned 406 patients (84.7% men; median age, 66 years) to receive intravesical instillation of either gemcitabine (2 g in 100 mL of saline; n = 201) or saline (100 m; n = 205) for an hour immediately following transurethral resection of a bladder tumor.
All patients had suspected low-grade nonmuscle-invasive urothelial cancer. Eligible patients had no high-grade or no more than two low-grade urothelial cancer episodes within 18 months leading up to surgery.
The researchers performed follow-up cystoscopy and cytology every 3 months for 2 years, then semiannually for another 2 years.
Time to recurrence served as the primary outcome. Secondary endpoints included time to muscle invasion and all-cause death.
The intention-to-treat analysis showed that 67 patients (35%) in the gemcitabine group experienced recurrence in a median follow-up of 4 years, compared with 91 patients (47%) in the saline group (HR = 0.66; 95% CI, 0.48-0.9).
Among 215 patients with low-grade nonmuscle-invasive urothelial cancer who underwent both surgery and drug instillation, recurrence occurred among 34% of patients in the gemcitabine group (n = 34 of 102) compared with 54% (n = 59 of 113) of the saline group (HR = 0.53; 95% CI, 0.35-0.81).
A total of 15 patients progressed to muscle invasion (five in the gemcitabine group, 10 in the saline group). Forty-two patients died of any cause (17 in the gemcitabine group, 25 in the saline group).
No patients experienced grade 4 or grade 5 adverse events, and both groups experienced similar rates of low-grade adverse events.
“The thoughtfully designed, executed and interpreted study by Messing et. al provides important results for patients and physicians alike, to the extent that the investigators focused on a problem with meaningful implications for individual patients, population health and the value of care,” Samuel D. Kaffenberger, MD, assistant professor of urology at University of Michigan, and colleagues wrote in an accompanying editorial. “Given the potential benefits of these findings, 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.” – by Andy Polhamus
Disclosures: Messing reports no relevant financial disclosures. Please see the study for a list of all other authors’ relevant financial disclosures. Kaffenberger reports no relevant financial disclosures.