The results of SWOG S0337were recently reported, which assessed the effectiveness of immediate installation of gemcitabine versus saline in patients with low grade bladder cancer. Gemcitabine is a pyrimidine analog that interferes with DNA synthesis and is a medication is commonly used in the systemic treatment of metastatic bladder cancer patients in combination with cisplatin. Following phase 1 studies proving the safety profile of intravesical gemcitabine SWOG S0337 was approved in 2003. The study recruited 416 patients of which 345 received a TUBRT and complete installation per protocol. The patients in the trial received either gemcitabine (2 grams/100cc of saline) or saline alone, leaving the medication to dwell for 60 minutes. On review of side effect profiles there were no significant differences in those receiving the gemcitabine installation compared to placebo, and most of the side effects reported were those associated with the bladder resection. Of the 345 patients evaluated, 62% had the correct pathology (low grade disease) for installation, noting the accurate cystoscopy assessment by urologists of the potential tumor grade.
On evaluation of the primary end point (disease recurrence), immediate installation of gemcitabine following TURBT reduced disease recurrence by 33% in the intention to treat analysis. On subgroup analysis in those with low grade disease tumor recurrence rate was reduced by 47%. Gemcitabine did not have a significant effect in any of the secondary end points: time to recurrence (HG or CIS), time to muscle invasive disease, and time to death. A similar study done in Germany (Boehle et al, Eur Urol, 2009), intravesical gemcitabine did not have any added benefit compared to placebo. Review key study design differences between the two trials may explain the contradictory results. In the German trial the dwell time of the medication was half (35 min) of the American trial; in addition, continuous bladder irrigation was used in all patients following 35 min dwell time which could have reduced concentration of the medication in the urothelium and decrease the burden of tumor cells in the placebo group leading to negative results.
Lastly, gemcitabine ($ 36.90) is significantly more cost effective than mitomycin-c ($ 1068) which is the most common used agent in the US. In a cost-effectiveness analysis gemcitabine was found to be $ 3,000 dollars cheaper than mitomycin-c per installation leading to the saving of approximately 100 million health spending dollars.
In summary, intravesical installation with gemcitabine reduces the recurrence rate in patients with low grade disease by almost 50%. The installation is safe, well tolerated and cost-effective compared to the current standard (mitomycin-c). Gemcitabine should become the standard installation agent for those suspected with low or intermediate risk non-muscle invasive bladder cancer.
Presented by: Edward Messing, Professor and Chair of Urology of University of Rochester, Rochester, NY
Written by: David B. Cahn, DO, MBS, Fox Chase Cancer Center, Philadelphia, PA, Twitter: @dbcahn at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC