Addressing Unmet Needs for Patients With Low-grade Upper Tract Urothelial Carcinoma

Despite being one of the most common types of bladder cancer, urothelial carcinoma presents several challenges to patients due to the diseases’ tendency to expand and spread cells to other parts of the urinary tract, including the kidney.

Low-grade upper tract urothelial carcinoma (UTUC) comprises 30% of UTUC cases^1,2 and is usually associated with less aggressive papillary tumors. However, low-grade tumors can lead to urinary obstruction and other problems which need to be addressed to avoid further complications or spread of cancer cells.

Standard management of UTUC could include major surgical procedures, such as radical nephroureterectomy, which create the risk of short-term morbidity or potentially long-term decline in renal function.

“For low grade UTUC patients, choosing between [radical nephroureterectomy] and a kidney-sparing procedure requires an assessment of the risk of surgical complications, of renal insufficiency with its attendant complications, and of recurrence and progression associated with a non-extirpative approach,” wrote Drs Rayam and Shore.³ “Chemoablation, which is a technique that improves contact of drug with the urothelium, could provide an alternative  kidney-sparing approach for primary tumor eradication.”

According to the National Comprehensive Cancer Network Bladder Guidelines Version 2.2022,⁴ following initial evaluation, recommended treatment can include transurethral resection of bladder tumors, examination under anesthesia, imaging if not previously done, and intravesical chemotherapy dosing with either gemcitabine or mitomycin.

Mitomycin was approved⁵ by the US Food & Drug Administration (FDA) on April 15, 2020, for adult patients with low-grade UTUC based on efficacy results demonstrated in the OLYMPUS trial.

For the phase 3, open-label, single-arm study, 74 patients received at least one dose of mitomycin, a reverse thermal pyelocalyceal gel solution, once a week for 6 weeks. At the primary disease evaluation visit (3 months), 59% of patients had a complete response. Median follow up for patients with a complete response was 11 months.⁶

At the time of its approval, Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research said, “Although our nation’s emphasis is on the need to combat COVID-19, patients with cancer and their unique needs continue to be a top priority…[mitomycin] gives patients, for the first time, an alternative treatment option for low-grade UTUC.”

References:

1. American Cancer Society. What is bladder cancer? Revised January 30, 2019. Accessed August 16, 2022. https://www.cancer.org/cancer/bladder-cancer/about/what-is-bladder-cancer.html
2. Browne BM, Stensland KD, Moynihan MJ, Canes D. An analysis of staging and treatment trends for upper tract urothelial carcinoma in the National Cancer Database. Clin Genitourin Cancer. 2018;16:e743–e750.
3. Raman J, Shore ND. Management of Low-grade Upper Tract Urothelial Carcinoma: An Unmet Need. Rev Urol. 2020;22(1):1-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265178
4. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Bladder Cancer, NCCN Evidence Blocks. Accessed August 15, 2022. https://www.nccn.org/professionals/physician_gls/pdf/bladder_blocks.pdf
5. US Food & Drug Administration. FDA approves mitomycin for low-grade upper tract urothelial cancer. April 15, 2020. Accessed August 16, 2020. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mitomycin-low-grade-upper-tract-urothelial-cancer
6. Kleinmann N, Matin SF,  Pierorazio PM, et al. Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): an open-label, single-arm, phase 3 trial. Lancet Oncol. 2020;21(6):776-785. Doi:10.1016/S1470-2045(20)30147-9
7. US Food & Drug Administration. FDA approves approves first therapy for treatment of low-grade upper tract urothelial cancer. April 15, 2020. Accessed August 16, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-treatment-low-grade-upper-tract-urothelial-cancer