SUO 2023: Trials in Upper Tract Urothelial Carcinoma and Unmet Needs

( The 2023 SUO annual meeting included a session on urothelial cancer, featuring a presentation by Dr. Jennifer Linehan discussing trials in upper tract urothelial carcinoma and unmet needs. Dr. Linehan started her presentation with a great summary slide of the current upper tract urothelial carcinoma trials delineated by disease space:

Dr. Linehan notes that in the neoadjuvant disease space, a recent trial from Coleman et al.assessed neoadjuvant chemotherapy in 57 patients (most patients got at least 3 cycles), with a 63% pathologic response, 19% complete response rate, as well as improved progression free and overall survival:1

For the remainder of the presentation, Dr. Linehan highlighted several of the ongoing trials that are most impactful and the trials she’s most excited about. First, the EA8192 trial is testing the addition of durvalumab to chemotherapy before surgery for patients with high grade upper tract urothelial carcinoma. In cisplatin eligible patients, randomization will be to accelerated MVAC + durvalumab versus accelerated MVAC followed by surgery for both arms. In the cisplatin ineligible cohort, all patients will be treated with gemcitabine + durvalumab followed by surgery:image-2.jpg
Previously, EV-103 cohort H in muscle invasive bladder cancer patients showed that treatment with enfortumab vedotin led to a complete response rate of 36%, and 50% of patients were downstaged from muscle-invasive disease. In the upper tract urothelial carcinoma trial, enfortumab vedotin will be given neoadjuvant for patients with high-grade disease. Patients require histologically confirmed disease and/or radiographically visible tumor stage T2-T4a N0/Nx M0 disease with positive selective urinary cytology. Additionally, patients must be cisplatin ineligible.

Dr. Linehan then discussed the Endoluminal LIGHT Acted Treatment of Upper Tract Urothelial Cancer (ENLIGHTED) study (UCM301). In the phase I space, response rate at 30 days for VTP was 94% (50% complete response, 44% partial response). There were 8 patients that received a second VTP treatment, with a final observed complete response rate of 68%. In this trial, the induction treatment phase consists of 1-3 padeliporfin VTP (TOOKAD) treatments provided 4 weeks apart. If complete response is not achieved, an additional two treatments of padeliporfin VTP are given. The primary response evaluation is performed at 28 days after the last VTP treatment. Repeated maintenance VTP treatments during this period will be provided for patients who show evidence of tumor recurrence; 12 months of treatment will comprise the maintenance phase of the study.

The GEMINI study is assessing gemcitabine for the prevention of intravesical recurrence of urothelial cancer in patients with upper urinary tract urothelial cancer undergoing radical nephroureterectomy. The historical event rate for no treatment is 30%, with a 40% relative reduction when treated with gemcitabine. The primary endpoint is 1-year intravesical recurrence-free survival. Thus far, 23 patients have been analyzed and we await complete results.

Next, there is a randomized trial comparing intravesical gemcitabine to continuous bladder irrigation with sterile water to prevent bladder cancer implantation in patients undergoing surgery for upper tract urothelial carcinoma. There have been two prospective studies using mitomycin or pirarubicin following radical nephroureterectomy, leading to an 11-25% absolute reduction in the risk of bladder urothelial carcinoma recurrence. The 12 and 24 month recurrence rates were 10.8% and 14.4%. The current study is a randomized, non-inferiority study.

The last trial discussed is a phase II study of pembrolizumab and BCG as first line treatment for high grade non-muscle invasive upper tract urothelial carcinoma. BCG will be given antegrade through a percutaneous nephrostomy tube and will start on week 3 after the first infusion of pembrolizumab (400 mg). Patients must be BCG-naïve, have clinical stage CIS, Ta or T1, concomitant ureteral disease is allowable, and CIS patients must be confirmed with a positive high grade selective cytology. CT or MRI must confirm no metastatic disease and the patient must have refused cystectomy or radical nephroureterectomy.

Dr. Linehan concluded her presentation discussing trials in upper tract urothelial carcinoma and unmet needs by emphasizing that we really need to recruit upper tract urothelial carcinoma patients to clinical trials.

Presented by: Jennifer A. Linehan, MD, Saint John’s Cancer Institute, Santa Monica, CA

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2023 Society of Urologic Oncology (SUO) Annual Meeting, Washington, D.C., Tues, Nov 28 – Fri, Dec 1, 2023.


  1. Coleman JA, Yip W, Wong NC, et al. Multicenter phase II clinical trial of gemcitabine and cisplatin as neoadjuvant chemotherapy for patients with high-grade upper tract urothelial carcinoma. J Clin Oncol. 2023 Mar 10;41(8):1618-1625.