Plenary: Next Frontier, Sunday, Afternoon Session
Presentation Authors: Jonathan A. Coleman*, Nathan C. Wong, Daniel D. Sjoberg, Nicholas Silva, Bernard H. Bochner, Guido Dalbagni, S. Machele Donat, Harry W. Herr, Eugene Cha, Timothy Donahue, Eugene Pietzak, Hikmat Al-Ahmadie, Nicole Benfante, New York, NY, Anoop Meraney, Steven Shichman, Jeffrey Kamradt, Hartford, CT, Suresh Nair, Angelo A. Baccala Jr., Phillip Abbosh, Paul Palyca, Bradley W. Lash, Muhammad A. Rizvi, Lehigh County, PA, Antonio Muina, Miami, FL, Min Yuen Teo, Gopa Iyer, Jonathan E. Rosenberg, Dean F. Bajorin, New York, NY
Introduction: Neoadjuvant chemotherapy (NAC) has established survival benefits prior to radical cystectomy for invasive urothelial carcinoma, yet its role in managing high risk upper tract urothelial carcinoma (UTUC) prior to nephroureterectomy is less clear. To address the question of potential clinical benefits in this setting, we initiated a phase II clinical trial of NAC with gemcitabine and cisplatin (GC) in patients with UTUC.
Methods: Patients with high-risk localized UTUC were recruited to receive 4 cycles of GC prior to planned nephroureterectomy or distal ureterectomy. The primary objective is pathologic response rate, defined as
Results: As of January 2019, 55 patients have been recruited with 6 patients awaiting surgery within 2-3 months. Evaluable pathology for 48 patients was available at time of analysis. Among the 48 evaluable patients, 28 (58%) pathologic responses have been observed, meeting the primary endpoint, and 9 (19%) patients achieved pT0N0 disease. The majority of patients (40/48; 85%) tolerated all 4 cycles of GC. The 90-day grade ≥ 3 surgical complication rate was 6.2%. With a median follow up of 2.6 year among survivors, 6 patients died of disease. Two-year overall survival was 89% (95% CI 79%, >99%). Patients demonstrating pathologic response had improved survival compared to those who did not respond (2-year survival 100% vs 74%, log-rank p = 0.02).
Conclusions: At time of preliminary analysis, NAC for UTUC demonstrated outcomes of favorable pathologic response, is well tolerated requiring minimal delay to surgery without significant perioperative complication risk. Better survival in patients with favorable pathologic features after NAC indicates a potential clinical benefit to this approach. Data analysis for the entire cohort is anticipated by May 2019. (NCT01261728).
Source of Funding: This research was supported by the Sidney Kimmel Center for Prostate and Urologic Cancers and funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748.