MDACC 2018: Neoadjuvant Strategies for Upper Tract Urothelial Carcinoma

Houston, Texas (UroToday.com) The complexities that exist in managing upper tract urothelial carcinoma (UTUC), chief among them involves problems with adequate staging. As a result, risk factors for muscle invasion or lymph node-positive disease must be considered. Dr. Shah noted that low risk UTUC tumors include those that are histologically low-grade, with a tumor size <1 cm, unifocal in presentation, and with a papillary architecture. High-risk UTUC tumors, in contrast, are those that show evidence of local invasion on imaging, high-grade disease on biopsy, a sessile architecture, and potentially present in the presence of hydronephrosis.

There is a dearth of prospective neoadjuvant chemotherapy data in the UTUC space due to the fact that the disease is rare. Retrospective neoadjuvant studies suggest the potential for pathologic downstaging and improvement in disease-specific and overall survivals. The chemotherapy agents used have been extrapolated from the muscle-invasive bladder cancer arena, with ddMVAC favored as the first line for those who are eligible. Those who are not candidates for ddMVAC may be eligible instead for gemcitabine/taxol/doxorubicin (GTA), gemcitabine/cisplatin, cisplatin/gemcitabine/ifosfamide (CGI),ifosfamide/doxorubicin/gemcitabine (IA-Gem), as well as schedule/dose modifications.

With respect to available prospective data, results from the POUT trial were presented recently at the 2018 GU Cancers Symposium. In this trial, patients who underwent an en bloc radical nephroureterectomy for pT2-T4 N0 M0 or pT-any N1-3 M0 UTUC were randomized to either surveillance or platinum-based chemotherapy typed by GFR. Chemotherapy was administered within 90 days after surgery. Patients received either adjuvant gem/cis or gem/carbo depending on GFR, with a goal of 4 cycles. Two-thirds of the patients were able to receive all 4 cycles of neoadjuvant chemotherapy. The primary endpoint of disease-free survival was met, and at 2 years, 71% of patient who received adjuvant chemotherapy were disease free.

MDACC 2018 POUT Trial Design

Dr. Shah also noted that although the POUT trial is the largest prospective trial to date, it still had to close early due to challenges with accrual. Chemotherapy was indeed found to be active in improving outcomes in localized curative-intent UTUC. In a subgroup analysis, cisplatin was found to be superior to carboplatin. Dr. Shah argues that pre-operative chemotherapy may be better for these patients, as it allows clinicians time to ascertain disease biology prior to surgery, potentially allowing for better selection of those who would benefit most from surgery. Neoadjuvant administration of chemotherapy also allows for more optimal renal function during therapy administration. Patients also tend to have a better performance status prior to surgery. Dr. Shah concluded that there are multiple ongoing trials considering neoadjuvant immunotherapy and combination agents, with promising early results. 

Presented by: Amishi Y. Shah, MD, Assistant Professor, Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas

References:
1. Sfakianos JP, Cha EK, Iyer G, Scott SN, Zabor EC, Shah RH, et al. Genomic Characterization of Upper Tract Urothelial Carcinoma. Eur Urol [Internet]. 2015 Dec;68(6):970–7. 
2. Moss TJ, Qi Y, Xi L, Peng B, Kim T-B, Ezzedine NE, et al. Comprehensive Genomic Characterization of Upper Tract Urothelial Carcinoma. Eur Urol [Internet]. 2017;72(4):641–9. 

Written by Dr. Vikram M. Narayan (@VikramNarayan), Urologic Oncology Fellow and Ashish M. Kamat (@UroDocAsh), Professor of Urologic Oncology & Cancer Research, University of Texas MD Anderson Cancer Center, Houston, TX at the 13th Update on the Management of Genitourinary Malignancies, The University of Texas (MDACC - MD Anderson Cancer Center)  November 9-10, 2018, Dan L. Duncan Building, Houston, TX