ASCO GU 2019: Challenges of Therapy in Upper-Tract Urothelial Carcinoma

San Francisco, CA (  Dr. Matin, a Urologic Oncologist at The University of Texas MD Anderson Cancer Center, Houston, presented on challenges of therapy in upper-tract urothelial carcinoma (UTUC). He started his talk with current challenges in the management of UTUC which includes risk stratification, endoscopic management, renal dysfunction, neoadjuvant and adjuvant chemotherapy, and lymph node dissection.

Since biopsy staging is imperfect and grading is subject to undersampling/undergrading, imaging has been suggested which is also not ideal. The real question is how good and bad players can be separated. Nomograms have been developed for risk stratification with international collaboration, and Dr. Matin’s team recently updated their nomogram with an impressive 82% accuracy. However, the nomograms are reaching their threshold with clinical data and need genomic markers to improve accuracy. He highlighted the study from MSKCC which looked at TP53, MDM2, and altered FGFR3 to come with a score which correlated well with patient’s clinical factors and stratified patient into three risk categories.  

Urologists are also limited by endoscopic management of the UTUC. The endoscopic tools were developed for stone disease, and there is a need for accurate tumor sampling that is safe and high yield regardless of the location. At the same time, preventing lower and upper tract recurrences is also essential. He then highlighted the Mitogel trial which is closed for accrual and is awaiting FDA approval. Even if approved by the FDA, it will have a narrow indication, but he acknowledged the remarkable strides that have been made by using this platform. 

Dr. Matin then presented on the renal dysfunction challenges which significantly impacts patient care and outcomes. He then talked about a patient of his who had large volume low-grade renal pelvis tumor with very low eGFR. She was given GTA x3 chemotherapy and remarkably had a complete response. However, she subsequently progressed. Nonstandard approaches for the trial-ignored and guideline-neglected patients may be needed. He then summarized the data from neoadjuvant and adjuvant trials such as EA8141 and POUT. Both these trials have their challenges with overtreatment in neoadjuvant setting and ineligibility after nephroureterectomy in the adjuvant setting. URANUS study is underway looking at some of the answers, and patients are randomized based on kidney function. The results from this European trial will be interesting.

Dr. Matin concluded his summary, talking about lymphadenectomy but the templates for lymph node dissection are controversial, and the therapeutic role is not defined. He highlighted a Japanese study which showed that complete lymph node dissection results in a significant reduction of local recurrence, metastases, and improvement in survival.In summary, he stressed on risk stratification of patients before considering nephroureterectomy and taking kidney function into account in treatment decision making. Triaging patients into endoscopic management versus nephroureterectomy with or without chemotherapy should be based on risk stratification, and lymph node dissection should be considered for high-risk cases. 

Presented by:  Surena F. Matin, MD, FACS, The University of Texas MD Anderson Cancer Center

Written by: Abhishek Srivastava, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Philadelphia, PA. Twitter: @shekabhishek at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA