NEXT GENERATION

Upper Tract Urothelial Carcinoma

Section Editor: Seth P. Lerner, MD

Upper tract urothelial carcinoma (UTUC) is cancer of the transitional urothelial cells that line the upper urothelial tract of the renal pelvis and ureter. This type of cancer accounts for between 5% and 10% of urothelial cancer cases. It’s the fourth most common cancer in men, but less common in women. In UTUC, the mean age of a patient diagnosed is 73 years. It can occur 3% of the time in both upper tracts (ureters or renal pelvis). Seventeen percent of the time, it occurs concurrently with bladder cancer. UTUC has similarities to bladder cancer in that it can become muscle invasive, which worsens the prognosis. UTUC is associated with a high local recurrence rate and a high rate of metastasis, and the prognosis also correlates to the stage of cancer at initial diagnosis. It is estimated that 60% of UTUC cases are invasive at initial diagnosis.

New therapeutic options for UTUC would be highly influential in treating UTUC patients, because there are currently no FDA-approved drugs for the disease. Recently, promising research has been published. In 2017, the European Association of Urology (EAU) Guidelines Panel on Upper Urinary Tract Urothelial Carcinoma (UTUC) has prepared updated guidelines to aid clinicians in the current evidence-based management of UTUC and to incorporate recommendations into clinical practice. Data from the phase III POUT clinical trial, presented in February 2018, demonstrated that adjuvant platinum-based chemotherapy improves disease-free survival (DFS) and metastasis-free survival (MFS) in patients with UTUC.

In May 2018, an interim analysis of the ongoing pivotal Phase 3 OLYMPUS clinical trial of UGN-101, an investigational mitomycin formulation for the non-surgical treatment of low-grade UTUC, was released. The international, multi-center trial displayed a complete response (CR) rate of 59% in 34 patients who were evaluated for primary disease evaluation (PDE, or the primary endpoint) in the interim analysis. According to the data, 20 of the interim analysis intent to treat the population of 34 patients (59%) achieved a CR, defined as a negative ureteroscopic evaluation and a negative wash cytology. Five of 34 patients (15%) experienced a partial response, and 39%, roughly, of tumors treated were categorized as unresectable by surgery at baseline. The OLYMPUS trial is continuing to enroll patients, and in the second half of 2018, top-line results are expected.

PLATINUM LECTURE

Dr. Lerner - UTUC

Advances in Treating Upper Tract Urothelial Cancer

Seth P. Lerner, MD, discusses developments in UTUC treatment, including adjuvant and neoadjuvant therapies, UGN 101, and nephroureterectomy.

NEED TO KNOW

ADDITIONAL LECTURES

Dr. Pal - FGFR3 Inhibitors

FGFR3 Inhibitors for Upper Tract Urothelial Cancer

Sumanta Kumar Pal, MD, looks at FGFR3 inhibitors for treating upper tract urothelial cancer, focusing on infigratinib.
Dr. Cross - Upper Tract Urothelial Carcinoma Nephroureterectomy

Management of High-Grade Upper Tract Urothelial Cell Carcinoma

Brian W. Cross, MD, Assistant Professor of Urology at the University of Oklahoma College of Medicine, discusses chemotherapy options in patients undergoing nephroureterectomy (NU). He goes on to discuss the advantages of perioperative chemotherapy following NU, the role of neoadjuvant chemotherapy in patients with high-risk upper tract urothelial carcinoma prior to NU, and surgical techniques for the management of the distal ureter during NU.
UTUC & Bladder Cancer

Clinical Implications of Similarities and Differences Between Upper-Tract and Bladder Urothelial Carcinoma

Peter Black, MD, FACS, FRCSC, a Urologic Oncologist at Vancouver General Hospital, a Senior Research Scientist at the Vancouver Prostate Centre, and a Professor in the Department of Urologic Sciences at the University of British Columbia, examines key differences between upper-tract and bladder urothelial carcinomas, and their impact on diagnosis and treatment of each respective disease
Dr. Black Diagnostic Challenges

Diagnostic Challenges with Upper-Tract Urothelial Carcinoma

Peter Black, MD, FACS, FRCSC, discusses questions, challenges, and methods in diagnosing upper-tract urothelial cancer. He analyzes established criteria for when to conduct a biopsy, discusses various methods and tools used for obtaining sufficient tissue for diagnosis, and how risk stratification impacts the selection of options for management of the disease.

Current Treatment Options and Future Treatment Options: Addressing the Unmet Needs in Treating UTUC

Jennifer A. Linehan, MD, surveys the current landscape of treatment for upper tract urothelial cancer (UTUC), difficulties with current methods, and promising future treatment options, including kidney-sparing options for low-grade disease.
Nephron-Sparing Management of Low Grade UTUC with UGN-101 for Instillation-The OLYMPUS Trial

Nephron-Sparing Management of Low Grade UTUC with UGN-101 for Instillation-The OLYMPUS Trial

E. David Crawford, MD, and Brian R. Hu, MD, discuss the results of the use of UGN-101 to treat upper-tract urothelial cancer in the OLYMPUS trial, where it was shown to ablate low-grade tumors with a high initial complete response rate.
Management of Upper Tract Urothelial Cancer

Management of Upper Tract Urothelial Cancer

Guilherme Godoy, MD, MPH, provides a brief overview of the pathogenesis and epidemiology of upper tract urothelial carcinoma (UTUC). He then reviews genomic classification, diagnosing and staging, current oncological principles of surgical therapy, and new risk-adapted treatment options for the disease.

Bladder Cancer Journal Vol. 4 Issue 3

Bladder Cancer is a multidisciplinary journal published by IOS Press. It facilitates progress in understanding treatment of tumors of the bladder.
Localized Upper Tract Urothelial Carcinoma

Localized Upper Tract Urothelial Carcinoma Managed with “Watchful Waiting”

Peter Schulam MD, PhD, compares and contrasts the SEER database and the NCDB in terms of reliability for assessing upper tract urothelial carcinoma (UTUC) outcomes and risk factors when determining whether to treat a patient with definitive therapy or the “Watchful Waiting” strategy.
The Evolving Treatment of Upper Tract Urothelial Carcinoma (UTUC)

The Evolving Treatment of Upper Tract Urothelial Carcinoma (UTUC)

Seth P. Lerner, MD, discusses standard of care treatments for UTUC, the quality of life burdens they pose, and the importance of elective nephron sparing to assuage those negative effects. He describes current and future nephron-sparing methods, especially the use of Mitomycin C (MitoGel), which is under review in the OLYMPUS trial.

ADDITIONAL RESOURCES

SECTION EDITOR

Seth P. Lerner, MD
Baylor College of Medicine
Houston, Texas

Seth P. Lerner, MD, professor of urology, is a board-certified urologist specializing in urologic oncology and urinary tract reconstruction, minimally invasive surgery, and management of patients with bladder, testicular, and kidney cancer. After earning his medical degree from Baylor College of Medicine, Dr. Lerner received his residency training in the Scott Department of Urology. He was awarded an NIDDK fellowship and completed fellowship training in urologic oncology and urinary tract reconstruction at the University of Southern California in Los Angeles. He has since received post-graduate training in minimally invasive surgery and offers both laparoscopic surgery for kidney and testicular cancer and robotic prostatectomy. A leader in collaborative multi-institutional studies of bladder cancer, he is senior editor of the recently published Textbook on Bladder Cancer. He holds the Beth and Dave Swalm Chair in Urologic Oncology.

This educational portal is supported in part by UroGen Pharma Ltd.