Highlighting Upper Tract Urothelial Carcinoma

Highlighting Upper Tract Urothelial Carcinoma
New online clinical resource for a complex and understudied condition.

Upper tract urothelial carcinoma is a heterogeneous disease presenting multiple challenges to diagnosis and treatment. It remains relatively understudied in large prospective trials, and therapy has been guided primarily by retrospective data or by trials of urothelial bladder cancer (which is genetically and molecularly distinct).¹ The location of upper tract urothelial carcinoma also complicates collection of high-quality biopsy specimens.

“I have focused my clinical and research efforts on prostate and bladder cancer, but many times patients with urothelial cancer of the kidney and/or ureters, the so-called upper tract, can be the most challenging to treat.” said Sam Chang, M.D., Patricia and Rodes Hart Professor and vice chair of urologic surgery at Vanderbilt University Medical Center. “The least obvious tumors can be the most dangerous, and those that appear obvious can be the most benign. Patients often are overtreated or undertreated, undermining quality of life and disease-free survival.”

Chang recently announced in UroToday that he will serve as editor of a new Center of Excellence section on upper tract urothelial carcinoma for the website. The section will provide a resource on the latest study data and will cover typical and atypical cases, treatment nuances, complications of therapy, and best-practice approaches, including multidisciplinary care models.

Progress in Diagnosis, New Research

“Now more than ever, we are able to combine surgery with medical therapy and adapt treatment.”

Progress is accelerating in diagnosing upper tract urothelial carcinoma. Diagnostics have evolved from imaging only to next-generation sequencing and molecular subtyping of visually biopsied tumor samples.² Technical advances and improved training have made it possible to collect larger and higher-quality biopsies.³

“As the AUA Guidelines Chair for Bladder Cancer and past Chair of the SUO Guidelines on Advanced Prostate Cancer, I have carefully monitored significant inroads in detecting and treating these tumors. Now more than ever, we are able to combine surgery with medical therapy and adapt treatment based on risk of recurrence, progression and metastasis for upper tract cancers,” Chang said.

Studies such as POUT, in which adjuvant chemotherapy improved disease-free survival in pT2-T4 N0-3 M0 disease, and URANUS, which is comparing neoadjuvant versus adjuvant chemotherapy, have shown that it is possible to accrue upper tract urothelial carcinoma trials. They have spurred interest in other studies of novel diagnostics and more tolerable therapies, such as immune checkpoint inhibitors and FGFR3 inhibitors.4

Resolving Knowledge Gaps

Without treatment guidelines for upper tract urothelial carcinoma, urologists and medical oncologists are grappling with many questions. Are there helpful biomarkers for upper tract urothelial carcinoma? How do genetic disease processes and variants affect risk, surveillance, and therapeutic options? Which are the best surgical therapies and chemotherapies to avoid both under or overtreatment? How should other organs that contain urothelial cells, namely the bladder and prostatic urethra, be managed for patients with this diagnosis?

Chang hopes that developing the Center of Excellence resource for UroToday will be a step toward resolving these questions, and may inform future practice guidelines.

“It is our hope is that this Center of Excellence will help fill the sizable gap that we as clinicians face across the spectrum of genitourinary care when managing this complex disease,” Chang said. “This Center will engage leaders on the forefront of important translational and clinical work that will help shape and define how we can improve our care for these patients.”