Topic: Upper Tract Urothelial Carcinoma

Kidney Preservation for Upper-Tract Urothelial Carcinoma: Current State and Future Directions

by Jay D. Raman, MD | Aug 2024

Jay D. Raman, MD, examines the evolving strategies and treatment paradigms aimed at preserving kidney function in patients with upper-tract urothelial carcinoma (UTUC). Dr. Raman highlights the clinical significance of kidney preservation, given the substantial morbidity associated with radical nephroureterectomy, the traditional standard of care.

Dr. Raman emphasizes the importance of patient selection, detailing how advancements in diagnostic imaging and risk stratification enable more precise identification of candidates for kidney-sparing approaches. He discusses the role of endoscopic management, such as laser ablation and segmental ureterectomy, underscoring their efficacy and safety in appropriately selected patients. Furthermore, he examines the integration of perioperative therapies, including intraluminal chemotherapy and immunotherapy, as adjuncts to enhance local control and reduce recurrence rates.

What Should I Do About Micropapillae? Do I Treat it Differently than Standard?

by Donna E. Hansel, MD, PhD | Dec 2022

Dr. Donna E. Hansel, MD, PhD, addresses micropapillary and standard forms of bladder cancer, characteristics and treatment.

Methods and Guidelines to Stage and Grade (Low vs. High) UTUC and How Should We Treat

by Seth P. Lerner, MD, FACS | Dec 2022

Seth P. Lerner, MD explores low-grade and high-grade upper tract urothelial carcinoma (UTUC), covering CT urography, MRI, and ureteroscopy.

High Risk and Advanced Upper Tract Urothelial Carcinoma – Still a Role for Surgery

by Jennifer A. Linehan, MD | Dec 2022

Jennifer A. Linehan, MD explores the treatment of advanced upper tract urothelial carcinoma (UTUC), focusing on therapeutic strategies.

UTUC Is it Biologically Distinct

by Donna E. Hansel, MD, PhD | Dec 2022

Donna E. Hansel, MD, PhD delves into the molecular and genetic differences that define Upper tract urothelial carcinoma (UTUC).

Updates in Upper Tract Urothelial Cancer

by Seth P. Lerner, MD, FACS | Jun 2021

Seth P. Lerner, MD, Professor of Urology and holder of the Beth and Dave Swalm Chair in Urologic Oncology in the Scott Department of Urology at Baylor University, provides an update on recent trials and treatment options for Upper Tract Urothelial Cancer (UTUC). He begins with the OLYMPUS study, outlines the rationale for neoadjuvant therapy, reviews ECOG’s EA8141 trial, and concludes with a discussion of adjuvant therapy.

FGFR3 Inhibitors for Upper Tract Urothelial Cancer

by Sumanta Kumar Pal, MD | Mar 2021

E. David Crawford, MD, Professor of Urology at the University of California, San Diego, and Editor-in-Chief of Grand Rounds in Urology, interviews Sumanta Kumar Pal, MD, Clinical Professor in the Department of Medical Oncology & Therapeutics Research and Co-Director of the Kidney Cancer Program at City of Hope in Duarte, California, about his recent paper looking at FGFR3 inhibitors for treating upper tract urothelial cancer. Dr. Pal explains that upper tract urothelial cancer, which is both more rare and more aggressive than lower tract urothelial cancers, seems to be enriched in mutations in FGFR3, making FGFR3 inhibition a potentially good treatment for this disease state. While one such inhibitor, erdafitinib, is already approved for treating upper tract urothelial cancer, Dr. Pal suggests that a different inhibitor, infigratinib, has a profile that might lend itself better to clinical practice, with lower incidence of hyperphosphatemia and other side effects. He goes over the results of the initial phase 1 study of infigratinib, noting the 25% response rate and considering different biomarkers as indicators of response. Dr. Pal concludes by introducing the Proof 302 study, a phase 3 trial looking at infigratinib for upper tract urothelial cancer which he hopes urologists will consider signing eligible patients up for.

Advances in Treating Upper Tract Urothelial Cancer

by Seth P. Lerner, MD, FACS | Feb 2021

Seth P. Lerner, MD, Professor of Urology and holder of the Beth and Dave Swalm Chair in Urologic Oncology in the Scott Department of Urology at Baylor College of Medicine, discusses developments in upper tract urothelial carcinoma (UTUC) treatment. He delivers a rationale for adjuvant therapy based on a lack of clinical staging accuracy, a lack of high-level evidence to support perioperative systemic therapy, the perceived benefit in cases of high-risk bladder cancer, and the ability of pathologic staging to identify patients most likely to benefit. He then reviews the POUT trial of adjuvant chemotherapy, noting that it found a statistically significant benefit in disease-free survival and metastasis-free survival. Dr. Lerner continues by summarizing guideline statements. The EAU statement recommends perioperative chemo to patients with muscle invasive UTUC. ICUD states that it is unknown if adjuvant chemotherapy or waiting for the development of clinically evident disease is better. The French ccAFU recommends adjuvant chemotherapy after radical nephroureterectomy in pT2-T4 N0-3 M0 disease. Dr. Lerner then discusses neoadjuvant therapy, which studies suggest is beneficial to patients with optimized renal function. A Hopkins study specifically displayed a pathologic complete response of 9.4%, while the EA8141 trial found a total pathologic complete response of 13.8%. Dr. Lerner continues with a review of management options for low-grade UTUC, a rare disease with limited treatment options. He posits that a kidney-sparing treatment option is needed for patients, as there is a high chance of recurrence and kidney damage with the treatments currently available. Dr. Lerner theorizes that if durability of complete response following ablation with UGN-101 is demonstrated, this could provide a potential new kidney-sparing treatment for patients with low-grade UTUC. Dr. Lerner concludes with a discussion of the OLYMPUS study on UGN-101, which found a complete response in 59% of patients.

Updates in Upper Tract Urothelial Cancer: Challenges in Diagnosis and Treatment

by Surena F. Matin, MD | Dec 2020

Surena F. Matin, MD, the Monteleone Family Foundation Distinguished Professor in the Department of Urology at MD Anderson Cancer Center, gives an overview of upper tract urothelial carcinoma (UTUC), comparing it to bladder UC and outlining risk factors, imaging options, and possible treatment paths. He posits that the lack of research on UTUC is a major reason for the challenges in diagnosing and treating the illness. When compared to bladder UC, UTUC has more imprecise staging options, more anatomical barriers for therapy, and unclear lymphadenectomy templates. Dr. Matin identifies UTUC risk factors such as tobacco, exposure to aromatic amines and arsenic, and also discusses classification issues related to patients with hereditary UTUCs. He then discusses how imaging is the backbone of staging and grading, but has limitations, recommending a CT chest scan or chest X-ray to rule out metastases, a cystoscopy to assess bladder capacity, and a ureteroscopy to assess tumor size. Dr. Matin concludes with a discussion of radical nephroureterectomy as a treatment option, stating that it is highly curative but at the cost of kidney function. He believes that adjuvant topical therapy could help solve the problem of treatment options but notes that there is not enough data to be certain of this yet.

The Unique Experience of Upper Tract Urothelial Carcinoma in Taiwan

by Hsiang Ying Lee, MD | Nov 2020

Hsiang Ying Lee, MD, Assistant Professor of Urology at Kaohsiung Medical University Hospital, discusses upper tract urothelial carcinoma’s (UTUC) unusual prevalence in the Taiwanese population, along with the national effort to gather more information on the disease. She explains that while there are 1-2 cases of UTUC per 100,000 people in Western countries, there are 4.09-4.37 cases per 100,000 people in Taiwan, as well as a much higher ratio of UTUC to all urothelial carcinomas and a higher proportion of men with the disease compared to the West. Dr. Lee notes several possible reasons for this, including the high rates of exposure to aristolochic acid and arsenic in Taiwan. She then discusses the efforts of a whole Taiwan collaborative clinical study designed to identify high-risk patients in the country, explore new treatments, and develop a UTUC guideline for Taiwan. The presentation concludes with a Q&A session in which Dr. Lee emphasizes the need to find better biomarkers for UTUC.

Updates in Upper Tract Urothelial Carcinoma

by Seth P. Lerner, MD, FACS | Sep 2020

Seth P. Lerner, MD, Professor of Urology, Director of Urologic Oncology and the Multidisciplinary Bladder Cancer Program, and Faculty Group Practice Medical Director for the Urology Clinic at Baylor College of Medicine discusses the impact of several upper tract urothelial carcinoma studies on the treatment of the disease. The POUT phase III trial used adjuvant therapy for high-risk patients who didn’t receive neoadjuvant therapy and through increased survival rates supported the establishment of the new adjuvant therapy standard of care. ECOG, a phase II trial of neoadjuvant systemic chemotherapy followed by extirpative surgery in high-risk upper tract urothelial carcinoma found about a 10% pathological complete response rate from treatment. QED, an ongoing adjuvant trial, tested infigratinib, an oral FGFR1-3 selective kinase inhibitor, so far finding increased survival rates in patients. Dr. Lerner concludes with the Olympus Study, a phase III prospective study on patients with low-grade disease in the renal pelvis using mitomycin gel for treatment and found a 58% complete response rate and led to the treatment’s approval by the FDA.

Ureterocutaneostomy: A Valuable Option for Urinary Diversion in the Elderly Patient?

by Margit Fisch, MD, FEAPU, FEBU | Aug 2020

Margit Fisch, MD, FEAPU, FEBU, Director and Chair of the Department of Urology and Pediatric Urology at University Medical Center Hamburg-Eppendorf in Hamburg, Germany, discusses the value of ureterocutaneostomy as a urinary diversion technique for the increasing number of older, sicker patients with urothelial carcinoma of the bladder. Dr. Fisch explains that, compared with other urinary diversions, ureterocutaneostomy is a simpler, shorter procedure with no significant quality of life differences. She then summarizes the findings of a cystectomy series, which showed that even though patients who had undergone ureterocutaneostomy were older, more likely to have comorbidities, and more likely to have had prior pelvic/abdominal surgeries and irradiation compared with patients who had received ilial/colonic conduit or continent diversion, they had the shortest surgeries and hospital stays during cystectomy, as well as no difference in 30-day complication rate. The benefits of ureterocutaneostomy are further corroborated by a study which compared ureterocutaneostomy to urinary diversion with use of bowel, and found that ureterocutaneostomy patients had shorter operating room time, shorter time in the ICU, and fewer serious complications, although they did experience higher long-term morbidity, probably because of comorbidities. Dr. Fisch notes that ureterocutaneostomy has late complications such as abscess formation, ureteral necrosis, stoma stenosis, and pyelonephritis, but concludes that conduits are no better in this area, and that the benefits of ureterocutaneostomy make it a valuable and useful diversion in elderly patients.

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