Erdafitinib Update – Metastatic Urothelial Cancer
Arlene O. Siefker-Radtke, MD, explores the evolving role of erdafitinib in treating FGFR3-altered urothelial carcinoma.
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Topic: Upper Tract Urothelial Carcinoma
UTUC Staging, Diagnosis, Intraureteralpelvis Therapy, Endoscopic Management
Jennifer A. Linehan, MD, examines strategies for managing upper tract UTUC, highlighting diagnosis, staging, and treatment selection.
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Perioperative Chemotherapy for Upper Tract Urothelial Cancer
Robert Dreicer, MD, MS, MACP, FASCO, highlights the complexities of managing high-grade urothelial carcinoma of the upper tract.
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Kidney Preservation for Upper-Tract Urothelial Carcinoma: Current State and Future Directions
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.
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What Should I Do About Micropapillae? Do I Treat it Differently than Standard?
Dr. Donna E. Hansel, MD, PhD, addresses micropapillary and standard forms of bladder cancer, characteristics and treatment.
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Methods and Guidelines to Stage and Grade (Low vs. High) UTUC and How Should We Treat
Seth P. Lerner, MD explores low-grade and high-grade upper tract urothelial carcinoma (UTUC), covering CT urography, MRI, and ureteroscopy.
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High Risk and Advanced Upper Tract Urothelial Carcinoma – Still a Role for Surgery
Jennifer A. Linehan, MD explores the treatment of advanced upper tract urothelial carcinoma (UTUC), focusing on therapeutic strategies.
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UTUC Is it Biologically Distinct
Donna E. Hansel, MD, PhD delves into the molecular and genetic differences that define Upper tract urothelial carcinoma (UTUC).
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Updates in Upper Tract Urothelial Cancer
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.
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FGFR3 Inhibitors for Upper Tract Urothelial Cancer
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.
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Advances in Treating Upper Tract Urothelial Cancer
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.
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Updates in Upper Tract Urothelial Cancer: Challenges in Diagnosis and Treatment
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.
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