An Update on Upper Tract Urothelial Carcinoma

Sam Chang | March 31, 2021

Low-grade upper tract urothelial carcinoma (UTUC) comprises a substantial percentage of UTUCs. While mortality risk is low, diagnostic choices, therapeutic care, and continued management of these carcinomas are complex decisions. Low-grade UTUC can cause hematuria and urinary obstruction, and tumors tend to recur.  Periodic radiographic imaging is required as well as ureteroscopic interventions not only to treat disease, but also to monitor for recurrence.

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Sam S. Chang, MD, MBA, Patricia and Rodes Hart Endowed Professor of Urologic Surgery and Oncology, is the Oncology Fellowship Director and Vice-Chair of Urologic Surgery at Vanderbilt University Medical Center. His clinical practice focuses on urologic oncology and he has led numerous guideline panels in prostate, bladder and kidney cancer and formerly chaired the American Joint Committee on Cancer GU Staging Task Force. Author of more than 275 articles and recipient of multiple awards such as the SUO’s first-ever Distinguished Service Award, a CaPCURE Prostate Cancer Young Investigator Award, multiple Journal of Urology Best Reviewer, and the AUA Gold Cystoscope Award, he currently serves as Assistant Secretary of the AUA.

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Written by Zachary Klaassen, MD, MSc and Christopher J.D. Wallis, MD, PhD
April 13, 2021
Upper tract urothelial carcinoma (UTUC) is a rare malignancy with an incidence of 1 case per 50,000 people in developed countries. Because symptoms are often non-specific, there are delays in presentation and diagnosis and, as a result, more than half of patients present with muscle-invasive or locally advanced disease.
Written by Christopher J.D. Wallis, MD, PhD and Zachary Klaassen, MD, MSc
May 20, 2020
While radical nephroureterectomy remains the gold standard treatment for patients with UTUC, this approach may not be suitable for some patients and for some tumors. More recently, the topical treatment of patients with UTUC advanced with the FDA approval of mitomycin (JELMYTO™). Results from the OLYMPUS Phase III study represent the first agent specifically approved for

 

Written by Zachary Klaassen, MD, MSc and Christopher J.D. Wallis, MD, PhD
May 1, 2020
Over the last several months, the diagnosis, treatment, and surveillance of genitourinary malignancies has been transformed by the global COVID-19 pandemic. The heavy demand for resources, exacerbated by limited excess health system capacity, means that health care systems have become quickly overwhelmed and hospitals have become sources for virus transmission.
Written by Christopher J.D. Wallis, MD, PhD and Zachary Klaassen, MD, MSc
April 15, 2020

Upper tract urothelial carcinoma, which may affect the renal pelvis or ureter, is a relatively rare disease, accounting for less than 10% of all urothelial carcinomas. In parallel to how we view urothelial carcinoma of the bladder, the risk of recurrence and progression from upper tract urothelial carcinoma depends on tumor grade and stage. 

Written by Zachary Klaassen, MD, MSc and Christopher J.D. Wallis, MD, PhD
December 10, 2019
The urothelium lines the urinary tract from the renal pelvis to urethra. While cancers may arise anywhere along the urothelium, the vast majority (90-95%) occur in the lower urinary tract (bladder and urethra) while the remainder (5-10%) occur in the upper tract (ureter and renal pelvis)1.
Written by Zachary Klaassen, MD, MSc
April 15, 2019
Upper tract urothelial carcinoma, comprising either the renal pelvis or ureter, is rarer than urothelial carcinoma of the bladder accounting for only 5-10% of all urothelial carcinomas. However, similar to bladder urothelial carcinoma,
Written by Christopher J.D. Wallis, MD, PhD
January 29, 2019
Upper tract urothelial carcinoma (UTUC) comprises any malignancies arising from the urothelium between the level of the renal pelvis and the distal ureter. Owing to their relatively rarity, there is generally little data to guide the management of patients with these tumors and much of practice is extrapolated from the management of urothelial cancer of the bladder.
Physician-Scientist Commentaries
State of the Evidence Review Articles
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
The definitive treatment for high-grade localized upper tract urothelial carcinoma (UTUC) is radical nephroureterectomy (RNU). Neoadjuvant pembrolizumab was tested in patients with muscle-invasive bladder cancer before radical cystectomy and demonstrated promising efficacy in the PURE-01 trial.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Gross hematuria is a distressing symptom for patients with upper urinary tract urothelial cancers (UTUC). Invasive procedures are usually employed to control hematuria, including surgical resection, endoscopic laser ablation, and percutaneous nephroscopic resection.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Upper urinary tract urothelial carcinoma (UTUC) arises from the renal pelvicalyceal system and ureters and accounts for 5–10% of all urothelial carcinomas. After definitive UTUC treatment by radical nephroureterectomy with bladder cuff excision (RNU)
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Upper urinary tract urothelial carcinoma (UTUC) constituted 5-10% of urothelial carcinomas. The management of UTUC has significantly changed in the last decade with the introduction of neoadjuvant chemotherapy options and kidney-sparing surgery (KSS)
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine
Arsenic exposure is associated with a higher risk of developing urothelial carcinoma (UC). Previous studies mostly focused on UC of the bladder.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Upper tract urothelial (UTUC) is an uncommon malignancy. Defining the impact of adjuvant chemotherapy on long term outcomes in UTUC patients is a critical clinical question. Recently, Birtle et al. reported
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Defining the prognosis of patients who develop intravesical recurrence (IVR) after radical nephroureterectomy (RNU) is critical for the optimal management of these patients.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Intravesical recurrence (IVR) rates remain high in urothelial carcinoma of the upper urinary tract (UTUC) patients following radical nephroureterectomy
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Lynch syndrome (LS), caused by a mutation in the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2). LS increases the individual’s risk of getting upper urinary tract urothelial carcinoma (UTUC).
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Although urothelial carcinomas of the bladder and upper tract urothelial carcinoma (UTUC) can have similar histology, they significantly differ in prevalence and risk factors.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Upper tract urothelial carcinoma (UTUC) is a distinct clinical entity with poor clinical outcomes.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Lynch Syndrome (LS) is a common hereditary cancer syndrome that is characterized by mutations in the mismatch repair (MMR) genes.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Circulating tumor cells (CTCs) are cancer cells shed from the tumor that enter the circulation.
Written by Bishoy M. Faltas, MD
Englander Institute for Precision Medicine, Weill Cornell Medicine
Upper tract urothelial carcinoma is less common than bladder urothelial carcinoma. The biological characteristics of this form of the disease is not completely understood.
Conference Coverage
Conference Highlights Written by Physician-Scientist
Presented by Alison J. Birtle, MD, MBBS, MRCP, FRCR, BSc
In a session entitled Clearer Vision chaired by Dr. Bertrand Tombal at the 2021 ANZUP Annual Scientific Meeting, Dr. Alison Birtle discussed what she described as wishful thinking in genitourinary oncology, with a focus on optimal therapy for systemic therapy in upper tract urothelial carcinoma (UTUC).
Presented by Karim Chamie, MD
The AUA 2021 virtual annual meeting included a late-breaking abstract session with a presentation by Dr. Karim Chamie discussing long-term recurrence free survival following UGN-101 treatment for low-grade upper tract urothelial carcinoma.
Presented by Jennifer Linehan, MD
In this study by Linehan and colleagues, the authors focus on the outcomes of female patients from the OLYMPUS trial [NCT02793128], in which patients with low grade upper tract urothelial carcinoma (LG-UTUC) were treated with a novel reverse thermal gel containing mitomycin.
Presented by William Huang, MD
Most patients newly diagnosed with bladder cancer have non-muscle invasive disease (NMIBC). For patients with intermediate or high-risk NMIBC and those with carcinoma in situ (CIS), adjuvant treatment with BCG is guideline-recommended on the basis of proven benefits in disease recurrence.
Presented by Surena F. Matin, MD
The 2021 American Urological Association (AUA) Summer School session on Upper Tract Urothelial Carcinoma included a case-based discussion led by moderator Dr. Surena Matin who was joined by panelists Dr. Sima Porten and Dr. Vitaly Margulis.
Presented by Nadine Houede, PhD
The Controversies in Onco-Urology session at the EAU 2021 annual meeting included a presentation by Dr. Nadine Houede who discussed the adjuvant approach to the optimal timing of perioperative systemic therapy for high-risk upper tract urothelial carcinoma.
Presented by Yasuyoshi Miyata, MD, Ph.D
Yasuyoshi Miyata from Japan presented results of a randomized clinical trial of intravesical mitomycin C plus cytarabine (Ara-C) versus mitomycin C for patients with non-muscle invasive bladder cancer (NMIBC) at the European Association of Urology 2021 annual meeting.
Presented by Arnulf Stenzl, MD
The Urology Beyond Europe thematic sessions included the Joint Session of the European Association of Urology (EAU) and the Arab Association of Urology, as well as a presentation by Dr. Arnulf Stenzl discussing established treatment and guidelines for upper tract urothelial carcinoma.
Presented by Morgan Roupret, MD, PhD
The joint session of the European Association of Urology (EAU) and the Japanese Urological Association at the 2021 EAU virtual annual meeting included a presentation by Dr. Morgan Roupret highlighting the updated guidelines on the management of upper tract urothelial carcinoma. This update was published in 2020 in European Urology.1
Presented by Bishoy M. Faltas, MD
Most patients newly diagnosed with bladder cancer have non-muscle invasive disease (NMIBC). For patients with intermediate or high-risk NMIBC and those with carcinoma in situ (CIS), adjuvant treatment with BCG is guideline-recommended on the basis of proven benefits in disease recurrence.
Presented by Alison J. Birtle, MD, MBBS, MRCP, FRCR, BSc
The POUT trial (CRUK/11/027; NCT01993979) previously reported that adjuvant chemotherapy improves disease free survival (HR 0.45, 95% CI 0.30-0.68) for patients with histologically confirmed pT2-T4 N0-3 M0 upper tract urothelial carcinoma over a median follow-up of 30.3 months.1
Presented by Jen-Jane Liu, MD
Neoadjuvant chemotherapy (NAC) is the standard of care for muscle-invasive bladder cancer.  However, upper tract urothelial carcinoma (UTUC) is not the same as bladder cancer, with a higher rate of invasive disease.
Presented by Surena F. Matin, MD
Dr. Surena Matin presented the final results of the OLYMPUS trial, Optimized DeLivery of Mitomycin for Primary UTUC Study (Olympus) at the Best of Bladder Cancer poster session.
Presented by Shahrokh F. Shariat, MD
At the European Multidisciplinary Congress on Urological Cancers (EMUC) 2020 virtual meeting, Dr. Shahrokh Shariat discussed the role of kidney sparing surgery for upper tract urothelial carcinoma. Dr. Shariat notes that radical nephroureterectomy is not the standard of care for all patients with upper tract urothelial carcinoma, in particular those with low-grade Ta tumors, as it has been estimated that 18-25% of patients may be over-treated (pT0, pTa, pTis) with radical nephroureterectomy.
Presented by Karim Chamie, MD
In a sponsored educational session at the American Urologic Association Virtual Annual Meeting, Karim Chamie, MD, presented on the recently expanded kidney-sparing options for patients with low-grade upper tract urothelial cancer.
Presented by Chana Weinstock, MD
Washington, DC (UroToday.com) The expert panel of providers and FDA discussed ongoing and future collaborations with the FDA and bladder cancer. The FDA Oncology Center of Excellence (OCE) leverages the combined skills of regulatory scientists and reviewers. The panel reviewed the structure of the OCE and how expedited programs within the FDA strive to accelerate drug development and approval.
Presented by Seth Lerner, MD, FACS
Chicago, IL (UroToday.com) Low grade upper tract urothelial carcinoma (LG UTUC) can be managed with endoscopic resection/ablation however, the associated high recurrence rate requires repetitive intervention and intercavitary therapy for the frequently recurrent and multifocal disease.
Presented by Srikala (Kala) Sridhar, MD, MSc, FRCPC
Barcelona, Spain (UroToday.com)  Dr. Kala Sridhar, a medical oncologist from the University of Toronto, provided a summary of the current status of chemotherapy for upper tract urothelial carcinoma (UTUC).  UTUC accounts for 5-10% of urothelial malignancies, of which 60% are invasive at disease presentation. Radical nephroureterectomy remains the standard of care for localized and invasive disease.
Presented by Juan Palou, MD, PhD
Barcelona, Spain (UroToday.com) Upper tract urothelial carcinoma (UTUC) is a rare condition, making large clinical trials difficult to accrue for. More importantly, known concerns with the accuracy of pre-operative staging, and therefore, difficulties in accurately identifying high-risk patients...
Presented by Morgan Roupret, MD, Ph.D
Barcelona, Spain (UroToday.com) Upper tract urothelial carcinoma (UTUC) is a rare condition, making large clinical trials difficult to accrue for. More importantly, known concerns with the accuracy of pre-operative staging, and therefore, difficulties in accurately identifying high-risk patients make clinical trial accrual and accuracy difficult. As such, much of the data for UTUC is often extrapolated
Presented by Seth Paul Lerner, MD, FACS
San Francisco, CA (UroToday.com) -- UroGen Pharma Ltd., a clinical-stage biopharmaceutical company developing treatments to address unmet needs in the field of urology, with a focus on uro-oncology,  announced a new data presentation from an interim analysis of the ongoing pivotal Phase 3 OLYMPUS clinical trial of UGN-101 (MitoGel™),
Presented by Alison J. Birtle, MD, MRCP, FRCR
San Francisco, CA (UroToday.com) The management of patients with upper tract urothelial carcinoma (UTUC) is challenging due to the lack of high-level evidence, which results from the disease’s overall rarity. The standard of care for patients with high-grade disease or those suspected to have invasive disease is a radical nephroureterectomy,
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