Upper tract urothelial carcinoma: Key considerations and patient cases

Katie S. Murray, DO, MS

Urology Times recently hosted a pair of roundtable discussions on upper tract urothelial carcinoma (UTUC). The programs, moderated by Katie S. Murray, DO, MS, professor in the Department of Urology at NYU Grossman School of Medicine and chief of the Urology Service at Bellevue Hospital Center in New York, New York, encompassed a range of topics related to UTUC, including clinical guidelines, treatment considerations, and patient cases.

This summary was generated by artificial intelligence and edited by humans for clarity.

Roundtable #1

At the outset, Murray set the stage by outlining the prevalence of UTUC, noting that it affects 1 to 2 individuals per 100,000 people in the United States, representing about 6% of all urothelial carcinoma cases. Symptoms such as hematuria and urinary obstruction were discussed, underscoring the necessity for regular risk stratification to inform treatment decisions, particularly as one-third of patients are diagnosed with low-grade tumors. The association between upper tract tumors and concurrent bladder cancer was also emphasized, revealing that up to 13% of patients may have concomitant bladder carcinoma.

The Importance of Tumor Grade and Location

The conversation touched upon the American Urological Association (AUA) guidelines for the treatment of UTUC, which categorize tumors as low or high risk. Factors influencing this stratification include tumor size, urinary cytology results, biopsy findings, and imaging characteristics from CT scans. The further subcategorization of low-risk and high-risk variations guides therapeutic options tailored to individual patient profiles. Participants noted that their clinical practices varied significantly, reflecting their interpretations and experiences regarding the incidence of low-grade disease. Many indicated that they see approximately 20% to 30% of patients diagnosed with isolated low-grade upper tract disease.

Murray emphasized that treatment choices for low-grade UTUC depend fundamentally on tumor grade and location. Traditionally, the gold standard treatment has been radical nephroureterectomy with bladder cuff excision; however, alternatives such as segmental ureterectomy, endoscopic treatments, antegrade or retrograde ablation techniques, and adjuvant intracavitary therapies are increasingly common. The roundtable attendees shared their perspectives on how the location of a tumor—whether in the renal pelvis or ureter—plays a crucial role in treatment decisions. The importance of individualized approaches was underscored, taking into account not only the tumor’s characteristics but also the patient's overall health and preferences.

In exploring treatment innovations, the conversation highlighted the approval of a reverse thermal gel formulation of mitomycin C (Jelmyto), stemming from trial data such as the OLYMPUS trial. This product is indicated for patients with unifocal tumors less than 1.5 cm, demonstrating a 59% complete response rate for low-grade disease when applied after surgical interventions aimed at debulking the tumor. Murray posited using adjuvant therapies like this to "mop up" residual disease after extensive attempts at clearance, emphasizing the collaborative nature of modern oncology where clinical trials inform treatment practices.

Special attention was also given to the complexities of endoscopic management in upper tract disease. Although ureteroscopy is commonly performed, the inherent challenges of high recurrence rates necessitated frank discussions about the potential for stricture formation and the complications tied to nephroureterectomy, which include significant impacts on renal function and associated risks, such as surgical infections and blood transfusions.

Case Discussion

During the roundtable, several patient cases were presented that illuminate the complexities of managing low-grade UTUC. The participants shared their clinical experiences and strategies in relation to these cases, sparking a thoughtful dialogue about treatment options and decision-making processes.

One case involved a patient with high-volume, low-grade disease. The presenting physician raised concerns about the potential for undetected high-grade tumors despite biopsy results indicating low-grade pathology. This scenario ignited conversations regarding the appropriateness of nephroureterectomy, with some participating advocating for immediate surgical intervention based on the patient's symptomatic presentation, including issues such as bleeding. The uncertainty inherent in low-grade diagnoses led to different opinions on whether to proceed with radical surgery or to adopt a more conservative, kidney-sparing approach, particularly in patients with solitary kidneys.

Another case included discussions about patients who were deemed too high-risk for nephroureterectomy. Here, the focus turned to endoscopic techniques and kidney-sparing methodologies, exploring the possibility of managing high-grade tumors endoscopically. Attendees highlighted the need for individualized discussions with patients about treatment options, weighing the chance of disease progression against the quality-of-life implications of more invasive procedures. Options such as segmental ureterectomy and emerging treatments, including intraluminal therapies, were raised as alternatives worth considering for select patients.

A notable case involved the use of adjuvant treatments for patients who demonstrated residual low-grade disease after an initial resection. The introduction of therapies like mitomycin gel was discussed, particularly for patients who would not be candidates for aggressive surgical approaches. This allowed for a more conservative management strategy, circumventing major surgeries while still aiming to manage the disease effectively.

Participants underscored the importance of follow-up strategies, particularly in cases where residual disease or multifocality raised concerns about recurrence. The consensus was that rigorous surveillance protocols, including regular ureteroscopy, were vital for ensuring ongoing tumor management. Timelines for follow-up and patient education on the likely frequency of procedures were emphasized as essential components of care.

Roundtable #2

As in the first program, Murray and the participants discussed the prevalence of UTUC, the role of the AUA guidelines, and the importance of risk stratification. A significant portion of the discussion was devoted to treatment modalities, where participants shared their approaches to managing patients with low-grade UTUC. The consensus emphasized the role of endoscopic resection, often utilized as the primary treatment for low-grade tumors. In certain cases, this may be followed by perioperative intravesical therapy with chemotherapeutics like BCG or mitomycin C. The discussion also touched on the feasibility and implications of kidney-sparing surgeries, emphasizing the need to carefully evaluate patients based on tumor characteristics and individual health factors.

One participant introduced a critical point regarding the rate of undergrading in biopsies, noting findings from a recent systematic review that indicated an undergrading rate of approximately 30%. This highlighted the inherent challenges in diagnosing UTUC accurately and how these ambiguities could affect treatment decisions significantly. The group acknowledged that this undergrading could lead to either overly conservative management or more aggressive treatment than necessary, stressing the importance of comprehensive evaluation and shared decision-making with patients.

Participants discussed their experiences with recurrent cases and tailored their treatment strategies accordingly. For instance, the discussion referenced specific patient cases where clinicians had to decide between nephroureterectomy and kidney-sparing approaches based on tumor location, grade, and patient comorbidities. They acknowledged the importance of weighing risks, such as potential surgical complications and renal insufficiency, especially in patients with solitary kidneys or chronic health issues.

Mitomycin Gel

During the discussion, the application and benefits of mitomycin gel in treating low-grade UTUC were central themes. The discussion highlighted that although traditional treatment often involves nephroureterectomy or intraluminal therapies, the introduction of mitomycin gel presents an additional, lower-risk option to manage low-grade cases without necessitating more invasive surgical interventions.

Participants noted that the National Comprehensive Cancer Network guidelines suggest the use of mitomycin as an adjuvant therapy following endoscopic tumor ablation. This recommendation stems from its effectiveness in achieving near or complete ablation of low-grade tumors and is supported by some clinical trial data. This gel can be administered intravesically after tumor resection, allowing for a localized treatment that minimizes systemic exposure and potentially reduces adverse events.

The conversation also addressed the risk of adverse events associated with mitomycin gel, including ureteral stenosis, which was noted to be around 29% in some patients. The participants discussed managing these risks through careful monitoring and consideration of individual patient factors when recommending this treatment option.

The methods of administering mitomycin gel were also discussed. The participants shared their experiences regarding the logistical aspects, such as whether to administer the gel using a retrograde or antegrade approach, and how these methods might differ based on institutional practices. Notably, there was a focus on the crucial role of ureteral access sheaths during the procedure, which facilitated the effective delivery of the gel while allowing for thorough tumor ablation.

Case Discussion

As in the previous program, several patient cases were discussed, including a female patient who was a longstanding smoker and had low-grade upper tract disease treated with endoscopic resection. Post-treatment, she initially achieved a complete response while using mitomycin gel, remaining in remission for approximately 2 years.

However, upon follow-up, imaging revealed a new renal pelvic mass approximately 1 cm in size, which was subsequently confirmed to be low-grade urothelial cancer. This case exemplified the high risk of recurrence associated with endoscopic treatments, with the recurrence rate estimated at approximately 60% to 70%.

Another case involved a patient with a solitary kidney and chronic renal insufficiency, which raised considerations about potential nephron loss if nephroureterectomy were performed. The discussion highlighted the challenges of predicting future complications in the contralateral kidney, especially in patients with risk factors such as diabetes and hypertension. This case underscored the importance of individualized patient assessment, considering the overall health, risk factors, and preferences related to treatment strategies.