UTUC roundtables: Grade and location drive care

Katie S. Murray, DO, MS

On January 28, 2025, and February 25, 2025, Urology Times conducted case-based roundtable discussions on the topic of upper tract urothelial cancer (UTUC). The programs were 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. What follows is a summary of these discussions.

This summary was AI generated and edited by human editors for clarity.

Roundtable 1

Adherence to Guidelines

At the beginning of the conversation, Murray highlighted the relevance of recent guidelines issued by the American Urological Association (AUA) regarding UTUC, indicating a shift in focus toward this specific category of cancer, which was previously perceived as a lesser variant of bladder cancer. She inquired whether the participating clinicians were utilizing these guidelines in their practice, prompting a discussion that illustrated a spectrum of awareness and application among the participants. One participant expressed his unfamiliarity with these guidelines but indicated a straightforward approach to grading biopsies, perceiving a clear distinction between low and high-grade cases. In contrast, another participant mentioned that his understanding of the guidelines was evolving and had influenced his approach to treatment modalities, particularly in differentiating management strategies for low versus high-grade tumors.

Treatment Strategy: Tumor Grade, Location Key

The conversation moved to treatment options, emphasizing that management strategies heavily depend on tumor grade and location. Historically, radical nephroureterectomy was the standard procedure for treating UTUC. However, Murray pointed out an increasing trend toward kidney-sparing techniques. Participants discussed various kidney-sparing procedures such as segmental ureterectomy and endoscopic management, which could include oncological interventions like BCG and mitomycin C. Murray further probed how participants approach patient discussions regarding treatment, particularly with low-risk tumors, noting the importance of patient education around multifocality and the risks of bladder cancer.

One participant contributed to the dialogue by emphasizing the role of tumor size and location in determining the recommended treatment, suggesting that the characteristics of a tumor would crucially influence the management plan. As the participants shared insights from their practices, a consensus emerged favoring kidney-sparing approaches when feasible, particularly for younger patients or those with low-grade tumors. One participant stressed the need to weigh environmental risk factors and patient preferences during treatment decision-making.

Another topic discussed was mitomycin reverse thermal hydrogel (Jelmyto), which has gained attention for its kidney-sparing potential. During the conversation, participants noted that Jelmyto can be employed after endoscopic tumor ablation to provide adjunctive therapy. Some practitioners shared their experiences with using Jelmyto, highlighting its effectiveness in achieving complete responses in patients and discussing outcomes from clinical trials, such as the OLYMPUS trial. This trial demonstrated a significant proportion of patients achieving tumor resolution with Jelmyto after receiving the treatment. However, concerns were raised about potential adverse events, particularly ureteral stenosis, associated with higher doses. Overall, the treatment was recognized as a useful option for managing low-grade UTUC, facilitating kidney preservation while enabling effective management of the disease.

The Importance of Accurate Diagnosis

The methodology of ensuring accurate diagnosis and grading was brought to the forefront, with discussions around potential diagnostic challenges. The National Comprehensive Cancer Network (NCCN) guidelines play a pivotal role in shaping initial treatment protocols for patients with confirmed low-grade disease, advocating for endoscopic management combined with postoperative intracavitary chemotherapy in selected cases. The intricacies of obtaining accurate biopsies were discussed, as participants recognized the significance of confirming low-grade classification prior to considering conservative treatment options.

One participant mentioned employing mitomycin gel using a nephrostomy tube as part of his therapeutic approach, demonstrating an innovative method of delivering this treatment with the potential for reducing recurrence rates. Yet, he also recounted a case where neoplasm progression necessitated a nephroureterectomy, underscoring risks inherent in the management of low-grade malignancies. Another participant interjected to bring forth the topic of percutaneous approaches and the challenge posed by potential seeding of cancer cells in the bladder, highlighting procedural outcomes vs persistent cellular risks post-ablation.

As the roundtable continued, there was an exploration of size criteria for tumors, where 1 participant pointed out the NCCN's guideline suggesting a cut-off at 2 cm. Participants reiterated that the anatomy and growth pattern of tumors also influenced surgical decisions significantly. Another participant noted how the tumor characteristics could obscure typical categorization, which might complicate management. The discussion illustrated a shared understanding among participants regarding the multifactorial considerations that must inform clinical choices.

Case Discussion

Murray and the panel also discussed patient cases of UTUC. One of the highlighted cases involved a 71-year-old man with a history of low-grade papillary non-invasive bladder cancer that had persisted for the past 10 years. He presented with new-onset hematuria and was identified as a former smoker with a body mass index of 32 kg/m² and a well-controlled history of diabetes. Diagnostic imaging through a CT urogram showed no evidence of metastatic disease, although his GFR was noted to be 52. During a diagnostic left ureteroscopy, multiple small tumors were discovered in the distal ureter, along with scattered multifocal tumors in the renal pelvis, the largest measuring between 3.5 mm to 5 mm in size. Subsequent biopsies indicated low-grade tumors, whereas washings and cytology results were negative for malignancy. The management discussion revolved around the treatment options following this diagnostic procedure, particularly concerning whether to pursue kidney-sparing methods or to consider nephroureterectomy given the overall tumor burden and the specifics of the patient's condition.

The case discussions emphasized that for patients with low-grade tumors, endoscopic management should be prioritized. This approach may be supplemented by intravesical therapy as needed, especially considering the risk of multifocality and potential bladder recurrences. Participants highlighted the importance of transparent communication with patients about their disease, treatment options, recurrence risks, and how their medical history may influence decision-making. Furthermore, the conversations revealed that some patients may require more aggressive treatment due to factors such as the presence of multifocal tumors, a prior history of bladder cancer, and the impacts of age or comorbidities on treatment decisions. The complexity of managing recurrences and the necessity of balancing renal function preservation with effective cancer treatment emerged as critical themes in the discussions. Overall, the case discussions illustrate the nuances involved in treating low-grade upper tract tumors and underscore the significance of individualized care based on tumor characteristics, patient history, and existing clinical guidelines, showcasing a collaborative approach among various specialists in effectively managing their patients.

Roundtable 2

Risk Stratification

A central theme of this roundtable was the risk stratification of patients diagnosed with low-grade UTUC. Murray noted that current guidelines focus on categorizing patients based on factors such as tumor grade, size, focality, and biopsy results. This stratification helps differentiate between low-risk and high-risk patients, ultimately guiding treatment decisions. During this portion of the discussion, participants articulated their views on the inherent uncertainties in diagnosing low-grade tumors, particularly given that approximately 40% of initial low-grade biopsy results ultimately reveal higher grade tumors upon nephroureterectomy. This discrepancy has left many practitioners hesitant to fully trust biopsy outcomes without thorough confirmation.

The gathering of opinions revealed a consensus about the challenges associated with ensuring accurate diagnoses. One participant remarked on the difficulty of defining what constitutes a low-grade tumor, urging caution in proceeding with kidney-sparing surgery unless robust evidence supports the low-grade classification. Another participant echoed this sentiment, adopting a conservative stance by treating low-grade UTUC as inherently aggressive until there is incontrovertible evidence of non-invasiveness. This perspective highlights the cautious approach many urologists take, emphasizing the potential risks of misdiagnosis and the life-altering ramifications of delayed treatment.

A poignant discussion arose regarding the decision-making processes tied to nephroureterectomy, especially for low-grade cases. Participants exchanged thoughts on the frequency of upgrading tumors during surgery, with varied experiences influencing their practice. A notable concern was raised about how often pre-surgical assessments align with final pathology findings. Differences in practitioners’ experiences and interpretations of diagnostic tools emphasized the variability that exists in clinical approaches.

Alternative Treatment Options

The group explored alternative treatment options available for low-grade UTUC. Options discussed included radical nephroureterectomy, segmental ureterectomy, and various endoscopic techniques, such as ureteroscopic laser ablation. These procedures aim to manage smaller, solitary lesions while minimizing the impact on overall kidney function. One participant emphasized discussing these endoscopic options comprehensively with patients, particularly when considering low-grade tumors, unless there are multiple lesions or the tumors are of significant size. The discussion illustrated the diverse frameworks used by urologists to conceptualize treatment paths, incorporating aspects of patient education and shared decision-making.

As the conversation continued, participants highlighted the vital role of patient follow-up and monitoring to manage the risk of recurrence effectively. Urologists shared insights on establishing rigorous follow-up regimens to help detect any potential field recurrences in bladder cancer that might accompany upper tract tumors, given that a significant percentage of UTUC patients may present with concomitant bladder cancer. One participant brought attention to the prevalence of challenges faced in follow-up protocols, stemming from misconceptions or unclear cancer status following treatment, and discussed the necessity of establishing a firm understanding of the patient’s overall health landscape.

As part of the discussion, Murray asked participants about their experiences with intravesical therapies, such as Jelmyto and other forms of chemotherapy like BCG and mitomycin C.

Participants shared varying levels of familiarity and usage of Jelmyto. One discussant reported using it extensively, whereas others mentioned limited experience, with a few cases involving BCG in reflux situations. Jelmyto's application was highlighted for patients with low-grade, low-volume tumors who are not candidates for nephroureterectomy, with the administration possible via ureteral catheters or nephrostomy tubes.

The efficacy of Jelmyto was also discussed, referencing clinical trial data that indicated a 58% complete response rate in patients after initial treatment. Participants noted the importance of monitoring potential adverse events and complications that can arise with frequent treatments. There was recognition that although Jelmyto presents a promising option, practical challenges, such as ensuring adequate contact time with the tumor and managing patient follow-up, remain crucial considerations for practitioners.

Case Discussion

As in the previous roundtable, several patient cases were presented to highlight the complexities of managing low-grade UTUC and the varying treatment approaches that practitioners may consider. The first case involved a 62-year-old female patient who presented with intermittent and painless gross hematuria over the preceding months. Her medical history included a former smoking habit, managed hypertension, and controlled chronic obstructive pulmonary disease. A CT scan showed a filling defect in the lower pole of the left kidney, which was confirmed through cystoscopy and ureteroscopy. The biopsy results indicated that the lesion was low-grade, with additional tests revealing no concerning findings, such as hydro or adenopathy.

Throughout the discussion regarding this specific case, participants deliberated on the appropriateness of different treatment options considering the size and location of the tumor. One participant pointed out the challenges associated with resecting a 1.5-cm tumor in the lower pole of the kidney, emphasizing that such locations can complicate endoscopic interventions, even for skilled surgeons. The need for careful consideration of the risks vs benefits of surgical resection vs kidney-sparing approaches was a central theme in the group’s analysis of this case.

In addition to this patient, the conversation noted that practitioners often encounter patients with multifocal tumors or those presenting with larger masses. This leads to considerations regarding the balance between thorough treatment and potential implications on the patient's kidney function. As the discussions progressed, the participants touched on factors like patient age, comorbidities, and kidney function as critical elements influencing treatment strategies. These considerations highlighted the necessity for individualized treatment plans tailored to each patient’s specific circumstances while accommodating their overall health and personal values regarding aggressive interventions.