In a recent interview for GU Oncology Now, David Ambinder, MD, a urology resident at New York Medical College/Westchester Medical Center, sat down with Surena F. Matin, MD, of the University of Texas MD Anderson Cancer Center, a renowned expert in upper tract urothelial carcinoma (UTUC) research, to discuss various topics related to urologic surgery. Dr. Matin shared valuable insights on lymph node dissection and kidney-sparing management, as well as the findings of the OLYMPUS trial.
This article provides a summary of their conversation, which sheds light on the current understanding of and advancements in UTUC treatment.
Lymph Node Dissection in Urologic Surgery
Lymph node dissection in urologic surgery serves not only a staging purpose, but is also potentially therapeutic, Dr. Matin explained. However, much of what is known about its benefit is extrapolated from previous understanding of bladder cancer treatment. Dr. Matin highlighted the research conducted by Japanese investigators, particularly Tsunenori Kondo, MD, who pioneered the systematic investigation of lymph node dissection for upper tract disease.
Dr. Kondo and colleagues investigated lymph node mapping and the construction of lymph node dissection templates for tumors that arise in the proximal ureter or renal pelvis. Their findings further demonstrated the therapeutic benefits of lymph node dissection, especially for patients with more locally advanced disease. Similar to bladder cancer treatment, where lymph node removal effectively addresses microscopic lymph node disease, lymphadenectomy proved beneficial for patients with T3 disease in upper tract cases.1
However, determining the precise lymph nodes to target has been challenging. Dr. Matin’s research has since attempted to corroborate the data and investigate the appropriate lymph node dissection for patients with mid or distal ureteral tumors. He and his colleagues observed that patients with distal ureteral tumors tended to develop metastases cranially to the upper retroperitoneum, indicating that pelvic node dissection alone may be insufficient. This phenomenon suggests that the current lymph node removal practices for lower ureteral tumors, which are limited to pelvic lymph nodes, may not consistently identify the correct lymph nodes to remove.
Risk Stratification and Lymph Node Dissection
For patients with lower-risk disease, the data do not necessarily support a benefit for lymph node dissection. However, Dr. Matin emphasized that the benefits are primarily seen in cases of locally advanced disease, where the risk of micrometastatic disease is higher. Still, accurately identifying low-risk patients presents a challenge. While many urologists may rely on simple grade of disease, a high grade does not always signify high-risk disease. To address this issue, Dr. Matin relies on clinical nomograms and reviews 3 specific nomograms for each case. When all 3 nomograms indicate the same direction, he feels confident about the disease risk. Depending on the nomograms’ indications, Dr. Matin determines the extent of lymph node dissection, choosing between no dissection, limited dissection, or more extensive dissection.
Kidney-Sparing Procedures
Dr. Matin also discussed the ideal candidates for kidney-sparing procedures, as outlined in the American Urological Association and European guidelines. He explained that low-risk patients with a single tumor smaller than 2 cm and no evidence of high-grade disease are well-suited for ureteroscopy and laser ablation, treatments that allow for kidney preservation. However, accurately predicting the risk of recurrence remains challenging, making it difficult to determine the most appropriate approach in urgent situations involving patients with a solitary kidney, chronic kidney disease, or indications of high-grade disease.
Standard Procedures for Endoscopic Resection
Dr. Matin highlighted the lack of a standardized approach for patients who undergo complete endoscopic resection or minimal ureter resection. While ureterectomy has been considered the gold standard, other methods are uncharted territory. Topical therapy has been used in various ways, but it requires reliable delivery. The introduction of mitomycin hydrogel has played a significant role in establishing a standardized approach for this patient population.
Insights From the OLYMPUS Trial
The OLYMPUS trial investigated a unique formulation of mitomycin combined with a hydrogel. Dr. Matin described how this approach allows for the slow release of mitomycin, ensuring consistent dissolution in urine. The trial focused on patients with biopsy-proven, low-grade upper tract cancer, and the results demonstrated a 59% complete response rate. However, approximately 35% to 40% of patients experienced ureteral narrowing or stenosis, which could be managed by placing patients on a drug holiday and considering steroid treatment.2
Innovative Approaches to Mitigate Strictures
Dr. Matin discussed the promise shown by percutaneous or antegrade approaches to minimize the risk of strictures. He initially had reservations but, after consulting with experts and implementing similar processes, found success with these methods. The percutaneous approach showed no strictures or narrowing, simplifying the process for both patients and the medical team.
Dr. Matin’s innovative approaches to mitigating strictures offer potential benefits to patients undergoing these procedures. As research continues, advancements in urologic surgery hold promise for improved outcomes in patients with UTUC.
David Ambinder, MD is a urology resident at New York Medical College/Westchester Medical Center. His interests include surgical education, GU oncology and advancements in technology in urology. A significant portion of his research has been focused on litigation in urology.
References
- Lange S, Calleris G, Matin SF, Rouprêt M. Optimizing lymph node dissection at the time of nephroureterectomy for high-risk upper tract urothelial carcinoma. Eur Urol Focus. 2023;9(2):280-282. doi:10.1016/j.euf.2023.01.001
- Matin SF, Pierorazio PM, Kleinmann N, et al. Durability of response to primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel: OLYMPUS trial final report. J Urol. 2022;207(4):779-788. doi:10.1097/JU.0000000000002350
