Lymphadenectomy for UTUC: Staging and Therapeutic Considerations

Surena F. Matin, MD, The University of Texas MD Anderson Cancer Center, and David Ambinder, MD, Urology Resident, New York Medical College/Westchester Medical Center, discuss the data that supports performing lymph node dissection at time of surgery for UTUC, as well as the risk factors for individual patients.

Dr. Ambinder: It’s great to meet you, Dr. Matin. You have made significant contributions to upper tract disease research, and I’m eager to hear your insights on various topics. Let’s start with lymph node dissection, and then we can discuss kidney-sparing management and the latest additions to this year’s guidelines. Regarding lymph node dissections, could you provide some background on the supporting data for performing lymph dissection during surgery?

Dr. Matin: Certainly. In terms of overall disease perspective, we have data from bladder cancer indicating that lymphadenectomy serves not only a staging purpose but also a potential therapeutic role for urothelial disease. We extrapolate this knowledge to upper tract disease. However, determining which lymph nodes to target has been a challenge. The Japanese researchers were the first to systematically investigate this matter. Dr. Kondo in Japan has been at the forefront of this research since the early 2000s. They conducted an initial mapping study and defined criteria for an adequate or inadequate template, forming the basis of their subsequent evaluations. They created a registry and prescribed lymph node templates for proximal ureter and renal pelvis tumors.

The data from this registry demonstrated therapeutic benefits, particularly for patients with more locally advanced disease. Patients with T3 disease who underwent an adequate lymphadenectomy had better outcomes than those who did not undergo lymphadenectomy. This aligns with findings in bladder cancer, where microscopic lymph node disease undetectable by imaging can be effectively addressed through lymph node removal.

We conducted a multi-institutional study to corroborate the Japanese data. Our study focused on patients with either biopsy-proven nodes or pathologically proven lymph nodes, and we also included a smaller subset of patients with mid and distal ureter tumors. Our findings indicate that metastases in patients with distal ureter tumors tend to migrate cranially. Consequently, pelvic node dissection alone may not be sufficient, as many patients develop metastases in the upper retroperitoneum, albeit not reaching the hilum. We have observed this phenomenon repeatedly. This may explain why the data supporting lymphadenectomy for lower ureter tumors is not as robust, as it is possible that we are not consistently removing the correct lymph nodes in many of these cases.

Dr. Ambinder: Is there a distinction between low-risk and high-risk patients?

Dr. Matin: Indeed, the data does not suggest any benefits from lymph node dissection in low-risk patients. The advantages are primarily seen in cases of locally advanced disease, where the risk of micrometastatic disease is higher. However, identifying low-risk patients accurately poses a challenge. Sometimes, during a procedure, a fellow might question the need for a node dissection, particularly if the tumor is low grade. In such cases, I explain that although we believe it is low grade, there may be multifocality or high volume disease, and the available biopsy sample might not capture the full picture. I am concerned about the possibility of upgrading and upstaging. Therefore, even in potentially low-risk scenarios, I may perform some level of lymph node dissection. While its therapeutic value remains uncertain, I know it aids in staging. If the patient does get upgraded or upstaged, I feel more confident knowing that I have performed the additional procedure, even if it takes an extra 15 to 20 minutes.

Dr. Ambinder: You briefly mentioned risk factors. What indicators prompt you to consider a lymph node dissection for a patient? What factors do you assess?

Dr. Matin: That’s a great question. It’s an evolving field. One could simplify it by solely considering grade—low grade versus high grade—and perform lymph node dissection in high-grade cases, which is not unreasonable. However, we know that not all high-grade diseases are highly risky. The new guidelines attempt to provide more granularity by introducing favorable and unfavorable high-risk classifications.

In my practice, I rely on clinical nomograms. I find 3 particular nomograms to be fairly reliable, although none of them is perfect. Consequently, for each case, I review all 3 nomograms, which can be quite time-consuming. When all 3 nomograms indicate the same direction, I feel very confident about the situation. If 2 out of 3 are in agreement, I have a reasonable level of confidence, recognizing that there is still room for discrepancy. It is rare for all 3 nomograms to present conflicting information. Typically, at least 2 of them align. Of course, each nomogram represents a slightly different population, as is the case with any nomogram. I utilize these nomograms as guides and determine the extent of lymph node dissection accordingly. If the nomograms indicate favorable high-risk disease, I may opt for no node dissection or a more limited one. Conversely, for cases involving high-risk disease or patients receiving neoadjuvant chemotherapy, where concerns are elevated, I may opt for a more extensive node dissection. Therefore, I have 3 levels of dissection gradations available.

View their other comments on the Right Patents and Optimal Techniques for Kidney Sparing in UTUC and the OLYMPUS trial for Patients With Low-Grade UTUC.