Dr. Venkat discusses radical nephroureterectomy vs segmental ureterectomy for patients with UTUC

Treatment for upper tract urothelial carcinoma (UTUC) remains a challenge for urologists, as they observe many negative outcomes in this patient population post surgery. More recently, clinicians are looking towards nephron-sparing techniques to mitigate some of the poor outcomes of radical nephrectomy.

At the 2021 Society of Urologic Oncology Annual Meeting, a study was presented by Siv Venkat, MD, FRCSC, that evaluates the outcomes of the bladder-sparing method of segmental ureterectomy versus radical nephroureterectomy.¹ Venkat is a urologic oncology fellow at Weill Cornell Medicine and New York-Presbyterian Hospital in New York City, New York.

Please discuss the background for this study.

As many people know, upper tract urothelial carcinoma is a disease that has fairly bad outcomes. It's a disease that we catch later on, and people don't do as well as urothelial carcinoma of the bladder. Traditionally, the gold standard treatment for upper tract urothelial carcinoma has been radical nephroureterectomy; however, the problem with radical nephroureterectomy is obviously that it’s not nephron sparing. Often, there are lesions and your whole kidney has to come out. Segmental ureterectomy, which is just removal of the area where their is disease and potentially a lymph node dissection around it, has had an increased adoption for upper tract urothelial carcinoma in selected cases. However, its oncologic equivalence remains unclear. So, [for] this study, we had a few goals. The first is [that] we wanted to see the current trends in our radical nephrou[reterectomy] and segmental ureterectomy. The second is [that] we wanted to see what factors predict a patient getting segmental ureterectomy. The third is [that] we wanted to look at rates of lymph node dissection overall in the 2 different types of surgeries, and we wanted to also stratify by high-risk features. By high-risk features, I mean high-grade tumors, tumors over 2 cm, and P2, PT2, T3, and T4 disease, which are some of the high-risk features in the European guidelines. We also wanted to look at survival. We want to see how these patients with segmental ureterectomy and radical nephrou[reterectomy] do overall.

What were some of the notable findings? Were any of them surprising to you or your co-authors?

Looking at the first question that we asked, we found that segmental ureterectomy is more likely to be performed in older patients, at academic centers, patients with lower grade tumors, and patients with lower stage tumors. None of these were particularly surprising, and that's generally what we see in practice.

The second question we had a more interesting answer to. When we looked at rates of lymphadenectomy, we actually found that patients that had segmental ureterectomies had higher rates of lymphadenectomy overall. It was about 32% for segmental ureterectomy, and 23% for radical nephrou[reterectomy]. When we stratified by high-risk subgroups, we found that this was consistent across all high-risk subgroups. So, across all of them, patients who had segmental ureterectomies were having a higher rate of lymph node dissection. We also found that when they did have lymph node dissection, they had a higher nodal yield with segmental ureterectomy versus radical nephrou[reterectomy]. Finally, in terms of survival, we found that overall segmental ureterectomy patients did better in terms of overall survival. Now, obviously, these patients are a selected group. We talked about how they are generally lower stage and lower grade. But overall, we found that they did better. When we looked at subgroup analysis and we looked at just the high-risk features alone, which was the more interesting portion, we found that they were not inferior to radical nephrou[reterectomy], across all the different high-risk features that we talked about. So, that was an interesting finding.

Is further research on this topic planned, and if so, what will its focus be?

Obviously, this is a retrospective study, and I think we need quality prospective data comparing apples to apples vs apples to oranges. Until we have that, it's hard to recommend with certainty in 1 way or the other. However, this is very interesting data. I think further research should be directed towards a prospective, randomized control trial, comparing patients with similar tumors, randomizing them to either radical nephroureterectomy or segmental ureterectomy. At our center, we don't have any current plans of doing that, but we do have some prospective data that we're collecting, and we're planning to look at this data down the road.

What is the take-home message for the practicing urologist?

I think there's been a couple of interesting findings of this study, obviously keeping in mind its limitations. The first is that, overall, it still appears that rates of lymph node dissection are still quite low for this disease. In patients with high-risk tumors, it's generally accepted to do a lymphadenectomy. We know that there's a benefit in terms of staging for sure, and we know that there's a possible benefit in terms of cancer-specific survival and overall survival in doing a lymphadenectomy in high-risk upper tract urothelial carcinoma. That being said, the European Association of Urology recommends a lymphadenectomy performed in these cases. However, we found that overall, the rates are still quite low: 23% for [radical nephroureterectomy] and 32% for segmental ureterectomy. So, the first take-home message for urologists is that we're not doing enough lymph node dissections in upper tract disease, and it's something that I think needs to be pushed a little bit more. The second take-home message, when we're looking at radical nephrou[reterectomy] and segmental ureterectomy is that I think that in selected cases, segmental ureterectomy appears non-inferior to radical nephroureterectomy. These selected cases may include patients where[by] nephron-sparing is a priority, patients with solitary kidneys, patients who prefer to spare their kidney, patients with favorable anatomic characteristics, such as distal ureteric tumors, as well as patients with comorbidities or that are older. I think in all these carefully selected cases, it does appear that even in high-risk disease, we can have good outcomes with segmental ureterectomy.

Is there anything else you feel our audience should know about the research?

I do want to point out some of the limitations of our research. Obviously, it's a retrospective analysis. We looked at the National Cancer Database. When you look at retrospective analysis, obviously there is a risk of bias, and because it was not randomized and controlled, surgeons were more likely selecting patients that they felt were favorable for segmental ureterectomy. So, that's the first thing to keep in mind. The major limitation of this is that we did not stratify in terms of apples to apples. So, the individual tumor, although it may be high-grade or over 2 cm, may have additional features that make it higher risk or low risk even within the subgroups. That's something else to keep in mind. That being said, I do think that it's interesting data that we're getting out of this, and it's something to think about. It gives us another tool in managing this very challenging disease.

References

1. Venkat S, Lewicki P, Basourakos S, et al. Comparison of radical nephroureterectomy and segmental ureterectomy in upper tract urothelial carcinoma. Paper presented at: 2021 Society of Urologic Oncology Annual Meeting; December 1-3, 2021; Orlando, Florida. Poster #114