The Latest UTUC Guideline With Dr. Peter Clark

Peter Clark, MD, Professor and Chair of Urology, Atrium Health, highlights relevant updates to the American Urological Association (AUA) guidelines for upper tract urothelial carcinoma (UTUC).

A panel member for the development of this guideline, Dr. Clark explains the rationale behind diagnostic ureteroscopy, as well as reducing the risk of metachronous bladder recurrence, and an increased focus on Lynch syndrome.

UTUC is a rare entity. How does that change how you approach writing this AUA guideline and appraising evidence for guideline inclusion?

It clearly creates some challenges because automatically if you have a rarer entity, the number of trials and amount of level 1 evidence you have is going to be less. There’s a little more reliance on systematic reviews of existent literature. You have to expand a bit because you’re not going to have as many level 1 prospective randomized trials in that space.

There’s definitely more thought that has to go into what you’re going to include as part of your systematic reviews and evidence gathering. You’re also going to get more of expert opinion and clinical practice statements than you might get otherwise in a guideline that has more prospective randomized trials that it could incorporate.

What are the updates to evaluation of patients with suspected UTUC?

The guideline very much made an attempt to create risk-stratified approaches to UTUC, not only the diagnosis but also the treatment. We all know as urologists that there are limitations to some of the tools we have to accurately and appropriately stage these patients—unlike, for example, bladder cancer, where you can resect the entire tumor fairly readily. It’s much more difficult to do that in upper tract disease.

Our imaging is known to be somewhat limited, so we tried to risk stratify our approaches to the diagnosis and then, based on the risk of having occult T2 disease or frank T2 disease, we try to substratify out how we approach the treatment algorithms.

What is the rationale behind diagnostic ureteroscopy, as well as reducing the risk of metachronous bladder recurrence?

Ureteroscopy and actual tissue biopsy is something we always would want. You’re going to have more confidence in your ability to say how you’re going to approach something if you can get actual tissue, and the tool that we tend to use for that is ureteroscopy. That is a bread-and-butter tool that we use all the time.

There’s always a concern in the thought process around if that changes your risk in other locations. Typically, these are done with a little bit of pressure. Could that in fact be influencing your risk of recurrence? The data there is a bit mixed. I say most of us just try and minimize the amount of trauma that we induce in the process of doing ureteroscopy. For example, if you can’t get access, maybe you put up a stent and let things self-dilate or maybe use other maneuvers to try and reduce the trauma that you’re inducing in the process of doing the procedure.

I would say the definitive data around whether or not you should metachronously treat bladder cancer and upper tract disease is not really there, so that’s actually a fruitful space for us to investigate further.

What does this AUA guideline say about genetic testing?

One of the takeaways that we hope people get out of this guideline is to not forget about Lynch syndrome. Lynch syndrome is quite common in the context of UTUC, unlike most other urologic malignancies, and I continue to feel that that’s a little bit underappreciated in the wider community. That was definitely a focus of the guidelines, to get people to think about the fact that if you have UTUC in a patient, you have got to think about the possibility of Lynch syndrome.

There is some new data on the use of NAC that builds on data from POUT for adjuvant therapy. What are the pros and cons of these two approaches?

There’s a plus or minus to everything. POUT is probably our best randomized data with respect to chemotherapy in the context of UTUC, but it’s an adjuvant trial, so it was designed to say if you get the nephroureterectomy, if you get platinum-based chemotherapy, you do better than if you don’t.

The advantage to adjuvant therapies is you have a final pathologic diagnosis. You know the stage. You’ve reduced the disease burden. The amount of “work” chemo has to do is less. There are advantages to that approach.

However, it often, not always but often, means you’ve lost a kidney. For the con, if you lose a kidney, your kidney function may lower. That may move you from being eligible for cisplatin to carboplatin, and whether that actually makes a difference, I don’t believe we know completely. In bladder cancer, we feel it does, so the presumption is that that’s true in UTUC, so that would suggest maybe you should do it before because maybe then you could get cisplatin and after you lose a kidney you cannot. You also don’t have as good pathologic information, so how confident are you that they in fact have invasive disease that would qualify you for chemo? Chemo is non-trivial.

There’s a yin and yang to everything, as I tell my patients all the time. There’s no free lunch. If you give platinum-based chemotherapy, you could induce toxicity, you could get neuropathy, you could have a bunch of different things occur that you wouldn’t want to do unnecessarily if they didn’t actually have invasive disease. So there’s an argument there to say maybe you ought to wait until you know they need it rather than just doing it in everybody.

Watch Dr. Petros Grivas dive further into the level 1 data for the adjuvant approach from POUT.

How can physicians incorporate nephron-sparing treatment approaches in low-risk disease into their practice?

This perhaps will generate more controversy than some of the other aspects of the guideline. One of the things we were trying to emphasize is that if somebody has low-risk UTUC, there should be every attempt made to try and spare that kidney because the risk of progression to metastatic disease in that context is relatively low.

Like any guideline, this is not proscriptive. It’s not robotic, like you don’t walk in and say, oh it goes low risk, therefore thou shalt automatically do X. However, we felt it important to emphasize that you should at least think through and try and emphasize those approaches wherever feasible.

We intentionally were a little vague about exactly how to do that because there’s a variety of ways you could approach ablative therapies in the context of low-risk UTUC. There’s various ureteroscopic laser approaches. Jelmyto might be appropriate in certain contexts. If it’s isolated, perhaps to the distal ureter for example, you could consider a distal ureterectomy and re-implant. There’s a variety of ways to spare that kidney, recognizing that there’s going to be scenarios where that’s not possible, either just to do the multifocality or disease burden, etc. We try to give some wiggle room around that but by the same token, we wanted to emphasize that where feasible, an attempt probably should be made.

Expanding on the AUA guidelines, Dr. Surena Matin defines these as the ideal candidates and techniques for kidney sparing in UTUC.

View more updates and insights from the AUA 2023 meeting.