Clinicopathological or Radiological Factors That May Predict a Diagnosis of Upper Urinary Tract Urothelial Cell Carcinoma Without the Delay for Diagnostic Ureteroscopy - Alexander Laird

March 21, 2023

Alexander Laird joins Sam Chang in conversation to discuss data aimed at identifying clinical and radiological factors that could predict upper tract urothelial carcinoma to avoid diagnostic ureteroscopy in selected patients. The study found that patients with a final diagnosis of upper tract urothelial carcinoma tended to be older, smokers, had a history of previous abdominal surgery, presented with visible hematuria, and had solid lesions on the CT urogram. These factors were independently predictive on multivariate analysis for a final cancer diagnosis and therefore proceeded to nephroureterectomy. The study found that with appropriate selection and counseling, these patients may be able to avoid diagnostic ureteroscopy, speeding up the pathway and ensuring early treatment. The study also found that 9.2% of patients underwent nephron-sparing treatment, and about one-third of patients had benign or other pathology on their ureteroscopy, which allowed the patient to avoid an unnecessary nephroureterectomy.


Alexander Laird, MBChB, MRCS (Ed), PhD, Consultant Urologist NHS Lothian, Honorary Clinical Senior Lecturer, University of Edinburgh, Edinburgh, Scotland

Sam S. Chang, M.D., M.B.A. Patricia and Rodes Hart Endowed Chair of Urologic Surgery Professor Department of Urology at Vanderbilt University Medical Center

Read the Full Video Transcript

Sam Chang: Hello everyone. My name is Sam Chang. I'm a urologist in Nashville, Tennessee, and work at Vanderbilt. We are quite fortunate today to have a real leader across the pond. We have Mr. Alexander Laird, who's a consultant urologist in the NHS Lothian, and an honorary clinical senior lecturer at the University of Edinburgh.

He will be speaking today on perhaps something a little bit controversial, a little bit perhaps ahead of its time, regarding the fact that we may be able to avoid diagnostic ureteroscopy prior to radical nephroureterectomy. We've asked him today to talk about the article that he's put together that was recently published in the British Journal of Urology International. Alex, thanks so much for joining us and I look forward to your presentation.

Alexander Laird: Thanks very much, Sam. It's a pleasure to be here and speak with you, and hopefully spark some discussion. I've got some slides that I'll bring up and we can run through some of the results.

We've published our recent results on diagnostic evaluation of upper tract urothelial carcinoma, whether we can omit diagnostic ureteroscopy in BJUI. As you and the viewers know, urothelial carcinoma of the upper tract is a relatively rare disease affecting only, counting for about 5% of urothelial carcinoma overall. We don't see it that frequently, but our standard in our unit was to perform diagnostic uteroscopy in almost all patients with select and with suspected upper tract urothelial carcinoma.

However, we noticed that the diagnostic pathway was often protracted, and as we were all hit with the COVID pandemic, we had limited access to theater, and really we started to wonder, can we omit this test in selected patients? We aim to identify clinical and radiological factors that could predict upper tract urothelial carcinoma to avoid diagnostic ureteroscopy. We retrospectively reviewed all of our cases between 2011 and 2017 who presented with an abnormal CT urogram, and underwent diagnostic ureteroscopy, either with or without biopsy, or proceeded directly to nephroureterectomy.

There were 260 patients identified in the study period overall, and importantly, all cases were reviewed by a subspecialist uroradiologist within our own multidisciplinary team meeting. You can see that almost 90% of patients, as I said, had diagnostic ureteroscopy prior to treatment. Importantly, 6% to 8.5% of patients were found to have an underlying diagnosis of upper tract urothelial carcinoma overall. But there are two really key points that I wanted to show here. One was that 14 patients, 9.2%, underwent nephron-sparing treatment, so those patients were saved from nephroureterectomy, and about a third of patients overall, 77 had benign or other pathology on their ureteroscopy, again being saved from unnecessary nephroureterectomy. There's definitely a group of patients where we 100% need to be finding these patients and avoiding nephroureterectomy.

But when we looked at the cases who had a final diagnosis of upper tract urothelial carcinoma versus having no diagnosis of upper tract urothelial carcinoma on ureteroscopy, we found that patients with cancer tended to be older. They tended to be smokers as you'd expect. Interestingly, they tended to have a history of previous abdominal surgery, which was a curious finding, but they mainly presented with visible hematuria and they were often had solid lesions on CT urogram.

When we looked at these factors to determine which factors were predictive of a final diagnosis of upper tract urothelial cancer, we found that age, smoking history, again abdominal surgery, visible hematuria and a solid lesion on CT urogram, were all independently predictive on multivariate analysis for a final diagnosis of cancer, and therefore proceeded to nephroureterectomy.
When we look at those three particular factors, being smoking, a history of visible hematuria and a solid lesion on CT urogram, we found that 53 patients had all three factors, and of those all 51 had a final diagnosis of upper tract urothelial carcinoma on radical nephroureterectomy. So 96.2% of these patients, and it's these patients that we are starting to advocate with appropriate selection, and key is appropriate discussion with the patient and counseling, that they may be able to avoid diagnostic ureteroscopy, both to speed up the pathway and make sure that they get the right treatment early on.

Sam Chang: Alex, that's great. There are a couple other points from this article that I wanted to touch base with you on. First you brought up, which I thought was great, that about 10% in this study were able to go to nephroureterectomy without any diagnostic ureteroscopy. Then an additional about 10% had your ureteroscopy without tissue confirmation. I can see these days where if you do ureteroscopy, you don't necessarily have to have a biopsy, if things are so convincing that you don't have to have tissue diagnosis and being able to proceed with nephroureterectomy.

Let's look on the other side. Let's look at those patients that you were able to, as you emphasized early on, the nephron-sparing and/or avoid surgery. What were the common findings? Were there characteristics that were predictive of that? Like, oh, we should definitely do this to make sure that we are not over-treating.

Alexander Laird: For this paper, we've not specifically looked at that, and really ureteroscopy is key for those because it's only the low grade tumors. We did look at whether the CT urogram could predict grade, and it wasn't very good at predicting grade of tumor. You couldn't really tell whether something was going to be low grade or not. It was better at predicting stage, and certainly there was a higher proportion of patients with solid lesions who had muscle invasive disease on the final pathology.

I think what we're saying is that the CT's better at picking up more advanced disease where nephron-sparing surgery may not be appropriate. If it's not giving those factors away, then we should be thinking this isn't definitely urothelial cancer, or it might be low grade, more superficial and maybe those are the patients that we should be doing the ureteroscopy.

Certainly in our department, we've got a great endourology team who do these diagnostic URSs for us, and they've published on their series of laser management of these with very good outcomes. There are definitely patients we should be doing URSs on and definitely should be thinking about nephron-sparing surgery, but I think the CT can pick up those who we probably don't have that option.

Sam Chang: In the discussion of your paper, you also mentioned the possible added benefit, or perhaps discriminating benefit of cytology and that cytology is somewhat inconsistently used, and it definitely at our institution, definitely inconsistently used there. There are times you do it, sometimes we'll do just a voided specimen. Sometimes we'll do the actual irrigation back and forth. Tell me where you see urine cytology fitting into this algorithm.

Alexander Laird: Yeah, so I think, I guess if you've got a solid tumor, it's probably going to be more advanced. Cytology may well then be more likely to be high grade and it might be more useful then. The problem is cytology is not great for low grade disease, so in that group where there's more uncertainty, then actually it may be another test potentially if you're having to do three voided specimens and what have you.

Our pathologists find it very difficult to get good samples to look at and confidently get results, and that's why we tend not to use it so much. One of the reviewers was keen to point out that we weren't using that and that's when we did this survey across Scotland, and actually most people aren't using it routinely. Whether things like urine-based cell-free DNA, where there's a more definite output, something like that, you could see that being used a lot more reliably. It may be that urine-based markers may be more predictive in the future.

Sam Chang: Alex, what's the next step? What's the next study? Where are you guys thinking at evaluating this? Because I think we have always emphasized, at least in the US, doing the right treatments, doing the right treatments, but we don't do as good a job, I think, of de-escalating our evaluation and our treatment and surveillance. Some of our newer guidelines, we're trying to avoid that because sure, it's easy to do a CT or a cysto every few months, etc. It's more difficult, but honestly, much better for so many of our patients if we can start de-escalating. What's the next project? Where are you guys going to go next?

Alexander Laird: Yeah, so I think from this we've really focused on improving our own pathway in our own department. Now I mentioned in the paper we've got dedicated slots for URSs, so that if patients do need one, they get it within a week or two. We are starting, and we are now having consultations with patients to say we could do a URS, but we are fairly certain now that you don't need it. We are changing our own management.

But I think this isn't finished. I think we need to do some prospective work, make it larger so that we can look at some of the other factors. Tumor size I think is a massive bearing. You're right, whether we can start picking out the patients who definitely need URS where nephron-saving surgery, which is much I think we're moving towards. Gone are the days that if you've got suspected upper tract urothelial carcinoma, everyone needs a nephroureterectomy. That's not the case.

But those that do need it, I think need it quicker than we are providing in most places now. I think being able to look at that prospectively across a number of centers, and look at some of the other factors and really tighten it up and make sure that we're doing the best for our patients.

Sam Chang: Well, Alex, thank you so much for spending some time with us and really starting to explore options, I think, that ultimately will be beneficial for so many patients. Thanks once again. Look forward to seeing you in person.

Alexander Laird: Yeah, thank you very much for the opportunity, and hopefully next time in person would be great.