Large Study Finds Low Upper Tract Cancer Rates After NMIBC

In a large, multi-institutional retrospective cohort study of over 3,000 patients treated for non–muscle-invasive bladder cancer (NMIBC) between 2005 and 2022, researchers found that metachronous upper tract urothelial carcinoma (UTUC) remains uncommon, particularly in low- and intermediate-risk patients.¹

Over a median follow-up of nearly 5 years (IQR, 2.7–8.4), 104 patients developed UTUC. The risk of UTUC at 10 years was just 2.7% for low-risk patients, 3.9% for intermediate-risk, and 6.3% for high/very high-risk groups. Importantly, only about half of these cases were identified through routine imaging, raising questions about the utility of regular upper tract surveillance in low- and intermediate-risk populations.

Alexandre R. Zlotta, MD, PhD, FRCSC, emphasized that these contemporary data challenge older assumptions and could inform updates to clinical guidelines.

“I think we will now provide additional granular data compared with what was in the past. We should continue to challenge what we have learned in the past with contemporary data, and look forward to improving the patient care,” Zlotta, director, uro-oncology, Division of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Mount Sinai Hospital; professor and Howard Sokolowski Chair in Uro-Oncological Research, Department of Surgery (Urology), University of Toronto, told Targeted Oncology in an interview.

Given the low incidence of UTUC and limited detection by imaging, especially in low-risk patients, the study supports reevaluating the need for routine upper tract imaging in NMIBC surveillance, potentially sparing many patients from unnecessary radiation and follow-up procedures.

In the interview, Zlotta, evaluated this retrospective cohort study and further analyzed the findings.

Targeted Oncology: Can you provide an overview of this research?

Alexandre R. Zlotta, MD, PhD, FRCSC: Non–muscle-invasive bladder cancer has a tendency to come back inside the bladder and can recur and then even progress to be a more lethal disease at times. Now, because the lining—the urothelium—is the same throughout the entire system, from the kidneys down to the ureter and the bladder, those patients are at risk of developing new tumors in the upper tract. Therefore, patients have been followed with upper tract imaging: CAT scan, ultrasound, MRI on a regular basis.

There has been what we called a risk-adaptive strategy, where patients who were low-risk non–muscle-invasive bladder cancer did not have exactly the same kind of monitoring as those patients with intermediate- to high-risk. Now, if you look at guidelines, patients who have high-risk disease need to have a follow-up in terms of imaging at least once every other year—often once a year. For intermediate risk, it’s unclear. For low risk, some people say you don’t need it after a couple of years; some don’t do it at all.

If we look into the data and the literature, actually, the series are really kind of outdated—20 years, 25 years—and the series are really small. Many people from my generation live with the idea that the risk for high-risk non–muscle-invasive bladder cancer can be as high as 20% to 25%. So, in order to get a sense of what is the contemporary risk on a large series of patients, we can guide and inform patients and also probably inform guidelines. We embarked on a pan-Canadian study with several institutions where, from 2005 onwards, we gathered all the data. We looked at the progression of those patients, and also the upper tract incidence of what we call metachronous tumors, which is after the resection.

What was assessed in the study?

We gathered a series of about 3000 patients with a follow-up that was just short of 5 years. Many patients had a longer follow-up. With a little bit of a different distribution where there were a little bit more high-risk tumors than generally speaking, overall, there was a large number of patients.

What the findings showed were kind of both sobering and helpful. We showed that in low-risk non–muscle-invasive bladder cancer—and low-risk means small tumors, low grade, Ta—at 5 and 10 years, the risk of upper tract disease was only 2%. Even worse than that, only half of them were picked up by imaging. We basically would image 99% of people to pick up 1, which often was simply a low-grade tumor in the upper tract.

The second observation was that in the intermediate-risk disease—which is usually recurrent low-grade Ta, or some smaller Ta high grade—the risk at 5 and 10 years were in the ballpark of 2% up to 3.9%, again, with only half picked up by upper tract imaging. This means that at best, we would pick up 2% at 10 years. In high-risk and very high-risk disease, we ended up at 6% at 10 years—a bit less, way less than what was expected to happen according to older studies, often from the 1990s. And half of them again, maybe a little bit more, were picked up by conventional serial imaging.

So, what do we conclude here? I think that for low-risk non–muscle-invasive bladder cancer, one has to seriously ask whether they need even any imaging. I think that it would even be a stretch that for intermediate-risk disease, maybe we could actually get rid of that or adjust the timing. For high risk, I would say that with a risk of around 6%, probably a lot of people will say—especially since these are high-grade when they come back—that it’s not unreasonable to continue to monitor. But high-risk disease is only 20% of the patients, so the large majority of the patients probably can be spared of unnecessary imaging.

What are the implications of these findings? What do they have on long-term surveillance?

I would anticipate that several guidelines will pay attention to a really large series with long follow-up, well annotated. It reinforces the AUA [and other] guidelines, with the fact that low risk basically should be waived.

I also think that we are at a time when we have shared decision-making with patients. One probably heard that there’s a paper showing some additional risk of cancer induced by radiation of X-rays. We have to consider whether we are not harming some patients with additional imaging for a very low yield.

Given the multi-institutional nature of the study, how robust are these findings and what future directions might be important?

I completely understand that these are not randomized studies. These are retrospective studies, with all the potential caveats of retrospective studies, and you can always control—some of the follow-ups are different between institutions and those kinds of things. I think what is very specific here is that we went into the nitty-gritty of the follow-up: what exams were performed, how much was picked up, and what was the grade and stage of the upper tract disease. I think we will now provide additional granular data compared with what was in the past. We should continue to challenge what we have learned in the past with contemporary data and look forward to improving the patient care.

REFERENCE:
Kwong J, Randhawa H, Pace K, et al. Metachronous upper tract urothelial following non-muscle invasive bladder cancer: A retrospective multi-institutional study. Presented at: 2025 AUA Annual Meeting; April 26-29, 2025; Las Vegas, NV.