When and How To Perform Active Surveillance for Low-risk Non–muscle-invasive Bladder Cancer - Roberto Contieri

June 1, 2023

Ashish Kamat hosts Roberto Contieri, who shares his work on active surveillance as a treatment approach for low-risk non-muscle-invasive bladder cancer. Highlighting that 75% of bladder cancer patients present with non-muscle-invasive disease, he explores the merits of a conservative approach, noting its cost-effectiveness, safety, and minimal surgical risk. Contieri presents findings from the BIAS project, a prospective active surveillance protocol, emphasizing promising results and discussing potential future directions. The discussion wraps up with the identification of optimal patient candidates and the importance of strict compliance to the active surveillance regimen. While Contieri asserts that randomized trials are needed for robust evidence, the conversation underscores active surveillance as a valuable treatment strategy, balancing patient well-being, medical costs, and oncological outcomes.


Roberto Contieri, MD, Humanitas University, Rozzano, Italy

Ashish Kamat, MD, MBBS, Professor, Department of Urology, Division of Surgery, University of Texas MD Anderson Cancer Center, President, International Bladder Cancer Group (IBCG), Houston, Texas

Read the Full Video Transcript

Ashish Kamat: Hello and welcome to UroToday's Bladder Cancer Center of Excellence. I'm Ashish Kamat, Professor of Urological Oncology at MD Anderson Cancer Center, and it's a pleasure to welcome today Dr. Roberto Contieri from Milan, Italy, who's here today to talk to us about his recent publication and work that he has done on active surveillance for low-risk non-muscle-invasive bladder cancer. Dr. Contieri is a 4th-year resident currently at the Humanitas University. He has spent some time with me here at MD Anderson and he's an up and coming rising star, and we look forward to your presentation, Roberto.

Roberto Contieri: Thank you so much for that kind introduction, Dr. Kamat, and thank you to UroToday for having me here today. It's a real pleasure to be here and to share this work, which was recently published in European Urology Focus. Essentially, our goal was to create a clinical guide based on published evidence that may provide essential information about active surveillance in low-grade non-muscle-invasive bladder cancer.

If we consider the broad field of oncology, it is widely accepted to employ watchful waiting or active surveillance in several low-risk conditions. This includes selected cases of low/intermediate-risk prostate cancer, as well as elderly patients with small renal tumors or well-selected cases of germ cell tumors. When discussing bladder cancer, it is important to note that, at presentation, approximately 75% of patients have non-muscle-invasive disease and about 50% of these cases are low grade. While these tumors are associated with the high recurrent rate, they typically have a low rate of grade and stage progression and a negligible cancer-specific survival rate.

Another consideration is that bladder cancer is recognized as one of the malignancies with the highest healthcare cost. This is particularly true for low-grade cases, where patients may undergo excessive testing and examination during the followup. A recent study by the [inaudible 00:02:06] group demonstrated that the cost of managing low-risk bladder cancer has nearly doubled over 10 years. Furthermore, the costs are even higher for patients who experience disease recurrence.

Although TUR is generally regarded as a minor surgical procedure, it is not free from risk, with complications occurring in around 5% of cases. In addition, we must also consider the anesthesiologic risk, especially in patients with multiple comorbidities, which is frequently the case for those diagnosed with bladder cancer.

Our ultimate goal is to achieve treatment intensification without compromising oncological outcome. Dr. Soloway was the first to propose a conservative approach in low-grade non-muscle-invasive bladder cancer patients almost 20 years ago. In 2003, emphasizing the statement, first of all, do no harm and avoid overtreatment, he proposed a surveillance protocol for these small bladder tumors as an alternative to TUR and fulguration. Finally, after 20 years, European guidelines have introduced active surveillance as one of the possible approaches for the management of low-grade recurrent Ta tumors. However, this indication is limited to patients for whom fulguration is not feasible.

Another interesting aspect to note is that the guidelines refer to presumed low-grade tumors. This raises an important question. Can we accurately predict that Ta low-grade tumor? A prospective study conducted in the UK with 240 patients sought to answer this question. The study found that cystoscopy alone was able to correctly predict the low-grade nature of 86% of the tumors without the support of urine cytology. I want also to focus on the point that, according to the new risk group of EAU, all recurrent low-grade tumors are classified at least as intermediate-risk tumors. In this regard, the International Bladder Cancer Group has recently proposed a new subclassification of recurrent low-grade tumors based on clinical factors that may be used to select the most appropriate treatment for each patients.

So far, several studies on active surveillance for bladder cancer have been published. However, the criteria for patients' inclusion and failure vary among different courts and follow up was not standardized. Some older series even included patients with high-grade tumors and carcinoma in situ. Nevertheless, the oncological outcome of these studies have been consistently favorable, with low rates of grade progression ranging from 10% to a maximum of 20%, and a very low rate of progression to muscle-invasive bladder cancer.

In 2013, we initiated the BIAS project that is a prospective active surveillance protocol at the Humanitas Institute in Milan. This protocol was specifically designed for patients with a history low-grade Ta or T1a tumors who have suspected recurrence during follow up cystoscopy. To be eligible for the protocol, patients should have five or fewer suspicious lesion, each with a maximum diameter or 1 centimeter and should not have gross hematuria or positive urinary cytology. Patients who develop any of the criteria during active surveillance should undergo active treatment with TUR. Active surveillance monitoring includes urine cytology and cystoscopy every 3 months for the first year and then every 6 months. However, the inclusion criteria and the follow-up scheme are based on expert opinions and still need validation.

In our most recent published cohort, 251 active surveillance events were enrolled. A total of 130 reached exit criteria and then underwent TUR after being monitored with active surveillance. We showed that the treatment-free probability was 60% at 12 months and 40% at 36 months. It should be noted also that the exit from active surveillance does not necessarily correspond to something negative. In fact, in 20% of the cases, patients were negative at histology and less than 10% had high-grade disease.

Also, among the various studies on active surveillance by our group, I want to quickly show you this one in which we analyzed the resources saved on average by the hospital for each TUR avoided, resources that can be relocated to other needs. We are also working on how to implement the follow-up of these patients. Expert bladder cancer monitor assay might be used with cytoscopy or as an alternative to cystoscopy to reduce the number of annual cystoscopies in the follow-up of active surveillance patients.

However, there is a clear need for further evidence regarding active surveillance. Among the various ongoing projects, one is aimed to validating collaboration with IBCG, the intermediate risk scoring system in an active surveillance cohort. Additionally, we are collecting data on the follow-up of patients who exit from active surveillance to evaluate the risk of recurrence and progression. However, only a randomized trial will provide the higher quality evidence to support the use of active surveillance.

In conclusion, we can affirm that active surveillance is a safe approach and it reduces the patient's anxiety related to surgery, it is related to a saving of researchers for the healthcare system, and furthermore, all the patients who meet the inclusion criteria can be enrolled, even those using anticoagulants, for example. It allows us to assess the morphological changes of the tumor and the speed at which they occur. However, attention must be paid to the following points. Optimal patient selection is crucial and should follow standardized approaches. Patient must be fully informed about active surveillance and the available alternatives, follow-up cystoscopy should be performed by an experienced urologist dedicated to bladder cancer, and strict compliance with the follow-up schedule is critical for ensuring safety and efficacy. Thank you very much.

Ashish Kamat: That was great, Roberto, and that was a nice overview of the data that you currently have when it comes to active surveillance. Now, obviously since you're still in training and you don't actually have any patients of your own, I'm not going to put you on the spot and ask any specific questions about your experience, but you have worked a lot on this topic, and of course you are in the process of looking at some of the IBCG risk classifications and seeing how we can optimally identify which patients might qualify or do best with active surveillance. Could you highlight some of those findings for our audience just briefly based on the literature work that you've done? Are there patients that you would recommend you consider for active surveillance over the others?

Roberto Contieri: Yes. What we have seen in our studies is that there are several risks that can affect the outcome of patients. By this I mean the time they are under active surveillance and the time they reach exit criteria once they are enrolled in these criteria. For example, we found that the number of previous TUR before active surveillance enrollment is related to active surveillance exit. Also, the time from the last TUR to active surveillance might be affected.

In fact, what we have done was to evaluate the clinical risk proposed by IBCG in our cohort, and we are working on this. We saw that, effectively, that clinical risk fit in our cohort, in particular the rate of recurrence and overall past recurrence, the ones that happen until 1 year after TUR may affect the inclusion in active surveillance. But I repeat, exit from active surveillance does not mean that the patient progressed to muscle invasive or upgraded or upstaged. It means just that it reached this exit criteria that were decided based on expert opinion. We still need to validate these criteria, actually.

Ashish Kamat: Right. And again, this is recapitulating the whole process of active surveillance when it came to prostate cancer, like you mentioned, and small renal masses. Initially, there was a lot of resistance, people were afraid, and clearly you need well-defined endpoints, because patient satisfaction, patient safety, patient's own sense of whether they are doing well on a particular program is important.

But for the urologist, it's very important that we exclude any potential high high-grade patients. So negative cytology for high-grade disease is very important. A prior history of absence of high-grade disease is, again, very important. And if you select the right patients, again, in my practice I have several patients who now are so comfortable with their active surveillance, have been watching this little tumor and the bladder for a while, that they are very relieved that they don't have to go to the operating room. Obviously with the improvement of office anesthesia, local sedation, and fulguration and laser, there's, in some centers, a push towards just fulgurating these in the clinic, which is another a very acceptable alternative to this option.

But Roberto, I want to thank you for all the work that you've done on this field and your interest in this and for your leadership on these projects. It was great to have you here today.

Roberto Contieri: It was my pleasure. Thank you very much.