Low-Intensity Surveillance Demonstrates Utility in NMIBC

Low-intensity surveillance may be comparable to high-intensity surveillance for cancer control in patients with high-risk non-muscle invasive bladder cancer (NMIBC). Results presented as part of the virtual science sessions of the 2020 American Urological Association (AUA) Annual Meeting demonstrated that patients who had low-intensity cystoscopy surveillance underwent fewer transurethral resections but did not experience an increased risk of progression or bladder cancer death compared with those who had high-intensity surveillance.^1,2

In an analysis of 1542 veterans diagnosed with high-risk NMIBC, patients who underwent low-intensity surveillance (33.7%; n = 520) were found to have almost 3-times fewer transurethral resections than those with high-intensity surveillance (37 vs 99 per 100 person-years, respectively; P <.001). Similarly, low-intensity surveillance patients underwent approximately 3-times fewer resections with cancer in the specimen (28 vs 77 per 100 person-years, P <.001), and 2-times fewer resections without cancer in the specimen (7.5 vs 16 per 100 person-years; P <.001).

“Low-intensity surveillance was associated with fewer transurethral resections or fewer times going into the bladder to remove or scrape these tumors and we found no increased risk in bladder cancer death whether [a patient] underwent low- or high-intensity cystoscopy surveillance of high-risk bladder cancer,” said Michael E. Rezaee, MD, MPH, lead author and urology resident at Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, during the virtual presentation.

Despite noting that low-intensity surveillance may be a reasonable option for high-risk muscle-invasive bladder cancer, Rezaee concluded that there is a need for “a trial to assess whether decreasing surveillance frequency in high-risk disease is actually safe.”

Stratified results showed that among a subset of patients with a baseline diagnosis of Ta disease, low-intensity surveillance was associated with a decreased risk of progression to invasive disease (T1 or T2) or bladder cancer death (cumulative incidence, 19.3% vs 31.3% at 5 years; P = .002). Similarly, the patients with non-invasive disease who underwent fewer cystoscopies did not have an increased risk of death (5.7% vs 8.2% at 5 years; P = .24).²

NMIBC accounts for 70% to 80% of new bladder cancer diagnoses and high-risk NMIBC lesions (high-grade Ta and T1 disease) have an 80% risk of recurrence 5 years following treatment and a 50% risk of progression.^1,2 Patients who receive a diagnosis of high-risk NMIBC first undergo a transurethral resection or endoscopic scraping of their bladder tumor to remove the tumor from the bladder wall. Once the tumor has been removed patients then have to undergo a series of procedures where a cystoscope is inserted through the urethra and then into the bladder to examine if there is any evidence of the tumor coming back or any progression of the tumors.

The hypothesis-emerging findings provide rationale for clinical trial designs aimed at challenging the current, expert opinion standard of care. “According to AUA, the current recommendation of cystoscopy or looking at the bladder should happen every 3 to 4 months for the first 2 years after diagnosis of high-risk bladder cancer,”³ Rezaee said. “However, this recommendation is based on expert opinion and minimal scientific evidence, so there is not a lot of research supporting this AUA recommendation. For us this raised the question of whether this level of intensity or frequency of looking into the bladder is actually necessary for high-risk non-muscle invasive bladder cancer.”

The retrospective cohort study reviewed the association of low-intensity surveillance cystoscopies (1 to 5 procedures) versus high-intensity cystoscopies (≥6 procedures) with frequency of transurethral resections, as well as risk of progression and bladder cancer death of 1542 patients from the Department of Veterans Affairs who received a diagnosis of high-risk NMIBC between 2005 and 2011 with follow-up care through 2014. Intensity was defined according to the number of procedures received over a 2-year surveillance window. The primary outcome was progression to fatal bladder cancer at 5 years.²

Noting the limitations of the study, Rezaee said that despite the strength of the sample size, there were unmeasured patient and provider characteristics that could not be accounted for in the study despite rigorous analysis. “This is an observational study with both unobserved and unmeasured confounding [factors]. Therefore, it is really difficult for us to understand why some high-risk patients underwent low-intensity surveillance in the first place when they should have been undergoing high-intensity surveillance.”

The surveillance window was 21.5 months to 24.0 months for 458 patients who underwent low-intensity surveillance (88.1%) compared to 365 patients who underwent high-intensity surveillance (35.7%; P <.001). A lower proportion of patients in the low-intensity cohort experienced a recurrence at 2 years (13.3%) versus those in the high-intensity cohort (64.1%). The median number of cystoscopies for patients who underwent low and high-intensity surveillance over at least 21.5 months was 4 and 7, respectively.²

The Future of Surveillance and COVID-19 Data

The authors concluded that the study provides a strong rationale for a future randomized trial to assess whether low-intensity surveillance of patients with high-risk NMIBC is comparable to high-intensity surveillance in terms of cancer control and should not guide current clinical practice. “We cannot say that performing less surveillance for high-risk disease can be recommended at this time,” Rezaee said. “This is not the study design nor the type of platform to make that recommendation.”

The discussion turned to how the coronavirus disease 2019 (COVID-19) pandemic might potentially impact the field as the experience of having to delay cystoscopies could provide real-world evidence of what would happen if cystoscopies are performed less frequently than usual.

“I think there is a lot of impact from COVID-19 not even necessarily just relating to surveillance cystoscopy but urology surgeries and procedures in general,” Rezaee said. “I would not be surprised to learn that there have been some delays especially for [patients] who have low-risk disease, but I think that could be some real-world data that could potentially be worth harvesting…The implications of that data wouldn’t be known for a few years.”

Senior author, Florian Schroeck, MD, MS, added, “We’re always looking for natural experiments so that we can get rid of some of the confounding that is often in the data…COVID-19 is an opportunity for such a natural experiment, likely starting in March in 2020, there [potentially may be] a huge drop in the number of cystoscopies, there might be none for a period of time that is likely still ongoing and will hopefully end soon. I agree that moving forward there might be an opportunity to use that data to see how [it] applies to all of the cancer care that we are currently doing and see how much of an impact it has on cancer outcomes.” Schroeck is an associate professor at The Dartmouth Institute for Health Policy and Clinical Practice.

References

1. Rezaee ME. The impact of low- vs. high-intensity surveillance cystoscopy on surgical care and cancer outcomes in patients with high-risk non-muscle-invasive bladder cancer. Presented at: American Urological Association 2020 Virtual Science Session; May 15, 2020.
2. Rezaee ME, Lynch KE, Li Z, et al. The impact of low- versus high-intensity surveillance cystoscopy on surgical care and cancer outcomes in patients with high-risk non-muscle-invasive bladder cancer (NMIBC). PLoS ONE. 15(3):e0230417. doi:10.1371/journal.pone.0230417
3. Chang SS, Boorjian SA, Chou R, et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J Urol. 2016;196(4):1021-9. doi:10.1016/j.juro.2016.06.049