All high-grade noninvasive bladder cancer should be regarded as high risk, study suggests
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Key takeaways:
- 13% of patients with high-grade, high-risk nonmuscle-invasive tumors did not respond to bacillus Calmette-Guérin therapy, compared with 14% of those with high-grade, intermediate-risk tumors and none of those with intermediate-risk, low-grade tumors.
- Researchers found no significant differences among risk groups with respect to OS, time to disease recurrence, time to disease progression or time to developing muscle-invasive/metastatic disease.
- Small changes in certain guidelines would lead to patients being classified more appropriately as high risk.
Patients who received treatment for high-grade nonmuscle-invasive bladder cancer had similar outcomes irrespective of European Association of Urology risk status, results of a retrospective study showed.
Investigators found similar nonresponse rates to induction therapy with bacillus Calmette-Guérin (BCG) among patients with high-grade tumors regardless of being categorized as having high-risk or intermediate-risk nonmuscle-invasive tumors.
The findings suggest certain clinical practice guidelines should be updated so that all patients with high-grade nonmuscle-invasive bladder cancer are classified as high risk, the researchers noted.
Background
Variations exist between European Association of Urology (EAU) and American Urological Association (AUA) guidelines for risk stratification of high-grade tumors.
The current risk stratification model puts patients at risk for undertreatment or incorrect treatment, according to Ashish M. Kamat, MD, MBBS, professor of urologic oncology and Wayne B. Duddlesten professor of cancer research at The University of Texas MD Anderson Cancer Center, and president of International Bladder Cancer Group.
“[Because] existing guidelines imply that some [high-grade nonmuscle-invasive] tumors be classified as intermediate-risk tumors, some patients might undergo inadequate treatment [that] would otherwise be adequate for intermediate-risk tumors that are low grade,” he told Healio.
As a result, Kamat said, his group’s study aimed to “improve risk stratification of patients to guide appropriate use of best therapy.”
Methodology
Kamat and colleges conducted a retrospective study of patients with nonmuscle-invasive bladder cancer who received “adequate” BCG treatment at MD Anderson Cancer Center between 2000 and 2018. The study included 49 patients (median age, 63 years; interquartile range, 58-70; 71% men) with low-grade nonmuscle-invasive tumors and 202 patients (median age, 69 years; interquartile range, 61-76; 81% men) with high-grade nonmuscle-invasive tumors.
The researchers defined adequate BCG as at least five of six induction instillations plus at least two additional instillations as part of either maintenance or reinduction therapy.
The investigators classified patients using prognostic risk groups outlined in 2021 EAU revised clinical practice guidelines. After risk stratification, they classified 16% of patients as having intermediate-risk, low-grade nonmuscle-invasive tumors, 40% as having intermediate-risk, high-grade tumors and 44% with high-grade, high-risk tumors.
Median follow-up was 47 months (interquartile range, 25–88).
Key findings
Researchers found that 13% of patients with high-grade, high-risk nonmuscle-invasive tumors did not respond to BCG therapy, compared with 14% of those with high-grade, intermediate-risk tumors and 0% of those with intermediate-risk, low-grade tumors (P = .003).
The investigators noted no significant differences among risk groups with respect to OS, time to disease recurrence, time to disease progression or time to developing muscle-invasive/metastatic disease.
No patients with low-grade, intermediate-risk tumors experienced disease progression. Additionally, researchers observed similar disease progression rates when comparing intermediate- vs. high-risk patients with high-grade noninvasive tumors — 13% of both high- and intermediate-risk patients progressed to T1 stage tumors. A total of 5.9% of high-risk patients progressed to stage T2 or higher compared with 6.5% of intermediate-risk patients.
Clinical implications
Current EUA and AUA guidelines attempt to “deintensify treatment,” Kristian S. Stensland, MD, MPH, a urologic oncology and health services research fellow in University of Michigan’s department of urology, and Harras B. Zaid, MD, a urologist at Urology Austin, wrote in an accompanying editorial. The EUA and AUA accomplish this deintensification by downgrading patients who may not benefit from maintenance BCG therapy based on several clinical factors, they noted.
“These data suggest that treatment deintensification for patients with high-grade tumors may be misguided,” they wrote. “In other words, all high-grade tumors may benefit from being treated as high-risk disease.
“While attempts at treatment deintensification should continue when possible, these data support a return to the risk stratification for nonmuscle-invasive bladder cancer, where high grade denotes high risk,” Stensland and Zaid added.
Kamat said the results have the potential to impact clinical practice because small changes in certain guidelines would lead to patients being classified more appropriately as high risk and receive appropriate treatment with BCG.
“This is already built into the EAU guidelines, which recommend BCG for intermediate-risk tumors but not specifically by the AUA guidelines,” he told Healio.
“Our data show that among patients treated with adequate BCG, rates of BCG unresponsiveness and progression were similar in all patients with [high-grade nonmuscle-invasive] tumors,” Kamat said. “[This suggests] that all [high-grade nonmuscle-invasive] tumors are at risk for progression and patients should be treated as high risk.”
References:
- Bree KK, et al. J Urology. 2022;doi:10.1097/JU.0000000000002678.
- Chang SS, et al. J Urology. 2016;doi:10.1016/j.juro.2016.06.049.
- European Association of Urology. EAU guidelines on non-muscle-invasive bladder cancer (TaT1 and CIS). Available at: uroweb.org/guidelines/non-muscle-invasive-bladder-cancer. Accessed July 30, 2022.
- Stensland KS, et al. J Urol. 2022;10.1097/JU.0000000000002678.01.
For more information:
Ashish M. Kamat, MD, MBBS, can be reached at Department of Urology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1373, Houston, TX 77030; email: akamat@mdanderson.org.
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