Introduction:

The prognosis of non-muscle invasive bladder cancer (NMIBC) is largely dependent on tumor grade, as evidenced by differences in recurrence rates and time to progression. These differences by tumor grade have important implications for its management, which is reflected in the AUA Treatment Guideline and Risk Stratification for NMIBC. The most recent WHO classification of urothelial tumors continues to recommend grading non-invasive papillary urothelial carcinomas as low-grade or high-grade based on the highest grade identified. The current classification system, however, does not account for heterogeneous NMIBC composed of both low- and high-grade lesions not infrequently seen in clinical practice. We sought to compare the outcomes of mixed-grade bladder tumors based on varying degrees of high-grade predominance.

Methods:

We identified patients in the Columbia Urology Database who had a transurethral resection of bladder tumor(s) for pathologically confirmed NMIBC from 2008-2019. Patients whose pathology reports described specimens as having any amount of mixed high-grade and low-grade characteristics were identified. All mixed-grade tumors were reanalyzed by an expert GU pathologist and assigned the percentage high-grade component. Mixed-grade tumors were stratified into ≤ 5% high-grade and > 5% high-grade, based on previous literature. All other patients were classified as either having pure low-grade or high-grade tumors. Patients with carcinoma-in-situ tumors were excluded. We summarized descriptive data using medians and percentages. Differences in recurrence-free survival were assessed by log-rank test. A multivariable Cox regression model was used to evaluate the impact of tumor grade category on the likelihood of recurrence, controlling for tumor stage, immediate postoperative intravesical therapy (IVT), induction IVT, multifocality, and tumor size.

Results:

Two hundred and thirty-seven patients with NMIBC were followed for a median of 2 years. One hundred forty patients (59%) had pure low-grade disease, 66 patients (28%) had pure high-grade disease, and 31 patients (13%) had mixed-grade NMIBC. Among patients with mixed-grade cancer, tumors had percentage high-grade ranging from 1-80% of the specimen. Mixed-grade patients received induction IVT at lower rates than those with high-grade disease. However, there was little correlation between percentage high-grade and the administration of induction IVT among mixed-grade patients (r=0.02). Recurrence rates across all groups ranged from 45-76.5%. There was no significant difference in intravesical recurrence free survival among the grade categories as assessed by log-rank test (Figure 1, log-rank p=0.13). On multivariable Cox regression analysis (Table 1), grade category was not significantly associated with an increased likelihood of recurrence after adjusting for other clinicopathologic features.

Conclusion:

Mixed-grade histology is not an uncommon finding in NMIBC. We observed significant variability in use of induction IVT across patients with mixed-grade tumors. We did not observe that the percentage high-grade of mixed-grade tumors was an independent significant predictor of recurrence. However, the recurrence rate for mixed-grade tumors was quite high overall. Further studies are required to better understand appropriate risk stratification and treatment of mixed-grade NMIBC.

Funding: N/A