Long-term recurrence risk, metastatic potential and length of cystoscopic surveillance of low-grade non-muscle invasive bladder cancer

Patients with Ta low-grade (LG) nonmuscle-invasive bladder cancer (NMIBC) rarely develop metastases or die of it. Long-term data are scant and length of follow-up poorly defined. This retrospective study included 521 patients diagnosed with primary TaLG NMIBC (n = 491) or papillary urothelial neoplasm of low malignant potential (n = 30) from 1989 to 2019 at an academic center. Patient data were acquired using patient records chart review and a bladder cancer informatics registry at the center. Risk of recurrence and progression in stage to muscle invasion, metastases, and death due to bladder cancer (BC) were analyzed. RNAseq assessed the transcriptomic profiles of 4 TaLG NMIBCs that metastasized. Interobserver variability in pathological grading (WHO 2004/2022 and 1973, n = 80) was blindly assessed by 3 expert pathologists. The median follow-up was 9.6 (95% CI: 8.6-10.2) years. Among 521 patients (73% men, median age 67.0 years), 350 recurred, 57 progressed in stage, 20 developed metastases, and 15 died of BC (median 9.6 years after diagnosis). Cancer-specific survival probabilities were 0.99, 0.98, and 0.96 at 5, 10, and 15 years, respectively. Fifty patients who were recurrence free for the first 5 years developed late recurrences and 2 of them died of BC. Metastatic TaLG NMIBC had more adverse transcriptomic findings in keeping with higher-grade tumors despite being phenotypically similar to indolent tumors. Grading concordance for the 2004/2022 system and WHO 1973 was 0.78 (95% CI: 0.65-0.90) and 0.41 (95% CI: 0.32-0.50), respectively. This study with long-term data challenges the assumption that primary TaLG NMIBC nearly never progresses to lethal disease if followed long enough. However, the risk of BC-related mortality is extremely low in patients who are recurrence free for the first 5 years. Minimizing variability in pathological grading remains an unmet need.