Purpose: Patients with Ta low-grade (LG) non-muscle invasive bladder cancer (NMIBC) rarely develop metastases or die from it. Long-term data are scant and length of follow-up poorly defined.
Material and methods: This retrospective study included 521 patients diagnosed with primary TaLG (n=491) or papillary urothelial neoplasm of low malignant potential (PUNLMP, n=30) from 1989-2019 at an Academic center. Patient data was acquired using patient records chart review and a bladder cancer informatics registry at the center. Risk of recurrence, progression in stage, to muscle invasion, metastases and death due to BC were analyzed. RNAseq assessed the transcriptomic profiles of four TaLG that metastasized. Interobserver variability in pathological grading (WHO 2004/2022 and 1973, n=80) was blindly assessed by three expert pathologists.
Results: 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 from BC (median of 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 had more adverse transcriptomic findings in keeping with higher grade tumors despite 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.
Conclusion: 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.
Keywords: Bladder Cancer; Low Grade; Non-Muscle Invasive.