PURPOSE Patients with Ta low-grade (LG) NMIBC rarely develop metastases or die of it. Long-term data are scant and length of follow-up poorly defined. MATERIALS AND METHODS 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 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. RESULTS 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 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 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. CONCLUSIONS 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.

中文翻译：

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低级别非肌层浸润性膀胱癌的长期复发风险、转移潜力和膀胱镜监测时间。


目的 Ta 低级别 （LG） NMIBC 患者很少发生转移或死于转移。长期数据很少，随访时间不明确。材料和方法 这项回顾性研究包括 521 年至 1989 年在学术中心诊断为原发性 TaLG NMIBC （n = 491） 或低恶性潜能状尿路上皮肿瘤 （n = 30） 的患者。使用中心的患者记录图表审查和膀胱癌信息学登记处获取患者数据。分析了 BC 导致的阶段复发和进展、肌肉浸润、转移和死亡的风险。RNAseq 评估了 4 个转移的 TaLG NMIBCs 的转录组谱。病理分级的观察者间变异性 （WHO 2004/2022 和 1973，n = 80） 由 3 位病理学家专家盲法评估。结果 中位随访时间为 9.6 （95% CI： 8.6-10.2） 年。在 521 例患者 （73% 为男性，中位年龄 67.0 岁） 中，350 例复发，57 例进展，20 例发生转移，15 例死于 BC （诊断后中位为 9.6 年）。5 年、 10 年和 15 年的癌症特异性生存概率分别为 0.99 、 0.98 和 0.96。50 例前 5 年无复发的患者出现晚期复发，其中 2 例死于 BC。转移性 TaLG NMIBC 具有更多与更高级别肿瘤一致的不良转录组学发现，尽管其表型与惰性肿瘤相似。2004/2022 系统和 WHO 1973 的分级一致性分别为 0.78 （95% CI： 0.65-0.90） 和 0.41 （95% CI： 0.32-0.50）。结论 这项研究具有长期数据，挑战了原发性 TaLG NMIBC 如果随访足够长，几乎永远不会发展为致命疾病的假设。 然而，在前 5 年无复发的患者中，BC 相关死亡的风险极低。最大限度地减少病理分级的可变性仍然是一个未满足的需求。