Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States.
Division of Research, Kaiser Permanente Northern California, Oakland, CA, United States.
Am J Clin Nutr. 2023 Jun;117(6):1110-1120. doi: 10.1016/j.ajcnut.2023.04.006. Epub 2023 Apr 11.
High recurrence and progression rates are major clinical challenges for non-muscle-invasive bladder cancer (NMIBC). Dietary isothiocyanates (ITCs), phytochemicals primarily from cruciferous vegetables (CV), show strong anticancer activities in preclinical BC models, yet their effect on NMIBC prognosis remains unknown.
This study aimed to investigate the associations of dietary ITC exposure at diagnosis with NMIBC recurrence and progression.
The study analyzed 1143 participants from the Be-Well study, a prospective cohort of newly diagnosed NMIBC cases in 2015-2019 with no prior history of BC. Dietary ITC exposure was indicated by self-reported CV intake, estimated ITC intake, urinary metabolites, and plasma ITC-albumin adducts. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and progression, and unconditional logistic regression models were used to calculate odds ratios (ORs) and 95% CIs for delayed and multiple recurrence.
Over a mean follow-up of 25 mo, 347 (30%) developed recurrence and 77 (6.7%) had disease progression. Despite no significant associations with the overall risk of recurrence, urinary ITC metabolites (OR: 1.96; 95% CI: 1.01, 4.43) and dietary ITC intake (OR: 2.13; 95% CI: 1.03, 4.50) were associated with late recurrence after 12-mo postdiagnosis compared with before 12-mo postdiagnosis. Raw CV intake was associated with reduced odds of having ≥2 recurrences compared with having one (OR: 0.34; 95% CI: 0.16, 0.68). Higher plasma concentrations of ITC-albumin adducts were associated with a reduced risk of progression, including progression to muscle-invasive disease (for benzyl ITC, HR: 0.40; 95% CI: 0.17, 0.93; for phenethyl ITC, HR: 0.40; 95% CI: 0.19, 0.86).
Our findings indicate the possible beneficial role of dietary ITCs in NMIBC prognosis. Given the compelling preclinical evidence, increasing dietary ITC exposure with CV intake could be a promising strategy to attenuate recurrence and progression risks in patients with NMIBC.
非肌肉浸润性膀胱癌（NMIBC）的高复发和高进展率是临床面临的主要挑战。膳食异硫氰酸盐（ITC）是十字花科蔬菜（CV）中的主要植物化学物质，在膀胱癌的临床前模型中显示出强烈的抗癌活性，但它们对 NMIBC 预后的影响尚不清楚。
本研究旨在探讨诊断时的膳食 ITC 暴露与 NMIBC 复发和进展的关系。
该研究分析了 2015 年至 2019 年间新诊断为 NMIBC 病例且无膀胱癌既往史的 Be-Well 研究中的 1143 名参与者。膳食 ITC 暴露通过自我报告的 CV 摄入量、估计的 ITC 摄入量、尿代谢物和血浆 ITC-白蛋白加合物来指示。使用 Cox 比例风险回归模型计算复发和进展的风险比（HR）和 95%置信区间（CI），使用无条件逻辑回归模型计算延迟和多次复发的优势比（OR）和 95%CI。
在平均 25 个月的随访中，347 例（30%）发生复发，77 例（6.7%）发生疾病进展。尽管与复发的总体风险无显著关联，但与诊断后 12 个月前相比，尿 ITC 代谢物（OR：1.96；95%CI：1.01，4.43）和膳食 ITC 摄入量（OR：2.13；95%CI：1.03，4.50）与 12 个月后延迟复发相关。与发生一次复发相比，摄入未经加工的 CV 与发生≥2 次复发的几率降低相关（OR：0.34；95%CI：0.16，0.68）。较高的血浆 ITC-白蛋白加合物浓度与进展风险降低相关，包括进展为肌肉浸润性疾病（苯乙基 ITC：HR：0.40；95%CI：0.17，0.93；苯乙基 ITC：HR：0.40；95%CI：0.19，0.86）。
我们的研究结果表明，膳食 ITC 可能对 NMIBC 的预后具有有益作用。鉴于强有力的临床前证据，增加 CV 摄入量可能是一种有前途的策略，可以降低 NMIBC 患者的复发和进展风险。
