PURPOSE: Investigating the impact of circadian syndrome (CircS) on the prognosis of NMIBC, identifying potential indicators affecting prognosis, and explaining NMIBC prognosis from the perspective of circadian rhythm disruption to provide a preventable risk factor.
MATERIALS AND METHODS: A total of 438 patients with non-muscle-invasive bladder cancer (NMIBC) who received intravesical Bacillus Calmette-Guérin (BCG) immunotherapy after transurethral resection of bladder tumor (TURBT) were selected for retrospective analysis by retrieving medical records. The primary outcomes were recurrence-free survival (RFS) and progression-free survival (PFS). The secondary endpoints were safety parameters. Least absolute shrinkage and selection operator (LASSO) regression was used to screen variables for COX regression. Subgroup analysis and sensitivity analyses were used to validate the robustness of the results. Bootstrap and K-fold cross-validations were used to validate the robustness of the models. All adverse events (AEs) were further quantified for association strength using a logistic regression analysis.
RESULTS: This retrospective study screened 406 patients who met the inclusion criteria for further analysis. Survival analysis demonstrated significantly lower RFS in patients with CircS compared to the non-CircS cohort (Log-rank P = 0.018; HR = 1.58, 95% CI: 1.08-2.31). Multivariable analysis of LASSO-selected variables identified CircS (HR = 1.72, 95% CI: 1.09-2.73, P = 0.021), male gender (HR = 2.04, 95% CI: 1.12-3.72, P = 0.02), recurrence history (HR = 1.79, 95% CI: 1.17-2.73, P = 0.007), and tumor diameter >3 cm (HR = 1.88, 95% CI: 1.24-2.87, P = 0.003) as independent predictors of inferior RFS in NMIBC. Notably, elevated serum albumin levels exhibited protective effects (HR = 0.91, 95% CI: 0.85-0.98, P = 0.008). The prognostic significance of CircS remained robust across multiple RFS validation models, though no significant association was observed with PFS. In the analysis of AEs, patients with CircS showed significantly higher odds, such as lower urinary tract symptoms (LUTS) (OR = 1.64, 95% CI: 1.02-2.63, P = 0.041), hematuria (OR = 2.94, 95% CI: 1.55-5.50, P<0.001), dysuria (OR = 4.26, 95% CI: 1.67-11.08, P = 0.002), lower abdominal pain (OR = 4.28, 95% CI: 1.59-11.73, P = 0.004), fatigue (OR = 3.86, 95% CI: 1.60-9.34, P = 0.002) and arthralgia or flu-like symptoms (OR = 7.30, 95% CI: 1.40-53.31, P = 0.023).
CONCLUSION: CircS may serve as a potential risk factor affecting the prognosis of NMIBC, manifesting as worse RFS and AEs. Along with gender, tumor size, and recurrence history, it constitutes a high-risk factor for RFS. This finding provides clues for exploring potential causal relationships between clinical syndromes caused by circadian rhythm disruption and bladder tumor prognosis, while also reshaping the understanding of connections between chronic non-neoplastic diseases and neoplastic diseases.
