The Cancer of the Bladder Risk Assessment (COBRA) score accurately predicts cancer-specific survival after radical cystectomy: external validation and lymphovascular invasion assessment value to improve its performance

The Cancer of the Bladder Risk Assessment (COBRA) score is a predictive tool for estimating Cancer Specific Survival (CSS) after Radical Cystectomy (RC) for urothelial carcinoma. COBRA score variables are: age at RC, Tumor stage and Lymph Node Density (LND). We sought to externally validate the COBRA score and to improve its performance in estimating CSS adding Lymphovascular Invasion (LVI) as a further variable (Modified COBRA score). Clinicopathological and survival data from 789 patients who underwent RC and Pelvic Lymph Node Dissection (PLND) between January 2007 and December 2020 in two European referral centers (Paris, France and Badalona, Spain) were analyzed. COBRA score was applied to our cohort and CSS Kaplan-Meier curves were performed. Univariable and Multivariable analysis was performed in order to identify risk factors for Cancer Specific Mortality (CSM) and a score was assigned for any statistically significant risk factor; afterward, c-index calculation was performed and CCS curves have been plotted for the model after having integrated LVI variable to the COBRA score. Finally, we compared both COBRA score and Modified COBRA score models with the established AJCC model. A total of 789 patients underwent RC during the observation period. Complete data were available for 731 patients with a median follow-up of 32 months (8-47). CSM was 27.6% (no. 218 patients) at follow-up. When COBRA score was applied to our cohort, c-index was 0.76. Regression COX analysis has shown HR 0.36, CI 95% (0.16-0.83), P = .016 for patients with COBRA score 1; HR 0, CI 95% (0-1.77), P =.94 for score 2; HR 0.51, CI 95% (0.39 -0.67), P =.001 for score 3; HR 1.67, CI 95% (1.23-2.27), P =.001 for score 4; HR 2.45, CI 95% (1.51-3.99), P =.001 for score 5; HR 2.01, CI 95% (1.42-2.85), P =.001 for score 6 and HR 0.66, CI 95% (0.09-4.73), P =.682 for score 7. When the LVI variable was added to the CSS predictive model the discriminatory power increased to a c-index of 0.78. COBRA score adequately identifies those patients with a higher risk of CSM, with a c-index of 0.76. Moreover, LVI variable further improves its predictive accuracy from c-index of 0.76 to c-index of 0.78. LVI variable could be integrated in the COBRA score to optimizing prognosis stratification for patients who undergo RC.