DISCUSSION
heterogeneous malignancy, bladder cancer
SOLID TUMORS, BLADDER CANCER
Despite improvement in diagnosis and surgery, bladder cancer remains a heterogeneous malignancy with poor prognosis.Considering this situation, several modified LN status factors has been proposed to predict the survival of BC, including PLN, LNR and LODDS.The N classification of AJCC staging system evaluates LN status mainly by detecting in certain regional areas, which was unsatisfactory due to the unclear number of negative and removed LNs.The current study suggested that the prognostic models with LODDS had best predictive capability for OS and CSS, which was similar to Jin et al.'s study for OS of BC patients. However, we paid more attention to clinical utilization and constructed two novel nomograms incorporating LODDS for predicting OS and CSS of BC patients for the first time. Then, the nomograms were further validated in internal and external validation cohorts. The calibration curves showed stable linearity and appropriate efficacy of the nomograms, and the calculated C‐indexes and time‐dependent AUCs were most above 0.70 and 0.75 in three cohorts, respectively. In terms of clinical utility, the DCA curves demonstrated that the nomogram showed consistent larger net benefit across a broad range of threshold probabilities. We believed that the nomograms had satisfactory applicability in predicting survival for BC patients. Taken together, better predictive accuracy and clinical validity were verified in our nomograms compared with AJCC and other LN status systems.Furthermore, risk classifiers for OS and CSS were established on basis of the total scores from nomograms, stratifying BC patients into different risk groups. Patients in two high‐risk groups had worse survival in each cohort. We subsequently explored the biological function between the two groups. The results showed that there were major differences in immunoglobulin production and secretion, ECM organization, epithelial mesenchymal transition, adipogenesis and DNA reparation. It has been reported that the immunoglobulin, produced by B lymphocytes and plasma cells in response to immunogen, was associated with the prognosis in solid tumors.Indeed, as a retrospective study, we need prospective and multicenter study to verify the prognostic value of LODDS. Secondly, the details of surgical approach, such as the extent of LN dissection at specific nodal level are not recorded in detail, which is worth further investigation. Despite these limitations, our study proves better predictive value of LODDS and firstly incorporates it into prognostic nomograms for both OS and CSS in BC patients.