Developing and validating a prognostic nomogram for ovarian clear cell carcinoma patients: A retrospective comparison of lymph node staging schemes with competing risk analysis

Abstract

Purpose: Lymph node (LN) involvement is a key factor in ovarian clear cell carcinoma (OCCC) although, there several indicators can be used to define prognosis. This study examines the prognostic performances of each indicator for OCCC patients by comparing the number of lymph nodes examined (TNLE), the number of positive lymph nodes (PLN), lymph node ratio (LNR), and log odds of metastatic lymph nodes (LODDS).

Methods: 1,300 OCCC patients who underwent lymphadenectomy between 2004 and 2015 were extracted from the Surveillance Epidemiology and End Results (SEER) database. Primary outcomes were Overall Survival (OS) and the cumulative incidence of Cancer-Specific Survival (CSS). Kaplan-Meier's and Fine-Gray's tests were implemented to assess OS and CSS rates. After conducting multivariate analysis, nomograms using OS and CSS were constructed based upon an improved LN system. Each nomograms' performance was assessed using Receiver Operating Characteristics (ROC) curves, calibration curves, and the C-index which were compared to traditional cancer staging systems.

Results: Multivariate Cox's regression analysis was used to assess prognostic factors for OS, including age, T stage, M stage, SEER stage, and LODDS. To account for the CSS endpoint, a proportional subdistribution hazard model was implemented which suggested that the T stage, M stage, SEER stage, and LNR are all significant. This enabled us to develop a LODDS-based nomogram for OS and a LNR-based nomogram for CSS. C-indexes for both the OS and CSS nomograms were higher than the traditional American Joint Committee on Cancer (AJCC), 8th edition, staging system. Area Under the Curve (AUC) values for predicting 3- and 5-year OS and CSS between nomograms also highlighted an improvement upon the AJCC staging system. Calibration curves also performed with consistency, which was verified using a validation cohort.

Conclusions: LODDS and LNR may be better predictors than N stage, TNLE, and PLNs. For OCCC patients, both the LODDS-based and LNR-based nomograms performed better than the AJCC staging system at predicting OS and CSS. However, further large sample, real-world studies are necessary to validate the assertion.

Keywords: competing risk model; lymph node staging; nomogram; ovarian clear cell carcinoma; prognosis.

Figure 1

Kaplan–Meier curves for overall survival with cumulative incidence curves for cancer-specific deaths, stratified by lymph node staging schemes: (A, B) LODDS; (C, D) LNR; (E, F) TNLE; (G, H) N stage.

Figure 2

Correlation analysis of: (A) Survival time and continuous LODDS; (B) Survival time and continuous LNR; (C–F) LODDS with age at diagnosis, T stage, M stage, and SEER stage; (G–I) LNR with T stage, M stage and SEER stage. (ns, P>0.05; *P < 0.05; **P < 0.01; and ****P < 0.0001).

Figure 3

Nomogram testing of: (A) Overall survival; (B) CSS nomogram at predicting 3- and 5-year survival; (C, D) 3- and 5-year survival curves for OS; (E, F) ROC analysis of age, T stage, M stage, SEER stage and LODDS for OS; (G, H) 3- and 5-year calibration curves for predicting CSS; (I, J) ROC analysis of stage, M stage, SEER stage and LNR for CSS.

Figure 4

Internal validation cohort analysis of; (A, C) 3- and 5-year calibration curves of OS predictions; (B, D) 3- and 5-year ROC analysis of age, T stage, M stage and LODDS for OS; (E, G) 3- and 5-year calibration curves of CSS predictions; (F, H) ROC analysis of age, T stage, M stage, Seer stage and LNR for CSS.