Survival outcome prediction in cervical cancer: Cox models vs deep-learning model

Abstract

Background: Historically, the Cox proportional hazard regression model has been the mainstay for survival analyses in oncologic research. The Cox proportional hazard regression model generally is used based on an assumption of linear association. However, it is likely that, in reality, there are many clinicopathologic features that exhibit a nonlinear association in biomedicine.

Objective: The purpose of this study was to compare the deep-learning neural network model and the Cox proportional hazard regression model in the prediction of survival in women with cervical cancer.

Study design: This was a retrospective pilot study of consecutive cases of newly diagnosed stage I-IV cervical cancer from 2000-2014. A total of 40 features that included patient demographics, vital signs, laboratory test results, tumor characteristics, and treatment types were assessed for analysis and grouped into 3 feature sets. The deep-learning neural network model was compared with the Cox proportional hazard regression model and 3 other survival analysis models for progression-free survival and overall survival. Mean absolute error and concordance index were used to assess the performance of these 5 models.

Results: There were 768 women included in the analysis. The median age was 49 years, and the majority were Hispanic (71.7%). The majority of tumors were squamous (75.3%) and stage I (48.7%). The median follow-up time was 40.2 months; there were 241 events for recurrence and progression and 170 deaths during the follow-up period. The deep-learning model showed promising results in the prediction of progression-free survival when compared with the Cox proportional hazard regression model (mean absolute error, 29.3 vs 316.2). The deep-learning model also outperformed all the other models, including the Cox proportional hazard regression model, for overall survival (mean absolute error, Cox proportional hazard regression vs deep-learning, 43.6 vs 30.7). The performance of the deep-learning model further improved when more features were included (concordance index for progression-free survival: 0.695 for 20 features, 0.787 for 36 features, and 0.795 for 40 features). There were 10 features for progression-free survival and 3 features for overall survival that demonstrated significance only in the deep-learning model, but not in the Cox proportional hazard regression model. There were no features for progression-free survival and 3 features for overall survival that demonstrated significance only in the Cox proportional hazard regression model, but not in the deep-learning model.

Conclusion: Our study suggests that the deep-learning neural network model may be a useful analytic tool for survival prediction in women with cervical cancer because it exhibited superior performance compared with the Cox proportional hazard regression model. This novel analytic approach may provide clinicians with meaningful survival information that potentially could be integrated into treatment decision-making and planning. Further validation studies are necessary to support this pilot study.

Keywords: Cox proportional hazard; cervical cancer; deep learning; survival prediction.