Prediction Models for Prognosis of Cervical Cancer: Systematic Review and Critical Appraisal

Abstract

Objective: This work aims to systematically identify, describe, and appraise all prognostic models for cervical cancer and provide a reference for clinical practice and future research. Methods: We systematically searched PubMed, EMBASE, and Cochrane library databases up to December 2020 and included studies developing, validating, or updating a prognostic model for cervical cancer. Two reviewers extracted information based on the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modeling Studies checklist and assessed the risk of bias using the Prediction model Risk Of Bias ASsessment Tool. Results: Fifty-six eligible articles were identified, describing the development of 77 prognostic models and 27 external validation efforts. The 77 prognostic models focused on three types of cervical cancer patients at different stages, i.e., patients with early-stage cervical cancer (n = 29; 38%), patients with locally advanced cervical cancer (n = 27; 35%), and all-stage cervical cancer patients (n = 21; 27%). Among the 77 models, the most frequently used predictors were lymph node status (n = 57; 74%), the International Federation of Gynecology and Obstetrics stage (n = 42; 55%), histological types (n = 38; 49%), and tumor size (n = 37; 48%). The number of models that applied internal validation, presented a full equation, and assessed model calibration was 52 (68%), 16 (21%), and 45 (58%), respectively. Twenty-four models were externally validated, among which three were validated twice. None of the models were assessed with an overall low risk of bias. The Prediction Model of Failure in Locally Advanced Cervical Cancer model was externally validated twice, with acceptable performance, and seemed to be the most reliable. Conclusions: Methodological details including internal validation, sample size, and handling of missing data need to be emphasized on, and external validation is needed to facilitate the application and generalization of models for cervical cancer.

Keywords: cervical cancer; prediction model; predictors; risk of bias; statistical analysis.

Figure 1

Flow chart of the literature search for prognostic models related to cervical cancer.

Figure 2

Thirteen most frequently used predictors in 77 prognostic models for the prognosis of cervical cancer patients presented by clinical stage. PI, parametrium invasion; LVSI, lymph vascular space invasion; DOI, depth of stromal invasion; BMI, body mass index. *p < 0.05.

Figure 3

Risk of bias assessment (using PROBAST) based on four domains across 77 prognostic model development studies related to cervical cancer (A) and across 27 external validation efforts of prognostic models related to cervical cancer (B).