External evaluation of the Manchester score in a contemporary SCLC cohort

The Manchester Score, a prognostic model developed in 1987, was used to stratify patients with Small Cell Lung Cancer (SCLC) by mortality risk, including stage, performance status, and three blood tests as risk factors. Many tools have since been developed for this purpose, but few have seen clinical use, with lack of robust external validation frequently cited as a barrier. In this study we apply a robust and pragmatic external validation approach to the Manchester Score to understand if it remains valid in an unselected modern patient cohort.

SCLC patients treated in an academic centre between 2013 and 2022 (N = 1783) were included in the validation cohort. Discrimination was assessed using Kaplan-Meier curves, AUC, and Harrell's C-index for the Manchester score and its underlying Cox model. Three levels of Cox model updating were used to address missing baseline hazard data: recalibration, recalibration with rescaling, and model refitting. Calibration was then evaluated with optimism adjustment at 6-, 12-, and 24-months post-diagnosis.

The Manchester score shows good discrimination in the modern patient cohort. There is clear separation between risk groups in the Kaplan-Meier curves, with AUC = 0.75 and C-index = 0.68 for the Manchester Score and (AUC = 0.79, C-index = 0.70) for the underlying Cox model. Median survival in the 'good' prognostic group (meeting < 2/5 risk criteria) has increased compared to that from 1987. All model updating methods reported good calibration, with recalibration alone providing the best observed-to-expected ratio at 6 months (1.012 [0.978,1.045]).

The original Manchester Score prognostic groups remain discriminative of survival, and when updated can predict survival probability at multiple timepoints.