International validation of the Locally Recurrent Rectal Cancer-Quality of Life (LRRC-QoL) patient reported outcome measure.

Background: Locally recurrent rectal cancer (LRRC) occurs in 4-8% of patients following previous curative treatment. However, it has a significant impact on patients' clinical status and health-related quality of life (HrQoL). International collaboration has positively impacted clinical outcome reporting in this setting, however, has not extended to patient-reported outcomes such as HrQoL. Establishing an international measure of HrQoL for patients with LRRC is central to understanding its impact from a patient perspective. The LRRC-QoL measure of HrQoL in LRRC was developed and validated for use in the UK and Australia. The aim of this study was to externally validate the LRRC-QoL as an international measure of HrQoL in LRRC. Methods: Patients with LRRC undergoing treatment with both curative and palliative intent were recruited between 05/11/2020 and 04/12/2023 to a prospective, longitudinal cohort study of HrQoL in LRRC following cross-cultural adaptation in all participating countries. Scale structure was assessed through confirmatory factor analysis (CFA). Reliability was assessed using Cronbach's Alpha and Intraclass Correlation Coefficient (ICC). Convergent validity was assessed against EORTC QLQ-CR29, and FACT-C scales using Pearson's Correlation Coefficient (r). Known groups comparison was assessed through independent t-tests and ANOVA. Responsiveness was assessed through effect size (ES) and standardised response mean (SRM). The study was registered on the ISRCTN registry (reference: ISRCTN13692671). Findings: Overall, 321 patients were included in the validation of the LRRC-QoL from 14 countries. The LRRC-QoL scale structure demonstrated excellent goodness of fit. Most scales demonstrated good reliability, with Cronbach's Alpha and ICC values > 0.7. Convergent validity confirmed several hypothesised correlations. Known groups validity was demonstrated for gender, pattern of recurrence, pre-operative treatment, treatment intent, and presence of metastases. The LRRC-QoL demonstrated excellent responsiveness; patients undergoing surgery reported worse HrQoL at three (p < 0.0001, ES 0.57, SRM 0.50) and six months (p = 0.001, ES 0.37, SRM 1.11). Interpretation: The LRRC-QoL has demonstrated excellent psychometric properties in this international validation analysis and is now validated for use in 14 countries. Funding: Funding was provided by Bowel Research UK and Pelican Cancer Foundation.