Validation of the Prognostic Utility of ESTRO/EORTC Oligometastatic Disease Classification: A Secondary Analysis from the Population-Based Phase II SABR-5 Trial

Abstract

<h3>Purpose/Objective(s)</h3> The recently developed ESTRO/EORTC oligometastatic disease (OMD) classification has not been validated in terms of its prognostic significance. This study stratified patients from the phase II SABR-5 trial based on ESTRO/EORTC criteria, and compared progression-free survival (PFS) and overall survival (OS) to determine the prognostic significance of the classification scheme. <h3>Materials/Methods</h3> The SABR-5 trial was a single arm phase II study conducted at the 6 regional cancer centers across British Columbia, where SABR for oligometastases was only offered on trial. Patients with up to 5 oligometastases (total or not controlled by prior treatment, and including induced oligometastatic disease) underwent SABR to all lesions. Patients were 18 years of age or older, ECOG 0-2, and life expectancy ≥ 6 months. PFS and OS were calculated using the Kaplan-Meier method and differences between OMD groups were assessed with log-rank tests. Univariable and multivariable analyses were performed using Cox regression modelling. <h3>Results</h3> Between November 2016 and July 2020, 381 patients underwent SABR on trial. Prostate was the most frequent primary tumor histology (32%), followed by colorectal (17%) and breast (11%). Most patients (69%) underwent SABR to one metastasis and 10% received SABR to 3 or more lesions. Median follow-up was 27 months (IQR 18–36). The most frequent OMD group was de-novo oligometastatic disease (69%), followed by repeat (16%) and induced (13%). In total, 62 patients received SABR to oligoprogressive lesions. OMD groups differed significantly in PFS (p<0.001) but not OS (p=0.069). The OMD classification was an independent predictor of both PFS (p=0.005) and OS (p=0.002). Of the five classification factors, only chronicity (synchronous, HR=0.54, p=0.027) and oligoprogression (HR=2.05, p=0.004) were independently prognostic for OS. Classifying OMD states by only these two factors resulted in a 3 groups (synchronous, oligorecurrence/oligopersistence and oligoprogression) with more statistically significant differences in OS and PFS. <h3>Conclusion</h3> In this large prospective cohort, the EORTC/ESTRO classification was an independent predictor of PFS and OS and should be used to identify specific patient groups for clinical trials. In this cohort, the prognostic power is largely attributable to chronicity and oligoprogression. Simplification of the framework may be possible in the future and allow for greater ease-of-use, however, further data on underrepresented histologies and OMD groups will be required.