Predictors of Early Polymetastatic Relapse Following Stereotactic Ablative Radiotherapy for up to 5 Oligometastases: A Secondary Analysis of the Phase II SABR-5 Trial

Abstract

<h3>Purpose/Objective(s)</h3> A subset of patients with oligometastatic cancer experience early widespread cancer dissemination and do not benefit from metastasis-directed therapy such as stereotactic ablative radiotherapy (SABR). This study aimed to identify factors associated with early polymetastatic relapse (PMR). <h3>Materials/Methods</h3> The SABR-5 trial was a single arm phase II study conducted at all 6 regional cancer centers across British Columbia. SABR for oligometastases was only offered on trial. Patients with up to 5 oligometastatic lesions (total, progressing or induced) received SABR to all lesions. Patients were 18 years of age or older, ECOG 0-2 and life expectancy ≥ 6 months. This secondary analysis evaluated factors associated with early PMR, defined as disease recurrence within 6 months of SABR which is not amenable to further local treatment. Univariable and multivariable analyses were performed using binary logistic regression. The Kaplan Meier method and log-rank tests assessed PMR-free survival and differences between risk groups, respectively. <h3>Results</h3> Between November 2016 and July 2020, 381 patients underwent treatment on SABR-5. 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 only 10% received SABR to 3 or more lesions. Oligoprogression represented 16% of cases. A total of 16% of patients experienced PMR. Worse performance status (ECOG 1-2 vs 0; HR=2.01, p=0.018), non-prostate/breast histology (HR 3.64, p<0.001) and oligoprogression (HR=3.84, p<0.001) were independent predictors for early PMR. Risk groups were identified with median PMR-free survival ranging from 5 months to not yet reached at the time of analysis. Rates of 3-year OS were 0%, 53% (SE=5%), 77% (SE=4%) and 93% (SE=3%) in groups 1-4, respectively (p<0.001). <h3>Conclusion</h3> Four distinct risk groups for early PMR are identified, which differ significantly in PMR-free survival and overall survival. The group with all three risk factors had a median PMR-free survival of 5 months and may not benefit from local ablative therapy alone. This model should be externally validated with data from other prospective trials.