Patterns of progression in patients with synchronous oligometastatic non-small cell lung cancer after systemic and local radical treatment

Oligoprogressive disease (OPD) occurs when a limited number of disease sites show progression. Data on OPD incidence during systemic therapy for metastatic non-small cell lung cancer (NSCLC) are increasing, while data on progression patterns after systemic therapy with local radical treatment (LRT) in patients with synchronous oligometastatic disease (sOMD) are limited. We conducted a retrospective multicenter study to assess progression patterns, factors associated with progression and survival outcomes in sOMD NSCLC patients treated with systemic therapy and LRT. Between January 2015 and December 2022, 199 patients were included. With a median follow-up of 68.4 months, 78% experienced progression: 63% OPD and 37% widespread PD. Significant differences between OPD and widespread PD were found for performance status (62% WHO PS 0 vs 42%), tumor histology (squamous 13% vs 28%), KRAS mutation (36% vs 26%), N stage (N0-1 40% vs 21%), number (1 metastasis 72% vs 53%), and metastasis location. Patterns of PD were not associated with first-line therapy type (chemo-only vs immune checkpoint inhibitor [ICI]-based). Median PFS and OS were longer for OPD vs widespread PD: median PFS 10.5 (95% CI 8.9-12.1) vs 8.1 months (95% CI 7.7-8.6) (p < 0.001), median OS 30.9 (95% CI 23.0-38.9) vs 15.2 months (95% CI 11.4-18.9), p < 0.001. These findings suggest clinical and molecular features reflecting disease biology and may help identify patients likely to develop oligoprogression after combined therapy, a pattern associated with improved PFS and OS. Further prospective studies are needed to better predict progression and select patients benefiting from LRT.