Oligometastatic non-small-cell lung cancer (OMD-NSCLC) has emerged as a biologically and clinically distinct subtype of advanced disease, characterized by limited metastatic burden and a more indolent course. In this narrative review, we examine the current definition of OMD-NSCLC, diagnostic tests, possible biomarkers, and current therapeutic strategies. Biological insights highlight the role of microRNAs in differentiating true oligometastatic state from polymetastatic disease. The main local ablative therapies (LAT) include surgery and radiotherapy. The integration of LAT with systemic therapies has been explored in clinical trials, yielding promising but occasionally inconsistent results. As the therapeutic landscape of OMD-NSCLC patients continues to evolve, refining definitions, identifying predictive biomarkers, and individualizing care are essential steps toward achieving the potential of radical-intent therapy.

Purpose: NGS tissue testing is recommended in advanced biliary tract cancers (aBTC) due to increasing approval of targeted therapies. However, tissue NGS is frequently limited by poor access and insufficient tumor. We exploited ctDNA as an alternative for molecular profiling in aBTC. Methods: We retrospectively analyzed 10,937 patients with aBTC to characterize the molecular landscape and assess the clinical validity of ctDNA profiling. In a second retrospective cohort of 126 pts from nine Spanish referral centers with available clinical and tumor tissue annotations, paired tissue and ctDNA NGS testing and turnaround time (TAT), were evaluated. Blood samples were analyzed using a comprehensive ctDNA NGS assay (Guardant Health). Genomic alterations (GA) were classified according to ESCAT. Results: In the global cohort, ctDNA-NGS revealed a molecular landscape comparable to tissue-based sequencing, including detection rates of ESCAT actionable GA. Higher ctDNA burden was associated with worse overall survival (27.7 months (95%CI 24.1–33.8) in undetectable ctDNA, 18.5 months (95%CI 16.7–20.2) in low ctDNA burden, and 13.6 months (95%CI 12.5–15.0) in high ctDNA burden; log-rank p< 0.0001). In the independent cohort, ctDNA-NGS was available in 90% of patients versus 50% for tissue NGS. Overall concordance for ESCAT GA was 83%, including 80% for FGFR2 fusions. Median TAT was shorter for ctDNA than tissue (8 vs. 27 days). Survival appeared longer in the small subset receiving ESCAT-matched therapy. Conclusions: In this retrospective analysis, ctDNA represents a practical alternative to tumor tissue for NGS-based biomarker testing in aBTC, offering improved access and faster results.

Background/Objectives: Anti–PD-1/PD-L1 blockers have revolutionized the treatment landscape of non–small cell lung cancer (NSCLC) lacking oncogene-addicted alterations, particularly in tumors with high PD-L1 expression (tumor proportion score [TPS] ≥ 50%). Cemiplimab is approved as first-line monotherapy in this setting. However, real-world data remain scarce. This study aimed to evaluate the efficacy and safety of single-agent cemiplimab in a multicenter Spanish cohort and compare outcomes with a historical pembrolizumab cohort. Methods: Cemi-SPA is a retrospective multicenter study including 150 patients with advanced NSCLC and PD-L1 ≥ 50% treated with cemiplimab as first-line monotherapy across 21 Spanish centers. Clinical outcomes were analyzed and compared with a historical cohort of 144 patients treated with pembrolizumab. Propensity score matching (PSM) was performed to adjust for baseline differences. Results: Median progression-free survival (PFS) and overall survival (OS) were 8.1 and 12.6 months, respectively. ECOG performance status ≥ 2 was independently associated with worse outcomes, whereas the development of immune-related adverse events correlated with improved PFS and OS. After PSM, no significant differences were observed between cemiplimab and pembrolizumab in terms of efficacy. Conclusions: Cemiplimab demonstrated comparable real-world efficacy and safety to pembrolizumab in patients with advanced NSCLC and PD-L1 ≥ 50%. ECOG performance status emerged as the strongest prognostic factor, highlighting the importance of patient selection in routine clinical practice.

Kaplan-Meier survivl estimates according to tumor tissue heterogeneity in 64 patients with aBTC

CtDN to track tumor response in selected patients treated with matched targeted therapy.

Kaplan-Meier survival estimates according to ctDNA burden and to ctDNA heterogeneity in 126 patients with aBTC