Definitive Radiotherapy to the Primary Tumor in Stage IV NSCLC: A Consensus Statement From the International...

The role of radiotherapy (RT) in stage IV NSCLC has traditionally been palliative; however, with advancements in systemic therapies and insights into the evolutionary processes underpinning advanced disease, the rationale for aggressive primary-tumor control has received renewed interest. This International Association for the Study of Lung Cancer (IASLC) consensus statement evaluates the current evidence for the role, timing, dosing, target volumes, and safety of primary-tumor RT in both actionable genomic alterations (AGA) and non-AGA metastatic NSCLC populations. The IASLC Advanced Radiation Technology subcommittee convened a multidisciplinary, international expert panel including radiation oncologists and medical oncologists from the IASLC Multidisciplinary Clinical Sciences Committee. Randomized studies published from 2010 to 2025 evaluating RT to the primary lung tumor in metastatic NSCLC populations (AGA and non-AGA) were identified through PubMed, and relevant published and presented abstracts were included. Evidence was synthesized and discussed to achieve consensus recommendations. In EGFR-mutant oligometastatic NSCLC, randomized phase III evidence supports early delivery of RT, conveyed as consolidation after induction systemic therapy, as a promising life-prolonging approach. In non-AGA populations, direct randomized evidence isolating the impact of primary irradiation remains limited. Emerging randomized data suggest dose escalation of definitive thoracic RT regimens may improve locoregional control compared with lower-dose approaches. Fractionation should be individualized to the primary tumor location to mitigate cardiopulmonary adverse events. Optimal target volumes remain uncertain, and the benefit of excluding involved thoracic lymph nodes has not yet been formally investigated in large, randomized trials. Safety data indicate toxicity is generally additive when RT is integrated with systemic agents; however, careful monitoring and recording of adverse events are important to ensure the addition of RT does not affect systemic therapy discontinuation rates. Definitive-dose RT to the primary lung tumor in metastatic NSCLC is supported by a growing biologic rationale and emerging trial data, with the strongest evidence in EGFR mutant populations. For patients without AGAs, preliminary findings are encouraging but insufficient for definitive treatment recommendations. The paucity of data necessitates prospective trials that isolate the contribution of primary-tumor RT, confirm its safety, and define the optimal RT sequencing, dose, and target volumes.