Dr Federico Monaca, (The Christie NHS Foundation Trust, UK) discusses new insights into consolidative thoracic radiotherapy (cTRT) following first-line chemo-immunotherapy in extensive-stage small cell lung cancer (ES-SCLC). Results of his multicentre analysis of 336 patients that were presented at the IASLC World Conference on Lung Cancer 2025, showed cTRT improved intrathoracic control, particularly at higher doses and in those without liver metastases, though survival benefits remain uncertain. Dr Monaca highlights the need for randomized data to clarify safety, dose and patient selection, while also reflecting on the most promising advances presented at WCLC 2025, from DLL3-targeted therapies to novel immunotherapy combinations in lung cancer.
Q1. What are the benefits and potential risks of cTRT after chemoimmunotherapy in ES-SCLC?
Consolidative thoracic radiotherapy (cTRT) after first-line chemo-immunotherapy improves intrathoracic control. In our multicentric study, which included 336 patients, cTRT reduced intrathoracic progression from 57.8% to 40.5% (p=0.003), with only 24.1% of thoracic failures occurring in-field, suggesting effective local control. Survival signals favoured cTRT on univariable analysis, but the effect attenuated after multivariable adjustment and propensity matching. Signals of benefit appeared stronger with ≥45 Gy and in patients without liver metastases. Risks are largely theoretical in this context: treatment-related lymphopenia may blunt immunotherapy, and the TREASURE study’s early closure for fatal events underscores the need for prospective safety data and careful selection. Overall, cTRT offers better chest control with uncertain survival magnitude.
Q2. What was the methodology and design of your retrospective analysis?
We retrospectively reviewed consecutive ES-SCLC patients treated with first-line platinum–etoposide plus a PD-L1 inhibitor (atezolizumab or durvalumab) across four European centres between January 2020 and January 2024. Of 336 eligible patients, 111 received cTRT. Primary endpoint was intrathoracic control, while secondary endpoints were PFS and OS. Because proportional-hazards assumptions were sometimes violated, we prespecified restricted mean survival time alongside Cox models. To mitigate confounding, we performed 1:1 propensity-score matching (gender, ECOG, liver/CNS metastases, age, PCI), achieving excellent balance. Median follow-up for censored patients was 31.3 months. Radiotherapy technique/dose followed institutional protocols; most received 30 Gy/10 fractions, with a subset ≥45 Gy.
Q3. Please summarize your main findings, and what conclusions can be drawn from the data, especially in terms of safety and toxicity?
cTRT significantly lowered intrathoracic recurrence (40.5% vs 57.8%; p=0.003); only 24.1% of thoracic failures were in-field. Survival trends favoured cTRT (univariable OS HR 0.68, PFS HR 0.72), but after multivariable adjustment the effect was not statistically significant (OS HR 0.82; PFS HR 0.89). Exploratory analyses suggested greater benefit with higher doses (≥45 Gy) and absence of liver metastases. Consolidative radiotherapy enhances locoregional control and may help selected patients, but the survival benefit remains uncertain and should be clarified in randomised trials with robust safety and quality-of-life endpoints.
Q4. What questions remain unanswered in this area and are there any further investigations planned?
Open questions include who benefits most, the optimal dose/fractionation, and timing relative to immunotherapy. Robust toxicity/QoL data and biomarkers are needed to investigate lymphopenia risk. Randomised evidence is pending (e.g., RAPTOR testing consolidative radiation with maintenance immunotherapy), while TREASURE closed early for safety, highlighting why prospectively adjudicated toxicity is essential. Our next project will retrospectively assess toxicity and patient-reported outcomes in this cohort to inform selection and future trial design.
Q5. Please summarize your highlights and key, most exciting data and presentations from the WCLC 2025 conference
Beyond FLAURA2, several pipelines look practice-shaping. The DLL3-TOP1 ADC SHR-4849 showed clear early activity in relapsed SCLC with manageable haematological toxicity, enough signal to justify rapid expansion. In first-line maintenance ES-SCLC, tarlatamab + anti-PD-L1 delivered a strong objective response rate with durable disease control; cytokine-release events were mostly low-grade and tended to taper, suggesting the regimen can be learned and safely managed in routine practice. For ICI-refractory NSCLC, intratumoral CAN-2409 produced unexpectedly long survivals alongside immune activation, keeping oncolytic-style strategies firmly in play. Finally, the MTA-cooperative PRMT5 inhibitor BMS-986504 achieved meaningful, durable responses in MTAP-deleted NSCLC, including post-TKI EGFR/ALK, pointing to a new, biomarker-driven option in an area with few effective therapies.
About Federico Monaca
Dr Federico Monaca graduated in 2012 from Università Cattolica del Sacro Cuore, Rome, Italy and completed his residency at Fondazione Policlinico Universitario A. Gemelli, Rome, Italy with top honours, earning full marks cum laude. Currently, he serves as a Senior Clinical Research Fellow at The Christie NHS Foundation Trust, UK where he leads clinical and translational research projects focused on identifying predictive factors of response in extensive-stage small cell lung cancer. He is also a PhD candidate, focusing his research in exploring the role of cancer stem cells in lung cancer in the neoadjuvant setting. He has authored over 25 publications, including abstracts and peer-reviewed papers, and has contributed as a sub-investigator to more than 40 clinical trials.
Disclosure: Federico Monaca has no financial or non-financial conflicts of interest to declare in relation to this article.
Cite: WCLC 2025 highlights: Consolidative thoracic radiotherapy in ES-SCLC. touchONCOLOGY. September 18th, 2025
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