Consolidative thoracic radiotherapy after first-line chemoimmunotherapy in extensive-stage small-cell lung cancer: a multicenter retrospective study

Introduction

Extensive-stage small-cell lung cancer (ES-SCLC) is an aggressive malignancy with a historically poor prognosis. For decades, the standard first-line therapy was platinum-etoposide chemotherapy, yielding a median overall survival (mOS) of only 9–10 months (1-3). The integration of immune checkpoint inhibitors (ICIs) has fundamentally shifted this paradigm. Phase III trials such as IMpower133 (atezolizumab) and CASPIAN (durvalumab) established chemoimmunotherapy as the new global standard, with more recent trials like ASTRUM-005 pushing mOS to approximately 15 months (4-7).

Despite these advances, most patients progress within the first year, with the thorax being a predominant site of failure (6,8). While the survival benefit of consolidative thoracic radiotherapy (cTRT) in ES-SCLC is well-established in the chemotherapy-only era, which was demonstrated by the Jeremić trial and the pivotal phase III CREST trial (9,10), the treatment landscape has fundamentally shifted with the adoption of first-line chemotherapy combined with immunotherapy as the new global standard (4-7). The key point is that pivotal trials (such as IMpower133 and CASPIAN) establishing this new paradigm did not systematically incorporate cTRT (4,5). Consequently, as noted in the National Comprehensive Cancer Network (NCCN) Guidelines (Version 2, 2026), there is limited data on the optimal sequence, dosage, and safety of cTRT in patients who have undergone immunotherapy (11). The complex biological interactions between radiotherapy and ICIs, particularly regarding toxicities such as radiation pneumonitis, remain unclear. Consequently, the optimal role of cTRT in the era of immunotherapy remains undefined, and evidence from previous eras cannot be simply extrapolated. While small-scale studies show promise, questions persist about which patient subgroups benefit the most and how to balance efficacy with toxicity (12,13). This retrospective study therefore aims to evaluate the real-world efficacy and safety of cTRT in patients with ES-SCLC after initial chemotherapy combined with immunotherapy. Our findings seek to address these critical gaps and provide a reference for the design of future prospective trials. We present this article in accordance with the STROBE reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-1-0126/rc).

Methods

Study design

A retrospective, multicenter cohort analysis was conducted from West China Hospital of Sichuan University and Second People’s Hospital of Yibin. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Biomedical Ethics Committee of West China Hospital, Sichuan University (No. 2025-427) and the Institutional Review Board of the Second People’s Hospital of Yibin (No. 2022-173-01). Individual consent for this retrospective analysis was waived.

Patient selection

Eligibility was assessed in consecutive, treatment-naïve patients with a histological diagnosis of ES-SCLC according to the Veterans Administration (VA) Lung Study Group’s two-stage system, with staging further classified by the American Joint Committee on Cancer (AJCC) 8th edition. All patients had commenced first-line platinum-etoposide chemotherapy combined with an ICI at either West China Hospital (Jan 2019–Oct 2024) or the Second People’s Hospital of Yibin (Apr 2020–Aug 2024). To be included, patients must have been aged ≥18 years, received ≥2 cycles of induction therapy, attained disease control [complete response (CR), partial response (PR), or stable disease (SD)] by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, and had ≥1 baseline measurable lesion.

The following patients were excluded from the analysis: those with limited-stage or mixed-type SCLC; those who did not undergo the specified first-line chemoimmunotherapy or who progressed within the first two induction cycles; individuals with a history of other active malignancies (within 5 years) or a concurrent primary tumor; and those with incomplete baseline data or who were lost to follow-up within 3 months of treatment initiation. To minimize potential biases inherent in retrospective studies, we applied additional exclusion criteria based on methodological considerations. First, to eliminate immortal time bias and align with the landmark analysis framework, we excluded patients who died within 3 months after first-line chemoimmunotherapy initiation (the post-chemoimmunotherapy landmark cohort). This ensures that all included patients had an equal opportunity to receive cTRT and constitutes the primary analytical cohort for comparing cTRT vs. non-cTRT. Secondly, as a sensitivity analysis to assess the long-term benefits of cTRT in patients, we excluded patients who died within 2 months after initiating cTRT (post-treatment conditional analysis). Unlike the main post-chemoimmunotherapy analysis, it evaluates the efficacy of cTRT in patients who survived the early stages after radiotherapy, and supplements the main analysis by confirming that the observed survival benefits extend to patients with sufficient follow-up time. Third, to ensure timely administration of prophylactic cranial irradiation (PCI) consistent with clinical trial standards, we excluded patients with an interval >6 months between first-line chemoimmunotherapy initiation and PCI initiation.

Treatment exposure

Immunotherapy regimens were primarily based on programmed death-ligand 1 (PD-L1) inhibitors (atezolizumab 1,200 mg, durvalumab 1,500 mg, or adebrelimab 20 mg/kg) or the programmed death-1 (PD-1) inhibitor serplulimab (4.5 mg/kg). Other agents were used in a small number of cases contingent on drug access or clinical considerations. Patients demonstrating a response (CR or PR) or SD after induction chemoimmunotherapy were eligible for maintenance immunotherapy. This was administered at 3-week intervals until either disease progression or intolerable adverse events occurred.

cTRT was initiated following recovery from treatment-related toxicities, with timing varying relative to chemotherapy cycles based on individualized assessment. Radiotherapy techniques included intensity-modulated radiotherapy (IMRT), image-guided radiotherapy (IGRT), volumetric modulated arc therapy (VMAT), and stereotactic body radiotherapy (SBRT), mostly with IGRT; PCI, when administered, was typically delivered using three-dimensional conformal radiotherapy (3D-CRT). cTRT doses were individualized and adapted to patient-specific risk profiles, ranging from conventional fractionation to escalated regimens. Immunotherapy was suspended during radiotherapy and resumed one month later, pending confirmation of pulmonary safety. Baseline laboratory values (including complete blood count, biochemistry panels, etc) were defined as the most recent measurements obtained within the 2 weeks prior to treatment initiation.

Outcomes and assessments

The primary outcome was overall survival (OS), measured from the start of therapy until either death or the final assessment. Key secondary outcomes encompassed progression-free survival (PFS), defined as the duration until disease progression or death, along with the rate of thoracic relapse. Disease assessments followed RECIST v1.1 via serial imaging. Assessment frequency was every 6 weeks during induction, quarterly for 2 years, and biannually thereafter. Adverse events were classified using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Statistical analysis

All statistical analyses were performed using R software (version 4.5.2). Categorical variables and continuous variables that were categorized for analysis are presented as frequencies and percentages. Comparisons for these variables were performed using the Chi-squared test and Fisher’s exact test. To address the immortal time bias, we defined a primary landmark cohort by excluding patients who died within 3 months after first-line chemoradiotherapy, ensuring that all patients have an equal opportunity to receive cTRT. At the same time, we conducted a secondary post-treatment conditional analysis by excluding patients who died within 2 months after cTRT initiation to evaluate the long-term benefits of treatment tolerant individuals. Both OS and PFS were analyzed using the Kaplan-Meier method, and survival curves were compared with the log-rank test. Median follow-up was calculated with the inverse Kaplan-Meier method and survival distributions were estimated using the Kaplan-Meier method. Missing data were minimal (<5%) and handled by complete-case analysis; for propensity score matching (PSM), patients with missing covariates were excluded. Loss to follow-up was addressed by censoring at last contact. A two-step Cox regression approach was used: significant variables (P<0.05) from the univariable analysis were subsequently included in a multivariable model. To reduce selection bias, we performed 1:1 nearest-neighbor PSM (caliper 0.2) on key covariates, after which multivariable Cox regression was repeated. Time-dependent Cox regression (cTRT as a time-varying covariate) was conducted for OS to account for timing of treatment administration. To evaluate sensitivity to unmeasured confounding, an E-value analysis was applied (14). We tested for heterogeneous treatment effects via subgroup interaction analyses. Statistical significance was established using a two-sided threshold of P<0.05.

Results

Cohort characteristics

From January 2019 to December 2024, 838 consecutive patients with ES-SCLC from two medical centers in Southwest China (West China Hospital of Sichuan University and the Second People’s Hospital of Yibin) were initially screened. After applying the exclusion criteria outlined in Figure 1, including the exclusion of patients who died within 3 months after first-line chemoimmunotherapy initiation (the 3-month landmark analysis), a final cohort of 171 patients was formed for analysis, including 80 patients in the non-cTRT group and 91 patients in the cTRT group. Baseline characteristics were generally well-balanced between the two groups (Table 1). While some numerical differences were observed, most notably a higher proportion of M1 disease in the non-cTRT group (78.8% vs. 65.9%, P=0.09) and a trend toward more liver metastases (31.2% vs. 22.0%, P=0.23), the overall distribution of key prognostic factors was comparable. PCI use was 3.8% in the non-cTRT group vs. 9.9% in the cTRT group (P=0.21).

Figure 1 Patient selection flowchart. cTRT, consolidative thoracic radiotherapy; LS/M-SCLC, limited stage/mixed type small-cell lung cancer.

Survival analysis

The median follow-up time for the cohort was estimated to be 41.3 months [95% confidence interval (CI): 35.2–52.8]. At the final analysis (December 1, 2025), the overall cohort comprised 171 patients (80 non-cTRT, 91 cTRT). A total of 96 deaths (56.1%) and 139 progressive disease (PD) events (81.3%) were observed. The non-cTRT group experienced 37 deaths and 70 PD events, while the cTRT group had 59 deaths and 69 PD events. The median OS for the entire cohort was 12.3 months (95% CI: 11.1–13.7). In the cTRT group, median OS reached 13.4 months (95% CI: 12.6–15.6), demonstrating a significant improvement compared with the median OS of 9.9 months (95% CI: 7.6–13.3) observed in the non-cTRT group (log-rank P<0.001). The adjusted hazard ratio (HR) with 95% CI was 0.37 (95% CI: 0.15–0.91, P=0.03). The corresponding 1- and 2-year OS rates were 65.5% (95% CI: 54.0–79.3%) and 12.7% (95% CI: 6.4–25.4%) in the cTRT group vs. 37.5% (95% CI: 25.1–55.9%) and not reached in the non-cTRT group, respectively. The addition of cTRT was also associated with a significant improvement in PFS (adjusted HR: 0.22, 95% CI: 0.11–0.43; P<0.001), evidenced by a median PFS of 9.2 months (cTRT) vs. 7.2 months (non-cTRT). The corresponding survival curves are shown in Figure 2. Detailed univariable and multivariable analyses for both OS and PFS are provided in Table 2.

Figure 2 Kaplan-Meier survival analysis (pre-PSM and post-PSM). (A) OS (pre-PSM). (B) PFS (pre-PSM). (C) OS (post-PSM). (D) PFS (post-PSM). CI, confidence interval; cTRT, consolidative thoracic radiotherapy; HR, hazard ratio; OS, overall survival; PFS, progression-free survival; PSM, propensity score matching.

Independent prognostic factors

The multivariate Cox regression analysis identified multiple independent prognostic factors for OS and PFS in the primary cohort (based on the 3-month post-chemoimmunotherapy landmark analysis), as detailed in Table 2. For OS, cTRT (HR 0.37, 95% CI: 0.15–0.91, P=0.03) and an increased number of immunotherapy cycles (HR per cycle 0.86, 95% CI: 0.75–0.99, P=0.04) were independently associated with improved survival, while advanced T stage (T3–4 vs. T1–2, HR 3.30, 95% CI: 1.01–10.78, P=0.048) remained a significant negative prognostic factor after adjustment. After PSM, cTRT remained significantly associated with OS (HR 0.30, 95% CI: 0.11–0.84, P=0.02), while brain metastasis emerged as an independent adverse prognostic factor (HR 3.71, 95% CI: 1.06–13.03, P=0.04).

For PFS, cTRT showed strong independent protective effects before PSM (HR 0.22, 95% CI: 0.11–0.43, P<0.001) and after PSM (HR 0.51, 95% CI: 0.34–0.77, P=0.001). The number of immunomaintenance therapy cycles (HR 0.85, 95% CI: 0.77–0.95, P=0.003) and multiple immune therapy drugs (such as serplulimab, durvalumab, and adebrelimab vs. atezolizumab) were also independently associated with PFS improvement. Bone metastasis was identified as an independent risk factor for PFS after matching (HR 2.01, 95% CI: 1.24–3.26, P=0.005).

Additionally, we employed restricted cubic spline (RCS) regression to explore the potential nonlinear relationship between continuous variables and survival outcomes. In the Pre-PSM cohort, granulocyte-to-lymphocyte ratio (GLR) demonstrated a significant nonlinear association with OS (nonlinear P=0.007; overall P=0.02), with an estimated turning point of approximately 2.95 (Figure S1), indicating that GLR exerted a protective effect when above 2.95 and a risk effect when below this threshold. For PFS, no significant overall or nonlinear association was observed. After PSM, the nonlinear relationship between GLR and OS weakened (nonlinear P=0.06; overall P=0.12), while PFS remained nonsignificant (Figure S2). These findings suggest that the observed nonlinear association may be partially influenced by baseline confounding factors. Detailed RCS results for other continuous variables are provided in the Supplementary Data Set (available online: https://cdn.amegroups.cn/static/public/tlcr-2026-1-0126-1.pdf).

Exploratory subgroup analyses

Exploratory subgroup analyses for OS and PFS are presented in Figure 3 and Table S1 respectively. The survival benefit of cTRT was consistently observed across most predefined subgroups. Notably, liver metastasis and drinking status significantly influenced PFS efficacy (P for interaction <0.05), while the number of chemotherapy cycles significantly influenced OS efficacy (P for interaction =0.042), suggesting these factors may serve as important basis for treatment stratification. Specifically, cTRT demonstrated greater efficacy in patients without liver metastasis, those who did not drink, and those who received ≤4 cycles of chemotherapy.

Figure 3 Subgroup analysis and interaction analyses on OS. AJCC, American Joint Committee on Cancer; BMI, body mass index; CI, confidence interval; CR, complete response; cTRT, consolidative thoracic radiotherapy; HR, hazard ratio; M, metastasis; N, node; OS, overall survival; PR, partial response; PS, performance status; SD, stable disease; T, tumor; y, years old.

Of note, we further explored the association of radiotherapy parameters with survival outcomes. Within the cTRT cohort, univariate analysis showed that standard-dose definitive radiotherapy (~60 Gy/30 f) was associated with improved OS (median 17.6 vs. 11.3 months; HR 0.48, 95% CI: 0.24–0.95, P=0.03) and PFS (median 14.4 vs. 8.4 months; HR 0.43, 95% CI: 0.23–0.81, P=0.009) compared to lower-dose regimens (≤30 Gy/≤10 f). After multivariable adjustment, the PFS benefit remained independent (HR 0.45, 95% CI: 0.22–0.89, P=0.02), while the OS effect was no longer significant. In terms of safety, higher radiation doses are associated with higher incidence of radiation-related pneumonia and esophagitis. Specifically, the standard-dose definitive group showed higher toxicity (pneumonitis: 16.7% grade I/II, 8.3% grade III/IV; esophagitis: 20.8% grade I/II, 4.2% grade III/IV) compared to the palliative/low-dose (≤30 Gy/≤10 f) group, which had minimal toxicity (pneumonitis: 2.9% grade I/II, 2.9% grade III/IV; esophagitis: 5.7% grade I/II, no grade III/IV). Detailed toxicity data for different dose groups and fractionation schemes can be found in Tables S2,S3.

Sensitivity analysis

To address potential immortal time bias, selection bias, and unmeasured confounding factors, we conducted a series of preset sensitivity analyses, including landmark analysis, time-dependent Cox regression analyses, PSM, and E-value analysis. During PSM, 45 patients were excluded due to missing key covariates or lack of suitable matches, reducing the analytical sample from 171 to 126 patients (63 per group).

In the primary 3-month post-chemoimmunotherapy landmark analysis, cTRT was significantly associated with OS improvement in all models: original multivariate Cox (HR 0.37, 95% CI: 0.15–0.91, P=0.03), post-PSM multivariate Cox (HR 0.30, 95% CI: 0.11–0.84, P=0.02), and time-dependent Cox (HR 0.26, 95% CI: 0.09–0.73, P=0.01) (Table 3). In the secondary post-cTRT landmark analysis, cTRT also demonstrated consistent survival benefits: original multivariate Cox (HR 0.36, 95% CI: 0.14–0.90, P=0.03), post-PSM (HR 0.26, 95% CI: 0.09–0.75, P=0.01), and time-dependent Cox (HR 0.24, 95% CI: 0.07–0.77, P=0.02). The E-values for all significant associations on OS ranged from 4.85 to 7.80 (Table 3), indicating that the observed treatment effects are highly robust to potential unmeasured confounding.

Parallel findings were observed for PFS. In the primary landmark cohort, cTRT remained independently associated with improved PFS in both multivariable Cox (HR 0.22, 95% CI: 0.11–0.43, P<0.001) and post-PSM analyses (HR 0.51, 95% CI: 0.34–0.77, P=0.001) (Table 2). Similarly, in the post-cTRT landmark cohort, cTRT significantly improved PFS in all models (multivariable Cox: HR 0.20, 95% CI: 0.10–0.40, P<0.001; post-PSM: HR 0.22, 95% CI: 0.10–0.47, P<0.001) (Table S4 and Figure S1). Detailed univariate and multivariate analyses for the post-cTRT landmark cohort, including PSM adjustment, are provided in Table S4. Collectively, these sensitivity analyses confirm that the survival advantage associated with cTRT is not driven by immortal time bias, selection bias, or unmeasured confounding.

Disease progression patterns

Analysis of the first site of disease progression after first-line chemoimmunotherapy showed comparable objective response rates between the cTRT (84.6%) and non-cTRT (88.8%) groups. Patients who received cTRT had a numerically lower incidence of thoracic relapse as the first site of progression (20.2% vs. 34.3%). Distant metastasis remained the predominant pattern of treatment failure, with no significant difference in the overall distribution of initial distant relapse sites. Among patients with documented relapse, brain relapse was the most common first distant site in both cohorts, followed by liver metastasis. At data cutoff, 27.4% of cTRT patients and 17.9% of non-cTRT patients remained event-free or were lost to follow-up (Table S5).

Adverse events

The spectrum and severity of treatment-related adverse events are detailed in Table 4. The overall safety profile of the chemoimmunotherapy regimen, with or without cTRT, was manageable. Hematological toxicity was the most common adverse effect. In cTRT and non-cTRT groups, anemia occurred in 35.2% vs. 36.3%, with grade III/IV events in 2.2% vs. 3.8%. Decreased white blood cell count occurred in 40.7% vs. 37.4%, with Grade III/IV events in 6.6% vs. 11.2%. Neutropenia occurred in 40.7% vs. 26.2%. Thrombocytopenia occurred in 16.5% vs. 27.5%. Radiotherapy-specific toxicities, including radiation pneumonitis and esophagitis, were confined to the cTRT arm and were predominantly low-grade. For non-radiation toxicities, Grade I–II events like abnormal liver function and pulmonary infection were numerically more frequent in the cTRT group, whereas abnormal coagulation showed the opposite trend. Regarding immune-related adverse events (irAEs), most low-grade toxicities such as pneumonitis, thyroiditis, and rash were observed more frequently in the cTRT group. Grade III–IV irAEs were generally uncommon in both arms.

Discussion

In this study, the results showed the survival benefit of cTRT, a principle established by chemotherapy era trials such as CREST, which was preserved in ES-SCLC patients receiving modern first-line chemoimmunotherapy treatment. By evaluating a cohort uniformly treated with this new standard of care, our study provides contemporary real-world data and fills the knowledge gap left unanswered by key immunotherapy trials. We acknowledge that cTRT is already an established standard of care in the chemotherapy-only era based on the CREST trial (10). Our study does not claim to overturn this paradigm, but rather extends these observations into the immunotherapy era, where prospective data remain limited.

These findings are corroborated by a recent large-scale meta-analysis (including 20 studies and over 5,000 patients), which reported that cTRT significantly improves OS (effect size 0.57) and PFS (effect size 0.53) in ES-SCLC (15). Consistent with our findings, a recent large multicenter retrospective study also confirmed that patients with ES-SCLC receiving cTRT after first-line chemoimmunotherapy demonstrated significantly improved thoracic control rates. However, after PSM analysis, the survival benefit of cTRT was diminished, with neither PFS nor OS reaching statistical significance, highlighting the impact of baseline prognostic factors such as liver metastasis (16). In contrast, our study consistently observed sustained survival benefits across multiple sensitivity analyses, which may be attributed to differences in patient selection, radiotherapy techniques, or statistical power. These convergent yet not entirely consistent findings highlight the need for prospective randomized trials to definitively establish the role of cTRT in the immunotherapy era.

By focusing on cohorts receiving first-line chemoimmunotherapy treatment, this study provides several observational findings relevant to current literature: firstly, it supports the survival advantage associated with cTRT remains undiminished when combined with immunotherapy, enhancing its potential role in contemporary treatment paradigms. Secondly, it provides real-world safety data on the combination, particularly regarding irAEs and radiation pneumonitis, addressing a key consideration in clinical practice. Thirdly, in exploratory analysis, standard-dose definitive radiotherapy was independently associated with improved PFS in the cTRT subgroup compared with palliative/low-dose (≤30 Gy/≤10 f) group, while the OS benefit was not sustained after multivariable adjustment, suggesting potential impact on intrathoracic control. Fourth, we identified GLR as an independent prognostic factor in ES-SCLC patients receiving chemoimmunotherapy. RCS analysis revealed a nonlinear relationship between GLR and OS, with an inflection point of approximately 2.95. Patients with GLR above this threshold exhibited better survival outcomes, suggesting that GLR can serve as a potential biomarker for risk stratification in this treatment context.

Despite the survival benefit achieved with contemporary ICI-based combinations as initial systemic therapy for ES-SCLC, disease progression within the chest remains a predominant challenge (4,17). Consistent with this, our exploratory analysis suggests that higher doses of cTRT may help improve intrathoracic control. However, when analyzing treatment failure modes, although our study observed a trend toward reduced thoracic relapse with cTRT, metastasis remained the predominant form of failure, and distant recurrence most frequently involved the brain. This pattern is congruent with long-term data from major Phase III trials, emphasizing that while improving local control is necessary, it is insufficient alone. The high incidence of brain failure highlights the imperative to integrate more effective systemic agents and brain-directed prophylactic strategies into future treatment paradigms (18,19).

Safety, particularly the risk of pneumonitis, is a paramount concern. In our cohort, the incidence of any-grade radiation pneumonitis was 14.3%, aligning with the manageable toxicity reported in several studies (20,21). However, a higher incidence was reported in another real-world analysis, underscoring that toxicity is influenced by multiple factors including dosimetry and patient selection (22). The generally acceptable safety profile reported in retrospective series requires definitive validation in prospective trials.

This persistent challenge underscores the unmet need that cTRT may address. The biological rationale for combining radiotherapy with immunotherapy is compelling. Radiotherapy can remodel the tumor immune microenvironment, induce immunogenic cell death, and promote systemic anti-tumor immunity effects that may synergize with ICIs (23). However, this interaction is complex. While radiotherapy recruits immune cells to the tumor microenvironment, it may also deplete these effector cells or induce immunosuppressive pathways when administered after immunotherapy (24-26). Therefore, an important unresolved biological issue is the optimal sequence of cTRT relative to immunotherapy. Some preclinical and clinical data also yield conflicting results (27), and no prospective trials have directly compared different sequences in ES-SCLC (13,28). Our data provide real-world evidence that administering cTRT following chemoimmunotherapy is feasible and associated with improved survival, although this does not prove that this sequence is optimal.

Several limitations should be acknowledged. Notably, the retrospective design carries risks of selection bias and unmeasured confounding, while missing data and the modest sample size may affect the external validity of our findings. Even with multivariable adjustment for known confounders, the impact of unmeasured factors remains possible. To mitigate these concerns, we performed PSM, time-dependent Cox regression, and E-value analyses, all of which yielded consistent results and support the robustness of our findings. In addition, the ES-SCLC population defined by the Veterans Administration (VA) staging system exhibits inherent heterogeneity, as this system classifies some patients as extensive-stage based on extensive intrathoracic lesions rather than distant metastases. This discrepancy between the VA and AJCC staging systems, where such patients would be categorized as stage III (M0) under AJCC, may contribute to variations in treatment outcomes (11). Hence, prospective validation is needed. Ongoing trials, including SAKK 15/19 (NCT04472949) and NRG-LU007 (NCT04402788), are assessing the integration of cTRT into initial therapy, and their findings are expected to clarify its optimal use (21,29).

Conclusions

In conclusion, this real-world multicenter analysis confirms that patients with ES-SCLC derive significant survival benefits and acceptable toxicity from cTRT, which enhances both local control and long-term outcomes (OS and PFS). The dominant pattern of treatment failure remains distant metastasis, particularly to the brain. These findings support the integration of effective local consolidation with optimized systemic and brain-directed strategies in the modern treatment paradigm, guided where possible by prognostic biomarkers for refined patient selection.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-1-0126/rc

Data Sharing Statement: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-1-0126/dss

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-1-0126/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-1-0126/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Biomedical Ethics Committee of West China Hospital, Sichuan University (No. 2025-427) and the Institutional Review Board of the Second People’s Hospital of Yibin (No. 2022-173-01). Individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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