Effect of neoadjuvant vs. adjuvant systemic therapy on survival in patients with surgical resected limited stage small-cell lung cancer: a real-world retrospective cohort study from SEER database

Introduction

Small cell lung cancer (SCLC) is a highly aggressive malignancy characterized by rapid progression and early metastasis (1). Despite its relatively low incidence compared to non-small cell lung cancer (NSCLC), SCLC remains one of the most lethal cancers worldwide, with a 5-year survival rate of less than 7% (2). Over the last decades, the combination of chemotherapy and radiotherapy has been the standard treatment for SCLC, providing short-term efficacy but rapidly developing resistance (3).

Accumulating studies have highlighted that surgical resection conferred greater survival benefits to SCLC patients compared to non-surgical treatment (4-7). For instance, several cohort studies have consistently reported improved survival outcomes in patients with limited stage SCLC who underwent surgical resection in contrast to chemoradiotherapy (5,6). A real world study utilizing propensity score matching (PSM) also revealed that stage III SCLC patients achieved prolonged overall survival (OS) and lung cancer-specific survival (LCSS) following surgical resection (7). Although these evidences mainly derived from retrospective cohort studies, they are grounded in the era of refined thoracic surgical techniques and standardized systemic therapy protocols, necessitating rigorous reevaluation of surgery as primary treatment strategy for limited stage SCLC.

Recently, immune checkpoint inhibitors have shown remarkable potential in both extensive and limited stage SCLC as evidenced by several phase III clinical trials such as IMPOWER133 (8), CASPIAN (9), ASTRUM-005 (10), and ADRIATIC (11) studies. However, the role of perioperative immunotherapy in surgical resected SCLC is unexplored. On the other hand, neoadjuvant chemoimmunotherapy has become the standard approach for stage II–III NSCLC without EGFR mutation or ALK rearrangement (12,13). Whether immunotherapy combined with chemotherapy can achieve the same significant neoadjuvant therapeutic effects in limited stage SCLC remains unknown. Some small-sample phase II trials, such as NeoSCI and NIUS, reported notable pathological responses [61.5% pathological complete response (pCR), 92.3% major pathological response (MPR)] with neoadjuvant chemoimmunotherapy in stage I–III SCLC (14,15). The results indicated that with the rapid development of perioperative systemic therapy protocols, surgery may play an important role in multimodality treatment of limited stage SCLC patients, even for those with locally advanced disease. However, the clinical significance of these surrogate pathological endpoints remains unvalidated due to the lack of mature survival outcomes.

Here, we conducted a cohort study to describe the perioperative systemic treatment modality for limited stage SCLC in the real world, trying to investigate whether neoadjuvant therapy could bring survival benefits for SCLC patients who underwent surgical resection of primary tumor. We present this article in accordance with the STROBE reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-457/rc).

Methods

Study cohort

We used the National Cancer Institute SEER*Stat version 8.4.4 (www.seer.cancer.gov/seerstat) to select patients from the Incidence-Surveillance, Epidemiology, and End Results (SEER) Research Data, 17 Registries (2000–2021) based on the November 2023 submission, which covers approximately 26.5% of the U.S. population. Histological subtypes were coded using the third version of the International Classification of Disease for Oncology (ICD-O-3) (16). Cases diagnosed as primary malignant (Behavior code ICD-O-3: “Malignant”) SCLC (Histology code ICD-O-3: “8041-8045”) of lung and bronchus (Site recode ICD-O-3/WHO 2008 = “Lung and Bronchus”) were included in initial eligibility screening process.

Among these cases, 4,606 patients underwent surgery of primary site were included in the study. Cases were excluded if (I) stage was unknown or had stage IV disease after modifying the 6^th or 7^th American Joint Committee on Cancer (AJCC) tumor node metastasis classification (TNM) staging system into the 8^th edition; (II) absence of pathological diagnostic confirmation; (III) local tumor destruction or excision was performed (surgery codes: 12–19); (IV) sequencing of systemic therapy and surgical procedure was unknown; and (V) underlying cause of death was unknown. Finally, we used the item “SYSTEMIC/SUR SEQ” to identify patients who underwent different types of perioperative systemic treatment modality: (I) no systemic therapy; (II) systemic therapy after surgery (adjuvant therapy); and (III) systemic therapy before surgery or systemic therapy both before and after surgery (neoadjuvant therapy).

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. All data in the SEER database was de-identified, and no patient had the risk of personal information leakage. Thus, the requirement of informed consent and ethical approval of the study was exempted from the institutional review board of Peking University People’s Hospital.

Covariables and endpoint

Baseline clinicopathological characteristics were extracted from the SEER database. The covariables included age, sex, year of diagnosis, race, tumor grade, surgical procedure, radiation therapy, T/N descriptors, and the 8^th edition of AJCC TNM stage. The year of diagnosis was categorized into 2007–2010, 2011–2015, and 2016–2021. Surgery of primary site was classified according to the SEER Surgery Codes of Lung: (I) sublobar resection: wedge or segmental resection, including lingulectomy (codes: 20–25); (II) lobectomy: lobe, bilobectomy or pneumonectomy (codes: 30–66); and (III) not otherwise specified (NOS): resection of lung, NOS (code: 80).

The endpoints of the study were OS and LCSS. OS was defined as the time interval from diagnosis of the disease to all-cause death, whereas LCSS was defined as time interval from diagnosis to death only attributed to lung cancer. The follow-up cutoff date for vital status was December 2021.

Statistical analysis

To compare the baseline clinicopathological characteristics between adjuvant and neoadjuvant cohorts, we analyzed normally distributed continuous variables by Student’s t-test and categorical variables using Pearson’s Chi-squared test or Fisher’s exact test as appropriate. The Kaplan-Meier method with log-rank test was performed to compare survival curves for OS. Competing risk analysis was applied to analyze cumulative incidence of lung cancer-specific death, considering non-cancer-specific death as competing events. Cox proportional hazards regression models were constructed to determine predictors for OS, while Fine and Gray’s competing risk regression models were built to identify predictors for LCSS and to estimate subdistribution hazard ratio (SHR) (17). Multivariate regression models were constructed incorporating both covariables with P values <0.10 identified in univariate analyses and key exposure variable of the study. Multivariate analyses were applied to adjust for covariates in all subgroup analyses in this study.

To further diminish potential confounding bias between adjuvant and neoadjuvant cohorts, PSM was performed. A logistic regression model was established to calculate propensity score based on significantly unbalanced covariates between the two above-mentioned cohorts: age, tumor grade, T descriptor, and the TNM stage. Patients who received neoadjuvant systemic therapy were matched with those treated with adjuvant therapy by a 1:5 greedy algorithm without replacement.

All statistical analyses were performed using R software version 4.4.2 (www.r-project.org). No correction for multiple testing was performed. All statistical tests were 2-sided, and P values of <0.05 were considered statistically significant.

Results

Patient selection process is presented in Figure S1. A total of 1,702 limited stage SCLC patients who underwent surgical resection of primary tumor were included in the study. Of these patients, 1,187 (70%) received perioperative systemic therapy, including 1,132 (67%) received adjuvant therapy and 55 (3%) received neoadjuvant therapy; while 515 (30%) patients underwent no systemic therapy at all in the real world. In the entire cohort, Kaplan-Meier analysis was conducted to compare the OS between surgical resected SCLC patients who received perioperative systemic therapy and who did not. Not surprisingly, patients received systemic therapy had significantly longer OS than those who underwent surgery alone [median survival time (MST): 39 vs. 26 months, log-rank P<0.001, Figure 1A]. Besides, patients with earlier TNM stages and who underwent lobectomy had improved OS (stage IA vs. IB vs. II vs. III MST: 61 vs. 44 vs. 31 vs. 18 months, log-rank P<0.001, Figure 1B; lobectomy vs. sublobar resection MST: 46 vs. 25 months, log-rank P<0.001, Figure 1C); however, no survival benefit was found for surgical resected SCLC patients who further underwent perioperative radiation therapy (log-rank P=0.27, Figure 1D).

Figure 1 Kaplan-Meier survival curves of OS stratified by systemic therapy (A), pathological stage (B), surgical procedure (C), and radiation therapy (D) in entire cohort (N=1,702). NOS, not otherwise specified; OS, overall survival; RT, radiation therapy.

Baseline clinicopathological characteristics are summarized in Table 1. For those received perioperative systemic therapy, patients treated with neoadjuvant therapy were significantly younger (median age: 64.1 vs. 67.0 years, P=0.03), but exhibited more advanced TNM stages (stage III: 49.1% vs. 29.2%, P=0.009) than those received adjuvant therapy. Survival outcomes of OS and LCSS between neoadjuvant and adjuvant groups were then assessed according to TNM stages. No OS difference was found between the two above-mentioned groups across the entire, stage I and II cohorts (all log-rank P>0.10, Figure 2A-2C). However, in stage III cohort, OS benefit was observed in neoadjuvant group although not statistically significant (MST: 33 vs. 19 months, log-rank P=0.055, Figure 2D). Similarly, no LCSS difference was found between neoadjuvant and adjuvant groups across the entire, stage I and II cohorts (all P>0.10, Figure 3A-3C), while neoadjuvant therapy was associated with decreased lung cancer-specific mortality in stage III cohort (P=0.07, Figure 3D).

Figure 2 Kaplan-Meier survival curves of OS stratified by perioperative systemic therapy (neoadjuvant vs. adjuvant) in surgical resected entire (A), stage I (B), stage II (C), and stage III (D) SCLC cohorts (N=1,187). OS, overall survival; SCLC, small cell lung cancer.

Figure 3 Cumulative incidence of mortality (LCSD and non-LCSD) stratified by perioperative systemic therapy (neoadjuvant vs. adjuvant) in surgical resected entire (A), stage I (B), stage II (C), and stage III (D) SCLC cohorts (N=1,187). CIF, cumulative incidence function; LCSD, lung cancer-specific death; SCLC, small cell lung cancer.

Results of univariate and multivariate Cox proportional hazards regression and competing risks regression for the entire surgical resected SCLC patients who received perioperative systemic therapy are summarized in Table 2. In multivariate analyses, age and the TNM stage were independent prognostic factors for both OS and LCSS. Patients who were older or exhibited more advanced TNM stages had significant worse prognosis. In terms of perioperative systemic therapy, neoadjuvant therapy was independent favorable prognostic factor for OS [hazard ratio (HR) =0.69, 95% confidence interval (CI): 0.48–0.99, P=0.04] after adjusting for covariates such as age, sex, and the TNM stage; however, it was not independently associated with improved LCSS (SHR =0.83, 95% CI: 0.56–1.23, P=0.35) in multivariate analyses.

Subgroup analyses stratified by sex, race, tumor grade, T/N descriptors, and the TNM stage were performed with multivariate regression models adjusting for covariates (Figure 4 and Tables S1-S3). Generally speaking, patients with locally advanced disease tended to gain remarkable survival benefits from neoadjuvant therapy, whereas patients with early-stage tumor tended to achieve better survival outcomes through adjuvant therapy (although P for trend across different TNM stages was not significant: P=0.28). Neoadjuvant therapy was favorable prognostic factor for patients with T3/4 (OS: HR =0.57, 95% CI: 0.32–1.03, P=0.06; LCSS: SHR =0.56, 95% CI: 0.29–1.05, P=0.07), and stage III disease (OS: HR =0.61, 95% CI: 0.37–0.99, P=0.048; LCSS: SHR =0.60, 95% CI: 0.35–1.01, P=0.056). Conversely, adjuvant therapy was associated with improved survival outcomes in patients with T1 (LCSS: SHR =2.16, 95% CI: 1.16–4.03, P=0.02), N0 (LCSS: SHR =1.52, 95% CI: 0.95–2.43, P=0.08), and stage I disease (LCSS: SHR =1.99, 95% CI: 1.18–3.37, P=0.01).

Figure 4 Adjusted multivariate regressions comparing neoadjuvant vs. adjuvant systemic therapy for OS (A) and LCSS (B) in different surgical resected SCLC subgroups stratified by sex, race, tumor grade, T/N descriptor, and the 8^th edition of AJCC TNM stage. AJCC, American Joint Committee on Cancer; CI, confidence interval; HR, hazard ratio; LCSS, lung cancer specific-survival; N, node; OS, overall survival; SCLC, small cell lung cancer; T, tumor; TNM, tumor node metastasis classification.

Finally, PSM was performed to further balance confounding covariates between neoadjuvant and adjuvant groups. No significant difference regarding baseline clinicopathological characteristics was observed across the two above-mentioned groups after matching (Table 3). In the entire matched cohort, neoadjuvant therapy was not significantly associated with improved survival outcomes (OS: HR =0.71, 95% CI: 0.47–1.09, P=0.12, Figure 5A; LCSS: SHR =0.85, 95% CI: 0.57–1.26, P=0.47, Figure 5B). However, it contributed to significant OS and LCSS benefits for patients with locally advanced stage III disease (OS: HR =0.54, 95% CI: 0.29–0.98, P=0.04, Figure 5C; LCSS: SHR =0.49, 95% CI: 0.26–0.91, P=0.04, Figure 5D).

Figure 5 Kaplan-Meier survival curves of OS stratified by perioperative systemic therapy (neoadjuvant vs. adjuvant) in matched entire (A) and stage III (C) cohorts; cumulative incidence of mortality (LCSD and non-LCSD) stratified by perioperative systemic therapy in matched entire (B) and stage III (D) cohorts (N=288 after PSM). CIF, cumulative incidence function; LCSD, lung cancer-specific death; OS, overall survival; PSM, propensity score matching.

Discussion

SCLC is highly invasive neuroendocrine malignancy for which surgery is an accepted element of multimodality treatment if the disease is diagnosed in its very early stages (18). According to the National Comprehensive Cancer Network (NCCN) guideline, stage I–IIA (T1–2N0M0) SCLC are recommended to receive surgical resection followed by adjuvant therapy; while for those with locally advanced disease (limited stage IIB–IIIC), the prevailing consensus supports definitive radiotherapy over surgery as the standard local treatment modality (19). However, clinical evidences in favor of radiation therapy have limited applicability to resectable SCLC today as they were either conducted in an era prior to minimally invasive thoracic surgery and modern chemotherapy regimens or excluded patients with peripheral nodules and normal bronchoscopies (20-22).

Recently, several retrospective cohort studies revealed the fact that the addition of surgery to multimodality treatment of limited stage SCLC appeared to improve local control and OS in real-world practice (23,24). Liang et al. performed a meta-analysis incorporating 19 studies and 30,185 stage I–III SCLC patients who received surgical or non-surgical treatment during the last 20 years (4). Compared with non-surgical treatment, surgical resection brought significant OS benefits not only for stage I (HR =0.42, 95% CI: 0.24–0.71, P<0.01) and II (HR =0.61, 95% CI: 0.52–0.73, P<0.01), but also for locally advanced stage III (HR =0.66, 95% CI: 0.51–0.86, P<0.01) SCLC patients. In this study, we included 1,702 stage I–III SCLC patients who underwent surgical resection of primary tumor, among which up to 46.7% (795) had locally advanced diseases (stage IIB–III). The median OS for surgical resected stage I–III SCLC was 39 months, which was not inferior to the 33.4 months median OS in the standard-of-care group of the ADRIATIC study, who received concurrent chemoradiotherapy and prophylactic cranial irradiation without immunotherapy (11,25). Thus, the role of surgery as primary treatment for limited stage SCLC necessitates rigorous reevaluation, especially for those with locally advanced diseases.

Immunotherapy is profoundly altering the approach to lung cancer treatment owing to its sustained therapeutic response and tolerable safety profile. From the PACIFIC to ADRIATIC study, researchers have successfully bridged NSCLC-derived evidence to SCLC (26). The ADRIATIC study was the first and only phase III trial investigating durvalumab as consolidation therapy following concurrent chemoradiotherapy in limited stage SCLC (11), ushering in the era of immunotherapy for limited stage SCLC. Aside from radiotherapy, surgery is also an effective local treatment strategy for lung cancer. As is well known, neoadjuvant chemoimmunotherapy has become the recommended treatment for “driver gene negative” stage II–III NSCLC (27). Whether immunotherapy combined with chemotherapy can achieve the same significant neoadjuvant therapeutic effects in limited stage SCLC remains to be explored. A multicenter, single-arm phase II trial (NeoSCI) enrolled 17 stage I–IIIB SCLC patients who received 3 cycles of neoadjuvant atezolizumab combined with chemotherapy (14). The pCR and MPR rates of the per-protocol cohort reached 61.5% and 92.3% respectively. Another ongoing single-arm phase II trial (NIUS) recruits resectable limited stage I–III SCLC who undergo 3 cycles of neoadjuvant adebrelimab combined with chemotherapy, followed by surgery and 1 cycle of adjuvant chemoimmunotherapy with immunemaintenance therapy (15). Although there is currently limited evidence suggesting the superiority of perioperative [e.g., KEYNOTE-671 (28)] over pure neoadjuvant approach [e.g., CheckMate 816 (12)] in NSCLC (29), researchers have already begun to explore the therapeutic efficacy of different perioperative systemic treatment modalities [pure neoadjuvant approach (e.g., NeoSCI) vs. perioperative approach (e.g., NIUS)] in resectable limited stage SCLC.

Notably, instead of enrolling traditionally resectable early-stage I–IIA SCLC (T1–2N0M0), recent neoadjuvant trials for SCLC also recruit stage IIB-III patients, pushing the surgical eligible boundaries towards a more locally advanced population (14,15,30,31). In this study, the real-world data revealed that nearly half of surgical resection occurred in stage IIB–III SCLC. Compared with adjuvant therapy, neoadjuvant therapy was independent favorable prognostic factor for OS (HR =0.69, 95% CI: 0.48–0.99, P=0.04) in the entire surgical resected cohort; however, the mortality reduction for LCSS was not significant (SHR =0.83, 95% CI: 0.56–1.23, P=0.35). These findings led us to hypothesize that not all surgical resected SCLC could derived survival benefit from neoadjuvant therapy. Subgroup analyses showed that only patients with more advanced tumor stages tended to achieve prolonged survival through neoadjuvant systemic therapy, particularly for those with T3/T4 and stage III disease. These findings are not surprising since neoadjuvant therapy could induce tumor downstaging, increase R0 resection rate, eradicate micrometastatic disease, enhance tumor-specific T-cell activation and robust adaptive immune response particularly in locally advanced lung cancer, and thus yield significant OS benefits in this population. On the contrary, neoadjuvant systemic therapy was associated with significant survival disadvantage in early-stage SCLC, such as patients with T1, N0, and stage I disease. Unlike locally advanced disease, early-stage SCLC is characterized by its low tumor burden and high complete resection rate (32). Thus, the toxicities and potential risks of neoadjuvant therapy may offset its theoretical benefits in this population. This finding is concordant with the current NCCN guidelines, which recommend upfront surgical resection followed by adjuvant systemic therapy for early-stage I–IIA (T1–2N0M0) SCLC (19).

Our results were further validated in the PSM cohort. Neoadjuvant therapy contributed to significant OS and LCSS benefits for patients with locally advanced stage III disease. However, we have to clarify that instead of receiving chemoimmunotherapy, most surgical resected SCLC patients in our study were treated with pure chemotherapy as systemic treatment. This was because patients enrolled in our study were diagnosed between 2007 to 2021. During this period of time, platinum-based cytotoxic chemotherapy is the standard systemic treatment for SCLC. In 2019, the FDA approved atezolizumab in combination with carboplatin and etoposide, for the first-line treatment of extensive-stage SCLC based on IMpower133 (33), marking the entry of SCLC into immunotherapy era. Thus, the survival advantages observed in this study were mainly derived from neoadjuvant chemotherapy. As is known, neoadjuvant immunotherapy plus chemotherapy significantly improved pathological responses and event-free survival as compared with neoadjuvant chemotherapy alone in resectable NSCLC (12,28). So, we have reasons to believe that neoadjuvant chemoimmunotherapy may further amplify the survival benefits observed in this study.

In addition, we preliminarily explored the role of radiation therapy in surgical resected limited stage SCLC. No survival benefit was found for surgical patients who further underwent perioperative radiation therapy (log-rank P=0.27). Moreover, for patients who underwent neoadjuvant therapy followed by surgery, no significant OS differences was found between those who received neoadjuvant chemoradiotherapy and pure neoadjuvant systemic therapy (log-rank P=0.60). This is not surprising since in complete resected locally advanced NSCLC, phase III randomized trials did not show OS benefit of postoperative radiation therapy either, although locoregional control was significantly improved (34,35). Thus, surgery-based radiation-free treatment modality might be a potential choice for limited stage SCLC in the future, though there is still a long way to go.

Nevertheless, this study has several inherited limitations due to its retrospective nature. Firstly, the selection bias was inevitable. All SCLC patients enrolled in this study underwent surgical resection of primary tumor, including those with limited stage IIB-IIIC disease. Instead of receiving systemic therapy plus concurrent or sequential radiotherapy, these locally advanced SCLC patients underwent surgical intervention in the real world. However, the reason why they were selected for surgery remained unexplained. In addition, patients failed to underwent surgery due to tumor progression or severe adverse events after receiving neoadjuvant therapy were not included, leading to survivorship bias in favor of neoadjuvant treatment in the study. Thus, results from this highly selected SCLC cohort should be interpreted with cautions when attempting to generalize them to a broader population. Secondly, although this study included 1,702 surgically resected limited stage SCLC from SEER 17 Registries over fourteen years, only 55 (3%) patients received neoadjuvant systemic therapy in the real world. Such extremely low neoadjuvant therapy rate remained explainable, since the standard-of-care for limited stage SCLC was either surgical resection followed by adjuvant therapy or definitive chemoradiotherapy plus consolidation immunotherapy. Neoadjuvant approaches for SCLC in real-world practice were predominantly individualized and exploratory, rendering such data scarce yet highly precious. However, the limited sample size would definitely compromise the robustness and statistical power of the findings. Further studies with expanded sample sizes are essential to validate our conclusions. Thirdly, although we performed both multivariate analyses and PSM to balance the baseline clinicopathological characteristics between neoadjuvant and adjuvant groups. Potential confounding factors that were not captured in SEER database, such as Eastern Cooperative Oncology Group (ECOG) performance status and comorbidities index, could still cause confounding bias during the survival analyses. Fourthly, misclassification bias should be noticed when using the variable “RX SUMM--SYSTEMIC/SUR SEQ” to identify patients that could have received neoadjuvant treatment (36,37). Although this variable emphasized the sequence of surgery and systemic treatment modalities, it did not consider the timing of the events. It was possible that systemic therapy might have been given more than 6 months, or just 6 days prior to surgery. Thus, the systemic treatment administered before surgery might not have had neoadjuvant intent or would not have been administered long enough to expect a relevant tumor response. Besides, there might be missing information about systemic therapy, which may, on the other hand, underestimate the frequency of neoadjuvant treatment. Finally, detailed information about systemic therapy, such as the chemotherapy regimens, was not available in SEER database. More importantly, whether SCLC patients received chemotherapy alone or chemoimmunotherapy as perioperative systemic therapy during a long time-period (from 2007 to 2021) remained unknown. The IMpower133 trial (33) led to the first FDA approval of immunotherapy for SCLC in March 2019. Thus, it was reasonable to conclude that survival benefits observed in this study were primarily attributable to neoadjuvant chemotherapy, rather than chemoimmunotherapy. Therefore, our results could be debatable in the immunotherapy era for SCLC. However, numerous clinical trials [e.g., CheckMate 816 (12) and KEYNOTE-671 (28)] have proved that compared to chemotherapy alone, neoadjuvant chemoimmunotherapy achieved superior pCR/MPR rates and enhanced EFS/OS in NSCLC. In addition, single-center small-sample retrospective studies have showed that neoadjuvant chemoimmunotherapy could achieve greater advantages in tumor downstaging and pathological regression while providing similarly safety and surgical feasibility in SCLC patients (38,39). Hence, there are compelling reasons for optimism that neoadjuvant chemoimmunotherapy would consistently provide enhanced benefits for limited stage SCLC patients in the current immunotherapy era. Further rigorous studies, particularly well-designed randomized controlled trials, are warranted to investigate the optimal sequencing and combination of multimodality treatments for resectable SCLC.

In conclusion, this real-world study revealed that compared with traditional adjuvant therapy, neoadjuvant systemic therapy was associated with improved survival in limited stage SCLC patients, particularly for those with stage III disease. This indicates that neoadjuvant therapy followed by radical surgery might be a promising treatment modality for resectable locally advanced SCLC. We believe that with the rapid development of novel perioperative systemic treatment drugs, surgery-centered multimodality therapy will play an important role in the treatment of limited stage SCLC.

Conclusions

In clinical practice, neoadjuvant systemic therapy has been associated with improved survival outcomes in surgically resected SCLC, particularly among patients with stage III disease. These findings suggest that neoadjuvant therapy represents a promising therapeutic strategy for resectable locally advanced SCLC.

Acknowledgments

We would like to thank all the staff members who work with the SEER program.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-457/rc

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-457/prf

Funding: This work was supported by Peking University People’s Hospital Research and Development Funds (No. RDL2023-10 to Z.S.).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-457/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.The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

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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