Skip to main content
NCBI home page
Thoracic Cancer logoLink to Thoracic Cancer
. 2023 Aug 11;14(25):2525–2535. doi: 10.1111/1759-7714.15062

Survival analysis of surgical versus nonsurgical treatment in stage I to III small cell lung cancer in the last 20 years: A systematic review and meta‐analysis

Zhijian Liang 1, Xiaoqi Li 1, Xiao Li 1,✉
PMCID: PMC10481146  PMID: 37567777

Abstract

More and more patients with small cell lung cancer (SCLC) have received surgical treatment in the last 20 years. This meta‐analysis compared whether surgical treatment can bring greater survival benefits to patients with stage I–III SCLC compared with chemotherapy, radiotherapy and chemoradiotherapy. Pubmed, Embase, Web of Science, Cochrane library database, and ClinicalTrials were searched for relevant articles. The main outcomes were overall survival (OS), reported as hazard ratios (HRs), and 95% confidence intervals (CIs). A total of 19 articles containing 30 185 patients (3940 patients receiving surgical treatment and 26 245 patients receiving nonsurgical treatment) were included in this study. Surgical resection significantly improved OS when compared to nonsurgical treatment in retrospective studies (HR: 0.55, 95% CI: 0.47–0.64, p < 0.01). In the subgroup analysis for retrospective studies, surgical resection was associated with superior OS in stage I (HR: 0.42, 95% CI: 0.24–0.71, p < 0.01), stage II (HR: 0.61, 95% CI: 0.52–0.73, p < 0.01), and stage III diseases (HR: 0.66, 95% CI: 0.51–0.86, p < 0.01). Sublobar resection resulted in worse OS than a lobectomy (HR: 0.78,95% CI: 0.60–1.00, p < 0.01) for patients undergoing surgical resection. Compared with nonsurgical treatment, surgical treatment can indeed bring more significant survival benefits to patients with stage I–III SCLC, and lobectomy can bring longer survival compared with sublobectomy. More prospective studies are needed to confirm these findings.

Keywords: nonsurgical treatment meta‐analysis, small cell lung cancer, surgical treatment

INTRODUCTION

Small cell lung cancer (SCLC) constitutes approximately 10%−15% incidence of all malignant lung tumors, associated with extremely rapid disease progression and early metastasis. Currently, chemoradiotherapy has been acknowledged as the essential primary medical care for its promising therapeutic progress and clinical performance. The efficacy of surgical treatment has also been underestimated for the disappointing results reported in the two randomized clinical trials carried out in the last century. However, the survival rates in SCLC patients remain poor. In the past 20 years, several retrospective studies have demonstrated that surgery may have potential benefits in the limited stage SCLC with increased overall survival (OS). We therefore systematically searched and analyzed the available literature to evaluate the efficiency and potential advantages of surgery compared with nonsurgical treatment in the last 20 years.

METHODS

Literature search

The study was conducted following the preferred reporting items for systematic reviews and meta‐analysis (PRISMA) criteria. To identify eligible studies, comprehensive research was performed for the past 20 years in the five databases including Cochrane Library, PubMed, Web of Science, Embase and ClinicalTrials with inception by two researchers (X.L and Z.L). We used the following combinations of medical subject headings (MeSH) and non‐MeSH terms (((Small Cell Lung Carcinoma [Title/Abstract]) OR (small cell lung cancer [Title/Abstract])) NOT ((nonsmall cell lung cancer [Title/Abstract]) OR (non‐small cell lung carcinoma [Title/Abstract]))) AND ((surgery [Title/Abstract]) OR (surgical [Title/Abstract])). The complete search strategy is provided in the supplemental materials. The reference sections of all studies were identified to include related studies and manual search of key journal abstracts from the major annual meetings in the field of SCLC was conducted. The study protocol was registered with the PROSPERO database (CRD42022371145).

Inclusion and exclusion criteria

The inclusion criteria of the eligible studies were: randomized controlled trials (RCTs), or cohort studies that compared surgical versus nonsurgical treatment in clinical or pathological stage I to III SCLC; the study provided sufficient survival data and the hazard ratios (HRs) could be calculated; and the most recent or completed study if based on overlapping patients.The exclusion criteria were as follows: papers published in Chinese or without any relevant data for analysis, commentaries, case reports, abstracts, conference reports, reviews, letters and experiments.

Data extraction

Two reviewers independently extracted data using a predefined data extraction form. Disagreements were resolved by discussion or consensus with a third reviewer. The data extracted included the first author; study characteristics (i.e., year of publication, duration of study, the sample size of both groups, systemic therapy, primary outcome), and participant. For studies with insufficient information, the reviewers contacted the corresponding authors, when possible, to acquire and verify the data.

Quality assessment

We applied the Newcastle‐Ottawa Quality Assessment Scale (NOS) tool to all studies. Quality assessment involved patient selection, comparability of the study groups, and assessment of outcomes. We considered a study with six or greater to be high quality.

Statistical analysis

For meta‐analysis, the total effectiveness rates of dichotomous data were pooled using risk ratios (RRs). The aggregated results and 95% CIs for effect size were calculated using inverse‐variance weighted random‐effects meta‐analysis. I2 was used to assess heterogeneity across studies, with I2 values of 0, 25, 50 and 75% representing no, low, moderate and high heterogeneity, respectively. Meta‐regression was conducted to investigate the potential covariates that might have substantial impacts on between‐study heterogeneity. Sensitivity analysis was also conducted to determine whether an individual study affected the aggregate result or not. Visual inspection of the funnel plot and Egger's linear regression test was done to assess publication bias. Subgroup analyses were performed according to the type of study design.

RESULTS

Literature search results and characteristics of included studies

The process and results of literature screening are shown in Figure 1. A total of 5133 articles were initially retrieved from the database. After removing the duplication in Endnote 20.4, a total of 4113 articles were included for further reading of titles and abstracts, of which 2253 articles had research topics that were not relevant to this study and 1795 articles did not meet the requirements by study type. The full text of the remaining 65 articles was read for further screening. A total of 22 articles based on Surveillance, Epidemiology and End Results (SEER) and the National Cancer Database (NCDB) covered the same study population, and were excluded. Finally, a total of 19 articles which contained 30 185 patients (3940 patients receiving surgical treatment and 26 245 patients receiving nonsurgical treatment) were included in this study (Figure 1).

FIGURE 1.

FIGURE 1

Open in a new tab

Literature search and selection.

Assessment of included studies

Both researchers showed good consistency in assessing the quality of the 19 studies. All the retrospective studies demonstrated a score ≥6. Table 1 shows the details of the literature included in the study.

TABLE 1.

Baseline characteristics of included studies.

Study Time range Country of origin Patients (n) (surgery/NST) Study design NOS score
Yu et al.1 2007–2016 China 68/71 RS 7
Ning et al. 2 2000–2015 China 182/384 RS 7
Kauffmann‐Guerrero et al. 3 2002–2015 Europe 117/3728 RS 8
Bian et al. 4 2004–2015 China 108/108 RS 7
Li et al. 5 2005–2015 China 40/29 RS 8
Gao et al. 6 1998–2016 China 418/418 RS 8
Zhong et al. 7 2011–2018 China 50/102 RS 6
Wang et al. 8 2004–2014 China 475/475 RS 7
Uprety et al. 9 2004–2014 USA 475/534 RS 7
Li et al. 10 1998–2013 China 236/458 RS 7
Chen et al. 11 2000–2016 China 69/69 RS 7
Yin et al. 12 2010–2015 China 70/70 RS 7
Combs et al. 13 1998–2011 USA 403/16089 RS 8
Takenaka et al. 14 1974–2011 Japan 88/47 RS 6
Weksler et al. 15 1998–2007 USA 895/2671 RS 7
Zhou et al. 16 1996–2006 China 96/49 RS 7
Li et al. 17 1989–2008 China 25/170 RS 7
Badzio et al. 18 1984–1996 Europe 67/67 RS 6
Rostad et al. 19 1993–1999 Europe 58/706 RS 6
Open in a new tab

Abbreviations: NOS, Newcastle‐Ottawa quality assessment scale score; NST, nonsurgical treatment; RCT, randomized controlled trial; RS, retrospective cohort study.

Comparison of OS between the surgery and nonsurgical treatment (NST) groups

We divided 19 articles into 24 studies, because three articles involved different clinical stages or control groups. The OS of 30 185 patients included in the study was summarized and analyzed (Figure 2). The statistical heterogeneity between the studies was significant (I2 = 79%, p < 0.01), and the random effect model was used for data analysis. The results showed that there was a significant statistical difference between the surgical and nonsurgical groups (HR: 0.55, 95% CI: 0.47–0.64, p < 0.01).

FIGURE 2.

FIGURE 2

Open in a new tab

Forest plots of HR for OS in retrospective studies; C, chemotherapy; CI, confidence interval; ED, extensive disease; HR, hazard ratio; LD, limited disease; OS, overall survival; R, radiotherapy; S, surgical treatment; VLD, very limited disease.

Cumulative meta‐analysis was conducted for the included retrospective studies in the order of publication time, and the results showed that there was still a significant statistical difference between the surgical and nonsurgical groups (Figure 3).

FIGURE 3.

FIGURE 3

Open in a new tab

Cumulative meta‐analysis for the comparison of overall survival (OS) between surgical and nonsurgical treatments in retrospective studies.

Considering the significant statistical heterogeneity among the studies, we explored the causes of heterogeneity from two aspects: the sample size and the publication time of the study. All studies were divided into two groups according to whether the sample size was greater than 200. The results of meta‐regression showed that sample size could explain 13.34% heterogeneity, suggesting that sample size was not the source of statistical heterogeneity among studies. The publication time of all studies was divided into two groups according to whether the publication time was later than 2016. Meta‐regression results showed that publication time could explain 28.27% heterogeneity.

It was suggested that the publication time may be the source of statistical heterogeneity among the studies. A bubble plot of the results was drawn (Figure 4) and subgroup analysis was carried out with the publication time (Figure 5). There was significant statistical heterogeneity among the 10 studies published earlier than 2016 (I2% 83% p < 0.01), so the random effect model was used. The results showed that there was a significant statistical difference between the surgical and nonsurgical groups (HR: 0.44,95% CI: 0.32–0.61, p < 0.01). There was a significant statistical heterogeneity among the 14 studies published later than 2016 (I2 = 79%, p < 0.01), so the random effect model was used. The results showed that there was a significant statistical difference between the surgical and nonsurgical groups (HR: 0.55, 95% CI: 0.47–0.64, p < 0.01).

FIGURE 4.

FIGURE 4

Open in a new tab

Bubble plot drawn by meta‐regression according to publication time.

FIGURE 5.

FIGURE 5

Open in a new tab

Forest plots of hazard ratio (HR) for overall survival (OS) in retrospective studies published in earlier 2016 and in later 2016.

According to the seventh edition of AJCC staging standard, the heterogeneity of the study in stage I patients was significant (I2 = 81%, p < 0.01), so using the random effect model, there was a significant statistical difference between the surgical and nonsurgical groups (HR: 0.42,95% CI: 0.24–0.71, p < 0.01). There was no significant statistical heterogeneity among the studies in stage II (I2 = 0%, p = 0.64), so using the fixed effect model, there was a significant statistical difference between the surgical and nonsurgical groups (HR: 0.61,95% CI: 0.52–0.73, p < 0.01). The statistical heterogeneity between the studies of stage III patients was not significant (I2 = 27%, p = 0.25), so using the fixed effect model, there was a significant statistical difference between the operation and nonoperation groups (HR: 0.66,95% CI: 0.51–0.86, p < 0.01) (Figure 6).

FIGURE 6.

FIGURE 6

Open in a new tab

Forest plots of hazard ratio (HR) for overall survival (OS) in retrospective studies of patients with stage I, II and III.

In addition, we also conducted a sensitivity analysis to evaluate whether individual studies affected the final results (Figure 7). When individual studies were deleted from the analysis one by one, any single study did not significantly change the corresponding pooled HR, and the change to fixed effect model did not significantly change the pooled HR, which indicated the stability of the results presented.

FIGURE 7.

FIGURE 7

Open in a new tab

Sensitivity analysis for the comparison of overall survival (OS) between surgical and nonsurgical treatments in retrospective studies.

Comparison of OS between the lobectomy and sublobar resection groups

In the surgical group, a total of five studies were included, including 1003 patients who underwent sublobectomy and 2383 patients who underwent lobectomy. The results showed that OS benefit of lobectomy was more significant (HR: 0.78, 95% CI: 0.60–1.00, p < 0.01) and heterogeneity was significant (I2 = 74%, p < 0.01) (Figure 8).

FIGURE 8.

FIGURE 8

Open in a new tab

Forest plots of hazard ratio (HR) for overall survival (OS) with respect to lobectomy versus sublobar resection.

Assessment of publication bias

A funnel plot was used to evaluate the publication bias of the literature (Figure 9). The figure was in the shape of an inverted funnel, which was basically symmetrical, suggesting that the publication bias was small. The trim‐and‐fill method demonstrated that one missing study was detected. The additional points fell outside the confidence interval, indicating that there were no meaningful studies that had not yet been published. Egger's test results also indicated no publication bias (p = 0.73).

FIGURE 9.

FIGURE 9

Open in a new tab

(a) Funnel plot of all studies with a pseudo 95% confidence interval (CI). (b) One missing study was added by trim‐and‐fill method.

DISCUSSION

SCLC is a highly invasive lung cancer, which often has lymph node and other organ metastasis in the early stage. For a long time, chemotherapy and radiotherapy have been the main schemes for the treatment of SCLC, while the application of surgical treatment in SCLC is controversial. Based on this, this study conducted a meta‐analysis of related studies in the past 20 years to compare the survival benefits of surgical and nonoperative stage I–III SCLC.

Chemotherapy and radiotherapy have been the cornerstones of limited and extensive SCLC therapy for decades. This cognition mainly stems from two randomized controlled trials in the 20th century. The Medical Research Council 20 published the first study in 1973, comparing the efficacy of radiotherapy (n = 73) and surgery (n = 71) in patients with resectable SCLC. The results of 2‐, 5‐ and 10‐year follow‐up showed that the survival rate of patients who received surgery was lower than that of the radiotherapy group (4% vs. 10% at 2 years, 1% vs. 4% at 5 years and 0% vs. 4% at 10 years). However, this study had some limitations, First, the study included only patients with central lung cancer diagnosed by bronchoscopy, thus excluding patients with peripheral lung cancer that could be surgically removed. In addition, limited to the level of surgery at that time, only 48% of the patients who underwent surgery had R0 resection. This obviously affects the survival rate of surgical patients. Lad et al. 21 conducted a second study in 1994. A total of 146 patients with limited SCLC were randomly divided into the surgical treatment group (surgery + thoracic radiotherapy + whole brain radiotherapy, n = 70) and radiotherapy group (thoracic radiotherapy + whole brain radiotherapy, n = 76). All patients received neoadjuvant chemotherapy before being randomly enrolled in the group. The study found that there was no difference in median survival time between the radiotherapy group and the surgical treatment group (18.6 months vs. 15.4 months, p = 0.78). Therefore, it was concluded that adding surgical treatment to the comprehensive treatment model of SCLC could not bring survival benefits. However, in the surgical group of this study, only 41% of patients with mediastinal lymph nodes were negative. The late clinical stage is also one of the reasons for the low benefit of surgery.

These two studies are crucial to the development of a treatment model for SCLC. Because of this, the combination of chemotherapy and radiotherapy has become the first choice for patients with SCLC, and the role of surgical treatment in SCLC has been denied. However, with the progress of auxiliary examination technology and the improvement of surgical level, more and more studies have shown that surgical treatment has a more positive effect on the survival of patients with SCLC than radiotherapy and chemotherapy.

Although no randomized controlled trials have confirmed the survival benefits of surgical resection in the past 20 years, a number of retrospective studies have shown that surgical treatment can improve the prognosis of patients with early T1‐2N0 SCLC. Schreiber et al. 22 included 14 179 patients with T1‐4N0 based on the SEER database, of whom 863 underwent surgery. Compared with patients who received nonsurgical treatment, the five‐year survival rate (34.6% vs. 9.9%) and the median survival time (28 months vs. 13 months, p < 0.001) of patients undergoing surgical resection were improved. In subgroup analysis, the five‐year survival rate of patients with T1‐2N0 was 44.8%, while that of patients with T3‐4N0 was 26.3%. These findings suggest that surgery alone can bring survival benefits to early stage patients.

This is consistent with the results of this study. A total of 19 retrospective studies and 30 185 patients were included in this study. The aggregate analysis of OS showed that the OS after surgical treatment was better than that of nonsurgical treatment (HR: 0.55,95% CI: 0.47–0.64, p < 0.01). The benefit of OS in the surgical group was statistically significant, and the time cumulative meta showed that the benefit of OS had not changed since the study was published in 2002, although there is obvious heterogeneity in the study. However, the results of sensitivity analysis show that when the included studies are deleted one by one, the effect value HR does not change significantly, which indicates that the analysis results are stable.

Combined with the results of a number of retrospective studies, it is generally believed that surgical treatment can bring survival benefits to stage I patients. However, it is still controversial whether stage II–III patients are also suitable for surgical treatment. The University of Toronto Lung Oncology Research Group 23 enrolled 38 patients who underwent surgical resection after chemotherapy. The study found that after a combination of neoadjuvant chemotherapy and surgery, the 5‐year survival rate of stage I patients (n = 7) was 51%. However, stage II patients (n = 9) and stage III patients (n = 22) had no significant survival benefits. Yu et al. 1 retrospectively analyzed the survival data of SCLC patients in lymph node stage N1 in Shanghai Thoracic Hospital from 2007 to 2016. There were 68 patients in the surgery group and 71 patients in the radiotherapy and chemotherapy groups. The median total survival time of the surgery group and radiotherapy and chemotherapy groups was 29.600 months and 21.133 months (p < 0.001), respectively. The 2‐ and 5‐year survival rates in the surgery group were 55.9% and 33.7%, respectively, while those in the chemotherapy and radiotherapy group were 39.8% and 9.4%, respectively. This suggests that surgery may benefit patients with stage N1 SCLC.

Because it is controversial whether surgery can bring survival benefits to SCLC patients with stage II–III disease, this study conducted a subgroup analysis of patients with different stages of disease. The results showed that there was a significant statistical difference in OS between the operation and the nonoperation groups with stage II disease (AJCC seventh) (HR: 0.61,95% CI: 0.52–0.73, p < 0.01). There was also a significant difference in patients with stage III disease (HR: 0.66,95% CI: 0.51–0.86, p < 0.01). These results may provide a scientific basis for the controversy over surgical treatment of stage II–III disease.

Radical lobectomy has always been the standard procedure for the treatment of SCLC, but with the continuous development of technology, the proportion of wedge pneumonectomy and segmental lobectomy is increasing. Yang et al. 24 retrospectively analyzed 125 patients with SCLC in a single center. The results showed that sublobectomy (lobectomy vs. sublobectomy: 50.0 vs. 26.0 months, HR: 0.4801; p = 0.0134) was an adverse prognostic factor for OS. Another single‐center study 25 included 205 patients, which also showed that patients had a longer overall survival after lobectomy. In this study, lobectomy and sublobectomy were compared by subgroup analysis. The results showed that OS benefit of lobectomy was more significant (HR: 0.78,95% CI: 0.60–1.00, p < 0.01).

At present, two meta‐analyses have made a comprehensive analysis of the application of surgical resection in the treatment of stage I–III SCLC. In 2018, Liu et al. 26 conducted a meta‐analysis of two RCTs and 13 retrospective studies. The results showed that in the retrospective study, surgical treatment significantly improved the OS rate of patients compared with nonsurgical treatment (HR: 0.56,95% CI: 0.49–0.64, p < 0.001), but two earlier RCTs showed that surgical treatment did not improve the prognosis of patients (HR: 0.77, 95% CI: 0.32–1.84, p = 0.55). In addition, the subgroup analysis of the retrospective study showed that the OS rate of patients who received surgical treatment was higher regardless of whether they had stage I (HR: 0.56,95% CI: 0.49–0.64, p < 0.001), II (HR: 0.75, 95% CI: 0.57–0.99, p = 0.04) or III disease (HR: 0.70, 95% CI: 0.56–0.88, p = 0.002). In 2022, Doerr et al. 27 conducted a meta‐analysis of 11 241 stage I–II SCLC patients in seven studies between 1984 and 2015. The results showed that the average survival time of stage I patients was 36.7 ± 10.8 months in the surgical group and 20.3 ± 5.7 months in the nonsurgical group (p = 0.0084). In patients with stage II, the surgical treatment group also had a survival advantage (21.4 ± 3.6 months vs. 16.2 ± 3.9 months; p = 0.0493). On the basis of the above two studies, our study evaluated the survival benefits of surgical treatment of stage I–III SCLC in the past 20 years or more and included some high‐quality studies in the past five years. The results are consistent with the two meta‐analyses.

Of course, our study still had some limitations. Firstly, the studies included in our meta‐analysis were retrospective and there was a lack of randomized controlled trials with a higher level of evidence. Secondly, part of the literature did not directly report the HR needed for data analysis in our study, so the Kaplan–Meier curve must be used for extracting the data needed. Although the two researchers in this study had calculated independently, it may still have led to bias. Thirdly, there was a high heterogeneity in the conclusions of this study. Through meta‐regression and subgroup analysis, this study searched for the causes of heterogeneity from many aspects such as publication time, sample size, staging of cases, etc., which explains the heterogeneity to a certain extent and proves the stability of the conclusions through sensitivity test and subgroup analysis. But due to the inherent limitations of the observational data, there are still many clinical factors that could not be clearly obtained. For example, because the selected research was published within 20 years, different versions of SCLC stages have been used in different studies. At the same time, as for the nonoperative treatment in the control group, the types of chemotherapy, whether chemotherapy is combined with radiotherapy and the measurement of radiotherapy is difficult to balance among the studies. In addition, in the aspect of staging of SCLC, some patients were staged according to chest CT and bronchoscopy, while some studies used more modern tools such as PET‐CT and mediastinoscopy, resulting in differences in clinical diagnostic accuracy between studies. All these may be the reasons for the high heterogeneity of our study.

In conclusion, this study conducted a meta‐analysis of the surgical treatment of patients with stage I–III SCLC in the past 20 years and revealed that surgical treatment can bring survival benefits in stage I, II and III patients. According to the results of meta‐analysis, this study believes that surgical treatment can be performed on patients with I–III SCLC.

Although all the data analyzed in this study were retrospective, they still provide high‐level evidence of evidence‐based medicine. Multicenter randomized controlled trials are urgently needed in the future to confirm the role of surgery in SCLC, which is likely to change the comprehensive treatment model of SCLC.

AUTHOR CONTRIBUTIONS

Zhijian Liang was responsible for literature screening, statistical analyses, and manuscript writing. Xiaoqi Li was responsible for literature screening, statistical analyses. Xiao Li was responsible for literature screening. All authors read and approved the final manuscript.

CONFLICT OF INTEREST STATEMENT

The authors have no relevant financial or nonfinancial interests to disclose.

CONSENT FOR PUBLICATION

All the authors consent to publish the paper.

Supporting information

Data S1. Supporting Information.

Click here for additional data file. (16.8KB, docx)

ACKNOWLEDGMENTS

We greatly appreciate the assistance of the staff of the Department of Thoracic Surgery, Peking University People's Hospital, and thank them for their efforts.

Liang Z, Li X, Li X. Survival analysis of surgical versus nonsurgical treatment in stage I to III small cell lung cancer in the last 20 years: A systematic review and meta‐analysis. Thorac Cancer. 2023;14(25):2525–2535. 10.1111/1759-7714.15062

REFERENCES

  • 1. Yu L, Xu J, Qiao R, Han B, Zhong H, Zhong R. Pathological stage N1 limited‐stage small‐cell lung cancer patients can benefit from surgical resection. Clin Lung Cancer. 2022;33:S101. [DOI] [PubMed] [Google Scholar]
  • 2. Ning J, Ge T, Zhu S, Han Y, Ruan S, Ma Y, et al. The role of surgery in older patients with T1‐2N0M0 small cell lung cancer: a propensity score matching analysis. Front Oncol. 2022;12:958187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. Kauffmann‐Guerrero D, Walter J, Kovács J, Sellmer L, Hatz RA, Behr J, et al. The role of thoracic surgery in small cell lung cancer – a large longitudinal analysis (2002–2015) based on real‐world data. Clin Lung Cancer. 2022;23(3):244–252. [DOI] [PubMed] [Google Scholar]
  • 4. Bian D, Jiang S, Xiong Y, Qi M, Wu J, Addeo A, et al. Efficacy evaluation of surgery combined with chemotherapy for stage IIIA small cell lung cancer patients: a retrospective analysis. Transl Lung Cancer Res. 2022;11(8):1631–1642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. Li S, Jin K, Pan Y, Wu C, Ren S, Jiang G, et al. Role of surgery in a case‐control study of patients with clinical stage IIIA small cell lung cancer. J Thorac Dis. 2021;13(5):2738–2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Gao L, Shen L, Wang K, Lu S. Propensity score matched analysis for the role of surgery in stage III small cell lung cancer based on the eighth edition of the TNM classification: a population study of the US SEER database and a Chinese hospital. Lung Cancer. 2021;162:54–60. [DOI] [PubMed] [Google Scholar]
  • 7. Zhong L, Suo J, Wang Y, Han J, Zhou H, Wei H, et al. Prognosis of limited‐stage small cell lung cancer with comprehensive treatment including radical resection. World J Surg Oncol. 2020;18(1):27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. Wang Y, Zheng Q, Jia B, An T, Zhao J, Wu M, et al. Effects of surgery on survival of early‐stage patients with SCLC: propensity score analysis and nomogram construction in SEER database. Front Oncol. 2020;10:626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. Uprety D, Arjyal L, Vallatharasu Y, Bista A, Borgert A, Fitzsimmons AJ, et al. Utilization of surgery and its impact on survival in patients with early stage small‐cell lung cancer in the United States. Clin Lung Cancer. 2020;21(2):186–193.e2. [DOI] [PubMed] [Google Scholar]
  • 10. Li Y, Hu S, Xie J, Zhang X, Zong Y, Xu B, et al. Effects of surgery on survival of elderly patients with stage I small‐cell lung cancer: analysis of the SEER database. J Cancer Res Clin Oncol. 2019;145(9):2397–2404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. Chen M, Hu X, Qi X, Xu Y, Dong B, Chen Y, et al. Comparison of clinical prognosis of chemo‐radiotherapy and surgical treatment for patients with limited stage small cell lung cancer after matching. Chin J Cancer Radiat Oncol. 2019;28(11):821–825. [Google Scholar]
  • 12. Yin K, Song D, Zhang H, Cai F, Chen J, Dang J. Efficacy of surgery and prophylactic cranial irradiation in stage II and III small cell lung cancer. J Cancer. 2018;9(19):3500–3506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Combs SE, Hancock JG, Boffa DJ, Decker RH, Detterbeck FC, Kim AW. Bolstering the case for lobectomy in stages I, II, and IIIA small‐cell lung cancer using the national cancer data base. J Thorac Oncol. 2015;10(2):316–323. [DOI] [PubMed] [Google Scholar]
  • 14. Takenaka T, Takenoyama M, Inamasu E, Yoshida T, Toyokawa G, Nosaki K, et al. Role of surgical resection for patients with limited disease‐small cell lung cancer. Lung Cancer. 2015;88(1):52–56. [DOI] [PubMed] [Google Scholar]
  • 15. Weksler B, Nason KS, Shende M, Landreneau RJ, Pennathur A. Surgical resection should be considered for stage I and II small cell carcinoma of the lung. Ann Thorac Surg. 2012;94(3):889–893. [DOI] [PubMed] [Google Scholar]
  • 16. Zhou Z, Zhu H, Wang L, Chen D, Xiao Z, Feng Q, et al. Treatment modality selection and prognosis of early‐stage small cell lung cancer: retrospective analysis from a single cancer institute. Int J Radiat Oncol Biol Phys. 2011;81(2):S600. [Google Scholar]
  • 17. Li AF‐Y, Hsu HS, Hsu CY, Li ACH, Li WY, Liang WY, et al. A 20‐year retrospective study of small‐cell carcinomas in Taiwan. J Surg Oncol. 2010;102(5):497–502. [DOI] [PubMed] [Google Scholar]
  • 18. Badzio A, Kurowski K, Karnicka‐Mlodkowska H, Jassem J. A retrospective comparative study of surgery followed by chemotherapy vs. non‐surgical management in limited‐disease small cell lung cancer. Eur J Cardiothorac Surg. 2004;26(1):183–188. [DOI] [PubMed] [Google Scholar]
  • 19. Rostad H, Naalsund A, Jacobsen R, Strand TE, Scott H, Heyerdahl Strøm E, et al. Small cell lung cancer in Norway. Should more patients have been offered surgical therapy? Eur J Cardiothorac Surg. 2004;26(4):782–786. [DOI] [PubMed] [Google Scholar]
  • 20. Fox W, Scadding JG. Medical Research Council comparative trial of surgery and radiotherapy for primary treatment of small‐celled or oat‐celled carcinoma of bronchus. Ten‐year follow‐up . Lancet. 1973;2(7820):63–65. [DOI] [PubMed] [Google Scholar]
  • 21. Lad T, Piantadosi S, Thomas P, Payne D, Ruckdeschel J, Giaccone G. A prospective randomized trial to determine the benefit of surgical resection of residual disease following response of small cell lung cancer to combination chemotherapy. Chest. 1994;106(6 Suppl):320s–323s. [DOI] [PubMed] [Google Scholar]
  • 22. Schreiber D, Rineer J, Weedon J, Vongtama D, Wortham A, Kim A, et al. Survival outcomes with the use of surgery in limited‐stage small cell lung cancer: should its role be re‐evaluated? Cancer. 2010;116(5):1350–1357. [DOI] [PubMed] [Google Scholar]
  • 23. Shepherd FA, Evans WK, Feld R, Young V, Patterson GA, Ginsberg R, et al. Adjuvant chemotherapy following surgical resection for small‐cell carcinoma of the lung. J Clin Oncol. 1988;6(5):832–838. [DOI] [PubMed] [Google Scholar]
  • 24. Yang H, Xu J, Yao F, Liang S, Zhao H. Analysis of unexpected small cell lung cancer following surgery as the primary treatment. J Cancer Res Clin Oncol. 2018;144(12):2441–2447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. Zhao X, Kallakury B, Chahine JJ, Hartmann D, Zhang YW, Chen Y, et al. Surgical resection of SCLC: prognostic factors and the tumor microenvironment. J Thorac Oncol. 2019;14(5):914–923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. Liu T, Chen Z, Dang J, Li G. The role of surgery in stage I to III small cell lung cancer: a systematic review and meta‐analysis. PLoS One. 2018;13(12):13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27. Doerr F, Stange S, Michel M, Schlachtenberger G, Menghesha H, Wahlers T, et al. Stage I and II small‐cell lung cancer‐new challenge for surgery. Lung. 2022;200(4):505–512. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Data S1. Supporting Information.

Click here for additional data file. (16.8KB, docx)

Articles from Thoracic Cancer are provided here courtesy of Wiley

RESOURCES