Closing the RCT Gap-A Large Meta-Analysis on the Role of Surgery in Stage I-III Small Cell Lung Cancer Patients

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2024 Jun 19

PMID 38893197

Authors

Fabian Doerr

Sebastian Stange

Sophie Salamon

Konstantinos Grapatsas

Natalie Baldes

Maximilian Michel

Hruy Menghesha

Georg Schlachtenberger

Matthias B Heldwein

Lars Hagmeyer

Jurgen Wolf

Eric D Roessner

Thorsten Wahlers

Martin Schuler

Khosro Hekmat

Servet Bolukbas

Affiliations

Soon will be listed here.

Abstract

Introduction: Despite clear guideline recommendations, surgery is not consistently carried out as part of multimodal therapy in stage I small cell lung cancer (SCLC) patients. The role of surgery in stages II and III is even more controversial. In the absence of current randomized control trials (RCT), we performed a meta-analysis comparing surgery versus non-surgical treatment in stage I to III SCLC patients.

Methods: A systematic review of the literature was conducted on 1 July 2023, focusing on studies pertaining to the impact of surgery on small cell lung cancer (SCLC). These studies were evaluated using the ROBINS-I tool. Statistical analyses, including I² tests, Q-statistics, DerSimonian-Laird tests, and Egger regression, were performed to assess the data. In addition, 5-year survival rates were analyzed. The meta-analysis was conducted according to PRISMA standards.

Results: Among the 6826 records identified, 10 original studies encompassing a collective cohort of 95,323 patients were incorporated into this meta-analysis. Heterogeneity was observed across the included studies, with no discernible indication of publication bias. Analysis of patient characteristics revealed no significant differences between the two groups (-value > 0.05). The 5-year survival rates in a combined analysis of patients in stages I-III were 39.6 ± 15.3% for the 'surgery group' and 16.7 ± 12.7% for the 'non-surgery group' (-value < 0.0001). SCLC patients in stages II and III treated outside the guideline with surgery had a significantly better 5-year survival compared to non-surgery controls (36.3 ± 20.2% vs. 20.2 ± 17.0%; -value = 0.043).

Conclusions: In the absence of current RCTs, this meta-analysis provides robust suggestions that surgery might significantly improve survival in all SCLC stages. Non-surgical therapy could lead to a shortening of life. The feasibility of surgery in non-metastatic SCLC should always be evaluated as part of a multimodal treatment.

References

Hou S, Cheng Z, Wu Y, Sun Y, Liu B, Yuan M . Evaluation of short-term and long-term efficacy of surgical and non-surgical treatment in patients with early-stage small cell lung cancer: A comparative study. Cancer Biomark. 2017; 19(3):249-256. DOI: 10.3233/CBM-160332. View

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: 10.1378/chest.106.6_supplement.320s. View

Verschakelen J, Bogaert J, De Wever W . Computed tomography in staging for lung cancer. Eur Respir J Suppl. 2002; 35:40s-48s. DOI: 10.1183/09031936.02.00270802. View

Combs S, Hancock J, Boffa D, Decker R, Detterbeck F, Kim A . Bolstering the case for lobectomy in stages I, II, and IIIA small-cell lung cancer using the National Cancer Data Base. J Thorac Oncol. 2014; 10(2):316-23. DOI: 10.1097/JTO.0000000000000402. View

Jett J, Schild S, Kesler K, Kalemkerian G . Treatment of small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013; 143(5 Suppl):e400S-e419S. DOI: 10.1378/chest.12-2363. View

Ahmed Z, Kujtan L, Kennedy K, Davis J, Subramanian J . Disparities in the Management of Patients With Stage I Small Cell Lung Carcinoma (SCLC): A Surveillance, Epidemiology and End Results (SEER) Analysis. Clin Lung Cancer. 2017; 18(5):e315-e325. DOI: 10.1016/j.cllc.2017.03.003. View

Weksler B, Nason K, Shende M, Landreneau R, Pennathur A . Surgical resection should be considered for stage I and II small cell carcinoma of the lung. Ann Thorac Surg. 2012; 94(3):889-93. DOI: 10.1016/j.athoracsur.2012.01.015. View

Engelhardt K, Odell D, DeCamp M . Under-treatment of small cell lung cancer: the case for surgical resection. J Thorac Dis. 2017; 9(10):3509-3513. PMC: 5723810. DOI: 10.21037/jtd.2017.08.156. View

Varlotto J, Recht A, Flickinger J, Medford-Davis L, Dyer A, DeCamp M . Lobectomy leads to optimal survival in early-stage small cell lung cancer: a retrospective analysis. J Thorac Cardiovasc Surg. 2011; 142(3):538-46. DOI: 10.1016/j.jtcvs.2010.11.062. View

10.

Schreiber D, Rineer J, Weedon J, Vongtama D, Wortham A, Kim A . Survival outcomes with the use of surgery in limited-stage small cell lung cancer: should its role be re-evaluated?. Cancer. 2010; 116(5):1350-7. DOI: 10.1002/cncr.24853. View

11.

Barnes H, See K, Barnett S, Manser R . Surgery for limited-stage small-cell lung cancer. Cochrane Database Syst Rev. 2017; 4:CD011917. PMC: 6478097. DOI: 10.1002/14651858.CD011917.pub2. View

12.

Liao M, Zhao J, Zhou Y . [Multimodality therapy of late stage lung cancer]. Zhonghua Zhong Liu Za Zhi. 1995; 17(5):384-6. View

13.

DerSimonian R, Laird N . Meta-analysis in clinical trials. Control Clin Trials. 1986; 7(3):177-88. DOI: 10.1016/0197-2456(86)90046-2. View

14.

Wang S, Zimmermann S, Parikh K, Mansfield A, Adjei A . Current Diagnosis and Management of Small-Cell Lung Cancer. Mayo Clin Proc. 2019; 94(8):1599-1622. DOI: 10.1016/j.mayocp.2019.01.034. View

15.

Rostad H, Naalsund A, Jacobsen R, Strand T, Scott H, Strom E . Small cell lung cancer in Norway. Should more patients have been offered surgical therapy?. Eur J Cardiothorac Surg. 2004; 26(4):782-6. DOI: 10.1016/j.ejcts.2004.06.011. View

16.

Takenaka T, Takenoyama M, Inamasu E, Yoshida T, Toyokawa G, Nosaki K . Role of surgical resection for patients with limited disease-small cell lung cancer. Lung Cancer. 2015; 88(1):52-6. DOI: 10.1016/j.lungcan.2015.01.010. View

17.

Doerr F, Stange S, Michel M, Schlachtenberger G, Menghesha H, Wahlers T . Stage I and II Small-Cell Lung Cancer-New Challenge for Surgery. Lung. 2022; 200(4):505-512. PMC: 9360162. DOI: 10.1007/s00408-022-00549-8. View

18.

Kalemkerian G, Akerley W, Bogner P, Borghaei H, Chow L, Downey R . Small cell lung cancer. J Natl Compr Canc Netw. 2013; 11(1):78-98. PMC: 3715060. DOI: 10.6004/jnccn.2013.0011. View

19.

Moher D, Liberati A, Tetzlaff J, Altman D . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009; 6(7):e1000097. PMC: 2707599. DOI: 10.1371/journal.pmed.1000097. View

20.

Reinmuth N, Hoffmann H . [Small Cell Lung Cancer]. Zentralbl Chir. 2018; 143(1):103-116. DOI: 10.1055/s-0043-110185. View