Adjuvant Treatment for Patients With Incidentally Resected Limited Disease Small Cell Lung Cancer

A Retrospective Study

Kai-Qi Jin; Xiao-Gang Liu; Yan-Hua Guo; Chun-Xiao Wu; Jie Dai; Jia-Qi Li; Fabrizio Minervini; Mara B. Antonoff; Alex Friedlaender; Alfredo Addeo; Gregor J. Kocher; Francesco Grossi; Yu-Ming Zhu; Peng Zhang; Ge-Ning Jiang


Transl Lung Cancer Res. 2022;11(9):1951-1960. 

In This Article

Abstract and Introduction


Background: With the exception of very early-stage small cell lung cancer (SCLC), surgery is not typically recommended for this disease; however, incidental resection still occurs. After incidental resection, adjuvant salvage therapy is widely offered, but the evidence supporting its use is limited. This study aimed to explore proper adjuvant therapy for these incidentally resected SCLC cases.

Methods: Patients incidentally diagnosed with SCLC after surgery at the Shanghai Pulmonary Hospital in China from January 2005 to December 2014 were included in this study. The primary outcome was overall survival. Patients were classified into different group according to the type of adjuvant therapy they received and stratified by their pathological lymph node status. Patients' survival was analyzed using a Kaplan-Meier analysis and Cox regression analysis.

Results: A total of 161 patients were included in this study. Overall 5-year survival rate was 36.5%. For pathological N0 (pN0) cases (n=70), multivariable analysis revealed that adjuvant chemotherapy (ad-chemo) was associated with reduced risk of death [hazard ratio (HR): 0.373; 95% confidence interval (CI): 0.141–0.985, P=0.047] compared to omission of adjuvant therapy. For pathological N1 or N2 (pN1/2) cases (n=91), taking no adjuvant therapy cases as a reference, the multivariable analysis showed that ad-chemo was not associated with a lower risk of death (HR: 0.869; 95% CI: 0.459–1.645, P=0.666), while adjuvant chemo-radiotherapy (ad-CRT) was associated with a lower risk of death (HR: 0.279; 95% CI: 0.102–0.761, P=0.013).

Conclusions: Patients who incidentally receive surgical resection and are diagnosed with limited disease SCLC after resection should be offered adjuvant therapy as a salvage treatment. For incidentally resected pN0 cases, ad-chemo should be considered and for pN1/2 cases, ad-CRT should be received.


Historically, small cell lung cancer (SCLC) has been considered a non-operable disease. Two completed prospective randomized control trials[1,2] suggested that surgery had no benefits compared to radiation in the treatment of limited-stage SCLC. Over the past 20 years, several retrospective single-institution[3–7] or database-based studies[8–15] have reported favorable results for surgical resection in patients with early-stage SCLC. Under the current National Comprehensive Cancer Network (NCCN) guidelines,[16] American College of Chest Physician (ACCP) guidelines,[17] and European Society for Medical Oncology (ESMO) guidelines,[18] surgery with adjuvant therapy is now recommended for the treatment of patients with clinical T1–2N0M0 or stage I SCLC.

It is currently recommended that only T1–2N0M0 or stage I SCLC cases receive surgical resection;[16–18] however, a considerable number of patients with N1 or N2 lymph node metastatic SCLC ultimately undergo surgical resection in clinical practice. This may partially attributed to some patients receiving an incidental diagnosis after resection for what was initially presumed to be non-small cell lung cancer (NSCLC), pulmonary metastatic disease, or other diseases when the decision for surgical resection is made.[6,11] This problem is not new; already three decades ago, incidental SCLC findings occurred in 4–12% of surgeries for solitary lung nodules.[19]

Surgery without chemotherapy has been shown to provide no benefit to patients with SCLC.[1] Thus, adjuvant therapy, as a salvage treatment, might improve the survival of patients with incidentally resected SCLC. However, the proper adjuvant therapy for SCLC patients who undergo resections (both purposely and incidentally) is still unclear.

According to ESMO guidelines, adjuvant chemotherapy (ad-chemo) is recommended for pT1–2N1 patients who receive complete surgical resection (R0), while adjuvant chemo-radiotherapy (ad-CRT) is recommended for N2 patients.[18] According to NCCN guidelines, ad-CRT is recommended for both N1 and N2 patients, though data to support this recommendation are sparse.[16] In sum, the use of proper adjuvant therapy for N1–2 cases remains controversial and needs further study.

NCCN[16] and ACCP guidelines[17] would suggest that ad-chemo is recommended for patients with T1–2N0 (stage I) resected SCLC. Due to the relative infrequency of such surgical candidates, this recommendation is only supported by 4 quite dated phase-II single-arm studies[20–23] and a database-based retrospective study.[24] It is clear that further research needs to be conducted on the use of adjuvant therapy for patients with incidentally resected N1–2 SCLC. In addition, further research also needs to be conducted on the use of adjuvant therapy for patients with incidentally resected N0 cases because the evidence is limited.

This study aimed to evaluate outcomes of patients with incidentally resected SCLC to explore the use of salvage adjuvant therapy, stratified by absence (pN0) or presence (pN1–2) of pathologic lymph node metastasis. We hypothesized that ad-chemo and/or ad-CRT could improve survival of patients after incidentally resected. We present the following article in accordance with the STROBE reporting checklist (available at