A retrospective real-world single-arm study evaluating the efficacy and safety of neoadjuvant chemotherapy in patients with selected limited-stage small-cell lung cancer

Abstract

Background: With the advancement of surgical techniques and the introduction of neoadjuvant therapies, the risk of recurrence or distant metastases has been significantly decreased for non-small-cell lung cancer (non-SCLC) after surgery. In recent years, the application of these advanced techniques and therapies in SCLC has also shown promise. This study aims to explore the efficacy and safety of neoadjuvant chemotherapy combined with surgery in selected limited-stage SCLC (LS-SCLC).

Methods: In this retrospective, single-arm clinical trial, we conducted a thorough review of electronic medical records from the Shanghai Pulmonary Hospital between December 2015 and December 2022. Patients with a pathological diagnosis of SCLC who underwent neoadjuvant chemotherapy followed by radical surgery were enrolled. Baseline demographic and clinical characteristics, specifics of neoadjuvant therapy and surgery, survival outcomes, and safety profiles of included patients were systematically collected and analyzed.

Results: A total of 47 patients [7 (14.89%) females and 40 (85.11%) males; median age 61.00 years, interquartile range (IQR), 55.50-67.50 years] were enrolled. The disease control rate was 100%, with an objective response rate of 70.21% and a downstaging rate of 65.9%. The percentage of patients with a complete pathological response (CPR) and major pathological response (MPR) was 10.64% (5/47) and 12.77% (6/47, excluding CPR), respectively. In subgroups stratified by baseline demographic and clinical characteristics, the MPR rate showed no significant differences, yet a trend toward higher MPR was observed among smoking patients. At the data cutoff (October 2, 2024), the median follow-up period was 35.367 months [IQR, 26.367 months-not reached (NR)]. The median event-free survival (EFS) was 16.27 months [95% confidence interval (CI): 12.20-30.53] and the median overall survival (OS) was NR, with 2-, 3-, and 4-year survival rates of 79.96% (95% CI: 68.36-93.52%), 71.39% (95% CI: 57.12-89.22%), and 64.90% (95% CI: 48.52-86.82%), respectively. The stratified analysis revealed that patients achieving an MPR and those undergoing postoperative adjuvant radiotherapy exhibited longer EFS and OS. Treatment-related adverse events of grade 3-4 were observed in 21.28% of patients, with the most frequent occurrences being a decrease in neutrophil count (12.77%), followed by a decrease in platelet count (8.51%), and a decrease in white blood cell count (4.26%).

Conclusions: Neoadjuvant chemotherapy combined with surgery could be a potential treatment strategy for LS-SCLC, with a high proportion of patients achieving an MPR, and manageable safety profile, that did not compromise surgical resection. Further prospective clinical trials are warranted to delineate the benefits of neoadjuvant chemotherapy and optimize LS-SCLC treatment.

Keywords: Small-cell lung cancer (SCLC); major pathological response (MPR); neoadjuvant chemotherapy; surgery.

Figure 1

Overview of clinicopathological characteristics. (A) Overview of baseline characteristics and neoadjuvant information for the neoadjuvant SCLC. Baseline characteristics including sex, age, smoking history, histology, and clinical stage were annotated for each patient. (B) Overview of surgical information and adjuvant therapy for the neoadjuvant SCLC. AC, abraxane + carboplatin; C-SCLC, combined small-cell lung cancer; EC, etoposide + carboplatin; EL, etoposide + lobaplatin; EN, etoposide + nedaplatin; EP, etoposide + cisplatin; IP, irinotecan + cisplatin; N, lymph nodes; P-SCLC, pure small-cell lung cancer; PC, paclitaxel + carboplatin; RATS, robotic-assisted thoracoscopic surgery; STAS, spread through air spaces; T, tumor; VATS, video-assisted thoracoscopic surgery.

Figure 2

Radiological and pathological remission. (A) Waterfall plots of radiological regression of target lesions for patients after neoadjuvant chemotherapy treatment (n=47). (B) Waterfall plots of pathologic tumor regression (percentage reduction of viable tumor cells) in resected tumors and lymph nodes following neoadjuvant treatment with chemotherapy (n=47). (C) Multivariable logistic regression analysis of the pathologic response MPR vs. N-MPR across subgroups including sex, age, smoking history, pathology subtype, clinical stage, and neoadjuvant cycle. C-SCLC, combined small-cell lung cancer; CI, confidence interval; CPR, complete pathological response; Inf, infinity; MPR, major pathological response; N-MPR, non-major pathological response; OR, odds ratio; PR, partial response; PT, patient; SD, stable disease.

Figure 3

Kaplan-Meier survival curves. (A) Kaplan-Meier estimates of the duration of EFS. (B) Kaplan-Meier estimates of the duration of OS. EFS, event-free survival; OS, overall survival.

Figure 4

EFS analysis based on pathologic response and adjuvant therapy. (A) Kaplan-Meier estimates of the duration of EFS among the CPR, the MPR (excluding CPR), and the N-MPR. (B) Kaplan-Meier estimates of the duration of EFS between the CPR and the N-CPR. (C) Kaplan-Meier estimates of the duration of EFS between the MPR (including CPR) and the N-MPR. (D) A comparison of EFS based on adjuvant radiotherapy in overall patients. (E) A comparison of EFS based on adjuvant chemotherapy in overall patients. (F) A comparison of EFS based on adjuvant cycle in overall patients. (G) A comparison of EFS based on adjuvant radiotherapy in patients achieving MPR. (H) A comparison of EFS based on adjuvant chemotherapy in patients achieving MPR. (I) A comparison of EFS based on adjuvant cycle in patients achieving MPR. (J) A comparison of EFS based on adjuvant radiotherapy in patients not achieving MPR. (K) A comparison of EFS based on adjuvant chemotherapy in patients not achieving MPR. (L) A comparison of EFS based on adjuvant cycle in patients not achieving MPR. CI, confidence interval; CPR, complete pathological response; EFS, event-free survival; HR, hazard ratio; Inf, infinity; MPR, major pathological response; N-MPR, non-major pathological response; RT, radiotherapy.

Figure 5

EFS analysis based on pathologic stage and adjuvant therapy. (A) A comparison of EFS based on pathological T stage in overall patients. (B) A comparison of EFS based on pathological N stage in overall patients. (C) A comparison of EFS based on comprehensive pathological staging in overall patients. (D) A comparison of EFS based on adjuvant chemotherapy in patients with pathologically negative lymph nodes. (E) A comparison of EFS based on adjuvant cycle in patients with pathologically negative lymph nodes. (F) A comparison of EFS based on adjuvant radiotherapy in patients with pathologically negative lymph nodes. (G) A comparison of EFS based on adjuvant chemotherapy in patients with pathologically positive lymph nodes. (H) A comparison of EFS based on adjuvant cycle in patients with pathologically positive lymph nodes. (I) A comparison of EFS based on adjuvant radiotherapy in patients with pathologically positive lymph nodes. CI, confidence interval; EFS, event-free survival; HR, hazard ratio; N, lymph nodes; RT, radiotherapy; T, tumor.