Neoadjuvant immunochemotherapy demonstrated improved efficacy and comparable safety to neoadjuvant chemotherapy for limited-stage small-cell lung cancer: a cohort study.

Background: Small-cell lung cancer (SCLC) accounts for 10-15% of all lung cancers. Neoadjuvant therapy followed by surgery has been applied in treatment of limited-stage SCLC (LS-SCLC). The synergistic effect of neoadjuvant immunochemotherapy (NIC) has been validated in the treatment of non-small cell lung cancer (NSCLC). Therefore, we compared the safety and efficacy between NIC and neoadjuvant chemotherapy (NC) for treating LS-SCLC.

Methods: This retrospective study included 10 patients diagnosed with LS-SCLC (stage I-IIIB) from 2019 to 2021. Five patients received NIC, while the other five received NC. Patients received two cycles of etoposide and cisplatin chemotherapy (EP) regimen (75 mg/m² of cisplatin and 160 mg/m² of etoposide) with or without immunotherapy (durvalumab or pembrolizumab) every 3 weeks before surgery. Imaging evaluation was performed before neoadjuvant therapy and surgery. Imaging and pathological tumor response, neoadjuvant treatment-related adverse events, perioperative information, and complications were evaluated. The follow-up data were obtained from the regular reviews in hospital and by telephone. The follow-up was terminated at December 2023 or if the patient died or experienced recurrence.

Results: The objective response rate (ORR) was 80% (4/5) in the NIC group and 100% (5/5) in the NC group. No patients experienced progressive disease (PD). Patients in the NIC group achieved more improvement of pulmonary function than did those in the NC group. All NIC and NC patients had R0 resection. No significant difference in surgical information was found between the two groups. One of the five patients in the NIC group experienced alveolopleural fistula, while one of the five patients in the NC group experienced respiratory failure postoperatively and died thereafter. One patient in the two groups was diagnosed with hydrothorax after tube removal. Pathological downstaging occurred in 4 patients in the NIC group and 2 patients in the NC groups. The rate of pathological complete remission (pCR) and major pathological response (MPR) was 20% and 40% in the NIC group, respectively, while in the NC group, it was 20% and 20%, respectively. In one patient with NIC, adjuvant therapy was abandoned due to hepatic insufficiency. During the period of follow-up, one patient in the NIC group experienced brain metastasis 1 year after surgery, while one patient in the NC group was diagnosed with local lymph node metastasis and distant metastasis half a year later.

Conclusions: NIC might provide greater advantages in downstaging, pulmonary function improvement and pathological regression in patients with LS-SCLC than NC while providing similarly safety and surgical feasibility. These findings may help clinicians develop more individualized therapy. However, randomized controlled trials are required to further validate our findings.