Introduction
The introduction of immunotherapy (IO) in the management of locally advanced non-small cell lung cancers (NSCLCs) has significantly improved patient outcomes. In 2017, our center introduced compassionate IO for stage III NSCLC as follows: induction chemo-IO followed by surgery for potentially resectable and chemo-radiation therapy followed by IO for non- operable NSCLCs. Here, we report the outcomes of 68 stage III NSCLCs (45 single N2 and 23
bulky N2 or N3) managed by multimodal therapy including IO and surgery or radiation therapy.
Methods
This study is retrospective and was conducted at the Lausanne University Hospital (CHUV). We reviewed all stage III NSCLC patients treated in our institution between 2017 and 2023 with chemo-IO and surgery or radiation therapy. We recorded and analyzed, for each patient, clinico-pathological characteristics, perioperative complications and long-term outcomes. Descriptive statistics were performed using Stata software®.
Results
A total of 68 patients were included in the study: 32 underwent surgery and 36 underwent radiation therapy. Tumor oncological stages were less advanced in the surgical group (81% stage IIIA-single N2 and 19% stage IIIB-bulky N2/N3) than in the radiation therapy group (53% stage IIIA-single N2 and 47% stage IIIB-bulky N2/N3 disease). Also, compared to radiation therapy group, patients from the surgery group were younger (63 years [56-69] vs 75 years [63-73]) and had better pulmonary functions (FEV1 85.47 ± 16.88, DLCO 74.88 ± 17.15 vs FEV1
61.44 ± 27.42, and DLCO 45.23 ± 21.46). Of the 33 patients induced by chemo-IO, 32 underwent surgery while one progressed and underwent radiation therapy. Surgical procedures included 31 lobectomies or bilobectomies (97%) and 1 pneumonectomy (3%). Complete resection (R0) was achieved in 30 patients (94%), while two patients (6%) had an R1 resection due to lymph node effraction. Treatment-related complications were comparable (14% of cardiac and 36% of pulmonary vs 19% cardiac and 41% pulmonary in the radiation and surgery groups respectively). There was no 30-day mortality reported in either group. A complete pathological response (CPR) was observed in 7 surgical patients, including 6 of 26 with single N2 disease and 1 of 6 with bulky N2/N3 disease. Mean patient survival was of 100% in the CPR patients and tended to be higher in the surgery group compared to the radiation therapy group.
Conclusion
The inclusion of IO has significantly improved tumor response rates irrespective of the local treatment modality. Chemo-IO induction protocols can be considered in fit patients for more advanced stage III disease with good results. Nevertheless, careful patient selection through multidisciplinary tumor boards remains essential as the radiation alternative is a good option.
Further research is required to validate these findings.