BACKGROUND:Chemoradiotherapy with durvalumab consolidation has yielded excellent results in stage III non-small-cell lung cancer (NSCLC). Therefore, it is essential to identify patients who might benefit from a surgical approach. MATERIAL AND METHODS:Data from 437 patients with operable stage III NSCLC enrolled in four consecutive Swiss Group for Clinical Cancer Research (SAKK) trials (16/96, 16/00, 16/01, 16/08) were pooled and outcomes were analyzed in 431 eligible patients. All patients were treated with three cycles of induction chemotherapy (cisplatin/docetaxel), followed in some patients by neoadjuvant radiotherapy (44 Gy, 22 fractions) (16/00, 16/01, 16/08) and cetuximab (16/08). RESULTS:With a median follow-up time of 9.3 years (range 8.5-10.3 years), 5- and 10-year overall survival (OS) rates were 37% and 25%, respectively. Overall, 342 patients (79%) underwent tumor resection, with a complete resection (R0) rate of 80%. Patients (n = 272, 63%) with R0 had significantly longer OS compared to patients who had surgery but incomplete resection (64.8 versus 19.2 months, P < 0.001). OS for patients who achieved pathological complete remission (pCR) (n = 66, 15%) was significantly better compared to resected patients without pCR (86.5 versus 37.0 months, P = 0.003). For patients with pCR, the 5- and 10-year event-free survival and OS rates were 45.7% [95% confidence interval (CI) 32.8% to 57.7%] and 28.1% (95% CI 15.2% to 42.6%), and 58.2% (95% CI 45.2% to 69.2%) and 45.0% (95% CI 31.5% to 57.6%), respectively. CONCLUSION:We report favorable long-term outcomes in patients with operable stage III NSCLC treated with neoadjuvant chemotherapy with cisplatin and docetaxel ± neoadjuvant sequential radiotherapy from four prospective SAKK trials. Almost two-third of the patients underwent complete resection after neoadjuvant therapy. We confirm R0 resection and pCR as important predictors of outcome.

T-cell receptor (TCR) repertoire assessment in blood and tissue has emerged as a novel predictive marker for response to immune checkpoint inhibitor therapy in advanced stage cancers. However, its relevance and predictive significance in the setting of resectable stage IIIA(N2) non-small cell lung cancer (NSCLC) has yet to be demonstrated. Here, we performed TCR sequencing in patients from the phase 2 trial SAKK 16/14 undergoing neoadjuvant chemotherapy with three cycles of cisplatin/docetaxel followed by treatment with the PD-L1 antibody durvalumab.

Surgical treatment of patients with T3/4 locally advanced NSCLC including single or multilevel N2 remains a matter of debate across countries. Several trials have demonstrated that selected patients benefit from surgery, when radical (R0) resection can be achieved. We aimed to assess resectability and outcome of resections for locally advanced T3/T4 tumors after induction treatment with chemo- or sequential chemoradiotherapy in a pooled analysis of three prospective multicenter clinical trials.