Pathologic Complete Response Predicts Long-Term Survival Following Neoadjuvant Induction Chemotherapy and...

To analyze the association of pathologic-complete-response (PCR) and survival after neoadjuvant concurrent chemo-radiotherapy, we evaluated a large cohort of patients with potentially resectable stage IIIA-IIIC non-small cell lung cancer (NSCLC) treated with a trimodality approach.

Consecutive patients underwent neoadjuvant induction chemotherapy, followed by concurrent chemo-radiotherapy and surgery. Patients received established imaging, and diagnostics. Leave-one-out cross-validation was employed to identify the most effective prognostic classifier.

Altogether, 403 patients treated between 06/2000 and 01/2020 were included. Median follow-up was 111 months (IQR: 71-127 months). PCR was achieved in 34% (137 patients) after neoadjuvant therapy and major-pathologic response without PCR in 30% (MPR_{> 0%-≤ 10%} defined as viable cells in > 0% and ≤ 10% of the sample). PCR was significantly dependent on histology (p = 0.0005) and radiotherapy fractionation schedule (p = 0.027). PCR rates were higher for squamous than for non-squamous carcinoma with 46.2% (95% CI: 37.8%-54.7%) versus 27.3% (95% CI: 22.0%-33.2%). PCR was the most significant prognostic factor for long-term survival with an associated hazard ratio of 0.272 (0.192-0.386), while MPR was associated with a hazard ratio of 0.671 (0.498-0.905) in comparison to lesser response. Overall survival at 5/10 years with PCR was 72.9% (95% CI: 64.4%-79.6%)/ 62.8% (53.0%-71.1%)/ event-free survival at 5 years 69.5% (60.9%-76.7%). Identified through cross-validation, key prognostic features included PCR, MPR, and treatment period following ¹⁸F-FDG-PET/CT-guided staging.

Induction chemotherapy followed by chemo-radiotherapy results in high PCR rates. In this investigation, PCR is followed by high event-free and overall survival rates. These data warrant further investigation of chemo-radiotherapy as a significant component of neoadjuvant treatment regimens in trials combined with immunotherapy. This strategy may increase the PCR rates, particularly for patients with more advanced, potentially resectable stage III NSCLC.