Pathological response to neoadjuvant therapy with chemotherapy vs chemoradiotherapy in stage III NSCLC. Contribution of IASLC recommendations

Abstract

BACKGROUND Neoadjuvant treatment (NT) with chemotherapy (Ch) is a standard option for resectable stage III (N2) NSCLC. Several studies have suggested benefits with the addition of radiotherapy (RT) to NT Ch. The International Association for the Study of Lung Cancer (IASLC) published recommendations for the pathological response (PHR) of NSCLC resection specimens after NT. AIM To contribute to the IASLC recommendations showing our results of PHR to NT Ch vs NT chemoradiotherapy (ChRT). METHODS We analyzed 67 consecutive patients with resectable stage III NSCLC with positive mediastinal nodes treated with surgery after NT Ch or NT ChRT between 2013 and 2020. After NT, all patients were evaluated for radiological response (RR) according to Response Evaluation Criteria in Solid Tumours criteria and evaluated for surgery by a specialized group of thoracic surgeons. All histological samples were examined by the same two pathologists. PHR was evaluated by the percentage of viable cells in the tumor and the resected lymph nodes. RESULTS Forty patients underwent NT ChRT and 27 NT Ch. Fifty-six (83.6%) patients underwent surgery (35 ChRT and 21 Ch). The median time from ChRT to surgery was 6 wk (3-19) and 8 wk (3-21) for Ch patients. We observed significant differences in RR, with disease progression in 2.5% and 14.8% of patients with ChRT and Ch, respectively, and partial response in 62.5% ChRT vs 29.6% Ch ( P = 0.025). In PHR we observed ≤ 10% viable cells in the tumor in 19 (54.4%) and 2 cases (9.5%), and in the resected lymph nodes (RLN) 30 (85.7%) and 7 (33.3%) in ChRT and Ch, respectively ( P = 0.001). Downstaging was greater in the ChRT compared to the Ch group (80% vs 33.3%; P = 0.002). In the univariate analysis, NT ChRT had a significant impact on partial RR [odds ratio (OR) 12.5; 95% confidence interval (CI): 1.21 - 128.61; P = 0.034], a decreased risk of persistence of cancer cells in the tumor and RLN and an 87.5% increased probability for achieving downstaging (OR 8; 95%CI: 2.34-27.32; P = 0.001). CONCLUSION We found significant benefits in RR and PHR by adding RT to Ch as NT. A longer follow-up is necessary to assess the impact on clinical outcomes.

Neoadjuvant Nivolumab and Chemotherapy in Patients with Locally Advanced Non-Small Cell Lung Cancer: A Retrospective Study

“…6 Huang et al reported a better pathological response in neoadjuvant immunotherapy compared with neoadjuvant chemotherapy in stage III (N2) NSCLC, 18 with a MPR of 12.8% and a pCR of 2.6% in the neoadjuvant chemotherapy group. In terms of neoadjuvant chemoradiotherapy, a retrospective multi-institutional Phase II study compared the pathological responses of neoadjuvant chemotherapy or chemoradiotherapy in stage III (N2) NSCLC, 28 which reported a MPR of 54.5% in the tumor and 80% downstaging in the neoadjuvant chemoradiotherapy group, and 9.5% and 33.3% in the neoadjuvant chemotherapy group, respectively. Neoadjuvant immunotherapy or chemoradiotherapy appeared to obtain better pathological responses than neoadjuvant chemotherapy, and more well-designed head-to-head studies should be conducted comparing neoadjuvant immunotherapy and chemoradiotherapy with robust results.…”