Adjuvant chemotherapy appears less effective in undernourished lung cancer patients as assessed by the controlling nutritional status score: a retrospective cohort study

Background: Platinum-based adjuvant chemotherapy improves survival in resectable non-small cell lung cancer (NSCLC), but its benefit in undernourished patients-who are often excluded from clinical trials-remains unclear. Simple, objective indices that identify patients unlikely to benefit from platinum-based regimens could help individualize perioperative treatment. This study aimed to clarify whether preoperative nutritional status, particularly the controlling nutritional status (CONUT) score, predicts the survival benefit of platinum-based adjuvant chemotherapy in resectable pathological stage IIA-IIIA NSCLC. Methods: We conducted a single-center retrospective cohort study of consecutive patients with pathological stage IIA-IIIA NSCLC who underwent complete lobectomy at Tohoku University Hospital between January 2010 and December 2018. Preoperative nutritional status was evaluated using the C-reactive protein-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), and CONUT score. Patients were categorized into surgery-only and platinum-based adjuvant chemotherapy groups. Overall survival (OS) was estimated by the Kaplan-Meier method and compared using the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models stratified by nutritional indices, with particular focus on the CONUT score (low, 0-1; high, ≥2). Results: Among 135 eligible patients (median age, 70 years; 68.1% male), 68 (50.4%) received platinum-based adjuvant chemotherapy. Depending on the index used, 38.5-62.2% of patients were classified as undernourished; 45.9% had high CONUT scores. In patients with low CONUT scores, adjuvant chemotherapy was associated with significantly improved OS compared with surgery alone (HR 0.318, 95% CI: 0.137-0.737; P=0.008), and platinum-based therapy remained an independent prognostic factor in multivariable analysis (HR 0.065, 95% CI: 0.010-0.423; P=0.004). In contrast, in patients with high CONUT scores, adjuvant chemotherapy did not significantly improve OS (HR 0.539, 95% CI: 0.227-1.277; P=0.16). Other nutritional indices did not clearly discriminate the benefit of adjuvant chemotherapy. Conclusions: The preoperative CONUT score appears useful for identifying resectable stage IIA-IIIA NSCLC patients who are likely to benefit from platinum-based adjuvant chemotherapy. Patients with low CONUT scores derive substantial survival benefit, whereas those with high CONUT scores appear to gain limited benefit. CONUT-based risk stratification may help individualize perioperative systemic therapy, especially in the era of immune checkpoint inhibitors (ICIs) and molecular targeted agents.