**Background:** Although phase III trials have demonstrated improved overall survival with nivolumab compared to taxane chemotherapy in advanced esophageal squamous cell carcinoma, only a limited number of patients benefit from immunotherapy. Nutritional status is known to affect treatment outcomes in gastrointestinal cancers, and simple screening tools such as the prognostic nutritional index (PNI), Glasgow prognostic score (GPS), and neutrophil-to-lymphocyte ratio (NLR) are commonly used. This study aimed to determine whether pretreatment nutritional status correlates with prognosis in advanced esophageal cancer patients treated with either taxane or nivolumab therapy.
**Methods:** The medical records of 35 patients who received taxane monotherapy (paclitaxel or docetaxel) for advanced esophageal cancer between October 2016 and November 2018 (taxane cohort) and 37 patients who received nivolumab monotherapy between March 2020 and September 2021 (nivolumab cohort) at Hyogo Cancer Center Hospital, Japan, were retrospectively reviewed. Eligibility criteria included age ≥20 years, histologically confirmed esophageal cancer, measurable or evaluable lesions per RECIST version 1.1, ECOG PS ≤2, and refractoriness or intolerance to fluoropyrimidine-based and platinum-based chemotherapy. PNI was calculated as [10 × albumin (g/dL) + 0.005 × absolute lymphocyte count/μL] with a cut-off of 45. GPS assigned scores of 0, 1, or 2 based on CRP (>1.0 mg/dL) and albumin (<3.5 g/dL) levels. NLR used a threshold of 5. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier methods and log-rank tests, with univariate Cox proportional hazards models for hazard ratios.
**Key Results:** The median age was 64 years (range 46–81) in the taxane cohort and 67 years (range 46–84) in the nivolumab cohort. Squamous cell carcinoma was the predominant histology in both groups. The nivolumab cohort had significantly more patients with two or more prior therapies (p=0.013). The overall response rate was 20.0% (5/25) for taxane and 22.2% (6/27) for nivolumab, with two complete responses in the nivolumab group. Median OS was 9.1 months (95% CI: 5.0–13.2) in the taxane cohort and 12.5 months (95% CI: 5.3–19.8) in the nivolumab cohort. In the taxane cohort, nutritional status markers did not significantly predict OS (PNI: HR=1.326, p=0.437; GPS: HR=1.831, p=0.105; NLR: HR=1.501, p=0.314). In contrast, in the nivolumab cohort, patients with good nutritional status had significantly better OS: by PNI, 18.1 vs. 7.6 months (p=0.009); by GPS, 15.5 vs. 4.3 months (p=0.012). Univariate analysis in the nivolumab cohort showed significant associations with OS for number of prior therapies (HR=2.947, p=0.008), PNI (HR=2.725, p=0.012), GPS (HR=2.691, p=0.016), albumin (HR=4.406, p=0.007), and CRP (HR=2.577, p=0.025). NLR showed a non-significant trend (13.0 vs. 8.1 months, p=0.312). PFS analysis showed low PNI was significantly associated with better PFS (5.1 vs. 1.9 months, p=0.018).
**Clinical Implications:** This study demonstrates that pretreatment nutritional status is a key prognostic factor specifically for patients with advanced esophageal cancer receiving nivolumab immunotherapy, whereas it has less impact on outcomes with taxane chemotherapy. The findings suggest that nutritional assessment using simple, readily available markers (PNI, GPS) could help identify patients most likely to benefit from nivolumab. Importantly, unlike genetic or molecular biomarkers, nutritional status is modifiable through interventions, raising the possibility that pre-treatment nutritional optimization could improve immunotherapy outcomes. The authors note they are conducting a prospective clinical trial (ENTRANCE study; UMIN 000043548) to evaluate the efficacy of nivolumab combined with nutritional counseling. Limitations include the retrospective design, small sample size, lack of PD-L1 and CD8+ tumor analysis, and inability to perform subgroup analysis by histology. Despite these limitations, the study provides a strong rationale for incorporating nutritional management into the treatment paradigm for advanced esophageal cancer patients being considered for immunotherapy.