Esophageal cancer is a global health crisis, ranking as the 11th most common cancer and the 7th deadliest. In East Asia, particularly China, esophageal squamous cell carcinoma (ESCC) is the most prevalent type. For locally advanced ESCC, the standard treatment involves neoadjuvant therapy (chemotherapy, chemoradiotherapy, or chemoimmunotherapy) followed by curative esophagectomy.
Despite surgical advancements, severe postoperative complications (SPCs) remain a significant concern, especially those graded as Clavien–Dindo III or higher. These complications lead to prolonged hospital stays, increased healthcare costs, and poorer long-term survival. Therefore, identifying preoperative predictors of SPCs and oncologic outcomes is crucial for personalized treatment strategies and perioperative management.
Preserved ratio impaired spirometry (PRISm) is a unique spirometric pattern, often overlooked, affecting 7–13% of the population. It is characterized by a forced expiratory volume in one second (FEV1) below 80% predicted, with a preserved FEV1/FVC ratio (≥ 0.7). PRISm has been linked to systemic inflammation, cardiometabolic conditions, and increased mortality. However, its prognostic value in thoracic malignancies like ESCC is not well understood.
Systemic inflammation plays a critical role in surgical recovery and cancer progression. Several inflammation-based hematologic indices, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI), have emerged as cost-effective markers of immune imbalance and tumor-promoting inflammation. These indices have shown prognostic value in various solid tumors, including ESCC.
This study aimed to investigate the combined predictive value of preoperative PRISm and systemic inflammatory markers in ESCC patients undergoing neoadjuvant therapy and surgery. The goal was to develop and validate predictive nomograms for personalized clinical decision-making and improved perioperative risk stratification.
The study included patients with histologically confirmed ESCC who underwent neoadjuvant therapy followed by curative esophagectomy. Pulmonary function tests and hematological analyses were performed preoperatively. Patients received one of three neoadjuvant regimens: chemotherapy, chemoimmunotherapy, or chemoradiotherapy. Curative esophagectomy was performed using minimally invasive or robotic-assisted techniques.
Results showed that preoperative PRISm was significantly associated with a higher incidence of SPCs and poorer long-term outcomes (overall survival and recurrence-free survival). PRISm was characterized by small airway dysfunction, which may contribute to postoperative complications. Multivariable logistic regression identified PRISm and decreased SIRI as independent predictors of SPCs. These findings suggest that preoperative SIRI may reflect treatment-related immunosuppression or immune paralysis.
In survival analyses, PRISm was independently associated with worse OS and RFS. The study also validated the prognostic significance of systemic inflammatory biomarkers, with decreased SIRI predicting SPCs and low LMR predicting worse OS. These indices reflect the dynamic interaction between tumor-promoting inflammation and host immune surveillance.
The study developed nomograms integrating PRISm, inflammation, and pathology, which outperformed TNM staging in predicting complications and survival. These tools can support personalized risk stratification and guide perioperative decision-making. However, the study has limitations, including its retrospective design, heterogeneity in neoadjuvant regimens, and the need for prospective multicenter validation to confirm the predictive value of PRISm and systemic inflammatory markers across diverse populations.
In conclusion, preoperative PRISm independently predicted severe postoperative complications and worse survival in ESCC patients undergoing neoadjuvant therapy and surgery. Systemic inflammatory markers, especially SIRI and LMR, also held prognostic value. The developed nomograms offer powerful decision-support aids for clinicians, but further validation is warranted to ensure their clinical translation.
