Esophageal cancer, a significant global health concern, is the 11th most common cancer and the 7th leading cause of cancer-related deaths worldwide. In East Asia, particularly China, esophageal squamous cell carcinoma (ESCC) is the predominant subtype. For patients with locally advanced ESCC, the standard treatment involves neoadjuvant therapy (chemotherapy, chemoradiotherapy, or chemoimmunotherapy) followed by curative esophagectomy. However, despite advancements in surgical techniques and perioperative care, severe postoperative complications (SPCs) remain a substantial issue, impacting patient outcomes and survival.
Identifying reliable preoperative predictors of SPCs and understanding their impact on long-term survival is crucial for personalized treatment planning and improved patient care. One such predictor is preserved ratio impaired spirometry (PRISm), a distinct spirometric pattern indicating small airway dysfunction. PRISm, often overlooked, affects a significant portion of the population and is linked to systemic inflammation, cardiometabolic comorbidities, and increased mortality. Its role in thoracic malignancies, including ESCC, has not been thoroughly explored.
Systemic inflammation, a key player in surgical recovery and cancer progression, is assessed using various hematologic indices like the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and others. These indices provide insights into immune imbalance and tumor-promoting inflammation, offering prognostic value in solid tumors, including ESCC.
This study aimed to evaluate the impact of preoperative PRISm and inflammatory biomarkers on short-term (SPC incidence) and long-term outcomes (overall survival and recurrence-free survival) in ESCC patients undergoing neoadjuvant therapy and surgery. The goal was to develop predictive models to guide personalized clinical decisions and enhance perioperative risk stratification.
The study included 224 ESCC patients who underwent neoadjuvant therapy and curative esophagectomy. Results showed that PRISm was significantly associated with a higher incidence of SPCs and poorer long-term survival. Mechanistically, PRISm's small airway dysfunction predisposes patients to respiratory complications post-surgery. Multivariate analysis identified PRISm and the systemic inflammation response index (SIRI) as independent predictors of SPCs.
Survival analyses revealed that PRISm was independently associated with worse overall survival and recurrence-free survival. Potential mechanisms include reduced cardiopulmonary reserve, comorbid conditions, and a persistent pro-inflammatory state. The study also validated the prognostic significance of systemic inflammatory biomarkers, with decreased SIRI and low lymphocyte-to-monocyte ratio (LMR) predicting poorer outcomes.
Pathological nodal status and suboptimal tumor regression were also significant predictors of survival, highlighting the importance of nodal downstaging and histopathological response. Interestingly, patients who received neoadjuvant chemoradiotherapy had shorter recurrence-free survival compared to those treated with chemotherapy or chemoimmunotherapy, suggesting the need for individualized treatment approaches.
The study developed nomograms integrating PRISm, inflammation, and pathology, which outperformed TNM staging in predicting complications and survival. These tools offer a comprehensive understanding of the core factors contributing to all-cause mortality and can support personalized risk stratification and perioperative decision-making.
While the study provides valuable insights, it has limitations, including its retrospective, single-center design and potential selection and information biases. Further prospective, multicenter validation is essential to confirm the predictive value of PRISm and systemic inflammatory markers across diverse populations. Additionally, exploring the biological mechanisms underlying PRISm-associated inflammation and its role in tumor progression is crucial for advancing our understanding and treatment strategies.
In conclusion, preoperative PRISm is an independent predictor of severe postoperative complications and poorer survival in ESCC patients undergoing neoadjuvant therapy and surgery. Systemic inflammatory markers, particularly SIRI and LMR, also hold prognostic value. The developed nomograms offer a powerful tool for personalized risk assessment and clinical decision-making. Further research and validation are warranted to enhance our understanding and improve patient outcomes in ESCC.
