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 form. For locally advanced ESCC, the standard treatment involves neoadjuvant therapy (chemotherapy, chemoradiotherapy, or chemoimmunotherapy) followed by curative esophagectomy. However, severe postoperative complications (SPCs) remain a significant challenge, impacting recovery and survival.
This study focuses on preserved ratio impaired spirometry (PRISm), a distinct lung function pattern, and its role in predicting SPCs and long-term outcomes in ESCC patients undergoing neoadjuvant therapy and surgery. PRISm, often overlooked, affects 7-13% of the population and is linked to systemic inflammation, cardiometabolic issues, and increased mortality. Yet, its prognostic value in ESCC is unclear.
Systemic inflammation is a key player in surgical recovery and cancer progression. Hematologic indices like 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) are cost-effective markers of immune imbalance and tumor-promoting inflammation. These indices have shown promise in various solid tumors, including ESCC.
The 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. It also sought to develop predictive nomograms for personalized clinical decision-making and improved risk stratification.
The study included ESCC patients who underwent neoadjuvant therapy and curative esophagectomy. PRISm was significantly associated with a higher SPC rate and poorer long-term outcomes. Multivariable analysis identified PRISm and decreased SIRI as independent predictors of SPCs. These findings suggest that PRISm, characterized by small airway dysfunction, may contribute to postoperative complications, while SIRI reflects the immune state in the context of neoadjuvant therapy.
The study also highlighted the prognostic significance of systemic inflammatory biomarkers, with decreased SIRI linked to SPCs and low LMR predicting worse overall survival. These markers capture the dynamic interplay between inflammation and immune surveillance. Notably, pathological nodal status and suboptimal tumor regression significantly predicted poorer survival, emphasizing the importance of nodal downstaging and histopathological response.
The study developed nomograms integrating PRISm, inflammation, and pathology, which outperformed TNM staging in predicting complications and survival. These tools offer personalized risk assessment and perioperative decision support. However, the study has limitations, including its retrospective design and the need for external validation. Further research is needed to explore the biological mechanisms and clinical translation of PRISm-associated inflammation in ESCC.
In conclusion, preoperative PRISm and systemic inflammatory markers are valuable predictors of postoperative complications and survival in ESCC patients undergoing neoadjuvant therapy and surgery. The developed nomograms show promise in personalized risk stratification and clinical decision-making. This study contributes to a more comprehensive understanding of the factors influencing ESCC outcomes and paves the way for improved patient care.
