Prognostic Value of Dynamic Lactate Dehydrogenase Trends in Immunotherapy for Advanced Esophageal Squamous Cell Carcinoma: Retrospective Cohort Study.

Background: Immune checkpoint inhibitors (ICIs) have emerged as a pivotal treatment for advanced esophageal squamous cell carcinoma (ESCC). However, their efficacy can significantly differ among patients, highlighting the need for reliable prognostic markers to enhance treatment outcomes. Lactate dehydrogenase (LDH) plays a key regulatory role in the complex relationship between cancer metabolism and the immune system, suggesting that monitoring LDH levels may provide valuable insights into treatment efficacy and inform personalized therapeutic strategies for advanced ESCC. Objective: This study aimed to explore the prognostic significance of dynamic changes in LDH levels during ICI therapy in predicting treatment outcomes. Methods: We retrospectively analyzed the clinical data of 126 patients with advanced ESCC who received first-line ICI therapy at the Department of Radiation Oncology, Cancer Center, Shandong Provincial Hospital, between April 2018 and November 2022. Serum LDH levels were measured after every 3 cycles of combined immunotherapy and chemotherapy. Receiver operating characteristic curve analysis determined the optimal LDH reduction threshold. Kaplan-Meier survival curves and Cox regression models assessed progression-free survival (PFS) and overall survival. Results: Among the 126 patients, 55 (43.6%) were classified into the LDH-increased group, while 71 (56.4%) belonged to the LDH-decreased group. Within the LDH-increased group, 78.2% (43/55) of the patients were male, compared to 90.1% (64/71) in the LDH-decreased group. The median age of patients in the LDH-increased group was 59 (range 55-68) years, whereas the median age in the LDH-decreased group was 65 (range 58-65) years. LDH decrease following first-line ICI therapy was associated with improved outcomes compared to LDH increases (median PFS 13.4, IQR 8.1-24.3 mo vs median 10.8, IQR 4.8-20.6 mo; P= .03). Patients with a posttreatment LDH decrease of more than 14.4% had a median PFS of 11.1 (IQR 7.2-24.3) months, whereas those with an LDH decrease between 0% and 14.4% had a median PFS of 21.7 (IQR 9.4-34.5) months. Conversely, an increase in LDH resulted in a median PFS of 10.8 (IQR 4.8-20.6) months. Patients with tumor reduction exhibited a significantly greater decrease in LDH levels compared with those without tumor reduction (P<.001). Multivariate analysis identified LDH decrease as an independent predictor of a 41% lower mortality risk (hazard ratio 0.59, 95% CI 0.36-0.96; P=.04). Conclusions: In patients with advanced ESCC, a decrease in serum LDH levels ranging from 0% to 14.4% after treatment initiation was significantly associated with prolonged PFS. Notably, an early decrease in LDH levels observed after 3 cycles of immunotherapy further correlated with improved clinical outcomes. These results highlight the potential of LDH as a valuable biomarker for risk stratification and personalized treatment optimization in advanced ESCC.