Recurrence-free survival as a surrogate endpoint for overall survival after neoadjuvant chemotherapy and surgery for oesophageal squamous cell carcinoma

Br J Surg. 2024 Jan 31;111(2):znae038. doi: 10.1093/bjs/znae038.

Abstract

Background: Overall survival is considered as one of the most important endpoints of treatment efficacy but often requires long follow-up. This study aimed to determine the validity of recurrence-free survival as a surrogate endpoint for overall survival in patients with surgically resectable advanced oesophageal squamous cell carcinoma (OSCC).

Methods: Patients with OSCC who received neoadjuvant cisplatin and 5-fluorouracil, or docetaxel, cisplatin and 5-fluorouracil, at 58 Japanese oesophageal centres certified by the Japan Esophageal Society were reviewed retrospectively. The correlation between recurrence-free and overall survival was assessed using Kendall's τ.

Results: The study included 3154 patients. The 5-year overall and recurrence-free survival rates were 56.6 and 47.7% respectively. The primary analysis revealed a strong correlation between recurrence-free and overall survival (Kendall's τ 0.797, 95% c.i. 0.782 to 0.812) at the individual level. Subgroup analysis showed a positive relationship between a more favourable pathological response to neoadjuvant chemotherapy and a higher τ value. In the meta-regression model, the adjusted R2 value at the institutional level was 100 (95% c.i. 40.2 to 100)%. The surrogate threshold effect was 0.703.

Conclusion: There was a strong correlation between recurrence-free and overall survival in patients with surgically resectable OSCC who underwent neoadjuvant chemotherapy, and this was more pronounced in patients with a better response to neoadjuvant chemotherapy.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols
  • Biomarkers
  • Cisplatin / therapeutic use
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / surgery
  • Esophageal Squamous Cell Carcinoma* / drug therapy
  • Esophageal Squamous Cell Carcinoma* / surgery
  • Fluorouracil / therapeutic use
  • Humans
  • Neoadjuvant Therapy
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Cisplatin
  • Biomarkers
  • Fluorouracil