# Survival after pathological complete response following neoadjuvant chemotherapy versus chemoradiotherapy for oesophageal squamous cell carcinoma

## TL;DR

Patients with oesophageal cancer who achieve a complete response after chemotherapy have better long-term survival than those after chemoradiotherapy, suggesting chemotherapy-induced complete responses may be better for future treatment strategies.

## Contribution

This study is the first to show that pCR after chemotherapy, not chemoradiotherapy, is associated with superior survival outcomes in oesophageal squamous cell carcinoma.

## Key findings

- Patients achieving pCR after chemotherapy had 5-year OS of 97.5% versus 70.4% after chemoradiotherapy.
- Recurrence-free survival was 80.8% after chemotherapy versus 63.7% after chemoradiotherapy among pCR patients.
- Multivariable analysis confirmed a significant survival advantage for chemotherapy in pCR patients.

## Abstract

Although several oesophageal squamous cell carcinoma (OSCC) studies have reported no definitive overall survival (OS) differences between neoadjuvant chemoradiotherapy (NACRT) and neoadjuvant chemotherapy (NAC), the higher pCR rate with NACRT has been viewed as a potential advantage. Beyond ongoing concerns about the validity of pCR as a surrogate endpoint, it remains uncertain whether survival differs between these modalities among patients with OSCC who achieve pCR.

An integrated analysis of individual patient data (IPD) from phase III trials evaluating perioperative therapies for resectable OSCC was conducted, emphasizing prognostic differences between NAC and NACRT, particularly among patients who achieved pCR.

IPD from seven phase III RCTs across six countries included data for 1044 patients with OSCC (83.5% male; mean age of 62.3 years). Of these patients, 605 (58.0%) received NAC and 439 (42.0%) received NACRT, with R0 resection rates of 89.6% versus 84.7% and pCR rates of 6.9% versus 34.2% respectively. Among patients who achieved pCR (192 patients), 5-year OS was 97.5% in the NAC group and 70.4% in the NACRT group, while 5-year recurrence-free survival was 80.8% and 63.7% respectively. Multivariable analysis demonstrated a significant survival advantage for NAC among patients who achieved pCR.

Among patients who achieved pCR, postoperative outcomes varied considerably by neoadjuvant treatment modality. The markedly favourable prognosis associated with pCR after NAC suggests that these patients may represent an optimal candidate cohort for future evaluation of surgery-avoidance and watch-and-wait strategies.

In an integrated analysis of individual patient data from seven phase III randomized trials of resectable oesophageal squamous cell carcinoma, survival outcomes among patients achieving pCR differed substantially by neoadjuvant treatment modality. Despite a higher pCR rate with neoadjuvant chemoradiotherapy, patients achieving pCR after neoadjuvant chemotherapy had significantly superior long-term overall and recurrence-free survival. These findings indicate that pCR is not an equivalent prognostic endpoint across treatment modalities and suggest that pCR after chemotherapy may identify patients suitable for organ-preserving strategies.