Neoadjuvant Chemotherapy and Chemoradiotherapy Strategies in Esophageal Cancer

Esophageal cancer remains a major global health challenge with persistently poor survival when managed by surgery alone. Neoadjuvant approaches, administered prior to resection, seek to downstage tumours, improve margin-negative (R0) resection rates and eradicate occult micrometastatic disease. Neoadjuvant chemotherapy typically combines platinum‐based agents with fluoropyrimidines or taxanes, whereas chemoradiotherapy incorporates concurrent radiotherapy to enhance locoregional tumour control. Landmark trials have shown that chemoradiotherapy prior to surgery significantly prolongs overall and disease-free survival in both squamous cell carcinoma and adenocarcinoma subtypes. Perioperative chemotherapy regimens, including modified MAGIC protocols and four-drug combinations such as FLOT, have similarly extended survival in adenocarcinomas of the oesophagus and gastro-oesophageal junction. More recently, integration of immune checkpoint inhibitors into neoadjuvant platforms has yielded higher rates of pathological complete response, heralding a shift towards immunochemotherapy. Optimal strategy selection is guided by tumour histology, anatomical location and patient fitness, within a multidisciplinary framework. Ongoing research focuses on biomarker-driven patient stratification, treatment de-escalation, organ preservation and quality-of-life endpoints to refine the balance between efficacy and toxicity.

Research from Nature Portfolio

A multicentre phase 3 trial evaluated neoadjuvant camrelizumab, a PD-1 inhibitor, combined with albumin-bound paclitaxel and cisplatin in locally advanced oesophageal squamous cell carcinoma. Dual immunochemotherapy yielded markedly higher pathological complete response rates (28.0% and 15.4%) compared with chemotherapy alone (4.7%), while maintaining a tolerable safety profile. These findings introduce immunotherapy into the neoadjuvant setting and support further investigation of checkpoint blockade to enhance tumour eradication prior to surgery.

Neoadjuvant Chemotherapy and Chemoradiotherapy Strategies in Esophageal Cancer publication trend

The graph below shows the total number of articles in neoadjuvant chemotherapy and chemoradiotherapy strategies in esophageal cancer across all publications each year (not limited to Nature Index journals).

Technical terms

Neoadjuvant therapy: Treatment administered before primary surgery to reduce tumour burden and improve surgical outcomes.

Chemoradiotherapy: Combined chemotherapy and radiotherapy delivered concurrently to enhance tumour cell kill and locoregional control.

Pathological complete response (pCR): Absence of viable tumour cells in resected specimen following neoadjuvant treatment.

Trimodality therapy: A treatment approach combining preoperative chemoradiotherapy with surgical resection.

Perioperative chemotherapy: Systemic chemotherapy given before and after surgery to target micrometastases and improve survival.

References

1. Neoadjuvant chemotherapy with or without camrelizumab in resectable esophageal squamous cell carcinoma: the randomized phase 3 ESCORT-NEO/NCCES01 trial. Nature Medicine (2024).
2. Trimodality therapy versus perioperative chemotherapy in the management of locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction (Neo-AEGIS): an open-label, randomised, phase 3 trial. The Lancet Gastroenterology & Hepatology (2023).
3. Individual Participant Data Network Meta-Analysis of Neoadjuvant Chemotherapy or Chemoradiotherapy in Esophageal or Gastroesophageal Junction Carcinoma. Journal of Clinical Oncology (2023).
4. Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): A Phase III Multicenter, Randomized, Open-Label Clinical Trial. Journal of Clinical Oncology (2018).
5. Neoadjuvant chemoradiation followed by surgery versus surgery alone for patients with adenocarcinoma or squamous cell carcinoma of the esophagus (CROSS). BMC Surgery (2008).