Neoadjuvant Chemoradiotherapy Added to Surgery for Locally Advanced Esophageal Squamous Cell Carcinoma

Squamous cell carcinoma of the esophagus. Hematoxylin and eosin staining
Investigators compared the efficacy of neoadjuvant chemoradiotherapy plus surgery vs surgery alone for treatment of advanced esophageal squamous cell carcinoma.

Patients with advanced esophageal squamous cell carcinoma (ESCC) who received neoadjuvant chemoradiotherapy (NCRT) prior to surgery had improved overall survival and disease-free survival, according to results from a study published in JAMA Surgery.

Individuals in this randomized, open-label, phase 3 clinical trial were patients with T1-4N1M0/T4N0M0 thoracic ESCC that was histologically proven and potentially resectable (ClinicalTrials.gov Identifier: NCT01216527). A total of 451 patients, predominantly men, aged 18 to 70 years, with a Karnofsky score of 90 or higher were randomized to the experimental NCRT plus surgery (n=224) and control surgery (n=227) groups.

Participants in the NCRT group received vinorelbine and cisplatin every 3 weeks for 2 cycles, with concurrent radiotherapy administered 5 days per week, prior to surgery. The control participants underwent surgery after randomization. Of note, dissection of the bilateral recurrent nerve lymph node was mandated for all study participants who underwent surgery, independent of treatment group.

The primary endpoint of the study was overall survival, defined as the time from the randomization date to the date of death or last follow-up. The secondary endpoint was disease-free survival, defined as the time from the margin-negative resection date to the date of death or recurrence.

Findings indicated a significant improvement in overall survival for patients in the NCRT plus surgery group compared with the surgery group (HR, 0.74; 95% CI, 0.57-0.97; P =.03). After 3 years, patients in the NCRT group had an overall survival rate of 65.8% (95% CI,

59.1%-71.7%) compared with the surgery group at 57.8% (95% CI, 51.0%-64.0%). After 5 years, patients in the NCRT group had an overall survival rate of 59.9% (95% CI, 52.9%-66.1%) compared with the surgery group at 49.1% (95% CI, 42.3%-55.6%).

Disease recurrence was lower in the NCRT plus surgery group (42.3%) compared with the surgery group (59.4%), with results demonstrating significant improvement in disease-free survival (HR, 0.60; 95% CI, 0.45-0.80; P <.001).

Researchers noted that additional research would be necessary before applying the results of this study to those not included in the trial. This includes patients with ESCC who have a lower Karnofsky score and those of more advanced age than the selection criteria considered. This also includes patients outside of China, who are more likely to have esophagogastric junction adenocarcinoma instead of ESCC.

Despite these limitations, researchers believe that, “Neoadjuvant chemoradiotherapy followed by surgical resection may be considered a standard of care for patients with potentially resectable locally advanced ESCC.”

Reference

Yang H, Liu H, Chen Y, et al. Long-term efficacy of neoadjuvant chemoradiotherapy plus surgery for the treatment of locally advanced esophageal squamous cell carcinoma. JAMA Surg. Published online June 23, 2021. doi:10.1001/jamasurg.2021.2373