Although esophageal cancer in the United States is relatively rare—affecting about 22,400 people each year and making up about 1% of all cancer cases—the disease is common in East and Central Asian countries. Nearly 90% of patients with esophageal cancer in Asia are diagnosed with the squamous cell carcinoma subtype.

Although standard treatment for locally advanced, resectable esophageal squamous cell carcinoma is neoadjuvant chemoradiation followed by esophagectomy, the surgery is associated with complications and a reduced quality of life.

Results from the preSINO trial showed that patients with esophageal squamous cell carcinoma who experience a clinical complete response after neoadjuvant chemoradiation therapy may be able to postpone or avoid surgery and additional systemic therapy by using clinical response evaluations at regular intervals to detect residual tumor cells or distant disease recurrence. The use of an active surveillance strategy for the cancer may help to optimize treatment approaches, according to findings to be presented by Li et al during the 2024 ASCO Breakthrough meeting in Yokohama, Japan (Abstract 196).

Study Methodology

The goal of the preSino trial, a prospective multicenter diagnostic cohort study in Asia, was to assess the accuracy of response evaluations after neoadjuvant chemoradiotherapy based on the results of the preSANO trial, including positron-emission tomography with computed tomography (PET-CT), endoscopy with bite-on-bite biopsies, and endoscopic ultrasonography with fine-needle aspiration in patients with potentially curable esophageal squamous cell carcinoma.

Patients were eligible to enroll in the study after neoadjuvant chemoradiotherapy followed by standard surgery. Patients received their first clinical response evaluations (bite-on-bite biopsies) 4 to 6 weeks after completion of neoadjuvant chemoradiotherapy.

Patients with locoregional residual tumor and without distant metastases underwent immediate surgery. For patients with a clinical complete response at their first clinical response evaluation, a second evaluation was done 10 to 12 weeks after completion of neoadjuvant chemoradiotherapy using PET-CT, bite-on-bite biopsies, and endoscopic ultrasonography with fine-needle aspiration (EUS-FNA) of suspicious lymph nodes.

All patients underwent surgery regardless of the outcome of the second clinical response evaluation, in the absence of distant metastases. Circulating tumor DNA (ctDNA) analyses based on a tumor-informed assay were performed at baseline and clinical response evaluations for exploratory analysis. The primary endpoint was the accuracy of clinical response evaluations for detecting tumor regression grade (TRG) 3–4 or TRG 1–2 with ypN+ residual tumor. A false-negative rate of 19.5% was considered acceptable according to the study protocol.

Key Results

From August 2019 to January 2023, researchers enrolled 309 patients, and 250 patients underwent neoadjuvant chemoradiotherapy plus surgery. Of 133 patients with TRG 3–4 or TRG 1–2 with ypN+ residual tumor, 18 were not detected by bite-on-bite biopsies and EUS-FNA (false-negative rate = 13.5%). Sensitivity, specificity, negative predictive value, and positive predictive value of detecting any residual tumor were 82%, 93%, 69%, and 97%, respectively. PET-CT detected interval distant metastases in 13 of 268 patients (5%) prior to surgery. Postoperative distant recurrence rates among patients with ctDNA-positive and ctDNA-negative results during clinical response evaluations were 15.1% (11/73) and 3.3% (2/59), respectively.

“Bite-on-bite biopsies and EUS-FNA for lymph nodes were accurate for detecting locoregional residual disease after neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma. Post–neoadjuvant chemoradiotherapy ctDNA-positive [status] during clinical response evaluations may indicate an increased risk of long-term distant metastasis, potentially serving as a diagnostic tool to identify patients who would benefit from postponement of surgery and additional systemic therapy. The long-term follow-up results of this trial will further answer this question,” concluded the study authors.

Clinical Significance

“Our study is important because it addresses whether we can accurately and safely evaluate residual tumors in esophageal squamous cell carcinoma after neoadjuvant treatment,” said Zhigang Li, MD, PhD, lead author of the study and Chief in the Department of Thoracic Surgery at Shanghai Chest Hospital, in a statement. “Our preSINO study adapted methods from the previous European preSANO trial in esophageal adenocarcinoma to esophageal squamous cell carcinoma in Asia and explored ctDNA testing to enhance accuracy. This research helps expand the use of an active surveillance strategy for esophageal adenocarcinoma to optimize treatment approaches.”

Disclosure: For full disclosures of the study authors, visit coi.asco.org.