New Research Highlights Potential for Surgery-Free Management of Esophageal Cancer at ASCO Breakthrough 2024

Several significant studies highlighting new cancer research advances will be presented at the 2024 American Society of Clinical Oncology (ASCO) Breakthrough Meeting in Yokohama, Japan, and online from August 8-10. One of the key topics is esophageal cancer. Researchers report that patients with esophageal squamous cell carcinoma (ESCC) who achieve a complete response to neoadjuvant chemoradiation might delay or avoid surgery by using regular clinical response evaluations to monitor for residual cancer cells or distant recurrence.

Active Surveillance Could Spare Squamous Cell Esophageal Cancer Patients from Surgery

ESCC forms in the cells lining the inner layer of the esophagus. While ESCC accounts for only 30% of esophageal cancers in the United States, it is the most prevalent type in Asia, with diagnoses there comprising about half of all esophageal cancer cases globally.

The current treatment for locally advanced, resectable ESCC includes neoadjuvant chemoradiation followed by an esophagectomy. Surgery for esophageal cancer involves significant risks of complications and reduced quality of life. Consequently, identifying patients with a true complete response after neoadjuvant chemoradiation remains a critical need. Given the high pathological complete response rate observed in esophageal adenocarcinoma post-neoadjuvant chemoradiation, the preSINO study (NCT03937362) aims to determine whether diagnostic tests can effectively detect residual disease and accurately identify patients with a clinical complete response after neoadjuvant chemoradiation.

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

Among 250 Patients Post-Chemoradiation, 82% Accuracy in Detecting Residual Disease

After neoadjuvant chemoradiation, patients who showed no signs of cancer cells or metastasis underwent another round of clinical response evaluations 10 to 12 weeks later. These evaluations included a PET-CT scan, a bite-on-bite biopsy, and an endoscopic ultrasound with fine-needle aspiration of lymph nodes. During these evaluations, a blood test for circulating tumor DNA (ctDNA) was also conducted. Unless distant cancer spread was detected on the PET-CT scan, patients proceeded to surgery.

The study included 250 patients who received neoadjuvant chemoradiation, followed by diagnostic tests and surgery. The primary endpoint was to determine the false-negative rate of the diagnostic tests in detecting significant residual disease in the resected specimen. Out of 133 patients, 18 had significant residual disease that the bite-on-bite biopsies and endoscopic ultrasound with fine-needle aspiration did not detect. This resulted in a false-negative rate of 13.5%, meeting the study’s predetermined primary endpoint.

Furthermore, researchers assessed the accuracy of the diagnostic tests in predicting any remaining cancer. The bite-on-bite biopsies and endoscopic ultrasound with fine-needle aspiration identified residual cancer with 82% accuracy and correctly confirmed the absence of residual cancer 93% of the time.

Combining PET/CT, Bite-on-Bite Biopsy, and ctDNA Enhances Accuracy in Identifying Distant Metastasis Risk

The study examined the utility of ctDNA testing during clinical response evaluations in predicting distant metastasis after neoadjuvant chemoradiation and surgery. Among the 75 patients who tested positive for ctDNA, 21 (28%) developed distant metastases. In comparison, only 3 (5%) of the 57 patients with negative ctDNA tests experienced distant metastases.

Furthermore, the bite-on-bite biopsies and endoscopic ultrasound with fine-needle aspiration accurately detected remaining local-regional cancer cells. Additionally, ctDNA testing demonstrated potential in predicting higher risk for systemic residual disease.

“The preSINO trial is a novel prospective study demonstrating the importance of clinical response evaluation after neoadjuvant chemoradiation in patients with esophageal squamous cell carcinoma. Combining PET/CT and bite-on-bite biopsy with ctDNA based minimal residual disease detection demonstrated improved accuracy in identifying patients with an increased risk of distant metastases and can help support clinicians in determining whether to escalate or de-escalate treatment,” stated Dr. Vishwanath Sathyanarayanan, a medical oncologist at the Apollo Hospitals in Bangalore.

Author

Bernice Lottering