Active surveillance after neoadjuvant chemoradiotherapy for esophageal cancer

Abstract

For patients with locally advanced esophageal cancer who have a clinical complete response rate after neoadjuvant chemoradiotherapy, active surveillance could be introduced as an alternative approach to standard surgery during patient counseling based on the results of a trial showing the noninferiority of active surveillance to standard surgery.¹

The phase 3, multicenter, cluster-randomized, noninferiority Surgery as Needed for Oesophageal Cancer (SANO) trial included both an intention-to-treat analysis, which included 776 patients (275 had a clinical complete response and were assigned to active surveillance [n = 156] or standard surgery [n = 118]), and a modified intention-to-treat analysis (allowing for patients with a complete response to cross over into the active surveillance group), which included 309 patients (198 underwent active surveillance, and 111 underwent standard surgery). Most of these patients had adenocarcinoma (147 in the active surveillance cohort and 84 in the surgery cohort), which was followed by squamous cell carcinoma (47 and 32 patients, respectively) and other types of carcinomas (four patients in each cohort). Clinical complete response was defined as no tumor detected based on endoscopic biopsy, ultrasound, or positron emission tomography–computed tomography (PET-CT). All patients were at least 18 years old, had locally advanced esophageal cancer, and were treated with curative intent. No patients were excluded based on comorbidities or performance status.

After a minimum 2-year follow-up, overall survival (OS) with active surveillance was noninferior to OS with standard surgery (71%) after the modified intention-to-treat analysis. It remained noninferior in the intention-to-treat analysis (75%), with no significant differences in OS between the modified intention-to-treat analysis (hazard ratio [HR], 1.14; 95% CI, 0.74–1.78) and the intention-to-treat analysis (HR, 0.83; 95% CI, 0.53–1.31).

According to a patient-reported quality-of-life assessment, patients who underwent active surveillance had significantly better global health-related quality of life than those who underwent surgery at both 6 months (increase of 10.4 points, p = .001) and 9 months (increase of 8.5 points, p = .009). No significant differences between the two cohorts in global health-related quality of life were seen at 12 months.

The lead author of the study, Berend J. van der Wilk, MD, PhD, a surgical resident in the Department of Surgery at the Erasmus MC Cancer Institute of the University Medical Centre in Rotterdam, the Netherlands, says that the results suggest that oncologists consider organ-sparing active surveillance for their patients with locally advanced esophageal cancer.

“If you proceed with active surveillance, please be sure to perform clinical response evaluations according to SANO protocol,” he emphasizes. This includes evaluating the clinical response with PET-CT, endoscopy with bite-on-bite biopsies, and endoscopic ultrasound and fine-needle aspiration of all suspected lymph nodes.

Commenting on the study, Michael Gibson, MD, PhD, an associate professor of medicine and the director of translational research for esophagogastric cancer at the Vanderbilt University Medical Center in Nashville, Tennessee, says that the results indicate that “active surveillance followed by salvage surgery for local recurrence is an option for patients treated with concurrent chemoradiotherapy with curative intent.”

He notes, however, that 75% of the patients in the study had adenocarcinoma and may have been candidates for perioperative chemotherapy. For such candidates, treatment is now shifting toward omitting radiotherapy based on the recent results of the ESOPEC trial, which established perioperative chemotherapy as the standard of care for esophageal adenocarcinoma treated with curative intent via surgery.²

“However, the treatment approach in the SANO trial of using neoadjuvant chemoradiotherapy remains an option for patients and providers who do not choose the ESOPEC approach,” he says. “It is also an option for patients who may not want surgery, and it still applies to those with squamous cell carcinoma.”