Active surveillance may be a feasible strategy for improving quality of life and potentially avoiding surgery in patients with locally advanced esophageal cancer who have a clinical complete response to neoadjuvant chemoradiation, according to updated findings from a phase 3 study.

Among more than 300 patients in the non-inferiority SANO trial, those who underwent active surveillance had a similar 5-year overall survival rate as those who received standard surgery following chemoradiation. At a median of 76 months, roughly half of patients in both treatment groups were still alive.

However, distant metastases were more common in the active surveillance group, as were deaths from esophageal cancer, specifically.

The findings, presented at the European Society for Medical Oncology 2026 annual meeting in Madrid, build on prior data from the trial showing that active surveillance was non-inferior to surgery in terms of 2-year overall survival. There was a numerically higher rate of distant metastases with surveillance, but overall, the approach gave patients a better health-related quality of life vs esophagectomy.

“We think these findings support the concept of active surveillance after chemoradiotherapy,” said presenter Sanjiv Gangaram Panday, MD, of Erasmus University Medical Center in Rotterdam, the Netherlands.

However, the comparable long-term overall survival with active surveillance needs to be interpreted cautiously, according to study discussant Filippo Pietrantonio, MD, of Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy.

He suggested that for now, the approach be reserved for select patients seen at experienced centers.

Neoadjuvant chemoradiotherapy followed by esophagectomy has long been a standard treatment for patients with locally advanced esophageal cancer. While nearly a third of patients will achieve complete clinical response after these two interventions, Panday said, 30%–40% still develop distant metastases. 

Meanwhile, 60% of patients undergoing esophagectomy experience complications, and the procedure can take a significant toll on quality of life.

So the SANO (Surgery As Needed for Oesophageal Cancer) trial sought to determine whether some patients can safely undergo active surveillance rather than immediate surgery after neoadjuvant therapy.

The cluster-randomized trial enrolled 309 patients with locally advanced esophageal cancer who achieved complete clinical response — based on no tumor detected on endoscopic biopsies, ultrasound, or PET-CT — following neoadjuvant chemoradiotherapy. A total of 198 patients were assigned to active surveillance, while 111 underwent esophagectomy. Patients (median age, 68-69 years) were mostly male (78%) and most had adenocarcinoma (75%). 

Active surveillance involved planned clinical response evaluations every 3 months in the first year, every 4 months in the second year, and every 6 months thereafter. Patients found to have residual disease or regrowth without distant metastases underwent esophagectomy. 

Over a median of 76 months, 5-year overall survival was similar in the active surveillance and standard surgery groups, at 50% vs 54%, respectively (hazard ratio [HR], 1.17; P = .46). There was also no significant difference in disease-free survival, at 42% with surveillance and 50% with surgery (HR, 1.39; P = .10). 

However, the distant dissemination rate did differ significantly, at 46% with surveillance vs 29% with surgery (HR, 2.04; P < .01). 

To further explore that “paradoxical finding,” Panday said, the researchers looked at cause-specific mortality. And they found a higher rate of death from esophageal cancer with active surveillance than with surgery: 40% vs 30% (sHR, 1.67; P = .04).

In contrast, death from other causes was not significantly different between the groups, at about 10% with active surveillance and 15% with surgery (sHR, 0.49; P = .08). 

In the active surveillance group, 16% of participants developed distant metastases, including 11% who developed metastases within the first 6 months after chemoradiotherapy. In addition, 51% developed locoregional regrowth, while 1% developed a second primary esophageal tumor.

On the other hand, 32% of patients on surveillance maintained a complete clinical response. That group, along with the 11% of patients who rapidly developed metastatic disease after neoadjuvant therapy, translates to 43% of patients being spared esophagectomy, Panday said.

He cautioned, however, that the trial was powered for a 2-year follow-up.

“We really have to interpret these findings with the proven 2-year non-inferiority, combined with the proven better health-related quality of life at the short-term, and also the demonstrated cost-effectiveness of active surveillance compared to standard surgery,” Panday said.

Pietrantonio also underscored that point, noting that the updated overall survival results are “not a second non-inferiority test.”

Importantly, he said, “similar survival does not mean similar disease control and does not establish long-term oncological safety.”

Pietrantonio also noted some important considerations in the trial’s surgery arm that may have contributed to “potentially suboptimal” disease-free survival outcomes. For one, patients with residual disease did not receive adjuvant nivolumab, which has been shown to improve disease-free survival in patients without a pathological complete response.

Relatedly, Pietrantonio said, the trial’s yardstick of clinical complete response “does not necessarily mean pathological complete response,” and only 37% of patients in the surgery group had a pathological complete response.

Going forward, use of circulating tumor DNA (ctDNA) may aid in making treatment decisions, according to Pietrantonio. 

“In the future, I think that lack of ctDNA clearance may help exclude patients from the surveillance strategy, and serial monitoring may trigger earlier clinical reassessment,” he said. 

For now, Pietrantonio offered some thoughts on how to translate the SANO findings into clinical practice. 

“I believe that the go [or] no-go decision about surgery should be made upfront when defining the initial treatment strategy,” based on factors including histology, resectability, and patient fitness, he said.

However, Pietrantonio added, active surveillance “may still be discussed” for carefully selected patients with clinical complete remission — though he also specified that the approach is suited to “experienced, high-volume centers.”

Discussions around surveillance, Pietrantonio said, should include informing patients of the need for intensive monitoring, as well as the significant rates of locoregional recurrence and distant metastases.

The research was funded by the Dutch Cancer Society and Netherlands Organization for Health Research and Development. The authors reported no relevant financial relationships. Pietrantonio reported financial relationships with numerous sources, including Lilly, BMS, Incyte, AstraZeneca, and Amgen.