SANO Trial Results Show Active Surveillance in Esophageal Cancer

Updated data from a phase 3 trial shared at the European Society for Medical Oncology 2026 annual meeting in Madrid indicate that active surveillance could represent a viable approach to enhance quality of life and potentially forgo surgery for locally advanced esophageal cancer patients who attain a complete clinical response following neoadjuvant chemoradiotherapy.

The Tech TL;DR:

Active surveillance yielded a 5-year overall survival rate of 50%, compared with 54% for standard surgery following chemoradiation in the SANO trial.
Distant metastases and esophageal cancer-specific deaths were higher in the active surveillance group.
Roughly 43% of patients in the surveillance arm successfully avoided esophagectomy, reporting better health-related quality of life.

Active Surveillance Shows Similar Survival to Surgery

Among more than 300 patients in the non-inferiority SANO trial, those who underwent active surveillance demonstrated a similar 5-year overall survival rate compared with those who received standard surgery following chemoradiotherapy. At a median of 76 months, roughly half of patients in both treatment groups remained alive. Following neoadjuvant chemoradiotherapy, the cluster-randomized trial recruited 309 patients diagnosed with locally advanced esophageal cancer who reached a complete clinical response verified by PET-CT, ultrasound, or endoscopic biopsies. A total of 198 patients were assigned to active surveillance, while 111 underwent esophagectomy.

Patients had a median age of 68 to 69 years, were mostly male at 78%, and predominantly presented with adenocarcinoma at 75%. Over the median follow-up of 76 months, 5-year overall survival reached 50% in the active surveillance group versus 54% in the standard surgery group, yielding a hazard ratio of 1.17 at a P value of .46. Disease-free survival showed no significant difference either, registering at 42% with surveillance and 50% with surgery at a hazard ratio of 1.39 and a P value of .10.

Distant Metastases and Esophageal Cancer Deaths

Despite comparable overall survival, distant metastases occurred more frequently in the active surveillance group. The distant dissemination rate reached 46% with surveillance compared to 29% with surgery, representing a hazard ratio of 2.04 with a P value under .01. To explore this paradoxical finding, presenter Sanjiv Gangaram Panday, MD, of Erasmus University Medical Center in Rotterdam, the Netherlands, noted that researchers examined cause-specific mortality.

The analysis revealed a higher rate of death specifically from esophageal cancer in the active surveillance group at 40%, compared to 30% in the surgery group, with a subdistribution hazard ratio of 1.67 at a P value of .04. Conversely, death from other causes showed no significant difference between the cohorts, resting at about 10% with active surveillance and 15% with surgery.

Surveillance Spares Some Patients from Esophagectomy

Within the active surveillance group, 16% of participants developed distant metastases, including 11% who experienced metastatic spread within the first 6 months following chemoradiotherapy. Also, 51% developed locoregional regrowth, and 1% developed a second primary esophageal tumor. Conversely, 32% of patients on surveillance maintained a complete clinical response.

That stable group, combined with the 11% of patients who rapidly developed metastatic disease after initial therapy, translated to 43% of patients being spared an esophagectomy, Panday stated. For patients on active surveillance, scheduled clinical response assessments took place every 3 months throughout year one, every 4 months during year two, and every 6 months from then onward. Patients found to have residual disease or regrowth without distant metastases subsequently underwent esophagectomy.

Experts Caution Against Interpreting Long-Term Survival Data

Panday cautioned that the trial was originally powered for a 2-year follow-up, emphasizing that researchers must interpret the updated data alongside proven short-term health-related quality of life benefits and demonstrated cost-effectiveness. Study discussant Filippo Pietrantonio, MD, of Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, concurred that the comparable long-term overall survival needs cautious interpretation, noting the results are not a second non-inferiority test.

Similar survival does not mean similar disease control and does not establish long-term oncological safety, Pietrantonio warned.

Future Monitoring and Patient Selection

Pietrantonio suggested that the approach be reserved for select patients seen at experienced centers.