Active Surveillance After Chemoradiotherapy for Esophageal Cancer: 5-Year Survival Similar in SANO, Distant Metastasis More Frequent

Deferring Surgery in Esophageal Cancer: What Do the 5-Year SANO Results Show?

In esophageal cancer, when the tumor disappears after preoperative chemoradiotherapy, can close surveillance be used instead of immediate surgery? The 5-year results of the Dutch SANO trial were presented as a late-breaking abstract (LBA78) at ESMO 2026 and published in Annals of Oncology. Five-year overall survival was similar in the active surveillance and standard surgery arms (50% vs 54%). However, distant metastasis (46% vs 29%) and esophageal cancer-related loss of life were more frequent with active surveillance. From the same congress, we have covered the DEWI trial, which investigated non-surgical treatment in gastric cancer, and before the congress ESMO's new guideline on gastric and esophageal cancer; you can find the overall congress agenda in our preview article.

Why does this matter?

Esophageal cancer is the 11th most common cancer worldwide and ranks 7th in cancer-related loss of life (GLOBOCAN 2022). There are two main types: squamous cell carcinoma, which is more common in regions such as Eastern Anatolia and is associated with hot tea, smoking and alcohol, and adenocarcinoma, which is rising in Western countries and is associated with reflux and obesity. For locally advanced disease, the standard treatment is preoperative chemotherapy or chemoradiotherapy followed by removal of the esophagus (esophagectomy).

Esophagectomy is a major operation: the chest and abdominal cavities are opened, the esophagus is removed, and the stomach is pulled up to create a new food passage. The postoperative complication rate is high, and problems such as difficulty swallowing, early satiety, reflux, weight loss and malnutrition can last for years. On the other hand, in about 30% of patients who receive chemoradiotherapy with the Dutch CROSS regimen (about half of those with squamous cell cancer), no tumor at all remains in the surgically removed tissue. The question "Do these patients really benefit from surgery?" has brought organ preservation onto the agenda for the esophagus as well, similar to the watch-and-wait approach in rectal cancer.

What is active surveillance in esophageal cancer?

Active surveillance means that in patients with no detectable tumor on endoscopy, biopsy, endoscopic ultrasound and PET-CT after preoperative chemoradiotherapy (clinical complete response), the esophagus is checked at regular intervals instead of being removed right away, and surgery is performed only if the tumor regrows. The aim is to avoid the side effects of surgery while preserving the chance of curative surgery when needed.

How was the SANO trial conducted?

Results

Survival

Five-year overall survival was 50% with active surveillance and 54% with standard surgery (HR 1.17; 95% CI 0.77–1.77; p=0.46). Disease-free survival was also not statistically different (42% vs 50%; HR 1.39; p=0.10). Overall survival followed a similar course in squamous cell cancer and adenocarcinoma. In the 2-year analysis, overall survival had been 74% vs 71%.

Distant metastasis and cancer-related loss of life

The most notable finding is the difference in distant metastasis. Within 5 years, distant metastasis developed in 46% of patients in the active surveillance arm and 29% in the surgery arm (HR 2.04; p<0.01). Esophageal cancer-related loss of life was also more frequent with active surveillance (40% vs 30%; HR 1.67; 95% CI 1.02–2.73). In contrast, loss of life from other causes was numerically lower in the surveillance arm (10% vs 15%; HR 0.49; not significant). In other words, the similar overall survival may have been partly balanced by fewer losses in the surveillance arm stemming from the risks of surgery itself and from other illnesses.

Of the 91 metastases in the active surveillance arm, 22 were detected within the first 6 months after chemoradiotherapy, that is, most likely in disease that would have appeared regardless of the arm; 44 developed after delayed surgery. Local regrowth of the tumor increased the subsequent risk of distant metastasis about 2.5-fold (HR 2.49). This trial cannot distinguish whether this association results from tumor spread or from more aggressive tumor biology.

How many patients were spared surgery?

In the active surveillance arm, 43% of patients did not undergo esophagectomy. However, 11 percentage points of this figure consist of patients who developed distant metastasis in the first months after chemoradiotherapy and were therefore not operated on. The true organ preservation rate was 32%, and 21% of patients completed 5 years of follow-up with their esophagus preserved. In about half of the patients in the surveillance arm (51%), the tumor regrew locally; most of these patients were treated with delayed surgery. The 2-year analysis had reported that complication and loss-of-life rates after delayed surgery were similar to those after standard surgery, and that active surveillance improved quality of life in the first months and was less costly.

What do the experts say?

Dr. Sanjiv Gangaram Panday of Erasmus Medical Center in Rotterdam, who presented the trial, emphasized that the trial was powered for the 2-year analysis and that the long-term results should be weighed together with the short-term quality-of-life and cost benefits. The discussant, Dr. Filippo Pietrantonio (Milan), stated that the similar overall survival should be interpreted with caution, that similar survival does not mean similar disease control and does not prove long-term oncological safety; he recommended limiting the approach to selected patients at experienced centers. Some commentators also pointed out that 41.4 Gy is a preoperative dose, that is, below the dose used for definitive radiotherapy.

How should the results be interpreted?

Strengths

• The largest controlled trial with the longest follow-up comparing organ preservation with surgery in esophageal cancer.
• Median follow-up of 76 months; 5-year overall survival, disease-free survival, metastasis and cause-specific loss of life were reported together.
• Response assessment was carried out with a standardized, rigorous protocol (PRE-SANO).
• Unfavorable findings (the increase in metastasis) were reported openly and discussed in the presentation.

Points to consider

• Not definitive equivalence: The trial was not designed to show non-inferiority at 5 years; the absence of a significant difference does not prove that the two approaches are equivalent. The confidence interval (0.77–1.77) does not rule out meaningful harm.
• Increase in metastasis and cancer-related loss of life: This points to a real oncological risk and should be explained clearly to patients.
• Randomization not at the patient level: The stepped-wedge cluster design may lead to differences in time period and center between the arms.
• Predominantly adenocarcinoma and a single country: Three quarters of the patients had adenocarcinoma; generalizing to countries such as Turkey, where squamous cell cancer is more common, requires caution.
• The standard of care has changed: After the ESOPEC trial, preoperative FLOT chemotherapy began to be preferred over CROSS for adenocarcinoma; postoperative treatments such as nivolumab were also not widely used when the trial was designed.
• Intensive surveillance burden: It requires frequent endoscopy, biopsy, endoscopic ultrasound and PET-CT for years; adherence to surveillance is critical.

What does this mean in practice?

• Shared decision-making is essential: Patients should know, in numbers, the balance between "the chance of living without surgery" and "the increase in the risk of distant metastasis." The decision should be made by a board that brings together the surgeon, the radiation oncologist and the medical oncologist.
• Experienced center: Response assessment (deep biopsy, endoscopic ultrasound, PET-CT) and delayed surgery require a team experienced in this field. False-positive PET-CT results and radiotherapy-related changes can make interpretation difficult.
• The first 2 years of surveillance are critical: Most local regrowths occur during this period; check-up appointments should not be missed.
• Tumor type: Most patients in SANO had adenocarcinoma. In squamous cell cancer, complete response to chemoradiotherapy is more common and definitive chemoradiotherapy without surgery is already an option; the organ preservation discussion in this group should take place within a different framework.
• Parallels with other organs: Organ preservation approaches such as watch-and-wait after chemoradiotherapy in rectal cancer and bladder-sparing treatment are likewise used in selected patients; the debate over surgery versus radiotherapy in prostate cancer involves a similar question of balance.

Practical advice for patients and their families

• If your tumor has disappeared after chemoradiotherapy, ask your team about the possible benefits and risks of both surgery and active surveillance, in numbers.
• If you choose active surveillance, get your check-up schedule in writing and do not miss any appointment; endoscopy and imaging are the foundation of this approach's safety.
• If you have symptoms such as difficulty swallowing, weight loss, chest or back pain, vomiting blood or black stools, seek care without waiting for your check-up date.
• The surveillance period can be stressful; share these feelings with your team and seek psychological support if needed.
• Pay attention to your diet; our advice on nutrition and exercise during treatment may be helpful.
• Stop smoking and drinking alcohol; quitting smoking also reduces the risk of a new esophageal or head and neck cancer.
• If you are finding it hard to decide, get a second opinion; where appropriate, ask about taking part in clinical trials.

Frequently asked questions

Is surveillance without surgery after chemoradiotherapy safe in esophageal cancer?

In the SANO trial, among patients whose tumor disappeared after chemoradiotherapy, the difference in 5-year overall survival between active surveillance and standard surgery was not significant (50% vs 54%). However, distant metastasis (46% vs 29%) and cancer-related loss of life were more frequent with active surveillance. It is therefore an option for selected patients at experienced centers, not a standard for everyone.

How many patients who choose active surveillance are spared surgery?

In SANO, 43% of patients in the active surveillance arm did not undergo surgery, but part of this was due to early metastasis. The proportion of patients followed tumor-free with their esophagus preserved was 32%; 21% of patients completed 5 years with their esophagus preserved. In about half, the tumor regrew and delayed surgery was performed.

How is active surveillance carried out?

Check-ups including endoscopy with biopsy, endoscopic ultrasound and PET-CT are performed every 3 months in the first year, every 4 months in the second year and every 6 months thereafter. If the tumor regrows and there is no distant metastasis, surgery is performed.

Is active surveillance available in Turkey?

The necessary tests are available at major centers and are covered by the SGK; however, active surveillance is not yet routine practice. It may be considered for selected patients with an experienced multidisciplinary team, access to regular check-ups and detailed patient information.

Glossary

Esophagectomy

Surgical removal of the esophagus; a new food passage is usually created from the stomach in its place.

Chemoradiotherapy

Chemotherapy and radiotherapy given together; in the CROSS regimen, weekly carboplatin-paclitaxel and 41.4 Gy radiotherapy.

Clinical complete response

No tumor detected on endoscopy, biopsy and imaging after treatment; it differs from pathological complete response, which refers to no tumor remaining in the surgical specimen.

Active surveillance

An approach in which surgery is deferred in a patient with a clinical complete response, who is followed with regular check-ups and operated on only if the tumor regrows.

Endoscopic ultrasound

Examination of the esophageal wall and surrounding lymph nodes with an endoscope that has an ultrasound probe at its tip; a needle biopsy is taken if needed.

Non-inferiority trial

A trial that aims to show that a new approach is not worse than the standard by more than a prespecified margin.

Stepped-wedge cluster randomization

A design in which hospitals, rather than patients, switch to the new approach in turn, at randomly determined times.