ESMO Congress 2026

Whether patients with complete response after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer can be spared surgery is a central controversy in the field. The evidentiary starting point was the Dutch prospective multicentre diagnostic cohort preSANO: after weekly carboplatin (AUC 2) plus paclitaxel (50 mg/m²) with concurrent 41.4 Gy in 23 fractions, roughly half of squamous cell carcinoma patients and about a quarter of adenocarcinoma patients achieved a pathological complete response in surgical specimens, leading the authors to argue that the necessity of standard oesophagectomy for sufficient responders should be reconsidered ^[3]; the study also compared the accuracy of different diagnostic approaches and their combinations for detecting residual disease, providing a methodological basis for a de-surgery strategy gated by clinical complete response (cCR) ^[3]. The 41.4 Gy/23 fx dose repeatedly mentioned at this meeting derives from this preoperative chemoradiotherapy prescription ^[3].

At ESMO26, LBA78 presented the 5-year long-term results of the cluster-randomised controlled trial SANO built on this foundation, with a concomitant paper published in Annals of Oncology. The study enrolled 309 patients with locally advanced esophageal cancer who achieved cCR after nCRT, randomized to active surveillance or standard surgery, with a median follow-up of 76 months. 5-year OS was 50% vs 54% (HR 1.17, 95% CI 0.77–1.77, p=0.46), with no statistically significant difference; DFS HR 1.39 (95% CI 0.94–2.06, p=0.10) was also not significant; however, the 5-year cumulative incidence of distant metastases was significantly higher with surveillance: 46% vs 29% (sHR 2.04, p<0.01). Additionally, 43% of patients avoided oesophagectomy — noting that this figure includes both patients with sustained response and patients in whom metastases were detected within 6 months after chemoradiotherapy.

Relative to prior knowledge, this readout moves the organ-preservation question from feasibility to long-term survival: in a strictly selected cCR population, active surveillance and surgery showed no significant difference in 5-year OS, with the 43% surgery-avoidance rate as its core benefit; but the significantly higher distant metastasis rate and an OS confidence interval crossing 1 make the risk of distant dissemination under surveillance explicit. Multiple commentators at the meeting stressed that a nonsignificant OS difference does not establish noninferiority or equivalence, and that 41.4 Gy/23 fx is a preoperative, arguably non-definitive dose — particularly in a population with ~75% adenocarcinoma; the applicability of this strategy in the DFLOT + post-CROSS era was also publicly questioned.

Overall, the data suggest that non-surgical management of upper GI cancer is harder than hoped: a nonsignificant OS difference is not evidence of equivalence, and the significant increase in distant metastases means that active surveillance, if implemented in practice, still requires finer patient selection and more reliable surveillance and rescue strategies; the constraints imposed by radiation dose and histology mix on interpretation and generalizability should be read alongside the efficacy numbers.