Active Surveillance Shows Noninferior OS vs Surgery in Esophageal Cancer

The 2-year OS rate for active surveillance was below the predefined noninferiority margin of 15% worse OS.

Active surveillance for patients with esophageal cancer who achieved a clinical complete response to neoadjuvant chemoradiotherapy and esophagectomy showed noninferior overall survival (OS) vs standard surgery after 2 years, according to results from the noninferiority phase 3 SANO trial (NTR-6803) published in Lancet Oncology.

Findings from the study showed that at a median follow-up of 38 months (IQR, 32-48) from time of clinical response, the median OS among patients who underwent active surveillance for esophageal cancer was 43 months (95% CI, 39-not reached [NR]) vs 53 months (95% CI, 40-NR) in those who underwent standard surgery, according to a modified intention-to-treat analysis. Additionally, the 2-year OS rates in the respective groups were 74% (95% CI, 69%-78%) vs 71% (95% CI, 62%-78%); the rate for active surveillance was below the predefined noninferiority margin of 15% worse OS (one-sided 95% boundary, 7% lower). An intention-to-treat analysis also showed noninferiority in OS for active surveillance (one-sided 95% boundary, 6% lower).

Furthermore, among 198 patients undergoing active surveillance and 111 undergoing standard surgery in the modified intention-to-treat population, 50 and 79 patients in respective groups had died (HR, 1.14; 95% CI, 0.74-1.78; P = .55). In the intention-to-treat population, 59 patients in the standard surgery group (n = 101) and 56 patients in the active surveillance group (n = 83) had died (HR, 0.83; 95% CI, 0.53-1.31; P = .42). Additional delta-residual mean survival times showed no differences in estimated OS (0.95; 95% CI, –1.55 to 3.46; P = .46).

“[Patients] undergoing active surveillance after clinical complete response had noninferior 2-year [OS] compared with those undergoing standard surgery,” lead investigator Berend J. van der Wilk, MD, PhD, of the department of Surgery at the Erasmus M.C. Cancer Institute, University Medical Centre, Rotterdam, wrote in the publication with study coinvestigators. “However, longer follow-up is needed to assess the robustness of this strategy. Of [patients] with clinical complete response undergoing active surveillance, almost half were spared unbeneficial esophagectomy, resulting in improved short-term health-related quality of life [HRQOL].”

Patients 18 years and older with locally advanced esophageal carcinoma or esophagogastric junction carcinoma who were scheduled for neoadjuvant chemoradiation were assigned based on stepped-wedge cluster randomization to undergo active surveillance or standard surgery, depending on cluster and time of recruitment.

Patients undergoing active surveillance received clinical response evaluations every 3 months at a year after response, every 4 months at 2 years after response, every 6 months in year 3, and annually for years 4 and 5. Those in this group only underwent esophagectomy in the case of pathologically confirmed or highly suspected locoregional regrowth without signs of distant metastases.

Standard surgery consisted of postoperative follow-up with PET-CT at 16 months and 30 months after neoadjuvant chemoradiation. Surgical approaches differed by access, technique, and nodal dissection based on tumor location and surgeons’ preferences.

Across the modified intent-to-treat population, patients in the active surveillance and standard surgery cohorts had a median age of 69 years (IQR, 63-74) and 68 years (IQR, 61-73), respectively. In each respective group, 79% vs 77% were male, 74% vs 76% had adenocarcinoma, and 49% vs 46% had tumor differentiation grade 2.

The most common tumor stages in the respective populations included IIB (31% vs 36%), IIIA (29% vs 24%), and IIIB (16% vs 12%); most patients had cT3 (71% vs 68%) or cT2 (22% vs 22%) disease; and most patients had cN0 (42% vs 44%) or cN1 (36% vs 33%) disease. World Health Organization performance statuses were most commonly 0 (66% vs 61%) or 1 (27% vs 29%). Most tumors were located in either the distant third esophagus (61% vs 58%) or the esophagogastric junction (26% vs 24%).

The primary end point of the study was OS. Secondary end points included disease-free survival (DFS), recurrent locoregional disease after esophagectomy, distant metastases, all-cause mortality, operative and pathological outcomes, and HRQOL.

A total of 82% of the active surveillance and 84% of the standard surgery groups experienced at least 1 postoperative complication. Additionally, 4% and 5% of each respective group died within 90 days of surgery. The median DFS in the respective groups was 35 months (95% CI, 28-NR) and 49 months (95% CI, 31-NR).

Reference

Van der Wilk BJ, Eyck BM, Wijnhoven BP, et al, Neoadjuvant chemoradiotherapy followed by active surveillance versus standard surgery for oesophageal cancer (SANO trial): a multicentre, stepped-wedge, cluster-randomised, non-inferiority, phase 3 trial. Lancet Oncol. 2025;26:425-436. doi:10.1016/S1470-2045(25)00027-0