Oncology · Medical Literature
Surveillance vs Standard Surgery and Cost-Effectiveness After Neoadjuvant Chemoradiotherapy for Esophageal Cancer: Secondary Analysis of a Randomized Clinical Trial.
Abstract
Active surveillance is noninferior to standard surgery for 2-year survival and improves short-term health-related quality of life among patients with a complete clinical response (CCR) after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. Although active surveillance reduces the upfront costs of surgery and hospital stay, it requires repeated diagnostic tests and, for some patients, delayed surgery and hospitalization during follow-up. To assess the cost-effectiveness of active surveillance compared with standard surgery after nCRT. This prespecified cost-effectiveness analysis from a health care perspective conducted at 12 hospitals in the Netherlands as a secondary analysis of the Surgery as Needed for Oesophageal Cancer (SANO) trial, a noninferiority, cluster randomized study, enrolled patients with esophageal cancer who achieved a CCR after nCRT between November 8, 2017, and January 17, 2021, with follow-up for up to 5 years. Data were analyzed on June 1, 2025. Active surveillance, consisting of repeated response evaluations at 6, 9, 12, 16, 20, 24, 30, 36, 48, and 60 months after nCRT, compared with standard surgery. Incremental cost-effectiveness of active surveillance vs standard surgery and quality-adjusted life-years (QALYs) with 95% CIs up to 5 years were derived with bootstrapping, with 80% of patients (247 of 309) having complete follow-up. Incremental net monetary benefit (iNMB) was calculated at varying willingness-to-pay thresholds. All analyses followed the modified intention-to-treat principle. Costs are given in Euros (currency exchange rate of €1 = US $1.16 as of June 11, 2026). Among 309 patients (198 in the active surveillance group; median age, 69 years [IQR, 63-74 years]; 156 men [79%]; and 111 in the standard surgery group; median age, 68 years [IQR, 61-73 years]; 86 men [77%]), those in the active surveillance group had a mean of 2.99 QALYs (95% CI, 2.73-3.26) at 5 years vs 2.88 QALYs (95% CI 2.69-3.06) in the standard surgery group. Mean health care costs per patient at 5 years were €36 733 (95% CI, €33 530-€40 009) in the active surveillance group vs €45 106 (95% CI, €39 449-€51 545) in the standard surgery group. The incremental QALY for active surveillance was 0.11 (95% CI, -0.10 to 0.33) and mean costs were €8374 lower (95% CI, €1792-€15 355) compared with standard surgery. At a willingness-to-pay threshold of €80 000 per QALY, the mean iNMB was €17 568 (95% CI, -€725 to €37 497), indicating that active surveillance is cost-effective. Bootstrap analysis showed that 97% of replications fell in the cost-effective region. In this secondary analysis of a randomized clinical trial of patients with esophageal cancer achieving a CCR after nCRT, active surveillance was cost-effective over a 5-year horizon compared with standard surgery. Broader implementation of this strategy among appropriately selected patients would most likely reduce health care costs without compromising health outcomes. The Dutch Trial Register: NTR 6803.
Clinical relevance
This study addresses a critical clinical decision point for esophageal cancer patients who achieve a complete clinical response (CCR) after neoadjuvant chemoradiotherapy (nCRT) — specifically, whether immediate esophagectomy is necessary or whether active surveillance with surgery-as-needed is a viable, cost-effective alternative. Given the high morbidity and mortality associated with esophagectomy, this evidence is directly relevant to thoracic oncologists, gastroenterologists, and multidisciplinary tumor boards managing this patient population. The 5-year cost-effectiveness data from this prespecified analysis of the SANO trial provide the economic justification needed to support broader institutional adoption of surveillance protocols.
Key findings
1. Active surveillance yielded a mean of 2.99 QALYs (95% CI, 2.73–3.26) at 5 years versus 2.88 QALYs (95% CI, 2.69–3.06) for standard surgery, with an incremental QALY gain of 0.11 (95% CI, −0.10 to 0.33) favoring surveillance. 2. Mean 5-year health care costs per patient were €36,733 (95% CI, €33,530–€40,009) in the active surveillance group versus €45,106 (95% CI, €39,449–€51,545) in the standard surgery group — a mean cost savings of €8,374 (95% CI, €1,792–€15,355) per patient with surveillance (approximately US $9,714 at the reported exchange rate of €1 = US $1.16). 3. At a willingness-to-pay threshold of €80,000 per QALY, the mean incremental net monetary benefit (iNMB) of active surveillance was €17,568 (95% CI, −€725 to €37,497), meeting the threshold for cost-effectiveness. 4. Bootstrap probabilistic sensitivity analysis demonstrated that 97% of replications fell within the cost-effective region, indicating a high degree of robustness in the cost-effectiveness conclusion. 5. The analysis was conducted from a health care perspective across 12 hospitals in the Netherlands as a prespecified secondary analysis of the cluster-randomized SANO trial, with 80% of 309 patients (247/309) having complete 5-year follow-up data, lending credibility to the long-term estimates. 6. The study population comprised patients with esophageal cancer achieving a CCR after nCRT (median age ~68–69 years; ~77–79% male), with active surveillance consisting of structured response evaluations at 10 time points over 60 months post-nCRT.
Practice implications
For esophageal cancer patients who achieve a CCR after nCRT, multidisciplinary teams should consider offering active surveillance with surgery-as-needed as the preferred strategy over immediate esophagectomy, given demonstrated noninferiority in 2-year survival, improved short-term health-related quality of life, and now confirmed 5-year cost-effectiveness with ~€8,374 in mean per-patient savings. Patient selection should be rigorous — limited to those with confirmed CCR after nCRT — and surveillance must follow a structured, protocol-driven schedule (e.g., SANO-protocol evaluations at 6, 9, 12, 16, 20, 24, 30, 36, 48, and 60 months) to ensure timely detection of locoregional recurrence amenable to salvage resection. Health systems and payers should recognize that the upfront cost reduction from deferred surgery outweighs the downstream costs of repeated diagnostic evaluations and delayed surgeries, supporting reimbursement frameworks that facilitate active surveillance program implementation in high-volume esophageal cancer centers.