Active Surveillance Cost-Effective After Esophageal Cancer Response

Key Takeaways

• In the randomized SANO trial, patients with esophageal cancer who achieved a complete clinical response after CROSS-regimen neoadjuvant chemoradiotherapy had slightly higher 5-year QALYs and lower mean health care costs with active surveillance than with standard surgery.
• At a willingness-to-pay threshold of €80 000 per QALY, 97% of bootstrap replications placed active surveillance in the cost-effective region.
• Lower surgery and readmission or reintervention spending accounted for most of the savings with active surveillance, despite higher diagnostic-test and radiotherapy or palliative-care costs.
• Sensitivity analyses that added CCR-determination costs or removed most routine EUS procedures continued to favor active surveillance as cost-effective.

Management after complete clinical response in esophageal cancer involves balancing organ preservation against the possibility of delayed intervention. Avoiding routine esophagectomy may reduce treatment burden, but repeated surveillance evaluations and postponed surgery for locoregional regrowth can shift resource use and patient-reported outcomes over time. That tradeoff becomes more consequential as follow-up extends beyond neoadjuvant treatment and into survivorship. Investigators examined this question in a prespecified economic comparison embedded within randomized post-treatment care.

Investigators conducted a prespecified cost-effectiveness secondary analysis alongside the phase 3, multicenter, stepped-wedge cluster randomized Surgery as Needed for Oesophageal Cancer (SANO) trial at 12 hospitals in the Netherlands, as detailed in the SANO secondary analysis. The modified intention-to-treat population included 309 patients with locally advanced esophageal or esophagogastric junction cancer who received the CROSS (Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study) regimen of neoadjuvant chemoradiotherapy (nCRT) and achieved a complete clinical response (CCR), with 198 assigned to active surveillance and 111 to standard surgery. Active surveillance consisted of repeated clinical response evaluations at 6, 9, 12, 16, 20, 24, 30, 36, 48, and 60 months after nCRT, including fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), esophagogastroduodenoscopy with biopsies, and endoscopic ultrasonography (EUS) with fine-needle aspiration of suspicious lymph nodes. Effectiveness was measured in quality-adjusted life-years (QALYs) using the EuroQoL 5-dimension 5-level questionnaire (EQ-5D-5L) and Dutch value set, while costs were measured from a health care perspective from the time of CCR with a nonparametric bootstrap framework using 2000 replications and a prespecified willingness-to-pay threshold of €80 000 per QALY.

Mean 5-year QALYs were 2.99 with active surveillance and 2.88 with standard surgery for an incremental QALY of 0.11 (95% CI, −0.10 to 0.33). Mean 5-year health care costs were €36 733 per patient with active surveillance and €45 106 with standard surgery, for mean savings of €8374 (95% CI, €1792-€15 355). Lower overall spending was attributed mainly to reduced surgery costs and fewer readmissions or reinterventions, while diagnostic-test costs and radiotherapy or palliative-care costs were higher with active surveillance. These estimates favored surveillance on both effectiveness and cost over the 5-year horizon.

At the €80 000-per-QALY threshold, mean incremental net monetary benefit (iNMB) was €17 568 (95% CI, −€725 to €37 497), and 97% of bootstrap replications fell in the cost-effective region. Sensitivity analyses showed that assigning CCR-determination costs to active-surveillance patients narrowed the cost advantage, whereas removing 97.8% of routine EUS procedures widened it. Across all prespecified scenarios, the economic signal continued to favor active surveillance. The bootstrap and sensitivity analyses therefore supported the robustness of the main cost-effectiveness finding.

Five-year follow-up was not fully complete, with overall complete follow-up in 80% of patients (247 of 309) and 5-year follow-up complete for 71% of the active-surveillance group and 96% of the standard-surgery group, so the estimates relied partly on modeled outcomes from available health-related quality-of-life and cost data. The standard-surgery group may not fully reflect usual practice because both groups underwent 2 clinical response evaluations before management assignment. Societal cost analyses were also limited because outpatient medical consumption was not captured and productivity-loss questionnaire response rates were low, and implementation in specialized high-volume centers may limit generalizability to settings with different endoscopic or surgical resources. Within those bounds, the findings support a lower-cost profile for surveillance-based management in this trial population.

The authors concluded that active surveillance was cost-effective over 5 years compared with standard surgery in patients with esophageal cancer who achieved CCR after nCRT. That interpretation was bounded to this prespecified secondary economic analysis within the randomized SANO trial and was set alongside previously reported noninferior 2-year survival in the parent study.

Clinician Questions

What surveillance schedule was used after complete clinical response in the SANO cost-effectiveness analysis?

The SANO active-surveillance protocol used repeated clinical response evaluations at 6, 9, 12, 16, 20, 24, 30, 36, 48, and 60 months after neoadjuvant chemoradiotherapy (approximately 3, 6, 9, 13, 17, 21, 27, 33, 45, and 57 months after complete clinical response), with evaluations including FDG-PET/CT, esophagogastroduodenoscopy with biopsies, and EUS with fine-needle aspiration of suspicious lymph nodes.

How did 5-year QALYs and health care costs compare between active surveillance and standard surgery after complete clinical response in esophageal cancer?

In patients with esophageal cancer who achieved complete clinical response after CROSS-regimen neoadjuvant chemoradiotherapy, mean 5-year QALYs were 2.99 with active surveillance and 2.88 with standard surgery, and mean health care costs were €36 733 versus €45 106 per patient, respectively.

Was active surveillance cost-effective at €80 000 per QALY after neoadjuvant chemoradiotherapy in esophageal cancer?

At a willingness-to-pay threshold of €80 000 per QALY, mean iNMB was €17 568 and 97% of bootstrap replications fell in the cost-effective region for active surveillance versus standard surgery in esophageal cancer after complete clinical response.

What limitations affected the 5-year economic comparison of active surveillance versus surgery in the SANO analysis?

In the SANO analysis of esophageal cancer after complete clinical response, 5-year follow-up was incomplete and outcomes were partly modeled from available HRQOL and cost data; the standard-surgery group may not fully reflect usual practice because both groups underwent 2 clinical response evaluations before assignment; societal cost data were limited by missing outpatient medical consumption and low productivity-questionnaire response rates; and the protocols were implemented in specialized high-volume centers, which may limit generalizability.