Active Surveillance vs Standard Surgery Post-Neoadjuvant Chemoradiotherapy for Esophageal Cancer
1. Overall survival at 2 years was 74% for active surveillance and 71% for standard surgery.
2. Median disease-free survival was 35 months for active surveillance and 49 months for standard surgery with an HR 1.25 (non-significant).
Evidence Rating Level: 1 (Excellent)
Study Rundown: Neoadjuvant chemoradiotherapy followed by surgery is the standard treatment for locally advanced esophageal cancer, but many patients achieve a pathological complete response, raising questions about the necessity of surgery for all individuals. Active surveillance, involving frequent clinical evaluations with surgery reserved for locoregional regrowth, has been proposed as an alternative to avoid unbeneficial esophagectomy, which carries significant morbidity. This trial was conducted to compare active surveillance and standard surgery. The primary endpoint was overall survival (OS) with primary outcome being non-inferiority at 2 years, and secondary endpoints included disease-free survival (DFS), operative and pathological outcomes, quality of life (QoL). Median OS was 43 months for active surveillance vs 53 months for standard surgery, with OS at 2 years being 74% for active surveillance and 71% for standard surgery, which was below the predefined non-inferiority margin of 15% worse OS. In the active surveillance arm, 17% developed distant metastases without undergoing surgery, 35% had persistent clinical complete response, and 48% developed isolated locoregional regrowth. With regards to operative outcomes, 82% in the active surveillance group and 84% in the standard surgery group had at least one postoperative complication, with similar frequency of postoperative complications was between groups. Median DFS was 35 months for active surveillance and 49 months for standard surgery with an HR 1.25 (non-significant). At 30 months post-neoadjuvant chemoradiotherapy, 43% in the active surveillance group vs 34% in the standard surgery group had distant metastases, with OR 1.45 (non-significant). With regards to QoL, the active surveillance arm compared to the standard surgery arm had an increase of 10.4 for global health-related quality of life (significant) at 6 months and an increase of 8.5 (significant) at 9 months, however after 12 months, no statistically significant differences were seen between groups. The strength of this study included its methodology, and the limitations included potential selection bias given the cluster randomization. Overall, this study found those undergoing active surveillance for advanced esophageal cancer post neoadjuvant chemoradiation after clinical complete response had some non-inferior outcomes compared with those undergoing standard surgery.
Click to read the study in Lancet Oncology
In-Depth [randomized controlled trial]: This multicenter, non-inferiority, phase 3 trial enrolled patients with locally advanced esophageal cancer who had clinical complete response after neoadjuvant chemoradiotherapy (CROSS regimen) and randomized them (stepped-wedge cluster randomization) to active surveillance (n=198) vs standard surgery (n=111). Active surveillance occurred every 3 months in year 1, every 4 months in year 2, every 6 months in year 3, and annually in years 4–5. Median follow-up was 38 months (range, 32-48). Median OS was 43 months (95%CI, 39-NA) for active surveillance vs 53 months (40-NA) for standard surgery, with OS at 2 years being 74% (95%CI, 69-78) for active surveillance and 71% (62-78) for standard surgery, which was below the predefined non-inferiority margin of 15% worse OS. In the active surveillance arm, 17% developed distant metastases without undergoing surgery, 35% had persistent clinical complete response, and 48% developed isolated locoregional regrowth (86% of those underwent esophagectomy after a median time of 5.9 months (range, 3.3-33.8) after reaching clinical complete response). With regards to operative outcomes, 82% in the active surveillance group and 84% in the standard surgery group had at least one postoperative complication, with similar frequency of postoperative complications was between groups. Median DFS was 35 months (95%CI, 28-NA) for active surveillance and 49 months (31-NA) for standard surgery with an HR 1.25 (95%CI, 0.83-1.89, p=0.29). At 30 months post-neoadjuvant chemoradiotherapy, 43% in the active surveillance group vs 34% in the standard surgery group had distant metastases, with OR 1.45 (95%CI, 0.85-2.48, p=0.18). With regards to QoL, the active surveillance arm compared to the standard surgery arm had an increase of 10.4 for global health-related quality of life (95%CI, 4.1-16.5, p=0.0010) at 6 months and an increase of 8.5 (2.0-15.0, p=0.0099) at 9 months, however after 12 months, no statistically significant differences were seen between groups. Overall, this study found those undergoing active surveillance for advanced esophageal cancer post neoadjuvant chemoradiation after clinical complete response had some non-inferior outcomes compared with those undergoing standard surgery.
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