Chemoradiotherapy Followed by Active Surveillance Versus Standard Esophagectomy for Esophageal Cancer

Abstract

Objective: To compare overall survival of patients with a cCR undergoing active surveillance versus standard esophagectomy. Summary of Background Data: One-third of patients with esophageal cancer have a pathologically complete response in the resection specimen after neoadjuvant chemoradiotherapy. Active surveillance may be of benefit in patients with cCR, determined with diagnostics during response evaluations after chemoradiotherapy. Methods: A systematic review and meta-analysis was performed comparing overall survival between patients with cCR after chemoradiotherapy undergoing active surveillance versus standard esophagectomy. Authors were contacted to supply individual patient data. Overall and progression-free survival were compared using random effects meta-analysis of randomized or propensity score matched data. Locoregional recurrence rate was assessed. The study-protocol was registered (PROSPERO: CRD42020167070). Results: Seven studies were identified comprising 788 patients, of which after randomization or propensity score matching yielded 196 active surveillance and 257 standard esophagectomy patients. All authors provided individual patient data. The risk of all-cause mortality for active surveillance was 1.08 [95% confidence interval (CI): 0.62-1.87, P ¼ 0.75] after intention-totreat analysis and 0.93 (95% CI: 0.56-1.54, P ¼ 0.75) after per-protocol analysis. The risk of progression or all-cause mortality for active surveillance was 1.14 (95% CI: 0.83-1.58, P ¼ 0.36). Five-year locoregional recurrence rate during active surveillance was 40% (95% CI: 26%-59%). 95% of active surveillance patients undergoing postponed esophagectomy for locoregional recurrence had radical resection. Conclusions: Overall survival was comparable in patients with cCR after chemoradiotherapy undergoing active surveillance or standard esophagectomy. Diagnostic follow-up is mandatory in active surveillance and postponed esophagectomy should be offered to operable patients in case of locoregional recurrence.

Radiotherapy combined with immune checkpoint inhibitors in locally advanced/metastatic esophageal squamous cell carcinoma: clinical trials, efficacy and future directions

“…Can esophageal cancer learn from the “watch and wait” strategy of rectal cancer in complete remission after neoadjuvant chemoradiotherapy, and use esophagectomy as a salvage method for local recurrence? Multiple retrospective studies have demonstrated that among good responders after neoadjuvant therapy, active surveillance of patients who refused esophagectomy or were ultimately deemed unsuitable for surgery had comparable survival rates to those who underwent surgery ( 173 – 178 ). In the ongoing prospective SANO trial and ESOSTRATE trial, patients with a clinical response assessment of cCR after standard neoadjuvant chemoradiotherapy will be randomly assigned to either the active surveillance group or the immediate surgery group, comparing survival and quality of life for both groups ( 179 – 181 ).…”

Use of a non-endoscopic immunocytological device (Cytosponge™) for post chemoradiotherapy surveillance in patients with oesophageal cancer in the UK (CYTOFLOC): A multicentre feasibility study

“… 13 , 14 As such, there is growing interest in the use of organ preservation using upfront CRT followed by surveillance and salvage procedures as a means to minimising treatment-related morbidity; with at least three randomised controlled trials planned within this space. 15 , 16 However, the effectiveness of these approaches is contingent on the timely identification of residual and recurrent disease in order to permit salvage resection or reirradiation through a brachytherapy boost or external beam proton therapy. 24 …”

“…Finally, the overall role of the primary non-surgical management of oesophageal cancer also remains uncertain and requires further investigation within the phase 3 trial setting. 15 Further work is also required to optimise the use of laboratory biomarkers, clinical factors and the Cytosponge to identify patients who require or who should endoscopic assessment. 6 …”

“…Survival outcomes following the use of this strategy appear promising, though the results of ongoing randomized controlled trials are awaited. 15 , 16 Early use of a brachytherapy boost may also be considered where patients have residual disease but are unfit for salvage resection. 17 …”

Nomogram for predicting pathologic complete response to neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma

“…It is estimated that around 20%–40% of patients treated with nCRT would achieve a pCR, which has been demonstrated to be associated with improved recurrence‐free survival (RFS) and overall survival (OS) 5,6 . A meta‐analysis confirmed that OS was comparable in patients with clinically complete response (cCR) after chemoradiotherapy undergoing active surveillance or standard esophagectomy 7 . If pCR could be predicted with high accuracy, surgery could potentially be utilized as a salvage procedure instead of a planned procedure 8 .…”