Management of Ct2n0m0 Esophageal Cancer: A Protocol for Systematic Review and Clinical Practice Guidelines

Background The management of cT2N0M0 esophageal cancer is challenging due to staging limitations and a lack of high-quality evidence. While neoadjuvant therapies have demonstrated survival benefits in advanced esophageal cancer stages, their role in cT2N0M0 remains unclear. These patients are underrepresented in randomized controlled trials, and the variations in treatment response between adenocarcinoma (EAC) and squamous cell carcinoma (SCC) further complicate decision-making. As a result, the International Society for Diseases of the Esophagus (ISDE) undertook a systematic review to synthesize available evidence on treatment outcomes of cT2N0M0 esophageal cancer. The findings will inform expert consensus statements, guiding therapeutic decision-making. Methods A comprehensive search strategy encompassed MEDLINE, EMBASE, and CENTRAL to 25 November 2024. Additional searches included ClinicalTrials.gov, the Australian New Zealand Clinical Trials Registry and the WHO ICTRP portal for published clinical trials. Search terms, developed in collaboration with experienced research librarian, included ‘esophageal cancer,’ ‘cT2N0M0,’ and related terms. Eligible studies included English-language studies evaluating adult patients (≥18 years old) with confirmed SCC or EAC staged as cT2N0M0. Exclusions included studies on recurrent disease, and small case reports. Two independent reviewers screened titles, abstracts, and full texts for eligibility. Disagreements were resolved by a third reviewer. Results The search identified 444 articles, of which 300 unique articles were eligible for screening after duplicate removal. Two independent reviewers screened full texts for included articles. Data extraction was completed by two reviewers independently and in duplicate to synthesize evidence on treatment outcomes of cT2N0M0 esophageal cancer. Conclusion This systematic review evaluates the management of cT2N0M0 esophageal cancer and has found a marked paucity of evidence supporting any management approach. There is limited consensus on diagnostic workup and even less on best practice treatment. These findings will support the development of ISDE clinical practice guidelines which by necessity will need to be of consensus expert opinion level only, and will aid clinical decision making for this patient population.