Abstract Background Esophageal carcinoma; sixth most common cancer worldwide, presents a significant clinical challenge due to its aggressive nature and often late-stage diagnosis, resulting in poor prognosis and limited treatment options. Various treatment modalities, including surgery, chemotherapy, radiation therapy, immunotherapy, and targeted therapy, are utilized in clinical practice. However, the optimal treatment strategy remains uncertain, as the comparative effectiveness of these modalities is not well-defined. Past studies have provided conflicting evidence, necessitating a comprehensive evaluation to guide clinical decision-making. Therefore, this systematic review aims to compare the efficacy and safety of different treatment modalities for esophageal carcinoma, with the objective of informing evidence-based treatment approaches and improving patient outcomes. Methods Total 350 publications from PubMed, EMBASE, Cochrane, Google Scholar and Semantic Scholar databases were identified on the effectiveness of different treatment modalities for esophageal carcinoma between 2000 and 2024. Following deduplication, two independent reviewers initially screened the articles for eligibility with titles and abstracts, and then, with complete articles. Bias assessment using GRADE guidelines for observational studies was done. Non-English studies, case-series/case-reports/essays/book-chapters/conference-abstracts/editorials/thesis/dissertations and studies without full-texts were excluded. Results Overall, the effectiveness of each treatment modality for esophageal carcinoma depends on various factors, including tumor stage, histology, patient characteristics, and treatment regimen. Combination approaches, such as chemoradiotherapy or multimodal therapy, are often used to maximize treatment efficacy and improve patient outcomes. Conclusion Multidisciplinary collaboration, personalized treatment approach, integration of novel therapies, such as immunotherapy and targeted therapy, into standard treatment regimens, survivorship care and advocate for further research to identify optimal treatment sequencing, identify predictive biomarkers of treatment response, and explore novel therapeutic targets to improve outcomes for patients with esophageal carcinoma is recommended.
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