Dataset Information

Survival of Neoadjuvant and Adjuvant Therapy Compared With Surgery Alone for Resectable Esophageal Squamous Cell Carcinoma: A Systemic Review and Network Meta-Analysis

ABSTRACT:

Objective

The optimal treatment for resectable esophageal squamous cell carcinoma (ESCC) remains controversial. Surgery is the primary treatment but with poor results. Attempts to improve patient survival have been made by introducing chemotherapy, radiotherapy, or both. However, randomized comparisons for all these strategies are not always available. This network meta-analysis compared the overall survival of neoadjuvant and adjuvant therapy with surgery alone to identify the most effective approach.

Methods

We systematically searched electronic databases (PubMed, Embase, and Cochrane Library) for relevant studies published before April 2021. Only phase II and III randomized controlled trials comparing the following treatments were included: surgery alone, neoadjuvant chemotherapy (NCT), radiotherapy (NRT) or chemoradiotherapy (NCRT), adjuvant chemotherapy (ACT), radiotherapy (ART), or chemoradiotherapy (ACRT). The hazard ratios (HR) and 95% confidence intervals (CIs) of overall survival (OS) was identified as the measurement of effectiveness. A network meta-analysis was conducted to synthesize the evidence under the Bayesian framework, and the relative effects of all possible comparisons were made. The ranking analysis was performed to support the decision in clinical practice.

Results

A total of 19 relevant trials with 3,749 patients were identified. Compared with surgery alone, NCRT (HR 0.76, 95% CI 0.65–0.89) and NCT (HR 0.81, 95% CI 0.70–0.94) significantly improved OS, while other treatments, including NRT (HR 0.86, 95% CI 0.66–1.08), ACRT (HR 0.73, 95% CI 0.49–1.08), ACT (HR 0.96, 95% CI 0.75–1.21), and ART (HR 0.86, 95% CI 0.66–1.14), provided no significant survival advantage. None of the neoadjuvant and adjuvant treatments showed a statistically significant difference in OS to each other when compared in pairs.

Conclusion

For resectable esophageal squamous cell carcinoma, this network meta-analysis showed that NCRT may be the optimal strategy, NCT may be the second choice, while other multimodality treatments could not improve OS compared with surgery alone. It remains unclear whether ESCC will benefit from adding radiotherapy into the neoadjuvant treatment.

Systematic Review Registration

We registered this meta-analysis protocol at the prospective register of systematic reviews, PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=172745 (Identification code: CRD42020172745).

SUBMITTER: Ma Z

PROVIDER: S-EPMC8564474 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCarcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. The large and growing number of patients affected, the high mortality rates, the worldwide geographic variation in practice, and the large body of good quality research warrants a systematic review with meta-analysis.MethodsA systematic review and meta-analysis investigating the impact of neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer to inform evidence-based practice was produced.MEDLINE, CANCERLIT, Cochrane Library, EMBASE, and abstracts from the American Society of Clinical Oncology and the American Society for Therapeutic Radiology and Oncology were searched for trial reports. Included were randomized trials or meta-analyses of neoadjuvant or adjuvant treatments compared with surgery alone or other treatments in patients with resectable thoracic esophageal cancer. Outcomes of interest were survival, adverse effects, and quality of life. Either one- or three-year mortality data were pooled and reported as relative risk ratios.ResultsThirty-four randomized controlled trials and six meta-analyses were obtained and grouped into 13 basic treatment approaches. Single randomized controlled trials detected no differences in mortality between treatments for the following comparisons:- Preoperative radiotherapy versus postoperative radiotherapy.- Preoperative and postoperative radiotherapy versus postoperative radiotherapy. Preoperative and postoperative radiotherapy was associated with a significantly higher mortality rate.- Postoperative chemotherapy versus postoperative radiotherapy.- Postoperative radiotherapy versus postoperative radiotherapy plus protein-bound polysaccharide versus chemoradiation versus chemoradiation plus protein-bound polysaccharide. Pooling one-year mortality detected no statistically significant differences in mortality between treatments for the following comparisons:- Preoperative radiotherapy compared with surgery alone (five randomized trials).- Postoperative radiotherapy compared with surgery alone (five randomized trials).- Preoperative chemotherapy versus surgery alone (six randomized trials).- Preoperative and postoperative chemotherapy versus surgery alone (two randomized trials).- Preoperative chemoradiation therapy versus surgery alone (six randomized trials). Single randomized controlled trials detected differences in mortality between treatments for the following comparison:- Preoperative hyperthermia and chemoradiotherapy versus preoperative chemoradiotherapy in favour of hyperthermia. Pooling three-year mortality detected no statistically significant difference in mortality between treatments for the following comparison:- Postoperative chemotherapy compared with surgery alone (two randomized trials). Pooling three-year mortality detected statistically significant differences between treatments for the following comparisons:- Preoperative chemoradiation therapy versus surgery alone (six randomized trials) in favour of preoperative chemoradiation with surgery.- Preoperative chemotherapy compared with preoperative radiotherapy (one randomized trial) in favour of preoperative radiotherapy.ConclusionFor adult patients with resectable thoracic esophageal cancer for whom surgery is considered appropriate, surgery alone (i.e., without neoadjuvant or adjuvant therapy) is recommended as the standard practice.

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