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The Efficacy of Neoadjuvant Versus Adjuvant Therapy for Resectable Esophageal Cancer Patients: A Systematic Review and Meta-Analysis

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Abstract

Objective

Inconclusive results are available as to whether chemo/radiotherapy should be administered to resectable esophageal cancer patients before surgery (neoadjuvant therapy) or after surgery (adjuvant therapy). The paper, via a meta-analysis of effects of treatment modalities when administering chemo/radiotherapy, aims to systematically evaluate the effect of timing of chemo/radiotherapy and surgery.

Methods

We performed a systematic literature search for clinical trials of neoadjuvant and adjuvant therapy for patients with esophageal cancer. Using meta-analysis, we conducted direct and adjusted indirect comparisons of overall survival, complete resection rate (R0 resection), perioperative mortality, leakage rate and local recurrence in patients with resectable esophageal cancer.

Results

A total of 32 studies involving 7985 patients with esophageal cancer were included in the meta-analysis. Twenty-five randomized controlled studies indirectly compared neoadjuvant/adjuvant therapy with surgery alone, while five non-randomized controlled studies and two randomized controlled studies directly compared neoadjuvant with adjuvant therapy. Neoadjuvant therapy followed by surgery, compared with surgery along with adjuvant therapy, showed a significant overall survival advantage in our pooled analysis (HR 0.88; 95% CI 0.79–0.98). Directly compared with adjuvant therapy, neoadjuvant therapy demonstrated a lower local recurrence rate (OR 0.56; 95% CI 0.43–0.74) with low heterogeneity (I2 = 1%). Neoadjuvant therapy, comparing to surgery with or without adjuvant therapy, showed a significantly higher R0 resection rate (OR 2.86; 95% CI 2.02–4.04) with moderate heterogeneity (I2 = 38%) and no significant differences in postoperative anastomotic leakage (P = 0.50). However, neoadjuvant therapy, compared with surgery adjuvant therapy, significantly increased perioperative mortality in both direct and indirect comparisons (P < 0.01).

Conclusions

We found that neoadjuvant therapy was associated with higher overall survival and R0 resection rate without increasing postoperative anastomotic leakage for patients with resectable esophageal cancer, whereas neoadjuvant therapy was associated with higher perioperative mortality after esophagectomy.

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Funding

This study is supported by funding to Sichuan Science and Technology Program (2018HH0150) and Chengdu Science and Technology Board (2017-GH02-00072-HZ) and 1.3.5 project for disciplines of excellence, West China Hospital (Grant No. ZYJC18010). The funder had no roles in the design, execution and writing up of this study.

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Author notes

  1. **n **ao and Hyokyoung G. Hong are joint first authors.

Authors and Affiliations

  1. Department of Thoracic Surgery, West China Hospital, No. 37, Guoxue Alley, Chengdu, Sichuan, China

    **n **ao, Yu-Shang Yang, Si-Yuan Luan, Long-Qi Chen & Yong Yuan

  2. Department of Statistics and Probability, Michigan State University, East Lansing, MI, USA

    Hyokyoung G. Hong

  3. Big Data Center, West China Hospital, No. 37, Guoxue Alley, Chengdu, Sichuan, China

    **aoxi Zeng

  4. Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA

    Yi Li

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  1. **n **ao
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Correspondence to Yong Yuan.

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**ao, X., Hong, H.G., Zeng, X. et al. The Efficacy of Neoadjuvant Versus Adjuvant Therapy for Resectable Esophageal Cancer Patients: A Systematic Review and Meta-Analysis. World J Surg 44, 4161–4174 (2020). https://doi.org/10.1007/s00268-020-05721-w

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