Systematic review and meta-analysis of the outcomes following neoadjuvant therapy in upfront resectable gastric cancers compared to surgery alone in phase III randomised controlled trials.

BACKGROUND: Gastric cancer is the fifth most common malignancy and the fourth most common cause of cancer mortality globally. The role of neoadjuvant chemotherapy in upfront resectable gastric cancer is a subject of ongoing research. In recent meta-analyses, R0 resection rate and superior outcomes were not consistently observed in such regimens.

AIM: To describe the outcomes following phase III randomised control trials; comparing neoadjuvant therapy followed by surgery against upfront surgery with and without adjuvant therapy in resectable gastric cancers.

METHODS: The Cochrane Library, CINAHL, EMBASE, PubMed, SCOPUS and Web of Science was searched from January 2002 to September 2022.

RESULTS: 13 studies were included (3280 participants). R0 resection rates were in neoadjuvant therapy arms as compared to adjuvant therapy with odds ratio (OR) 1.55[95% CI: 1.13, 2.13](p=0.007) and compared to surgery alone OR 2.49[95% CI: 1.56, 3.96](p=0.0001). 3-year and 5-year progression-, event- and disease-free survival in neoadjuvant therapy as compared to adjuvant therapy were not significantly increased, 3-year OR 0.87[0.71, 1.07](p=0.19). Meanwhile, comparing neoadjuvant therapy to adjuvant therapy, 3-year overall survival (OS) hazard ratio was 0.88[95% CI: 0.70, 1.11](p=0.71) while 3- and 5-year OS OR was 1.18[95% CI: 0.90, 1.55], p=0.22 and 1.27[95% CI: 0.67, 2.42](p=0.47) respectively. Surgical complications were also more common with neoadjuvant therapy.

CONCLUSION: Neoadjuvant therapy yields higher rates of R0 resection. However, improved long-term survival was not seen as compared to adjuvant therapy. Large multi-centred randomised control trials with D2 lymphadenectomy should be performed to better evaluate the treatment modalities.