Correlation of pathological complete response with survival after neoadjuvant chemotherapy in gastric or gastroesophageal junction cancer treated with radical surgery: A meta-analysis

Abstract

Background: Neoadjuvant chemotherapy before radical gastrectomy is preferred for locally advanced gastric cancer. To avoid the problematic use of pTNM for patients after neoadjuvant chemotherapy, the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC) gastric cancer TNM staging system (8th edition) added ypTNM for the first time. But patients achieving pathological complete response were not covered by the new ypTNM staging system. To investigate whether pathological complete response is associated with better outcome in gastric cancer, as was reported in rectal, breast and bladder cancer.

Methods: We systematically searched the databases of PubMed, EMBASE, Web of Science and Cochrane Collaboration's Central register of controlled trials from January 1988 to April 2015 for publications which reported outcomes of patients with and without pathological complete response (pCR) (pT0N0M0) to investigate whether pCR after neoadjuvant chemotherapy in gastric or gastroesophageal junction (GEJ) treated with radical surgery is associated with better survival. The primary outcome was overall survival (OS). The secondary outcome was disease-free survival (DFS). Both were measured with a relative risk (RR). A meta-analysis was performed using the fixed effects model. Forest plots and the Q test was used to evaluate overall heterogeneity for OS and DFS.

Results: A total of seven trials, 1143 patients were included and analyzed after neoadjuvant chemotherapy and radical surgery with no other preoperative treatment. The average rate of pCR was 6.74% (range: 3%-15%). The RR of patients who achieved pCR in the primary tumor and lymph nodes is 0.5 (95% confidence interval [CI], 0.25-0.98; p = 0.04), 0.34 (95% CI, 0.21-0.55; p<0.0001) and 0.44 (95% CI, 0.30-0.63; p<0.0001) for one-year-OS, three-year-OS and five-year-OS, respectively. The summary RR for three-year-DFS was 0.43 (95% CI, 0.25-0.72; p = 0.002).

Conclusion: Patients with resectable gastric or GEJ cancer who achieved pCR after neoadjuvant chemotherapy can gain a better outcome than patients without pCR.

Fig 1. PRISMA diagram.

The figure displays the information retrieval process for valuable articles and exclusion process of irrelative articles for this research.

Fig 2. Forest plot of pooled relative risk for one-year OS from eligible studies.

The area of each square represents the weighting, and the positions of each square demonstrate the risk ratio point estimate. Horizontal lines represent 95% confidence interval (CI). M-H = Mantel-Haenszel. Events = patients died from any cause within one year.

Fig 3. Forest plot of pooled relative risk for three-year OS from eligible studies.

The area of each square represents the weighting, and the positions of each square demonstrate the risk ratio point estimate. Horizontal lines represent 95% confidence interval (CI). M-H = Mantel-Haenszel. Events = patients died from any cause within three years.

Fig 4. Forest plot of pooled relative risk for five-year OS from eligible studies.

The area of each square represents the weighting, and the positions of each square demonstrate the risk ratio point estimate. Horizontal lines represent 95% confidence interval (CI). M-H = Mantel-Haenszel. Events = patients died from any cause within five years.

Fig 5. Forest plot of pooled relative risk for three-year DFS from eligible studies.

The area of each square represents the weighting, and the positions of each square demonstrate the risk ratio point estimate. Horizontal lines represent 95% confidence interval (CI). M-H = Mantel-Haenszel. Events = recurrence or metastasis happened within three years.

Fig 6. Funnel plots for publication bias of one-year OS (a), three-year OS (b), five-year OS (c), and three-year DFS (d).

The vertical line indicates the pooled estimate of the overall risk ratio, with the sloping lines representing the expected 95% CI for a given standard error.