Ann Hepatobiliary Pancreat Surg.  2023 Feb;27(1):28-39. 10.14701/ahbps.22-052.

Neoadjuvant chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer: Meta-analysis and trial sequential analysis of randomized controlled trials

Affiliations
  • 1Department of General Surgery, University Hospital of Wales, Cardiff & Vale NHS Trust, Cardiff, United Kingdom
  • 2Hepatobiliary and Pancreatic Surgery and Liver transplant Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom
  • 3Department of Hepatobiliary and Pancreatic Surgery, Manchester Royal Infirmary Hospital, Manchester, United Kingdom
  • 4Department of General Surgery, Wrexham Maelor Hospital, Betsi Cadwaladr University Health Board, Wrexham, United Kingdom
  • 5Department of Internal Medicine, Mount Sinai Morningside and West Hospitals, New York, NY, United States
  • 6Department of General Surgery, North Manchester General Hospital, North Manchester Care Organisation, Manchester, United Kingdom
  • 7Department of Hepatobiliary and Pancreatic Surgery, Royal Blackburn Hospital, Blackburn, United Kingdom

Abstract

We aimed to compare resection and survival outcomes of neoadjuvant chemoradiotherapy (CRT) and immediate surgery in patients with resectable pancreatic cancer (RPC) or borderline resectable pancreatic cancer (BRPC). In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards, a systematic review of randomized controlled trials (RCTs) was conducted. Random effects modeling was applied to calculate pooled outcome data. Likelihood of type 1 or 2 errors in the meta-analysis model was assessed by trial sequential analysis. A total of 400 patients from four RCTs were included. When RPC and BRPC were analyzed together, neoadjuvant CRT resulted in a higher R0 resection rate (risk ratio [RR]: 1.55, p = 0.004), longer overall survival (mean difference [MD]: 3.75 years, p = 0.009) but lower overall resection rate (RR: 0.83, p = 0.008) compared with immediate surgery. When RPC and BRPC were analyzed separately, neoadjuvant CRT improved R0 resection rate (RR: 3.72, p = 0.004) and overall survival (MD: 6.64, p = 0.004) of patients with BRPC. However, it did not improve R0 resection rate (RR: 1.18, p = 0.13) or overall survival (MD: 0.94, p = 0.57) of patients with RPC. Neoadjuvant CRT might be beneficial for patients with BRPC, but not for patients with RPC. Nevertheless, the best available evidence does not include contemporary chemotherapy regimens. Patients with RPC and those with BRPC should not be combined in the same cohort in future studies.

Keyword

Chemoradiotherapy; Neoadjuvant therapy; Pancreatic cancer

Figure

  • Fig. 1 PRISMA flow chart.

  • Fig. 2 Risk of bias summary and graph showing authors’ judgments about each risk of bias item for randomized trials.

  • Fig. 3 Results of comparison of meta-analysis model: (A) resection rate; (B) R0 resection rate; and (C) overall survival. SD, standard deviation; CI, confidence interval; M-H, Mantel-Haenszel; IV, inverse variance; CRT, chemoradiotherapy.

  • Fig. 4 Results of trial sequential analysis model: (A) resection rate; (B) R0 resection rate; and (C) overall survival. CRT, chemoradiotherapy.

  • Fig. 5 Results of subgroup analyses for patients with resectable pancreatic cancer and borderline resectable pancreatic cancer: (A) resection rate; (B) R0 resection rate; and (C) overall survival. SD, standard deviation; CI, confidence interval; M-H, Mantel-Haenszel; IV, inverse variance; CRT, chemoradiotherapy.


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