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Postoperative chemotherapy with single-agent fluoropyrimidines after resection of colorectal cancer liver metastases: a meta-analysis of randomised trials
  1. Davide Mauri1,2,
  2. George Zarkavelis1,2,
  3. Panagiotis Filis1,2,
  4. Lampriani Tsali3,
  5. Georgia Zafeiri1,2,
  6. Alexandra Papadaki1,
  7. Amalia Vassou4,
  8. Christos Georgopoulos1,
  9. George Pentheroudakis1
  1. 1 Department of Medical Oncology, Medical School, University of Ioannina, Ioannina, Greece
  2. 2 Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN)
  3. 3 Department of Internal Medicine, General Hospital of Arta, Arta, Greece
  4. 4 Department of Hematology, Ioannina University Hospital, Ioannina, Greece
  1. Correspondence to Dr George Pentheroudakis; gpenther{at}otenet.gr

Abstract

Surgical resection is the only option of cure for patients with metastatic colorectal cancer. Risk of recurrence after metastasectomy is around 75%. Use of adjuvant chemotherapy after metastasectomy is controversial.

Aim To address whether adjuvant systemic therapy after colorectal cancer metastasectomy offers any survival benefit compared with surgery alone.

Methods Systematic review of literature and meta-analysis of all available randomised evidence. Relative hazards (RHs) were summarised across trials and heterogeneity was assessed with the Q and I2 statistics.

Results Five trials were eligible. Three trials, all using single-agent fluoropyrimidine chemotherapy, presented data valuable for analyses. 482 patients were included in the meta-analysis: 238 randomly assigned to receive postoperative chemotherapy and 244 to metastasectomy only. We found no overall survival (OS) benefit with the use of postoperative single-agent fluoropyrimidines compared with surgery alone, even if a trend for benefit was observed (relative hazard (RH)=0.781, 95% CI 0.593 to 1.030, p=0.080). Significant disease-free survival benefit with the use of postoperative chemotherapy was observed (RH=0.645, 95% CI 0.509 to 0.818, p=0.001). No quality of life (QL) data were available. All trials showed accrual delay, two stopped and one recruiting after 10 years. Long follow-up needs were evidenced since OS curves split only after 3.5 years.

Conclusions No OS benefit was documented from the use of postoperative monochemotherapy. Metastasectomy alone continues to be the standard of care. Combination chemotherapy regimens should be evaluated along with QL assessment in future trials appropriately designed for long-term accrual and follow-up.

  • postoperative chemotherapy
  • liver metastasectomy
  • colorectal cancer metastases
  • meta-analisys
  • fluoropyrimidines

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Footnotes

  • Contributors All authors participated in the design of the study. DM and GZar: literature search was performed by two independent reviewers. LT and GZaf: independently searched medical libraries. PF: independently performed specific journals searches. AP: independently performed scrutinized 2014-2017 conferences. GP: in case of disagreement between independent searches (gastrointestinal oncology expert) supervised the data. DM, PA and TL: performed data extraction. DM and GC: performed statistical analyses. DM, GZar, PA and GP: interpret results. DM and GP: wrote the manuscript. GZr, LT, GZf, PF, AP and GC: reviewed and commented on the final manuscript. All authors had full access to all data in the study and take responsibility for the integrity of the data and accuracy of the data analysis.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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