Table 4

Summary of findings and recommendations for future research

TopicIn vitro dataAnimal dataHuman dataPotential areas for future research*
Surgical stress response and cancer recurrence+++Direct correlation between the extent of the primary cancer surgery and risk of metastasis.No data.+++Direct correlation between the extent of the primary cancer surgery and risk of tumor recurrence.RCTs evaluating the effect of laparoscopic vs open surgery on the rate of metastasis after other tumors.†
Intraspinal anesthesia/analgesia and the influence on immunomodulation and immune cell functionNo data.+++Effect on immune function and immunomodulation.+Effect on immune function and immunomodulation.RCT of intraspinal anesthesia and analgesia without parenteral opioids to determine whether the impact on immune cell function translates into longer survival rates after cancer surgery.
Perioperative parental opioid use and cancer recurrence++Detrimental effect promoting cancer cell migration and invasion.++Effect on facilitating tumor spread and reduce disease-free survival.+On increasing risk of metastasis in some solid tumors.RCT of multimodal analgesia without parenteral opioids to determine the impact on tumor metastasis.
Perioperative NSAID and cancer recurrenceNo data.No data.++Aspirin reduces metastasis in colorectal cancer but +reducing the risk of recurrence or metastasis in breast cancer.RCT on the use of NSAIDs vs none in patients with breast and colorectal cancer may be warranted.
Ketamine and cancer recurrence+Suppression of proinflammatory cytokine production and immunoregulatory activity of mast cell, macrophages, and neutrophil in human whole blood.No data.+Reduced number of lung metastasis vs fentanyl.RCT of multimodal analgesia without parenteral opioids to determine the impact on tumor metastasis.
Intravenous lidocaine and cancer recurrence+++Suggesting the protective effect of local anesthetics on cancer recurrence.+++(Limited) Suggesting the protective effects of local anesthetics on cancer recurrence.No data.There is a need for pilot studies to determine if intravenous lidocaine infusions may alter cancer cell biology and thus reduce recurrence.
Alpha-2 agonists and cancer recurrenceNo data.No data.No data.An RCT is warranted considering the wide use of dexmedetomidine in the perioperative period and the known role of alpha-2 adrenoceptors in breast cancer.
Steroids and cancer recurrenceNo data.No data.+That dexamethasone may reduce the risk of recurrence or metastasis.RCT on the use of dexamethasone vs placebo in patients with cancer may be warranted.
Perioperative regional anesthesia and cancer recurrenceNo data.+With conflicting results.A number of clinical trials are registered evaluating various regional analgesia techniques, usually against opioid analgesia in various forms of cancer.
  • +++Strong evidence; ++moderate evidence; +weak evidence.

  • *Recommendations are made recognizing that the size of the change likely to be present with a therapeutic intervention is a relative reduction of 20%, from an absolute recurrence rate of <10% in some of the patients with cancer. Thus, more than 3000 patients may be needed, with a minimum of 5-year follow-up.

  • †May be difficult to get approved by an ethics committee as surgical practice favors the routine use of laparoscopic procedures.

  • NSAID, non-steroidal anti-inflammatory drug; RCT, randomized controlled trial.