The surgical stress response can accelerate clinical metastasis formation. Perioperative glucocorticoids might modulate this response and the metastatic process. We aimed to describe associations between perioperative glucocorticoids and long-term outcomes after cancer surgery. We searched four databases for eligible trials and performed meta-analyses on frequency and time-to-event data. We included sixteen studies that evaluated eight different cancer types. No association was found between perioperative glucocorticoids and recurrence in either the frequency meta-analysis, risk ratio (RR) 1.04, 95% confidence interval (CI) (0.87-1.25), or in the time-to-event meta-analysis, hazard ratio (HR) 1.18, 95% CI (0.78-1.79). Increased 1-year overall survival, RR 0.70, 95% (0.51-0.97), and disease-free survival, RR 0.77, 95% CI (0.60-0.97), was found for the glucocorticoid group, but five years after surgery, overall survival was reduced for the glucocorticoid group, RR 1.64, 95% CI (1.00-2.71). An exploratory subgroup analysis revealed decreased overall survival, HR 1.78, 95% CI (1.57-2.03), for patients undergoing colorectal cancer surgery while receiving glucocorticoids. Perioperative glucocorticoids were not associated with recurrence after cancer surgery. We found neither beneficial or deleterious associations between glucocorticoids and overall survival or disease-free survival. The available evidence remains heterogenous; low in quality and amount; and cancer-specific at present.Cancers 2020, 12, 76 2 of 22 such as glucocorticoids. Preliminary animal studies have investigated the effect of steroids on cancer progression and the results are not conclusive [6,7]. Some suggest that endogenous glucocorticoids released from prolonged stress response may hinder natural killer (NK) cell activity, which is essential in malignant defence, but the effect might not be as significant as the NK cell suppression mediated by stress related catecholamines [8]. On the other hand, the anti-inflammatory effects of glucocorticoids might prove beneficial in breaking the inflammatory cycle.Glucocorticoids are known to modulate the inflammatory stress response and are increasingly used in the perioperative period. Administration of low-dose perioperative dexamethasone is used for prevention of postoperative nausea and vomiting (PONV). Use of high dose glucocorticoids has been shown to have analgesic effects and may even decrease the risk of postoperative complications [9] without increasing short-term adverse events [10]. It appears that glucocorticoids are safe and beneficial for immediate postoperative outcomes. However, evaluation of safety and possible benefits on long-term oncologic outcomes remain to be shown. Furthermore, it has been recommended that the effect of adjunct medications for anaesthesia on oncological outcomes should be prioritized by researchers [11].In this study, we hypothesized that the use of perioperative glucocorticoids may impact long-term survival after cancer surgery. We aimed to describe the possible assoc...