Opioids and premature biochemical recurrence of prostate cancer: a randomised prospective clinical trial

BackgroundProstate cancer is one of the most prevalent neoplasms in male patients, and surgery is the main treatment. Opioids can have immune modulating effects, but their relation to cancer recurrence is unclear. We evaluated whether opioids used during prostatectomy can affect biochemical recurrence-free survival.MethodsWe randomised 146 patients with prostate cancer scheduled for prostatectomy into opioid-free anaesthesia or opioid-based anaesthesia groups. Baseline characteristics, perioperative data, and level of prostate-specific antigen every 6 months for 2 yr after surgery were recorded. Prostate-specific antigen >0.2 ng ml−1 was considered biochemical recurrence. A survival analysis compared time with biochemical recurrence between the groups, and a Cox regression was modelled to evaluate which variables affect biochemical recurrence-free survival.ResultsWe observed 31 biochemical recurrence events: 17 in the opioid-free anaesthesia group and 14 in the opioid-based anaesthesia group. Biochemical recurrence-free survival was not statistically different between groups (P=0.54). Cox regression revealed that biochemical recurrence-free survival was shorter in cases of obesity (hazard ratio [HR] 1.63, confidence interval [CI] 0.16–3.10; p=0.03), high D'Amico risk (HR 1.58, CI 0.35–2.81; P=0.012), laparoscopic surgery (HR 1.6, CI 0.38–2.84; P=0.01), stage 3 tumour pathology (HR 1.60, CI 0.20–299) and N1 status (HR 1.34, CI 0.28–2.41), and positive surgical margins (HR 1.37, CI 0.50–2.24; P=0.002). The anaesthesia technique did not affect time to biochemical recurrence (HR −1.03, CI −2.65–0.49; P=0.18).ConclusionsIntraoperative opioid use did not modify biochemical recurrence rates and biochemical recurrence-free survival in patients with intermediate and high D'Amico risk prostate cancer undergoing radical prostatectomy.Clinical trial registrationNCT03212456.