阿片类药物与前列腺癌早期生化复发：一项随机前瞻性临床试验。

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

机构信息

Division of Anaesthesia, Hospital das Clínicas da Faculdade de Medicina (HCFMUSP) da Universidade de São Paulo, São Paulo, Brazil; Serviços Médicos de Anestesia (SMA), São Paulo, Brazil.

Division of Anaesthesia, Hospital das Clínicas da Faculdade de Medicina (HCFMUSP) da Universidade de São Paulo, São Paulo, Brazil; Department of Anaesthesiology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil; Anaesthesia Department, Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, Brazil.

出版信息

Br J Anaesth. 2021 May;126(5):931-939. doi: 10.1016/j.bja.2021.01.031. Epub 2021 Mar 10.

DOI:10.1016/j.bja.2021.01.031

Abstract

BACKGROUND

Prostate 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.

METHODS

We 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 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.

RESULTS

We 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).

CONCLUSIONS

Intraoperative 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 REGISTRATION

NCT03212456.

摘要

背景

前列腺癌是男性患者中最常见的肿瘤之一，手术是主要治疗方法。阿片类药物具有免疫调节作用，但它们与癌症复发的关系尚不清楚。我们评估了前列腺切除术期间使用阿片类药物是否会影响生化无复发生存率。

方法

我们将 146 名计划接受前列腺切除术的前列腺癌患者随机分为无阿片类药物麻醉组或阿片类药物麻醉组。记录基线特征、围手术期数据以及术后 2 年内每 6 个月的前列腺特异性抗原水平。前列腺特异性抗原>0.2ng/ml 被认为是生化复发。生存分析比较了两组之间的生化复发时间，Cox 回归模型评估了哪些变量影响生化无复发生存率。

结果

我们观察到 31 例生化复发事件：无阿片类药物麻醉组 17 例，阿片类药物麻醉组 14 例。两组之间的生化无复发生存率无统计学差异（P=0.54）。Cox 回归显示，肥胖（危险比[HR]1.63，置信区间[CI]0.16-3.10；p=0.03）、高 D'Amico 风险（HR 1.58，CI 0.35-2.81；P=0.012）、腹腔镜手术（HR 1.6，CI 0.38-2.84；P=0.01）、肿瘤病理分期 3 期（HR 1.60，CI 0.20-299）和 N1 状态（HR 1.34，CI 0.28-2.41）以及阳性手术切缘（HR 1.37，CI 0.50-2.24；P=0.002）的生化无复发生存率较短。麻醉技术不影响生化复发时间（HR-1.03，CI-2.65-0.49；P=0.18）。