Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Queensland Centre for Gynaecological Cancer Research, The University of Queensland, Brisbane, QLD, Australia.
Lancet Oncol. 2020 Jun;21(6):851-860. doi: 10.1016/S1470-2045(20)30081-4.
In the phase 3 LACC trial and a subsequent population-level review, minimally invasive radical hysterectomy was shown to be associated with worse disease-free survival and higher recurrence rates than was open radical hysterectomy in patients with early stage cervical cancer. Here, we report the results of a secondary endpoint, quality of life, of the LACC trial.
The LACC trial was a randomised, open-label, phase 3, non-inferiority trial done in 33 centres worldwide. Eligible participants were women aged 18 years or older with International Federation of Gynaecology and Obstetrics (FIGO) stage IA1 with lymphovascular space invasion, IA2, or IB1 adenocarcinoma, squamous cell carcinoma, or adenosquamous carcinoma of the cervix, with an Eastern Cooperative Oncology Group performance status of 0 or 1, who were scheduled to have a type 2 or 3 radical hysterectomy. Participants were randomly assigned (1:1) to receive open or minimally invasive radical hysterectomy. Randomisation was done centrally using a computerised minimisation program, stratified by centre, disease stage according to FIGO guidelines, and age. Neither participants nor investigators were masked to treatment allocation. The primary endpoint of the LACC trial was disease-free survival at 4·5 years, and quality of life was a secondary endpoint. Eligible patients completed validated quality-of-life and symptom assessments (12-item Short Form Health Survey [SF-12], Functional Assessment of Cancer Therapy-Cervical [FACT-Cx], EuroQoL-5D [EQ-5D], and MD Anderson Symptom Inventory [MDASI]) before surgery and at 1 and 6 weeks and 3 and 6 months after surgery (FACT-Cx was also completed at additional timepoints up to 54 months after surgery). Differences in quality of life over time between treatment groups were assessed in the modified intention-to-treat population, which included all patients who had surgery and completed at least one baseline (pretreatment) and one follow-up (at any timepoint after surgery) questionnaire, using generalised estimating equations. The LACC trial is registered with ClinicalTrials.gov, NCT00614211.
Between Jan 31, 2008, and June 22, 2017, 631 patients were enrolled; 312 assigned to the open surgery group and 319 assigned to the minimally invasive surgery group. 496 (79%) of 631 patients had surgery completed at least one baseline and one follow-up quality-of-life survey and were included in the modified intention-to-treat analysis (244 [78%] of 312 patients in the open surgery group and 252 [79%] of 319 participants in the minimally invasive surgery group). Median follow-up was 3·0 years (IQR 1·7-4·5). At baseline, no differences in the mean FACT-Cx total score were identified between the open surgery (129·3 [SD 18·8]) and minimally invasive surgery groups (129·8 [19·8]). No differences in mean FACT-Cx total scores were identified between the groups 6 weeks after surgery (128·7 [SD 19·9] in the open surgery group vs 130·0 [19·8] in the minimally invasive surgery group) or 3 months after surgery (132·0 [21·7] vs 133·0 [22·1]).
Since recurrence rates are higher and disease-free survival is lower for minimally invasive radical hysterectomy than for open surgery, and postoperative quality of life is similar between the treatment groups, gynaecological oncologists should recommend open radical hysterectomy for patients with early stage cervical cancer.
MD Anderson Cancer Center and Medtronic.
在 3 期 LACC 试验和随后的人群水平回顾中，与开放性根治性子宫切除术相比，微创根治性子宫切除术与早期宫颈癌患者的无病生存率更差和更高的复发率相关。在这里，我们报告 LACC 试验的次要终点，即生活质量的结果。
LACC 试验是一项在全球 33 个中心进行的随机、开放标签、3 期、非劣效性试验。符合条件的参与者为年龄在 18 岁或以上的国际妇产科联合会（FIGO）IA1 期伴血管淋巴管侵犯、IA2 期或 IB1 期宫颈癌的患者，包括腺癌、鳞状细胞癌或腺癌-鳞癌，东部合作肿瘤组表现状态为 0 或 1，计划行 2 型或 3 型根治性子宫切除术。参与者被随机分配（1:1）接受开放性或微创根治性子宫切除术。随机分配由中央计算机化最小化程序完成，按中心、FIGO 指南规定的疾病阶段和年龄分层。参与者和研究者均不了解治疗分配情况。LACC 试验的主要终点是 4.5 年无病生存率，生活质量是次要终点。符合条件的患者在手术前和手术后 1 周、6 周、3 个月和 6 个月完成了经过验证的生活质量和症状评估（FACT-Cx 还在手术后 54 个月的额外时间点完成）（12 项简明健康调查 [SF-12]、癌症治疗宫颈功能评估 [FACT-Cx]、欧洲五维健康量表 [EQ-5D] 和 MD 安德森症状量表 [MDASI]）。使用广义估计方程评估治疗组之间随时间变化的生活质量差异。改良意向治疗人群包括所有接受手术并完成至少一次基线（治疗前）和一次随访（手术后任何时间点）问卷的患者，该人群包括所有接受手术并完成至少一次基线（治疗前）和一次随访（手术后任何时间点）问卷的患者。LACC 试验在 ClinicalTrials.gov 注册，NCT00614211。
2008 年 1 月 31 日至 2017 年 6 月 22 日期间，共纳入 631 例患者；312 例分配至开放性手术组，319 例分配至微创手术组。631 例患者中，有 496 例（79%）完成了至少一次基线和一次随访的生活质量调查，纳入改良意向治疗分析（开放性手术组 244 例[78%]，微创手术组 252 例[79%]）。中位随访时间为 3.0 年（IQR 1.7-4.5）。在基线时，开放性手术组（129.3 [18.8]）和微创手术组（129.8 [19.8]）的 FACT-Cx 总分均值无差异。手术后 6 周（开放性手术组 128.7 [19.9]与微创手术组 130.0 [19.8]）和 3 个月（132.0 [21.7]与 133.0 [22.1]），两组间的 FACT-Cx 总分均值也无差异。
由于微创根治性子宫切除术的复发率较高，无病生存率较低，且两组术后生活质量相似，妇科肿瘤医生应为早期宫颈癌患者推荐开放性根治性子宫切除术。
MD 安德森癌症中心和美敦力。
