早期输卵管切除术（输卵管切除）联合延迟卵巢切除术以改善生活质量，作为BRCA1/2突变携带者降低风险的输卵管卵巢切除术的替代方案（TUBA研究）：一项前瞻性非随机多中心研究。
Early salpingectomy (TUbectomy) with delayed oophorectomy to improve quality of life as alternative for risk-reducing salpingo-oophorectomy in BRCA1/2 mutation carriers (TUBA study): a prospective non-randomised multicentre study.
作者信息
Harmsen Marline G, Arts-de Jong Marieke, Hoogerbrugge Nicoline, Maas Angela H E M, Prins Judith B, Bulten Johan, Teerenstra Steven, Adang Eddy M M, Piek Jurgen M J, van Doorn Helena C, van Beurden Marc, Mourits Marian J E, Zweemer Ronald P, Gaarenstroom Katja N, Slangen Brigitte F M, Vos M Caroline, van Lonkhuijzen Luc R C W, Massuger Leon F A G, Hermens Rosella P M G, de Hullu Joanne A
机构信息
Department of Obstetrics & Gynaecology, Radboud University Medical Center, PO Box 9101, , 6500 HB, Nijmegen, The Netherlands.
Department of Human Genetics, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
出版信息
BMC Cancer. 2015 Aug 19;15:593. doi: 10.1186/s12885-015-1597-y.
BACKGROUND
Risk-reducing salpingo-oophorectomy (RRSO) around the age of 40 is currently recommended to BRCA1/2 mutation carriers. This procedure decreases the elevated ovarian cancer risk by 80-96% but it initiates premature menopause as well. The latter is associated with short-term and long-term morbidity, potentially affecting quality of life (QoL). Based on recent insights into the Fallopian tube as possible site of origin of serous ovarian carcinomas, an alternative preventive strategy has been put forward: early risk-reducing salpingectomy (RRS) and delayed oophorectomy (RRO). However, efficacy and safety of this alternative strategy have to be investigated.
METHODS
A multicentre non-randomised trial in 11 Dutch centres for hereditary cancer will be conducted. Eligible patients are premenopausal BRCA1/2 mutation carriers after completing childbearing without (a history of) ovarian carcinoma. Participants choose between standard RRSO at age 35-40 (BRCA1) or 40-45 (BRCA2) and the alternative strategy (RRS upon completion of childbearing and RRO at age 40-45 (BRCA1) or 45-50 (BRCA2)). Women who opt for RRS but do not want to postpone RRO beyond the currently recommended age are included as well. Primary outcome measure is menopause-related QoL. Secondary outcome measures are ovarian/breast cancer incidence, surgery-related morbidity, histopathology, cardiovascular risk factors and diseases, and cost-effectiveness. Mixed model data analysis will be performed.
DISCUSSION
The exact role of the Fallopian tube in ovarian carcinogenesis is still unclear. It is not expected that further fundamental research will elucidate this role in the near future. Therefore, this clinical trial is essential to investigate RRS with delayed RRO as alternative risk-reducing strategy in order to improve QoL.
TRIAL REGISTRATION
ClinicalTrials.gov ( NCT02321228 ).
背景
目前建议BRCA1/2基因突变携带者在40岁左右进行降低风险的输卵管卵巢切除术（RRSO）。该手术可将卵巢癌风险升高降低80 - 96%，但也会引发过早绝经。后者与短期和长期发病率相关，可能影响生活质量（QoL）。基于最近对输卵管作为浆液性卵巢癌可能起源部位的认识，提出了一种替代预防策略：早期降低风险的输卵管切除术（RRS）和延迟卵巢切除术（RRO）。然而，这种替代策略的有效性和安全性有待研究。
方法
将在荷兰11个遗传性癌症中心进行一项多中心非随机试验。符合条件的患者是已完成生育且无卵巢癌（病史）的绝经前BRCA1/2基因突变携带者。参与者可在35 - 40岁（BRCA1）或40 - 45岁（BRCA2）进行标准RRSO与替代策略（生育完成后进行RRS，40 - 45岁（BRCA1）或45 - 50岁（BRCA2）进行RRO）之间做出选择。选择RRS但不想将RRO推迟到当前推荐年龄以上的女性也包括在内。主要结局指标是与绝经相关的生活质量。次要结局指标是卵巢/乳腺癌发病率、手术相关发病率、组织病理学、心血管危险因素和疾病以及成本效益。将进行混合模型数据分析。
讨论
输卵管在卵巢癌发生的确切作用仍不清楚。预计在不久的将来，进一步的基础研究也无法阐明这一作用。因此，本临床试验对于研究RRS联合延迟RRO作为替代降低风险策略以改善生活质量至关重要。
试验注册
ClinicalTrials.gov（NCT02321228）
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