Key Points

• The age-adjusted incidence rates of opportunistic salpingectomy (OS) for sterilization and during hysterectomy increased nearly 18-fold and nearly 8-fold, respectively, between the years 2010 and 2017.
• There was higher uptake of OS for sterilization in the Northeast and West and within urban locations.
• OS use during hysterectomy was higher among women undergoing an abdominal hysterectomy (vs a vaginal one) and among women with uterine fibroids (vs other indications).

Ovarian cancer screening is not recommended for women at average risk because the combination of low test specificity and low prevalence results in an unacceptably low positive predictive value. Even for women at increased risk, screening has not been proven to be an effective tool in lowering ovarian cancer mortality. For these reasons as well as this disease's high case fatality rate, clinicians have turned to “risk-reducing” surgeries such as prophylactic oophorectomy. Because of this procedure's morbidity in premenopausal women, it is an option largely for those who are deemed to be at high risk. However, growing evidence has emerged showing that because the majority of high-grade serous ovarian cancers predominantly originate in the fallopian tubes (and involve the ovaries secondarily), OS is becoming a preferred surgical approach to reduce ovarian cancer risk, especially for women at average risk. The Society of Gynecologic Oncology and the American College of Obstetrics and Gynecology now recommend OS in place of tubal ligation for sterilization or during a benign hysterectomy in average-risk women.

However, there have been limited data on uptake and patterns of adherence to these recommendations for OS. A new study appearing in Cancer Prevention Research (doi:10.1158/1940-6207.capr-21-0121) addresses this question.

“This study offers one of the first evaluations regarding uptake and dissemination of opportunistic salpingectomy in the US that includes procedures done in both the inpatient and outpatient settings for women considering sterilization to reduce their risk of future pregnancy or hysterectomy,” says study author, Kala Visvanathan, MD, MHS, director of the Clinical Cancer Genetics and Prevention Service at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland. “The study also evaluates predictors of uptake of opportunistic salpingectomy.”

Study Details

According to the researchers of the new study, 3 earlier observational studies reported that OS may have resulted in a 42% to 64% reduction in ovarian cancer incidence; however, few studies have comprehensively assessed the dissemination of OS in clinical settings. Prior studies assessing OS uptake were limited to inpatient settings, which are not where most benign gynecologic surgeries occur.

In the current study, researchers evaluated 48,231,235 inpatients and outpatients from hospitals and ambulatory surgical centers across the United States who had no history of breast or gynecologic cancer on the basis of their insurance claims from the Truven Health Analytics MarketScan Commercial Claims and Encounters Database. Without revealing identities of the patients, the database includes some demographic information as well as admitting and discharge diagnoses and procedure codes.

The researchers found that between the years 2010 and 2017, there were 1,046,525 with claims filed for tubal ligation, OS, or hysterectomy. Among these, the researchers excluded 303,348 women who also had insurance claims for an oophorectomy or a salpingo-oophorectomy during hysterectomy as well as 97,021 hysterectomy patients whose claims did not reveal whether additional adnexal structures were removed and 7200 subjects who had an ectopic pregnancy, pelvic inflammatory disease, or pelvic infections. There were 863 patients aged 50 years or older who underwent sterilization; they were excluded because women in that age group rarely undergo tubal ligation and OS for sterilization.

The analytic sample of 638,093 women who had benign gynecologic surgeries, identified by International Classification of Diseases procedure codes (9th and 10th revisions) and Current Procedural Terminology codes, was divided into 4 groups:

• Tubal ligation: 308,833 patients.
• OS for sterilization: 13,462 patients.
• Hysterectomy alone without OS: 293,000 patients.
• Hysterectomy and OS: 22,798 patients.

Study Results

Between the years 2010 and 2017, the age-adjusted incidence rates of OS for sterilization and during hysterectomy increased 17.8-fold (95% CI, 16.2-19.5) and 7.6-fold (95% CI, 5.5-10.4), respectively. They noted that the rapid age-adjusted increases in quarterly rates of 109% and 250%, respectively, matched when national guidelines by the Society of Gynecologic Oncology were released in 2013.

Dr. Visvanathan says that one of the study's most important findings was that the dissemination of the procedure was not uniform with respect to patient demographic and clinical characteristics and especially with respect to where patients lived. For example, they identified greater OS use for younger women, with 94% of OS procedures performed in women aged 50 years or younger, and a higher uptake of OS for sterilization in women with a genetic predisposition for and/or a family history of breast and ovarian cancers. Dr. Visvanathan says that for women with a genetic predisposition, this could reflect salpingectomy before oophorectomy, which is currently being evaluated in a clinical trial among BRCA1 mutation carriers.

Another finding was that OS use during hysterectomy was higher among women undergoing an abdominal hysterectomy and among women with uterine fibroids. They also reported on a notable variation in OS uptake for high-risk women based on where they lived: “We found there were higher uptakes of OS in the Northeast and West and lower OS uptakes in the Midwest and South and in rural areas compared to urban locations.” They attributed these differences to variation in provider and patient knowledge and preferences regarding OS use and insurance coverage.

Study Interpretation

Debra L. Richardson, MD, associate professor and section chief of the Division of Gynecologic Oncology at the Stephenson Cancer Center/University of Oklahoma Health Science Center in Oklahoma City, Oklahoma, says that not only is the size of the study related to OS uptake important, but the study also includes a wider variety of subjects than earlier research. She served as a committee liaison in crafting the opinion by the American College of Obstetricians and Gynecologists Committee on Gynecologic Practice regarding OS in 2019.

“This is the largest study to date in the United States in regard to the uptake of opportunistic salpingectomy,” she says. “The majority of previous studies included only women who underwent inpatient surgery, but many of these procedures are done as an outpatient.” She says that it is noteworthy, however, that this study includes only women with private insurance. “So it is not generalizable to women with Medicare or Medicaid.”

Dr. Richardson adds that it is important that the uptake of OS increased during the study period. “This correlates with the release of guidelines advocating for opportunistic salpingectomy at the time of hysterectomy or sterilization procedures to reduce the risk of epithelial ovarian cancer given the lack of an effective screening test.”

Dr. Visvanathan says that more studies are needed to evaluate possible barriers that may exist regarding uptake. “National registry databases need to be put into place now to evaluate both the short- and long-term impact of this significant change in clinical practice on ovarian cancer incidence and mortality and any potential adverse effects.”

Dr. Richardson suggests that clinicians looking for guidance on this topic should refer to American College of Obstetricians and Gynecologists Committee Opinion 774 published in Obstetrics & Gynecology in April 2019 (doi:10.1097/aog.0000000000003165) and the meta-analysis by Yoon et al published in the European Journal of Cancer in 2016 (doi:10.1016/j.ejca.2015.12.003). “These documents demonstrated that salpingectomy is an effective means to reduce the risk of ovarian cancer in average-risk women.”

Photo credit: Voltaggio L, Cimino-Mathews A, Bishop JA, et al. Current concepts in the diagnosis and pathobiology of intraepithelial neoplasia: a review by organ system. CA Cancer J Clin. 2016;66:408-436. doi:10.3322/caac.21350

中文翻译：

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机会性输卵管切除术可降低卵巢癌风险

关键点

• 在 2010 年和 2017 年之间，用于绝育和子宫切除术的机会性输卵管切除术 (OS) 的年龄调整发生率分别增加了近 18 倍和近 8 倍。
• 在东北部和西部以及城市地区，使用 OS 进行绝育的比例更高。
• 在接受腹部子宫切除术的女性（相对于阴道切除术）和患有子宫肌瘤的女性（相对于其他适应症）中，子宫切除术期间的 OS 使用率更高。

不建议对处于平均风险的女性进行卵巢癌筛查，因为低检测特异性和低患病率导致阳性预测值低得令人无法接受。即使对于风险增加的女性，筛查也未被证明是降低卵巢癌死亡率的有效工具。由于这些原因以及这种疾病的高病死率，临床医生已转向“降低风险”的手术，例如预防性卵巢切除术。由于该手术在绝经前妇女中的发病率很高，因此对于那些被认为处于高风险中的人来说，它主要是一种选择。然而，越来越多的证据表明，由于大多数高级别浆液性卵巢癌主要起源于输卵管（其次是卵巢），OS 正在成为降低卵巢癌风险的首选手术方法，尤其是对于处于平均风险的女性而言。妇科肿瘤学会和美国妇产科学院现在推荐使用 OS 代替输卵管结扎术来绝育或在平均风险女性的良性子宫切除术中进行。

然而，关于对 OS 的这些建议的采纳和依从模式的数据有限。癌症预防研究(doi:10.1158/1940-6207.capr-21-0121)中出现的一项新研究解决了这个问题。

研究作者 Kala 说：“这项研究提供了关于在美国接受和传播机会性输卵管切除术的首批评估之一，其中包括在住院和门诊为考虑绝育的女性进行的手术，以降低她们未来怀孕或子宫切除术的风险。” Visvanathan，医学博士，MHS，马里兰州巴尔的摩约翰霍普金斯西德尼金梅尔综合癌症中心临床癌症遗传学和预防服务主任。“该研究还评估了接受机会性输卵管切除术的预测因素。”

学习详情

根据这项新研究的研究人员的说法，3 项较早的观察性研究报告称，OS 可能导致卵巢癌发病率降低 42% 至 64%；然而，很少有研究全面评估 OS 在临床环境中的传播。先前评估 OS 摄取的研究仅限于住院环境，而大多数良性妇科手术并不发生在这些环境中。

在当前的研究中，研究人员根据来自 Truven Health Analytics MarketScan 商业索赔和遭遇数据库的保险索赔，评估了来自美国各地医院和门诊手术中心的 48,231,235 名没有乳腺癌或妇科癌症病史的住院患者和门诊患者。在不透露患者身份的情况下，该数据库包括一些人口统计信息以及入院和出院诊断和程序代码。

研究人员发现，在 2010 年至 2017 年间，有 1,046,525 人提出了输卵管结扎、OS 或子宫切除术的索赔。其中，研究人员排除了 303,348 名在子宫切除术期间也有卵巢切除术或输卵管卵巢切除术保险索赔的女性，以及 97,021 名子宫切除术患者，其索赔并未显示是否切除了额外的附件结构，以及 7200 名异位妊娠、盆腔炎症性疾病或盆腔感染。50岁及以上绝育患者863人；他们被排除在外，因为该年龄组的女性很少接受输卵管结扎和 OS 绝育手术。

根据国际疾病分类程序代码（第 9 和第 10 修订版）和现行程序术语代码确定的 638,093 名接受良性妇科手术的女性的分析样本分为 4 组：

• 输卵管结扎术：308,833 名患者。
• 绝育 OS：13,462 名患者。
• 仅没有 OS 的子宫切除术：293,000 名患者。
• 子宫切除术和 OS：22,798 名患者。

研究结果

从 2010 年到 2017 年，绝育手术和子宫切除术的年龄调整 OS 发生率分别增加了 17.8 倍（95% CI，16.2-19.5）和 7.6 倍（95% CI，5.5-10.4）。他们指出，与 2013 年妇科肿瘤学会发布的国家指南相匹配，按年龄调整后的季度发病率分别快速增长 109% 和 250%。

Visvanathan 博士说，该研究最重要的发现之一是，该程序的传播在患者人口统计和临床特征方面并不一致，尤其是在患者居住地方面。例如，他们发现年轻女性更多地使用 OS，94% 的 OS 手术是在 50 岁或以下的女性中进行的，并且在具有乳房遗传易感性和/或家族史的女性中，OS 用于绝育的比例更高和卵巢癌。Visvanathan 博士说，对于有遗传倾向的女性，这可能反映了卵巢切除术之前的输卵管切除术，目前正在BRCA1突变携带者的临床试验中进行评估。

另一个发现是，在接受腹部子宫切除术的女性和患有子宫肌瘤的女性中，子宫切除术期间 OS 的使用率更高。他们还报告了高危女性的 OS 摄取量因居住地而异：城市地点。” 他们将这些差异归因于提供者和患者对操作系统使用和保险范围的了解和偏好的差​​异。

学习解释

俄克拉荷马州俄克拉荷马市斯蒂芬森癌症中心/俄克拉荷马大学健康科学中心妇科肿瘤科副教授兼科长 Debra L. Richardson 表示，研究的规模不仅与 OS 摄取有关重要，但该研究还包括比早期研究更广泛的主题。她担任委员会联络员，起草了美国妇产科学院妇科实践委员会关于 2019 年 OS 的意见。

“这是迄今为止美国关于机会性输卵管切除术的最大研究，”她说。“以前的大多数研究只包括接受住院手术的女性，但其中许多手术都是在门诊完成的。” 然而，她说值得注意的是，这项研究仅包括拥有私人保险的女性。“所以它不适用于拥有医疗保险或医疗补助的女性。”

理查森博士补充说，在研究期间增加 OS 的摄取很重要。“这与在子宫切除术或绝育手术时提倡机会性输卵管切除术的指南发布相关，以降低上皮性卵巢癌的风险，因为缺乏有效的筛查测试。”

Visvanathan 博士说，需要更多的研究来评估可能存在的摄取障碍。“现在需要建立国家注册数据库，以评估临床实践的这一重大变化对卵巢癌发病率和死亡率以及任何潜在不利影响的短期和长期影响。”

理查森博士建议，寻求该主题指导的临床医生应参考美国妇产科学院委员会 2019 年 4 月在妇产科发表的第 774 号意见(doi:10.1097/aog.00000000000003165) 和 Yoon 等人的荟萃分析2016 年发表在欧洲癌症杂志(doi:10.1016/j.ejca.2015.12.003)。“这些文件表明，输卵管切除术是降低中等风险女性患卵巢癌风险的有效手段。”

图片来源：Voltaggio L、Cimino-Mathews A、Bishop JA 等。上皮内瘤变的诊断和病理生物学的当前概念：器官系统综述。加州癌症杂志。2016；66:408-436。doi:10.3322/caac.21350