Prophylactic Salpingectomy for the Prevention of the Ovarian Cancer: Comparison Between Surgical Techniques
Condition: Uterine Fibroids; Contraception Desired
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Leiomyoma
Study type: Interventional

Summary: 
      The aim of this RCT of study is to compare the outcomes of the standard salpingectomy
      (removal of the fallopian tube) with the radical removal of the tube and the mesosalpinx in
      terms of ovarian reserve.
    

Detailed description: 
      Ovarian cancer accounts for 3% of all female cancers and represents the fifth leading cause
      of cancer death in the Western world (1). In 90% of cases, these are epithelial ovarian
      cancers (2).

      Because of the biological aggressiveness of this tumor and nonspecific symptoms, that causes
      a diagnosis at an advanced stage in 75% of cases, ovarian cancer is the gynecological cancer
      with the highest mortality rate (3).

      To date, an effective screening strategy to the early diagnosis of ovarian cancer doesn't
      exist, so the prophylactic adnexectomy is the only available tool to reduce the incidence and
      the mortality rate, even if the role of this surgical strategy is controversial, especially
      in premenopausal women (4). In fact, the American College of Obstetricians and Gynaecologists
      (ACOG) guidelines recommend the ovarian preservation in premenopausal women with no family
      history or other risk factors for ovarian cancer (5).

      Some clinical studies have shown that the prophylactic adnexectomy and the consequent
      surgical menopause increase significantly the long term risk of cardiovascular and
      psychosexual diseases. (6-8). In particular, a case-control study done in a population of
      29,380 women subjected to hysterectomy with and without adnexectomy, showed an increased risk
      of total mortality ( HRs 1.12 95 % CI 1:03 to 1:21 ), lethal and non- lethal cardiovascular
      disease ( HRs 1.17 95 % CI 1:02 to 1:35 ) and stroke ( HRs 1.14 95 % CI 0.98-1.33 ) (9) . In
      this population of women subjected to salpingectomy, the surgery wasn't able to lead to an
      improvement in general survival (10).

      Considering the new histopathological classification of the epithelial ovarian cancer,
      proposed by Kurman (11) and based on new acquisitions about the pathogenesis and the origin
      of these tumors, it is possible to conceive a new preventive strategy associated with a less
      morbidity.

      In fact, the carcinogenesis model proposed by Kurman, provides for the classification of the
      most important histological types of epithelial tumors into two types, diversified according
      to clinico-pathological and genetic features.

      The type I is composed of low-grade serous, low-grade endometrioid, clear cell and mucinous
      carcinomas, whose the ovarian borderline tumors and endometriosis represent the
      pre-neoplastic lesions. Conversely, the II type includes high-grade endometrioid carcinomas,
      carcinosarcomas and undifferentiated carcinomas and, more frequently, high-grade serous
      carcinomas, whose preneoplastic lesion, now, seems to be represented by the serous tubal
      intraepithelial carcinoma (STIC).

      Plenty of evidence, to support the correlation between the epithelial ovarian cancer and the
      STIC, has been obtained by immunohistochemical and molecular genetics investigations (11).
      However, from a clinical point of view, this association has been demonstrated only by a
      study on 55 patients affected by a high-grade serous carcinoma, whose results have shown an
      involvement in the endosalpinx in 70% of cases and the presence of STIC in about 50% of cases
      (12).

      Some studies, performed on BRCA1 / 2 populations, showed the presence of strongly sites
      reactive to p53, defined "p53 signature", in the distal tube (13). These sites seem to be
      more frequent and characteristically multifocal in those tubes with concomitant STIC (14).
      The finding of "p53 signature" may, therefore, identify an early clonal expansion of the
      neoplastic proliferation.

      This new theory has given the opportunity to prevent this devastating type of cancer by the
      addition of the prophylactic bilateral salpingectomy (PBS, with the only removal of the tube
      and the preservation of the ovaries) in all surgical procedures performed in those women with
      benign diseases once they have accomplished their reproductive desire. The PBS, in place of
      the current standard procedure (bilateral salpingo-oophorectomy) could reduce the risk of
      cancer, improving at the same time the quality of life and reducing the risk of premature
      death due to cardiovascular disease, seen in women subjected to salpingo-oophorectomy before
      the onset of natural menopause.

      Our preliminary data (17) show that, if the bilateral salpingectomy is performed with great
      care, no patient has negative effects in terms of ovarian function. In addition, in our
      experience, no perioperative complication is attributable to salpingectomy alone. Despite the
      retrospective design of our first study, according to the post hoc analysis, these data have
      shown a significant statistical reliability.

      However, the most recent acquisitions assume that also the tissue surrounding the tube seems
      to give rise to neoplastic sites, so it is conceivable that a greater oncological radicality
      can be obtained removing the tube and the adjacent structures (mesosalpinx). Now it remains
      to prove if also the radical technique of prophylactic salpingectomy causes no functional
      damage to the ovary.
    

Intervention name(s): Standard PBS; Radical PBS
Intervention type(s): Procedure; Procedure
Intervention description(s): the tube will be removed by coagulation and section of the tissue beginning from the very distal fimbrial and proceeding toward the uterine cornu. The resection will be performed at the level of the posterior tubal margin, sparing the mesosalpinx.; the tube will be removed by coagulation and section of the tissue beginning from the very distal fimbrial and proceeding toward the uterine cornu. The resection will be performed at the level of ovarian margin and the uterus-ovarian ligament, including the mesosalpinx removal.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Prevention
Keywords: PBS; Prophylactic bilateral salpingectomy; Ovarian cancer prevention; Ovarian reserve; Permanent contraception; Surgical sterilization