Borderline ovarian tumors: Guidelines from the French national college of obstetricians and gynecologists (CNGOF).

It is recommended to classify Borderline Ovarian Tumors (BOTs) according to the WHO classification. Transvaginal and suprapubic ultrasonography are recommended for the analysis of an ovarian mass (Grade A). In case of an undetermined ovarian lesion on ultrasonography, it is recommended to perform a pelvic MRI (Grade A) with a score for malignancy (ADNEX MR/O-RADS) (Grade C) included in the report and to formulate a histological hypothesis (Grade C). Pelvic MRI is recommended to characterize a tumor suspected of being BOT (Grade C). It is recommended to evaluate serum levels of HE4 and CA125 and to use the ROMA score for the diagnosis of indeterminate ovarian mass on imaging (grade A). If there is a suspicion of a mucinous BOT on imaging, serum levels of CA 19-9 may be proposed (Grade C). For Early Stages (ES) of BOT, if surgery without risk of tumor rupture is possible, laparoscopy with protected extraction is recommended over laparotomy (Grade C). For treatment of a bilateral serous ES BOT with a strategy to preserve fertility and/or endocrine function, bilateral cystectomy is recommended where possible (Grade B). For mucinous BOTs with a treatment strategy of fertility and/or endocrine function preservation, unilateral salpingo-oophorectomy is recommended (grade C). For mucinous BOTs treated by initial cystectomy, unilateral salpingo-oophorectomy is recommended (grade C). For serous or mucinous ES BOTs, routine hysterectomy is not recommended (Grade C). For ES BOTs, lymphadenectomy is not recommended (Grade C). For ES BOTs, appendectomy is recommended only in case of a macroscopically pathological appendix (Grade C). Restaging surgery is recommended in cases of serous BOTs with micropapillary architecture and an incomplete abdominal cavity inspection during initial surgery (Grade C). Restaging surgery is recommended for mucinous BOTs after initial cystectomy or in cases where the appendix was not examined (Grade C). If restaging surgery is decided for ES BOTs, the following procedures should be performed: peritoneal washing (grade C), omentectomy (grade B), complete exploration of the abdominal cavity with peritoneal biopsies (grade C), visualization of the appendix and appendectomy in case of a pathological macroscopic appearance (grade C) as well as unilateral salpingo-oophorectomy in case of a mucinous BOT initially treated by cystectomy (grade C). In advanced stages (AS) of BOT, it is not recommended to perform a lymphadenectomy as a routine procedure (Grade C). For AS BOT in a patient with a desire to fall pregnant, conservative treatment involving preservation of the uterus and all or part of the ovary may be proposed (Grade C). Restaging surgery aimed at removing all lesions, not performed initially, is recommended for AS BOTs (Grade C). After treatment, follow-up for a duration greater than 5 years is recommended due to the median recurrence time of BOTs (Grade B). It is recommended that a systematic clinical examination be carried out during follow-up of a treated BOT (Grade B). If the determination of tumor markers is normal preoperatively, the routine dosage of tumor markers in BOT follow-up is not recommended (Grade C). In case of an initial elevation in serum CA 125 levels, it is recommended to monitor CA 125 during follow up (Grade B). In case of conservative treatment, it is recommended to use transvaginal and transabdominal ultrasound during follow up of a treated BOT (Grade B). In the event of a BOT recurrence in a woman of childbearing age, a second conservative treatment may be proposed (Grade C). A consultation with a physician specialized in Assisted Reproductive Technique (ART) should be offered in the case of BOTs in women of childbearing age (Grade C). When possible, a conservative surgical strategy is recommended to preserve fertility in women of childbearing age (Grade C). In the case of optimally treated BOT, there is no evidence to contraindicate the use of ART. The use of hormonal contraception after serous or mucinous BOT is not contraindicated (Grade C). After management of mucinous BOT, for women under 45 years, given the benefit of Hormonal Replacement Therapy (HRT) on cardiovascular and bone risks, and the lack of hormone sensitivity of mucinous BOTs, it is recommended to offer HRT (Grade C). Over 45 years of age, HRT can be prescribed in case of a climacteric syndrome after individual benefit to risk assessment (Grade C).

Bourdel N ，Huchon C ，Abdel Wahab C ，Azaïs H ，Bendifallah S ，Bolze PA ，Brun JL ，Canlorbe G ，Chauvet P ，Chereau E ，Courbiere B ，De La Motte Rouge T ，Devouassoux-Shisheboran M ，Eymerit-Morin C ，Fauvet R ，Gauroy E ，Gauthier T ，Grynberg M ，Koskas M ，Larouzee E ，Lecointre L ，Levêque J ，Margueritte F ，Mathieu D'argent E ，Nyangoh-Timoh K ，Ouldamer L ，Raad J ，Raimond E ，Ramanah R ，Rolland L ，Rousset P ，Rousset-Jablonski C ，Thomassin-Naggara I ，Uzan C ，Zilliox M ，Daraï E ... -  《-》

Borderline ovarian tumors: French guidelines from the CNGOF. Part 2. Surgical management, follow-up, hormone replacement therapy, fertility management and preservation.

In the Early Stages (ES) of Borderline Ovarian Tumor (BOT), if surgery without risk of tumor rupture is possible, then laparoscopy with protected extraction is recommended over laparotomy (Grade C). In case of bilateral serous ES BOT treatment with a strategy to preserve fertility and/or endocrine function, bilateral cystectomy is recommended if possible (Grade B). In case of mucinous BOT treatment with a strategy to preserve fertility and/or endocrine function, unilateral adnexectomy is recommended (grade C). In the case of a mucinous BOT in a patient who has had an initial cystectomy, unilateral adnexectomy is recommended (grade C). In the case of treatment of a serous ES BOT in a patient who has had an initial cystectomy, with a strategy to preserve fertility and/or endocrine function, restaging surgery for adnexectomy is not recommended in the absence of suspicious residual lesions at the time of surgery and/or postoperative imaging (reference ultrasonography or pelvic MRI) (grade C). For serous or mucinous ES BOTs, routine hysterectomy is not recommended (Grade C). In cases of ES BOTs, lymphadenectomy is not recommended (Grade C). For ES BOTs, appendectomy is recommended only if there is a macroscopically pathological aspect to the appendix (Grade C). Restaging surgery is recommended in case of a serous BOT with a micropapillary aspect and an unsatisfactory inspection of the abdominal cavity during initial surgery (Grade C). Restaging surgery is recommended in cases of mucinous BOT if only a cystectomy has been performed or if the appendix has not been evaluated (Grade C). If restaging surgery is decided for an ES BOT, the following procedures should be performed: peritoneal cytology (grade C), omentectomy (there is no data in literature to recommend which type of omentectomy should be performed) (grade B), complete exploration of the abdominal cavity with peritoneal biopsies (grade C), visualization of the appendix +/- appendectomy in case of pathological macroscopic appearance (grade C) and unilateral adnexectomy in case of a mucinous BOT (grade C). In advanced stages of BOT it is not recommended to perform a lymphadenectomy as a routine procedure (Grade C). In cases of an advanced stage BOT, in a patient with a desire to fall pregnant, conservative treatment involving preservation of the uterus and all or part of the ovary may be proposed after a multidisciplinary meeting (Grade C). Second surgery aimed at removing all lesions, if not performed initially, is recommended in cases of advanced stage BOT (Grade C). It is not recommended to perform completion surgery after conservative treatment (preservation of the ovaries and the uterus) and after the achievement of fertility desire for a serous BOT (Grade B). After treatment for a BOT, follow-up beyond 5 years is recommended due to the median time to recurrence (Grade B). It is recommended that a systematic clinical examination be carried out during follow-up of a treated BOT (Grade B). In the particular case of an initial elevation of CA 125 levels, it is recommended to monitor CA 125 during follow up (Grade B). In cases treated conservatively (ovarian and uterine conservation), it is recommended to use endovaginal and transabdominal ultrasonography during the follow up period (Grade B). In the event of a recurrence of a BOT, in a woman of childbearing age, a conservative treatment strategy can again be proposed (Grade C). In the presence of non-invasive BOT implants, conservative treatment may be considered after a first non-invasive recurrence in women who wish to preserve their fertility (Grade C). Pelvic MRI is recommended after 12 weeks of amenorrhea in case of an undetermined adnexal mass and should be concluded with a diagnostic score (Grade C). The injection of gadolinium, in case of pregnancy, should be discussed on a case-by-case basis due to the proven risks for the foetus (Grade C). If feasible, a laparoscopic approach should be preferred during pregnancy (Grade C). A consultation with a specialist reproductive physician should be offered to patients with a BOT and of childbearing age (Grade C). It is recommended that patients be provided with full information on the risk of decreased ovarian reserve following to surgical treatment. It is recommended that the ovarian reserve be evaluated prior to surgical management of a suspected BOT (Grade C). When possible, a conservative surgical strategy is recommended to preserve fertility in women of childbearing age (Grade C). There is no specific data on the management of infertility following to conservative treatment of BOT. In case of durable infertility following to conservative treatment of BOT, a consultation with a specialist reproductive physician is required (Grade C). In the case of optimally treated BOT, there is no evidence in literature to contraindicate the use of Assisted Reproductive Techniques (ART). The use of hormonal contraception after serous or mucinous BOT is not contraindicated (Grade C). After treatment of a mucinous BOT, for women aged under 45 years, given the benefit of hormonal replacement therapy (HRT) on cardiovascular and bone risks, and the lack of hormone-sensitivity of mucinous BOTs, it is recommended to offer HRT (Grade C). After treatment of a mucinous BOT, for women over 45 years of age, there is no argument to contraindicate the use of HRT. HRT can be prescribed in case of a climacteric syndrome, as part of an individual benefit to risk assessment (Grade C).

Bourdel N ，Huchon C ，Abdel Wahab C ，Azaïs H ，Bendifallah S ，Bolze PA ，Brun JL ，Canlorbe G ，Chauvet P ，Chereau E ，Courbiere B ，De La Motte Rouge T ，Devouassoux-Shisheboran M ，Eymerit-Morin C ，Fauvet R ，Gauroy E ，Gauthier T ，Grynberg M ，Koskas M ，Larouzee E ，Lecointre L ，Levêque J ，Margueritte F ，D'argent Mathieu E ，Nyangoh-Timoh K ，Ouldamer L ，Raad J ，Raimond E ，Ramanah R ，Rolland L ，Rousset P ，Rousset-Jablonski C ，Thomassin-Naggara I ，Uzan C ，Zilliox M ，Daraï E ... -  《Journal of Gynecology Obstetrics and Human Reproduction》

[Borderline Ovarian Tumours: CNGOF Guidelines for Clinical Practice - Therapeutic Management of Early Stages].

To provide guidelines for clinical practice from the French College of Obstetrics and Gynecology (CNGOF), based on the best evidence available, concerning early stage borderline ovarian tumors (BOT). Bibliographical search in French and English languages by consultation of Pubmed, Cochrane, Embase, and international databases. Considering management of early stage BOT, if surgery is possible without a risk of tumor rupture, the laparoscopic approach is recommended compared to laparotomy (Grade C). In BOT, it is recommended to take all the measures to avoid tumor rupture, including the peroperative decision of laparoconversion (Grade C). In BOT, extraction of the surgical specimen using an endoscopic bag is recommended (Grade C). In case of early stage, uni or bilateral BOT, suspected in preoperative imaging in a postmenopausal patient, bilateral adnexectomy is recommended (Grade B). In cases of bilateral BOT and desire of fertility preservation, a bilateral cystectomy is recommended (Grade B). In case of mucinous BOT and desire of fertility preservation, it is recommended to perform a unilateral adnexectomy (Grade C). In case of endometrioid BOT and desire of fertility preservation, it is not possible to establish a recommendation of treatment choice between cystectomy and unilateral adnexectomy. In case of mucinous BOT at definitive histological analysis in a woman of childbearing age who had an initial cystectomy, surgical revision for unilateral adnexectomy is recommended (Grade C). In the case of serous BOT with definitive histological analysis in a woman of childbearing age who has had an initial cystectomy, it is not recommended to repeat surgery for adnexectomy in the absence of residual suspicious lesion during initial surgery and/or on postoperative imaging (referent ultrasound or pelvic MRI) (Grade C). An omentectomy is recommended for complete initial surgical staging when BOT is diagnosed on extemporaneous analysis or suspected on preoperative radiological elements (Grade B). There is no data in the literature to recommend the type of omentectomy to be performed. If restaging surgery is decided for a presumed early stage BOT, an omentectomy is recommended (Grade B). Multiple peritoneal biopsies are recommended for complete initial surgical staging when BOT is diagnosed on extemporaneous or suspected on preoperative radiological elements (Grade C). In case of restaging surgery for a presumed early stage BOT, exploration of the abdominal cavity should be complete and peritoneal biopsies should be performed on suspicious areas or systematically (Grade C). A primary peritoneal cytology is recommended in order to achieve complete initial surgical staging when BOT is suspected on preoperative radiological elements (Grade C). In case of restaging surgery for presumed early stage BOT, a first peritoneal cytology is recommended (Grade C). For early serous or mucinous BOT, it is not recommended to perform a systematic hysterectomy (Grade C). For early stage endometrioid BOT, and in the absence of a desire to maintain fertility, hysterectomy is recommended for initial surgery or if restaging surgery is indicated (Grade C). For endometrioid-type early stage BOT, if there is a desire for fertility preservation, the uterus may be retained subject to good evaluation of the endometrium by imaging and endometrial sampling (Grade C). In case of surgery (initial or restaging if indicated) for early stage BOT, it is recommended to evaluate the macroscopic appearance of the appendix (Grade B). In case of surgery (initial or restaging if indicated) for early stage BOT, appendectomy is recommended only in case of macroscopically pathological appearance of the appendix (Grade C). Pelvic and lumbar aortic lymphadenectomy is not recommended for initial surgery or restaging surgery for early stage BOT regardless of histologic type (Grade C). In case of BOT diagnosed on definitive histology, the indication of restaging surgery should be discussed in Multidisciplinary Collaborative Meeting. For presumed early stage BOT, it is recommended to use the laparoscopic approach to perform restaging surgery (Grade C). Restaging surgery is recommended for serous BOT with micropapillary appearance and unsatisfactory abdominal cavity inspection during initial surgery (Grade C). Restaging surgery is recommended in case of mucinous BOT if only a cystectomy has been performed or the appendix has not been visualized, then a unilateral adnexectomy will be performed (Grade C). If a restaging surgery is decided in the management of a presumed early stage BOT, the actions to be carried out are as follows: a peritoneal cytology (Grade C), an omentectomy (there is no data in the literature recommending the type of omentectomy to be performed) (Grade B), a complete exploration of the abdominal cavity with peritoneal biopsies on suspect areas or systematically (Grade C), visualization of the appendix± the appendectomy in case of pathological macroscopic appearance (Grade C), unilateral adnexectomy in case of mucinous TFO (Grade C).

Canlorbe G ，Lecointre L ，Chauvet P ，Azaïs H ，Fauvet R ，Uzan C ... -  《-》

Borderline ovarian tumors: French guidelines from the CNGOF. Part 1. Epidemiology, biopathology, imaging and biomarkers.

The incidence (rate per 100 000) of borderline ovarian tumors (BOTs) increases progressively with age, starting at 15-19 years and peaking at around 4.5 cases per 100 000 at an age of 55-59 years (LE3) with a median age of 46 years. The five year survival for FIGO stages I, II, III and IV is 99.7 % (95 % CI: 96.2-100 %), 99.6 % (95 % CI: 92.6-100 %), 95.3 % (95 % CI: 91.8-97.4 %) and 77.1 % (95 % CI: 58.0-88.3 %), respectively (LE3). An epidemiological association exists between the individual risk of BOT and family history of BOT and certain other cancers (pancreatic, lung, bone, leukemia) (LE3), a personal history of benign ovarian cyst (LE2), a personal history of tubo-ovarian infection (LE3), the use of a levonorgestrel intrauterine device (LE3), oral contraceptive use (LE3), multiparity (LE3), Hormonal replacement therapy (LE3), high consumption of Coumestrol (LE4), medical treatment for infertility with progesterone (LE3) and non-steroidal anti-inflammatory drug use (LE3). Screening for BOTs is not recommended for patients (Grade C). The overall risk of recurrence of BOTs varies between 2% and 24 %, with an overall survival greater than 94 % at 10 years, and the risk of an invasive recurrence of a BOT ranges from 0.5 % to 3.8 %. The use of scores and nomograms can be useful in assessing the risk of recurrence, and providing patients with information (Grade C). The WHO classification is recommended for classifying BOTs. It is recommended that the presence of a microinvasive focus (<5 mm) and microinvasive carcinoma (<5 mm with an atypical nuclei and a desmoplastic stroma reaction) within a BOT be reported. In cases of serous BOT, it is recommended to specify the classic histological subtype or micropapillary / cribriform type (Grade C). When confronted with a BOT, it is recommended that the invasive or non-invasive nature of peritoneal implants can be investigated based solely on the invasion and destruction of underlying adipose or peritoneal tissue which has a desmoplastic stromal reaction where in contact with the invasive clusters (Grade B). For bilateral mucinous BOTs and / or in cases with peritoneal implants or peritoneal pseudomyxoma, it is recommended to also look for a primitive digestive or pancreato-biliary cancer (Grade C). It is recommended to sample ovarian tumors suspected of being BOTs by focusing samples on vegetations and solid components, with at least 1 sample per cm in tumors with a size less than 10 cm and 2 samples per cm in tumors with a size greater than 10 cm (Grade C). In cases of BOTs and in the absence of macroscopic omental involvement after careful macroscopic examination, it is recommended to perform at least 4-6 systematic sampling blocks and to include all peritoneal implants (Grade C). It is recommended to consult an expert pathologist in gynecology when a BOT suspicion requires intraoperative extemporaneous histology (grade C). Endo-vaginal and suprapubic ultrasonography are recommended for the analysis of an ovarian mass (Grade A). In case of an undetermined ovarian lesion on ultrasonography, it is recommended that a pelvic MRI be performed (Grade A). To analyze an adnexal mass with MRI, it is recommended to use an MRI protocol with T2, T1, T1 Fat Sat, dynamic and diffusion sequences as well as gadolinium injection (Grade B). To characterize an adnexal mass with MRI, it is recommended to include a score system for malignancy (ADNEX MR/O-RADS) (Grade C) in the report and to formulate a histological hypothesis (Grade C). Pelvic MRI is recommended to characterize a tumor suspected of being a BOT (Grade C). Macroscopic MRI features should be analyzed to differentiate BOT subtypes (Grade C). Pelvic ultrasound is the first-line examination for the detection and characterization of adnexal masses during pregnancy (Grade C). Pelvic MRI is recommended from 12 weeks of gestation in case of an indeterminate adnexal mass and should provide a diagnostic score (Grade C). Gadolinium injection must be minimized as fetal impairment has been proven (Grade C). It is recommended that serum levels of HE4 and CA125 be evaluated and that the ROMA score for the diagnosis of an indeterminate ovarian mass on imaging be used (grade A). In case of suspicion of a mucinous BOT on imaging, dosage of serum levels of CA 19-9 can be considered (Grade C). If the determination of tumor markers is normal preoperatively, routine dosage of tumor markers in BOT follow-up is not recommended (Grade C). In case of preoperative elevation in tumor markers, the determination of serum CA 125 levels is recommended in the follow-up of BOT (Grade B). When conservative treatment of a BOT has been adopted, the use of endovaginal and transabdominal ultrasonography is recommended during follow-up (Grade B).

Huchon C ，Bourdel N ，Abdel Wahab C ，Azaïs H ，Bendifallah S ，Bolze PA ，Brun JL ，Canlorbe G ，Chauvet P ，Chereau E ，Courbiere B ，De La Motte Rouge T ，Devouassoux-Shisheboran M ，Eymerit-Morin C ，Fauvet R ，Gauroy E ，Gauthier T ，Grynberg M ，Koskas M ，Larouzee E ，Lecointre L ，Levêque J ，Margueritte F ，Mathieu D'argent E ，Nyangoh-Timoh K ，Ouldamer L ，Raad J ，Raimond E ，Ramanah R ，Rolland L ，Rousset P ，Rousset-Jablonski C ，Thomassin-Naggara I ，Uzan C ，Zilliox M ，Daraï E ... -  《Journal of Gynecology Obstetrics and Human Reproduction》

[Borderline Ovarian Tumours: CNGOF Guidelines for Clinical Practice - Short Text].

This work was carried out under the aegis of the CNGOF (Collège national des gynécologues et obstétriciens français) and proposes guidelines based on the evidence available in the literature. The objective was to define the diagnostic and surgical management strategy, the fertility preservation and surveillance strategy in Borderline Ovarian Tumor (BOT). No screening modality can be proposed in the general population. An expert pathological review is recommended in case of doubt concerning the borderline nature, the histological subtype, the invasive nature of the implant, for all micropapillary/cribriform serous BOT or in the presence of peritoneal implants, and for all mucinous or clear cell tumors (grade C). Macroscopic MRI analysis should be performed to differentiate the different subtypes of BOT: serous, seromucinous and mucinous (intestinal type) (grade C). If preoperative biomarkers are normal, follow up of biomarkers is not recommended (grade C). In cases of bilateral early serous BOT with a desire to preserve fertility and/or endocrine function, it is recommended to perform a bilateral cystectomy if possible (grade B). In case of early mucinous BOT, with a desire to preserve fertility and/or endocrine function, it is recommended to perform a unilateral adnexectomy (grade C). Secondary surgical staging is recommended in case of serous BOT with micropapillary appearance and uncomplete inspection of the abdominal cavity during initial surgery (grade C). For early-stage serous or mucinous BOT, it is not recommended to perform a systematic hysterectomy (grade C). Follow up after BOT must be pursued for more than 5 years (grade B). Conservative treatment involving at least the conservation of the uterus and a fragment of the ovary in a patient wishing to conceive may be proposed in advanced stages of BOT (grade C). A new surgical treatment that preserves fertility after a first non-invasive recurrence may be proposed in women of childbearing age (grade C). It is recommended to offer a specialized consultation for Reproductive Medicine when diagnosing BOT in a woman of childbearing age. Hormonal contraceptive use after serous or mucinous BOT is not contraindicated (grade C).

Bourdel N ，Huchon C ，Cendos AW ，Azaïs H ，Bendifallah S ，Bolze PA ，Brun JL ，Canlorbe G ，Chauvet P ，Chéreau E ，Courbiere B ，De La Motte Rouge T ，Devouassoux-Shisheboran M ，Eymerit-Morin C ，Fauvet R ，Gauroy E ，Gauthier T ，Grynberg M ，Koskas M ，Larouzee E ，Lecointre L ，Levêque J ，Margueritte F ，Mathieu D'argent E ，Nyangoh-Timoh K ，Ouldamer L ，Raad J ，Raimond E ，Ramanah R ，Rolland L ，Rousset P ，Rousset-Jablonski C ，Thomassin-Naggara I ，Uzan C ，Zilliox M ，Daraï E ... -  《-》