Keywords: ovarian cancer, tubal cancer, primary peritoneal cancer, surgery, chemotherapy, guidelines

Management of epithelial cancer of the ovary, fallopian tube, and primary peritoneum.

Management of epithelial cancer of the ovary, fallopian tube, and primary peritoneum.

Short text of the French Clinical Practice Guidelines issued by FRANCOGYN, CNGOF, SFOG, and GINECO-ARCAGY, and endorsed by INCa.

Lavoue V 1* , Huchon C 2 , Akladios C 3 , Alfonsi P 4 , Bakrin N 5 , Ballester M 6 , Bendifallah S 7 , Bolze PA [START_REF] Ferron | Chirurgie des cancers avancés de l'ovaire[END_REF] , Bonnet F 9 , Bourgin C 10 , Chabbert-Buffet N [START_REF] Uzan | Tumeurs épithéliales de l'ovaire : préservation de la fertilité[END_REF] , Collinet P 10 , Courbiere B [START_REF] Falandry | Tumeurs épithéliales de l'ovaire : les personnes âgées[END_REF] , De la motte rouge T [START_REF] Alfonsi | Soins péri-opératoires dans le cancer de l'ovaire. Recommandations Françaises communes dU FRANCOGYN, du CNGOF[END_REF] , Devouassoux-Shisheboran M [START_REF]Service d'anatomo-pathologie, Hospices civiles de Lyon[END_REF] , Falandry C 14 , Ferron G [START_REF]Service d'oncologie chirurgicale[END_REF] , Fournier L [START_REF]Service de radiologie[END_REF] , Gladieff L [START_REF]Service d'oncologie médicale[END_REF] , Golfier F 8 , Gouy S 18 , Guyon F 19 , Lambaudie E 20 , Leary A [START_REF]Service d'oncologie médicale[END_REF] , Lecuru F [START_REF]Service de chirurgie gynécologique et oncologique[END_REF] , Lefrere-Belda MA [START_REF]Service d'anatomo-pathologie[END_REF] , Leblanc E 24 , Lemoine A 9 , Narducci F 24 , Ouldamer L [START_REF]Service de chirurgie gynécologique[END_REF] , Pautier P [START_REF]Service d'oncologie médicale[END_REF] , Planchamp F 26 , Pouget N 27 , Ray-Coquard I [START_REF]Service d'oncologie médicale[END_REF] , Rousset-Jablonski C [START_REF]Service d'oncologie médicale[END_REF] , Senechal-Davin C 19 , Touboul C [START_REF]Service de chirurgie gynécologique[END_REF] , Thomassin-Naggara I 30 , Uzan C 31 , You B [START_REF]Auteur correspondant : Pr Vincent Lavoué, Service de chirurgie gynécologique[END_REF] , Daraï E [START_REF] Uzan | Tumeurs épithéliales de l'ovaire : préservation de la fertilité[END_REF] .

Affiliations:

1. Service de gynécologie, CHU de Rennes, Hôpital sud, 16

Summary:

An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (Grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed: an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (Grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). For FIGO stage III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (Grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery treatment sequences that differ substantially between centers for primary or interval surgery.

Similarly, the extent of surgery and the surgical staging procedures vary according to patient characteristics (young vs elderly women, for example). Perioperative management, whether it concerns early recovery or fertility preservation, has not been standardized, although it can cause physical or psychological morbidity. Finally, cancer centers vary widely in their use of chemotherapy (and how they administer it), as well as of targeted therapies; a national strategy remains to be defined, according to different clinical contexts. Work to develop Accordingly, the French research group for oncologic gynecologic surgery (FRANCOGYN), the French national college of gynecologists and obstetricians (CNGOF), the French society of gynecologic oncology (SFOG), and the national investigators' group for studies in ovarian and breast cancer (GINECO-ARCAGY) jointly brought together a working group to develop such guidelines. This text is a synthesis of clinical practice guidelines for the initial management of epithelial ovarian, tubal, or primary peritoneal cancers (excluding recurrence of ovarian cancer and borderline tumors). [START_REF] Huchon | Tumeurs épithéliales de l'ovaire. Méthodes et organisation. Recommandations françaises communes du CNGOF, FRANCOGYN, SFOG, GINECO-ARCAGY et labellisées INCa. Gynécologie, Obstétrique, Fertilité[END_REF] The development of these clinical practice guidelines followed the standards set by the French national authority for health (HAS) and the national cancer institute (INCa), with reviews by experts both within and outside the working group. [START_REF] Huchon | Tumeurs épithéliales de l'ovaire. Méthodes et organisation. Recommandations françaises communes du CNGOF, FRANCOGYN, SFOG, GINECO-ARCAGY et labellisées INCa. Gynécologie, Obstétrique, Fertilité[END_REF][START_REF] Thomassin-Naggara | valeur diagnostique de l'imagerie (échographie, doppler, scanner, IRM, et PET scan) pour le diagnostic ET LE BILAN D'EXTENSION d'un cancer de l'ovaire. Recommandations communes dU FRANCOGYN, du CNGOF[END_REF][START_REF] Devouassoux | Biopathologie des carcinomes ovariens des stades précoces et avancés : Recommandations françaises communes du CNGOF, FRANCOGYN, SFOG, GINECO-ARCAGY et labellisées INCa. Gynécologie, Obstétrique, Fertilité[END_REF] INCa has endorsed these clinical practice guidelines.

Their aim is to aid professionals (gynecologic surgeons, surgeons specialized in gynecologic oncology, medical gynecologists, gynecologist-obstetricians, pathologists, medical oncologists, radiologists, anesthetist-critical-care specialists, nuclear physicians, general practitioners, midwives, and paramedical personnel) in managing women with ovarian cancer or with suspected ovarian, tubal, or primary peritoneal cancer. -The mass is classified as malignant if at least one M (malignant) rule applies and no B (benign) rule applies.

I-

-The mass is classified as benign if at least one B rule applies and no M rule applies.

- The ROMA score (based on serum assays of HE4 and CA125) can be used for an adnexal mass that is indeterminate on ultrasound (grade A). [START_REF] Bendifallah | Pertinence des marqueurs tumoraux, scores (cliniques et biologiques) et algorithmes à visée diagnostique et pronostique devant une masse ovarienne suspecte d'un cancer épithélial: Recommandations de Pratique Clinique communes de FRANCOGYN, CNGOF, SFOG, ARCAGY-GINECO[END_REF] The CNAM-TS (French national health insurance fund) does not reimburse the HE4 serum assay.

It
A C C E P T E D M A N U S C R I P T
When an adnexal mass is suspected to be an ovarian cancer, an intraoperative pathology examination can be performed to enable optimal surgical staging during a single surgical procedure and thus avoid the need for reintervention (grade B). [START_REF] Devouassoux | Biopathologie des carcinomes ovariens des stades précoces et avancés : Recommandations françaises communes du CNGOF, FRANCOGYN, SFOG, GINECO-ARCAGY et labellisées INCa. Gynécologie, Obstétrique, Fertilité[END_REF] In presumed early-stage ovarian cancer, the following procedures have to be performed:

an omentectomy (at a minimum, infracolic), an appendectomy, peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (Grade B) except for the expansile mucinous subtypes, for which the lymphadenectomies can be omitted. Women who wish for fertility preservation must be informed that there is a risk of recurrence in the contralateral ovary ranging between 6 and 13%. Laparoscopy is recommended to assess the feasibility of surgical resection that leaves no macroscopic tumor residue (i.e., complete surgery) in a woman with ovarian, tubal, or primary peritoneal carcinomatosis before laparotomic surgery (grade A). [START_REF] Bendifallah | Pertinence des marqueurs tumoraux, scores (cliniques et biologiques) et algorithmes à visée diagnostique et pronostique devant une masse ovarienne suspecte d'un cancer épithélial: Recommandations de Pratique Clinique communes de FRANCOGYN, CNGOF, SFOG, ARCAGY-GINECO[END_REF] Several scores for assessing the extension of peritoneal carcinomatosis have been developed. The Fagotti score is a laparoscopic score based on 7 indicators rated 0 or 2 (Table 3).

For women with ovarian, tubal, or primary peritoneal carcinomatosis, the use of a carcinomatosis score (at least the Fagotti score) during laparoscopy is recommended to assess the risk of nonresectability during primary or interval surgery (grade C). A Fagotti score ≥8 is correlated with a low rate of complete primary surgery (LE4). A

Fagotti score ≥4 is correlated with a low rate of complete interval surgery (LE4). 4

In women undergoing laparotomy for ovarian, tubal, or primary peritoneal carcinomatosis, use of the Peritoneal Cancer Index (PCI) is recommended to assess the tumor burden (grade C).

The tumor residue after primary or interval surgery is an essential prognostic factor, Three published meta-analyses, including both published cohorts and 3 randomized trials, have assessed the systematic surgical dissection of pelvic and para-aortic lymph nodes in advanced cancer (LE2). They show a benefit from systematic dissection with an improvement in overall survival (HR=0.74; 95% CI 0.59-0.94, P=0.01) including for the procedures considered optimal (i.e., with a tumor residue 1 cm or less in maximum diameter).

Nonetheless, the only prospective randomized trial (Panici et al.) currently published concerning advanced stages (and included in these meta-analyses) found no improvement in 5-year overall survival but only a prolongation of recurrence-free survival (LE2). These data are consistent with the published abstract of the LION trial presented at ASCO in 2017, which randomized women with ovarian carcinomatosis and no observed adenopathy (not visible on CT nor palpable at primary surgery after complete resection) to either systematic dissection or no dissection. This study found an identical overall survival rate among women who did and did not have dissections among the selected population, i.e., women with neither radiologic nor clinical adenopathy (LE2). On the other hand, benefits for both overall and recurrencefree survival were observed for systematic dissections when clinically or radiologically suspicious lymph nodes were present (LE2).

In advanced ovarian, tubal, or primary peritoneal cancer with no macroscopic tumor residue at the end of surgery, para-aortic and pelvic lymphadenectomies are The treatment sequences of primary cytoreductive surgery and then adjuvant chemotherapy vs neoadjuvant chemotherapy and interval surgery after 3 or 4 treatments have not shown differences for overall or progression-free survival (LE1) (Table 4). The interval surgery strategies have shown a significant diminution of morbidity and mortality and an improved quality of life, especially in advanced stages with a high tumor burden (LE2). The A geriatric oncology assessment is recommended before the management of elderly women with ovarian, tubal, or primary peritoneal cancer (grade C).

Elderly with no frailty with ovarian, tubal, or primary peritoneal cancers should receive intravenous chemotherapy identical to that for younger women (i.e., two agents, platinum-based) (grade B).

A C C E P T E D M A N U S C R I P T
Neoadjuvant chemotherapy was most cost-effective in elderly women at high risk of complications (i.e., age ≥ 75 years and FIGO stage IV or age ≥ 75 years and stage III and at least 1 comorbidity) in the SEER database (LE4); in the EORTC study, it was associated with a lower complication rate and a higher rate of optimal surgery for elderly women (LE4).

In advanced ovarian, tubal, and primary peritoneal cancers, neoadjuvant chemotherapy diminishes the complexity of the surgical procedure and the perioperative morbidity and mortality of the interval surgery (LE1). In these advanced stage cancers, starting with chemotherapy is a good alternative for those 70 years or older with comorbidities or with extensive peritoneal carcinomatosis requiring complex initial surgery (LE4).

IV-Perioperative prehabilitation for and recovery from ovarian cancer surgery 12

Preoperative management

For women with ovarian, tubal, or primary peritoneal cancer, screening is recommended before surgery for nutritional deficiencies (Grade B) and anemia (grade C). No data justify recommendations about preoperative correction of nutritional deficiencies, immunonutritional deficiencies, or anemia in women with ovarian, tubal, or primary peritoneal cancers.

Similarly no specific data about these cancers justify guidelines for preoperative bowel preparation.

Intraoperative management

For women with advanced stage ovarian, tubal, or primary peritoneal cancers, individualized monitoring to ensure intraoperative goal-directed fluid management is recommended (Grade B). No data justify a recommendation about intravenous administration of lidocaine or ketamine during surgery or the perioperative prescription of gabapentine or pregabalin.

Postoperative management

Early oral feeding is recommended, including after gastrointestinal resection for ovarian, tubal, or primary peritoneal cancer (Grade B).

The establishment of protocols for enhanced recovery after surgery (ERAS), including early mobilization, is recommended to reduce the length of stay after surgery for these cancers (Grade C). In all cases, the prescription of HRT and its dosage and administration must follow the same guidelines as those for the general population (see, HAS guidelines 2014).

A C C E P T E

Declaration of interests

The authors' potential relationships of interests are listed at:

https://www.transparence.sante.gouv.fr.

  Bd de Bulgarie 35000 Rennes, France. INSERM 1242, Chemistry, Oncogenesis, Stress and Signaling, Centre Eugène Marquis, Rue Bataille Flandres-Dunkerques, Rennes, France. 2. Service de Gynécologie, CHI Poissy, France. 3. Service de Gynécologie, Hôpital Hautepierre, CHU Strasbourg, France 4. Service d'Anesthésie, Hôpital Saint Joseph, Paris, France. 5. Service de chirurgie digestive, CHU Lyon-Sud, Pierre-Bénite, Lyon, France. 6. Service de gynécologie, GH Diaconesses Croix Saint Simon, Paris, France. 7. Service de Gynécologie-Obstétrique et Médecine de la Reproduction, Hôpital Tenon, 4 rue de La Chine, APHP, Institut Universitaire de Cancérologie Sorbonne Université, UMRS-938. 8. Service de chirurgie gynécologique, CHU Lyon-Sud, Pierre Bénite, Lyon, France.

Introduction

  Initial management of epithelial ovarian cancers is relatively heterogeneous in France, with

  clinical practice guidelines is therefore necessary to enable practices to be homogenized in accordance with the best evidence and to improve prognosis for all patients.

  Management of early-stage ovarian or tubal cancer (FIGO stages I-IIa)Transvaginal and transabdominal (suprapubic) ultrasound are recommended for the analysis of an isolated ovarian mass (grade A). 2 Expert operators performing ultrasound should apply their subjective analysis to determine if the mass is benign or malignant (grade A). It is recommended that non-expert operators performing ultrasound use the Simple Rules (grade A). These rules must be combined with subjective analysis to equal expert ultrasonographers (grade A). According to theSimple Ultrasound Rules (

When an adnexal mass

  is complex or indeterminate on ultrasound, a pelvic MRI is recommended (grade A). MRI to characterize an adnexal mass should use T2, T1, T1 Fat Sat, dynamic contrast-enhanced, diffusion-weighted, and gadolinium-enhanced sequences (grade B) to improve diagnostic sensitivity (grade B). It is recommended that an MRI report characterizing an adnexal mass include a malignancy risk score (such as ADNEX MR, Table 2) (grade C). Moreover, the use of the apparent distribution coefficient (ADC) makes it possible to differentiate borderline from invasive tumors, in particular to differentiate seromucinous borderline tumors from invasive cancers on endometriomas of endometrioid or clear cells. A pathological hypothesis should be included in the MRI report of an adnexal mass (grade C).

7

 7 For high-grade serous carcinomas, an additional drug is recommended rather than use of this single agent (grade B). The chemotherapy recommended for early-stage ovarian or tubal cancer is based on the combination of carboplatin (AUC 5-6) on D1 and paclitaxel (175 mg/m2) on D1 every 3 weeks (grade B). Chemotherapy for stage IA or IB ovarian or tubal cancer must include at least 3 cycles and a maximum of 6 (grade A). For stage I high-grade serous carcinoma of the ovary or fallopian tubes and for the other histologic types of FIGO stages ≥ IC tumors, 6 cycles of chemotherapy are recommended (grade C).No guidelines can be issued about chemotherapy indications for stage IA or IB ovarian carcinomas of the following types: low-grade serous, low-grade endometrioid, clear-cell or mucinous. It may be useful to refer to the guidelines of the network of rare ovarian tumors.Modalities and strategies for fertility preservation for young women with FIGO stage I ovarian cancerWomen of child-bearing age should be informed about the possibility of conservative management of their fertility in cases of stage IA epithelial ovarian cancer (Grade C).Conservative surgical management of the uterus and the contralateral adnexa after a unilateral adnexectomy for a low-grade serous, mucinous, or endometrioid stage IA ovarian cancer may be offered to women of child-bearing age, on condition that complete peritoneal and lymph node staging are negative, along with the findings of the uterine curettage for the endometrioid and mucinous histologic subtypes (Grade C).

For

  FIGO stage IA or low-grade stages IC1 or IC2, a bilateral adnexectomy may be

8 In

 8 regardless of histologic type (serous or other, high or low grade) (LE2). Complete surgery (i.e., with no macroscopic tumor residue) of advanced ovarian, tubal, or primary peritoneal cancer is recommended (Grade B). Surgery for ovarian cancer should be high-volume hospital (defined by performance of at least 20 procedures for advanced ovarian cancer each year) (Grade C). Adjuvant chemotherapy should begin within 6 weeks after surgery for ovarian, tubal, or primary peritoneal cancer (Grade C). FIGO stage IV ovarian, tubal, and primary peritoneal cancer, surgery is recommended when a complete peritoneal abdominal resection (i.e., with no macroscopic tumor residue) is possible (grade C).

  I P T recommended when metastatic adenopathy is suspected, either clinically or radiologically (Grade B). In the absence of such suspected adenopathy and when complete peritoneal surgery is performed as the initial surgery for advanced ovarian, tubal, or primary peritoneal cancers, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). The other lymphadenectomies (suprarenal, mesenteric, laparoscopic hepatic, cardiophrenic angle) are not recommended in the absence of clinical invasion (grade C). Finally, it is not possible to make specific recommendations about the role of lymphadenectomy according to histologic subtype or grade, due to the lack of data.

5 - 9 2 A 9 A 6 -number of cycles of adjuvant chemotherapy after interval cytoreduction surgery will be 2 to 4 , for a minimum total of 6 cycles and a maximum of 9 (

 5929649 FIGO stages III-IV high-grade serous or endometrioid cancer with a BRCA1/2 mutation were

  of older women with ovarian, tubal, or primary peritoneal cancer[START_REF] Falandry | Tumeurs épithéliales de l'ovaire : les personnes âgées[END_REF] Women aged 70 years or older account for a constantly increasing portion of the population, given its continuous aging. Those with ovarian cancer have a poorer prognosis than younger women: overall survival at 1 year for women aged ≥ 80 years is 36.9%, from 75-79 years 59.3%, from 70-74 years 68.4%, and from 65-69 years 73.5% (LE4). Advanced age currently leads to especially heterogeneous management of ovarian cancer. The lower rates of complete and optimal surgery and of complete chemotherapy indicate undertreatment of elderly women with ovarian cancer. Older women with ovarian, tubal, or primary peritoneal cancer should receive cytoreduction surgery in high-volume centers (performing more than 20 procedures for advanced ovarian cancer annually) (grade C). This surgery is recommended in elderly women (Grade B) provided that comorbidities and the likelihood of complete surgery allow it. The risk-benefit ratio of surgery for ovarian, tubal, and primary peritoneal cancer should be assessed on a case-by-case for the populations at the highest risk of complications (LE4), defined by: o Age ≥ 80 years, especially with albuminemia ≤ 37 g/L o Age ≥ 75 years and FIGO stage IV o Age ≥ 75 years, FIGO stage III and ≥ 1 comorbidity.

  Women undergoing surgery for ovarian, tubal, or primary peritoneal cancer may be offered an infusion of a single dose of tranexamic acid to reduce intraoperative blood loss (Grade C).Epidural analgesia, in addition to general anesthesia, is recommended for the management of women undergoing laparotomic cytoreduction surgery for ovarian, tubal, or primary peritoneal cancer (Grade B). In the absence of epidural analgesia, patient-controlled administration of morphine is recommended, but without a continuous flow (Grade B).

  , it is recommended that ovarian carcinomas (histologic type and grade) be diagnosed positively from biopsy samples and not from cytology (grade C). A surgical biopsy with multiple samples from different tumor sites is recommended before neoadjuvant chemotherapy for women with carcinomatosis of a presumed ovarian, tubal, or primary peritoneal origin (Grade C). A needle larger than 16G is recommended for image-guided microbiopsies, and at least three biopsy cores should be taken (Grade C). If no immunohistochemical study has been performed on the sample before chemotherapy or in cases of major morphologic discordance, this examination can be performed on residual tumor material after chemotherapy (Grade C).After a biopsy for suspected ovarian, tubal, or primary peritoneal carcinomatosis, the tissue samples should be fixed in neutral buffered formalin (with 4% formaldehyde) as rapidly as possible (<1 h after excision) (for optimal morphologic, immunohistochemical, and nucleic acid preservation) (grade C). Vacuum packing and storage at +4°C can be an alternative, but only for very large pieces of excised tissue, to prolong this delay to a maximum of 48 h (grade C). Tissue samples (for biopsies) should be fixed for at least 6 h (grade C). For pathology examination of excised tissue containing ovarian, tubal, or primary peritoneal carcinomas, preferential sampling is recommended from the solid areas, the tumor capsule, and areas of different macroscopic appearance (Grade C). In view of the heterogeneous nature of mucinous ovarian masses, 1 to 2 tissue blocks should be collected for each cm of tumor (Grade C). To determine the origin of a high-grade ovarian versus tubal versus peritoneal), the tube and the entire tubal infundibulum should be sampled (Grade C). When there is no macroscopic involvement of the omentum, 6 tissue blocks should systematically be taken to detect most of the microscopic damage (Grade B). When macroscopic involvement of the omentum is observed, only one block should be taken, from the bulkiest macroscopic tumor nodule (Grade B). For the histologic diagnosis of the histologic subtypes and grade of an ovarian, tubal, or primary peritoneal carcinoma, the WHO 2014 classification should be used (Grade C) and an immunohistochemical study should be performed with a panel of antibodies (selected among the following: EMA, CK7, CK20, PAX8, WT1, p53, RE, RP, HNF1b, and/or napsin A) (Grade B). Women with somatic mutations of the BRCA genes must be referred for an oncogenetic consultation. A study by INCa published in 2017 describes the importance of looking for a constitutional BRCA mutation and its utility in monitoring women and their family members at risk. The pathology report of excised tissue after chemotherapy for ovarian, tubal, or primary peritoneal cancers should state the size and the site of the bulkiest residual tumor nodule (Grade C). The pathology report should also state if there are no (or < 5%) residual tumor cells after chemotherapy (Grade C). VI-Post-treatment follow-up of ovarian, tubal, and primary peritoneal cancers and the role of hormone therapy 13 After the conclusion of treatment of epithelial ovarian, tubal, or primary peritoneal cancer, an assessment of symptoms is recommended at 3, 6, 12, 18, and 24 months, and then yearly (Grade B) If paraclinical monitoring is indicated for a woman after treatment of an epithelial ovarian, tubal, or primary peritoneal cancer, HE4 serum assays can be recommended ). The CNAM-TS does not reimburse the HE4 serum assay. In the absence of possible HE4 monitoring, CA125 serum assays can also be proposed (grade B).After treatment of epithelial ovarian, tubal, or primary peritoneal cancer, any finding of elevated serum HE4 or CA125 levels should be followed by an imaging examination (grade B).Peritoneal cytology is not only invasive but also has poor sensitivity for the detection of a recurrence of ovarian cancer (LE4). Unless ascites is present, routine peritoneal cytology is not recommended for the diagnosis of a recurrence of ovarian, tubal, or primary peritoneal cancer (grade C).After treatment of these cancers, the strategy of monitoring by CT thorax/abdomen/pelvis scan for the first two years is less effective and three times more expensive per diagnosis of recurrence than the CA125 assay alone (LE4). After treatment of ovarian, tubal, or primary peritoneal cancer, routine monitoring by CT scan of the thorax/abdomen/pelvis is not recommended (Grade C).If epithelial ovarian, tubal, or primary peritoneal cancer recurs in asymptomatic women, treatment based solely on an elevated serum CA125 level does not increase overall survival, and it impairs their quality of life (LE1). For the follow-up of ovarian, tubal, or primary peritoneal cancer, women with complete initial surgery (no macroscopic tumor residue, CC0) and in good overall condition (ECOG 0) should be monitored by serum assays (HE4 or CA125) starting 6 months after the end of chemotherapy, then every 6 months, if the serum markers were Women younger than 45 years of age who have undergone nonconservative treatment for high-grade serous ovarian, tubal, or primary peritoneal cancer should be offered hormone replacement treatment (HRT) for menopause (grade C) HRT does not increase the risks of recurrence or mortality in women older than 45 years (LE2). HRT can be offered for menopausal symptoms to women with a history of highgrade serous ovarian, tubal, or primary peritoneal cancer, after an individual evaluation of her risk-benefit ratio (Grade B). Women younger than 45 years whose mucinous ovarian adenocarcinoma has been treated benefit from HRT in terms of cardiovascular and overall survival (LE4). HRT should be offered to women younger than 45 years after nonconservative treatment of mucinous ovarian cancer (grade C). HRT can be offered to a woman older than 45 years with a history of mucinous ovarian cancer for menopause symptoms after an individual evaluation of her risk-benefit ratio. Low-grade serous or endometrioid adenocarcinomas are hormone-sensitive histologic types, for which HRT use is a potential risk (LE4). Nonetheless, no specific data for these histologic types justify a guideline about HRT use in women with a history of low-grade serous or endometrioid ovarian cancer.

  Bendifallah S, Ouldamer L, Lecuru F, Akladios C, Rousset-Jablonski C. Surveillance après traitement initial d'une tumeur épithéliale de l'ovaire, possibilités de contraception et de traitement hormonal substitutif de la ménopause. Recommandations de Pratique Clinique communes de FRANCOGYN, CNGOF, SFOG et ARCAGY-GINECO, labélisées par l'INCa Gynécologie, Obstétrique, Fertilité, Sénologie 2018.

Figure 1 :

 1 Figure 1: Management of presumed early-stage ovarian cancer

Figure 2 :

 2 Figure 2: Management of a FIGO stage III ovarian, tubal, or primary peritoneal cancer

Figure 3 :

 3 Figure 3: Management of a FIGO stage IV ovarian, tubal, or primary peritoneal cancer

Figure 4 :

 4 Figure 4: Management strategy in the era of first-line Olaparib

Figure 5 :

 5 Figure 5: Post-treatment follow-up of women with ovarian, tubal, or primary peritoneal cancer

Table

  cannot be classified (or is indeterminate) if at least one M rule and one B rule both apply or if no rule applies.

Software is available without charge at the IOTA site (www.iotagroup.org), and an application is available for both Android and iOS. Around 25% of adnexal masses remain indeterminate with the Simple Rules and require a second-line examination.

5 If the initial staging was not performed or was incomplete (defined by any of: no omentectomy, no exploration or resection of the appendix, no pelvic or para-aortic lymphadenectomy or peritoneal biopsies) for a presumed early-stage ovarian cancer, surgical restaging is recommended, including omentectomy (at least infracolic) (grade C), appendectomy (grade C), pelvic and para-aortic lymphadenectomies (grade B) (except for expansile mucinous cancer), and peritoneal biopsies (grade C), especially in the absence of an indication for chemotherapy. 5 In presumed early-stage ovarian cancer, a minimally invasive approach is recommended if complete surgery is possible without the risk of tumor rupture (grade B). Otherwise, a midline laparotomy is recommended (grade B). Every precaution must be taken to avoid the intraoperative rupture of an ovarian tumor, including an intraoperative decision to convert to open surgery (grade B). For surgical restaging, a minimally invasive approach have to be preferred when the ovarian mass has already been removed (grade B). 5 Adjuvant chemotherapy is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). 6 Adjuvant chemotherapy for early-stage ovarian or tubal cancer must include a platinum compound (grade A), preferably carboplatin (grade A).

Table 1 :

 1 The 10 simple ultrasound rules for an adnexal mass

Rules for predicting a benign tumor Rules for predicting a malignant tumor B1

		Unilocular	M1	Irregular solid mass
	B2	The largest diameter of the largest	M2	Ascites
		solid component < 7 mm
	B3	Acoustic shadow	M3	≥4 papillary structures
	B4	Smooth multilocular tumor with	M4	Irregular multilocular tumor with
		largest diameter < 100 mm		maximum diameter ≥ 100 mm
	B5	No blood flow	M5	Intense vascularization on Doppler

Table 2 : ADNEX MR score to characterize the risk of malignancy of adnexal masses on MRI Risk of malignancy Classification

 2

	No mass visible on MRI

Table 4 : Summary of survival according to tumor residue and primary or interval surgery in advanced ovarian, tubal, and primary peritoneal cancers.

 4

	STAGE III -	Primary	Interval	Primary	Interval
	IV	surgery	surgery	surgery	surgery
		Recurrence-free survival	Overall survival (months)
		(months)
	No residue	20.1-33	16.4	64.1-71.9	66.6
	Residue < 1	13-16.8	9.8	28.7-42.4	39.7
	cm
	Residue > 1	12.9-14.1	7.4	30.7-35	28.4
	cm

Acknowledgments:

The authors want to thank Mme Marianne Duperray and Mme Sophie Morois for their valuable logistic support in the development of these clinical practice guidelines.

The authors thank the following professional societies: CNGOF, FRANCOGYN, SFOG, SFAR, GINECO-ARCAGY, SCGP, SFCO, and the RRC; the IMAGIN patient association, and the expert reviewers for their attentive review of these clinical practice guidelines: (list: https://www.e-cancer.fr/Professionnels-de-sante/Recommandations-et-outils-d-aide-a-lapratique).