Borderline ovarian tumors: clinical guidelines

List of Abbreviations

AFP – alpha-fetoprotein

WHO – World Health Organization

GI – gastrointestinal tract

MNT – malignant neoplasm

CT – computed tomography

ICD-10 – International Classification of Diseases 10th Revision

MRI – magnetic resonance imaging

BOT – borderline ovarian tumor

PET-CT – positron emission tomography combined with computed tomography

CEA – carcinoembryonic antigen

OC – ovarian cancer

CA-19.9 – tumor antigen 19.9

CA-125 – cancer antigen 125

SBOT – serous borderline ovarian tumor

US – ultrasound examination

hCG – human chorionic gonadotropin;

EGD – esophagogastroduodenoscopy;

ECOG – Eastern Cooperative Oncology Group

HE4 – human epididymis protein 4

ROMA – Risk of Ovarian Malignancy Algorithm

Terms and Definitions

Implants – extraovarian foci of a borderline tumor.

Invasive implants lie deep within the peritoneum or omentum, showing signs of cellular atypia and destruction of surrounding structures.

Non-invasive implants are located on the surface of the peritoneum or omentum, without marked cellular atypia.

Different types of implants can coexist in the same patient.

Low-grade invasive carcinoma – high-grade serous ovarian carcinoma (low-grade).

Low-grade non-invasive carcinoma – synonym for the micropapillary variant of serous borderline ovarian tumor.

Suboptimal cytoreductive surgery – hysterectomy with adnexectomy, removal of the greater omentum, and removal of tumor manifestations with macroscopically visible residual nodules, at least one of which is greater than 10 mm in diameter.

Optimal cytoreductive surgery – performance of hysterectomy with adnexectomy, removal of the greater omentum, as well as visible manifestations of the tumor process with macroscopically detectable residual tumor nodules, each not exceeding 10 mm in diameter.

Complete cytoreductive surgery – performance of hysterectomy with adnexectomy, removal of the greater omentum, as well as all visible manifestations of the tumor process without macroscopically detectable residual tumor masses.

Prehabilitation – rehabilitation from the moment of diagnosis until the start of treatment (surgical treatment/chemotherapy/radiation therapy).

Psammoma bodies – microscopic structures resulting from the precipitation of protein-lipid substances in tissues, subjected to incrustation with calcium salts.

Endosalpingiosis – dystopic tubal-type epithelium.

BRAF – gene encoding the B-Raf protein.

KRAS – proto-oncogene, member of the Ras protein family.

PTEN – phosphatase and tensin homolog, a tumor suppressor gene.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Borderline ovarian tumors (BOTs), or atypically proliferating tumors, are neoplasms with atypical epithelial proliferation without destructive stromal invasion. In most cases, BOTs are characterized by a favorable prognosis [1, 2].

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Borderline tumors develop from the surface epithelium of the ovaries. The exact cause of BOTs remains unclear. Epithelial ovarian tumors are believed to originate from inclusion cysts resulting from the isolation of invaginated surface mesothelium. The cells within cysts can differentiate into either tubal or endocervical epithelium. The bulk of hyperplasias of the ovarian surface epithelium occurs against the background of inflammatory and autoimmune processes, the vast majority of which are caused by ovulation. Recently, a theory has been put forward that the source of serous borderline ovarian tumors (SBOTs) and serous tumors in general are the epithelial cells of the fimbrial end of the fallopian tube. Both sources of histogenesis of these neoplasms may coexist. The factors of tumorigenesis in BOTs are mutations in the BRAF and KRAS genes. Serous cystadenomas of the ovary transform into SBOTs only when mutations in these genes occur. Mutations in the KRAS and BRAF genes are found in 2/3 of patients with SBOTs. Unlike BOTs, more than 50% of patients with low-grade ovarian adenocarcinoma have p53 gene mutations. Endometrioid BOTs are characterized by mutations in the KRAS, β-catenin, or PTEN genes, and endometriosis can be an important precursor for endometrioid and clear cell BOTs. Mutations characteristic of mucinous BOTs are also identified in invasive mucinous adenocarcinomas.

Borderline tumors have a relatively favorable clinical course because genetic alterations lead to proliferative processes rather than metastasis [2–4].

1.3 Epidemiology of the Disease or Condition

Borderline ovarian tumors account for 15–20% of all epithelial ovarian neoplasms. The most common variants of BOTs include serous (53%) and mucinous (43%) types. Endometrioid, clear cell, and Brenner borderline tumors occur in 4% of cases. The average age of patients with BOTs is 38–53 years [5].

1.4 Features of Coding the Disease or Condition

According to the International Classification of Diseases 10th Revision, the code for BOTs corresponds to D39.1 (code C56 was/is also used) – neoplasm of uncertain or unknown behavior of female genital organs [6].

1.5 Classification of the disease or condition

Serous BOTs are combined with extraovarian implants (extraovarian foci of BOTs) in 30–38% of cases. In 75% of cases, the implants are non-invasive. The division of implants into invasive and non-invasive is currently not performed, as invasive implants have been reclassified as low-grade serous carcinoma. SBOTs are frequently associated with foci of dystopic tubal-type epithelium – endosalpingiosis. Microinvasion may be observed in SBOTs (up to 5 mm in linear extent or an area of 10 mm²). One of the important features of SBOTs is the capacity for late recurrence. Extraovarian relapses can occur 15–30 years after the onset of the disease.

Borderline ovarian tumors of non-serous histological types (mucinous, endometrioid, Brenner, clear cell) are generally unilateral formations, are not characterized by peritoneal implants, and have a favorable prognosis [1–5, 7].

1.5.1. International Histological Classification (World Health Organization classification, 5th edition, 2020) [7]:

• serous tumors:

- 8442/1 Serous borderline tumor;

- 8460/2 Serous borderline tumor – micropapillary variant/non-invasive low-grade serous carcinoma;

• mucinous tumors:

- 8472/1 Mucinous borderline tumor;

• endometrioid tumors:

- 8380/1 Endometrioid tumor, borderline;

• clear cell tumors:

- 8313/1 Clear cell borderline tumor;

• Brenner tumors:

- Brenner tumor, borderline malignancy;

• seromucinous tumors:

- 8474/1 Seromucinous borderline tumor.

1.5.2. Staging

Staging of BOTs is performed according to the TNM (8th edition, 2016) and FIGO (2014) classifications (Table 1).

Table 1. Staging of BOTs according to the Ovarian Cancer TNM (8th edition, 2016) and FIGO (2014) classifications

1.6 Clinical presentation of the disease or condition

OVT have no specific clinical symptoms. Patients may complain of abdominal enlargement, pain of varying intensity, and acyclic spotting. In 37-40% of patients, the disease is asymptomatic. OVT are frequently detected during surgical interventions performed for other reasons. In 15-35% of patients with SOVT, infertility may be observed [8-11].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing the diagnosis of the disease or condition:

1. history data;

2. physical examination data;

3. data from diagnostic imaging methods (ultrasound, CT, MRI, etc.);

4. morphological verification of the diagnosis.

Morphological verification of the neoplasm is mandatory to establish a clinical diagnosis.

2.1 Complaints and Anamnesis

• All patients with suspected OVT are recommended a thorough collection of complaints and anamnesis to identify symptoms that will help establish the correct diagnosis [11].

強B (level of recommendation — B)УДД 3Level of Recommendation — B (Level of Evidence — 3)

Comment: In 37-40% of patients, the disease may be asymptomatic, and in 15-35%, it may be accompanied by infertility. The main complaints may be abdominal pain and abdominal enlargement. Complaints such as menstrual irregularities, genital spotting, and acute abdominal pain leading to emergency hospitalization are rare [8–11].

2.2 Physical Examination

• All patients with suspected OVT are recommended a thorough physical examination, including a rectovaginal examination, palpation of the abdominal organs and all groups of peripheral lymph nodes, auscultation and percussion of the lungs, and palpation of the mammary glands, in order to establish a preliminary diagnosis, determine the examination tactics, and the treatment algorithm. [8-12]

強B (level of recommendation — B)УДД 3Level of Recommendation — B (Level of Evidence — 3)

Comment: attention should be paid to assessing the patient's general condition using the ECOG and Karnofsky scales (see Appendix G1-2), as well as assessing pain syndrome, body temperature, hemodynamics, and the presence of ascites [8-11].

2.3 Laboratory Diagnostics

• All patients with suspected OVT are recommended to undergo a complete blood count (CBC) with differential, a general clinical biochemical blood test with evaluation of liver and kidney function parameters, a general urinalysis, and a coagulogram (exploratory study of the hemostasis system) to assess the general condition and determine the feasibility of a particular type of treatment [8-11].

GCP CLoE 5Grading of Recommendations Assessment, Development and Evaluation (GRADE) – C (Level of Evidence – 5)

Comment: Laboratory tests determine the state of various organs and systems in order to determine the feasibility of a particular type of treatment.

In the complete blood count (CBC) with differential, it is advisable to assess the following parameters: study of total hemoglobin, erythrocyte, platelet, and leukocyte levels in the blood, assessment of hematocrit, determination of mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, differential leukocyte count (leukocyte formula), study of the erythrocyte sedimentation rate; in the general clinical biochemical blood test assessing liver and kidney function parameters: study of total protein, glucose, total bilirubin, creatinine, blood urea, determination of the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) in the blood, study of total bilirubin levels in the blood; in some cases: plasma electrolytes (study of blood potassium, sodium, and chloride levels), etc.; in the general urinalysis: visual examination of urine (determination of urine color and transparency), determination of urine specific gravity (relative density), determination of protein in urine, determination of hydrogen ion concentration (pH) of urine, study of urine glucose levels, detection of ketone bodies in urine; microscopic examination of urine sediment.

As part of the blood coagulation study, a coagulogram (exploratory study of the hemostasis system) is evaluated (study of blood fibrinogen levels, prothrombin time (by Quick), determination of the international normalized ratio (INR), determination of prothrombin (thromboplastin) time (PTT) in the blood, activated partial thromboplastin time (APTT), determination of thrombin time (TT) in the blood. According to indications, additionally: determination of D-dimer concentration in the blood, determination of antithrombin III activity in the blood, etc.).

Comment: SOVT is characterized by an elevated CA-125 level (mean values correspond to 100 U/ml). However, in some patients, the concentration of CA-125 may be within the normal range or elevated only slightly [8-11].

An elevated HE4 level increases the specificity of the differential diagnosis between SOVT and ovarian cancer. [53-55]

• In all female patients with suspected mucinous tumor, it is recommended to determine blood levels of CEA and CA-19.9 for the differential diagnosis of ovarian neoplasms [15].

Level of Evidence BGrade of Recommendation 3Level of Clinical Effectiveness – B (level of evidence – 3)

Comment: CEA and CA-19.9 levels may be elevated in mucinous ovarian carcinoma, which subsequently allows monitoring of treatment efficacy [15].

• For differential diagnosis with sex cord-stromal ovarian tumors, it is recommended to determine the blood level of inhibin B, which is a highly specific marker of granulosa cell tumor of the ovary, especially in postmenopausal women [56].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

• In women under 40 years of age with a probability of germ cell ovarian tumors, it is recommended to determine serum levels of AFP, serum levels of hCG (free beta-subunit), and blood lactate dehydrogenase (LDH) activity for the differential diagnosis of ovarian tumors [16, 57, 58].

GIB CLOE 4Grade of Recommendation – C (Level of Evidence – 4)

Comment: Germ cell ovarian tumors predominantly occur in young women; for detailed information, see the clinical guidelines "Non-Epithelial Ovarian Tumors" [16, 57, 58].

2.4 Instrumental Diagnostics

• All patients with suspected epithelial ovarian cancer and epithelial ovarian cancer are recommended to undergo comprehensive ultrasound examination (US) of the pelvic organs, abdominal cavity, retroperitoneal space, and pelvic, lumbar, and inguinal lymph nodes to assess the primary tumor and the extent of the tumor process [17, 48].

GCR BLEL 2Grade of Recommendation – B (Level of Evidence – 2)

Comment: Ultrasound – is the most accessible and effective method for visualizing ovarian tumor masses [17, 48].

Instead of a comprehensive ultrasound of the abdominal cavity, retroperitoneal space, pelvic, lumbar, and inguinal lymph nodes, a CT or MRI of the abdominal cavity, retroperitoneal space, and pelvic, lumbar, and inguinal lymph nodes with/without intravenous contrast, or whole-body PET-CT, may be performed [17, 48].

• All patients with epithelial ovarian cancer or suspected epithelial ovarian cancer are recommended to undergo esophagogastroduodenoscopy (EGD) to rule out a primary gastrointestinal (GI) tract tumor and assess for concomitant GI diseases [18].

GCP CLoE 5Grading of Recommendations Assessment, Development and Evaluation (GRADE) – C (Level of Evidence – 5)

Comment: EGD – is a mandatory examination method for patients with suspected ovarian tumor, making it possible to rule out secondary (metastatic) ovarian involvement in malignant neoplasms of the GI tract.

• All patients with suspected epithelial ovarian cancer are recommended to undergo colonoscopy for differential diagnosis with GI malignancies and to assess for concomitant GI diseases [18].

GCP CLoE 5Grading of Recommendations Assessment, Development and Evaluation (GRADE) – C (Level of Evidence – 5)

Comment: Colonoscopy is a mandatory examination method for patients with suspected ovarian tumor, allowing to rule out secondary (metastatic) ovarian involvement in malignant neoplasms of the GI tract.

• All female patients with suspected epithelial ovarian cancer are recommended to undergo computed tomography (CT) of the abdominal cavity, and CT or MRI of the pelvic organs with intravenous contrast for differential diagnosis with ovarian malignancy, determination of the stage of the disease, selection of treatment tactics and algorithm, and assessment of disease prognosis [18].

GCP CLoE 5Grading of Recommendations Assessment, Development and Evaluation (GRADE) – C (Level of Evidence – 5)

Comment: CT allows visualization of the primary tumor, detection of dissemination, and assessment of the feasibility of optimal debulking surgery. If CT is contraindicated or has insufficient diagnostic value, magnetic resonance imaging (MRI) of the abdominal cavity and pelvic organs with intravenous contrast may be performed. In case of tumor dissemination or suspected low-grade ovarian cancer, positron emission tomography combined with CT (PET-CT) can be performed.

• All female patients with suspected ovarian tumor are recommended to undergo targeted chest radiography and/or chest CT to detect focal lesions in the lungs, pleura, mediastinal lymph nodes, determine the presence of fluid in the pleural cavity, and clarify the diagnosis [18].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment: CT of the chest cavity has greater sensitivity and specificity in detecting pleural effusion, secondary (tumorous) changes in the lungs, pleura, and mediastinal lymph nodes [18].

2.5 Other Procedures

1. tumor size, tumor extension to the capsule;

2. histological structure of the tumor;

3. presence of microinvasion or invasion;

4. presence of unfavorable structures (micropapillary, cribriform) in the tumor;

5. presence and nature of implants, endosalpingiosis, psammoma bodies in the peritoneal biopsy, greater omentum;

6. tumor spread or presence of implants on the fallopian tubes, uterus.

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment:

- Morphological examination of the removed tumor is the fundamental method for establishing the diagnosis of primary peritoneal cancer (PPC) [18].

- During morphological verification of the PPC diagnosis, the pathomorphological examination of the biopsy (surgical) material may be supplemented by an immunohistochemical examination

- It is advisable to re-evaluate (consultation) prepared micropreparations in medical organizations with specialists in the field of ovarian tumor morphology.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

The prescription and use of medicinal products specified in the clinical guideline are aimed at providing the patient with clinically effective and safe medical care; therefore, their prescription and use in a specific clinical situation are determined in accordance with the instructions for use of specific medicinal products, implementing the precautions described in the instructions, and dose adjustments may also be made taking into account the patient's condition.

• Surgical treatment as the main treatment method is recommended for all patients with PPC. Chemotherapy is ineffective in the treatment of PPC [10, 22–24].

GCR BLEL 2Grade of Recommendation – B (Level of Evidence – 2)

Comment: surgical intervention for PPC is the main and only method of treatment. High qualification of the morphologist is necessary for successful and effective conservative treatment of PPC.

Chemotherapy is not recommended for patients with PPC, regardless of the histological type of PPC and the stage of the disease.

• All patients with PPC are recommended to undergo abdominal revision and surgical staging to determine the extent of the tumor process and plan the treatment algorithm [13].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment: for surgical staging of PPC via laparotomy or laparoscopy, the following manipulations are performed:

• if there is no morphological verification of the diagnosis, laparotomy should be performed with urgent intraoperative morphological examination;

• if ascites is detected, the fluid is aspirated for cytological examination. In the absence of ascites, a cytological examination of peritoneal washings is performed (including from its diaphragmatic surface, lateral gutters, and small pelvis);

• revision of the pelvic and abdominal organs is performed;

• all sections of the abdominal cavity, including the subdiaphragmatic space, greater and lesser omentums, small and large intestines and their mesenteries, surfaces of the parietal and visceral peritoneum, and retroperitoneal space, are carefully and methodically examined; all areas of the peritoneum and adhesions suspicious for implants or metastases are biopsied. The entire peritoneal surface must be examined. Adhesions preventing revision must be noted;

• if the revision did not confirm the presence of implants or metastases, biopsies of randomly selected areas of the peritoneum of the pelvic walls, rectouterine pouch, urinary bladder, lateral gutters, and the right and left domes of the diaphragm are performed (scraping of the diaphragmatic surfaces may be performed);

• removal of the greater omentum is mandatory and is performed at the level of the transverse colon;

• pelvic and lumbar lymphadenectomy is not performed for BOT;

• appendectomy is advisable only if its involvement is suspected (examined thoroughly in mucinous BOT).

Since BOT frequently develop in women of reproductive age, fertility-sparing surgery may be performed.

Minimally invasive surgical interventions, in particular laparoscopic ones, can be used in the surgical treatment of patients with BOT, provided that the principles of ablating surgery are strictly observed. If there are signs of peritoneal tumor dissemination (according to ultrasound, CT, MRI), a laparotomic approach is recommended.

Comments: In the micropapillary variant of SBDT, if the surgery was initially performed without staging and omentectomy was not carried out, relaparotomy/relaparoscopy, staging, and omentectomy are advisable due to the high probability of invasive implants [7, 10, 22, 26-28].

3.1. Serous borderline ovarian tumors (SBOTs)

• For reproductive-aged patients with SBDT who wish to preserve reproductive and hormonal functions, fertility-sparing treatment is recommended, whereas for postmenopausal patients with SBDT – hysterectomy with bilateral adnexectomy. [7, 10, 22, 59-62].

GIB CLOE 4Grade of Recommendation – C (Level of Evidence – 4)

Comment: All patients with BOT are recommended to undergo abdominal cavity exploration and surgical staging (see above) in order to determine the extent of the tumor process and plan the treatment algorithm

• For reproductive-aged patients with SBDT presenting with a unilateral ovarian lesion, unilateral adnexectomy is recommended; for bilateral ovarian lesions, bilateral adnexectomy/hysterectomy with adnexectomy is recommended. If the tumor size is small and there is a sufficient volume of healthy ovarian tissue, ovarian resection (for unilateral lesions) or resection of both ovaries (for bilateral lesions) may be performed [25]. Biopsy/wedge resection of the contralateral leukocyte/ovary in the absence of visible pathology is not indicated in order to preserve ovarian reserve [7, 10, 22, 26-28, 60].

GIB CLOE 4Grade of Recommendation – C (Level of Evidence – 4)

Comment: during ovarian resection, intraoperative pathological examination of the surgical (biopsy) material is advisable (to rule out low-grade invasive carcinoma).

In patients with stage IIA-IIIA SBDT, fertility-sparing surgeries are possible (they require consultation with specialists from expert medical organizations specializing in ovarian tumors).

In patients with stage IIIB-IIIC SBDT without dissemination along the parietal and visceral peritoneum (implants in the greater omentum) of reproductive age who wish to preserve reproductive and hormonal functions, fertility-sparing surgeries are possible (consultation with an oncological specialist from an expert medical organization specializing in ovarian tumors is recommended)

In stage IIIB-IIIC SBDT, a complete or optimal cytoreductive surgery as described in the clinical guidelines "Ovarian Cancer" is recommended whenever possible.

In the micropapillary variant of SBDT, if the surgery was initially performed without staging and omentectomy was not carried out, relaparotomy/relaparoscopy, staging, and omentectomy are advisable due to the high probability of invasive implants

If the surgery was suboptimal with residual tumor and the invasive type of implants was determined after routine histological examination, this tumor is regarded as low-grade cancer. Treatment is carried out in accordance with the ovarian cancer treatment program.

Treatment tactics are determined by an oncologist from an expert medical organization specializing in ovarian tumors, taking into account the pathological report (or review of ready-made glass slides) of the surgical (biopsy) material. [7, 10, 22, 26-28].

3.2. Borderline ovarian tumors of non-serous histological types

• Patients with non-serous histological types of BOT are recommended to undergo surgical treatment in the scope of adnexectomy on the side of the affected ovary [7, 29–32].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5).

Comment: Since implants are not characteristic of mucinous BOT, restaging operations are not indicated for verified mucinous, endometrioid, and other non-serous BOT. If implants are detected in mucinous BOT, the malignant nature of the primary ovarian tumor or its metastatic involvement must first be ruled out. Appendectomy is recommended only for those patients with mucinous BOT who have pathology identified upon careful inspection of the appendix. Mucinous BOT are sometimes complicated by pseudomyxoma peritonei.

• All patients with BOT are recommended to undergo abdominal cavity exploration and surgical staging (see above) in order to determine the extent of the tumor process and plan the treatment algorithm [7, 29-32]

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5).

3.3. Recurrence of serous borderline ovarian tumors

3.3.1. Recurrence of SBOT in the ovary/ovaries

Recurrence of SBDT in the ovary/ovaries occurs in 35-50% of cases [10, 33].

• For patients of reproductive age with recurrent BOT (borderline ovarian tumor) in the ovary/ovaries (who wish to preserve reproductive function), it is recommended to perform ovarian resection; in the absence of healthy ovarian tissue, it is recommended to perform adnexectomy/hysterectomy with adnexa. For postmenopausal patients, it is recommended to perform hysterectomy with adnexa [10, 22, 33].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5).

Comment: surgical staging is performed in all patients who did not initially undergo this procedure, for the purpose of potentially detecting foci of cancer.

The occurrence of a recurrence in the ovary/ovaries is possible during pregnancy. In such cases, it is recommended to consult patients in expert clinics specializing in the treatment of patients with borderline ovarian tumors and to make a collegial decision on the further management strategy for the patient. It is possible to preserve and prolong the pregnancy in the presence of an ovarian BOT recurrence without surgery during pregnancy, depending on the size of the recurrent tumor and its growth dynamics according to ultrasound data.

3.3.2. Relapse of extragonadal/extragenital serous borderline ovarian tumors

Recurrence of BOT outside the ovary/ovaries (extragonadal, extragenital) occurs in 8–15% of cases and can be local or multifocal [10, 33].

• For patients with extragenital/extragonadal recurrence of BOT, it is recommended to perform surgical treatment consisting of the removal of recurrent tumor nodes. Repeated recurrences require repeated surgical interventions in the volume of complete cytoreduction. If low-grade cancer is detected in the recurrent tumor nodes, the management strategy for such patients must comply with the principles of ovarian cancer treatment [10, 22, 33].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5).

Comment: Surgical staging is performed in all patients who did not undergo this procedure initially. In patients with an isolated extragonadal recurrence (without tumor involvement of the ovary/ovaries) following organ-sparing initial surgery (ovarian resection/cystectomy, adnexectomy), hysterectomy with adnexal removal may be omitted (consultation with an onco-gynecologist at an expert research center is recommended).

3.5 Anesthesia

Procedures and recommendations for pain management in ovarian cancer correspond to the recommendations presented in the clinical guidelines "Chronic Pain Syndrome (CPS) in Adult Patients Requiring Palliative Medical Care".

3.6. Dietary therapy

• To date, data indicate an increased risk of postoperative complications in overweight and obese patients; therefore, measures aimed at reducing excess weight to normal values are recommended. Modifying the habitual diet in such patients will help prevent complications from the administered treatment (surgical, medical). [9-13].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

4. Medical Rehabilitation and Sanatorium-Resort Treatment

4.1. Pre-rehabilitation

Comments: Increasing physical activity 2 weeks prior to surgery improves postoperative quality of life, allowing a return to full daily activities as early as 3 weeks after surgery. Performing therapeutic exercise in the preoperative period reduces the incidence of postoperative complications [35].

Comment: testing and consultation with a medical psychologist include techniques aimed at stress management, which significantly improve patients' quality of life [35–38]

4.2. Rehabilitation after surgical treatment

5. Prevention and Dispensary Observation

Comment:

• Patients with BOT who have undergone organ-sparing surgeries are recommended to undergo follow-up by an oncologist (gynecologic oncologist), serum CA-125 testing, comprehensive abdominal ultrasound, and comprehensive pelvic ultrasound (transvaginal and transabdominal) – once every 3–4 months for the first 5 years, then once every 6–8 months for the subsequent 5 years, and then once every 12 months for 15 years. CT and MRI of the pelvis and abdominal cavity are performed as clinically indicated.

• The possibilities of realizing reproductive function, including through the use of ART methods, should be discussed with gynecologic oncologists and reproductive specialists at expert research centers.

• Pregnancy can be recommended 3 months after surgery [40–43].

• There are no contraindications to prescribing hormonal drugs (COCs) in BOT patients after organ-sparing surgeries, or hormone replacement therapy (HRT) in patients who underwent radical surgical interventions (provided there is no residual tumor and no disease recurrence) [52]

• Patients with BOT who have undergone radical surgery are recommended to undergo follow-up by an oncologist (gynecologic oncologist), serum CA-125 testing, comprehensive abdominal ultrasound, and comprehensive pelvic ultrasound – once every 6 months for the first 5 years, then once every 8–12 months for the subsequent 5 years, and then once every 12 months for 15 years. CT and MRI of the pelvis and abdominal cavity are performed as clinically indicated.

• For non-serous histological types of BOT, it is recommended to have follow-up by an obstetrician-gynecologist (since recurrences and implants do not occur in non-serous variants), comprehensive abdominal ultrasound, and comprehensive pelvic ultrasound once every 6 months for the first 5 years, followed by an annual preventive check-up.

6. Organization of Medical Care

Medical care, with the exception of medical care provided as part of clinical trials, in accordance with Federal Law No. 323-FZ dated November 21, 2011, "On the Basics of Protecting the Health of Citizens in the Russian Federation," is organized and provided:

1. in accordance with the regulations on the organization of medical care by types of medical care, which is approved by the authorized federal executive body;

2. in accordance with the procedures for the provision of medical care approved by the authorized federal executive body and mandatory for execution on the territory of the Russian Federation by all medical organizations;

3. based on these clinical guidelines;

4. taking into account the standards of medical care approved by the authorized federal executive body.

   Primary specialized health care is provided by an oncologist and other medical specialists at an ambulatory cancer care center, or, in its absence, at a primary oncology office or the outpatient department of an oncological dispensary (cancer hospital).

In case of suspicion or detection of an oncological disease in a patient, general practitioners, district general practitioners, general family physicians, medical specialists, and mid-level medical personnel shall refer the patient in the established manner for consultation to an outpatient oncological care center, or, in its absence, to a primary oncological office or the outpatient department of an oncological dispensary (oncological hospital) for the provision of primary specialized health care.

Consultation at an outpatient oncological care center, primary oncological office, or outpatient department of an oncological dispensary (oncological hospital) must be performed no later than 3 working days from the date of issuing the referral for consultation. The oncologist of the outpatient oncological care center (in the absence of such a center, the oncologist of the primary oncological office or outpatient department of the oncological dispensary/hospital) arranges for the acquisition of biopsy (surgical) material, as well as the performance of other diagnostic tests necessary to establish the diagnosis, including the extent of the oncological process and the stage of the disease.

If it is impossible to obtain biopsy (surgical) material or perform other diagnostic tests within the medical organization that includes the ambulatory cancer care center (primary oncology office), the patient is referred by the oncologist to an oncological dispensary (cancer hospital) or to a medical organization providing medical care to patients with oncological diseases.

The timeframe for performing pathological examinations necessary for the histological verification of malignant neoplasms shall not exceed 15 working days from the date of receipt of the biopsy (surgical) material by the pathoanatomical bureau (department).

The timeframe for diagnostic instrumental and laboratory examinations in case of suspected oncological disease shall not exceed the timeframes established in the state guarantee program for the free provision of medical care to citizens, approved by the Government of the Russian Federation, which is 7 working days from the date of prescribing the examinations.

The diagnosis of an oncological disease is established by a medical specialist based on the results of diagnostic examinations, including cytological and/or histological verification of the diagnosis, except for cases where obtaining biopsy and/or puncture material is not feasible.

An oncologist from an outpatient oncological care center (primary oncology office) refers the patient to an oncological dispensary (oncology hospital) or another medical organization providing medical care to cancer patients, including one subordinate to a federal executive body (hereinafter referred to as a federal medical organization), to clarify the diagnosis (if establishing the diagnosis is impossible, including the extent of the oncological process and disease stage), determine treatment tactics, and in the presence of medical indications for specialized, including high-tech, medical care.

For oncological diseases included in ICD-10 categories C37, C38, C40-C41, C45-C49, C58, D39, C62, C69-C70, C72, C74, as well as those corresponding to the codes of the International Classification of Diseases for Oncology (ICD-O), 3rd edition 8936, 906-909, 8247/3, 8013/3, 8240/3, 8244/3, 8246/3, 8249/3, an oncologist at an oncological dispensary (oncological hospital) or other medical organization providing medical care to patients with oncological diseases, in order to determine the treatment strategy, shall organize a consultation or medical board (consilium), including through the use of telemedicine technologies, at federal state budgetary institutions subordinate to the Ministry of Health of the Russian Federation that provide medical care (hereinafter referred to for the purposes of this Procedure as national medical research centers).

In complex clinical cases, to clarify the diagnosis (in the event of the impossibility of establishing the diagnosis, including the extent of the oncological process and the stage of the disease) for the purpose of evaluation, interpretation, and description of the results, the oncologist shall arrange for the referral of:

• digital images obtained from pathomorphological studies to the fourth-group pathologo-anatomical bureau (department) (reference center) via information interaction, including the use of teleconsultation technologies for remote interaction between medical personnel;

• of digital images obtained from diagnostic imaging methods to the remote diagnostic imaging consultation center via information interaction, including the use of telemedicine technologies for remote interaction between medical workers;

• biopsy (surgical) material for repeated pathomorphological, immunohistochemical, and molecular genetic studies: to the pathoanatomical bureau (department) of the fourth group (reference center), as well as to molecular genetic laboratories for molecular genetic testing.

Treatment tactics are established by a medical board (consilium) comprising oncologists, a radiation therapist, and a neurosurgeon (in cases of nervous system tumors) of the medical organization that includes departments of surgical methods for treating malignant neoplasms, antineoplastic drug therapy, and radiotherapy (hereinafter referred to as the oncological consilium), including an oncological consilium conducted using telemedicine technologies, with the involvement of other specialist physicians when necessary.

Dispensary follow-up by an oncologist for a patient with a diagnosed oncological disease is established and carried out in accordance with the procedure for dispensary observation of adults with oncological diseases.

For accounting purposes, information about a newly diagnosed case of an oncological disease is sent within 3 working days by the oncologist of the medical organization where the corresponding diagnosis was established to the oncological dispensary or the organization of a constituent entity of the Russian Federation that performs the registration of patients with newly diagnosed malignant neoplasms, including through the use of the Unified State Health Information System. If the presence of an oncological disease is confirmed in a patient, information about the refined diagnosis is sent from the oncological dispensary or the organization of the constituent entity of the Russian Federation that performs the registration of patients with newly diagnosed malignant neoplasms to the medical organization providing clinical follow-up of the patient.

Specialized, including high-tech, medical care in medical organizations providing medical care to the adult population for oncological diseases is provided based on medical indications stipulated by the regulations on organizing the provision of specialized, including high-tech, medical care.

Specialized medical care, excluding high-tech medical care, in medical organizations subordinate to federal executive authorities is provided based on medical indications provided for in clause 5 of the procedure for referring patients to medical organizations and other organizations subordinate to federal executive authorities to provide specialized (excluding high-tech) medical care, stipulated in the appendix to the regulations on organizing the provision of specialized, including high-tech, medical care. (Clause 5: to receive specialized medical care on a planned basis, the federal medical organization is chosen upon the referral of the attending physician.) If several federal medical organizations participating in the implementation of the Program provide specialized medical care for diseases and conditions (group of diseases and conditions) corresponding to the patient's diseases and conditions (group of diseases and conditions), the attending physician is obliged to inform the patient (the patient's legal representative) about the possibility of choosing a federal medical organization, including the potential waiting times for specialized medical care, which may exceed the waiting times established by the program of state guarantees of free provision of medical care to citizens.

The waiting time for the provision of specialized (excluding high-tech) medical care must not exceed the timeframe established in the program of state guarantees of free medical care for citizens, approved by the Government of the Russian Federation, which is 7 working days.

If a patient with an oncological disease has medical indications for medical rehabilitation, the oncologist arranges for it to be provided in accordance with the procedure for organizing adult medical rehabilitation.

If a patient with an oncological disease has medical indications for sanatorium-resort treatment, the oncologist arranges for it in accordance with the procedure for organizing sanatorium-resort treatment.

Palliative medical care for a patient with oncological diseases is provided in accordance with the regulations on organizing the provision of palliative medical care, including the procedure for interaction between medical organizations, social service organizations, and public associations and other non-profit organizations operating in the field of health protection.

If an oncological disease is suspected and/or detected in a patient during the provision of emergency medical care, the patient is transferred or referred to medical organizations providing medical care to patients with oncological diseases to determine management tactics and the need for additional other methods of specialized antitumor treatment.

Indications for hospitalization in a medical organization in an emergency or urgent form are:

1. presence of oncological disease complications requiring emergency and urgent specialized medical care;

2. presence of complications from cancer treatment (surgical intervention, radiotherapy, drug therapy, etc.) requiring the provision of emergency and urgent specialized medical care

Indications for hospitalization in a medical organization in a planned form are:

1. the need to perform complex interventional diagnostic medical procedures, as well as endoscopic examinations when they cannot be performed on an outpatient basis, requires subsequent monitoring in a round-the-clock or day hospital setting;

2. presence of indications for specialized antitumor treatment (surgical intervention, radiation therapy including brachytherapy, external beam radiation therapy, and other types of radiation therapy, drug therapy, etc.) requiring inpatient or day-hospital monitoring.

Indications for discharging a patient from a medical organization are:

1. completion of a course of treatment or one of the stages of providing specialized, including high-tech, medical care in a 24-hour or day hospital setting, provided there are no treatment complications requiring drug correction and/or inpatient medical interventions;

2. refusal of the patient or their legal representative from specialized, including high-tech, medical care in an inpatient or day-care setting, as determined by a medical concilium of the oncology-providing organization

3. in cases of non-compliance by the patient with prescriptions or internal regulations of the medical and prophylactic institution, provided this does not threaten the patient's life and the health of others;

4. need to transfer the patient to another medical organization in the relevant medical specialty.

The conclusion on the advisability of transferring a patient to a specialized medical organization is made after a preliminary consultation on the provided medical documents and/or a preliminary examination of the patient by specialist physicians of the medical organization to which the transfer is planned.

7. Additional Information

The prognosis of BOT depends on the type of implants, disease stage, and the presence of invasive low-grade cancer foci in the primary tumor or dissemination sites. Thus, in early-stage BOT, recurrences develop in an average of 5% of patients, and in advanced stages, in 25%. Five-year survival for stages I–II is 98%, and for stages III–IV, 82–90%, respectively. Ten-year survival for patients with non-invasive implants is 90–95%, and with invasive implants, 60–70%. The prognosis for non-serous histological types of BOT is favorable. The course of mucinous BOTs may be complicated by pseudomyxoma peritonei.

Criteria for Evaluating the Quality of Medical Care

Quality of care assessment criteria for adult female patients diagnosed with borderline ovarian tumors (ICD-10 code: C56)

References

Appendix A1. Working Group Composition

1. Ashrafyan L.A., Academician of the Russian Academy of Sciences, D.Sc. (Medicine), Professor, Deputy Director of the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health, Director of the Institute of Oncogynecology and Breast Diseases.

2. Novikova E.G., D.Sc. (Medicine), Professor, Head of the Oncogynecology Department, P. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center of the Russian Ministry of Health.

3. Khokhlova S.V., D.Sc. (Medicine), Head of the Oncological Department of Antineoplastic Drug Therapy, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health.

4. Urmancheeva A.F., D.Sc. (Medicine), Professor, Leading Researcher at the Oncogynecology Department, N.N. Petrov National Medical Research Center of Oncology of the Russian Ministry of Health.

5. Berlev I.V., D.Sc. (Medicine), Professor, Head of the Scientific Department of Oncogynecology, N.N. Petrov National Medical Research Center of Oncology of the Russian Ministry of Health.

6. Antonova I.B., D.Sc. (Medicine), Head of the Laboratory for Prevention, Early Diagnosis and Combined Treatment of Oncological Diseases, Russian Scientific Center of Roentgenology and Radiology of the Russian Ministry of Health.

7. Babaeva N.A., D.Sc. (Medicine), Leading Researcher at the Institute of Oncogynecology and Breast Diseases, Oncologist at the Oncological Department of Surgical Treatment Methods, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health.

8. Aleshikova O.I., PhD, Senior Researcher, Institute of Oncogynecology and Mammology, Oncologist at the Department of Surgical Oncology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health.

9. Mukhtarullina S.V., D.Sc. (Medicine), Head of the Oncogynecology Department, P. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center of the Russian Ministry of Health.

10. Verenikina E.V., Ph.D. (Medicine), Head of the Oncogynecology Department, Rostov Research Institute of Oncology of the Russian Ministry of Health.

11. Demidova L.V., D.Sc. (Medicine), Leading Researcher at the Radiation Therapy Department, P. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center of the Russian Ministry of Health.

12. Shevchuk A.S., Ph.D. (Medicine), Head of the Department of Combined and Radiation Treatment Methods for Oncogynecological Diseases, Research Institute of Clinical Oncology, N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health.

13. Ulrich E.A., MD, DSc, Professor, Chief Researcher at the Research Laboratory of Reproductive Technologies, Head of the "Oncofertility" Competence Center, Almazov National Medical Research Centre.

14. Krasilnikov S.E., D.Sc. (Medicine), Professor, Director of the Institute of Oncology and Neurosurgery, Oncologist, E.N. Meshalkin National Medical Research Center of the Russian Ministry of Health

15. Davydova I.Yu., D.Sc. (Medicine), Leading Researcher at the Pelvic Floor Oncosurgery Department, Moscow Clinical Scientific Center named after A.S. Loginov of the Moscow Healthcare Department

16. Krikunova L.I., D.Sc. (Medicine), Professor, Head of the Department of Radiation and Combined Treatment Methods for Gynecological Diseases, National Medical Research Radiological Center of the Russian Ministry of Health.

17. Kolomietz L.A., D.Sc. (Medicine), Professor, Head of the Gynecological Department, Research Institute of Oncology, Tomsk National Research Medical Center of the Russian Academy of Sciences.

18. Meshcheryakova L.A., MD, Physician, Federal Research and Clinical Center of Physical-Chemical Medicine of the Federal Medical-Biological Agency of Russia.

19. Kreynina Yu.M., MD, DSc, Leading Researcher at the Laboratory of Innovative Technologies of Radiotherapy and Chemoradiotherapy for Malignant Neoplasms, Russian Scientific Center of Roentgenoradiology of the Russian Ministry of Health.

20. Zhordania K.I., MD, Professor, Leading Researcher, Department of Surgical Oncology (Oncogynecology), National Medical Research Center of Oncology named after N.N. Blokhin of the Russian Ministry of Health.

21. Dubinina A.V., PhD, Senior Researcher, Department of Radiation Therapy, National Medical Research Center of Oncology named after N.N. Blokhin of the Russian Ministry of Health

22. Karseladze A.I., Professor, D.Sc. (Medicine), V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health.

23. Rubtsova N.A., MD, Head of the Department of Diagnostic Radiology, Radiologist, Herzen Moscow Research Oncological Institute – branch of the National Medical Research Center of Radiology of the Russian Ministry of Health

24. Bychenko V.G., PhD, Head of the Department of Diagnostic Radiology at the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health.

25. Solopova A.E., D.Sc. (Medicine), Associate Professor, Radiologist at the Diagnostic Radiology Department, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health.

26. Ryzhkova D.V., D.Sc. (Medicine), Professor of the RAS, Head of the Department of Nuclear Medicine and Radiation Technologies with Clinic, Chief Researcher at the Research Laboratory of Nuclear Medicine and Theranostics, Almazov National Medical Research Centre of the Russian Ministry of Health

27. Ovodenko D.L., MD, Department of Innovative Oncology and Gynecology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health.

28. Rumyantsev A.A., PhD, Oncologist at Chemotherapy Department No. 4, National Medical Research Center of Oncology named after N.N. Blokhin of the Russian Ministry of Health.

29. Slonov A.V., PhD, Chief Physician, Clinical Hospital No. 123 of the Federal Research and Clinical Center of Physical-Chemical Medicine of the Federal Medical-Biological Agency of Russia.

30. Yureneva S.V., Deputy Director for Science at the Institute of Oncogynecology and Breast Diseases, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health, D.Sc. (Medicine), Professor at the Department of Obstetrics and Gynecology.

31. Rumyantsev A.A., Ph.D. (Medicine), Head of the Antineoplastic Drug Therapy Department No. 4 of the Drug Treatment Division, N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health, Moscow

Medical Rehabilitation Section

1. Konchugova T.V., MD, PhD, Professor, Physiotherapist, Head of the Department of Preformed Physical Factors, National Medical Research Center for Rehabilitation and Balneology of the Russian Ministry of Health.

2. Eremushkin M.A., MD, PhD, Professor, Head of the Department of Exercise Therapy and Clinical Biomechanics, National Medical Research Center for Rehabilitation and Balneology of the Russian Ministry of Health.

3. Gilmutdinova I.R., Candidate of Medical Sciences, Head of the Department of Biomedical Technologies and Cell Technologies Laboratory, Transfusiologist, Dermatovenerologist, Cell Technology Specialist, National Medical Research Center for Rehabilitation and Balneology of the Russian Ministry of Health.

4. Filonenko E.V., MD, PhD, Professor, Head of the Center for Laser and Photodynamic Diagnostics and Tumor Therapy, P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center of the Russian Ministry of Health, Oncologist.

5. Bulanov A.A., MD, PhD, Senior Researcher at the Department of Clinical Pharmacology and Chemotherapy, N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health.

6. Butenko A.V., MD, PhD, Professor, Chief Physician of the Research Institute of Clinical Oncology, N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health, Chairman of the Scientific Council of the Association of Oncological Rehabilitation Specialists.

7. Nazarenko A.V., Candidate of Medical Sciences, Highest Qualification Category Physician, Head of the Radiology Department, N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health, Member of the Russian Association of Therapeutic Radiation Oncologists (RATRO), European Society for Radiotherapy & Oncology (ESTRO), Russian-American Cancer Alliance (ARCA), Russian Representative to the IAEA.

8. Obukhova O.A., Candidate of Medical Sciences, Physiotherapist, Head of the Rehabilitation Department, N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health, Member of the European Society for Clinical Nutrition and Metabolism (ESPEN), Russian Society for Parenteral and Enteral Nutrition (RESPEN).

9. Khulamkhanova M.M., Physiotherapist, Oncologist at the Rehabilitation Department, N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health.

10. Tkachenko G.A., Psychologist at the Rehabilitation Department, N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health.

11. Petrova T.A., Speech Therapist and Educator at the Rehabilitation Department, N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health.

12. Semiglazova T.Yu., MD, PhD, Leading Researcher at the Scientific Department of Innovative Methods of Therapeutic Oncology and Rehabilitation, N.N. Petrov National Medical Research Center of Oncology of the Russian Ministry of Health, Associate Professor at the Department of Oncology, I.I. Mechnikov North-Western State Medical University of the Russian Ministry of Health.

13. Ponomarenko G.N., MD, PhD, Professor, Honored Scientist of the Russian Federation, Director General of the G.A. Albrecht Federal Scientific Center of Rehabilitation of the Disabled of the Russian Ministry of Labour, Head of the Department of Balneology and Physiotherapy, S.M. Kirov Military Medical Academy of the Russian Ministry of Defense.

14. Kovlen D.V., MD, PhD, Associate Professor at the Department of Balneology and Physiotherapy, S.M. Kirov Military Medical Academy of the Russian Ministry of Defense.

15. Kasparov B.S., Candidate of Medical Sciences, Deputy Chief Physician for Outpatient Care, Head of the Clinical and Diagnostic Department, N.N. Petrov National Medical Research Center of Oncology of the Russian Ministry of Health.

16. Krutov A.A., Oncologist at the Clinical and Diagnostic Department, N.N. Petrov National Medical Research Center of Oncology, Russian Ministry of Health.

17. Zernova M.A., Exercise Therapy Instructor, N.N. Petrov National Medical Research Center of Oncology, Russian Ministry of Health.

18. Kondratyeva K.O., Medical Psychologist, N.N. Petrov National Medical Research Center of Oncology, Russian Ministry of Health.

19. Ivanova G.E., DSc, Chief Specialist in Medical Rehabilitation, Russian Ministry of Health; Head of the Department of Medical and Social Stroke Rehabilitation, Research Institute of Cerebrovascular Pathology and Rehabilitation, Pirogov Russian National Research Medical University, Russian Ministry of Health.

20. Romanov A.I., Academician of the Russian Academy of Sciences, DSc, Professor, Chief Physician, Rehabilitation Center, Administration of the President of the Russian Federation.

21. Stepanova A.M., Deputy Director for Science, Head of the Rehabilitation Department, Vosstanovlenie Private Multidisciplinary Diagnostic and Rehabilitation Center.

Healthcare Organization Section:

1. Nevolskikh A.A., DSc, Professor, Deputy Director for Clinical Work, A.F. Tsyb Medical Radiological Research Center – Branch of the National Medical Research Center for Radiology, Russian Ministry of Health.

2. Khaylova Zh.V., PhD, Chief Physician of the Clinic, A.F. Tsyb Medical Radiological Research Center – Branch of the National Medical Research Center for Radiology, Russian Ministry of Health.

3. Ivanov S.A., DSc, Professor of the Russian Academy of Sciences, Director of the A.F. Tsyb Medical Radiological Research Center – Branch of the National Medical Research Center for Radiology, Russian Ministry of Health.

4. Gevorkyan T.G., Deputy Director of the Research Institute of Clinical and Economic Radiology, N.N. Blokhin National Medical Research Center of Oncology.

No conflicts of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience of these clinical guidelines:

1. oncologists;

2. obstetricians-gynecologists;

3. general practitioners;

4. surgeons;

5. pediatric oncologists;

6. medical students, residents, and graduate students.

Table A2.1. Rating scale for levels of evidence for diagnostic methods (diagnostic interventions)

Table A2.2. Scale for assessing the levels of certainty of evidence for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Scale for assessing recommendation grades for preventive, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitation interventions)

Procedure for updating clinical guidelines. The mechanism for updating clinical guidelines provides for their systematic revision at least once every 3 years, as well as upon the emergence of new data from the perspective of evidence-based medicine regarding the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

Current instructions for medicinal products mentioned in these clinical guidelines can be found on the website http://grls.rosminzdrav.ru.

Appendix B. Physician Action Algorithms

Diagnostic and treatment flowchart for patients with borderline ovarian tumors. TAHBSO – total abdominal hysterectomy with bilateral salpingo-oophorectomy

Appendix C. Patient Information

1. If complaints of lower abdominal pain, abdominal enlargement, urinary disorders, or genital bleeding appear, consult an obstetrician-gynecologist or oncologist.

2. In case of reproductive or hormonal dysfunction, consult an obstetrician-gynecologist, endocrinologist, or oncologist.

3. For hormone replacement therapy, consult an obstetrician-gynecologist, endocrinologist, or oncologist.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. Eastern Cooperative Oncology Group / World Health Organization performance status scale

Russian title: Eastern Cooperative Oncology Group / World Health Organization performance status scale. [49]

Original title: The Eastern Cooperative Oncology Group/World Health Organization Performance Status (ECOG/WHO PS).

Source (official developer website, validation publication):

• https://ecog-acrin.org/resources/ecog-performance-status;

• Oken M.M., Creech R.H., Tormey D.C. et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982,5(6):649–55.

Type: rating scale.

Purpose: to describe the patient's level of functioning in terms of their ability to care for themselves, daily activities, and physical abilities (walking, working, etc.).

Content (template):

Scoring key (interpretation): provided within the scale itself.

Appendix G2. Karnofsky Performance Scale

Russian title: Karnofsky performance scale [50]

Original title (if applicable): KARNOFSKY PERFORMANCE STATUS

Source (official developer website, publication with validation): Karnofsky DA, Burchenal JH: The clinical evaluation of chemotherapeutic agents in cancer. In: Evaluation of chemotherapeutic agents. edn. Edited by MacLeod C. New York: Columbia University Press; 1949: 191-205

Type: rating scale

Purpose: to describe the patient's level of functioning in terms of their ability to care for themselves, daily activities, and physical abilities (walking, work, etc.).

Content (template):

Key (interpretation): provided within the scale itself