Linking To And Excerpting From “Newly diagnosed and relapsed epithelial ovarian cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up”

Note to myself: The resource below is not that helpful to a primary care physician. Instead, I recommend Adnexal Tumors from emedicine.medscape.com.
Updated: Apr 22, 2022
Author: Nelson Teng, MD, MS, MBA, PhD

Today, I review, link to and excerpt from Newly diagnosed and relapsed epithelial ovarian cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. [No abstract] [Full-Text HTML] [Full-Text PDF]. Volume 34, Issue 10p833-848October 2023 Open Archive.

All that follows is from the above resource.

Incidence and epidemiology

Epithelial ovarian cancer (EOC) represents a heterogeneous spectrum of disease entities at a clinical, pathological and molecular level. Ovarian cancer is the second most lethal gynaecological malignancy worldwide behind cervical cancer and the first in developed countries, with ∼200 000 women dying globally in 2020.1 A study of epidemiological trends from 1990 to 2019 showed that highly developed regions had the highest burden and mortality.2

Deleterious germline BRCA1/2 mutations (gBRCA1/2-muts) are associated with a 16%-65% increased risk of EOC, predominantly of high-grade serous histology.⁵ Women with mutations in mismatch repair genes (Lynch syndrome) have a 10%-12% lifetime risk of developing EOC, which tends to be of either EC or CCC subtype.⁶

Diagnosis, pathology and molecular biology

Diagnostic work-up

There is currently no reliable screening method for ovarian cancer. Most women are diagnosed based on symptoms, with the majority presenting at an advanced stage. Recognised symptoms include abdominal/pelvic pain, constipation, diarrhoea, urinary frequency, vaginal bleeding, abdominal distension and fatigue. In advanced disease, ascites and abdominal masses lead to bloating, nausea, anorexia, dyspepsia and early satiety. Extension of disease into the pleural cavities can produce effusions and respiratory symptoms.

The standard work-up for patients suspected of having EOC should include detailed history and clinical examination with relevant laboratory and imaging tests (Table 1). Measurement of serum cancer antigen 125 (CA-125) aids diagnosis and is elevated in ∼85% of patients with advanced disease. CA-125 is less useful in early-stage disease, as it is only elevated in ∼50% of International Federation of Gynecology and Obstetrics (FIGO) stage I cases. Elevated CA-125 is not specific to ovarian cancer and may be elevated in non-gynaecological malignancies and benign conditions (e.g. endometriosis and ovarian cysts).⁷

Work-up if EOC is suspected
• Detailed history and clinical examination • Serum CA-125 • Serum CEA and CA 19-9, in the case of MC, and endoscopy, if either or both are elevated • Transabdominal and transvaginal US by expert examiner • CT of thorax, abdomen and pelvis • Pathological examination of adequate tumour sample from diagnostic biopsy or surgical specimen • Cytological assessment of pleural effusion if present

Table 1

Diagnosis of EOC

CA 19-9, carbohydrate antigen 19-9; CA-125, cancer antigen 125; CEA, carcinoembryonic antigen; CT, computed tomography; EOC, epithelial ovarian cancer; MC, mucinous carcinoma; US, ultrasound.

Measuring serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 levels in addition to CA-125 may help distinguish primary mucinous ovarian tumours from a gastrointestinal metastasis. In this scenario, endoscopies should be considered, especially if the CA-125/CEA ratio is ≤25/1.⁸

Initial imaging should comprise pelvic ultrasound (US; transabdominal and/or transvaginal) and computed tomography (CT) of the thorax, abdomen and pelvis to complete clinical staging and aid surgical planning. US-based diagnostic models [International Ovarian Tumor Analysis (IOTA) Simple Rules risk model or IOTA Assessment of Different NEoplasias in the adneXa (ADNEX) model] are preferable to CA-125, the human epididymis protein 4 (HE4) or the Risk of Ovarian Malignancy Algorithm, as they are superior in distinguishing between benign and malignant ovarian tumours and performed better than the Risk of Malignancy Index in a randomised controlled trial (RCT).⁸

A definitive diagnosis of ovarian cancer requires pathological examination by an expert pathologist of tumour samples from either a diagnostic biopsy or, preferably, a surgical specimen. An adequate amount of tissue, particularly if neoadjuvant chemotherapy (ChT) is planned, allows genetic tumour testing for therapeutic stratification. If a complete pathological response is achieved, sufficient viable tumour tissue may be unavailable for genetic testing following interval cytoreductive surgery (ICS). Cytological assessment of ascites (in early-stage disease) and of pleural fluid (if present and safely assessable) is required to complete staging.