Complete Guide to Epithelial Ovarian Cancer: Diagnosis, Treatment and Follow-up

Table of Contents

• Introduction: Understanding Ovarian Cancer
• Diagnosis: How Ovarian Cancer is Detected
• Cancer Types and Molecular Features
• Cancer Staging and Risk Assessment
• Treatment for Early-Stage Cancer (Stage I-II)
• Treatment for Advanced Cancer (Stage III-IV)
• Source Information

Introduction: Understanding Ovarian Cancer

Epithelial ovarian cancer (EOC) represents a diverse group of diseases with different clinical, pathological, and molecular characteristics. Ovarian cancer is the second most lethal gynecological malignancy worldwide after cervical cancer, and it's the deadliest in developed countries. Tragically, approximately 200,000 women died from ovarian cancer globally in 2020.

Research from 1990 to 2019 shows that highly developed regions have the highest burden and mortality rates from this disease. Several factors can influence a woman's risk of developing ovarian cancer. Infertility, never having children, estrogen hormone treatment, and obesity have been reported as risk factors that might explain the rising incidence in developed countries.

Fortunately, some protective factors exist. Using oral contraceptives, especially over longer periods, and breastfeeding can reduce incidence. A recent large study revealed significant differences in risk factors across different ovarian cancer subtypes. Higher number of children, younger age at menopause, and tubal ligation were most strongly associated with reduced risk in certain cancer types, while endometriosis was associated with increased risk in others.

Diagnosis: How Ovarian Cancer is Detected

Currently, there is no reliable screening method for ovarian cancer. Most women are diagnosed based on symptoms, with the majority presenting at an advanced stage. Recognizing symptoms early is crucial, though challenging because they can be vague. Common symptoms include abdominal or pelvic pain, constipation, diarrhea, urinary frequency, vaginal bleeding, abdominal distension, and fatigue.

In advanced disease, fluid buildup in the abdomen (ascites) and abdominal masses lead to bloating, nausea, loss of appetite, indigestion, and feeling full quickly. If the disease spreads to the chest cavity, it can produce fluid buildup and respiratory symptoms.

The standard diagnostic work-up for patients suspected of having EOC should include:

• Detailed history and clinical examination
• Serum CA-125 measurement (a tumor marker)
• Additional tumor markers (CEA and CA19-9) for mucinous carcinoma
• Endoscopy if certain tumor markers are elevated
• Transabdominal and transvaginal ultrasound by expert examiner
• CT scan of chest, abdomen, and pelvis
• Pathological examination of adequate tumor sample
• Cytological assessment of pleural fluid if present

The CA-125 blood test aids diagnosis and is elevated in approximately 85% of patients with advanced disease. However, it's less useful in early-stage disease, as it's only elevated in about 50% of early-stage cases. Importantly, CA-125 is not specific to ovarian cancer and may be elevated in other cancers and benign conditions like endometriosis and ovarian cysts.

Cancer Types and Molecular Features

Epithelial ovarian cancer represents the majority (approximately 90%) of ovarian malignancies. Experts recognize at least five distinct subtypes based on detailed analysis:

High-grade serous carcinoma (HGSC) is the most common, representing 70% of cases. This aggressive form often has genetic mutations in BRCA1/2 genes and responds well to certain targeted therapies.

Endometrioid carcinoma (EC) accounts for 10% of cases and often has different genetic features including CTNNB1 and ARID1A mutations.

Clear-cell carcinoma (CCC) represents 6%-10% of cases and is associated with ARID1A and PI3KCA mutations.

Low-grade serous carcinoma (LGSC) accounts for 5% of cases and typically has KRAS and BRAF mutations.

Mucinous carcinoma (MC) represents 3%-4% of cases with CDKN2A and KRAS mutations.

Each subtype represents a distinct disease with different origin, development, clinical features, and prognosis. This complexity highlights why accurate tumor classification by expert pathologists is crucial for personalized treatment decisions.

Cancer Staging and Risk Assessment

All patients with ovarian cancer should be surgically staged according to the International Federation of Gynecology and Obstetrics (FIGO) system. This staging system classifies cancer from Stage I (confined to ovaries) to Stage IV (distant spread beyond abdomen).

There's a strong connection between the amount of tumor remaining after surgery and patient survival. Preoperative imaging can help predict whether complete tumor removal might be achievable. The assessment differentiates between tumor spread on organ surfaces versus actual organ invasion, which affects staging and treatment decisions.

When disease appears suitable for removal based on imaging, and there are no surgical or medical contraindications, surgical staging should be performed to explore the extent of disease and assess the likelihood of achieving optimal tumor removal.

Treatment for Early-Stage Cancer (Stage I-II)

The goal of surgery for early ovarian cancer is complete tumor removal and adequate staging. This typically includes comprehensive procedures to determine the exact extent of disease. Surgical staging provides crucial prognostic information and determines whether chemotherapy is needed.

Approximately 60% of patients with apparent early ovarian cancer will be found to have more advanced disease after comprehensive surgical staging, which significantly impacts treatment decisions and outcomes.

For patients who need chemotherapy after surgery, the standard treatment consists of six cycles of platinum-based chemotherapy. Research shows that the benefit of chemotherapy depends largely on the specific cancer subtype:

Adjuvant chemotherapy is generally recommended for most Stage I-IIB cancers, with either paclitaxel-carboplatin combination or carboplatin alone for six cycles. However, the benefit is uncertain and can be considered optional for certain lower-risk subtypes including low-grade serous carcinoma stage IB-IC, clear-cell carcinoma stage IA-IC1, low-grade endometrioid carcinoma stage IB-IC, and specific mucinous carcinoma types.

For young patients wishing to preserve fertility, fertility-sparing surgery can be considered after thorough discussion about potential risks. Patients with Stage IA any histotype or Stage IC1-2 with unilateral ovarian involvement and favorable histology may be candidates for preserving the unaffected ovary and uterus.

Treatment for Advanced Cancer (Stage III-IV)

In advanced ovarian cancer, surgery aims to achieve complete or optimal cytoreduction, meaning removal of all visible tumor. This has been shown to significantly increase both overall survival and progression-free survival. Achieving this often requires extensive surgical procedures that may include bowel resection, diaphragm surgery, spleen removal, and lymph node dissection.

Strong evidence suggests that surgical expertise and specialist training significantly improve complete tumor removal rates. Thus, patients with advanced disease are advised to undergo surgery in specialized centers with adequate infrastructure and experienced teams.

The timing of surgery relative to chemotherapy is carefully considered. The standard approach for patients with Stage III-IV disease is primary cytoreductive surgery if the patient is physically able and complete resection seems achievable, followed by systemic treatment. For patients where complete resection at initial surgery seems unlikely, or if extensive surgery isn't tolerable due to other health issues, chemotherapy may be given before surgery.

After surgery, systemic chemotherapy is recommended for all advanced ovarian cancer patients, with consideration for adding antiangiogenic therapy and maintenance treatments. Standard chemotherapy consists of six cycles of paclitaxel (175 mg/m²) plus carboplatin given intravenously every 3 weeks.

For patients with contraindications to paclitaxel (allergy, neuropathy, or intolerance), combining carboplatin with docetaxel or pegylated liposomal doxorubicin can be considered alternatives. For frailer patients, weekly chemotherapy with lower doses of both drugs may be an option that maintains effectiveness while potentially improving quality of life.

Source Information

Original Article Title: Newly diagnosed and relapsed epithelial ovarian cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

Authors: A. González-Martín, P. Harter, A. Leary, D. Lorusso, R.E. Miller, B. Pothuri, I. Ray-Coquard, D.S.P. Tan, E. Bellet, A. Oaknin & J.A. Ledermann on behalf of the ESMO Guidelines Committee

Publication: Annals of Oncology, Volume 34, Issue 10, 2023

Note: This patient-friendly article is based on peer-reviewed research and clinical guidelines from the European Society for Medical Oncology.