High-grade serous carcinoma (HGSC) is the most prevalent and aggressive subtype of ovarian cancer. “High-grade” signifies that the cancer cells appear highly abnormal under a microscope and are poorly differentiated, meaning they grow and spread rapidly. The term “serous” indicates that the cancer originates from serous epithelial cells, which are similar to the cells that line the fallopian tubes, ovaries, and the internal abdomen (peritoneum). “Carcinoma” is the medical term for a cancer that begins in epithelial tissue.
HGSC accounts for approximately 75% of all epithelial ovarian cancers. Because it develops and spreads quickly, it is often diagnosed at an advanced stage. Although frequently referred to as ovarian cancer, many cases of HGSC start in the fallopian tubes and spread to the ovaries or peritoneum. Due to this shared origin and behavior, cancers of the ovary, fallopian tube, and peritoneum are often grouped and treated together.
Origins and Risk Factors
For a long time, it was believed that HGSC arose from the surface layer of the ovary. Current research now points to the fimbriae, the finger-like projections at the end of the fallopian tubes, as the starting point for many cases. From there, the cancerous cells can travel to the ovary and the peritoneum, the membrane lining the abdominal cavity.
Genetic predisposition is a primary factor in developing HGSC, with mutations in the BRCA1 and BRCA2 genes being significant risk factors. These genes are tumor suppressors that repair DNA damage and prevent cells from growing and dividing too rapidly. When these genes are mutated and do not function correctly, the risk of developing certain cancers, including HGSC, increases substantially.
Beyond genetics, other factors can influence a person’s risk. Age is a prominent factor, with the majority of HGSC cases occurring in individuals after menopause. A strong family history of ovarian, breast, or peritoneal cancer can also indicate an elevated risk.
Symptoms and Diagnosis
The symptoms of high-grade serous carcinoma are often subtle and non-specific, leading to diagnostic delays as they can be mistaken for less serious gastrointestinal or urinary issues. The most common symptoms include persistent bloating, a feeling of fullness after eating only a small amount of food, and pelvic or abdominal pain. Some individuals may also experience urinary symptoms, such as an urgent or frequent need to urinate.
A physician will typically start with a physical and pelvic exam. If there is suspicion of an ovarian or related cancer, imaging tests are ordered. A transvaginal ultrasound is often one of the first imaging techniques used to get a detailed view of the ovaries and fallopian tubes. A computed tomography (CT) scan of the abdomen and pelvis may also be used to see if the cancer has spread.
A blood test to measure the level of a protein called CA-125 is another common diagnostic tool. CA-125 is a tumor marker, and elevated levels can be associated with HGSC. However, this test is not definitive on its own, as other non-cancerous conditions can also cause CA-125 levels to rise. A definitive diagnosis requires a biopsy, where a small sample of tissue is surgically removed and examined by a pathologist.
Treatment Approaches
The primary treatment for high-grade serous carcinoma typically involves a combination of surgery and chemotherapy. The initial surgical procedure, known as cytoreduction or debulking, aims to remove all visible signs of the tumor from the abdomen and pelvis. The success of this surgery, often measured by the amount of residual disease left behind, significantly impacts the patient’s prognosis.
Following recovery from surgery, the standard of care involves systemic chemotherapy. The most common chemotherapy regimen for HGSC is a combination of a platinum-based drug, such as carboplatin, and a taxane, like paclitaxel. These drugs are typically administered intravenously every few weeks for several cycles.
Targeted therapies have emerged in the management of HGSC, particularly for maintenance after initial treatment. PARP inhibitors are a class of drugs that have shown effectiveness, especially in patients with BRCA1 or BRCA2 mutations. These medications work by blocking a specific pathway that cancer cells use to repair their DNA, leading to cell death. PARP inhibitors are often used as a maintenance therapy to help delay or prevent the cancer from recurring after the completion of chemotherapy.
Prognosis and Monitoring
The prognosis for high-grade serous carcinoma is influenced by several factors, including the stage of the cancer at diagnosis and the effectiveness of the initial treatment. Because HGSC is an aggressive cancer that is often diagnosed at an advanced stage, it has a high rate of recurrence, even after successful surgery and chemotherapy.
Due to the high risk of recurrence, long-term monitoring is a standard part of post-treatment care. This surveillance typically includes physical exams and periodic blood tests to monitor CA-125 levels. A rising trend in CA-125 can be an early indicator of recurrence, often before any symptoms appear.
Imaging studies, such as CT or PET scans, may also be used as part of the monitoring process, though they are not always performed on a fixed schedule unless there is a specific concern. This ongoing surveillance allows doctors to detect a recurrence as early as possible, providing the best opportunity to begin subsequent lines of treatment.