High-grade serous carcinoma (HGSC) is the most common type of ovarian cancer. It starts when cells in the ovaries, fallopian tubes, or peritoneum (the inside lining of the abdomen) begin to grow out of control.

Doctors used to think ovarian cancer and fallopian tube cancer were two related but different cancers. However, research shows that many HGSC cases begin in the fallopian tubes and later spread to the ovaries or peritoneum. Now scientists usually group ovarian, fallopian tube, and primary peritoneal cancers together.

What Is High-Grade Serous Carcinoma?

Doctors classify ovarian cancers based on the type of cell where the cancer starts. The three main types of ovarian cancer are:

• Epithelial
• Germ cell
• Stromal

Nearly 9 in 10 cases of ovarian cancer are epithelial tumors, which develop in the cells that cover the ovaries and fallopian tubes. Epithelial ovarian cancer includes several subtypes — the most common is high-grade serous cell carcinoma.

Cancer grade describes how abnormal the cancer cells look under a microscope. Lower-grade serous tumors look more like healthy ovarian cells. Higher-grade serous tumors look more abnormal and grow faster, in a disorderly way. HGSC can spread quickly and tends to have a worse prognosis (outlook). About 3 in 4 cases of epithelial ovarian cancer are HGSC.

High-Grade Serous Ovarian Carcinoma: Causes and Risk Factors

Cancer develops when genes in cells change in abnormal ways. Genes give instructions that help cells function properly. When genes change, they can cause cells to grow too fast, ignore signals to stop growing, or fail to repair damage. In HGSC, nearly all cases — about 95 percent — involve mutations (changes) in a gene called TP53, which helps control cell growth and repair.

One small study found that about 25 percent of people with HGSC had inherited changes in the BRCA1 or BRCA2 genes. These mutations cause even more damage inside cells. BRCA mutations are often passed down in families. People born with changes in these genes have a higher risk of ovarian cancer and breast cancer.

High-Grade Serous Carcinoma Risk Factors

Most cases of ovarian cancer aren’t caused by inherited gene changes. Instead, they usually develop over time due to factors that increase the chances of these gene changes. Common risk factors for ovarian cancer include:

• Older age
• Endometriosis
• Radiation exposure in the pelvic area

Researchers have also found that people with pelvic inflammatory disease are more likely to develop HGSC. In addition, people who’ve had breast cancer are three times more likely to develop this subtype.

Some factors can lower the risk of ovarian cancer, including:

• Giving birth
• Breastfeeding
• Using oral contraceptives (birth control pills)

Symptoms of High-Grade Serous Carcinoma

High-grade serious carcinoma often doesn’t cause noticeable symptoms until the cancer has grown or spread. When symptoms do appear, they may include:

• Pain in the abdomen or pelvis
• Abdominal bloating
• Loss of appetite or feeling full quickly
• Frequent urination
• Urinary urgency (feeling the need to urinate right away)

If you notice any of these symptoms, talk to your doctor. These signs are often caused by something other than cancer, but it’s still important to get them checked.

Diagnosing High-Grade Serous Carcinoma

If your doctor suspects ovarian cancer, they may use several tests to help make a diagnosis. Testing can include:

• A pelvic exam — Feeling for changes in the reproductive organs that might suggest cancer
• Imaging tests, such as ultrasound, CT, or MRI scans — Looking for abnormal growths
• Blood tests — Checking for signs of cancer, including levels of specific proteins
• Surgery — Removing a mass to see if it’s cancerous
• Biopsy — Collecting a tissue sample for detailed lab testing

A pathologist (a doctor who studies tissue samples) will examine the biopsy samples to see if cancer is present and determine the cancer type. HGSC cells have a distinct appearance and often produce proteins that set them apart from other types of ovarian cancer.

One common blood test checks the level of a protein called cancer antigen 125 (CA-125). High levels of CA-125 can be a sign of ovarian cancer.

High-Grade Serous Carcinoma Stages

Doctors use a staging system called FIGO (International Federation of Gynecology and Obstetrics) to stage ovarian cancer. Staging describes how far the cancer has spread in the body, known as metastasis. (Stages may be written as Roman numerals, such as stage III or IV.) The FIGO stages for ovarian cancer are:

• Stage 1 — Cancer is in one or both ovaries or fallopian tubes but hasn’t spread elsewhere.
• Stage 2 — Cancer has spread from the ovaries or fallopian tubes to nearby organs in the pelvis, like the uterus, bladder, or rectum, but not to lymph nodes or distant organs.
• Stage 3 — Cancer has spread beyond the pelvis to lymph nodes or other areas in the abdomen but not to distant parts of the body.
• Stage 4 — Cancer has spread to distant organs such as the spleen, liver, lungs, or tissues outside the pelvis and abdomen.

About 70 percent of HGSC cases are diagnosed at an advanced stage (stage 3 or 4).

High-Grade Serous Carcinoma Treatments

Doctors typically recommend a combination of ovarian cancer treatments, including surgery, chemotherapy, and sometimes targeted therapy. Your treatment plan may also include radiotherapy or immunotherapy, depending on factors like the cancer’s stage and genetic features.

Surgery

HGSC treatment usually begins with surgery — sometimes called debulking surgery or cytoreductive surgery — with the goal of removing as much cancer as possible. For early-stage tumors, this may involve removing only one ovary and fallopian tube. For advanced stages, multiple tumors and possibly parts of other organs or tissues affected by cancer may be removed. Doctors also can assess the stage of cancer during the procedure.

Chemotherapy

Most people with HGSC receive chemotherapy, typically after surgery and depending on the stage of the cancer. Common options include platinum-based drugs like carboplatin and cisplatin, often combined with other types such as paclitaxel or docetaxel. Chemotherapy is sometimes given before surgery to shrink tumors — this is called neoadjuvant chemotherapy.

Targeted Therapy

Targeted therapies may be used for ovarian cancer that has specific gene changes. These drugs focus on specific cancer cell functions. Options include:

• Angiogenesis inhibitors such as bevacizumab, which block blood supply to tumors
• Poly (ADP-ribose) polymerase (PARP) inhibitors like olaparib and rucaparib, especially for cancers with BRCA mutations
• Antibody-drug conjugates, which deliver treatment directly to cancer cells

Targeted therapy may be used alone or with other treatments.

Treatment for Relapsed HGSC

Even after successful treatment, you’ll need regular follow-up visits with your healthcare team. They’ll look for signs that the ovarian cancer has relapsed (come back). In most cases, HGSC eventually returns, often within three years. Cancers with a later stage or grade have a greater chance of relapse. If the cancer returns, treatment options may include:

• A different chemotherapy regimen
• Repeat surgery
• Another targeted therapy
• Radiation or immunotherapy

Clinical Trials

Clinical trials may be an option for people at any stage of ovarian cancer. Participants in a clinical trial may be able to access new medications or treatment plans.

Prognosis for High-Grade Serous Carcinoma

Because HGSC usually isn’t discovered until after it has spread, it can be difficult to treat. The median overall survival for people with this type of ovarian cancer is about 3.3 years — meaning half of the people studied lived longer than 3.3 years after diagnosis, and half lived for less time. However, outcomes vary widely depending on several factors.

Your cancer stage is one important factor. People with early-stage HGSC tend to have better outcomes than those with advanced ovarian cancer.

Researchers have calculated survival rates across all stages of invasive epithelial ovarian cancer. Five-year relative survival rates estimate how likely someone is to live at least five years after diagnosis, compared to people without that cancer type:

• When cancer is located only in the ovaries or fallopian tubes, the five-year relative survival rate is 92 percent.
• When cancer has spread to nearby tissues, the rate is 71 percent.
• When cancer is metastatic (has spread to distant organs or tissues), the rate is 32 percent.

Other factors also influence outlook. For example, people with HGSC who are younger than 65 are more likely to live longer than those who are older. If you want to understand more about your individual prognosis, your oncologist or care team can help explain how your unique situation may affect treatment options and outcomes.

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