Metastatic Ovarian Cancer: What to Ask

Ovarian cancer spreads differently from most solid tumors. NCI describes the hallmark of ovarian epithelial, fallopian tube and primary peritoneal cancer as early peritoneal spread. The peritoneum is the lining of the abdominal cavity. Cells shed from the tumor and seed that lining, rather than travelling first through blood vessels.

Because of that, the word "metastatic" needs a second question attached. FIGO is the staging system used for these cancers. Stage III means spread to the peritoneum outside the pelvis, or to lymph nodes behind the abdomen. Stage IV means distant spread that is not peritoneal. Stage IVA is fluid around the lung with cancer cells in it. Stage IVB is spread into the substance of an organ, or to organs and nodes outside the abdomen.

Ask which of these describes your scan. Stage III and stage IV are both advanced. They are treated along similar lines. The words are still not interchangeable.

One more point about the diagnosis itself. NCI treats ovarian, fallopian tube and primary peritoneal cancer as one group. The evidence says many high-grade serous cancers, the most common subtype, actually begin in the fimbriae at the end of the fallopian tube. So if your report names the fallopian tube or the peritoneum, the treatment path is the same.

• What is my FIGO stage, and what is the exact cell type on the pathology report?
• Is the plan surgery first, or chemotherapy first with surgery in the middle?
• What is the goal you are aiming for with this plan?
• Has genetic testing been ordered, and when will the result come back?

NCI lists several accepted approaches for advanced disease. One is surgery followed by platinum-based chemotherapy. Another is surgery before or after chemotherapy, with more treatment added afterward. Other listed options add bevacizumab, add PARP inhibitors, or add heated chemotherapy into the abdomen, known as HIPEC. Chemotherapy alone is listed for people who cannot have surgery. NCI adds that its effect on overall survival has not been proven.

The order of surgery and chemotherapy is a real decision. Chemotherapy given first is called neoadjuvant treatment. Surgery in the middle of it is called interval debulking.

Whichever order is chosen, one surgical measure carries huge weight. NCI's list of favorable prognostic factors includes lower disease volume before surgery. It also includes smaller residual tumor after the first cytoreductive surgery. Cytoreductive surgery means taking out as much visible tumor as possible.

That gives you a specific, answerable question. How much visible disease was left at the end of my operation? Ask for the number in millimeters. Ask too whether "no gross residual disease" was achieved.

The rest of NCI's favorable list is worth seeing. It includes younger age, good performance status, a cell type other than mucinous or clear cell, a well-differentiated tumor, earlier stage, no ascites, and carrying a BRCA1 or BRCA2 variant.

Genetic testing here is treatment planning. It is not only about family risk.

BRCA1 and BRCA2 are DNA repair genes. When one is broken, the cell leans on a backup repair route. That route depends on an enzyme called PARP. Block PARP with a drug, and those cells pile up DNA breaks they cannot fix. They then die. Healthy cells with intact BRCA survive.

The trial that established this at diagnosis is SOLO-1 (NCT01844986). It enrolled 391 patients with newly diagnosed advanced high-grade serous or endometrioid ovarian cancer. All carried BRCA1 or BRCA2 variants and had responded to platinum chemotherapy. They received maintenance olaparib, taken as tablets twice a day, or placebo. Olaparib's licensed maintenance strength is 300 mg twice daily, but whether you take that amount is your oncologist's call and it is written on your own prescription — pharmacies and centres adjust it, so go by that sheet rather than by this paragraph. After a median follow-up of 41 months, the risk of progression or death was 70 percent lower with olaparib. Progression-free survival at 3 years was 60 percent with olaparib and 27 percent with placebo.

The trade-off is measurable too. Grade 3 and 4 adverse events hit 39 percent on olaparib, versus 18 percent on placebo. The most common were fatigue, vomiting and anemia. Twelve percent stopped the drug, versus 2 percent on placebo. Quality-of-life scores did not differ much between the groups.

Questions to bring:

• Have I had germline testing, which looks at inherited genes in my blood, and tumor testing as well?
• If I carry a BRCA1 or BRCA2 variant, would maintenance olaparib or another PARP inhibitor follow chemotherapy?
• If I do not carry one, has my tumor been tested for homologous recombination deficiency?

NCI notes that sensitivity to platinum chemotherapy is itself a sign of homologous recombination deficiency. A cancer that responds well to platinum is more likely to benefit from a PARP inhibitor. Our page on biomarker testing explains how these reports are ordered and read.

NCI lists the options for recurrent or persistent disease. They are platinum-containing chemotherapy; bevacizumab, other targeted drugs and PARP inhibitors, with or without chemotherapy; chemotherapy with or without bevacizumab; immune checkpoint inhibitors; and antibody-drug conjugates.

The dividing question at recurrence is time. How long did the cancer stay away after platinum treatment? That interval shapes whether platinum is used again. Ask your oncologist to say the interval out loud, in months. Then ask what it means for the choice in front of you.

One safety test deserves its own mention. The DPYD gene controls how the body clears capecitabine and fluorouracil. A harmful variant can cause severe toxicity from a standard dose. If either drug is on the table, ask whether DPYD testing applies to you.

Advanced ovarian cancer causes problems that are treatable when caught early. Bowel obstruction is the main one.

• Call 911 or go to an emergency department if you are breathless at rest, or you have severe abdominal pain with vomiting that will not stop and no bowel movement or gas. That combination points to a blocked bowel, which needs assessing at once. Go too for a temperature of 100.4°F (38°C) or higher while you are receiving platinum-based chemotherapy or a PARP inhibitor. Both push your white cells down, and CDC treats fever in someone on chemotherapy as a medical emergency, so it needs an emergency department rather than a same-day call.
• Call your care team the same day if you have colicky abdominal pain with repeated vomiting, or a belly that is swelling and tender. Also call the same day if you are on a PARP inhibitor and feel breathless, dizzy or unusually exhausted, which can mean anemia.
• Call your care team within a day or two if your belly is getting bigger over days, clothes feel tight at the waist, or you feel full after a few mouthfuls. Building ascites can be drained rather than endured.

Ask for these thresholds in writing, with a daytime number and an after-hours number.

Symptom-focused care belongs alongside treatment from the start, not at the end. Our page on palliative care explains what that team does, including draining ascites and controlling nausea.

For the disease overall, see ovarian cancer.

• NCI PDQ on ovarian and fallopian tube cancer, for doctors
• NCI PDQ on ovarian cancer, for patients
• SEER stat facts on ovarian cancer
• StatPearls (NCBI) — Bowel Obstruction
• NCI — Infection and Neutropenia During Cancer Treatment
• CDC — Watch Out for Fever (Preventing Infections in Cancer Patients)