When Ovarian Cancer Comes Back: Recurrence Questions

Ovarian cancer here also covers fallopian tube cancer and primary peritoneal cancer. The three are treated as one group. When the cancer returns, three facts shape the visit.

Is the return confirmed? How long has it been since the last platinum drug? Has the tumor been tested for folate receptor alpha?

NCI's PDQ summary for health professionals is blunt about how common this moment is. About 80% of people relapse after first-line chemo built on a platinum drug and a taxane.

CA-125 is a protein measured in blood. PDQ says checking it every 1 to 3 months after treatment became near-universal practice. A rise is the most common way a silent relapse is first spotted.

PDQ also reports the trial that tested whether acting on that early signal helps. It was the MRC OV05 trial, run with a European research group. It registered 1,442 patients in remission.

When CA-125 doubled above the normal range, patients were split at random. One group was told and treated at once. The other kept the result blinded and waited for symptoms.

Median survival was 25.7 months in the early group. It was 27.1 months in the group that waited. The hazard ratio was 0.98, with a 95% confidence interval of 0.8 to 1.2. That is no measurable gap.

Waiting pushed second-line chemo back by a median of 4.8 months. A quality-of-life study ran alongside. It found early treatment was worse for quality of life.

PDQ's follow-up section says it plainly. Early pickup by scan or by CA-125 has not been shown to change outcomes. PDQ adds that this evidence barely shifted CA-125 habits at five US cancer centers over a decade.

CA-125 still has two jobs PDQ names. It sorts a relapse as platinum-sensitive or platinum-resistant. It also helps pick who might benefit from repeat surgery.

PDQ splits recurrent disease by the gap since the first course of chemo ended.

• Platinum-sensitive. The cancer returns more than 6 months after that chemo stopped. PDQ says a platinum drug, such as carboplatin, should be considered again.
• Platinum-resistant. The cancer returns within 6 months of stopping.
• Platinum-refractory. The cancer grows before that first course even ends.

For the last two groups, PDQ says platinum is usually not useful. It says trials should be considered.

So one number does a lot of the routing: the months since the last carboplatin or cisplatin. It is worth confirming out loud. It is a dividing line rather than a switch, though. A relapse at five months and one at seven months are not opposites, and histology, whether you have already had a PARP inhibitor, your BRCA and HRD results, how you tolerated platinum last time and what you want out of treatment all move the plan as well.

PDQ tabulates the drug pairs used at first relapse. Two rows are worth knowing.

Cisplatin or carboplatin with paclitaxel was tested in 802 patients. It was compared with a platinum drug plus a non-taxane. PFS, meaning time before the cancer grew again, was 11 months versus 9. Overall survival was 24 months versus 19.

Carboplatin with gemcitabine was tested in 356 patients. The comparison was carboplatin alone. PFS was 8.6 months versus 5.8. Overall survival was 18 months versus 17.

One drug is only for tumors that carry a specific marker. PDQ describes the phase III MIRASOL trial. It enrolled 453 women with platinum-resistant, high-grade serous disease. Each had already had one to three courses of chemo.

Every woman had to have high tumor levels of folate receptor alpha. PDQ defines that as at least 75% of cells staining 2+ or higher on a lab stain.

Half received mirvetuximab soravtansine by vein every 3 weeks, at an amount worked out from body weight. The rest got the doctor's choice of paclitaxel, liposomal doxorubicin, or topotecan. Median PFS was 5.62 months with the new drug. It was 3.98 months with chemo.

The trade-off is easy to miss. Eye exams were required in the trial. And 56% of women on the new drug had an eye side effect.

That is why asking about folate receptor alpha testing is practical, not academic. Without the test result, the option is not on the table.

PDQ explains why this class is tied to the platinum question. Sensitivity to platinum drugs is a sign of homologous recombination deficiency, a flaw in DNA repair. Tumors with that flaw are the ones most likely to respond to a PARP inhibitor.

PDQ lists olaparib's approved use as maintenance in recurrent disease, for people with a complete or partial response to platinum chemo, regardless of BRCA status. The strength it lists is a 300 mg tablet twice a day. That is the label's reference figure, not a prescription. The amount your own oncologist writes is the one to take, and it is often lower, because the dose is commonly reduced for anaemia or other side effects. If your tablets do not match the label figure, ask why rather than assuming a mistake.

The SOLO2 trial tested those tablets against placebo. It enrolled 295 women with platinum-sensitive relapse and BRCA1 or BRCA2 changes. Of those, 196 got olaparib and 99 got placebo. Median PFS was 19.1 months with olaparib and 5.5 months with placebo.

Serious side effects occurred in 18% of the olaparib group and 8% of the placebo group. PDQ names anemia, belly pain, and bowel blockage as the most common.

PDQ names three randomized trials of a second debulking operation. They are GOG-0213, DESKTOP III, and SOC 1. Who could join differed in all three.

So did the share of women whose surgeons removed all visible cancer. It was 67% in GOG-0213, 75% in DESKTOP III, and 77% in SOC 1.

PDQ notes SOC 1 was published with immature survival data. A Dutch trial closed early in 2015. It had signed up only 27 of a planned 230 women in five years.

PDQ also says the role of radiation in recurrent ovarian cancer has not been defined. That is a real gap, not an oversight.

• How many months since the last platinum drug, and does that mean sensitive, resistant, or refractory?
• Has the tumor been tested for folate receptor alpha, and what did the stain show?
• Given the MRC OV05 result, why treat now rather than at symptoms?
• If repeat surgery is raised, what is the real chance of removing all visible cancer?
• Which trial is this advice based on, and what was the PFS gap?
• If mirvetuximab soravtansine is chosen, who does the eye exams, and how often?

• Call 911 or go to an emergency department if you keep vomiting and cannot pass stool or gas, or your belly is swollen and stays that way with pain that does not settle. Recurrent ovarian cancer can block the bowel, and a blockage needs treating at once.
• Call your care team at once, day or night, if you have a temperature of 100.4°F (38°C) or higher while on chemotherapy. CDC calls that a medical emergency, since the drugs may have left too few white cells to fight the infection off. Go to an emergency department if you cannot reach them quickly, and tell staff you are on chemotherapy.
• Call 911 or go to an emergency department if you have new breathlessness, or chest pain that gets worse when you breathe in or cough. Ovarian cancer and its treatment raise the risk of a blood clot in the lung, and that is treated in hours, not after a callback.
• Call your care team within a day or two if pain, bloating, or pelvic pressure is new or getting worse, you feel full after a few mouthfuls, or you need to pass urine far more often. PDQ lists these as the signs these cancers cause, and says they often go unrecognized, which delays diagnosis.
• Call your care team within a day or two if you are on mirvetuximab soravtansine and your vision blurs, or your eyes become dry, gritty, or painful. Eye problems affected 56% of people on that drug in MIRASOL.

Stage and restaging words are covered in cancer staging. The general shape of a return workup is in when cancer comes back. Tumor tests like the folate receptor alpha stain are explained in biomarker testing. Symptom care alongside treatment is in palliative care.

• NCI PDQ: ovarian cancer, health professional version
• NCI: drugs approved for ovarian cancer
• NCI: infections and neutropenia during cancer treatment
• MedlinePlus: intestinal obstruction
• CDC: understanding your risk for blood clots with cancer
• CDC: fever during cancer treatment