Approaching a Case of Advanced Serous Ovarian Cancer

David O’Malley, MD:This is a 69-year-old female who presented with classic symptoms consistent with ovarian cancer: increase in abdominal girth and increase in shortness of breath. She was found on imaging to have both pleural effusions and ascites. She had a CAT scan, which also showed upper abdominal disease. To help with her symptoms, she had a thoracentesis and a paracentesis and then a core biopsy of her omental mass. This was consistent with a high-grade serous ovarian cancer.

At that point, we had an extensive discussion with regard to the patient and the options of treatment. She elected for an attempt at surgical reduction. She was taken into the operating room, and an exploratory laparotomy was performed. We were able to remove a large volume of disease, but she did have some persistent disease, given the procedure. When she recovered from surgery, she elected to proceed on a clinical trial, which utilized a doublet of carboplatin and paclitaxel in addition to bevacizumab. Bevacizumab was then continued as a maintenance therapy.

This is a very typical patient presentation in ovarian cancer. Most patients will actually be seen by several practitioners before the diagnosis is made. Obviously, when we’re looking at this patient, she had a quick diagnosis because of the biopsy that was performed. They will often present with subtle symptoms for weeks or months before being diagnosed, often with early satiety, increase in abdominal girth, or vague abdominal symptoms. It is very important to differentiate these symptoms: which are worrisome versus those that aren’t worrisome.

If you ask primary care practitioners if their patients have these symptoms, most of them say, “Yes, they have them.” How do we differentiate those symptoms that are worrisome versus those that are not? Those symptoms that persist and increase over time are the more worrisome symptoms. Because of her ascites and pleural effusions, she had a quicker evaluation.

The most challenging or controversial aspect of this patient up to this point is the decision to proceed with attempted cytoreduction. Typically, for patients with pleural effusions—particularly if they’re large and require a thoracentesis—or significant upper abdominal disease, we do not think we’d be able to remove all of the visible disease. Obviously, we want to get an optimal outcome, which was previously defined as disease less than 1 cm, but we really modified that to patients who have no disease at the end of the surgery. Because of her pleural effusions, many practitioners and patients would elect to receive neoadjuvant chemotherapy, attempting to dry up the ascites and the pleural effusion and allow them to recover more easily after the surgery.

Typically, with neoadjuvant chemotherapy, we’re going to use 3 cycles prior to surgery and 3 cycles of cytotoxic chemotherapy afterward. With this particular patient, she elected to go onto a clinical trial, which utilized a platinum doublet, as well as bevacizumab.

Testing for germline, as well as somatic,BRCAmutations with molecular testing on the tumor has undergone a significant change recently. The big impact has been the approval for rucaparib in patients with somaticBRCAmutations. In addition, wonderful research performed throughout both the United States and the world has shown that not only do we haveBRCA1andBRCA2but we also have other HRD genes that could potentially have an impact on families, as well as treatment options for patients. In my practice, we utilize a combination of both germline and somatic testing in any patient who has been diagnosed with advanced ovarian cancer, and we really perform germline testing for any patient who has been diagnosed with ovarian cancer. By sending this test out, both the germline and the somatic or molecular testing, at the very least we’re looking forBRCAmutations, as well as those other HRD genes. In addition, in the tissue testing, we’ll look for mismatch repair proteins, as well as microsatellite instability.

Transcript edited for clarity.

Case: A 69-year-old Woman with Advanced Serous Ovarian Cancer

January 2017

• A 69-year-old Caucasian woman presented to the emergency department with shortness of breath
• PMH: mild HTN and DM, medically managed; morbid obesity
• PE: large volume ascites
• CT angiography (chest) showed large bilateral pulmonary effusions, no pulmonary thromboembolism
• Laboratory findings remarkable for CA 125, 525U/mL
• Thoracentesis (1500 cc); cytology showed high grade adenocarcinoma
• Paracentesis (4500 cc); cytology showed high grade adenocarcinoma
• Core biopsy of omentum; high grade serous carcinoma; p53 (+)/ PAX 8 (+) /WTI and CX 7 (+); BRCA1/2 wild-type
• The patient underwent debulking surgery with incomplete cytoreduction
• She was treated as part of a clinical trial with carboplatin/paclitaxel + bevacizumab followed by continuous bevacizumab maintenance

April 2018

• Fifteen months later, the patients complained of severe abdominal bloating and fatigue
• Imaging showed multifocal recurrence within the abdominal cavity
  • CA 125, 322 U/mL
  • ECOG 1
• She was started on carboplatin/docetaxel
• After 6 cycles of therapy she had a partial response to therapy with bulky residual disease
• She was initiated on rucaparib maintenance therapy, 600 mg BID
• Hb fell to 7.2 g/dl, managed with treatment interruption and then dose reduction to rucaparib 500 mg