Ovarian Cancer Patient Case: Prognosis and Molecular Testing

Expert Leslie Randall, MD, discusses the case of a 71-year-old woman who is diagnosed with ovarian cancer. Dr. Randall reviews data with PARP inhibitors and rationale for use of maintenance therapy in patients with platinum-sensitive disease.


Leslie M. Randall, MD: This is a common case we see in practice. A 71-year-old patient presents with progressive abdominal discomfort bloating and early satiety—which are the most common symptoms of ovarian cancer—new-onset constipation, and unintentional weight loss. She has a medical history significant for postmenopausal osteoarthritis but is otherwise healthy. And on physical examination has abdominal distension and tenderness to palpation in the right lower quadrant. Overall, her ECOG [Eastern Cooperative Oncology Group] performance status is fairly well-preserved, still at 1, and her clinical workup includes a pelvic exam with the findings noted above and an ultrasound which also shows a 4.5-cm complex right ovarian mass. A CT of the abdomen, pelvis, and chest was also performed which confirmed this right head adnexal mass. Also showed suspicious lymph nodes and the retroperitoneal spaces near the ovary and confirmed the presence of ascites, which was responsible for the distension and bloating. A paracentesis was performed which confirmed a high-grade serous tumor on cytology, which was highly consistent with epithelial ovarian cancer. The patient underwent germline testing for BRCA, which was noted to have a BRCA1 mutation. Her preoperative CA 125 [cancer antigen 125] was 335 and her presumptive diagnosis was a stage III high-grade serous epithelial ovarian cancer. For treatment, the patient initially underwent primary cytoreductive surgery, which was completed with a hysterectomy removal of the suspicious lymph nodes and optimal resection of the omentum and other small tumor deposits for an R0 or complete resection. She started treatment with carboplatin and paclitaxel [Taxol] every 3 weeks and was treated for 6 cycles. She then experienced only grade 2 nausea and vomiting throughout chemotherapy but responded well to supportive measures. The CA 125 normalized and the patient achieved an overall complete response. This patient is scheduled to start niraparib [Zejula] therapy 12 weeks after the end of chemotherapy within the next couple of weeks.

Now prognosis for this patient is interesting because patients go online and read about how ovarian cancer has this terrible prognosis but I would really consider this patient to have a fairly good prognosis overall for several reasons. Number one, she did have a fairly low-volume disease at presentation and was amenable to not only surgery before chemotherapy or a primary cytoreductive surgery but was also completely resected, so those are good prognostic factors. Secondly, she has a BRCA mutation and while it’s not good for family members or cancer risk to have a BRCA mutation, but for those patients who do get ovarian cancer if they harbor a BRCA mutation, their prognosis tends to be better than patients who don’t have a BRCA mutation baseline. And now with the advent of PARP inhibitors, their prognosis is even further improved with the addition of PARP in the maintenance phase to their therapy.

Molecular testing has really changed the face of how we treat ovarian cancer, especially the epithelial types specifically, mostly for high-grade serous and endometrioid. But all ovarian cancer patients should have germline testing for not only BRCA mutations but also our clear cell tumors and mucinous tumors that can harbor Lynch [syndrome]-type mutations. We typically advocate for panel germline testing for all of our ovarian cancer patients. Those with BRCA mutations are going to be predominantly in the epithelioid types, high-grade serous, and endometrioid subtypes. Those will be the ones that will harbor most of the BRCA mutations. Beyond the germline mutations, somatic mutations for BRCA or BRCA-like genes, such as RAD51C, RAD51D, BRIP1, all of these are really important and confer sensitivity to PARP inhibitors, so it’s important to know whether patients harbor these mutations.

When providers ask me when should testing be done, I think testing needs to be done as soon as the diagnosis is made. Of course, if you have a germline mutation that could run in the family, you want to know that as soon as possible so that others can benefit from risk-reducing procedures. For the somatic testing, you need that and the germline. You need both of those in order to guide their frontline therapy that will inform your maintenance therapy. And we’ll talk about maintenance more but I think every patient should get maintenance and these genomic tests help drive our decisions as to which maintenance therapy they should receive.

Transcript edited for clarity.

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