Overview of Guideline Recommendations for Molecular Testing in Ovarian Cancer
An expert gynecologic oncologist reviews guideline recommendations for molecular testing in ovarian cancer and shares his testing practices.
Case: A 49-Year-Old Woman with BRCA-WT Ovarian Cancer
- A 49-year-old presented to her primary care physician complaining of abdominal bloating and nausea
- PMH: mild HTN
- FH: mother died of breast cancer at age 59; cousin on mother’s side died of ovarian cancer at age 65
- Imaging: CT reveals small-volume ascites, bilateral 8-cm adnexal masses
- Labs: CA 125, 285 U/mL
- Surgical intervention: she underwent exploratory laparotomy followed by omentectomy, bilateral salpingo-oophorectomy, and resection of peritoneal nodules; optimal cytoreduction with < 1 cm of residual disease after surgery
- Diagnosis: stage IIIC HGSC
- Treatment: She was treated with IV carboplatin and paclitaxel w/ NK1, 5HT3, and dexamethasone CINV prophylaxis
- TRAEs: She experienced persistent daily nausea with vomiting on day 1 after chemotherapy
- Follow-up: After completion of chemotherapy, CA 125, 14.2; clinically NED; patient reports continuing daily nausea
Transcript:
Chad A. Hamilton, MD: ASCO [American Society of Clinical Oncology] has provided a very helpful guideline in 2020 on recommendations for molecular testing in ovarian cancer. And they state, to summarize, that all women diagnosed with epithelial ovarian cancer should have germline genetic testing for BRCA1 and BRCA2 and other ovarian cancer susceptibility genes. And then they take a cascade approach in women who do not carry a pathogenic germline mutation in BRCA1 or BRCA2, then they recommend [that] somatic tumor testing for BRCA1 and BRCA2 or other likely pathogenic variants should be performed. And that’s for women with ovarian cancer, but really focused on serous ovarian cancer or high-grade endometrioid. Now for patients with clear cell endometrioid or mucinous subtypes, then somatic testing should be offered [along with] consideration of mismatch repair deficiency in those populations.
The NCCN [National Comprehensive Cancer Network] guidelines echo ASCO to a great extent. There’s more parallel testing, I think, in the NCCN recommendations. They recommend that in addition to germline testing, somatic testing should be done to optimize identification of molecular alterations that can inform interventions. And they’re specifically referring to, of course, BRCA1 and BRCA2 mutations, but also potentially looking for signs of homologous recombination deficiency [HRD]. And that may be through an HRD scoring system or loss of heterozygosity, depending on which molecular platform you’re looking at. And certainly, these can help guide your discussions with your patients on magnitude of potential benefit of PARP inhibitors. SGO [Society of Gynecologic Oncology] and ESMO [European Society for Medical Oncology] have also recently echoed these recommendations. There’s pretty good concordance between the various specialty societies and guideline recommendations.
In the recurrent setting, we do look to identify a broader range of potential molecular targets. I mentioned the mismatch repair, but also potentially microsatellite instability, tumor mutational burden, BRAF mutations, folate receptor alpha, which has become very important because of its new indication in platinum-resistant ovarian cancer, NTRK fusions or mutations if these weren’t done previously. And these may be all the more important in less common histologies where there’s really limited approved therapeutic options for those patients.
My personal approach to testing and our group’s approach has been driven by a number of things. And this seems to be a little bit of an ever-changing landscape. We decided early on that we wanted to do testing in parallel between germline and somatic testing. And first, for full disclosure, I don’t have any financial holdings or dealings with any of the molecular platform corporations or companies. We looked at Myriad [Genetics, Inc] initially and have had a long-term relationship with them with our germline testing using the Myriad MyRisk platform. And we were also doing somatic testing, but decided that HRD, and specifically their HRD score, was important to us, so we moved towards the Myriad MyChoice platform to have an HRD scoring platform now. Our institution has also had relationships with Tempus molecular testing, so we do some of our next-generation sequencing with Tempus. And with the importance of folate receptor alpha coming on the scene, we have also transitioned to some of our testing through Caris [Life Sciences], which could provide us a platform for more extensive testing that also included the requisite testing for folate receptor alpha for the new indication for platinum-resistant disease and the folate receptor alpha–targeted therapies. So in short, it’s a shifting landscape. We have not been wed to one company, and they all have their pros and cons. But I think they’re all doing a great job of trying to adapt and provide us the information that we need to impact patients.
Transcript is AI-generated and edited for clarity and readability.
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