Appropriate Germline Testing for Ovarian Cancer Patients

Measure Specification

According to the National Cancer Institute, in 2024 there were approximately 19,680 new cases of ovarian cancer in the United States and an estimated 12,740 died of the disease. Knowledge about underlying molecular alterations in ovarian cancer could allow for more personalized diagnostic, predictive, prognostic, and therapeutic strategies for the patient but also have clinical implications for her family members.

Despite current recommendations for all women diagnosed with ovarian cancer to receive genetic testing, only approximately 30 percent of women undergo any genetic testing. Germline mutations in BRCA1 and BRCA2 have been identified in 13-15 percent of women diagnosed with ovarian cancer, and somatic mutations are found in an additional 7 percent. The high incidence of these mutations and the advent of therapy targeted toward BRCA mutations warrant testing in all individuals diagnosed with ovarian cancer for the purpose of determining treatment recommendations, risk of other cancers, and need for cascade testing of family members.

Testing for germline mutations should be done at the time of initial diagnosis. Presence of a germline mutation in a woman with advanced cancer identifies her as eligible for maintenance treatment with a poly (ADP-ribose) polymerase (PARP) inhibitor (olaparib) after response to initial chemotherapy. The NCCN Ovarian Cancer guideline similarly states that, since germline and/or somatic BRCA1/2 testing informs selection of maintenance therapy for those with stage II-IV disease who are in complete response (CR) or partial response (PR) after first-line platinum-based chemotherapy, it is important to establish BRCA1/2 mutation status for patients who may be eligible for maintenance therapy following completion of platinum-based first-line chemotherapy.

The goal of tumor testing in the upfront setting is to optimize identification of molecular alterations that can inform the use of interventions with demonstrated benefit in this setting, such as PARP inhibitors. Molecular alterations that should be probed for in this setting include BRCA1/2 status, loss of heterozygosity, or homologous recombination status, in the absence of a germline BRCA mutation.

Although the FDA recently approved frontline maintenance therapy for patients independent of mutation status following the publication of the ASCO guideline, emerging evidence is expected to indicate an overall survival benefit in ovarian cancer patients with germline mutations. Germline mutation testing therefore provides prognostic information for ovarian cancer patients, as those with germline mutations are expected to derive greater benefit from therapy.

Additionally, and consistent with other recommendations in the ASCO guideline, germline testing also informs potential clinical implications for the relatives of ovarian cancer patients with germline mutations, who should themselves be offered individualized genetic risk evaluation, counseling, and genetic testing as reflected in Recommendation 1.5 in the ASCO germline testing guideline.

The two evidence-based clinical guidelines listed below directly support that all women diagnosed with ovarian cancer should undergo germline testing, as mutation status informs treatment, and carries implications for the need for cascade testing in family members. The measure will enhance compliance with the clinical guidelines by assessing the rates by which eligible providers pursue germline testing in ovarian cancer patients, ideally improving patient outcomes, and identifying at-risk patient relatives.

Germline and Somatic Tumor Testing in Epithelial Ovarian Cancer: ASCO Guideline Recommendation 1.1: All women diagnosed with epithelial ovarian cancer should be offered germline genetic testing for BRCA1, BRCA2, and other ovarian cancer susceptibility genes, irrespective of their clinical features or family cancer history. Somatic tumor testing for BRCA1 and BRCA2 pathogenic or likely pathogenic variants should be performed in women who do not carry a germline pathogenic or likely pathogenic BRCA1/2 variant (Type: evidence- based, benefits outweigh harms; Evidence quality: intermediate; Strength of recommendation: strong).

Recommendation 3.1 Women with epithelial ovarian cancer should be offered testing, as outline in recommendation 1.1, at the time of diagnosis. This has implications for therapeutic decision making (Type: evidence-based, benefits outweigh harms; Evidence quality: high; Strength of recommendation: strong). NCCN Clinical Practices Guidelines in Oncology: Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer Recommendation: Because germline and/or somatic BRCA1 and BRCA2 status may inform future options for maintenance therapy, all patients with histologically confirmed ovarian, fallopian tube, or primary peritoneal cancer should undergo genetic risk evaluation and germline and somatic testing, if not previously performed.

In the absence of a BRCA1/2 mutation, homologous recombination deficiency testing may also be considered, as it may provide information about the magnitude of benefit of PARP inhibitor maintenance therapy following first-line chemotherapy (category 2B).

This measure contains one strata defined by a single submission criteria. This measure produces a single performance rate. For the purposes of MIPS implementation of this measure, this patient-process measure is submitted a minimum of once per patient during the performance period. The most advantageous quality data code will be used if the measure is submitted more than once.