New recommendations from a large, multidisciplinary consensus conference published this week in the Journal of Clinical Oncology suggest expanding use of genetic testing to guide treatment for men with prostate cancer, including the use of panel testing and testing patients with early stage disease.
The full consensus statement can be found in the Journal of Clinical of Oncology.
Taken together with research recently presented by Invitae, the publications underscore the utility of increased access to genetic testing for men with prostate cancer across all stages of disease.
Invitae was among the non-voting sponsors of the conference, which gathered more than 100 experts across a number of specialties with the goal of developing recommendations for how clinicians can use genetic testing to help patients benefit from precision medicine approaches to prostate cancer.
“This framework provides a very thoughtful approach to implementing genetic testing for prostate cancer treatment, screening and family testing,” Sarah Nielsen, a medical affairs liaison at Invitae who previously participated in the conference, said in a statement.
“Importantly, the framework recognizes that changes in a number of different genes can increase prostate cancer risk and therefore encourages greater use of panel testing for men with metastatic disease,” Nielsen said. “With new precision therapies linked to specific genetic changes, increased genetic testing can help identify patients who could benefit from these approaches.”
Among the consensus conference recommendations:
Larger panels are useful for patients with metastatic disease
Large germline panels and somatic testing were recommended for patients with metastatic prostate cancer. Of the approximately 12-17% of men with metastatic prostate cancer who harbor germline variants, the majority are found in DNA damage repair genes such as BRCA1, BRCA2, ATM, CHEK2, PALB2, and the DNA mismatch repair genes. Large panels provided information across these and other genes of significance, information which is increasingly informing options for PARP inhibitors, immune checkpoint inhibitors, platinum chemotherapy, and clinical trials.
Genetic information can support early diagnosis and inform disease surveillance
Germline test results are increasingly important for early detection, as men with BRCA2 variants exhibit higher rates of prostate cancer, often with a younger age at diagnosis and more clinically significant disease. Among patients with early-stage disease, emerging data suggest that men with germline BRCA2 mutations and possibly ATM mutations have higher rates of upgrading of prostate biopsies while on active surveillance, suggesting the utility of genetic information in shaping surveillance strategies after diagnosis.
Importance of using genetic information requires novel strategies to increase access to counseling resources
The guidelines recommend broad access to genetic counseling support but shortages of genetic counselors and wait times for traditional genetic counseling workflows will require development of alternate models for timely and responsible delivery of genetic testing for men and their families. The consensus framework provides suggestions for clinicians on how to counsel and provide alternatives to traditional in-person appointments for patients across a number of issues related to testing, including using pretest education materials and the use of telehealth genetic counseling sessions.
A study presented at the American College of Medical Genetics and Genomics online annual meeting further underscored the frequency of actionable variants expanded testing can help uncover.
The study of 2,252 men who participated in Invitae’s Detect Prostate Cancer program found an overall positive rate of 13% with no statistical differences in rates among stages of disease. Only half of patients with an actionable variant reported a family history suggestive of increased risk. Nearly three-quarters (71%) of positive patients were eligible for management guidelines and/or potentially eligible for approved precision therapies or clinical trials. These data suggest that broader testing criteria and greater access to testing leads to better informed care for patients and their families.
The consensus conference noted the need for additional research into the associations between genetics and prostate cancer in African-American men, who are 1.8 times more likely to be diagnosed with and 2.2 times more likely to die from prostate cancer. Importantly, this study included 16% participation among African-Americans, which is greater participation than previous similar studies, aligning to the consensus conference research priorities.
