Largest study to date on prostate cancer patients finds 17% have disease-causing variant

By Piper Nicolosi, Ph.D.

In collaboration with Tulane University School of Medicine and published in JAMA Oncology,1 Invitae’s team of scientists, medical geneticists, clinical oncologists, and genetic counselors examined 3,607 men with a personal history of prostate cancer and found that approximately 17% had a positive disease-causing genetic variant (defined as pathogenic, likely pathogenic, or increased risk allele).

Unlike previous studies in hereditary prostate cancer, study participants were unselected for Gleason score (a scale ranging from 2-10 that is used to evaluate the stage and prognosis of prostate cancer based on the appearance of tissue from a biopsy), ethnicity, family history, or stage of disease. To our knowledge, this represents the largest series of prostate cancer patients examined and includes the largest sampling of non-Caucasian patients studied to date.

Examination of this population within the context of clinical testing guidelines at the time of testing, which relied heavily on family history, found that 37% did not meet testing criteria. Although such guidelines have since been revised to include Gleason score and stage of disease, we found that these factors did not correlate with positive results.

Furthermore, current clinical guidelines for colorectal cancer state that “there is insufficient evidence to support high-risk prostate cancer screening among men with Lynch syndrome.” However, 8.7% of the positive variants detected in our study were identified in genes associated with Lynch syndrome, which have available targeted therapies that would directly impact the medical management of these patients.

Our findings highlight the need for simplification and expansion of testing guidelines. We propose that guidelines be expanded to include genetic testing of all men diagnosed with prostate cancer, similar to guidelines for pancreatic, male breast, and ovarian cancer.


We believe expanded guidelines can help facilitate early identification of positive variants that may result in more frequent tumor assessment, surgery before metastasis, treatment with targeted therapies or clinical trials, as well as increased screening for the prevention of additional primary cancers.

Identification of positive variants is critical not only for the treatment of patients with prostate cancer, but also their relatives (including female relatives), who may be at increased risk for other cancer types including breast, ovarian, pancreatic, and colon. Knowledge of the presence or absence of positive variants in at-risk family members can be used to tailor screening and preventive measures when family variants are detected or provide the opportunity to forego unnecessary and often costly testing if family variants are absent.

Invitae is committed to lowering barriers to genetic testing. We see this research as another example of why testing needs to be made more accessible.

Together we can ensure that all patients who need testing can get it. Learn more about prostate cancer genetic testing at Invitae.

1. Nicolosi P, Ledet E, Yang S et al. Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines. JAMA Oncol. Published online February 7, 2019.