Randomized Trial of Universal vs. Guideline-directed Germline Testing Among Young Adults With Cancer

The investigators will conduct a randomized trial among young adult (YA) cancer patients to rigorously test the hypothesis that universal testing identifies many YA patients with germline cancer risk who would be missed by conventional testing strategies, to improve adherence to risk reduction interventions among YAs with cancer susceptibility, and to increase ascertainment among relatives of these patients at increased genetic risk. The primary outcome of the randomized trial will be ascertainment of probands, but in a companion study, the investigators will also explore the incremental utility of universal testing with respect to ascertainment of risk among relatives.

Consenting patients will be immediately randomized using a computer-generated randomization algorithm using permuted variable block sizes with a concealed sequence. Randomization will be stratified by gender, National Comprehensive Cancer Network/American College of Medical Genetics and Genomics (NCCN/ACMG) referral criteria (meets/doesn't meet), and hospital (i.e., HUP vs. other Penn Medicine hospitals). Note that because of demographic differences between hospitals, the investigators are using hospital type as a proxy for race/ethnicity and so will not stratify for it separately. Randomization will occur in a 2:1 ratio (experimental: control).

Patient enrollment for genetic testing will be completed within the first 12 months. If patients receive a pathogenic or likely pathogenic result then they will be followed for up to five years to evaluate the impact of the clinical decision support. Recruitment will end when approximately 1238 subjects are enrolled. Subjects will be recruited across five Penn Medicine sites, including Hospital of the University of Pennsylvania (HUP), Penn Presbyterian Medical Center (PPMC), Pennsylvania Hospital (PAH), Chester County Hospital (CCH), and Lancaster General Hospital (LGH).

Patients who are notified of their eligibility status and indicate an interest in study participation will be directed to an educational website about hereditary cancer risk and the implications of genetic testing for patients and family members. They will also be provided information about the study. If they wish to consent after viewing the educational module, patients will be automatically sent to REDCap where, following consent, they also will complete a brief survey to obtain demographics and family history information. Patients will also have the option of reviewing information, providing consent, and completing sociodemographic and family history data collection via paper forms.

Upon provision of signed informed consent and determination of high/low risk (based on ACMG/NCCN guidelines and determined by either the study research coordinator or clinical genetic counselor as outlined above), patients will be randomized in a 2:1 ratio (experimental: control) into one of the two study arms stratified by gender, meeting NCCN/ACMG criteria, and hospital type (HUP vs. other). Study enrollees will be encouraged to sign up to use their local patient portal, if they haven't done so already, in order to receive study communications, health information, and heath maintenance alerts.