Streamlined Genetic Testing in Prostate Cancer
Phase: NA
Conditions: Prostate Cancer
Sponsor: Georgetown University

 
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Revised: October 30, 2018 
NCT04359758 
 
Streamlined Genetic Testing in Prostate Cancer 
 
October 24, 2022 
 
 

 
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1.0 
Study Summary 
 
Study Title 
Streamlined Genetic Testing In Prostate Cancer 
Study Design 
Pilot Randomized Controlled Trial 
Primary Objective 
To evaluate the impact and efficacy of a streamlined genetic 
education and testing intervention for men with prostate 
cancer. 
Secondary 
Objective(s) 
 
Research 
Intervention(s)/ 
Investigational 
Agent(s)  
Streamlined genetic education and testing intervention. 
IND/IDE #  
n/a 
Study Population 
Eligible participants are men who are currently being 
followed at MGUH or MWHC for metastatic prostate cancer 
or Gleason 7+ prostate cancer with Ashkenazi Jewish 
ancestry or Gleason 7+ with a family history of breast, 
ovarian, pancreatic or prostate cancer.  
Sample Size 
120 
Study Duration for 
individual 
participants 
Three-months. 
Study Specific 
Abbreviations/ 
Definitions  
MGUH: Medstar Georgetown University Hospital; MWHC: 
Medstar Washington Hospital Center; PV: Pathogenic 
Variant; VUS: Variant of Uncertain Significance; ST: 
Streamlined Testing; UC: Usual Care; EMR: Electronic 
Medical Record; SRBSR: Subject Recruitment and 
Biospecimen Shared Resource 
 
 

 
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2.0 
Objectives* 
 
Genetic testing is established as part of clinical care for women with breast and ovarian 
cancer. Clear guidelines have led to increasing genetic testing participation among eligible 
women. Identifying pathogenic variants (PVs) in cancer susceptibility genes has important 
treatment, management and risk reduction implications for breast and ovarian cancer 
patients and their family members. Men are just as likely as women to carry a PV in a 
cancer risk gene and men with prostate cancer are at particularly high risk for carrying a 
PV. NCCN guidelines recommend germline genetic testing in all men with metastatic 
prostate cancer or with Gleason 7+ prostate cancer and Ashkenazi Jewish ancestry or a 
family history of prostate, breast, ovarian or pancreatic cancer. These guidelines are likely 
to expand given recent studies suggesting that 17% of prostate cancer patients may harbor 
a cancer susceptibility PV and that current referral criteria miss many of these patients. 
Prostate cancer patients with a PV in BRCA1 or BRCA2 (BRCA) have more aggressive 
prostate cancers, are at risk for other primary cancers (e.g., male breast and pancreatic) and 
their family members are at risk for a variety of cancers. Thus, genetic testing of prostate 
cancer patients has implications for treatment, management, and risk reduction for the 
patient and his family members. 
Despite these benefits and existing referral guidelines, few men with prostate cancer are 
tested. This reflects low genetic counseling referral and participation, since men who attend 
genetic counseling get tested at the same high rate as women. Low participation in genetic 
counseling is likely due to men’s underestimation of the personal health relevance of 
testing and lack of physician genetic counseling referral. Thus, the requirement to obtain 
individual genetic counseling prior to genetic testing may be a barrier to the receipt of 
guideline consistent genetic testing. In fact, recent evidence suggests that traditional 
comprehensive, patient-centered, educationally focused pre-test genetic counseling often 
does not match the needs of patients. Further, as genetic referral guidelines continue to 
expand, demand for genetic counseling will outstrip delivery capacity. Thus, alternative 
approaches that raise awareness and facilitate access to genetic testing are needed to 
maximize our ability to extend the benefits of testing to prostate cancer patients and their 
family members while at the same time accommodating increased demand and conserving 
scarce genetic counseling resources.  
In the proposed pilot, we will develop and test a proactive and streamlined pre-test genetic 
education (ST) print intervention designed to speed, simplify and target genetic testing 
delivery for prostate cancer patients.  Participants randomized to ST will have the option 
to proceed directly to genetic testing bypassing traditional pre-test genetic counseling. In 
contrast, usual care (UC) participants will be informed that they meet guidelines for genetic 
counseling referral and will be provided with contact information to schedule a standard 
telephone pre-test genetic counseling session. All participants with a PV or variant of 
uncertain significance (VUS) will be scheduled for a telephone genetic counseling 
disclosure session. ST participants who are found not to carry a PV or VUS will have this 
result disclosed via clinical letter while disclosure for all UC participants will be per 
standard clinical care by the genetic counselor by phone. By proactively identifying eligible 
patients, providing streamlined information and facilitating genetic testing, the ST 
intervention will increase awareness, facilitate informed testing decisions, remove the 
barrier of pre-test genetic counseling and improve genetic testing delivery capacity. 

 
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We will enroll eligible prostate patients who were diagnosed between 2010 and 2019 and 
are being followed within radiation and medical oncology clinics at the MedStar 
Georgetown University Hospital (MGUH) and MedStar Washington Hospital Center 
(MWHC). In this initial pilot, we will not focus on newly diagnosed patients but instead 
will focus on patients who are being followed for a number of reasons: 1) Substantial 
numbers of patients who are currently being followed have now become candidates for 
genetic testing based on updated guidelines and 2) This will allow us to maximize our 
potential sample size within the one year framework of this grant, allowing us to obtain 
preliminary efficacy data in preparation for a planned multisite R01 study of newly 
diagnosed patients with high risk localized or metastatic disease. By providing information 
particularly salient to prostate cancer patients, reducing barriers to genetic testing and 
proactively facilitating genetic testing delivery, we expect that our proactive and 
streamlined approach will yield increased uptake of genetic testing. Our specific aims are: 
1: Evaluate the impact of ST vs. UC on genetic testing uptake. H1.1: Patients 
randomized to ST will be more likely to complete genetic testing compared to UC. H1.2: 
Participants randomized to ST will make better informed genetic testing decisions 
(characterized by high knowledge, risk comprehension and concordance with attitudes) 
compared to UC. H1.3: Few patients in the ST arm will opt for traditional genetic 
counseling prior to testing. 
2: Evaluate patient satisfaction and psychosocial outcomes in ST vs. UC. H2.1: 
Compared to UC, those randomized to ST will be more satisfied with their genetic testing 
decision and will have less decisional regret.    
3: Evaluate the impact of ST vs. UC on uptake of cascade testing in unaffected family 
members. In exploratory analyses designed to provide effect size estimates, we will 
compare the arms on rates of genetic testing in relatives of patients found to carry a PV.  
3.0 
Background* 
 
Germline Genetic Testing in Prostate Cancer. Up to 17% of men with prostate cancer 
have an inherited PV in a cancer gene. For many of these men, this knowledge may  impact 
their medical management. Prostate cancer patients with BRCA PV develop higher risk 
disease than non-carriers. Prostate cancer patients with a BRCA PV with localized disease 
have more frequent nodal involvement, higher Gleason scores, more T3/T4 disease and 
lower cause specific overall survival at 5 years. Men with metastatic castration-resistant 
prostate cancer have significantly shorter cause specific overall survival in BRCA2 carriers 
vs. non-carriers. The use of single agent PARP inhibitors in patients with BRCA PVs and 
metastatic castration-resistant prostate cancer was associated with high rates of response, 
leading the FDA to grant breakthrough therapy designation for olaparib and rucaparib in 
patients with BRCA positive metastatic castration resistant prostate cancer. NCCN 
guidelines suggest germline testing in patients with castration resistant metastatic prostate 
cancer to guide the early use of platinum chemotherapy as well as for eligibility for clinical 
trials using PARP inhibitors. In addition, prostate cancer patients with localized Gleason 
Grade 7+ prostate cancer are recommended to consider genetic testing if they have a family 
history of breast, ovarian, pancreatic or prostate cancer or are of Ashkenazi Jewish 
ancestry, regardless of family history . All prostate cancer patients with a BRCA PV are at 
increased risk for second malignancy (e.g., pancreatic cancer, male breast cancer, 
melanoma). The identification of a PV in a prostate cancer patient also has important 

 
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implications for his male and female family members who can use test results to guide their 
cancer risk reduction and management decisions. Thus, the identification of a PV in a 
prostate cancer patient may often have treatment and risk management implications for 
the patient and his unaffected family members. 
Awareness and Access to Genetic Testing. Despite clear benefits and established 
guidelines, few men with prostate cancer get genetic testing. Men underestimate the 
personal relevance of BRCA mutations and have poorer knowledge and awareness of 
testing. Although physicians are less likely to refer men for genetic counseling than women 
and genetic education materials are generally not targeted to men, evidence indicates that 
when provided with adequate information men have increased uptake rates. Finally, 
emerging evidence also suggests that the requirement for traditional in-person genetic 
counseling may be a barrier to genetic testing among men. While men and women have 
comparable rates of genetic testing uptake after genetic counseling, men are much less 
likely to participate in genetic counseling. Thus, our intervention is designed to increase 
appropriate uptake of genetic testing by proactively providing relevant genetic information 
emphasizing the personal and family relevance of testing to prostate cancer survivors while 
reducing barriers to genetic testing. 
These goals align with recent changes in genetic service delivery. Given rapidly increasing 
demand for genetic services, genetic counseling capacity has emerged as a rate limiting 
factor. This lack of capacity will become more significant as genetic testing expands in 
cancer and beyond - prompting consideration of alternative delivery approaches that 
improve access and efficiency. While studies have generally indicated that traditional 
genetic counseling results in positive participant outcomes, recent research suggest that the 
quantity, relevance and complexity of the information provided in genetic counseling does 
not always match patient needs. This is particularly true in the cancer setting where the 
issues covered in traditional genetic counseling may not be of primary concern. Further, 
most patients who meet clinical referral criteria will not be found to carry a PV. Thus, 
requiring comprehensive pre-test genetic counseling may not meet the needs of patients 
and survivors, is inefficient and may serve as a barrier to testing.    
Given the unsustainability of the entrenched genetic counseling model, alternative 
strategies must be considered. We are at the forefront of developing practice changing 
alternatives to traditional genetic service delivery. We were the first to document the 
impact of rapid presurgical genetic testing for newly diagnosed breast cancer patients and 
that access to genetic counseling can be safely and effectively expanded via telephone 
delivery. Both of these approaches are now part of standard care. More recently, we and 
others have focused on streamlining content and delivery to more effectively address 
access and demand while removing barriers that patients find overwhelming or irrelevant. 
An approach labeled ‘direct testing’ or ‘post-test only’, provides patients with brief print 
information prior to testing. This approach has been used in studies of population-based 
testing and in newly diagnosed breast, ovarian and colorectal cancer patients. A recent 
single-arm trial of a brief pre-test summary letter for newly diagnosed breast cancer 
patients yielded high patient satisfaction and only 2% of participants contacted the study 
genetic counselor with questions. Although these studies provide promising preliminary 
data, it is important to note the lack of RCTs and the focus on populations with high rates 
of testing. We propose an RCT designed to: 1) proactively deliver genetic education to 
increase awareness and knowledge among patients who underutilize testing; 2) eliminate 

 
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the pre-test genetic counseling requirement for patients who wish to proceed directly to 
testing; and 3) direct scarce genetic counseling resources to patients who receive a PV 
result – the patients most vulnerable to adverse outcomes. This pilot will provide 
preliminary data supporting a planned R01 for a multisite RCT of ST vs UC in newly 
diagnosed prostate patients. 
4.0 
Study Endpoints* 
4.1 
Primary and secondary endpoints:  
1. Genetic test uptake 
2. Receipt of pre-test genetic counseling 
3. Psychosocial outcomes (Satisfaction, distress, decision regret) 
4. Use of cascade testing among unaffected family members of 
mutation carriers 
5.0 
Study Intervention/Investigational Agent 
The streamlined testing (ST) intervention includes: proactive identification and contact of 
patients eligible for genetic services, streamlined pre-test genetic education, facilitated 
delivery of genetic testing, targeted genetic counseling disclosure for patients with a PV or 
variant of uncertain clinical significance (VUS) and a clinical disclosure letter for patients 
who do not carry a PV. We have developed a range of media for cancer risk 
communication, including print, electronic and in-person education. The ST print materials 
will include the following topics: 1) Introduction and explanation of genetic testing 
guidelines for prostate cancer patients; 2) Explanation of panel testing and potential genetic 
testing outcomes (positive, negative, uncertain variant); 3) Personal implications of a PV 
(cancer risks associated with a positive genetic testing result; treatment/management, risk 
management for second cancers); 4) Implications for family members; 5) Legislation to 
protect against genetic discrimination; 6) Process of genetic testing: DNA collection (saliva 
kit), costs, and insurance coverage; 7) Options for and logistics of genetic counseling: pre-
test counseling is optional unless required by insurance; post-test genetic counseling for all 
positives (no charge for telephone genetic counseling). Drawing on our prior work, the ST 
materials will include text, images, illustrations and graphics. We expect that the material 
will take 10-15 minutes to review. Participants randomized to the usual care (UC) arm 
will be sent a letter from their physician indicating that they meet eligibility criteria for 
genetic counseling and recommending that they schedule genetic counseling. UC 
participants can receive free telephone genetic counseling through the study. 
 
6.0 
Procedures Involved* 
6.1-6.4 The objective is to develop and pilot a novel streamlined approach to 
deliver genetic education and testing to the rapidly increasing number of 
prostate cancer patients who meet guidelines for genetic referral. Our 
streamlined genetic testing approach is designed to facilitate genetic education 
and testing for men with prostate cancer. The intervention will incorporate 
proactively delivered print educational materials in lieu of pre-test genetic 
counseling. The materials will increase awareness, expand access, provide 

 
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balanced information to foster informed genetic testing decisions and reduce 
barriers to facilitate the delivery of genetic testing. All men who are found to 
carry a PV or variant of uncertain significance (VUS) in a cancer risk gene will 
have an individual telephone genetic counseling disclosure session with a board-
certified genetic counselor. We will recruit 120 prostate cancer survivors who 
meet clinical referral criteria. After a baseline survey, we will randomize 
participants to: ST vs. UC. Participants will complete a follow-up survey at 2-
3-months post-randomization. Our primary outcome is genetic testing uptake.  
Eligibility and Accrual. Men eligible for this study are currently being followed at 
MGUH or MWHC for either:  
Metastatic prostate cancer;  
Gleason 7+ prostate cancer.  
We will exclude patients who have had, or are already scheduled for genetic 
counseling or testing for BRCA1 or BRCA2 mutations. We will also exclude men 
who cannot participate in English and provide meaningful consent. We will recruit 
participants from medical and radiation oncology clinics at MGUH and MWHC. 
These clinics currently follow well over 1000 eligible patients.   
Gender and Minorities. Participants will be adult men. Given the racial/ethnic 
breakdown of the clinics we are recruiting from. We expect that at least 30% of 
participants will be members of racial/ethnic minority groups. 
Recruitment. Working with our clinical collaborators and the Survey, Recruitment 
and Biospecimen Collection Shared Resource (SRBSR) will obtain contact 
information of potentially eligible patients from clinical databases and/or the EMR. 
We will mail an introductory letter describing the study (from the study MPIs and 
the patient’s physician), opt-out postcard/phone number, informed consent 
document and a print version of the baseline survey to all potentially eligible 
participants. We will also email electronic versions of these materials for patients 
who prefer to complete them online. Two-weeks following this mailing, an SRBSR 
research assistant (RA) will call patients who have neither opted out nor completed 
the baseline survey. For men who have not returned the consent document, we will 
use an IRB-approved verbal consent for completing the baseline survey and request 
return of the written consent prior to randomization. Following completion of print 
or electronic consent and the baseline survey, the RA will randomize participants. 
Men randomized to ST will be sent a priority mail packet with detailed genetic 
testing educational material. Men randomized to UC will be mailed a letter 
informing them that they meet guidelines for genetic counseling and provided with 
contact information to schedule a genetic counseling appointment with a LCCC 
genetic counselor. 
Randomization. Following completion of the baseline survey and consent 
document, an RA will randomize participants via computer-generated random 
numbers in blocks of 8 and a ratio of 1:1. Participants will be notified of their 
random assignment via letter and email. 

 
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Assessments. We will administer baseline (T0) and 2- to 3-month (T1) follow-up 
telephone/electronic surveys. Genetic testing uptake will be assessed via clinical 
records and basic clinical and demographic information abstracted from the EMR. 
See Table 1 for assessment instruments and schedule of administration. 
Table 1. Measures 
Variables 
Measures 
T0 
T1 
Covariates/Background 
Variables 
Demographics, clinical variables, family history (EMR/survey) 
X 
 
Health Literacy 
Brief Health Literacy Screening Tool 
X 
 
Genetic Test Uptake 
Study Records 
 
X 
Knowledge/Risk 
Comprehension 
Genetic Knowledge Scale and Perceived Mutation Risk.  
X 
X 
Attitudes 
Adapted version of the Multimodal Measure of Informed 
Choice (MMIC), Fatalism, Medical Mistrust Index 
X 
 
Decision Regret 
Decisional-Regret Scale.  
 
X 
Decision Satisfaction 
Satisfaction with Decision Scale.  
 
X 
Distress 
Cancer distress: PROMIS Anxiety and Depression; Genetic 
testing distress MICRA.  
X 
X 
Quality of 
Life/Functional Status 
PROMIS Physical Function and Social Function Short Forms 
X 
X 
Cascade Testing 
Number of relatives who have proceeded with genetic testing. 
 
X 
 
Streamlined Testing (ST) Intervention. Men randomized to ST will be sent a 
priority mail packet with the ST print education materials and information on how 
to proceed with genetic testing. ST participants will have the option of proceeding 
directly to genetic testing or scheduling a telephone genetic counseling session. The 
content of the ST intervention is described in section 5.0 above.   
Usual Care (UC). After completion of the baseline survey, UC participants will be 
sent a letter from their physician indicating that they meet eligibility criteria for 
genetic testing, recommending that they schedule genetic counseling and providing 
a contact telephone number to schedule their session. Patients may opt for free 
telephone genetic counseling.   
Genetic Testing. Participants who choose to pursue genetic testing will be offered 
a standard clinical multigene panel of at least 40 genes, including BRCA and genes 
associated with potential differential diagnoses (e.g., Lynch syndrome). All testing 
will be performed by Invitae, a CLIA certified clinical lab not affiliated with the 
GLCCC. Invitae offers genetic testing free of charge to eligible prostate cancer 
patients (all study participants will be eligible for free genetic testing through 
Invitae). Prior to proceeding with genetic testing, participants will be required to 
sign and return a clinical genetic testing consent form, after which we will mail 
them an at-home DNA kit for saliva collection which will be returned directly to 
Invitae (shipping costs are pre-paid). 
7.0 
Data and Specimen Banking* 
7.1 All information will be retained for five years after the completion of the study. 
Only the PI, research staff and data managers will have access to this information.  

 
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All paper documents will be securely stored in the participant’s research file, 
which will be kept in a locked cabinet in research team offices within secure 
buildings. In all data sets, including those with genetic testing and counseling 
information, we will use ID numbers only. A separate data set linking names with 
ID numbers will be accessible only through password protected and secure data 
programs and available only to trained study staff.  
7.2 What data will be stored: 
Hospital/physician medical records 
Lab, pathology and/or radiology results 
Interviews/questionnaires 
 
7.3 This data will not be shared.  
 
8.0 
Sharing of Results with Subjects* 
8.1 
Upon receipt of a positive genetic test result or a variant of uncertain 
clinical significance, participants in either arm will be contacted by a board-
certified genetic counselor to schedule a telephone disclosure session. This 
session will follow standard clinical protocols for the delivery of genetic 
test results. Participants in the ST arm who receive a negative result will be 
notified by mail only, but may choose to schedule a free telephone genetic 
counseling session if they wish.  They and their referring physician will 
receive a copy of the test report along with a standard clinical letter prepared 
by a board-certified genetic counselor.  
9.0 
Study Timelines* 
9.1 
Participants will remain in the study for 3 months after randomization. 
We expect participant enrollment to be completed within three-
months. 
The anticipated study completion date is 9/1/20. 
10.0 Inclusion and Exclusion Criteria* 
10.1 
Screening for Eligibility: The Survey, Recruitment and Biospecimen 
Collection Shared Resource (SRBSR) will work with our clinical collaborators to 
obtain a list of potentially eligible patients from the clinical databases and the EMR. 
To each potentially eligible patient, we will mail an introductory letter (from the 
study Principal Investigators and the patient’s physician), opt-out postcard/phone 
number, informed consent document and baseline survey (we will also email 
electronic versions of these materials). Two-weeks following this mailing, we will 
call all patients who have not opted out or completed the baseline survey. At the 
start of this telephone call we will confirm study eligibility.  
10.2 Inclusion Criteria:  
• Men who are being followed at MGUH or MWHC for metastatic prostate 
cancer or Gleason 7+ prostate cancer.  

 
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Exclusion Criteria: 
• Above age 80. 
• Previous cancer genetic counseling or currently scheduled for 
cancer genetic counseling related to the BRCA1 or BRCA2 genes. 
• Have had or are scheduled for germline cancer genetic testing of 
the BRCA1 or BRCA2 genes. 
• Cannot participate in English 
• Are not capable of providing informed consent  
10.3 
We will exclude adults unable to provide meaningful informed consent, 
individuals under the age of 18 and prisoners. Since the study focuses on prostate 
cancer survivors, women are ineligible. 
 
11.0 Vulnerable Populations* 
11.1 This research does not involve individuals from vulnerable populations.  
12.0 Local Number of Subjects 
12.1 120 subjects will be recruited locally.  
13.0 Recruitment Methods 
13.1 
Working with our clinical collaborators, the Survey, Recruitment and 
Biospecimen Collection Shared Resource (SRBSR) will obtain contact information 
of potentially eligible patients from the clinical databases and the EMR. We will 
mail an introductory letter (from the study MPIs and the patient’s physician), opt-
out postcard/phone number, informed consent document and baseline survey (we 
will also email electronic versions of these materials) to all potentially eligible 
patients. Participants who do not wish to be contacted further for the study or are 
ineligible for the study will be able to easily opt out using an enclosed postcard, 
toll-free telephone line or electronic mail address. Patients who have questions 
about the study can also contact the study team via the toll-free telephone line.  
Two-weeks following the initial study mailing, we will call patients who have not 
completed the baseline survey or opted out. After confirming eligibility, explaining 
the study and answering any questions, an SRBSR RA will administer an IRB-
approved verbal consent for the baseline survey. A verbal consent will allow us to 
complete the minimal risk baseline survey in a timely fashion. Participants will then 
be required to complete the print or electronic informed consent document prior to 
randomization. We have successfully used this approach in multiple previous trials. 
After providing informed consent, participants will complete the 10-minute 
baseline survey over the telephone (participants will have the option to complete 
the survey electronically).  
13.2 
Subject Source: Participants will be prostate cancer patients/survivors who 
are currently being followed by one of our physician co-investigators (i.e., have had 
an appointment in July 2017 or later).  

 
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13.3 
Method to identify subjects: Prostate cancer patients who are currently 
being followed by one of our physician co-investigators will be identified via 
clinical databases or through the EMR. We will generate a list of patients who 
potentially meet our eligibility criteria. Each of these patients will be mailed a 
packet of study information and will have eligibility confirmed via an eligibility 
screener or contact by the SRBSR.  
13.4 
Participants will be identified by their treating physician who will query 
the clinical records for patients who meet the study eligibility criteria.  
13.5 
Recruitment Materials: Study staff will mail a packet to potentially eligible 
patients. This mailing will include: an introductory letter describing the study, 
information about how to opt out of the study or to speak to a study team member 
with any questions, an informed consent document and a print version of the 
baseline survey. For patients with email addresses available, we will also send these 
materials electronically.  
13.6 
Participants will receive an incentive of $20 upon completion of 
the baseline survey and another $20 incentive upon completion of the 
follow-up survey.  
14.0 Withdrawal of Subjects* 
14.1 
A participant may be withdrawn from the study without their consent in 
order to maintain the integrity of the data (e.g., participant is not following 
procedures or is deliberately providing false information). 
14.2 
If a participant is withdrawn from the study without their consent, we will 
take the following steps: a) We will inform he participant in writing of the 
decision including an explanation for the decision; b) We will notify the IRB of 
our decision to withdraw the participant. 
14.3 
If subjects withdraw, their information will be kept and labeled as 
withdrawn. These withdrawn subjects will not be contacted further. If a subject 
chooses to withdraw from the study, we will continue to utilize all data collected 
up to the point of subject withdrawal. It states in the informed consent document 
that subjects are free to withdraw at any point during the study. Some subjects may 
decide to withdraw because they no longer wish, or have time, to do the follow-up 
interviews. From our previous genetic counseling studies, approximately 15% of 
participants withdraw prior to completion of the study. The majority of those who 
withdraw usually do so because they no longer want to complete study assessments. 
We will track withdrawals and report them in study findings. There are no 
biomedical safety implications from this type of partial withdraw. 
15.0 Risks to Subjects* 
15.1 
Risks associated with participating in this study fall into three 
categories. First is the risk associated with completing the study surveys. There is 
a low risk of adverse psychological reactions to the study surveys. Asking men with 
prostate cancer to reflect on their/their family’s cancer risks, their cancer screening 
behaviors, and their reactions to genetic testing could generate anxiety for some 

 
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individuals. However, because these individuals agreed to study participation, these 
are likely topics that they are willing to discuss. It is possible that persons likely to 
be overly concerned or harmed by the experience of discussing cancer risk will 
choose not to participate, although our prior data show that we have recruited 
participants reporting a broad continuum of cancer worry and risk perception with 
no adverse consequences. Thus, we consider this to be a minimal risk to patients.  
Second, there may be modest risks associated with participation in genetic 
education or genetic counseling. Participants may experience mild psychological 
distress regarding their risk for carrying a PV in a cancer risk gene and the potential 
increase in risk for cancer in the participant and his family members.  
Our plan for addressing adverse psychological reactions is comprehensive and is 
modeled on our current approach within the clinical cancer genetics program at 
LCCC (Dr. Isaacs, Medical Director; Ms. Peshkin Genetic Counseling 
Director). First, any participants who report high levels of distress during a study 
contact or on a study survey instrument will be referred for follow-up psychological 
assessment to a mental health provider. Second, all participants who undergo 
genetic testing and receive a PV or VUS result will have an individual genetic 
counseling disclosure session with a board-certified genetic counselor. As part of 
this session, the counselor will assess participant distress and coping difficulties. 
Specific follow-up referrals will be made for participants exhibiting psychosocial 
difficulties. Because attention to psychological issues has been a longstanding 
component of comprehensive genetic counseling, it is anticipated that 
psychological injury will be infrequent. In fact, quite to the contrary, considerable 
research documents beneficial psychosocial effects of counseling. Even for patients 
who receive positive test results, there is little evidence to suggest adverse 
psychological effects. 
There may also be risks for ST participants who proceed directly to genetic testing 
without an individual genetic counseling session. However, we believe that the risk 
to these participants is low for several reasons. A) In community practice 
approximately 50% of individuals who receive cancer genetic testing do so without 
any pre-test genetic education or counseling; B) All participants who are 
randomized to ST will have the option to request individual telephone genetic 
counseling free of charge through the study; C) All individuals who proceed to 
genetic testing and are found to carry a PV or VUS result will receive their test 
results in the context of a standard genetic counseling disclosure session with a 
board-certified genetic counselor; D) The population in the current study all meet 
guidelines for genetic referral. There are insufficient counseling resources to 
retrospectively contact and counsel all prostate cancer survivors who meet criteria 
for genetic testing. Thus, from a clinical perspective, it is critical to develop 
effective and efficient genetic education approaches to foster informed genetic 
testing decisions. Finally, the personal health implications of a positive genetic test 
result in men are much less pronounced and immediate than in women. Thus, the 
risk of adverse psychosocial outcomes (already low in women who undergo testing) 
is quite low.   

 
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For all patients who choose to proceed with genetic testing, there may be additional 
risks. Although participants will neither be encouraged nor discouraged from 
undergoing testing as part of this study, for those who choose to pursue 
testing, additional potential risks include insurance and employment discrimination 
and the small possibility of incorrect or inaccurate test results. The ST materials 
contain information about laws protecting against genetic discrimination, and the 
standard clinical laboratory consent form outlines the small possibility of incorrect 
or inaccurate test results.    
Finally, in addition to psychosocial risks that may be associated with genetic 
counseling, there may also be risks related to confidentiality and loss of privacy 
should an unauthorized third-party learn that the participant received genetic 
counseling and testing.  
16.0 Potential Benefits to Subjects* 
16.1 
The potential benefit of this study to the participants is an increased 
knowledge of genetic testing for cancer susceptibility and a better understanding of 
the implications for treatment, screening, and risk reduction in men who carry a PV 
and their family members. 
17.0 Data Management* and Confidentiality 
17.1 
Data Analysis: We will characterize participants by comparing them to 
decliners on key demographic and clinical variables derived from the EMR. After 
performing univariate analysis on dependent variables, we will apply any needed 
normalizing or variance stabilizing transformations. We will follow Consort 
guidelines for Intent-to-Treat analyses (ITT). We will compare groups at baseline 
with χ2 and t-tests and will include covariates that are associated with group (p 
<0.10) in our final models. 
Aim 1: Evaluate the impact of Proactive Streamlined Education and Testing 
(ST) vs. Usual Care (UC) on genetic testing. Analysis: H1.1: Patients randomized 
to ST will be more likely to complete genetic testing compared to UC. We will use 
logistic regression to test this hypothesis. After entering significant covariates, we 
will add intervention arm to test the overall intervention effect. H1.2: Participants 
randomized to ST will make better informed genetic testing decisions 
(characterized by high knowledge, risk comprehension and positive attitudes) 
compared to UC. Using multiple regression, we will enter control/confounding 
variables and intervention to test the impact of group on our informed decision 
making outcomes (knowledge, testing attitudes, risk comprehension). H1.3: Few 
patients in the ST arm will opt for traditional genetic counseling prior to testing. 
We will conduct descriptive analyses describing the proportion of ST participants 
who opt for genetic counseling vs. proceed directly to testing vs. opt against testing.  
Aim 2: Evaluate patient satisfaction and psychosocial outcomes in ST vs. UC. 
Analysis: H2.1: Compared to UC, those randomized to ST will be more satisfied 
with their genetic testing decision and will have less decisional regret. After 
identifying baseline confounders of each outcome, we will generate linear 
regression models in which we enter: 1) confounders; 2) genetic test result (dummy 

 
Page 14 of 18 
Revised: October 30, 2018 
coded to generate comparisons of carriers vs. non-carriers and non-carriers vs. 
untested); 3) group assignment. In the event that we have an insufficient number of 
PV carriers for these analyses, we will categorize test result into two levels (tested 
vs. untested) and evaluate results among PV carriers more descriptively. Results of 
Aim 2 analyses will be primarily focused on generating effect size estimates for our 
planned trial of newly diagnosed prostate cancer patients. 
Aim 3: Evaluate the impact of ST vs. UC on uptake of cascade testing in 
unaffected family members. In exploratory analyses designed to provide effect 
size estimates for our planned R01, we will use t-test to compare the ST to UC on 
the number of relatives of PV carriers who undergo cascade genetic testing.  
Power: Power estimates are for 2-tailed tests (α=.05). The study is powered based 
on our primary outcome of patient genetic testing uptake. We expect no attrition 
since data will be abstracted from clinic records.  With no relevant studies on which 
to base our effect sizes for this pilot study, 
Table 2 displays the necessary sample size (per 
group) to obtain 80% power for a range of 
potential clinically significant effects on test 
uptake (40%-50% for ST; 10%-20% for UC). 
Based on this analysis, we will enroll 120 
participants in order to attain 80% power to 
detect a clinically meaningful difference between 20% in UC and 45% in ST. For 
our secondary outcomes, a sample size of 120 and 10% attrition at 3-months (n=108 
in final sample) will provide > 80% power to detect medium sized effects of d=.54 
SDs on our secondary outcomes (e.g., decisional conflict, patient satisfaction). This 
effect size is well within the range that we have seen in previous studies and 
represents an effect that is generally considered to be clinically significant.  
17.2 Data Security: Our plan for maintaining confidentiality is as follows: 
The protection of privacy of participants in studies related to genetic risk 
information is of the utmost importance. Our plan to maintain confidentiality is as 
follows: 1) We will minimize communication that involves names or other 
identifying information. Where this is unavoidable, communications will be made 
via express mail, on a study dedicated fax machine, or via HIPAA compliant, access 
protected and SSL encrypted REDCap data capture system. 2) Clinical information 
such as personal and family cancer history and genetic testing results will not be 
communicated together with names in any written materials for study-related 
communication or data storage. However, as part of standard clinical practice, 
participants who opt for testing will receive a genetic testing report generated by 
the lab that will contain their name and other identifying information. This report 
will also be sent to the participant’s treating physician as per standard clinical 
practice. Similarly, the genetic counselors’ summary letters will contain 
participants’ names, test results, and other identifying information. 3) All paper 
documents will be securely stored in the participant’s research file, which will be 
kept in a locked cabinet in research team offices within secure buildings. 4) 
Information obtained during or as a result of this study will not be released without 
Table 2. Sample Size Calculation 
 
ST Uptake 
UC Uptake 
.40 
.45 
.50 
10% 
39 
25 
20 
15% 
49 
36 
27 
20% 
81 
54 
39 

 
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Revised: October 30, 2018 
the written consent of the participating individual. 5) In all data sets, including those 
with genetic counseling and testing info, we will use ID numbers only. A separate 
data set linking names with ID numbers will be accessible only though password 
protected and secure data programs and available only to trained staff. 
17.3 
Quality assurance reviews will be conducted throughout the course of the 
study to ensure data quality and protocol adherence. 
17.4 
Data Handling: Personal information will only be used to contact potential 
study participants. This information will not be stored with the survey data. Only a 
code number will be used to identify study-related data. A matching list will be 
created as a cross-reference for contact information and data. 
Matching lists of names and code numbers will be kept in locked storage facilities 
in the PI’s office and/or laboratory space. All data will be similarly stored in locked 
facilities. All computer files containing participant data will be accessed only 
through password protected security systems and are stored on a secure and private 
server used by the Cancer Prevention and Control Program at LCCC. Further, 
procedures for ensuring data integrity and security will be reviewed at regular 
intervals through team meetings between the PI and other members of the study 
team. Ethical issues and topics related to the responsible conduct of research will 
be also be discussed routinely with the overall study team, including the potential 
for adverse events, data safety and data management, handling misconduct, etc. 
Only the PI, research staff and data managers will have access to this information. 
Transfer of information will occur via the HIPAA compliant and fully secure 
REDCap system and through the HIPAA compliant and fully secure Georgetown 
Box system. 
Protected Health Information (PHI) that will be collected includes: lab results, 
interviews/questionnaires, data previously collected for research purposes under 
another approved GU or MedStar IRB study, and from a database. 
All study-related data will be stored in the secure REDCap system and within 
Georgetown Box. Only study investigators will have access to this information. All 
access to study-related data will be via password protected and encrypted access. 
Data from this study will be stored for seven years after the final publication from 
the study. During this time, the PI will be responsible for approving access to the 
study data. Any computer used to access the study-related data will have active and 
up to date software in place to protect against malware, all operating systems and 
software updates and patches will be applied regularly and two factor authentication 
will be in place for all systems accessing research data 
18.0 Provisions to Monitor the Data to Ensure the Safety of Subjects* 
This research does not involve more than minimal risk to subjects. 
19.0 Provisions to Protect the Privacy Interests of Subjects 

 
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Revised: October 30, 2018 
19.1 
To protect privacy interest of participants, we first contact potentially 
eligible patients by mail. This contact includes multiple options to easily opt out of 
further contact: a stamped and addressed opt-out card; a toll-free telephone number 
to opt out of the study and an e-mail address for opting out of the study. We will 
wait two weeks before contacting men who have not opted out/indicated their 
ineligibility.   
19.2 
Participants will be assured of the confidentiality of their data and that their 
data will be carefully protected and safeguarded. Only a code number will be used 
to identify study-related data. Participants will be told that during the survey, they 
may decline to answer any questions that do not wish to answer and can leave the 
study at any time and for any reason.  
19.3 
The research team will have access to study data on password protected 
servers or by password protected web interfaces.  Access to data will be strictly 
controlled.  
20.0 Compensation for Research-Related Injury 
20.1 The risk of injury in this study is minimal.  
21.0 Economic Burden to Subjects 
21.1 
Participation in this study will not result in any additional costs for 
the subjects.  
22.0 Consent Process 
22.1 We will follow the SOP: Informed Consent for Research. Consent 
will be obtained in one of two ways: 
1) Print Informed Consent Document. This document will be sent to all 
participants. This document will be reviewed by participants and any questions 
that they have will be addressed during a telephone call with the study RA. 
Those who wish to complete the written consent can return it directly to the 
study team in a postage paid return envelope. 
2) Electronic Consent. Participants who prefer to complete an electronic consent 
process can complete an electronic consent form immediately prior to the 
baseline study survey. This form is comparable to the print consent form - but 
adapted for electronic administration.  
Waiver or Alteration of Consent Process (consent will not be obtained, 
required information will not be disclosed, or the research involves 
deception): Not Applicable 
Subjects who are not yet adults (infants, children, teenagers): N/A 
Cognitively Impaired Adults: N/A 
Adults Unable to Consent: N/A 
23.0 Process to Document Consent in Writing 

 
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Revised: October 30, 2018 
23.1 
We will follow “SOP: Written Documentation of Consent (HRP-091).” We 
will obtain print or electronic consent from all participants prior to randomization. 
The written consent document will be sent to all participants. Those who wish to 
complete the written consent can return it directly to the study team in a postage 
paid return envelope. Participants who prefer to complete the consent form 
electronically can complete an electronic version of the consent form online prior 
to the baseline survey.   
23.2 
We are requesting a waiver of written consent so that participants who 
choose to complete the baseline study survey by telephone can complete the survey 
following an IRB-approved verbal consent process. Participants who we contact by 
telephone (who have not completed a print or electronic informed consent 
document), will complete an IRB-approved verbal consent process. Verbal consent 
will pertain only to the completion of baseline study survey. All study participants 
will be required to complete the print or electronic informed consent document 
prior to randomization. We believe this approach is justified for several reasons. 
First, the data collected during the baseline survey are limited to behavioral, 
psychosocial, attitudinal and demographic information. This survey represents 
minimal risk to participants. Second, with the increasing difficulty of reaching 
study participants by telephone, it becomes extremely important to be able to 
complete the baseline survey when we get a chance – rather than wait for the return 
of the consent documents. This process allows us to complete the minimal risk 
baseline survey while still requiring full informed consent prior to randomization 
and the delivery of the intervention. Finally, completing the survey does not in any 
way represent a commitment to participate in genetic counseling or testing. 
Participants can decline further study participation at any time.  
Participants will be required to sign a clinical consent form from the testing 
laboratory (Invitae). This form outlines the potential benefits, limitations, and risks 
of genetic testing.  
 
24.0 Setting 
24.1 
All study participants will be patients of our collaborating medical and 
radiation oncologists at MGUH and MWHC. Participants who are potentially 
eligible for the study (i.e., meet clinical genetic referral criteria) will be identified 
via EMR query and then contacted by the study team. All research procedures will 
be conducted remotely (survey completion, delivery of print genetic education and 
telephone genetic counseling). 
25.0 Resources Available 
25.1 
Recruiting Feasibility: Men eligible for this study are currently being 
followed at MGUH or MWHC for metastatic prostate cancer or Gleason 7+ prostate 
cancer with a family history of breast, ovarian, pancreatic or prostate cancer or 
Ashkenazi Jewish ancestry. We will exclude patients who have had or are 
scheduled for, genetic counseling or testing. We will also exclude men who cannot 
participate in English and provide meaningful consent. We will recruit participants 
from medical and radiation oncology clinics at MGUH and MWHC (see letters of 

 
Page 18 of 18 
Revised: October 30, 2018 
support in attached protocol). These clinics currently follow well over 1000 eligible 
patients. Although we routinely attain 70% case participation, we can attain our 
required sample size (n=120) with much lower rates of participation.   
Time: The project will be conducted over the next year with data analysis and 
manuscript preparation continuing for 1 years after the completion of participant 
follow-up. 
 
Facilities: Participants will be contacted via mail, telephone and electronically. The 
study staff will initiate these contacts from the Cancer Prevention and Control 
office suite and from the offices of SRBSR in MGUH. Each member of the study 
staff has a private or semi-private office with private telephone and private secured 
workstations. Each office is locked and accessible only by the study staff member 
and the PI or Project Director. All DNA will be collected using standard DNA 
saliva kits used by the study participants in the privacy of their home. DNA will be 
shipped by mail to the designated commercial genetic testing company for 
preparation and sequencing in a secure and CLIA-approved facility as is standard 
for all clinical genetic testing samples.  
Medical and Psychological Resources: This is a low-risk study. However, all 
participants will have access to a board-certified genetic counselor. All of these 
counselors are trained and experienced at recognizing signs of psychological 
distress. All positive genetic test results will be delivered by a board-certified 
genetic counselor who will assess psychological reactions to genetic test results and 
make referrals for additional services as needed. All negative or VUS results will 
be delivered via mailed clinical letter and will include contact information for the 
assigned genetic counselor in case the participant wishes to schedule a session. 
Training: All persons involved in this research study are trained on the protocol 
prior to their involvement in the study. All study personnel complete standard 
Georgetown University Human Subjects Training through the CITI program. All 
staff are supervised directly by the PI and participate in weekly study meetings. 
Further, procedures for ensuring data integrity and security will be reviewed at 
regular intervals throughout the study. Ethical issues and topics related to the 
responsible conduct of research will also be discussed routinely with the overall 
study team, including the potential for adverse events, data safety and data 
management, handling misconduct, etc.  
 
26.0 Multi-Site Research* 
26.1 
This is not a multisite study.