Genomic testing in cancer: Patient knowledge, attitudes, and expectations
Presented in part as a poster at the 2013 European Cancer Congress; September 27 to October 3, 2013; Amsterdam, the Netherlands.
We acknowledge all members of the Drug Development Program at Princess Margaret Cancer Centre for their help with data collection and thank all the patients for their important and valuable contribution to our research.
Genomic testing in cancer (GTC) characterizes genes that play an important role in the development and growth of a patient's cancer. This form of DNA testing is currently being studied for its ability to guide cancer therapy. The objective of the current study was to describe patients' knowledge, attitudes, and expectations toward GTC.
A 42-item self-administered GTC questionnaire was developed by a multidisciplinary group and patient pretesting. The questionnaire was distributed to patients with advanced cancer who were referred to the Princess Margaret Cancer Center for a phase 1 clinical trial or GTC testing.
Results were reported from 98 patients with advanced cancer, representing 66% of the patients surveyed. Seventy-six percent of patients were interested in learning more about GTC, and 64% reported that GTC would significantly improve their cancer care. The median score on a 12-item questionnaire to assess knowledge of cancer genomics was 8 of 12 items correct (67%; interquartile range, 7-9 of 12 items correct [58%-75%]). Scores were associated significantly with patients' education level (P < .0001). Sixty-six percent of patients would consent to a needle biopsy, and 39% would consent to an invasive surgical biopsy if required for GTC. Only 48% of patients reported having sufficient knowledge to make an informed decision to pursue GTC whereas 34% of patients indicated a need for formal genetic counseling.
Patients with advanced cancer are motivated to participate in GTC. Patients require further education to understand the difference between somatic and germline mutations in the context of GTC. Educational programs are needed to support patients interested in pursuing GTC. Cancer 2014;120:3066–3073. © 2014 American Cancer Society.
Rapid advances in tumor genetics and molecular biology have led to the genomic era with a hope of improving personalized cancer therapy.[1-3] Several targeted cancer drugs and their associated predictive biomarkers are now in wide-scale clinical use. Genome sequencing technology is now being used to profile a patient's tumor on a molecular basis with the primary goal of identifying significant somatic mutations of clinical relevance to guide ongoing treatment decisions. This novel form of genomic testing in cancer (GTC) is currently being studied by several centers to optimize patient selection for enrollment into clinical trials.[5, 6] However, very little is known about patients' knowledge of GTC and their attitudes toward this strategy. Such an understanding is very important as cancer care programs build the capacity and infrastructure to educate and support patients who are interested in GTC.
Past research has demonstrated the importance of education and counseling programs before germline genetic testing to identify inherited familial cancer syndromes. The majority of this research has been focused on hereditary breast cancer and BRCA1/2 testing.[8-10] Among women undergoing genetic testing for evidence of inherited breast cancer susceptibility, research has documented a poor general level of knowledge and understanding of cancer genetics.[11-14] This lack of knowledge often leads to a misunderstanding regarding the potential benefits, risks, and limitations of genetic testing. However, studies have also demonstrated that patient education and counseling before genetic testing can increase knowledge, decrease anxiety, and improve clinical decision making.[9, 10, 16-18]
Currently, there is very limited knowledge regarding patient perspectives toward genomic testing in cancer care. Only 2 published studies have reported patient attitudes of genomic cancer testing.[19, 20] Those studies demonstrated that patients have a very positive attitude toward GTC but are concerned about incidental findings and are afraid of being overwhelmed by test results and the potential to hear more “bad news” regarding their disease.
The objective of the current study was to assess the knowledge, attitudes, and expectations of patients with advanced cancer regarding the use of GTC testing to help guide cancer care using a self-administered questionnaire.
MATERIALS AND METHODS
A draft self-administered questionnaire to evaluate patients' knowledge, attitudes, and expectations of GTC was created based on a review of relevant literature.[11, 21-26] Two consensus meetings of a multidisciplinary panel of health professionals, including 3 medical oncologists, 1 medical geneticist, 1 genomic scientist, 2 medical ethicists, and 1 health policy expert, were conducted to refine the questionnaire.
The refined questionnaire was then pilot tested in a group of 8 patients with advanced solid tumors who were actively participating in a phase 1 clinical trial program. Patients were approached for study participation during a routine clinical trial assessment. After an informed consent discussion, participants completed the questionnaire and then underwent a 30-minute to 45-minute semistructured interview to assess the content, comprehension, clarity, appropriateness, and ease of administration of the questionnaire. The questionnaire was subsequently revised based on the comments and feedback received during pilot testing.
The study questionnaire was composed of 4 sections: Section A, personal cancer history (4 items); Section B, general knowledge (12 items); Section C, attitudes and expectations (16 items); and Section D, demographics (10 items) (Appendix 1; see online supporting information).
Patients with advanced solid tumors who were referred either for GTC testing or for phase 1 clinical trial participation at the Princess Margaret Cancer Center (Toronto, Ontario) were eligible. The inclusion criteria were: 1) age ≥18 years, 2) solid tumor malignancy, and 3) fluency in English. Local research ethics board approval was obtained for this study.
The final questionnaire was distributed to 148 patients from November 2012 to May 2013 at the Princess Margaret Cancer Center. Patients were approached for participation by their medical oncologist at their initial consultation or during a follow-up clinic visit. Consent was implied by completion and return of the questionnaire to protect the anonymity of the participants. Individuals were assigned a unique study number that was used to identify their returned questionnaires. Questionnaires could be completed at the hospital or taken home and returned by mail in a self-addressed envelope. The participants' reported diagnoses and previous cancer treatments were verified for accuracy by the study investigators through a review of patients' electronic medical records. If requested, a supplementary information sheet was mailed to the study participants after completion of the questionnaire. The supplementary information sheet included more detailed information about GTC along with answers to the completed general knowledge-based questions (Appendix 2; see online supporting information).
Descriptive statistics were used to summarize patient characteristics, genomic knowledge, and attitudes toward testing. Logistic regression models were constructed to test associations between patients' knowledge and 1) age, 2) sex, 3) education, 4) income, 5) previous use of a targeted cancer drug, 6) health care education or work experience, 7) family history of cancer, 8) patient report of sufficient knowledge to give informed consent for genomic cancer testing, and 9) patient desire for further genetic counseling before testing. Statistical analyses were performed using SAS version 9.3 (SAS Institute Inc., Cary, NC).
In total, 148 patients were approached to participate in the study, and 98 completed questionnaires were returned, representing a response rate of 66%. Reasons for failure to return the questionnaire were not recorded. Patient characteristics are reported in Table 1. The study population consisted of 24% men (n = 24) and 76% women (n = 74). The median patient age was 59 years (range, 22-77 years). All patients had received prior treatment, including: surgery (85%; n = 83), radiation therapy (58%; n = 57), chemotherapy (92%; n = 90), and targeted cancer drug therapy (49%; n = 48). Fifty-two percent of patients (n = 51) has previously participated in a clinical trial. The proportion of patients reporting a university level education or higher was 36% (n = 35). Thirty-two percent of patients (n = 31) reported a personal annual income of >50,000 dollars (Canadian). Fifty-six percent of patients (n = 55) reported a family history of cancer.
Table 1. Patient Characteristics, n = 98
|Colorectal cancer||25 (26)|
|Breast cancer||24 (25)|
|Ovarian cancer||16 (16)|
|Lung cancer||7 (7)|
|Endometrial cancer||4 (4)|
|Previous treatments|| |
|Targeted drug||48 (49)|
|Clinical trial participation||51 (52)|
|<High school||7 (7)|
|High school diploma||26 (27)|
|Technical or community college degree||23 (23)|
|University degree||35 (36)|
|Prefer not to say||1 (1)|
|Not answered||6 (6)|
|Personal income before taxes, Canadian dollars|| |
|50,000 to 99,999||22 (23)|
|100,000 to 149,000||4 (4)|
|Prefer not to say||20 (20)|
|Not answered||3 (3)|
|Health care education or work experience|| |
|Not answered||1 (1)|
|Family history of cancer|| |
|Not answered||3 (3)|
Patients' Knowledge of Cancer Genomics
The cumulative scores from the knowledge component of the questionnaire are presented in Table 2. The median number of correct answers on the 12-item questionnaire was 8 of 12 items correct (67%; interquartile range, 7-9 of 12 items correct [58%-75%]). Eighty-nine percent of patients (n = 87) correctly answered false to item 2 (“all cancers are aggressive”) and 85% (n = 83) correctly answered true to item 1 (“cancer is uncontrolled cell growth”). Seventy-five percent of patients (n = 73) correctly answered true to item 6 (“a mutation is a change in DNA”), and 66% (n = 65) correctly answered true to item 5 (“genes are made of pieces of DNA”). Two items were often answered incorrectly and may identify areas to target for further education. Only 21% of patients (n = 21) correctly answered false to item 4 (“hereditary [inherited within families] forms of cancer are common”), and 18% (n = 18) correctly answered false to item 8 (“cancers are usually caused by a change to a single gene”).
Table 2. Knowledge Assessment Questionnaire Regarding Cancer Genomics (n = 98)
|1. Cancer is uncontrolled cell growth (Answer: True)||85||7||8||0|
|2. All cancers are aggressive (Answer: False)||89||10||1||0|
|3. Cancer is caused by a combination of inheritance, environmental, and lifestyle factors (Answer: True)||70||18||11||1|
|4. Hereditary (inherited within families) forms of cancer are common (Answer: False)||21||50||29||0|
|5. Genes are made from pieces of DNA (deoxyribonucleic acid) (Answer: True)||66||7||26||1|
|6. A “mutation” is a change in DNA (Answer: True)||75||7||17||1|
|7. Any genetic change within a cell will give rise to cancer (Answer: False)||60||15||24||1|
|8. Cancers are usually caused by a change to a single gene (Answer: False)||18||26||55||1|
|9. GTC testing can be used to identify important genes that play an important role in cancer (Answer: True)||93||0||7||0|
|10. Cancers have the same genetic characteristics (Answer: False)||86||4||10||0|
|11. GTC testing can be used to help predict a patient's response to a specific cancer drug (Answer: True)||70||3||27||0|
|12. GTC testing (for acquired and inherited mutations) can potentially be used for the following (Answer: All of the above)||72||27||0||1|
|A. To confirm type of diagnosis|| || || || |
|B. To predict the risk of cancer for an individual and their relatives and children|| || || || |
|C. To select treatment and monitor patient responses|| || || || |
|D. To predict a disease outcome|| || || || |
|E. All of the above|| || || || |
Patients' Attitudes and Expectations of GTC
In total, 76% of patients (n = 74) indicated interest in learning more about GTC. Supplemental written information and answers to the knowledge questions were requested and delivered to 77 study patients (79%).
Nearly two-thirds or 66% (n = 65) of patients indicated that they would consent to a needle biopsy if required for GTC. Only 39% (n = 38) indicated that they would consent to a more invasive surgical biopsy that would require a general anesthetic.
The most important factors influencing a decision to pursue GTC testing are presented in Table 3. In total, 70% of patients (n = 68) reported that the potential for testing to guide treatment selection was the most important reason to undergo testing. The most important factors that might discourage a patient from testing were the potential for a serious biopsy complication, which was reported by 36% of patients (n = 35), and a potential delay in treatment while awaiting test results, which was reported by 22% of patients (n = 21).
Table 3. Factors That Influence a Patients' Decision to Pursue Genomic Testing For Cancer (n = 98)
|Influential factors to pursue genomic testing for cancer|| |
|Potential to guide treatment selection||70|
|Potential to learn more about my cancer||10|
|Potential to predict disease outcome||9|
|Desire to contribute to scientific research||7|
|Trust in my physician||0|
|Influential factors not to pursue genomic testing for cancer|| |
|Potential for serious complication from a tissue biopsy (if required for testing)||36|
|Potential for delay in treatment while awaiting test results||22|
|Potential of test results to lead to health, life, or disability insurance discrimination||15|
|Potential of test results to be of no clinical value||14|
|Concerns about privacy and confidentiality of test results||3|
Table 4. Patient Attitudes and Expectations of Genomic Cancer Testing (n = 98)
|Would you be interested in learning more about GTC?||76||6||17||1|
|Would you be willing to undergo a needle biopsy if required for GTC?||66||13||19||2|
|Would you be willing to undergo a surgical biopsy if required for GTC?||39||27||33||1|
|Do you believe GTC would significantly improve your cancer care?||64||5||30||1|
|Would you only want to receive GTC results that would influence your current cancer treatment?||35||53||11||1|
|Would you want disclosure of incidental GTC results regarding:|| || || || |
|A. Inherited familial risk of developing cancer||87||5||7||1|
|B. Inherited risk of developing diseases other than cancer||79||7||13||1|
|Would you consent to biobank your GTC results and tissue sample for future scientific research?||91||2||5||2|
|Do you think you have sufficient knowledge regarding the potential benefits and risks of GTC to make an informed decision to pursue testing?||48||29||21||2|
|Do you feel you would need more formal genetic counseling prior to pursuing GTC?||34||40||25||1|
In total, 64% of patients (n = 63) believed that GTC testing would significantly improve cancer care (Table 4). Patients reported a desire for full disclosure of incidental test results. This was reflected by the observations that 87% of patients (n = 85) said they would request to receive incidental test results that would have an impact on their families' risk of developing cancer, whereas 79% of patients (n = 77) said they would wish to receive incidental test results that would have an impact on their own risk of developing diseases other than cancer. However, 35% of patients (n = 34) said they would only want to receive GTC results that would directly influence their cancer treatment decisions.
A reported 48% of patients (n = 47) believed that their knowledge was sufficient to appreciate the benefits and risk of GTC to make an informed decision whether or not to pursue testing. However, 34% of patients (n = 33) wanted formal genetic counseling before participating in GTC testing.
The vast majority of patients (91%; n = 89) agreed to biobanking their GTC results and sharing their results for the purposes of scientific research. Biobanking was defined as the storage of GTC test results and biologic samples for the purpose of scientific research. In addition, 74% of patients (n = 73) were willing to share their test results with researchers outside their local hospital, both nationally and internationally.
Patients' Knowledge Scores and Significant Associations
Patient knowledge scores were not associated significantly with age, sex, use of prior targeted drugs, previous health care education or work experience, or a family history of cancer. Knowledge scores were associated significantly with education level and income. Patients with higher levels of education and personal incomes had significantly higher knowledge scores on the questionnaire (P < .0001 and P = .0048, respectively). Patient knowledge scores also were correlated with their perceived ability to be able to provide informed consent for testing (P < .0001). There also appeared to be a trend toward an association between knowledge scores and a patient's desire for formal genetic counseling (P = .0509), because patients with lower knowledge scores were more likely to desire formal counseling before undergoing GTC.
To our knowledge, this is the first study investigating patients' direct knowledge of GTC and desire for further education and counseling. Our study documents a strong basic understanding of cancer biology and genomics among a select group of patients with advanced cancer. However, we have also identified knowledge gaps that may provide guidance for future educational initiatives. The majority of study patients did not appear to appreciate the genomic complexity of cancer and overestimated the prevalence of hereditary forms of cancer. Patients often associate genes with familial inheritance and do not appear to realize that the majority of genetic mutations are acquired or occur spontaneously. The distinction between somatic and germline mutations is fundamental, especially because GTC is primarily focused on guiding the use of targeted cancer therapy based on somatic aberrations harbored within tumors, as opposed to identifying familial cancer syndromes. However, patients undergoing GTC must also be aware of the potential to uncover incidental germline mutations of potential clinical significance.
Patients have a strong interest in GTC and are likely to overestimate its potential benefit in their cancer care.[19, 20] Given the exciting potential of GTC, patients should be reminded that the use of targeted or whole genome sequencing for cancer care is still investigational. In our study, 64% of patients reported a strong belief that GTC would significantly improve their overall cancer care. Preliminary results from the Princess Margaret IMPACT study and the MOSCATO trial at the Gustave Roussy Institute have produced promising results using GTC, but only a limited proportion of patients who underwent genomic testing were matched to targeted treatment.[6, 27] These findings reflect the challenge of accessing novel and experimental targeted drugs for patients with cancer. It also reflects the reality that numerous mutations of clinical significance are not directly targetable by current anticancer therapies. Consequently, patients with advanced cancer should be provided with realistic information about expectations when undergoing GTC testing.
The most important factors that might discourage GTC were the potential for a complication from a biopsy if needed and a potential delay in treatment awaiting test results. Nonetheless, 66% of patients were willing to undergo a repeat biopsy to pursue GTC. This is consistent with our previously reported research, indicating a willingness of patients to undergo research biopsies for clinical trials associated with novel anticancer agents. Genotyping or targeted sequencing can also now be performed using stored paraffin-embedded tissue on archived pathology samples, negating the need for repetitive tissue biopsies. However, concerns have been raised that archival tissue samples may not reliably represent the molecular characteristics of the current tumor, given the potential development of tumor heterogeneity and clonal evolution, and may not be helpful in identifying mechanisms of drug resistance. Therefore, a repeat tissue biopsy may be of value in some patients. Hopefully, advances in GTC testing on circulating tumor cells and DNA will reduce the need for invasive tissue biopsies in the future.[31, 32]
Given their prognosis, most patients with advanced cancer in our study did not regard the potential for insurance discrimination as a major barrier influencing a decision to pursue GTC testing. However, the potential for insurance discrimination would likely be a greater concern for patients with early stage cancer who are receiving curative-intent treatment. The potential for health insurance discrimination may also present a greater concern in countries with privatized health care systems. This concern is currently being addressed by many countries, and several European nations and the United States have passed legislation preventing health insurance and employment discrimination based on genetic testing.[33-35]
Our results also clarify patient expectations of disclosure of incidental results identified during GTC. This is of considerable importance whenever whole genome sequencing is performed or if there is potential to uncover incidental genetic results. Almost 80% of patients in this study reported wishing disclosure of incidental genomic test results that could be relevant to their own health or influence their family's risk of developing cancer. It is noteworthy that 35% of patients reported only wanting to receive test results that would directly impact their treatment. The American College of Medical Genetics and Genomics has recently released guidelines on reporting of incidental findings in clinical exome and genome sequencing. These guidelines are controversial and are currently being reviewed.
Our recommendation is that patients should receive appropriate counseling and have the option whether or not they wish to receive incidental test results.[7, 37-39] Consent should occur before testing and should clearly document which specific incidental results will be disclosed and whether or not other family members have the patient's consent to access their genomic test results.[36, 37, 40] We believe further consensus is still needed to guide recommendations about the disclosure of results of uncertain significance and to determine the optimal and practical mechanisms for notifying patients of genetic results that are identified as clinically significant.
This group of patients was very supportive of biobanking their genomic tissue samples to help advance scientific research on local, national, and international levels. In our study, 82% of patients were in favor of giving blanket consent to share their genomic specimens for scientific research. The surveyed patients did not appear to be discouraged by privacy, confidentiality, or potential discrimination concerns. However, these issues, as well as the investigator's duty to notify study participants of significant clinical results uncovered during research testing, are currently being vigorously debated by the scientific community.[41-44]
In our current study, we did not interview patients after they completed the questionnaire except during the pretesting phase. Therefore, we were not able to explore patients' answers in greater depth. This would have been helpful given the complexity of this subject matter. Our study consisted of a very educated, motived, and knowledgeable group of cancer patients. Therefore, our results may not be generalizable to all cancer patients. In addition, there may be significant differences between the knowledge and attitudes of early stage versus advanced stage cancer patients with respect to GTC. Our study also required fluency in English and may have under-represented patients from ethnic minorities. Nonetheless, it clearly identifies knowledge gaps in patients with advanced cancer, and it provides strong evidence of the need for education across all patients interested in pursuing GTC. Overall, our study represents the largest documentation of cancer patients' knowledge, attitudes, and expectation of GTC to date.
The need for better education and counseling services to support patients who undergo GTC is apparent from our results. A wide variety of educational resources should be explored, including web-based technologies, videos, and written educational materials. Formal genetic counseling may also be required in some patients. Our center is currently developing and testing the effectiveness of a video-based educational resource to help improve patient education. Further research is needed to determine how clinicians can best communicate complex test results to patients in a manner that is effective, empowering, and meaningful and to understand patient concerns and barriers that would discourage GTC testing. This proactive approach will allow cancer centers to develop GTC in a patient-centered manner to optimize the benefits of testing for patients and their families.
No specific funding was disclosed.
CONFLICT OF INTEREST DISCLOSURES
The authors made no disclosures.