(UroToday.com) The 2023 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between June 2nd and June 6th was host to a prostate, testicular, and penile cancers poster session. Dr. Veda Giri presented the results of TARGET (Technology-enhanced acceleration of germline evaluation for therapy), a randomized controlled trial (RCT) of a pretest patient-driven webtool versus genetic counseling for prostate cancer germline testing.
Germline and somatic mutations have significant prognostic and predictive implications for treatment selection, particularly with the emergence of PARP inhibitors, and as such routine genetic testing is widely recommended for patients with evidence of advanced disease. Results of genetic testing also have important implications for familial hereditary cancer risk profiling and clinical trial eligibility. However, despite genetic testing being guideline-recommended, the clinical implementation of such testing has clearly been disappointing, with many barriers to routine genetic testing, including a shortage of genetic counselors. Novel technology-based tools have the potential to help address this implementation gap. In this study, Dr. Giri presented the results of an RCT of a pre-test patient-driven webtool versus genetic counseling for prostate cancer germline testing.
TARGET is a multicenter randomized trial that compared standard pre-test genetic counselling versus a nine module, patient-driven webtool created by the study team in tandem with the Prostate Cancer Foundation. Eligibility criteria were as follows:
- Metastatic disease
- T3 or worse disease
- PSA >20
- Grade Group 4 or 5
- Biochemical recurrence
- Intraductal/cribriform
- Ashkenazi Jewish ancestry
- Family history suggestive of hereditary cancer syndrome
As summarized in the figure below, after patients were deemed trial eligible and consented, they were randomized 1:1 to traditional genetic counseling or web-based genetic education.
The investigators used a mixed effects regression model with random intercepts to estimate the effects of webtool versus genetic counselling in the intention-to-treat population. This was a non-inferiority trial with a primary endpoint of changes in decisional conflict of webtool versus genetic counseling, with a pre-specified non-inferiority margin of δ = 4. Non-inferiority was tested using a one-sided 95% confidence interval.
This trial included a total of 315 patients, with 162 and 153 in the genetic counseling and webtool arms, respectively. The mean age was 63.7 years, most patients were White or Caucasian (90%), and 88% had some level of post-secondary education. Overall, 77% of patients underwent genetic testing, with 84% and 69% in the genetic counseling and webtool arms, respectively. The results of the genetic testing were as follows:
- Positive: 15.1%
- Negative: 49.4%
- Variant of uncertain significance: 35.5%
Compared to baseline, there were reductions in decisional conflict in both arms following pre-test genetic education. Adjusting for study site and baseline decisional conflict, non-inferiority testing demonstrated that the reduction in decisional conflict was non-inferior in the webtool arm (difference= -0.04, 95% CI: -∞ to 1.95).
Dr. Giri concluded as follows:
- Delivery of pre-test genetic education through a webtool was non-inferior to genetic counseling for reducing decisional conflict
- Lower uptake of genetic testing in the webtool arm may be due to multiple factors, including less favorable attitudes towards genetic testing and challenges with sample return.
- These results support a new standard-of-care for the use of patient-driven digital webtools for expanding access to informed decision-making for prostate cancer genetic testing
- Further studies are needed to examine methods for improving genetic testing uptake and evaluating this approach in more diverse patient populations
Presented by: Veda N. Giri MD, Assistant Director, Clinical Cancer Genetics, Cancer Genetics; Chief, Division of Clinical Cancer Genetics, Yale School of Medicine, New Haven, CT
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.
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Patient-Driven Webtool Challenges Traditional Counseling in Prostate Cancer Germline Testing - Veda Giri