Jun Gong, MD, gives his perspective on a review article published in ONCOLOGY about the necessary relationship between medical oncologists and genetic counselors to help treat patients with prostate cancer.
The authors of this timely review are to be applauded for providing a comprehensive analysis of the current literature supporting guidelines-based indications for germline testing in prostate cancer. As they describe, germline mutations in DNA repair genes, including BRCA1/2, can be found in a clinically significant proportion of men with metastatic prostate cancer—up to 11.8%.1 The impact of these germline mutations on the modern care of the patient with prostate cancer is multifold.
As the authors highlight, the presence of germline mutations in DNA repair genes can guide use of FDA-approved targeted agents in refractory and advanced prostate cancer, specifically the PARP inhibitors (PARPi) olaparib (Lynparza) and rucaparib (Rubraca). In the setting of DNA repair deficiency, sensitivity to platinum chemotherapy has also been well described. These associations have direct relevance to us, as medical oncologists, in our clinical management of patients with metastatic prostate cancer. It should be noted that 2 additional PARPi, talazoparib (Talzenna) and niraparib (Zejula), are separately undergoing phase 3 trials randomizing patients with metastatic castrate-resistant prostate cancer (mCRPC) who have not received systemic therapy in the castrate-resistant setting. Both of these trials seek to explore the effectiveness of moving PARPi to earlier settings in mCRPC with novel hormonal therapy in those with and without DNA damage repair deficiencies.2 As mentioned in the article, PARPi are also moving into the localized, high-risk prostate cancer setting; my group is participating in the NRG-GU007 (NADIR; NCT04037254) phase 2 trial in this setting, investigating niraparib in combination with standard-of-care radiation therapy and androgen deprivation therapy in patients with high-risk prostate cancer. As such, reasons for somatic and germline testing in prostate cancer are likely to evolve and expand in the near future.
Beyond the influence of germline testing on treatment decisions for our patients with metastatic prostate cancer, we cannot emphasize enough the importance of germline testing for patients’ families in patients who are positive for germline testing with our colleagues in genetic counseling. Here, the authors importantly highlight different care models to deliver germline testing. This topic has become increasingly relevant, given concerns for broadened recommendations for genetic testing and the resultant great demand that cannot be currently met by approximately 4000 genetic counselors in the United States.
One solution to this increased demand is the provider-led testing model, in which the oncologist performs the pretest counseling and discusses posttest results, with eventual referral to genetic counseling if there is a positive genetic test result. Similar models are also being described with primary care providers and genetic counselors.3 Such provider-led models are in accordance with the American Society of Clinical Oncology’s genetic testing guidelines, in that experienced clinicians who are not geneticists may provide pretest counseling so long as prior informed written consent from the patient is obtained. Important to the success of this model would likely be the degree of clinician experience (ie, how comprehensive their genetic counseling training has been), the clinician’s comfort level, and the supporting staff or resources available to the clinician to operate a provider-led germline testing model.4
Members of a consensus panel discussing germline testing have pointed out that clinicians who lack genetics training may experience numerous obstacles when counseling patients, in particular obstacles related to limited knowledge of the downstream impact of genetic testing, such as health insurance coverage, implications for life insurance, and protections afforded by the Genetic Information Nondiscrimination Act.5 Discussions about the importance and management of variants of unknown significance could be confusing for the patient even in the posttesting stage without appropriate knowledge and training on the clinician’s part. In addition, genetic counseling may not always be reimbursed by some insurers, such as Medicare and Medicaid.
The hybrid model as presented by the authors may allow oncologists to shoulder some of the burdens of pretest counseling and ordering germline testing, while the experienced genetic counselors take over in the posttest counseling stage. To additionally lessen the burdens on genetic counselors, limiting the number of in-person visits by patients may be another option. As we have all learned throughout the COVID-19 pandemic, telemedicine does have certain advantages in clinical practice. Mauer et al have described the value of virtual counseling and technological adaptations, including billing practices and coordination of education and outreach opportunities, that have been made during the pandemic and have helped genetic counselors.6 Such adaptations represent only a few of the evolving strategies that we as medical oncologists, in conjunction with our health care team, must seek out and implement to help our genetic counseling colleagues reach an expanding population of prostate cancer patients in need of evidence-based germline testing.
1. Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N Engl J Med. 2016;375(5):443-453. doi:10.1056/NEJMoa1603144
2. Gong J, Posadas E, Bhowmick N, et al. Integrating PARP inhibitors into advanced prostate cancer therapeutics. Oncology (Williston Park). 2021;35(3):119-125. doi: 10.46883/ONC.2021.3503.0119
3. Carroll JC, Morrison S, Miller FA, Wilson BJ, Permaul JA, Allanson J. Anticipating the primary care role in genomic medicine: expectations of genetics health professionals. J Community Genet. Published online August 11, 2021. doi: 10.1007/s12687-021-00544-1
4. Robson ME, Bradbury AR, Arun B, et al. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol. 2015;33(31):3660-3667. doi:10.1200/JCO.2015.63.0996
5. Bratslavsky G, Mendhiratta N, Daneshvar M, et al. Genetic risk assessment for hereditary renal cell carcinoma: clinical consensus statement. Cancer. Published August 3, 2021. doi:10.1002/cncr.33679
6. Mauer C, Zimmerman J, Lahiri S, et al. Adapting genetic counseling operations amidst the COVID-19 pandemic. J Genet Couns. 2021;30(4):949-955. doi:10.1002/jgc4.1474