Clinical Urology Practices Should Include More Genomic Screening for Prostate Cancer

Targeted Therapies in Oncology, December 2017, Volume 6, Issue 12

With genetic screening for mutations and biomarkers gaining more prevalence in diagnosing and treating cancer, genetic testing and counseling for patients with prostate cancer is becoming a pressing concept that urologists need to better understand. At the 2017 LUGPA Annual Meeting, Leonard Gomella, MD, gave a presentation stressing the importance of integrating genetic testing into clinical practice.

Leonard Gomella, MD

With genetic screening for mutations and biomarkers gaining more prevalence in diagnosing and treating cancer, genetic testing and counseling for patients with prostate cancer is becoming a pressing concept that urologists need to better understand. At the 2017 LUGPA Annual Meeting, Leonard Gomella, MD, gave a presentation stressing the importance of integrating genetic testing into clinical practice.

“I think everything we’re going to be doing in medicine in the next 5 to 10 years is going to be focused on personalized medicine, and when you say personalized medicine, you really mean genomics,” said Gomella, chair of the Department of Urology and director of the Kimmel Cancer Center Network at Jefferson University Hospitals.

Although there is a wealth of information on the topic, he noted that not many urologists who treat patients with prostate cancer have a deep knowledge of whom they should screen, or what to do with that data.

Gomella noted that urologists should be aware of the Personalized Health Care Initiative (PHCI), which was launched by the US Department of Health and Human Services.1This initiative proposed a set of goals “for achieving gene-based medical care combined with health information technology,” he said. The PHCI aims to accelerate the development of personalized treatment strategies and transform the practice of medicine toward individualized patient care.

There are currently 3 main genomic applications: risk assessment, pharmacogenomics, and decision making for treatment, including active surveillance and adjuvant therapy. This third space is where urology has been the most engaged, but there is an increased push to determine the risk of prostate cancer and aggressive disease.

Although urology has focused on tumor and tissue genomics, there are now more data on the role of inherited genes.2,3“We’ve known for a long time about familial clustering in prostate cancer, and we’ve known of linkages in prostate cancer among families, but now we’re starting to identify that there is a clear inherited component to prostate cancer in approximately 15% of our patients,” Gomella said.

According to Gomella, until 2016, there were no National Comprehensive Cancer Network (NCCN) guideline recommendations on genetic screening for prostate cancer. Investigators did, however, recognize that urologists needed to pay attention toBRCA1/2mutations,4and in the current NCCN guidelines, there is a consideration for family and personal history of theBRCA1/2mutation being factored into screening and early detection.

From a practical standpoint, particularly regarding germline mutation screening, the immediate push is for the management of metastatic castration-resistant prostate cancer (mCRPC). It is now known that many patients who develop mCRPC have genetic abnormalities that can be targeted. For example, if a patient with mCRPC has aBRCA1/2mutation, it may be appropriate to administer therapy including PARP inhibitors. And so screening for these abnormalities will be integrated into treatment planning moving forward.

“We’re very used to somatic mutations; the last 5 or 6 years, everything we’ve done is based on what’s in the tumor. However, the germline mutations are those that can be found in the tumor inherited from your mother and father, and therapeutics today are being directed toward germline mutations in [mCRPC],” Gomella said.

Urologists should understand the potential impact of screening not only the patient but also their family members, potentially understanding their risk for developing certain cancers and any inherited risks they may pass on. This is why it is crucial for urologists to take detailed family histories, so they can make proper referrals to a genetic counselor. When assessing whether a patient needs genetic screening, it is beneficial to ask about a family history of not only prostate cancer, but also breast, ovarian, and pancreatic cancers, and even Lynch syndrome.

Further, there is a greater push for investigators and treating urologists to pay attention to how various genes interact with each other to determine their role in prostate cancer. If a patient has a mutation of theBRCA1gene, it may not necessarily lead to a higher risk or a more aggressive prostate cancer, but when combined with a mutantPTENgene, for example, it allows for more malignancies or malignant transformation to take place. Similarly, if a patient has prostate cancer with aBRCA2mutationthat does not have a causative relationship with the disease, the patient’s prostate cancer is more likely to be metastatic with a high Gleason score and aggressive features. “We have plenty of diseases in medicine where it’s 1 gene that causes the problem but in prostate cancer, it’s a lot more complicated,” Gomella said.

Gomella predicts that there will be an ever-limited role for single-gene testing for prostate in cancer. Instead, the focus will be on panel testing for inherited risk and determining the interplay of various genes and how they influence prostate cancer.

Gomella also thinks there is potential to add genes onto these panels that could prove useful in the next few years. He noted thatBRCA1/2,ATM, andHOXB13are common genes included on prostate cancer panels but that the panels will continue to be refined over time, removing less useful genes and adding genes that could play a role in prostate cancers.

Because there is not yet a defined consensus on when to screen patients with prostate cancer, Gomella laid out general criteria for referring a patient with prostate cancer to genetic counseling: If the patient has more than 2 cases of prostate cancer diagnosed at age 55 or younger in close relatives, 3 first degree relatives with prostate cancer, or aggressive prostate cancer and more than 2 cases of breast, ovarian, or pancreatic cancer in close relatives, the urologist may want to refer them to a genetic counselor. “If you suspect someone may have an inherited risk for prostate cancer, figure out who your local resource is for genetic counseling,” Gomella said.

References

  1. Byrne J, Edelson V, Friedland A, Terry SF. The Department of Health and Human Services and personalized healthcare.Eyes on the Prize: Truth Telling About Genetic Testing.Washington, DC: Genetic Alliance; 2008.
  2. 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.
  3. Na R, Zheng SL, Han M, et al. Germline mutations in ATM and BRCA1/2 distinguish risk for lethal and indolent prostate cancer and are associated with early age of death.Eur Urol.2017;7(15):740747. doi: 10.1016/j.eururo.2016.11.033.
  4. Carroll PR, Parsons JK, Andriole G, et al. NCCN guidelines insights: prostate cancer early detection, version 2.2016.J Natl Compr Canc Netw.2016;14(5):509-519. doi: 10.6004/jnccn.2016.0060.