Raoul S. Concepcion, MD
Research into the biology of prostate cancer has resulted in a growing understanding of the molecular drivers of the malignancy, resulting in a rapid evolution of genetic testing that is poised to revolutionize the diagnosis and care of at-risk men as well as those who have the disease.
During a recent OncLive®
, a group of prostate cancer experts provided insights into heritable cancers and the current state of genetic and genomic testing. The discussion made clear that much progress is being made but that numerous challenges have yet to be overcome.
“Treatment of castration-resistant prostate cancer has become increasingly complex, not only because of the number of novel therapies available with distinct mechanisms of action but also because of the lack of comparative data or validated predictive markers to help guide choice of therapy,” said Raoul S. Concepcion, MD, who served as moderator of the panel discussion. “However, there is light at the end of the tunnel. As new platforms for molecular testing continue to emerge, we are entering an era of more personalized therapy.”
Panelist Neal D. Shore, MD, commented on the need to translate advancements into clinical practice. “We’re just at the beginning of the beginning,” he said.
Changing Role for PSA
Currently, prostate-specific antigen (PSA) testing remains the gold-standard screening tool for prostate cancer, but it has limitations, including an inability to determine genetic vulnerability to the disease or to distinguish clinically insignificant tumors that can be actively monitored from those that are likely to be aggressive and require immediate treatment.
Although PSA testing has revolutionized prostate cancer screening, enabling more patients with early-stage disease to be identified, it remains imprecise, and its utility has been called into question. In 2012, the United States Preventive Services Task Force (USPSTF) recommended eliminating screening for men in the general population, regardless of age.1
The recommendation did not extend to PSA surveillance following diagnosis or treatment of prostate cancer.1
The USPSTF’s stance has since softened. Although it still recommends against broad PSA-based screening in men aged ≥70 years, it encourages clinicians to discuss the benefits and harms of testing with men aged 55 to 69 years to enable them to make their own determination.2
Although some harms have been associated with PSA-based screenings, such as complications from potentially unnecessary biopsies, many clinicians have expressed concerns about eliminating PSA-based screenings altogether, including risks associated with not screening men who have a strong family history of prostate cancer or other heritable cancers that have been associated with prostate cancer.3
Data on Heritability
It has been recognized for some time that certain populations are at increased risk of prostate cancer, even after adjusting for socioeconomic and other factors.3
In the Detroit Surveillance, Epidemiology, and End Results registry database, black men were 4 times as likely to develop advanced prostate cancer as their white counterparts, suggesting prostate cancer grows more rapidly in black than in white men or that black men have earlier transformation from latent to aggressive disease.4
Many of these disparities in prostate cancer center around genetic susceptibility, with environment, behavioral, and healthcare factors contributing.5
Eliminating prostate cancer disparities requires understanding the role that genes play and how they interact with a variety of non-gene–related factors to drive prostate cancer.5
As the Peer Exchange®
panelists noted, this is an exceptionally challenging endeavor with prostate cancer because studies continue to show just how clinically and genetically heterogeneous these cancers are, with many somatic and germline mutations contributing, adding to the challenge of deciphering the constantly evolving data.
Michael A. Carducci, MD, explained the difference between germline and somatic mutations, both of which can have risk and treatment implications. “Germline
means you’re born with it—it’s in every cell, and it’s going to be with you from the beginning to the end—whereas somatic
are things that happen over time, particularly in tumor cells. As genes mutate, they can mutate again, and there’s an ongoing process that, whether our therapies affect that or just the environment, multiple hits occur over time,” he explained.