1. DiGiulio, Sarah

Article Content

"The need for genetic prognostic markers is critical, because the clinicopathological diversity of prostate cancer has confounded efforts to develop effective screening strategies that avoid overdetection and overtreatment yet capture cancers that are destined to affect survival," noted Michael F. Walsh, MD, a Geneticist and Pediatric Oncologist at Memorial Sloan Kettering Cancer Center (MSKCC), New York, N.Y., and 42 coauthors in a recent study published in The New England Journal of Medicine (2016;375;443-453).

Michael F. Walsh, MD... - Click to enlarge in new windowMichael F. Walsh, MD. Michael F. Walsh, MD

The findings from the researchers' work may have identified one of those genetic prognostic markers.


After earlier findings showed an unexpectedly high frequency of patients with metastatic prostate cancer who carried pathogenic germline mutations in DNA-repair genes, the researchers looked closer at whether such patients might be more likely to have heritable defects in DNA repair.


They used multiplex sequencing assays to assess how frequently they found 20 DNA-repair gene mutations in 692 men with metastatic prostate cancer who had been treated at cancer centers across the U.S. and the U.K. Neither family history of cancer nor age at diagnosis were part of the selection criteria for the patients.


What they found: "A significant percentage of men with metastatic prostate cancer [had] heritable mutations in DNA damage genes," Walsh said. The data showed 11.8 percent of the men in the study had mutations.


Here's what else Walsh told Oncology Times about the data-and how the findings will influence current standards of care.


1 Were you and your fellow researchers surprised by the findings?

"Yes-in regard to the extent of men with metastatic prostate cancer born with cancer predisposing mutations.


"The incidence in this group of patients was unknown until this study was performed. However, work out of MSKCC in 2010 by Kenneth Offit's group did highlight [that] among a certain population isolate men with prostate cancer harboring BRCA1/2 constitutional (germline) mutations did have a poorer outcome." Offit is Chief of the Clinical Genetics Service at MSKCC.


2 Do these findings have implications that might change current standards of care for diagnosing and/or treating patients with metastatic prostate cancer?

"Absolutely-12 percent of men with metastatic prostate cancer are born with mutations that may impact their care, and other relatives harboring the same mutations may benefit from screening.


"Having a clearer biologic understanding of the constitutional make up of men with metastatic prostate cancer allows for improved rationale in drug selection and possible toxicities. Understanding [that] some men harbor mutations in DNA damage genes begs providers to consider PARP inhibitors and platinum agents-particularly in settings where conventional therapies have failed.


"This study provides a rationale for all men with metastatic prostate cancer to be tested for heritable mutations in DNA damage genes.


"[The] next steps are to better understand the impact heritable DNA damage mutations have on outcomes, to properly address means to inform other family members at risk of carrying these mutations, and to gain awareness on a national level so germline testing will be reimbursed for men with metastatic prostate cancer.


"There are many [unanswered] questions, but the key is understanding the extent heritable mutations have on oncogenesis and the most appropriate means to treat these men and care for their families."


3 What would you say is most important for practicing oncologists to know about these findings?

"When treating a man with metastatic prostate cancer, there is a significant chance there is a heritable basis for their patients' disease-and this information has a multiplier effect in the possibility to inform relatives' care."