More Genetic Testing, New 
Drug Combinations Hold 
Promise for Prostate Cancer 
With Germline Variants
Pathogenic germline variants might be 
found in a relatively small percentage of 
prostate cancer patients, but they can 
make the prognosis much, much worse.  
Now, the future is looking brighter, with 
the VA and other healthcare systems 
spearheading more testing.  At the same 
time, drug combinations involving PARP 
inhibitors are showing some success in 
lengthening survival.  
PHILADELPHIA—How much of a role do pathogenic 
germline variants (PGV) play in raising prostate cancer 
risk? 
That was the question raised by a recent VA-led study. 
The answer is especially important because it informs 
genetic testing practices.
The study led by the Corporal Michael Crescenz 
VAMC, the Perelman School of Medicine at the 
University of Pennsylvania and the Abramson Cancer 
Center, all in Philadelphia, abstracted genetic testing 
results for 12 PCa risk genes, clinical, pathological and 
family history of cancer variables from clinical records for 
1,032 PCa patients who met National Comprehensive 
Cancer Network (NCCN) genetic testing criteria in 
oncology clinics and 3,602 PCa patients who underwent 
testing in the VA National Precision Oncology Program 
(VA-NPOP). The results of the preprint article were 
reported in medRxiv.1
The study team compared individual gene PGV 
rates in prostate cancer patients to cancer-free males. 
Also participating in the study were the VA Greater Los 
Angeles Healthcare System, the Puget Sound VAMC in 
Seattle and the Durham, NC, VAMC.
Results indicated that, of 4,634 prostate cancer patients, 
5.4% had PGVs in one of 12 PCa risk genes. PGVs in 
BRCA2 (1.7%), ATM (1.3%), CHEK2 (1.1%), Lynch 
genes (0.9%), and BRCA1 (0.5%) were most common. 
“The total PGV rate was significantly higher in 2825 
self-identified white vs. 1,527 self-identified Black PCa 
patients (6.3% vs 3.7%, adjp=0.0024), although rates 
of BRCA2 and BRCA1 PGVs were similar (1.9% vs. 
1.3%, adjp=0.0885 and 0.6% vs. 0.5%, adjp=0.8005, 
respectively),” the authors pointed out. “PGV rates were 
not significantly different in 311 Hispanic compared 
to 4188 non-Hispanic PCa patients (3.9% vs. 5.5%, 
adjp=1.000).”
They added that, in self-identified white patients, PGV 
rates in ATM, BRCA1, BRCA2, CHEK2 and Lynch genes 
were significantly higher compared to two cancer-free 
male cohorts. In addition, BRCA2 and Lynch genes PGV 
rates were significantly higher in PCa patients compared 
to a cancer-free control cohort in SIRE-Black men. 
	
	
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By Brenda L. Mooney

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