Age-Guided Prostate Cancer Screening Proposed For BRCA Mutation Carriers

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: BRCA1/2 germline mutation carriers with a high risk of prostate cancer may benefit from an age-stratified screening strategy, suggest the results of a study presented at the ESMO Virtual Congress 2020. 

Presenting author David Margel, from the Rabin Medical Center in Petah Tikva, Israel, explained that the study recruited men aged 40–70 years with a BRCA1 185delAG or 5382inSC alteration (n=108) or BRCA2 6174delT (n=80) mutation. 

The investigators combined multiparametric magnetic resonance imaging (MRI) with prostate-specific antigen (PSA) testing using an age-stratified cutoff of 1 ng/mL or above for participants aged 40–50 years, 2 ng/mL or above for those aged 50–60 years and 2.5 ng/mL or above for men aged 60–70 years. 

Overall, 177 men completed both the MRI and PSA test, of whom 67 had normal results for both investigations, 35 had an abnormal MRI but normal PSA finding, 43 had a normal MRI with elevated PSA and 32 had an abnormal MRI and elevated PSA. 

David Margel reported a “high rate” of prostate cancer of 8.5% among the 92 men with abnormal findings who went on to 12-core systematic prostate biopsy, noting that almost half (44%) of these patients had intermediate- or high-risk disease. 

There was no difference in the rates of cancer between the BRCA1 and BRCA2 carriers, the presenter said, but he reminded delegates that the study used a “Jewish founder mutation cohort, and therefore [this] may be different across other countries or other places in the world.” 

David Margel compared the efficacy of different screening strategies in the screening cohort. He reported that the IMPACT trial’s strategy of using a PSA above 3 ng/mL would have detected just 31% of the prostate cancers but avoided 73% of biopsies. 

The most effective strategy was MRI without PSA, which detected 94% of the prostate cancers, but this came at a “very high cost” in terms of imaging and the ability to avoid just 32% of biopsies, the investigator said. 

However, when assessing patients by age using decision curve analysis, he reported that patients younger than 55 years required an MRI because low concentrations in this group meant that “PSA is not informative” for the detection of cancer. By contrast, for patients aged over 55 years, PSA was useful to triage patients before MRI. 

“Carriers younger than 55 should be triaged with multiparametric MRI and carriers older should use PSA before MRI,” David Margel therefore concluded. 

Commenting on the findings in a discussant session, Eleni Efstathiou, from the University of Texas MD Anderson Cancer Center in Houston, USA, agreed that prostate cancer in men with a BRCA1/2 mutation “is not only more frequent and may occur at a young age but [also] likely more aggressive than in the general population.” 

Noting that PSA testing missed six prostate cancers in men aged over 55 years, however, she recommends that MRI should “take the lead as a screening tool” in this age group too. 

The discussant also emphasized the “need to figure out how to make […] biopsies safer and less invasive for our patients” and “that it is upon us to make [MRI] cheaper and reliable, and to continue making the most of the information that we have for our patients’ safety”. 

References 

LBA22 - Margel D, Ber Y, Segal N, et al. Imaging based PCa screening among BRCA mutation carriers: Results from the first round of screening. ESMO Virtual Congress 2020 (Science weekend 16–19 September).

Simultaneous publication:

Segal N, Ber Y, Benjaminov O, et al. Imaging-based prostate cancer screening among BRCA mutation carriers – results from the first round of screening. Ann Oncol; Advance online publication 18 September 2020. https://doi.org/10.1016/j.annonc.2020.06.025