PSA, Here’s Your Competition for Prostate Cancer Screening

MRI screening detected more clinically significant prostate cancers than did prostate-specific antigen (PSA) testing alone in the IP1-PROSTAGRAM study — and overdiagnosis of clinically insignificant cancers was not increased with the imaging approach.

The prospective, population-based study invited 2,034 men from seven primary care practices and two imaging centers in Great Britain to undergo prostate cancer screening. Of those invited, 408 men underwent screening MRI, ultrasonography, and PSA test; 310 had the tests on the same day. PSA of 3 ng/mL was the cutoff for positive results.

More men had positive MRI (score 3-5 on a five-point scale of suspicion) than had positive PSA test results (17.7% vs 9.9%; P<0.001), reported David Eldred-Evans, MBBS, of Imperial College London, and colleagues in JAMA Oncology.

As well, more men also had positive ultrasonography results (score 3-5) than positive PSA results (23.7%; P<0.001). When using a higher threshold of suspicion with a score of 4-5, the proportion of positive MRI results and ultrasonography results was similar to the proportion with positive PSA results.

“This study suggests that when screening the general population for prostate cancer, MRI using a score of 4 or 5 to define a positive test result, compared with PSA testing alone at a level of 3 ng/mL or higher, might lead to more men being diagnosed with clinically significant cancer,” Eldred-Evans and colleagues wrote.

“The IP1-PROSTAGRAM study lays the groundwork for future trials to examine the role of imaging in population-based prostate cancer screening,” commented Susanna I. Lee, MD, PhD, and Aileen O’Shea, MBBCh, both of Harvard Medical School in Boston, in an accompanying editorial.

Eldred-Evans and colleagues also looked at the number of clinically significant cancers — defined as any Gleason score of 3+4 of higher — along with insignificant lesions detected with each test used exclusively. MRI was associated with the detection of about twice as many clinically significant cancers; ultrasonography did not substantially outperform PSA testing.

PSA testing with the 3-ng/mL cutoff detected seven clinically significant cancers. In comparison, MRI with score 3-5 as cutoff detected 14 significant cancers; MRI with score 4-5, 11 significant cancers; ultrasonography with score 3-5, nine significant cancers; and ultrasonography with score 4-5, four significant cancers.

Insignificant cancers were diagnosed by PSA in four cases; MRI with score 3-5, seven cases; MRI with score 4-5, five cases; ultrasonography with score 3-5, 13 cases; and ultrasonography with score 4-5, seven cases.

Editorialists Lee and O’Shea commended the researchers on their efforts to measure reader agreement of MRI. In the study, results were reported by an experienced radiologist at one of two study sites. Readers were blinded to all other study data. In addition, 20% of the MRIs were randomly selected for review by a third reader. Interreader agreement was fair with the percentage agreements for MRI (score 3-5) of 61.5%, MRI (score 4-5) 70.5%, ultrasonography (score 3-5) 76.9%, and ultrasonography (score 4-5) 65.4%.

“If MRI is to be developed for use as a screening tool, additional efforts will need to be directed toward standardizing the imaging procedures for more reproducible results,” Lee and O’Shea noted.

They were also pleased that the study used a direct-to-community recruitment strategy to enroll a more diverse patient population than typically seen in population-based prostate cancer screening studies: 38% white, 32.4% Black, 23.0% Asian, 4.4% other, and 2.2% mixed race.

“Given that Black men are diagnosed with prostate cancer more often and at a younger age while Asian and Hispanic men are at lower risk of the disease,” Lee and O’Shea wrote, “the racial/ethnic composition of the cohorts of all prostate cancer screening trials should be scrutinized for generalizability.”