There are several teaching points in this case. A rising PSA level or an initial PSA level of greater than 1.5ng/mL are surrogates for the presence of cancer. In our recent publication on baseline PSA, a level of between 1.5ng/mL and 4.0ng/mL raises the relative risk of a diagnosis of prostate cancer by nearly 15-fold and up to 19-fold in African American men.1

Tables A and B

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Besides PSA velocity, the second risk factor in this patient is an elevated PCA3 test. In fact, this test was just approved by the FDA to suggest further biopsies in men who have had a prior negative biopsy. Additionally, we have recently demonstrated that PCA3 complements PSA, increasing both sensitivity and specificity of screening for prostate cancer.2

We investigated the value of the PCA3 urine test in predicting the likelihood of diagnosis of cancer prior to biopsy. Samples were obtained from 1,962 men with elevated serum PSA levels (>2.5ng/mL) and/or abnormal digital rectal examination results prior to TRUS-Bx. A total of 1,913 urine samples (97.5%) were adequate for PCA3 testing; 802 patients were diagnosed with prostate cancer with a median Gleason score of 7. Traditional PCA3 cutoff of 35 reduced the number of false positives from 1,089 to 249, a 77.1% reduction. However, false negatives (missed cancers) increased significantly from 17 to 413, an increase of >2300%. Lowering the PCA3 cutoff to 10 reduced the number of false positives by 35.4%, and false negatives only rose 5.6%. We concluded that urinary PCA3 testing in conjunction with PSA has the potential to significantly decrease the number of unnecessary biopsies of the prostate.3

About 20% of men with prostate cancer will harbor an anterior cancer, which can be missed by standard TRUS-Bx. These cancers can sometimes be identified in men who undergo an MRI imaging study. Below is an example of a 58-year-old pathologist whose TRUS-Bx revealed a Gleason score of 6 in 20% of one core; however, the whole mount radical prostatectomy specimen shows a high grade cancer in the transition zone. This would have been discovered with mapping biopsies, and likely by an endorectal coil MRI study.