Abstract

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• Biochemical parameters and pathological features as well as biopsy related morbidity of prostate cancer detected on second, third and fourth repeat prostate biopsy in men with a serum total PSA level between 4 ng/mL and 10 ng/mL were evaluated and compared to those cancers detected on initial prostate biopsy. In a prospective European Prostate Cancer Detection study, 1051 men with a total PSA level between 4 ng/mL and 10 ng/mL underwent transrectal ultrasound (TRUS)?guided sextant biopsy and two additional transition zone biopsies. All subjects whose biopsy samples were negative for prostate cancer (CaP) underwent a first repeat biopsy after 6 weeks. If also negative a third and even a fourth biopsy was performed at 8 weeks intervals. Those with clinically localized cancers underwent radical prostatectomy. Pathological and clinical features of patients diagnosed with cancer on either initial or repeat biopsy and clinically organ confined disease who agreed to undergo radical prostatectomy were compared. Cancer detection rates on first, second, third and fourth biopsy were 22% (231/1051), 10% (83/820), 5% (36/737) and 4% (4/94), respectively. Percent free PSA and PSA-TZ were the most powerful parameters to predict cancer on repeat biopsy. Overall, of patients with clinically localized disease (67% of cancers detected), 86% underwent radical prostatectomy and 14% opted for watchful waiting or radiation therapy. Overall, 58.0%, 60.9%, 86.3% and 100% had organ confined disease on first, repeat, third and fourth biopsy, respectively. Despite statistical significant differences with respect to multifocality (p=0.009) and cancer location (p=0.001) (cancers on second biopsy showing a lower rate of multifocality and a more apico-dorsal location), there were no differences with respect to stage (p=0.2), Gleason score (p=0.3), percentage Gleason grade 4/5 (p=0.2), serum PSA and patient age between first and second biopsy. However, cancers detected on third and fourth biopsy had a significantly lower Gleason score (p=0.001 and 0.001), lower rate of grade 4/5 cancer (p=0.02), lower cancer volume (p= 0.001 and 0.001) and lower stage (p= 0.001). Morbidity of first and repeat biopsy were similar, whereas third and fourth biopsy had a slightly higher complication rate. Interestingly, patients under 60 years of age reported a higher pain apprehension as quantified with the visual analog pain scale (VAS). Further, the use of the Vienna tables allowed an accurate calculation of the number of biopsy cores required based on prostate volume and age. Despite differences in location and multifocality, pathological and biochemical features of cancers detected on initial and second biopsy were similar, suggesting similar biological behavior. Cancers detected on third and fourth biopsy had a lower grade, stage and cancer volume as compared to cancers on first and repeat biopsy. Morbidity of first and repeat biopsy were similar, whereas third and fourth biopsy had a slightly higher complication rate. Hence, a second prostate biopsy in all cases of a negative finding on initial biopsy appears justified. Third and fourth repeat biopsies however, should only be obtained in very selected patients with high suspicion of cancer and/or poor prognostic factors on the first or second biopsy. Power Doppler TRUS will further enhance prostate cancer detection as will artificial neural networks as patient selecting tools