Prospective evaluation of prostate cancer detected on biopsies 1, 2, 3 and4: When should we stop?

Purpose: We evaluated biochemical parameters and pathological features, as well as biopsy related morbidity of prostate cancer detected on biopsies 2, 3 and 4 in men with total serum prostate specific antigen (PSA) between 4 and 10 ng./ml. These features were compared to those detected on prostate b iopsy 1. Materials and Methods: In this prospective European Prostate Cancer Detecti on study 1,051 men with total PSA between 4 and 10 ng./ml. underwent transr ectal ultrasound guided sextant biopsy and 2 additional transition zone bio psies. All patients in whom biopsy samples were negative for prostate cance r underwent biopsy 2 after 6 weeks. If also negative, biopsies 3 and even 4 were performed at 8-week intervals. Those patients with clinically localiz ed cancer underwent radical prostatectomy. Pathological and clinical featur es of patients diagnosed with cancer on either biopsy 1 or 2 and clinically organ confined disease who agreed to undergo radical prostatectomy were co mpared. Results: Cancer detection rates on biopsies 1, 2, 3 and 4 were 22% (231 of 1,051), 10% (83 of 820), 5% (36 of 737) and 4% (4 of 94), respectively. Ove rall, of the patients with clinically localized disease, which was 67% of c ancers detected, 86% underwent radical prostatectomy and 14% opted for watc hful waiting or radiation therapy. Overall, 58.0%, 60.9%, 86.3% and 100% of patients had organ confined disease on biopsies 1, 2, 3 and 4, respectivel y. Despite statistically significant differences in regard to multifocality (p = 0.009) and cancer location (p = 0.001), including cancer on biopsy 2 showing a lower rate of multifocality and a more apico-dorsal location, the re were no differences in regard to stage (p = 0.2), Gleason score (p = 0.3 ), percent Gleason grade 4/5 (p = 0.2), serum PSA and patient age between b iopsies I and 2. However, cancer detected on biopsies 3 and 4 had a signifi cantly lower Gleason score (p = 0.001 and 0.001), lower rate of grade 4/5 ( p = 0.02), and lower volume (p = 0.001 and 0.001) and stage (p = 0.001), re spectively. Conclusions: Despite differences in location and multifocality, pathologica l and biochemical features of cancer detected on biopsies 1 and 2 were simi lar, suggesting comparable biological behaviors. Cancer detected on biopsie s 3 and 4 had a lower grade, stage and volume compared with that on biopsie s 1 and 2. Morbidity on biopsies 1 and 2 was similar, whereas biopsies 3 an d 4 had a slightly higher complication rate. Therefore, biopsy 2 in all cas es of a negative finding on biopsy 1 appears justified. However, biopsies 3 and 4 should only be obtained in select patients with a high suspicion of cancer and/or poor prognostic factors on biopsy 1 or 2.