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There is little clinical information specifically regarding the clinical significance of Gleason pattern 5 in prostate biopsies. Accordingly, we have analyzed the effect of pattern 5 cancer on the prognosis of prostate cancer treated with Pd-103 brachytherapy.Intermediate-risk patients with a Gleason score of 7 or higher and/or a prostate-specific antigen level of 10–20 ng/mL and whose biopsy slides were available for review were treated on a randomized trial. The regimens consisted of implantation with Pd 103 (90 vs 115 Gy [National Institute of Standards and Technology; NIST-1999]), combined with 44 Gy versus 20 Gy of supplemental beam radiation, respectively. Beam radiation was delivered with a four-field arrangement, designed to cover the prostate and seminal vesicles with a 2-cm margin (reduced to 1.0 cm posteriorly). Isotope implantation was performed by standard techniques, using a modified peripheral loading pattern. All prostate biopsy specimens were reviewed for Gleason score by one investigator (L.T.). Along with assignment of a Gleason score based on established criteria, the presence of any pattern 5 cancer was separately noted and photographed for future review. Freedom from biochemical failure was defined as a serum prostate-specific antigen level ≤ 0.5 ng/mL at last follow-up. Four of the 156 patients had insufficient PSA follow-up for inclusion, leaving 152 patients for cancer control analysis.Overall actuarial biochemical freedom from failure was 86% at 3 years, with 20 patients having experienced biochemical failure. Patients with or without Gleason pattern 5 cancer in their biopsy specimen had similar overall biochemical control. There was no obvious trend toward poorer overall biochemical cancer control in patients with pattern 5 cancer, regardless of whether the pretreatment prostate-specific antigen was less than or greater than 10 ng/mL. Of the 17 patients with biochemical failure, clinically evident bone metastases has developed in five. Three of these five patients who had a positive bone scan had pattern 5 cancer in their biopsy.Although the presence of pattern 5 disease may be a risk factor for early systemic failure, we are encouraged that high-dose, brachytherapy-based treatment seems to provide a high likelihood of biochemical cancer control, even in patients with the highest-grade cancer.