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Objectives To assess change in functional outcomes after a second focal high-intensity focused ultrasonography (HIFU) treatment compared with outcomes after one focal HIFU treatment. Patients and methods In this multicentre study (2005-2016), 821 men underwent focal HIFU for localized non-metastatic prostate cancer. The patient-reported outcome measures of International Prostate Symptom Score (IPSS), pad usage and erectile function (EF) score were prospectively collected for up to 3 years. To be included in the study, completion of at least one follow-up questionnaire was required. The primary outcome was comparison of change in functional outcomes between baseline and follow-up after one focal HIFU procedure vs after a second focal HIFU procedure, using IPSS, Expanded Prostate Cancer Index Composite (EPIC) and International Index of Erectile Function (IIEF) questionnaires. Results Of 821 men, 654 underwent one focal HIFU procedure and 167 underwent a second focal HIFU procedure. A total of 355 (54.3%) men undergoing one focal HIFU procedure and 65 (38.9%) with a second focal HIFU procedure returned follow-up questionnaires, respectively. The mean age and prostate-specific antigen level were 66.4 and 65.6 years, and 7.9 and 8.4 ng/mL, respectively. After one focal HIFU treatment, the mean change in IPSS was -0.03 (P = 0.02) and in IIEF (EF score) it was -0.4 (P = 0.02) at 1-2 years, with no subsequent decline. Absolute rates of erectile dysfunction increased from 9.9% to 20.8% (P = 0.08), leak-free continence decreased from 77.9% to 72.8% (P = 0.06) and pad-free continence from 98.6% to 94.8% (P = 0.07) at 1-2 years, respectively. IPSS prior to second focal HIFU treatment compared to baseline IPSS prior to first focal HIFU treatment was lower by -1.3 (P = 0.02), but mean IPSS change was +1.4 at 1-2 years (P = 0.03) and +1.2 at 2-3 years (P = 0.003) after the second focal HIFU treatment. The mean change in EF score after the second focal HIFU treatment was -0.2 at 1-2 years (P = 0.60) and -0.5 at 2-3 years (P = 0.10), with 17.8% and 6.2% of men with new erectile dysfunction. The rate of new pad use was 1.8% at 1-2 years and 2.6% at 2-3 years. Conclusion A second focal HIFU procedure causes minor detrimental effects on urinary function and EF. These data can be used to counsel patients with non-metastatic prostate cancer prior to considering HIFU therapy.

OBJECTIVE To integrate the mapping of ERG alterations with the collection of expression microarray (EMA) data, as previous EMA analyses have failed to consider the genetic heterogeneity and complex patterns of ERG alteration frequently found in cancerous prostates. MATERIALS AND METHODS We determined genome-wide expression levels with GeneChip Human Exon 1.0 ST arrays (Affymetrix, Santa Clara, CA, USA) using RNA prepared from 35 specimens of prostate cancer from 28 prostates. RESULTS The expression profiles showed clustering, in unsupervised hierarchical analyses, into two distinct prostate cancer categories, with one group strongly associated with indicators of poor clinical outcome. The two categories are not tightly linked to ERG status. By analysis of the data we identified a subgroup of cancers lacking ERG rearrangements that showed an outlier pattern of SPINK1 mRNA expression. There was a major distinction between ERG rearranged and non-rearranged cancers that involves the levels of expression of genes linked to exposure to beta-oestradiol, and to retinoic acid. CONCLUSIONS Expression profiling of prostate cancer samples containing single patterns of ERG alterations can provide novel insights into the mechanism of prostate cancer development, and support the view that factors other than ERG status are the major determinants of poor clinical outcome.

OBJECTIVE To propose a standard for the conduct of visually directed transrectal high-intensity focused ultrasound (HIFU) and to offer a formal description of the changes observed on B-mode ultrasonography (US) during this procedure. We describe our early experience of using two different treatment methods; algorithm-based HIFU and visually directed HIFU for the treatment of organ-confined prostate cancer. PATIENTS AND METHODS Between November 2004 and October 2005, 34 men were treated using the Sonablate®-500 (Focus Surgery, Indianapolis, IN, USA) as primary therapy for T1 or T2 prostate cancer. None had had previous hormone therapy and all had ≥ 3-month PSA nadirs recorded at the follow-up. Nine men were treated using an algorithm-based protocol (group 1) and 25 using visually directed therapy (group 2). The conduct of visually directed treatment was described and changes seen using B-mode US were categorized using three ‘Uchida’ grades. RESULTS The mean PSA nadir achieved in group 2 was 0.15 ng/mL, vs 1.51 ng/mL in group 1 (P

OBJECTIVES To test the hypothesis that dendritic cells (DC), antigen-presenting cells with the potential to stimulate primary T-cell responses, may appear in the urine of patients with bladder cancer, and that their characteristics may reflect those of DC in cancer tissue. PATIENTS AND METHODS Cells from digested tissue of transurethral resection specimens from eight patients and urine from 18 with bladder cancers were analysed using flow cytometry, immunohistochemistry and electron microscopy. Urine samples from 12 patients were also analysed during intravesical bacillus Calmette-Guerin (BCG) therapy. RESULTS Immature DC positive for major histocompatibility complex class II antigens, negative for markers of other leukocyte lineages and with low levels of co-stimulatory markers, were identified in CD45-positive cells isolated immediately from cancer tissue or amongst cells migrating from tissue fragments after overnight culture. Immature-phenotype DC were also identified in the urine of patients with bladder cancer. Their identity was confirmed by immunohistochemistry and electron microscopy. Using these methods, DC were monitored from the bladder during BCG installation for bladder cancer in 12 patients for a mean of 10 months. Of six patients who developed a recurrence of their bladder cancer over this period, all but one showed a lower percentage of DC in their urine at the end of their initial treatment. CONCLUSION We identified DC in the urine of patients with bladder cancer for the first time. We speculate that variability in the percentage of urinary DC may reflect changes in immunological activity at the tumour site; prospective studies are required to evaluate the relevance of these DC counts and characteristics to clinical outcome.