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Prostate cancer is generally multifocal and consists of a dominant focus—measured by tumour volume and deemed the index lesion—and one or more separate, secondary tumour foci of smaller volume. Much laboratory and clinical evidence has shown that we need to rethink how we regard low-grade and low-volume prostate lesions. In this Personal View, we discuss why small, low-grade Gleason pattern prostate lesions, which are currently designated as prostate cancer, could be regarded as non-malignant. These lesions either do not meet the criteria of the hallmarks of cancer or robust evidence that they do so is absent, by contrast with large lesions with a high Gleason grade, which seem to cause most metastatic disease.

ObjectiveTo compare cancer control in anterior compared to posterior prostate cancer lesions treated with a focal HIFU therapy approach.Materials and methodsIn a prospectively maintained national database, 598 patients underwent focal HIFU (Sonablate®500) (March/2007–November/2016). Follow-up occurred with 3-monthly clinic visits and PSA testing in the first year with PSA, every 6–12 months with mpMRI with biopsy for MRI-suspicion of recurrence. Treatment failure was any secondary treatment (ADT/chemotherapy, cryotherapy, EBRT, RRP, or re-HIFU), tumour recurrence with Gleason ≥ 3 + 4 on prostate biopsy without further treatment or metastases/prostate cancer-related mortality. Cases with anterior cancer were compared to those with posterior disease.Results267 patients were analysed following eligibility criteria. 45 had an anterior focal-HIFU and 222 had a posterior focal-HIFU. Median age was 64 years and 66 years, respectively, with similar PSA level of 7.5 ng/ml and 6.92 ng/ml. 84% and 82%, respectively, had Gleason 3 + 4, 16% in both groups had Gleason 4 + 3, 0% and 2% had Gleason 4 + 4. Prostate volume was similar (33 ml vs. 36 ml, p = 0.315); median number of positive cores in biopsies was different in anterior and posterior tumours (7 vs. 5, p = 0.009), while medium cancer core length, and maximal cancer percentage of core were comparable. 17/45 (37.8%) anterior focal-HIFU patients compared to 45/222 (20.3%) posterior focal-HIFU patients required further treatment (p = 0.019).ConclusionTreating anterior prostate cancer lesions with focal HIFU may be less effective compared to posterior tumours.

ObjectivesAssessing medium-term functional results of a novel minimally-invasive treatment for lower urinary tract symptoms due to BPO with the second generation of the temporary implantable nitinol device (iTind; Medi-Tate Ltd®, Israel): 2-year follow-up of a single-arm, prospective, international multicenter study. Further, we aimed to identify preoperative baseline parameters predicting response to iTind treatment.MethodsFollowing local ethical committee approval in every participating centre, 81 men with symptomatic BPO (IPSS ≥ 10, peak urinary flow < 12 ml/s, and prostate volume < 75 ml) were enrolled in this study. Patients with PVR > 250 ml, obstructive median lobe, previous prostatic surgery, confounding bladder or sphincter dysfunction based on medical history, active urinary infection and unable to interrupt antithrombotic or antiplatelet treatment were exclusion criteria. A wash-out period of 1 month for alpha-blockers and 6 months for 5-ARIs was mandatory to avoid confounders. The procedure was performed as previously described: implantation under light sedation and removal 5–7 days later with topical sedation. Patients were assessed for perioperative results including OR-time, pain (VAS) and complications (Clavien–Dindo-Grading System); and for functional results (PVR, Qmax, IPSS) and quality of life (QoL) including sexual and ejaculatory function using two yes/no questions. Follow-up assessments were done at 1, 3, and 6 months, and 1 and 2 years.ResultsOf the 81 patients initially enrolled in this study, follow-up included 67 men at 1 year and 51 men at 2 years. For the 51 men included in the present analysis, the median age was 65 years, median prostate volume 37 ml (range 16–65 ml). Baseline values for IPSS and QoL were 20.51 ± 4.58, 3.96 ± 0.87. Qmax and PVR were 7.62 ± 2.25 ml/s and 65.84 ± 38.46, respectively. No intraoperative complications were observed and the average pain level recorded on the visual analogue scale (VAS) was 3.2 ± 1.6. A significant reduction in symptoms and improvement in urinary flow was observed (p < 0.0001) at all assessment points: IPSS-score and QoL improved to 8.51 ± 5.51 and 1.76 ± 1.32, respectively; and Qmax increased to 16.00 ± 7.43 ml/s. None of the patients who were previously sexually active reported a deterioration in sexual or ejaculatory functions according to two yes/no questions over the follow-up period. Excluding the patients lost at follow-up, five patients underwent surgery between 12 and 24 months. Upon investigation, it was discovered that four of the five patients requiring surgery had median lobes and were protocol deviators. A failure analysis was carried out for all 81 patients in order to identify baseline parameters that could predict treatment failure. 58.33% of patients in the failure group (7 out of 12) had median lobes which was found to be statistically significant (p < 0.0001). None of the other preoperative variables (age, prostate volume, IPSS scores, Qmax, PVR, and PSA) were found to predict response to iTind treatment.ConclusioniTind treatment for BPO-related LUTS showed marked and durable reduction in symptoms and improvement of functional parameters and quality of life at 24 months of follow-up. It was found that median lobe may predict failure of iTind treatment. According to the yes/no questions, ejaculatory and sexual functions do not seem to be effected following treatment, however, this finding must be supported with further studies using the accepted tools.

Penile carcinoma is a rare malignancy in developed countries but is more common in South America and East Africa. The small number of cases means there are limited resources to investigate disease pathogenesis. This report describes a method of generating primary cell lines from freshly isolated human penile tissue using a clonal expansion approach on mitotically inactivated fibroblasts. Matched normal and penile cancer cell lines from two patients were generated and characterised. Molecular karyotyping and targeted sequencing were performed to compare their genomic landscape. Gains in 8q13.3, 10q23.2, 10q25.1, 10q26.13,12p13.33, 20q13.33, Xq21.1 or losses in Yq11.23 were consistent in both tumour cell lines. Gains in 8q13.3 and Xq21.1 cytobands positively correlated with changes in the expression of nearby genes. The top 20 differentially expressed genes are involved in immune responses like interferon alpha/beta signalling. Additionally, there was an increase in integrin β1, transglutaminase 1, keratins 5, 10, 14 and 16, and a decrease in involucrin protein expression. The cell lines described in this study can provide an invaluable platform for new insights and testing of therapies for penile carcinoma.

AbstractIntroductionFocal therapy (FT) ablates areas of prostate cancer rather than treating the whole gland. We compared oncological outcomes of FT to radical prostatectomy (RP).MethodsUsing prospective multicentre databases of 761 FT and 572 RP cases (November/2005-September/2018), patients with PSA < 20 ng/ml, Gleason