Improved outcome in penile cancer with radiologically enhanced stratification protocol for lymph node staging procedures: a study in 316 inguinal basins with a mean follow-up of 5 years.

BACKGROUND: Lymph node metastasis is the main determinant of survival in penile cancer patients. Conventionally clinical palpability is used to stratify patients to Inguinal Lymph node dissection (ILND) if clinically node positive (cN +) or Dynamic sentinel node biopsy (DSNB) if clinically node negative (cN0). Studies suggest a false negative rate (FNR) of around 10% (5-13%) for DSNB. To our knowledge there are no studies reporting harder end point of survival and outcomes of all clinically node positive (cN +) patients. We present our outcome data of all patients with penile cancer including false negative rates and survival in both DSNB and ILND groups. METHODS: One hundred fifty-eight consecutive patients (316 inguinal basins), who had lymph node surgery for penile cancer in a tertiary referral centre from Jan 2008 to 2018, were included in the study. All patients underwent ultrasound (US) ± fine needle aspiration cytology (FNAC) and then MRI/ CT, if needed, to stage their disease. We used combined clinical and radiological criteria (node size, architecture loss, irregular margins) to stratify patients to DSNB vs ILND as opposed to clinical palpability alone. RESULTS: 11.2% i.e., 27/241 inguinal basins had lymph node positive disease by DSNB. 54.9% i.e., 39/71 inguinal basins (IBs) had lymph node-positive disease by ILND. 4 inguinal basins with no tracer uptake in sentinel node scans are being monitored at patient's request and have not had any recurrences to date. With a mean follow-up of 65 months (range 24-150), the false-negative rate (FNR) for DSNB is 0%. Judicious uses of cross-sectional imaging necessitated ILND in 2 inguinal basins with non-palpable nodes and negative US with false positive rate of 6.3% (2/32) for ILND. The same cohort of DSNB patients might have had 11.1% (3/27) FNR if only palpability criteria was used. 43 (28%) patients who did require cross sectional imaging as per our criteria had a low node positive rate of 4.7% (p = 0.03). Mean cancer specific survival of all node-positive patients was 105 months. CONCLUSION: The performance of DSNB improved with enhanced radiological stratification of patients to either DSNB or ILND. We for the first time report the comprehensive outcome of all lymph node staging procedures in penile cancer.

DESNT: A Poor Prognosis Category of Human Prostate Cancer.

BACKGROUND: A critical problem in the clinical management of prostate cancer is that it is highly heterogeneous. Accurate prediction of individual cancer behaviour is therefore not achievable at the time of diagnosis leading to substantial overtreatment. It remains an enigma that, in contrast to breast cancer, unsupervised analyses of global expression profiles have not currently defined robust categories of prostate cancer with distinct clinical outcomes. OBJECTIVE: To devise a novel classification framework for human prostate cancer based on unsupervised mathematical approaches. DESIGN, SETTING, AND PARTICIPANTS: Our analyses are based on the hypothesis that previous attempts to classify prostate cancer have been unsuccessful because individual samples of prostate cancer frequently have heterogeneous compositions. To address this issue, we applied an unsupervised Bayesian procedure called Latent Process Decomposition to four independent prostate cancer transcriptome datasets obtained using samples from prostatectomy patients and containing between 78 and 182 participants. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biochemical failure was assessed using log-rank analysis and Cox regression analysis. RESULTS AND LIMITATIONS: Application of Latent Process Decomposition identified a common process in all four independent datasets examined. Cancers assigned to this process (designated DESNT cancers) are characterized by low expression of a core set of 45 genes, many encoding proteins involved in the cytoskeleton machinery, ion transport, and cell adhesion. For the three datasets with linked prostate-specific antigen failure data following prostatectomy, patients with DESNT cancer exhibited poor outcome relative to other patients (p=2.65×10-5, p=4.28×10-5, and p=2.98×10-8). When these three datasets were combined the independent predictive value of DESNT membership was p=1.61×10-7 compared with p=1.00×10-5 for Gleason sum. A limitation of the study is that only prediction of prostate-specific antigen failure was examined. CONCLUSIONS: Our results demonstrate the existence of a novel poor prognosis category of human prostate cancer and will assist in the targeting of therapy, helping avoid treatment-associated morbidity in men with indolent disease. PATIENT SUMMARY: Prostate cancer, unlike breast cancer, does not have a robust classification framework. We propose that this failure has occurred because prostate cancer samples selected for analysis frequently have heterozygous compositions (individual samples are made up of many different parts that each have different characteristics). Applying a mathematical approach that can overcome this problem we identify a novel poor prognosis category of human prostate cancer called DESNT.

Mutation detection in formalin-fixed prostate cancer biopsies taken at the time of diagnosis using next-generation DNA sequencing.

AIMS: Assessing whether next-generation DNA sequencing (NGS) can be used to screen prostate cancer for multiple gene alterations in men routinely diagnosed with this disease and/or who are entered into clinical trials. Previous studies are limited and have reported only low success rates. METHODS: We marked areas of cancer on H&E-stained sections from formalin-fixed needle biopsies, and used these as templates to dissect cancer-rich tissue from adjacent unstained sections. DNA was prepared using a Qiagen protocol modified to maximise DNA yield. The DNA was screened simultaneously for mutations in 365 cancer-related genes using an Illumina HiSeq 2000 NGS platform. RESULTS: From 63 prostate cancers examined, 59(94%) of the samples yielded at least 30 ng of DNA, the minimum amount of DNA considered suitable for NGS analysis. Patients in the D'Amico high-risk group yielded an average of 1033 ng, intermediate-risk patients 401 ng, and low-risk patients 97 ng. NGS of eight samples selected from high-risk and intermediate-risk groups gave a median exon read depth of 962 and detected TMPRRS2-ERG fusions, as well as a variety of mutations including those in the SPOP, TP53, ATM, MEN1, NBPF10, NCOR2, PIK3CB and MAP2K5 (MEK5) genes. CONCLUSIONS: Using the methods presented here, NGS technologies can be used to screen a high proportion of patients with prostate cancer for mutations in cancer-related genes in tissue samples opening up its general use in the context of clinical trials or routine diagnosis.

Limited shock wave therapy vs sham treatment in men with Peyronie's disease: results of a prospective randomized controlled double-blind trial.

OBJECTIVE: To assess the role of extracorporeal shock wave therapy (SWT), in a prospective randomized controlled trial, comparing limited SWT vs sham therapy in men with Peyronie's disease. PATIENTS AND METHODS: In all, 36 men were randomized to six sessions of SWT or sham treatment. Geometrical measurements of penile length and deformity, and the abridged International Index of Erectile Function (IIEF) score and visual analogue score (VAS) were recorded and re-evaluated at 6 months. The patient and assessor were unaware of the treatment type. Standard nonparametric tests were used for the statistical analysis. RESULTS: A full set of outcome data was obtained for 16 patients in the intervention group and 20 in the sham/control group (mean age 58 and 60 years, respectively, mean duration of symptoms 15 and 33 months). There was no significant difference in the mean change between the control and intervention groups on any outcome measure. There were improvements in the mean (sd) dorsal and lateral angle, of 5.3 (11.66)° and 3.5 (17.38)° in the control group, and a deterioration of 0.9 (16.01)° and 0.9 (15.56)° in SWT group. Mean improvements in curved and straight lengths were 0.2 (0.58) and 0.1 (0.8) cm in the control and mean reductions of 0.1 (0.9) and 0.1 (1.49) cm in the SWT group. The mean changes in the IIEF and VAS scores were 0.1 (3.32) and -0.8 (1.77) for control and 0.56 (2.6) and -1.05 (1.79) for SWT group. CONCLUSION: There were no significant differences in changes of variables in Peyronie's disease treated with short-term SWT.

The impact of Improving Outcomes Guidance on the management and outcomes of patients with carcinoma of the penis.

INTRODUCTION: The Improving Outcomes Guidance (IOG) for patients with carcinoma of the penis states that treatment should be provided supraregionally to populations of 4 million or greater who treat over 25 cases of penis cancer each year. This study assesses the impact of this guidance on the management and outcomes of patients with the disease in our region. PATIENTS AND METHODS: We retrospectively compared the records of 44 patients with carcinoma of the penis treated in our institution between 1969 and 1990 with 101 patients treated between 2002 and 2006, i.e. after supraregional centralisation of the service. RESULTS: There was no significant change in the stage or grade of the tumours. However, the results show that, in modern times, there was a significant increase in the amount of penis-preserving and nodal surgery as well as a fall in mortality. The improved survival is greatest in patients with poorly-differentiated disease who may, therefore, have benefited from aggressive nodal surgery. CONCLUSIONS: The centralisation of surgery for carcinoma of the penis results in improved outcomes both in terms of penis preservation and improved survival and this supports the IOG guidance.

Dry gangrene of the foreskin after second attempt at prepuce-sparing surgery for congenital penile curvature: case report and literature review.

INTRODUCTION: Dry gangrene of the foreskin following corrective surgery for congenital penile curvature (CPC) or Peyronie's disease is extremely rare. It is noted as a consequence of intraoperative penile degloving. AIM: We report one such case with its natural history presented by serial clinical pictures, discuss the management dilemmas, and review a rather scant relevant literature. METHODS: A 32-year-old man with CPC underwent prepuce-sparing corrective surgery for penile curvature on two occasions resulting in dry gangrene of the foreskin following the second attempt. RESULTS: It was managed conservatively with a satisfactory result. CONCLUSION: Gangrene of the foreskin is most likely to occur as a complication after a second attempt at prepuce-sparing surgery. It can be managed nonsurgically with a satisfactory outcome.

Laser-capture microdissection in prostate cancer research: establishment and validation of a powerful tool for the assessment of tumour-stroma interactions.

OBJECTIVES: To describe our experience with the optimization and validation of laser-capture microdissection (LCM) for biomarker analysis in prostate tissues. As LCM allows the separation of benign and malignant epithelial structures and stromal elements, it not only allows identification of the source of the biomarker, but might also accentuate gene or protein expression changes by reducing contamination by other cellular elements. MATERIALS AND METHODS: In all, 19 fresh-frozen prostate tissue samples were subjected to LCM, with the cDNA being analysed using quantitative polymerase chain reaction for several genes, to identify the optimum number of cells for capture, as well as gene markers assessing for the purity of the captured cells. The localization was further confirmed by in situ hybridization. RESULTS: Prostate-specific antigen (PSA) and cytokeratin 8, were expressed solely by epithelial cells, whereas hepatocyte growth factor (HGF) and tissue inhibitor of metalloproteinases-3 (TIMP3) were expressed only by stromal cells, and the levels of transcripts of these genes were unaltered between benign and malignant tissues. CONCLUSIONS: These data suggest that PSA, cytokeratin 8, HGF and TIMP3 are reliable gene markers of purity of epithelial and stromal compartments for LCM of prostate tumours. Although this technique is not new and is increasingly used in laboratories, it needs optimization and stringent validation criteria before data analysis. This applies to all tissue types subjected to LCM.