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Penile intra-epithelial neoplasia (PeIN) is a known precursor for penile cancer. It may be undifferentiated or differentiated. The former is related to high-risk Human Papilloma Virus (HPV) and associated with p16 over-expression. Patients may present with red patches or lesions on the penis which on occasion may affect sexual activity.This study will assess associations between p16 status, patient parameters, treatment choice and outcomes. Data were collected on patients diagnosed with PeIN, who were referred to a single European Network, between 2008 and 2018. The following parameters were collected utilising patient records: demographics, smoking status, performance status, comorbidities, HPV/p16 status, lichen sclerosus (LS) status, treatment and clinical response. Log rank, Kaplan–Meier, Pearson Chi-Squared and Fishers Exact test were utilised to determine significance. One hundred thirty-seven patients were identified with PeIN and no invasive cancer. Staining for p16 was available in 91 patients and 74 patients were p16+. There were no significant differences in disease-free survival (DFS) for smoking status, performance status, comorbidities and lichen sclerosus, although patients with lichen sclerosus tended to recur sooner. Overall, p16+ patients showed significantly better DFS over p16− patients (n = 67; 10.4 vs 7.4 months; p = 0.023). In p16+ patients receiving treatment with imiquimod alone or with surgery, response rates were 100% vs 54% without imiquimod (n = 56; p = 0.017). In p16− patients receiving treatment with imiquimod alone or with surgery, response rates were 100% vs 56% without imiquimod (n = 17; p = 0.99). Overall 13.6% of patients progressed to cancer. The results indicate treatment combinations with immunotherapy tend to provide better responses despite p16 status. Patients with p16+ disease have a longer disease-free survival. Approximately 14% of patients progress to invasive disease. However, given the limitations in this study, further research is required to confirm these findings.

INTRODUCTION AND OBJECTIVE:Open inguinal lymph node dissection (oILND) has a high morbidity. Ascending saphenous sparing video-endoscopic inguinal lymph node dissection (VEILND-AS+) represents a mi...

BackgroundThe prostate cancer (PCa) diagnostic pathway is undergoing a radical change with the introduction of multiparametric magnetic resonance imaging (mpMRI), genomic testing, and different prostate biopsy techniques. It has been proposed that these tests should be used in a sequential manner to optimise risk stratification.ObjectiveTo characterise the genomic, epigenomic, and transcriptomic features of mpMRI-visible and -nonvisible PCa in clinically localised disease.Design, setting, and participantsMulticore analysis of fresh prostate tissue sampled immediately after radical prostatectomy was performed for intermediate- to high-risk PCa.InterventionLow-pass whole-genome, exome, methylation, and transcriptome profiling of patient tissue cores taken from microscopically benign and cancerous areas in the same prostate. Circulating free and germline DNA was assessed from the blood of five patients.Outcome measurement and statistical analysisCorrelations between preoperative mpMRI and genomic characteristics of tumour and benign prostate samples were assessed. Gene profiles for individual tumour cores were correlated with existing genomic classifiers currently used for prognostication.Results and limitationsA total of 43 prostate cores (22 tumour and 21 benign) were profiled from six whole prostate glands. Of the 22 tumour cores, 16 were tumours visible and six were tumours nonvisible on mpMRI. Intratumour genomic, epigenomic, and transcriptomic heterogeneity was found within mpMRI-visible lesions. This could potentially lead to misclassification of patients using signatures based on copy number or RNA expression. Moreover, three of the six cores obtained from mpMRI-nonvisible tumours harboured one or more genetic alterations commonly observed in metastatic castration-resistant PCa. No circulating free DNA alterations were found. Limitations include the small cohort size and lack of follow-up.ConclusionsOur study supports the continued use of systematic prostate sampling in addition to mpMRI, as avoidance of systematic biopsies in patients with negative mpMRI may mean that clinically significant tumours harbouring genetic alterations commonly seen in metastatic PCa are missed. Furthermore, there is inconsistency in individual genomics when genomic classifiers are applied.Patient summaryOur study shows that tumour heterogeneity within prostate tumours visible on multiparametric magnetic resonance imaging (mpMRI) can lead to misclassification of patients if only one core is used for genomic analysis. In addition, some cancers that were missed by mpMRI had genomic aberrations that are commonly seen in advanced metastatic prostate cancer. Avoiding biopsies in mpMRI-negative cases may mean that such potentially lethal cancers are missed.

Objective To determine the outcome of clinically negative node (cN0) patients with penile cancer undergoing dynamic sentinel node biopsy (DSNB), comparing the results of a 1- and 2-day protocol that can be used as a minimal invasive procedure for staging of penile cancer. Patients and Methods This is a retrospective analysis of 151 cN0 patients who underwent DSNB from 2008 to 2013 for newly diagnosed penile cancer. Data were analysed per groin and separated into groups according to the protocol followed. The comparison of the two protocols involved the number of nodes excised, γ-counts, false-negative rates (FNR), and complication rates (Clavien–Dindo grading system). Results In all, 280 groins from 151 patients underwent DSNB after a negative ultrasound ± fine-needle aspiration cytology. The 1-day protocol was performed in 65 groins and the 2-day protocol in 215. Statistically significantly more nodes were harvested with the 1-day protocol (1.92/groin) compared with the 2-day protocol (1.60/groin). The FNRs were 0%, 6.8% and 5.1%, for the 1-day protocol, 2-day protocol, and overall, respectively. Morbidity of the DSNB was 21.4% for all groins, and 26.2% and 20.1% for the 1-day and 2-day protocols, respectively. Most of the complications were of Clavien–Dindo Grade 1–2. Conclusions DSNB is safe for staging patients with penile cancer. There is a trend towards a 1-day protocol having a lower FNR than a 2-day protocol, albeit at the expense of a slightly higher complication rate.

Background: Although statins do not affect the incidence of prostate cancer (CaP), usage reduces the risk of clinical progression and mortality. Although statins are known to downregulate the mevalonate pathway, the mechanism by which statins reduce CaP progression is unknown. Methods: Bone marrow stroma (BMS) was isolated with ethical approval from consenting patients undergoing surgery for non-malignant disease. PC-3 binding, invasion and colony formation within BMS was assessed by standardised in vitro co-culture assays in the presence of different statins. Results: Statins act directly on PC-3 cells with atorvastatin, mevastatin, simvastatin (1 μℳ) and rosuvastatin (5 μℳ), but not pravastatin, significantly reducing invasion towards BMS by an average of 66.68% (range 53.93–77.04% P

Study Type – Preference (prospective cohort) Level of Evidence 1b What’s known on the subject? and What does the study add? In general the literature suggests that there is a need for improvement in aiding men diagnosed with early prostate cancer in their decision making about treatment options and that our understanding of this process is inadequate. There is limited data analyzing the reasons why these men decide between potentially curative or observational treatments and data evaluating patients’ views before and after definitive therapy are scarce. This study begins the process of understanding the reasons underlying a patient’s final treatment decision. Being a prospective study, it looks at the thought processes of these men before treatment during the time the decision is made. It also documents how satisfied patients are with their choice after their treatment and whether they would choose the same treatment again. OBJECTIVE • To identify the reasons for patients with localised prostate cancer choosing between treatments and the relationship of procedure type to patient satisfaction post-treatment. PATIENTS AND METHODS • 768 men with prostate cancer (stage T1/2, Gleason ≤7, PSA

To evaluate the accuracy of estimated glomerular filtration rate (eGFR) against the reference standard of isotopic GFR (iGFR) in monitoring renal function during follow-up after cystectomy and urinary diversion.Patients who had undergone cystectomy and ileal conduit urinary diversion at two centres between August 2001 and August 2006 were identified. eGFR calculated using the MDRD formula was compared to (51)Cr EDTA measured iGFR values measured at similar time-points during follow-up.Six hundred and fourteen paired iGFR and eGFR results were analysed from 166 patients (18% female, median age 70 years). There was a significant difference between paired iGFR and eGFR measurements (p0.0001) with a mean bias of +1.8 mls/min/1.73 m(2) (SD 18.0) and a 95% limit of agreement of -33.5 to 37.2 mls/min/1.73 m(2). iGFR and eGFR values converged at a GFR of approximately 45 mls/min/1.73 m(2). 70.6% of patients experienced a loss of renal function greater than expected (0.58 mls/min/1.73 m(2)/year). In 22.4% of these patients, a decline of greater than 10% in iGFR occurred that was undetected by eGFR measurements, which overestimated GFR. There was no significant relationship between patient height, weight or body mass index and the accuracy of eGFR measurements.iGFR measurement is recommended following ileal conduit urinary diversion if early signs of renal function loss are to be detected. eGFR overestimates GFR in critically relevant ranges and fails to detect loss in a clinically significant proportion of patients.

To review outcomes of the treatment of carcinoma in situ (CIS) of the penis at a large supra-regional penile cancer network, where centralisation has permitted greater experience with treatment outcomes, and suggest treatment strategies.The network penile cancer database, which details presentation, treatment and complications was analysed from 2003 to 2010, identifying patients with CIS, with a minimum follow-up of 2 years, looking at treatments administered and outcomes.In all, 57 patients with mean (range) age of 61 (34-91) years were identified. In all, 18 were treated by circumcision only, 20 by circumcision and local excision (LE) and 19 by circumcision and 5-flurouracil (5-FU). The mean (range) follow-up was 3.5 (2-8) years. Of those treated by circumcision none subsequently developed CIS on the glans. For those who underwent circumcision + LE, five of 20 (25%) developed recurrence requiring further treatment. Of those treated by circumcision + 5-FU, 14/19 (73.7%) completely responded. Of the five incomplete responders, two had focal invasive malignancy at repeat biopsy. One incomplete responder underwent glansectomy and four grafting. No complete responders relapsed. Complications of 5-FU included significant inflammatory response in seven (36.8%), with two requiring hospital admission and one neo-phimosis (5.3%).This study suggests that patients undergoing circumcision for isolated CIS and complete responders to 5-FU may require only short-term follow-up, as recurrence is unlikely, whereas longer follow up is required for all other patients. However, numbers in this study are small and larger studies are needed to support this. An incomplete response to 5-FU dictates immediate re-biopsy, as it carries a significant chance of previously undetected invasive disease.

Objective To assess the role of centralized pathological review in penile cancer management. Materials and Methods Newly diagnosed squamous cell carcinomas (SCC) of the penis, including squamous cell carcinoma in situ (CIS), from biopsy specimens were referred from 15 centres to the regional supra-network multidisciplinary team (Sn-MDT) between 1 January 2008 and 30 March 2011. Biopsy histology reports and slides from the respective referring hospitals were reviewed by the Sn-MDT pathologists. The biopsy specimens’ histological type, grade and stage reported by the Sn-MDT pathologist were compared with those given in the referring hospital pathology report, as well as with definitive surgery histology. Any changes in histological diagnosis were sub-divided into critical changes (i.e. those that could alter management) and non-critical changes (i.e. those that would not affect management). Results A total of 155 cases of squamous cell carcinoma or CIS of the penis were referred from 15 different centres in North-West England. After review by the Sn-MDT, the histological diagnosis was changed in 31% of cases and this difference was statistically significant. A total of 60.4% of the changes were deemed to be critical changes that resulted in a significant change in management. When comparing the biopsy histology reported by the Sn-MDT with the final histology from the definitive surgical specimens, a good correlation was generally found. Conclusions In the present study a significant proportion of penile cancer histology reports were revised after review by the Sn-MDT. Many of these changes altered patient management. The present study shows that accurate pathological diagnosis plays a crucial role in determining the correct treatment and maximizing the potential for good clinical outcomes in penile cancer. In the case of histopathology, centralization has increased exposure to penile cancer and thereby increased diagnostic accuracy, and should therefore be considered the ‘gold standard’.

To assess the role of centralized pathological review in penile cancer management.Newly diagnosed squamous cell carcinomas (SCC) of the penis, including squamous cell carcinoma in situ (CIS), from biopsy specimens were referred from 15 centres to the regional supra-network multidisciplinary team (Sn-MDT) between 1 January 2008 and 30 March 2011. Biopsy histology reports and slides from the respective referring hospitals were reviewed by the Sn-MDT pathologists. The biopsy specimens' histological type, grade and stage reported by the Sn-MDT pathologist were compared with those given in the referring hospital pathology report, as well as with definitive surgery histology. Any changes in histological diagnosis were sub-divided into critical changes (i.e. those that could alter management) and non-critical changes (i.e. those that would not affect management).A total of 155 cases of squamous cell carcinoma or CIS of the penis were referred from 15 different centres in North-West England. After review by the Sn-MDT, the histological diagnosis was changed in 31% of cases and this difference was statistically significant. A total of 60.4% of the changes were deemed to be critical changes that resulted in a significant change in management. When comparing the biopsy histology reported by the Sn-MDT with the final histology from the definitive surgical specimens, a good correlation was generally found.In the present study a significant proportion of penile cancer histology reports were revised after review by the Sn-MDT. Many of these changes altered patient management. The present study shows that accurate pathological diagnosis plays a crucial role in determining the correct treatment and maximizing the potential for good clinical outcomes in penile cancer. In the case of histopathology, centralization has increased exposure to penile cancer and thereby increased diagnostic accuracy, and should therefore be considered the 'gold standard'.

Preference (prospective cohort).1b. What's known on the subject? and What does the study add? In general the literature suggests that there is a need for improvement in aiding men diagnosed with early prostate cancer in their decision making about treatment options and that our understanding of this process is inadequate. There is limited data analyzing the reasons why these men decide between potentially curative or observational treatments and data evaluating patients' views before and after definitive therapy are scarce. This study begins the process of understanding the reasons underlying a patient's final treatment decision. Being a prospective study, it looks at the thought processes of these men before treatment during the time the decision is made. It also documents how satisfied patients are with their choice after their treatment and whether they would choose the same treatment again.To identify the reasons for patients with localised prostate cancer choosing between treatments and the relationship of procedure type to patient satisfaction post-treatment.768 men with prostate cancer (stage T1/2, Gleason≤7, PSA20 ug/L) chose between four treatments: radical prostatectomy, brachytherapy, conformal radiotherapy and active surveillance. Prior to choosing, patients were counselled by a urological surgeon, clinical (radiation) oncologist and uro-oncology specialist nurse. Pre-treatment reasons for choice were recorded. Post-treatment satisfaction was examined via postal questionnaire.Of the 768 patients, 305 (40%) chose surgery, 237 (31%) conformal beam radiotherapy, 165 (21%) brachytherapy and 61 (8%) active surveillance. Sixty percent of men who opted for radical prostatectomy were motivated by the need for physical removal of the cancer. Conformal radiotherapy was mainly chosen by patients who feared other treatments (n=63, 27%). Most men chose brachytherapy because it was more convenient for their lifestyle (n=64, 39%). Active surveillance was chosen by patients for more varied reasons. Post-treatment satisfaction was assessed in a subgroup who took part in the QOL aspect of this study. Of the respondents to the questionnaire, 212(87.6%) stated that they were satisfied/extremely satisfied with their choice and 171(92.9%) indicated they would choose the same treatment again.Men with early prostate cancer have clear reasons for making decisions about treatment. Overall, patients were satisfied with the treatment and indicated that despite different reasons for choosing treatment, they would make the same choice again.

The first case of a male adnexal tumour of probable wolffian duct origin to develop metastatic disease is reported. The characteristic histological appearance and immunohistochemical profiles of the primary and metastatic male tumours are discussed. The scanty experience relating to metastatic disease makes decisions about the most appropriate treatment challenging.

Objective To determine the survival of patients after percutanous nephrostomy drainage (PND) for obstructive uropathy secondary to pelvic malignant disease. Patients and methods The records of 77 patients undergoing PND for obstructive uropathy were reviewed. Patients were classified according to the nature of the obstructing lesion: Group I (primary untreated malignancy. 31 patients); Group II (recurrent malignancy with further treatment. 15 patients): Group III (recurrent malignancy with no further treatment. 12 patients): and Group IV (benign disease as a consequence of previous treatment, 19 patients). Outcome was assessed by survival over a mean follow-up of 20 months (range 2 days-8.3 years). Results Overall median survival was 26 weeks, with a 5-year survival of 22%. The survival in Groups I and II was not significantly different (median survival 27 and 20 weeks, respectively; 5-year survival, 10% and 20%. respectively). Group III patients had a poor prognosis (median survival 6.5 weeks) with no patient surviving beyond one year, whilst Group IV patients fared best with a 5-year survival of 64%. The commonest primary tumour type was carcinoma of the cervix (42 patients), and these patients were analysed as a subset. Benign post-radiation fibrosis was found in 16 of 27 patients (59%). Survival was related to the diagnostic group. Conclusion The nature and extent of the obstructing lesion and its potential for further treatment are the major determinants of post-nephrostomy survival. Every effort should therefore be made to identify the nature of the obstruction before deciding on PND.