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Introduction Neoadjuvant cisplatin-based combination chemotherapy improves survival in muscle-invasive bladder cancer. However, response rates and survival remain suboptimal. We evaluated the efficacy, safety, and tolerability of cisplatin plus cabazitaxel. Methods A phase II single-arm trial was designed to recruit at least 26 evaluable patients. This would give 80% power to detect the primary endpoint, an objective response rate defined as a pathologic complete response plus partial response (pathologic downstaging), measured by pathologic staging at cystectomy (p0 = 0.35 and p1 = 0.60, α = 0.05). Results Objective response was seen in 15 of 26 evaluable patients (57.7%) and more than one- third of patients achieved a pathologic complete response (9/26; 34.6%). Seventy-eight percent of the patients (21/27) completed all cycles of treatment, with only 6.7% of the reported adverse events being graded 3 or 4. There were 6 treatment-related serious adverse event reported, but no suspected unexpected serious adverse reactions. In the patients who achieved an objective response, the median progression-free survival and overall survival were not reached (median follow-up of 41.5 months). In contrast, the median progression-free survival (7.2 months) and overall survival (16.9 months) were significantly worse (P = .001, log-rank) in patients who did not achieve an objective response. Conclusion Cabazitaxel plus cisplatin for neoadjuvant treatment of muscle-invasive bladder cancer can be considered a well-tolerated and effective regimen before definitive therapy with higher rates (57.7%) of objective response, comparing favorably to that with of cisplatin/gemcitabine (23%–26%). These results warrant further evaluation in a phase III study.

Objectives To report on the methods, peri-operative outcomes and histopathological concordance between frozen and final section from the NeuroSAFE PROOF feasibility study (NCT03317990). Patients and methods Between May 2018 and March 2019, 49 patients at two UK centres underwent robot-assisted radical prostatectomy (RARP). Twenty-five patient were randomized to NeuroSAFE RARP (intervention arm) and 24 to standard RARP (control arm). Frozen section was compared to final paraffin section margin assessment in the 25 patients in the NeuroSAFE arm. Operation timings and complications were collected prospectively in both arms. Results Fifty neurovascular bundles (NVBs) from 25 patients in the NeuroSAFE arm were analysed. When analysed by each pathological section (n = 250, average five per side), we noted a sensitivity of 100%, a specificity of 99.2%, and an area under the curve (AUC) of 0.994 (95% confidence interval [CI] 0.985 to 1; P ≤0.001). On an NVB basis (n = 50), sensitivity was 100%, specificity was 92.7%, and the AUC was 0.963 (95% CI 0.914 to 1; P ≤0.001). NeuroSAFE RARP lasted a mean of 3 h 16 min (knife to skin to off table, 95% CI 3 h 2 min-3 h 30 min) compared to 2 h 4 min (95% CI 2 h 2 min-2 h 25 min; P ≤0.001) for standard RARP. There was no morbidity associated with the additional length of operating time on in the NeuroSAFE arm. Conclusion This feasibility study demonstrates the safety, reproducibility and excellent histopathological concordance of the NeuroSAFE technique in the NeuroSAFE PROOF trial. Although the technique increases the duration of RARP, this does not cause short-term harm. Confirmation of feasibility has led to the opening of the fully powered NeuroSAFE PROOF randomized controlled trial, which is currently under way at four sites in the UK.

AimTo examine the effects of specialist reporting on error rates in prostate core biopsy diagnosis.MethodBiopsies were reported by eight specialist uropathologists over 3 years. New cancer diagnoses were double-reported and all biopsies were reviewed for the multidisciplinary team (MDT) meeting. Diagnostic alterations were recorded in supplementary reports and error rates were compared with a decade previously.Results2600 biopsies were reported. 64.1% contained adenocarcinoma, a 19.7% increase. The false-positive error rate had reduced from 0.4% to 0.06%. The false-negative error rate had increased from 1.5% to 1.8%, but represented fewer absolute errors due to increased cancer incidence.ConclusionsSpecialisation and double-reporting have reduced false-positive errors. MDT review of negative cores continues to identify a very low number of false-negative errors. Our data represents a ‘gold standard’ for prostate biopsy diagnostic error rates. Increased use of MRI-targeted biopsies may alter error rates and their future clinical significance.

Objective: To investigate and document the surgical, functional and oncological outcomes following surgery for high-risk prostate cancer patients. Patients and methods: Patients with pathological T3a, T3b and N1 disease were extracted from our prospectively updated institutional database. Data include demographics, preoperative cancer parameters, short and long-term complications and functional results. Details of biochemical recurrence, type and oncological outcome of salvage treatments, cancer-specific and overall survival were also obtained. Results: A total of 669 patients were included; 58.9% had T3a disease, 35.9% had pT3b and 11.4% N1 disease. With a median follow-up of 66 months (8–129), overall survival was 94.3%, cancer-specific survival was 98.7% and biochemical recurrence was 45.6%. Average inpatient stay was 1 day and the overall complication rate was 9.1%; 54.2% experienced a biochemical recurrence and 90.3% went on to have one or more salvage treatments, which were varied. Significant predictors of biochemical recurrence included pathological stage, any positive margin and patient age ( PConclusions: Surgery is associated with encouraging surgical and functional outcomes, cancer-specific survival and overall survival rates in these patients. Pathological stage is a significant predictor of biochemical recurrence. The present analysis shows that long-term observation for certain patients with biochemical recurrence is appropriate and questions the effectiveness of further local salvage treatments in patients with an immediate biochemical recurrence postoperatively. Level of evidence: II

The foreskin is a common surgical specimen encountered by the practising histopathologist. Therapeutic circumcisions are performed to treat both benign and neoplastic foreskin lesions. Penile intraepithelial neoplasia (PeIN) is the precursor lesion of penile squamous cell carcinoma (SCC). The World Health Organisation (WHO) classifies PeIN into two subtypes based on the association with Human Papillomavirus (HPV); these include differentiated and undifferentiated PeIN. These subtypes of PeIN can be differentiated by specific cytological and architectural characteristics. This review article will discuss these histological characteristics and highlight potential difficulties that may arise in diagnosing PeIN. Furthermore, it will also consider common benign and preneoplastic foreskin lesions that may be encountered when reporting the foreskin specimen.

The International Collaboration on Cancer Reporting (ICCR) was formed in 2011 to harmonise the datasets, protocols and checklists for pathological reporting of various cancers and develop internationally agreed upon, evidence-based datasets. A dataset for prostate cancer in radical prostatectomy specimens was developed in 2011-2012 as part of a pilot project; however, it required substantial revision following the ISUP Consensus Conference on Gleason Grading in 2014, the publication of the World Health Organisation (WHO) Classification of Tumours of the Urinary System and Male Genital Organs in 2016, and the 8th edition of the Tumour-Node-Metastasis (TNM) staging system in late 2016. This article presents the up-to-date, evidence-based ICCR dataset and associated commentary for reporting prostate cancer in radical prostatectomy specimens. PubMed and Google search engines were used to review the published literature on the subject, and the dataset was developed in line with the previously published ICCR framework for the development of cancer datasets. Substantial changes have been incorporated into the second edition of the ICCR prostate cancer (radical prostatectomy) dataset. These include revisions to prostate cancer grading, reporting of intraductal carcinoma of prostate and surgical margins, among others. Up-to-date cancer datasets underpin structured reporting and facilitate the production of consistent and accurate pathological data for patient care as well as comparisons between different cohorts and populations internationally.

This case report presents a 34-year-old woman who was referred to our regional plastic surgery unit following a 32-year history of a progressively enlarging mass overlying the left maxilla. The mass was initially diagnosed and treated as a low-flow vascular malformation. However, subsequent histopathological assessment confirmed the diagnosis of a cutaneous neurofibroma. To the best of our knowledge, there are only two other reported cases of a solitary neurofibroma arising from the soft tissue of the face, and this is the first reported case in the United Kingdom (UK). This article highlights difficulties in pre-operative diagnosis of solitary facial neurofibromas. We present our experience in managing this unusual case, discuss radiological clues to aid diagnosis and provide a review of the literature. Keywords: Neurofibroma, Face, Solitary

Aims: Pathological evaluation of lymphadenectomy specimens plays a pivotal role in accurate lymph node (LN) staging. Guidelines standardising the gross handling and reporting of pelvic LN dissection (PLND) in prostate (PCa) and bladder (BCa) cancer are currently lacking. This study aimed to establish current practice patterns of PLND evaluation among pathologists. Methods and results: A web-based survey was circulated to all members of the European Network of Uropathology (ENUP), comprising 29 questions focusing on the macroscopic handling, LN enumeration and reporting of PLND in PCa and BCa. Two hundred and eighty responses were received from pathologists throughout 23 countries. Only LNs palpable at grossing were submitted by 58%, while 39% routinely embedded the entire specimen. Average LN yield from PLND was ≥10 LNs in 56% and

Prostate cancer is the second major cause of male cancer deaths. Obesity, type 2 diabetes, and cancer risk are linked. Insulin-like growth factor II (IGF-II) is involved in numerous cellular events, including proliferation and survival. The IGF-II gene shares its locus with the lncRNA, H19. IGF-II/H19 was the first gene to be identified as being “imprinted”—where the paternal copy is not transcribed—a silencing phenomenon lost in many cancer types. We disrupted imprinting behaviour in vitro by altering metabolic conditions and quantified it using RFLP, qPCR and pyrosequencing, changes to peptide were measured using RIA. Prostate tissue samples were analysed using ddPCR, pyrosequencing and IHC. We compared with in silico data, provided by TGCA on the cBIO Portal. We observed disruption of imprinting behaviour, in vitro, with a significant increase in IGF-II and a reciprocal decrease in H19 mRNA, the increased mRNA was not translated into peptides. In vivo, most specimens retained imprinting status apart from a small subset which showed reduced imprinting. A positive correlation was seen between IGF-II and H19 mRNA expression, which concurred with findings of larger Cancer Genome Atlas (TGCA) cohorts. This positive correlation did not affect IGF-II peptide. Our findings show that type 2 diabetes and/or obesity, can directly affect regulation growth factors involved in carcinogenesis, indirectly suggesting a modification of lifestyle habits may reduce cancer risk.

Background: Prostate cancer is the most frequently diagnosed cancer type and the second major cause of cancer deaths amongst men. A link exists between obesity, type 2 diabetes, and cancer risk. Insulin-like growth factor II (IGF-II) plays a role in numerous cellular events, including proliferation and survival. The IGF-II gene shares its locus with the lncRNA, H19. IGF-II/H19 was also the first gene to be identified as being ‘imprinted’ – where the paternal copy is not transcribed. This silencing phenomenon is lost in many cancer types. Methods: We disrupted imprinting behaviour in vitro through the alteration of metabolic conditions and quantified it using RFLP, qPCR and pyrosequencing; changes to peptide were measured using RIA. Prostate tissue samples were analysed using ddPCR, pyrosequencing and IHC. We then compared with in silico data, provided by TGCA on the cBIO Portal.Results: Disruption of imprinting behaviour, in vitro, occurs at the molecular level with no changes to peptide. In vivo, most specimens primarily retained imprinting status, apart from a small subset which showed reduced imprinting. A positive correlation was seen between IGF-II and H19 mRNA expression, which concurred with findings of larger Cancer Genome Atlas (TGCA) cohorts. This positive correlation did not affect IGF-II peptide. Conclusions: Type 2 diabetes and / or obesity directly affect regulation growth factors involved in carcinogenesis.Trial registration: Prostate Cancer Evidence of Exercise and Nutrition Trial: nutritional and physical activity interventions for men with localised prostate cancer – feasibility study (ISRCTN99048944). Registered on 17 November 2014

Background Prostate cancer is the most common cancer among men in the UK. Prostate-specific antigen testing followed by biopsy leads to overdetection, overtreatment as well as undertreatment of the disease. Evidence of treatment effectiveness has lacked because of the paucity of randomised controlled trials comparing conventional treatments. Objectives To evaluate the effectiveness of conventional treatments for localised prostate cancer (active monitoring, radical prostatectomy and radical radiotherapy) in men aged 50–69 years. Design A prospective, multicentre prostate-specific antigen testing programme followed by a randomised trial of treatment, with a comprehensive cohort follow-up. Setting Prostate-specific antigen testing in primary care and treatment in nine urology departments in the UK. Participants Between 2001 and 2009, 228,966 men aged 50–69 years received an invitation to attend an appointment for information about the Prostate testing for cancer and Treatment (ProtecT) study and a prostate-specific antigen test; 82,429 men were tested, 2664 were diagnosed with localised prostate cancer, 1643 agreed to randomisation to active monitoring (n = 545), radical prostatectomy (n = 553) or radical radiotherapy (n = 545) and 997 chose a treatment. Interventions The interventions were active monitoring, radical prostatectomy and radical radiotherapy. Trial primary outcome measure Definite or probable disease-specific mortality at the 10-year median follow-up in randomised participants. Secondary outcome measures Overall mortality, metastases, disease progression, treatment complications, resource utilisation and patient-reported outcomes. Results There were no statistically significant differences between the groups for 17 prostate cancer-specific (p = 0.48) and 169 all-cause (p = 0.87) deaths. Eight men died of prostate cancer in the active monitoring group (1.5 per 1000 person-years, 95% confidence interval 0.7 to 3.0); five died of prostate cancer in the radical prostatectomy group (0.9 per 1000 person-years, 95% confidence interval 0.4 to 2.2 per 1000 person years) and four died of prostate cancer in the radical radiotherapy group (0.7 per 1000 person-years, 95% confidence interval 0.3 to 2.0 per 1000 person years). More men developed metastases in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring, n = 33 (6.3 per 1000 person-years, 95% confidence interval 4.5 to 8.8); radical prostatectomy, n = 13 (2.4 per 1000 person-years, 95% confidence interval 1.4 to 4.2 per 1000 person years); and radical radiotherapy, n = 16 (3.0 per 1000 person-years, 95% confidence interval 1.9 to 4.9 per 1000 person-years; p = 0.004). There were higher rates of disease progression in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring (n = 112; 22.9 per 1000 person-years, 95% confidence interval 19.0 to 27.5 per 1000 person years); radical prostatectomy (n = 46; 8.9 per 1000 person-years, 95% confidence interval 6.7 to 11.9 per 1000 person-years); and radical radiotherapy (n = 46; 9.0 per 1000 person-years, 95% confidence interval 6.7 to 12.0 per 1000 person years; p Limitations A single prostate-specific antigen test and transrectal ultrasound biopsies were used. There were very few non-white men in the trial. The majority of men had low- and intermediate-risk disease. Longer follow-up is needed. Conclusions At a median follow-up point of 10 years, prostate cancer-specific mortality was low, irrespective of the assigned treatment. Radical prostatectomy and radical radiotherapy reduced disease progression and metastases, but with side effects. Further work is needed to follow up participants at a median of 15 years. Trial registration Current Controlled Trials ISRCTN20141297. Funding This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 37. See the National Institute for Health Research Journals Library website for further project information.

Localized prostate cancer (PCa) is a manageable disease but for most men with metastatic disease, it is often fatal. A western diet has been linked with PCa progression and hyperglycaemia has been associated with the risk of lethal and fatal prostate cancer.Using PCa cell lines, we examined the impact of IGF-I and glucose on markers of epithelial-to-mesenchymal transition (EMT), migration and invasion. We examined the underlying mechanisms using cell lines and tumour tissue samples.IGF-I had differential effects on the process of EMT: inhibiting in normal and promoting in cancer cells, whereas hyperglycamia alone had a stimulatory effect in both. These effects were independent of IGF and in both cases, hyperglycaemia induced an increase IGFBP-2(tumour promoter) and FOXA1. A positive correlation existed between levels of IGFBP-2 and FOXA1 in benign and cancerous prostate tissue samples and in vitro and in vivo data indicated that FOXA1 strongly interacted with the IGFBP2 gene in normal prostate epithelial cells that was associated with a negative regulation of IGFBP-2, whereas in cancer cells the level of FOXA1 associating with the IGFBP2 gene was minimal, suggesting loss of this negative regulation. IGF-I and hyperglycaemia-induced FOXA1/IGFBP-2 play important roles in EMT.

Objectives:Recruitment to pragmatic trials is often difficult, and little is known about factors associated with key participation and treatment decisions. These were explored in the Prostate cancer testing and Treatment (ProtecT) study. Study Design and Setting:Baseline sociodemographic, patient-reported outcome, clinical history, and prostate cancer biopsy data were collected for all patients eligible to take part in the ProtecT trial, in a comprehensive cohort design. Men who rejected randomization specified a preferred option and were followed up identically to the randomized cohort. Factors associated with participation decisions, patient preferences, and reasons for changing treatment were explored. Results:Of 2,664 men with clinically localized prostate cancer, 997 (37%) rejected randomization. Their treatment preferences and subsequent treatment choices/changes in both randomized and treatment choice cohorts were strongly associated with prostate cancer risk features: toward active monitoring for low-risk disease and toward radical options with higher risk prostate cancer. Among many factors measured, only a small number of weak associations were found for occupation groups and some patient symptoms. Similar percentages changed from the random allocation and initially stated preference. Conclusion:The comprehensive cohort design provided new insights into trial recruitment and participation decisions. Opportunities to improve recruitment by supporting recruiters with equipoise and patient preferences were identified.

The International Society of Urological Pathology (ISUP) hosts a reference image database supervised by experts with the purpose of establishing an international standard in prostate cancer grading. Here, we aimed to identify areas of grading difficulties and compare the results with those obtained from an artificial intelligence system trained in grading. In a series of 87 needle biopsies of cancers selected to include problematic cases, experts failed to reach a 2/3 consensus in 41.4% (36/87). Among consensus and non-consensus cases, the weighted kappa was 0.77 (range 0.68–0.84) and 0.50 (range 0.40–0.57), respectively. Among the non-consensus cases, four main causes of disagreement were identified: the distinction between Gleason score 3 + 3 with tangential cutting artifacts vs. Gleason score 3 + 4 with poorly formed or fused glands (13 cases), Gleason score 3 + 4 vs. 4 + 3 (7 cases), Gleason score 4 + 3 vs. 4 + 4 (8 cases) and the identification of a small component of Gleason pattern 5 (6 cases). The AI system obtained a weighted kappa value of 0.53 among the non-consensus cases, placing it as the observer with the sixth best reproducibility out of a total of 24. AI may serve as a decision support and decrease inter-observer variability by its ability to make consistent decisions. The grading of these cancer patterns that best predicts outcome and guides treatment warrants further clinical and genetic studies. Results of such investigations should be used to improve calibration of AI systems.

No abstract available.

AimTo determine how clinicians use data in contemporary prostate biopsy reports.MethodsA survey was circulated to members of the British Association of Urological Surgeons and the British Uro-oncology Group.ResultsResponses were received from 114 respondents (88 urologists, 26 oncologists). Ninety-seven (94%) use the number of positive cores from each side and 43 (42%) use the % number of positive cores. When determining the number and percentage of positive cores, 72 (71%) would not differentiate between targeted and non-targeted samples. If multiple Gleason Scores (GS) were included in a report, 77 (78%) would use the worst GS even if present in a core with very little tumour, 12% would use the global GS and 10% the GS in the core most involved by tumour. Fifty-five (55%) either never or rarely used perineural invasion for patient management.ConclusionsThe number of positive cores is an important parameter for patient management but may be difficult to determine in the laboratory due to core fragmentation so the biopsy taker must indicate the number of biopsies obtained. Multiple biopsies taken from a single site are often interpreted by clinicians as separate cores when determining the number of positive cores so pathologists should also report the number of sites positive. Clinicians have a non-uniform approach to the interpretation of multiple GS in prostate biopsy reports so we recommend that pathologists also include a single ‘bottom-line’ GS for each case to direct the clinician’s treatment decision.

Objectives\ud \ud Randomized controlled trials (RCTs) deliver robust internally valid evidence but generalizability is often neglected. Design features built into the Prostate testing for cancer and Treatment (ProtecT) RCT of treatments for localized prostate cancer (PCa) provided insights into its generalizability.\ud \ud \ud Study Design and Setting\ud \ud Population-based cluster randomization created a prospective study of prostate-specific antigen (PSA) testing and a comprehensive-cohort study including groups choosing treatment or excluded from the RCT, as well as those randomized. Baseline information assessed selection and response during RCT conduct.\ud \ud \ud Results\ud \ud The prospective study (82,430 PSA-tested men) represented healthy men likely to respond to a screening invitation. The extended comprehensive cohort comprised 1,643 randomized, 997 choosing treatment, and 557 excluded with advanced cancer/comorbidities. Men choosing treatment were very similar to randomized men except for having more professional/managerial occupations. Excluded men were similar to the randomized socio-demographically but different clinically, representing less healthy men with more advanced PCa.\ud \ud \ud Conclusion\ud The design features of the ProtecT RCT provided data to assess the representativeness of the prospective cohort and generalizability of the findings of the RCT. Greater attention to collecting data at the design stage of pragmatic trials would better support later judgments by clinicians/policy-makers about the generalizability of RCT findings in clinical practice.

Objective: The formation of multidisciplinary teams (MDTs) was formalised for urological cancer services by the National Institute for Health and Care Excellence (NICE) in the 2002 Improving Outcomes in Urological Cancer guidance. This project aimed to assess the variability of MDT recommendations when presented with the same patient. It covered the type and grade of tumour, recorded stage, treatment recommendations and whether clinical trials were considered. Materials and methods: Anonymised details of 10 patients were sent to South West Trust MDTs in two tranches. Details included age, clinical history, haematology and biochemistry results, digital radiology, and pathology text. A panel of representative urologists and urological oncologists from the region decided on optimal treatment and key points of management decisions. Results: The MDTs were not consistent in decision making. This agrees with a previous survey of urologists which also showed inconsistent decision making, and under-use of clinical cues. Some decisions contradicted NICE guidelines in force at the time. Conclusions: MDTs are now an instrumental, integrated part of cancer management. It is vital for assurance of best patient care and best outcomes that the MDT considering and planning treatment is fully functional and well informed on the evidence base, with effective communications. This audit suggests that this is not the case. The Oxford Centre for Evidence-based Medicine – Levels of Evidence is not applicable to this study.

Infiltration of the prostatic ducts by prostatic adenocarcinoma occurs relatively frequently, being most commonly associated with high grade disease. It is now recognised that intraductal carcinoma of the prostate (IDCP) has an associated poor prognosis and this is reflected in its histological, molecular and immunohistochemical features. The current recommendation of the World Health Organization is that IDCP not be taken into consideration when grading prostate adenocarcinoma. It is apparent that Gleason did not differentiate between IDCP and stromal invasive carcinoma when developing and validating his grading system, and recent studies suggest that the incorporation of IDCP grading into the overall grading of the specimen provides additional prognostic information.

Background There is limited evidence relating to the cost-effectiveness of treatments for localised prostate cancer. Methods The cost-effectiveness of active monitoring, surgery, and radiotherapy was evaluated within the Prostate Testing for Cancer and Treatment (ProtecT) randomised controlled trial from a UK NHS perspective at 10 years’ median follow-up. Prostate cancer resource-use collected from hospital records and trial participants was valued using UK reference-costs. QALYs (quality-adjusted-life-years) were calculated from patient-reported EQ-5D-3L measurements. Adjusted mean costs, QALYs, and incremental cost-effectiveness ratios were calculated; cost-effectiveness acceptability curves and sensitivity analyses addressed uncertainty; subgroup analyses considered age and disease-risk. Results Adjusted mean QALYs were similar between groups: 6.89 (active monitoring), 7.09 (radiotherapy), and 6.91 (surgery). Active monitoring had lower adjusted mean costs (£5913) than radiotherapy (£7361) and surgery (£7519). Radiotherapy was the most likely (58% probability) cost-effective option at the UK NICE willingness-to-pay threshold (£20,000 per QALY). Subgroup analyses confirmed radiotherapy was cost-effective for older men and intermediate/high-risk disease groups; active monitoring was more likely to be the cost-effective option for younger men and low-risk groups. Conclusions Longer follow-up and modelling are required to determine the most cost-effective treatment for localised prostate cancer over a man’s lifetime. Trial registration Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014).

ObjectiveDietary factors and physical activity may alter prostate cancer progression. We explored the feasibility of lifestyle interventions following radical prostatectomy for localised prostate cancer.DesignPatients were recruited into a presurgical observational cohort; following radical prostatectomy, they were offered randomisation into a 2×3 factorial randomised controlled trial (RCT).SettingA single National Health Service trust in the South West of England, UK.ParticipantsThose with localised prostate cancer and listed for radical prostatectomy were invited to participate.RandomisationRandom allocation was performed by the Bristol Randomised Trial Collaboration via an online system.InterventionsMen were randomised into both a modified nutrition group (either increased vegetable and fruit, and reduced dairy milk; or lycopene supplementation; or control) and a physical activity group (brisk walking or control) for 6 months.BlindingOnly the trial statistician was blind to allocations.Primary outcome measuresPrimary outcomes were measures of feasibility: randomisation rates and intervention adherence at 6 months. Collected at trial baseline, three and six months, with daily adherence reported throughout. Our intended adherence rate was 75% or above, the threshold for acceptable adherence was 90%.Results108 men entered the presurgical cohort, and 81 were randomised into the postsurgical RCT (randomisation rate: 93.1%) and 75 completed the trial. Of 25 men in the nutrition intervention, 10 (40.0%; 95% CI 23.4% to 59.3%) adhered to the fruit and vegetable recommendations and 18 (72.0%; 95% CI 52.4% to 85.7%) to reduced dairy intake. Adherence to lycopene (n=28), was 78.6% (95% CI 60.5% to 89.8%), while 21/39 adhered to the walking intervention (53.8%; 95% CI 38.6% to 68.4%). Most men were followed up at 6 months (75/81; 92.6%). Three ‘possibly related’ adverse events were indigestion, abdominal bloating and knee pain.ConclusionsInterventions were deemed feasible, with high randomisation rates and generally good adherence. A definitive RCT is proposed.Trial registration numberISRCTN 99048944.

Summary Background An increasing volume of prostate biopsies and a worldwide shortage of urological pathologists puts a strain on pathology departments. Additionally, the high intra-observer and inter-observer variability in grading can result in overtreatment and undertreatment of prostate cancer. To alleviate these problems, we aimed to develop an artificial intelligence (AI) system with clinically acceptable accuracy for prostate cancer detection, localisation, and Gleason grading. Methods We digitised 6682 slides from needle core biopsies from 976 randomly selected participants aged 50–69 in the Swedish prospective and population-based STHLM3 diagnostic study done between May 28, 2012, and Dec 30, 2014 (ISRCTN84445406), and another 271 from 93 men from outside the study. The resulting images were used to train deep neural networks for assessment of prostate biopsies. The networks were evaluated by predicting the presence, extent, and Gleason grade of malignant tissue for an independent test dataset comprising 1631 biopsies from 246 men from STHLM3 and an external validation dataset of 330 biopsies from 73 men. We also evaluated grading performance on 87 biopsies individually graded by 23 experienced urological pathologists from the International Society of Urological Pathology. We assessed discriminatory performance by receiver operating characteristics and tumour extent predictions by correlating predicted cancer length against measurements by the reporting pathologist. We quantified the concordance between grades assigned by the AI system and the expert urological pathologists using Cohen's kappa. Findings The AI achieved an area under the receiver operating characteristics curve of 0·997 (95% CI 0·994–0·999) for distinguishing between benign (n=910) and malignant (n=721) biopsy cores on the independent test dataset and 0·986 (0·972–0·996) on the external validation dataset (benign n=108, malignant n=222). The correlation between cancer length predicted by the AI and assigned by the reporting pathologist was 0·96 (95% CI 0·95–0·97) for the independent test dataset and 0·87 (0·84–0·90) for the external validation dataset. For assigning Gleason grades, the AI achieved a mean pairwise kappa of 0·62, which was within the range of the corresponding values for the expert pathologists (0·60–0·73). Interpretation An AI system can be trained to detect and grade cancer in prostate needle biopsy samples at a ranking comparable to that of international experts in prostate pathology. Clinical application could reduce pathology workload by reducing the assessment of benign biopsies and by automating the task of measuring cancer length in positive biopsy cores. An AI system with expert-level grading performance might contribute a second opinion, aid in standardising grading, and provide pathology expertise in parts of the world where it does not exist. Funding Swedish Research Council, Swedish Cancer Society, Swedish eScience Research Center, EIT Health.

Aims: The treatment of prostate cancer has evolved markedly over the last 40 years, including radiotherapy, notably with escalated dose and targeting. However, the optimal treatment for localised disease has not been established in comparative randomised trials. The aim of this article is to describe the history ofprostate radiotherapy trials, including their quality assurance processes, and to compare these with the ProtecT trial.Materials and methods: The UK ProtecT randomised trial compares external beam conformal radiotherapy, surgery and active monitoring for clinically localized prostate cancer and will report on the primary outcome (disease-specific mortality) in 2016 following recruitment between 1999 and 2009. The embedded quality assurance programme consists of on-site machine dosimetry at the nine trial centres, a retrospective review of outlining and adherence to dose constraints based on the trial protocol in 54 participants (randomly selected, around 10% of the total randomised to radiotherapy, n ¼ 545). These quality assurance processes and results were compared with prostate radiotherapy trials of a comparable era.Results: There has been an increasingly sophisticated quality assurance programme in UK prostate radiotherapy trials over the last 15 years, reflecting dose escalation and treatment complexity. In ProtecT, machine dosimetry results were comparable between trial centres and with the UK RT01 trial. The outliningreview showed that most deviations were clinically acceptable, although three (1.4%) may have been of clinical significance and were related to outlining of theprostate. Seminal vesicle outlining varied, possibly due to several prostate trials running concurrently with different protocols. Adherence to dose constraints inProtecT was considered acceptable, with 80% of randomised participants having two or less deviations and planning target volume coverage was excellent.Conclusion: The ProtecT trial quality assurance results were satisfactory and comparable with trials of its era. Future trials should aim to standardise treatment protocols and quality assurance programmes where possible to reduce complexities for centres involved in multiple trials. 2016 Published by Elsevier Ltd on behalf of The Royal College of Radiologists.

5030 Background: Neoadjuvant cisplatin-based combination chemotherapy (NAC) improves survival in muscle invasive bladder cancer (MIBC). However, response rates and survival remain suboptimal. We sought to evaluate the efficacy, safety and tolerability of cisplatin cabazitaxel combination in this patient group. Methods: A phase 2 single arm trial (Simon 2 stage), to recruit at least 26 evaluable patients was designed with 80% power to detect the primary endpoint, objective response rate (ORR) of > 35%. ORR was defined as pathological complete response (pCR) plus partial response (pathological downstaging), measured by pathologic staging (T2 or greater at diagnosis, to T1 or less at radical cystectomy). Treatment was with Cisplatin 70mg/m2 and Cabazitaxel 15mg/m2 on day 1 of a 21 day cycle, for 4 cycles prior to surgery. Toxicity was recorded using CTCAE v.4.03. Quality of Life (QoL) data were collected at baseline, prior to each cycle of chemotherapy and at 3-5 weeks after 4th cycle of chemotherapy using EQ-5D and EORTC QLQ-C30, BLM30 questionnaires. Results: Objective response was seen in 15 out of 26 evaluable patients, 57.7% and over a third of patients achieved pCR (9/26; 34.6%). 78% (21/27) of patients completed all cycles of treatment, with only 6.7% of the reported adverse events (AEs) being graded 3 or 4. There were 6 treatment related SAEs reported but no SUSARs. In patients who achieved objective response the median progression free (PFS) and overall survival (OS) were not reached (median follow up: 41.5m). In contrast, median PFS (7.2m) and OS (16.9m) were significantly worse (p = 0.001) in patients who did not respond. Response rates for EORTC QLQ-C30, BLM 30 and EQ5D questionnaires was 70.4, 70.4 & 63% respectively, at end of treatment. There was no significant difference in EORTC QLQ C30 summary, global health scores and EQ5D score with treatment. There was a significant decline in mean QLQ C30 domain scores after 1st cycle compared to baseline, but no further deterioration with subsequent cycles of chemotherapy. Conclusions: Cabazitaxel with cisplatin as NAC of MIBC can be considered a safe, well-tolerated and effective regimen with higher pCR rate of 34.6%. This compares favorably to that with Cisplatin/Gemcitabine (23-26%). Minimal changes in Global Health & EQ5D observed during NAC further demonstrates the excellent tolerability of this regimen and to our knowledge are the first data regarding QoL in NAC in MIBC. These results warrant further evaluation in a larger phase 3 study. Clinical trial information: 2011 004090 82 .

Summary The International Collaboration on Cancer Reporting (ICCR) is a project which issues datasets and guidelines for international standardisation of cancer reporting. This review summarises the required and recommended elements of the datasets for prostate core needle biopsies and transurethral resection (TURP) and enucleation specimens of the prostate. To obtain as much information as possible from needle biopsies there should be only one core in each specimen jar with the exception of saturation biopsies. The gross description of the specimens should include core lengths of needle biopsies and weight of resection specimens. The tumours should be classified according to the 4th World Health Organization (WHO) classification and graded both by Gleason scores and the grouping of these in International Society of Urological Pathology (ISUP) grades (Grade groups). Percent high-grade cancer is an optional component of the report. Tumour extent in needle biopsies should be reported both by number of cores positive for cancer and the linear extent measured in either millimetre or percent core involvement by tumour. In needle biopsies where low-grade cancer is discontinuous and seen in few cores, it is recommended that the tumour extent should be reported both by including and subtracting intervening benign tissue. For resection specimens, the percentage of the tissue area (or percentage of number of TURP chips) involved with cancer should be estimated. Extraprostatic extension should be reported when seen, while the reporting of perineural, seminal vesicle/ejaculatory duct and lymphovascular invasion is only recommended. Intraductal carcinoma of the prostate (IDC-P) should be reported when present, because of its strong link with aggressive cancer. The current recommendation is that the IDC-P component should not be graded. The structured and standardised reporting of prostate cancer contributes to safer and more efficient patient care and facilitates the compilation and understanding of multiparametric diagnostic and prognostic data.

Aims: Despite efforts to standardise grading of prostate cancer, even among experts there is still a considerable variation in grading practices. In this study we describe the use of Pathology Imagebase, a novel reference image library, for setting an international standard in prostate cancer grading. Methods and results: The International Society of Urological Pathology (ISUP) recently launched a reference image database supervised by experts. A panel of 24 international experts in prostate pathology reviewed independently microphotographs of 90 cases of prostate needle biopsies with cancer. A linear weighted kappa of 0.67 (95% confidence interval = 0.62-0.72) and consensus was reached in 50 cases. The interobserver weighted kappa varied from 0.48 to 0.89. The highest level of agreement was seen for Gleason score (GS) 3 + 3 = 6 (ISUP grade 1), while higher grades and particularly GS 4 + 3 = 7 (ISUP grade 3) showed considerable disagreement. Once a two-thirds majority was reached, images were moved automatically into a public database available for all ISUP members at www.isupweb.org. Non-members are able to access a limited number of cases. Conclusions: It is anticipated that the database will assist pathologists to calibrate their grading and, hence, decrease interobserver variability. It will also help to identify instances where definitions of grades need to be clarified.

Transperineal template prostate biopsies (TTPB) are performed for assessments after unexpected negative transrectal ultrasound biopsies (TRUSB), correlation with imaging findings and during active surveillance. The impact of TTPBs on pathology has not been analysed. The European Network of Uropathology (ENUP) distributed a survey on TTPB, including how specimens were received, processed and analysed. Two hundred forty-four replies were received from 22 countries with TTPBs seen by 68.4% of the responders (n = 167). Biopsies were received in more than 12 pots in 35.2%. The number of cores embedded per cassette varied between 1 (39.5%) and 3 or more (39.5%). Three levels were cut in 48.3%, between 2 and 3 serial sections in 57.2% and unstained spare sections in 45.1%. No statistical difference was observed with TRUSB management. The number of positive cores was always reported and the majority gave extent per core (82.3%), per region (67.1%) and greatest involvement per core (69.4%). Total involvement in the whole series and continuous/discontinuous infiltrates were reported in 42.2 and 45.4%, respectively. The majority (79.4%) reported Gleason score in each site or core, and 59.6% gave an overall score. A minority (28.5%) provided a map or a diagram. For 19%, TTPB had adversely affected laboratory workload with only 27% managing to negotiate extra costs. Most laboratories process samples thoroughly and report TTPB similarly to TRUSB. Although TTPB have caused considerable extra work, it remains uncosted in most centres. Guidance is needed for workload impact and minimum standards of processing if TTPB work continues to increase.

Angiogenesis is required for tumour growth and is induced principally by vascular endothelial growth factor A (VEGF-A). VEGF-A pre-mRNA is alternatively spliced at the terminal exon to produce two families of isoforms, pro- and anti-angiogenic, only the former of which is upregulated in prostate cancer (PCa). In renal epithelial cells and colon cancer cells, the choice of VEGF splice isoforms is controlled by the splicing factor SRSF1, phosphorylated by serine-arginine protein kinase 1 (SRPK1). Immunohistochemistry staining of human samples revealed a significant increase in SRPK1 expression both in prostate intra-epithelial neoplasia lesions as well as malignant adenocarcinoma compared with benign prostate tissue. We therefore tested the hypothesis that the selective upregulation of pro-angiogenic VEGF in PCa may be under the control of SRPK1 activity. A switch in the expression of VEGF165 towards the anti-angiogenic splice isoform, VEGF165b, was seen in PC-3 cells with SRPK1 knockdown (KD). PC-3 SRPK1-KD cells resulted in tumours that grew more slowly in xenografts, with decreased microvessel density. No effect was seen as a result of SRPK1-KD on growth, proliferation, migration and invasion capabilities of PC-3 cells in vitro. Small-molecule inhibitors of SRPK1 switched splicing towards the anti-angiogenic isoform VEGF165b in PC-3 cells and decreased tumour growth when administered intraperitoneally in an orthotopic mouse model of PCa. Our study suggests that modulation of SRPK1 and subsequent inhibition of tumour angiogenesis by regulation of VEGF splicing can alter prostate tumour growth and supports further studies for the use of SRPK1 inhibition as a potential anti-angiogenic therapy in PCa.

Objectives: The proto-oncogene ETS-related gene ( ERG ) is consistently overexpressed in prostate cancer. Alternatively spliced isoforms of ERG have variable biological activities; inclusion of exon 11 (72 base pairs [bp]) is associated with aggressiveness and progression of disease. Exon 10 (81 bp) has also been shown to be alternatively spliced. Within this study, we assess whether ERG protein, messenger RNA (mRNA), and ERG splice isoform mRNA expression is altered as prostate cancer progresses. Methods: Detection of the TMPRSS2-ERG fusion was done using direct methods (reverse transcription polymerase chain reaction [PCR] and fluorescence in situ hybridization) and indirect methods for ERG mRNA and protein expression using quantitative PCR and immunohistochemistry, respectively. A linear equation method was used to quantitatively determine relative proportions of ERG variants ( ERG72/Δ72 , ERG81/Δ81 ) for each sample. Results: ERG mRNA and protein expression is increased in patients with advanced prostate cancer, with higher levels of ERG expression significantly associated with seminal vesicle invasion (stage pT3b) and biochemical recurrence. Genes involved in cell migration and invasiveness (matrix metalloproteinase 7, osteopontin, and septin 9) are increased in prostate cancers that overexpress ERG . In addition, there is a clear indication of increased retention of exons 10 and 11 in prostate cancer. Conclusions: Analysis of ERG and its variants may be valuable in determining prognosis and development of prostate cancer.

AimsTo assess the lymph node content of anterior prostatic fat (APF) sent routinely at robot-assisted laparoscopic radical prostatectomy (RALP) and the incidence of positive nodes in the extended pelvic lymph node dissection.MethodsBetween September 2008 and April 2012, APF excised from 282 patients who underwent RALP was sent for pathological analysis. This tissue was completely embedded and lymph nodes counted.ResultsIn total, 49/282 (17%) patients had lymph nodes in the APF, median lymph node yield in this tissue was 1 (range 1–5). In four patients, the lymph nodes contained metastatic deposits. These patients did not have positive nodes elsewhere in the extended lymph node dissection.ConclusionsAPF contains lymph nodes in 1 in 6 patients and infrequently these may be malignant. APF should always be removed at radical prostatectomy. APF should be routinely sent for pathological analysis.

Aims To look at the incidence of tip margin involvement in skin excisions for basal cell carcinomas (BCCs) and to examine if any factors might be used to predict margin involvement. Methods and results All reports of BCCs by a single dermatopathologist were reviewed and 793 excisions were included from 642 patients. Whether there was BCC in the tip and whether this tip was involved were recorded together with macroscopic and microscopic factors based on the Royal College of Pathologists’ (RCPath) dataset. Statistical analysis was carried out to determine associations between these factors and tip involvement. In 43 (5%) specimens the tip margin was involved and in 35 (4%) cases the peripheral lateral margin was involved. Risk factors for tip margin involvement were a lesion that was non-discernible macroscopically and most importantly, involvement of a peripheral lateral margin. Conclusions The incidence of tip margin involvement is small and it appears unnecessary to embed the tips unless the lesion is non-discernible macroscopically or if the peripheral lateral margin is involved.

Serous carcinomas most commonly arise within the uterine corpus or ovary/fallopian tube, but there are 2 prior case reports of primary vaginal serous carcinoma. We report 2 examples of high-grade serous carcinoma arising within the urethra or a urethral diverticulum (1 case each). Both neoplasms exhibited the classic morphologic features of high-grade serous carcinoma, and a combination of clinical, radiologic, and pathologic examination excluded other possible sites of primary neoplasm.

Background The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. Methods We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. Results There were 17 prostate-cancer-specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3 to 2.0); the difference among the groups was not significant (P=0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3 events per 1000 person-years; 95% CI, 4.5 to 8.8) than in the surgery group (13 men; 2.4 per 1000 person-years; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0 per 1000 person-years; 95% CI, 1.9 to 4.9) (P=0.004 for the overall comparison). Higher rates of disease progression were seen in the active-monitoring group (112 men; 22.9 events per 1000 person-years; 95% CI, 19.0 to 27.5) than in the surgery group (46 men; 8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9) or the radiotherapy group (46 men; 9.0 events per 1000 person-years; 95% CI, 6.7 to 12.0) (P

Background: A growing body of observational evidence suggests that nutritional and physical activity interventions are associated with beneficial outcomes for men with prostate cancer, including brisk walking, lycopene intake, increased fruit and vegetable intake and reduced dairy consumption. However, randomised controlled trial data are limited. The 'Prostate Cancer: Evidence of Exercise and Nutrition Trial' investigates the feasibility of recruiting and randomising men diagnosed with localised prostate cancer and eligible for radical prostatectomy to interventions that modify nutrition and physical activity. The primary outcomes are randomisation rates and adherence to the interventions at 6 months following randomisation. The secondary outcomes are intervention tolerability, trial retention, change in prostate specific antigen level, change in diet, change in general physical activity levels, insulin-like growth factor levels, and a range of related outcomes, including quality of life measures. Methods/design: The trial is factorial, randomising men to both a physical activity (brisk walking or control) and nutritional (lycopene supplementation or increased fruit and vegetables with reduced dairy consumption or control) intervention. The trial has two phases: men are enrolled into a cohort study prior to radical prostatectomy, and then consented after radical prostatectomy into a randomised controlled trial. Data are collected at four time points (cohort baseline, true trial baseline and 3 and 6 months post-randomisation). Discussion: The Prostate Cancer: Evidence of Exercise and Nutrition Trial aims to determine whether men with localised prostate cancer who are scheduled for radical prostatectomy can be recruited into a cohort and subsequently randomised to a 6-month nutrition and physical activity intervention trial. If successful, this feasibility trial will inform a larger trial to investigate whether this population will gain clinical benefit from long-term nutritional and physical activity interventions post-surgery. Prostate Cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) is registered on the ISRCTN registry, ref number ISRCTN99048944. Date of registration 17 November 2014.

International audience; BACKGROUND: It is unclear whether the reported variation in the diagnosis of intraductal carcinoma of the prostate (IDC-P) is due to variable interpretation of borderline morphology, use of different diagnostic criteria or both. AIMS: We sought to determine the degree of variation in the diagnostic criteria and reporting rules for IDC-P in prostate biopsies employed by expert uropathologists. METHODS: A questionnaire survey was circulated to 23 expert uropathologists from 11 European countries. RESULTS: Criteria used for diagnosis of IDC-P included solid intraductal growth (100%), dense cribriform (96%), loose cribriform/micropapillary with nuclear size \textgreater6× normal (83%) or comedonecrosis (74%) and dilated ducts \textgreater2× normal (39%). 'Nuclear size' was interpreted as nuclear area by 74% and nuclear diameter by 21%. Pure IDC-P in needle biopsies was reported by 100% and Gleason graded by 30%. All would perform immunohistochemistry in such cases to rule out invasive cancer. An IDC-P component associated with invasive cancer would be included in the determination of tumour extent and number of cores involved by 74% and 83%, respectively. 52% would include IDC-P component when grading invasive cancer. 48% would perform immunohistochemistry in solid or cribriform nests with comedonecrosis to exclude IDC-P (17% routinely, 30% if the focus appeared to have basal cells on H&E). 48% graded such foci as Gleason pattern 5 even if immunohistochemistry demonstrated the presence of basal cells. CONCLUSIONS: There is a need for more clarity in the definition of some of the diagnostic criteria for IDC-P as well as for greater standardisation of IDC-P reporting

Aims To examine the clinicopathological features of a series of penile melanomas and screen for mutations in the BRAF and KIT genes, which are seen in melanomas from other sites. Methods and results 12 patients with penile melanoma were identified over a 10-year period in two supra-regional networks in the UK. The 2- and 5-year survival was 61% and 20%, respectively. Half the patients had lymph node involvement at presentation; this was a poor prognostic indicator. KIT exons 11, 13, 17 and 18, and BRAF codons 600 and 601 were analysed for mutations by Sanger sequencing and pyrosequencing, respectively. None of the tumours showed either KIT mutations or the BRAF V600E mutation. Conclusion Penile melanomas are extremely rare and have a similar prognosis to melanomas elsewhere, but they often present late, leading to a poor outcome. The mutations seen in melanomas from other sites appear to be rarely present in these tumours.

Oxley J D & Sen C (2011) Histopathology Error rates in reporting prostatic core biopsies58, 759–765 Aims: To evaluate the false-negative and false-positive error rates both in a screening and a non-screening population. Methods and results: A total of 4192 prostatic biopsies were reported in a 6-year period by 15 consultant histopathologists, two of whom had an interest in uropathology and were deemed to be specialists (J.O. and C.S.). All biopsies were reviewed prior to the multidisciplinary team (MDT) meeting. The overall false-negative rate was 1.7% (screening 2.1%, non-screening 1.5%). The overall false-positive rate was 0.5% (screening 0.9%, non-screening 0.4%). These error rates varied among pathologists, with the false-negative rate ranging from 0% to 9.3%, and the false-positive rate ranging from 0% to 3.8%. Conclusion: The false-negative rate was three times greater than the false-positive rate, showing that detection of significant pathology is far greater in the negative biopsies. More errors occurred in the screening population than in the non-screening population. The consultants making the most errors were non-specialists, but the specialists also made false-negative errors, suggesting that just using specialist reporting alone would not have eradicated errors.

468 Background: Neoadjuvant cisplatin-based combination chemotherapy improves survival in muscle invasive transitional cell carcinoma (MI-TCC). However response rates and survival remain suboptimal. We sought to evaluate the efficacy of cabazitaxel (CBZ) with cisplatin (CIS) in this setting. Methods: A single arm phase 2 study was designed with 80% power to detect an objective response rate (ORR) of >35%. Patients with MI-TCC were included if fit to receive neoadjuvant chemotherapy and to undergo radical cystectomy. Treatment was with CIS 70mg/m2 and CBZ 15mg/m2 on day 1 of a 21 day cycle, for 4 cycles prior to surgery. Primary prophylaxis was with pegylated GCSF. Toxicity was recorded using CTCAE v.4.03. Objective response was defined as a reduction in Tumour (T) stage from T2 or greater at diagnosis, to T1 or less at radical cystectomy. QoL data was assessed during and after chemotherapy using EQ-5D and EORTC-BLM30 questionnaires. Results: 28 patients were enrolled with median age 68.6 years (range 47-79). Response outcome (first 23 cases) and toxicity data (first 24 cases) are in this abstract; the remaining cases, currently scheduled for surgery, will be added to the final presentation. Pathological complete response (pCR) was observed in 7/23 patients (30.4%) and ORR was 56.5% (13/23). 18/24 (75%) completed 4 cycles; reasons for stopping were disease progression (2/24, 8.3%), adverse events (2/24, 8.3%) and patient choice (2/24, 8.3%). 7/24 patients (29%) experienced treatment related grade 3 and 4 adverse events. Conclusions: These results demonstrate that CIS and CBZ chemotherapy has an acceptable safety profile and is well tolerated in this setting. This combination shows promising efficacy (pCR 30.4%, ORR 56.5%) prior to definitive treatment for MI-TCC. Response outcomes for all patients and QoL data will be reported in the final presentation. Grade 3/4 adverse events. Clinical trial information: NCT01616875. [Table: see text]

Objective To evaluate p53 and bcl-2 immunohistochemistry in preoperative biopsies and radical prostatectomy specimens, as predictors of biochemical recurrence. Patients and methods Preoperative biopsies from 73 men, and the radical prostatectomies from these men and from a further 47 men, were evaluated. The serum prostate specific antigen (PSA) level, Gleason score, pathological stage and margin involvement were recorded. The immunohistochemical expression of p53 and bcl-2 was studied on a representative area of tumour with the highest Gleason grade. The median follow-up was 53 months. Results During the follow-up 47 of the 120 patients had a biochemical recurrence. Capsular penetration was present in 63 (53%) and the surgical margins were positive in 47 (39%). The Gleason score was

BACKGROUND A major problem encountered by the supranetwork team managing new cases of penile cancer is inadequate tissue preparation for pathological evaluation of specimens. The histological examination of a circumcision or wide local excision specimen, when there is a clinical suspicion of malignancy, relies on receiving an orientated and pinned-out specimen [1]. When a foreskin is placed directly into formalin the specimen immediately contracts. After fixation it is not possible to stretch the specimen to identify the dorsal slit, or to take representative sections for a histological assessment of surgical margins. Similarly, excision-biopsy specimens might be difficult to orientate. We describe a method that enables a foreskin and excision-biopsy specimens to be pinned and orientated using material readily available in any operating theatre. METHODS In combination with the pathologist, we have developed a method that maintains the integrity of the specimen and allows orientation (Figs 1 and 2). The pathologist can then identify the dorsal slit, which is not a true surgical margin. The distal (glans) and proximal (shaft) margins can be identified and marked by using two colours of ink. The specimen is sliced sagittaly and the location of each sample identified using a block code. This block code must appear in the text of the pathology report, as these specimens are often reviewed in a distant cancer centre which will not have access to any block code written on the form at the time of sectioning. DISCUSSION About 80% of penile carcinomas arise from the foreskin and/or glans [2]. The aim of surgical management is to achieve control of disease without compromising functional or cosmetic results; hence organ-sparing procedures are increasingly favoured. Traditionally, a surgical margin of 20 mm has been advised. However, one study examined men who had conservative treatment for carcinoma of the penis [3]; the surgical resection margin was

High grade solid variants of prostatic adenocarcinoma and urothelial carcinoma can show overlapping histological features and their differentiation may require careful histological and immunohistochemical evaluation. The presence of surface urothelial carcinoma in situ is considered a helpful clue in support of a diagnosis of urothelial carcinoma. We present a series of three cases in which the high grade prostatic adenocarcinoma mimics urothelial carcinoma in situ, through a partly intraductal growth pattern within the prostatic duct system and partial replacement of the urothelium of the prostatic urethra. This may be a potential diagnostic pitfall, especially if present in small superficial mucosal biopsies, or when represented in samples from the bladder neck or penile urethra. A 70-year-old male subject underwent radical prostatectomy with bilateral iliac lymph node dissection for prostatic adenocarcinoma, following diagnosis on needle core prostatic biopsies performed for an elevated serum prostate specific antigen (PSA) of 40 μg/l. Sections from the prostate gland showed bilateral multifocal Gleason score 4+3=7 prostatic adenocarcinoma of microacinar type, predominantly in the posterior peripheral zones of the gland. Focally there was a higher grade malignant proliferation (figure 1A,B), partly within prostatic ducts and partly invading the stroma. There was necrosis with calcification and the cells generally lacked nucleoli. Some glandular spaces were identified. This intraductal process …