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PURPOSE OF REVIEW Penile sparing surgery (PSS) is considered the standard of care in penile cancer where appropriate, as preservation of the penis may enable the patient to maintain urinary and sexual function. This review will focus on the latest developments over the past two years. RECENT FINDINGS In this review, we discuss the latest findings in oncological outcomes in PSS, specifically glansectomy. We also introduce technology that may be useful in improving the precision of surgical resection margins in PSS. Finally, we consider the value of patient-reported outcome measures (PROMs) and consider how research in this area can be improved. SUMMARY A recent study has found a correlation between local recurrences (LR) and worse overall and cancer-specific survival in glansectomy, which challenges the belief that LR do not confer worse oncological outcomes. Despite numerous studies evaluating PROMs in penile cancer/PSS, few of these studies provide quality evidence of the 'supportive care needs'. A shift in research is required to identify those men at most risk of distress and to identify ways to support men diagnosed with penile cancer.

Background Bulbar urethral stricture is a common cause for urinary symptoms in men and its two main treatment options both have drawbacks with little evidence on their relative cost-effectiveness. Current guidelines on the management of recurrent bulbar urethral stricture have been predominantly based on expert opinion and panel consensus. Objective To assess the relative cost-effectiveness of open urethroplasty and endoscopic urethrotomy as treatment for recurrent urethral stricture in men. Methods Set in the UK National Health Service with recruitment from 38 hospital sites, a randomised controlled trial of open urethroplasty and endoscopic urethrotomy with 6-monthly follow-up over 24 months was conducted. Two hundred and twenty-two men requiring operative treatment for recurrence of bulbar urethral stricture and having had at least one previous intervention for stricture were recruited. Effectiveness was measured by quality- adjusted life years (QALYs) derived from EQ-5D 5L. Cost-effectiveness was measured by the incremental cost per QALY gained over 24 months using a within trial analysis and a Markov model with a 10-year time horizon. Results In the within trial, urethroplasty cost on average more than urethrotomy (cost difference: £2148 [95% CI 689, 3606]) and resulted in a similar number of QALYs on average (QALY difference: − 0.01 [95% CI − 0.17, 0.14)] over 24 months. The Markov model produced similar results. Sensitivity analyses using multiple imputation, suggested that the results were robust, despite observed missing data. Conclusions Based on current practice and evidence, urethrotomy is a cost-effective treatment compared with urethroplasty. Keypoints Urethrotomy and urethroplasty both led to symptom improvement for men with bulbar urethral stricture—a common cause for urinary symptoms in men; Urethroplasty appeared unlikely to offer good value for money compared to urethrotomy based on current evidence. Trial registration: ISRCTN: 98009168 (date: 29 November 2012) and it is also in the UK NIHR Portfolio (reference 13507). Trial protocol: The latest version (1.8) of the full protocol is available at: www.journalslibrary.nihr.ac.uk/programmes/hta/105723/#/ and a published version is also available: Stephenson R, Carnell S, Johnson N, Brown R, Wilkinson J, Mundy A, et al. Open urethroplasty versus endoscopic urethrotomy—clarifying the management of men with recurrent urethral stricture (the OPEN trial): study protocol for a randomised controlled trial. Trials 2015;16:600. https://doi.org/10.1186/s13063-015-1120-4. Trial main clinical results publication: Goulao B, Carnell S, Shen J, MacLennan G, Norrie J, Cook J, et al. Surgical Treatment for Recurrent Bulbar Urethral Stricture: A Randomised Open-label Superiority Trial of Open Urethroplasty Versus Endoscopic Urethrotomy (the OPEN Trial), European Urology, Volume 78, Issue 4, 2020, Pages 572–580.

UNLABELLED: Dynamic sentinel lymph node biopsy (DSNB) and radical inguinal lymph node dissection (ILND) are important in the management of penile cancer patients, but high-level evidence for preoperative, perioperative, and postoperative management remains scarce. According to an online survey of 35 surgeons from ten European countries, 57% perform >10 ILND procedures per year and 86% offer DSNB. Furthermore, management differs substantially for dye injection site, use of lymphoscintigraphy, preferred incision sites, techniques for lymphatic control, duration of empiric antibiotic therapy, perioperative thromboprophylaxis, time points for drain removal, and definition of the ILND dissection floor. Consensus was observed for the use of perioperative antibiotics (although not duration and type) and the borders for ILND template definitions. We conclude that there is significant variation in patient management among eUROGEN penile cancer surgeons. This heterogeneity may confound multicentre studies; therefore, a consensus to standardise inguinal node management in penile cancer across European penile cancer centres is warranted. PATIENT SUMMARY: Our survey reveals that preferences and surgical techniques for inguinal lymph node sampling and removal varies significantly between European penile cancer surgeons. Consensus is needed to standardise the management approach for penile cancer. ispartof: EUROPEAN UROLOGY OPEN SCIENCE vol:24 pages:39-42 ispartof: location:Netherlands status: published

Objective To present the long‐term adjuvant radiotherapy outcomes of patients with pN3 squamous cell carcinoma of the penis (SCCp) treated at two UK centres. Patients and Methods We conducted a retrospective audit of all pN3 SCCp patients, deemed suitable for adjuvant therapy by a specialist multidisciplinary team at St George’s and Leeds Hospitals, who received adjuvant radiotherapy. Primary outcomes were recurrence‐free survival (RFS), cancer‐specific survival (CSS) and overall survival (OS). Secondary outcomes were time to adjuvant treatment, frequency of in‐field recurrence, site and side of recurrence, and dose and schedule of radiotherapy. Results A total of 146 patients were included: 121 completed radiotherapy, four did not complete radiotherapy and 21 did not start it. The median (interquartile range [IQR]) age was 59 (54–70)years. The 5‐year RFS was 51%, CSS was 51% and OS was 44%. Adjuvant radiotherapy was started at a median (IQR) of 75 (48–106) days. A dose of 45 Gy in 20 fractions was most commonly used. Of the 125 patients who started adjuvant treatment, 55 relapsed. Of these relapses, 30 occurred in an inguinal or pelvic nodal station and 26 of the 30 were in a radiation field. Relapses in 18 of the 55 cases were in visceral sites only and seven were in both nodal (non‐irradiated sites) and visceral sites. Doses of 50 Gy) were more commonly used after 2013. Conclusions Application of a standard radiotherapy protocol within a centralized supra‐network setting has achieved survival outcomes that would appear better than those previously documented for either radiotherapy or chemotherapy in a cohort with solely pN3 disease. The addition of adjuvant chemotherapy may improve these outcomes further. These data suggest that adjuvant radiotherapy has a role to play in the management of men with pN3 SCCp.

Objectives To develop and externally validate a risk calculator for prediction of any cancer recurrence in patients with penile squamous cell carcinoma (pSCC) and inguinal lymph node metastases (ILNM), as to date no validated prognostic tool is available for patients with pSCC and ILNM. Patients and methods The development cohort included 234 patients from seven referral centres. The external validation cohort included 273 patients from two additional referral centres. Cox regression identified predictors of any recurrence, which were used to develop a risk calculator. The risk-calculator grouped the development and the validation cohorts according to the individual risk of any recurrence at 24 months (24m-R). Adjuvant treatment effects were tested on overall survival (OS) according to the derived tertiles, within the development and validation cohorts. Results Positive surgical margins, pN3 , and ILNM ratio were associated with higher recurrence rate. The 2-year OS rates were lower for patients with high (>37%) and intermediate (19-37%) compared to low ( 0.1). Conclusion Adjuvant treatment planning is crucial in patients with pSCC with ILNM, where only weak evidence is available. The current tool proved to successfully stratify patients according to their individual risk, potentially allowing better tailoring of adjuvant treatments.

Purpose Red cell distribution width (RDW) measures red cells’ size variability. Metastatic penile cancer displays poor chemotherapy response. As no validated prognostic predictor exists, we investigated whether RDW correlates independently with survival outcomes in metastatic penile cancer treated by chemotherapy. Methods Electronic chemotherapy files of patients with metastatic penile cancer (M1 or N3) from a large academic supra-regional centre were retrospectively analysed between 2005 and 2018. Patients were stratified into RDW > 13.9% and Results 58 patients were analysed. The RDW-high group (n = 31) had a poorer survival than the RDW-low group (n = 27). Median overall survival (mOS) in all patients was 19.0 months (95% CI 13.1–24.9). mOS for RDW-high was 15.0 months (95% CI 10.1–19.9) and 37.0 months (95% CI 32.3–43.1) for RDW-low. Kaplan–Meier curves showed a clear disparity in survival (log rank p = 0.025). Cox proportional hazard ratio for death, corrected for T-stage, grade, age and deprivation score was 0.43 (p = 0.04). Sub-analysis of the M1 patients showed mOS in RDW-high of 17 m (95% CI 11.6–22.4) vs. NR; HR for death of 0.42. N3 patients’ mOS in RDW-high cohort was 30 months (95% CI 4.5–55.9) vs. 13 months (95% CI 1.8–24.2) in RDW-low; HR for death was 0.30. Conclusion RDW correlates independently with survival outcomes in metastatic penile cancer and may act as a potential predictor of survival outcomes for patients with metastatic penile cancer receiving chemotherapy.

Urethral stricture disease is a commonly presenting problem to the urologist. Any condition that damages the urethral epithelium or underlying spongy tissue has the potential to cause a stricture. Patients with a urethral stricture can present either acutely or chronically with a range of urinary symptoms. An understanding of urethral stricture disease and a systematic approach to the history and investigations will enable clinicians to manage patients appropriately. This article aims to give an overview, appropriate for surgeons in there early years of training, on the aetiology, presentation and investigation of urethral stricture disease, as well as a basic understanding of the principles of management.

Objectives To identify predictors of poor overall survival (OS) amongst patients with penile squamous cell carcinoma (pSCC) with clinical inguinal lymphadenopathy (cN+), in order to define the best candidates for neoadjuvant chemotherapy (NAC). Patients and methods Using an international, multicentre database of 924 patients with pSCC, we identified 334 men who harboured cN+ with available clinical and follow-up data. Lymph node involvement was defined either by the presence of palpable inguinal node disease or by preoperative computed tomography (CT) assessment. Fluorine-18 fluorodeoxyglucose positron-emission tomography (18 F-FDG-PET)/CT scan was performed based on clinical judgment of the treating physician. Regression-tree analysis generated a risk stratification tool for prediction of 24-month overall mortality (OM). Kaplan-Meier explored the OS benefit related to the use of NAC according to the regression-tree-stratified subgroups. Results Overall, 120 (35.9%), 152 (45.5%), and 62 (18.6%) patients harboured cN1, cN2, and cN3 disease. 18 F-FDG-PET/CT was performed in 48 (14.4%) patients, and 16 (4.8%) had inguinal and pelvic nodal PET detection. The median OS was 107 months, with a 24-month OS of 66%. At regression-tree analysis (area under the curve = 70%), patients with cN3 and cN2 with PET/CT-detected inguinal and pelvic nodal activity had a higher risk of 24-month OM (>50%). NAC was associated with improved 24-month OS rates (54% vs 33%) only in this subgroup of patients (P = 0.002), which was also confirmed after multivariable adjustment (hazard ratio 0.28, 95% confidence interval 0.13-0.62; P = 0.002). Conclusion Patients with pSCC with cN3 or cN2 and inguinal and pelvic 18F-FDG-PET/CT scan detected disease had higher 24-month OM rates according to our regression-tree model. NAC was associated with improved OS only in these subgroups of patients. Our novel decision model may help to stratify cN+ patients, and identify those who most likely will benefit from NAC prior to radical surgical resection.

Objective: To review the use of ultrasound imaging in the diagnosis of testicular rupture and in relation to current guidelines. Methods: Data was retrospectively collected for all patients diagnosed with testicular rupture at a major trauma centre between 2011 and 2018. Data included patient demographics, mechanism of trauma, specific findings on ultrasound and outcomes. On review of ultrasound imaging, specific findings identified include a breach in the tunica albuginea (currently advised in guidelines), heterogenicity and contour loss. Results: Eight patients were identified with average age 37 years old, mechanism of trauma was 50%, 37.5% and 12.5% for motorcycle road traffic collision, sporting injury and workplace injury respectively. A breach of tunica albuginea was identified on ultrasound in 65% of cases, compared with 100% of cases showing contour loss and heterogenicity. Of the 87.5% patients who were managed surgically one needed orchidectomy (and later testosterone replacement). Conclusion: Guidelines have varied on how to use ultrasound imaging in diagnosing a clinically difficult condition. Our case series demonstrates that diagnosing testicular rupture by looking for more easily identifiable characteristics (heterogenicity and contour loss) than currently recommended in the guidelines (breech in the tunica albuginea) will aid diagnosis and patient pathway and improve outcomes. Level of evidence: 5

INTRODUCTION AND OBJECTIVE:Patients with advanced penile squamous cell cancer (pSCC) have a poor prognosis and undergo treatments with high morbidity. Palliative care alongside treatments with cura...

PURPOSE: Our primary objective is to detail the incidence, site, and timing of penile squamous cell carcinoma (pSCC) recurrence after inguinal lymph node dissection (ILND). MATERIALS AND METHODS: We performed a retrospective analysis of 551 patients who underwent ILND for pSCC from 2000 to 2017. The primary outcome was pSCC recurrence after ILND. Recurrences were identified and stratified by site. Timing of recurrence was determined. Multivariable logistic regression analysis determined associations with recurrence. Multivariable Cox regression analysis determined associations with overall survival (OS). Sub-group analysis of the distant recurrences analyzed timing and OS by site of distant recurrence. RESULTS: After ILND pSCC recurred in 176 (31.9%) patients. Median time to recurrence was 10 months for distant recurrences, 12 for inguinal, 10.5 for pelvic, and 44.5 for local. Greater than 95% of distant, inguinal, and pelvic recurrences occurred within 48 months of ILND, versus 127 months for local recurrences. Post-ILND recurrence was associated with pN2 (OR 1.99, 95% CI 1.0-4.1), and pN3 (OR 7.2, 95% CI 4.0-13.7). Patients who had local recurrence had similar OS to those without (HR 1.5, 95% CI 0.6-3.8), and worse OS was identified in patients with inguinal (HR 4.5, 95% CI 2.8-7.1), pelvic (HR 2.6, 95% CI 1.5-4.5), or distant (HR 4.0, 95% CI 2.7-5.8) recurrences. Patients with lung recurrences had worse OS than other sites (HR 2.2, 95% CI 1.1-4.3). CONCLUSIONS: Of the patients 31.9% had post-ILND recurrence associated with high pN staging. Greater than 95% of distant, inguinal, and pelvic recurrences occurred within 48 months, suggesting surveillance beyond this is low yield. Local recurrences occurred over a longer timeline, emphasizing necessity of long-term surveillance of the primary site. ispartof: JOURNAL OF UROLOGY vol:206 issue:4 pages:960-968 ispartof: location:United States status: published

Penile squamous cell carcinoma is a rare malignancy with various distinct histological subtypes, each with distinct appearances, histotypic specific associations with human papillomavirus (HPV) and clinical behaviour. Despite a wealth of pathological knowledge, there still remains a limited understanding of the fundamental molecular drivers that govern penile carcinogenesis with their underlying prognostic and therapeutic importance. However, recent work has improved our fundamental understanding of the molecular pathogenesis of penile cancer: commonly divided into the HPV-dependent and HPV-independent pathways. This review aims to summarise current developments in the histopathology and the molecular pathogenesis of penile cancer, with the advent of next-generation sequencing, and the opportunities for the targeting of molecular drivers of metastatic disease.

Urethral stricture disease (USD) is initially managed with minimally invasive techniques such as urethrotomy and urethral dilatation. Minimally invasive techniques are associated with a high recurrence rate, especially in recurrent USD. Adjunctive measures, such as local drug injection, have been used in an attempt to reduce recurrence rates.To systematically review evidence for the efficacy and safety of adjuncts used alongside minimally invasive treatment of USD.A systematic review of the literature published between 1990 and 2020 was conducted in accordance with the PRISMA checklist.A total of 26 studies were included in the systematic review, from which 13 different adjuncts were identified, including intralesional injection (triamcinolone, n = 135; prednisolone, n = 58; mitomycin C, n = 142; steroid-mitomycin C-hyaluronidase, n = 103, triamcinolone-mitomycin C-N-acetyl cysteine, n = 50; platelet-rich plasma, n = 44), intraluminal instillation (mitomycin C, n = 20; hyaluronic acid and carboxymethylcellulose, n = 70; captopril, n = 37; 192-iridium brachytherapy, n = 10), application via a lubricated catheter (triamcinolone, n = 124), application via a coated balloon (paclitaxel, n = 106), and enteral application (tamoxifen, n = 30; deflazacort, n = 36). Overall, 13 randomised controlled trials were included in the meta-analysis. Use of any adjunct was associated with a lower rate of USD recurrence (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.27-0.50; p 0.001) compared to no adjunct use. Of all the adjuncts, mitomycin C was associated with the lowest rate of USD recurrence (intralesional injection: OR 0.23, 95% CI 0.11-0.48; p 0.001; intraluminal injection: OR 0.11, 95% CI 0.02-0.61; p = 0.01). Urinary tract infection (2.9-14%), bleeding (8.8%), and extravasation (5.8%) were associated with steroid injection; pruritis of the urethra (61%) occurred after instillation of captopril; mild gynaecomastia (6.7%) and gastrointestinal side effects (6.7%) were associated with oral tamoxifen.Adjuncts to minimally invasive treatment of USD appear to lower the recurrence rate and are associated with a low adjunct-specific complication rate. However, the studies included were at high risk of bias. Mitomycin C is the adjunct supported by the highest level of evidence.We reviewed studies on additional therapies (called adjuncts) to minimally invasive treatments for narrowing of the urethra in men. Adjuncts such as mitomycin C injection result in a lower recurrence rate compared to no adjunct use. The use of adjuncts appeared to be safe and complications are uncommon; however, the studies were small and of low quality.

Contains fulltext : 220648.pdf (Publisher’s version ) (Closed access) The coronavirus disease 2019 (COVID-19) pandemic is unlike anything seen before by modern science-based medicine. Health systems across the world are struggling to manage it. Added to this struggle are the effects of social confinement and isolation. This brings into question whether the latest guidelines are relevant in this crisis. We aim to support urologists in this difficult situation by providing tools that can facilitate decision making, and to minimise the impact and risks for both patients and health professionals delivering urological care, whenever possible. We hope that the revised recommendations will assist urologist surgeons across the globe to guide the management of urological conditions during the current COVID-19 pandemic.

INTRODUCTION AND OBJECTIVE:Nesbit’s-type procedures (tunical plication +/- incision) for Peyronie’s disease curvature necessarily shortens the convex side. Patient focused research has shown a comm...

With the passage of time, there has been a major paradigm shift in the surgical management of penile cancer from radical to organ preserving penile surgical techniques, with closer surgical margins which offer good oncological, cosmetic and functional outcomes with improved physical and psychosexual well-being. This article aims to provide an update of the current organ preserving surgical strategies for penile cancer.

Introduction Nodal involvement is the most important prognostic factor in patients with squamous cell carcinoma of the penis (SCCp). However, optimal staging of regional lymph node remains controversial. Methods The literature was reviewed to examine current management of regional lymph nodes in SCCp patients with clinically nonpalpable inguinal lymph nodes (cN0). Results Radiological staging and selective risk-profile nomograms are unreliable in the detection of occult micrometastases in cN0 patients. Prophylactic inguinal lymph node dissection (ILND) is associated with significant morbidity and a high rate of postoperative complications. Dynamic sentinel lymph node biopsy (DSNB) is a reliable minimally invasive surgical staging technique for cN0 patients. Ipsilateral ILND is indicated only in inguinal basins with positive DSNB. Conclusions DSNB has excellent performance characteristics in staging cN0 patients, with high sensitivity and a low morbidity rate.

// Anthony Adimonye 1 , Elzbieta Stankiewicz 1 , Sakunthala Kudahetti 1 , Giorgia Trevisan 2 , Brendan Tinwell 3 , Cathy Corbishley 3 , Yong-Jie Lu 1 , Nick Watkin 4 and Daniel Berney 1 1 Centre for Molecular Oncology, Bart’s Cancer Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom 2 Department of Histopathology, Royal London Hospital, Barts Health NHS Trust, London, United Kingdom 3 Department of Cellular Pathology, St George’s Hospital, London, United Kingdom 4 Department of Urology, St George’s Hospital, London, United Kingdom Correspondence to: Anthony Adimonye, email: anthony247@doctors.org.uk Keywords: phosphatidylinositol-4,5-bisphosphate 3- kinase; catalytic subunit alpha; penile squamous cell carcinoma; copy number gain; p-AKT Received: December 30, 2017 Accepted: February 27, 2018 Published: March 23, 2018 ABSTRACT Objectives: To determine whether phosphatidylinositol-4,5-bisphosphate 3- kinase, catalytic subunit alpha (PIK3CA) copy number gain is common and could prove a useful marker for the activation status of the PI3K-AKT-mTOR pathway in penile squamous cell carcinoma (PSCC). Methods: Fresh frozen tissue and archival blocks were collected from 24 PSCC patients with 15 matched normal penile epithelium (NPE) tissue from St George’s Hospital. PIK3CA mutational and copy number status (CNS) was assessed via Sanger sequencing and fluorescence in-situ hybridisation, respectively. PIK3CA RNA expression was quantified using TaqMan gene expression assay. HPV DNA was detected with INNO-LiPA assay. p-AKT and p-mTOR protein expression were assessed using western blot and immunohistochemistry. Results: PIK3CA copy number gain was found in 11/23 (48%) patients, with mutations present in only 2/24 (8%) patients. In comparison to NPE, PSCC showed significantly lower PIK3CA RNA expression (p=0.0007), p-AKT (Ser473) nuclear immunoexpression (p=0.026) and protein expression of p-AKT (Thr308) (p=0.0247) and p-mTOR (Ser2448) (p=0.0041). No association was found between PIK3CA CNS and p-AKT and p-mTOR protein expression. Conclusion: Based on our results the PI3K-AKT-mTOR pathway is not a key driver in PSCC carcinogenesis and the therapeutic targeting of this pathway is unlikely to produce significant clinical benefit.

OBJECTIVES To identify incidence and risk factors for upstaging from cN1 to pN2/N3 at inguinal lymphadenectomy (ILND) for penile cancer (pSCC). Our secondary objective is to assess survival outcomes and associations for cN1 patients undergoing ILND. SUBJECTS/PATIENTS AND METHODS Patients with pT≥1cN1cM0 pSCC who underwent bilateral ILND and had complete data were identified in a multi-institutional international cohort from 8 referral centers in 7 countries diagnosed from 1980 to 2017. Upstaging was defined as pN2/N3 at ILND. Multivariable logistic regression analysis was used to determine associations with upstaging, and Cox multivariable logistic regression analysis to determine associations with overall survival (OS). RESULTS Of 144 patients were included in the final study population. 84 patients (58%) were upstaged from cN1 to pN2/N3, and 25 (17%) were down staged to pN0. Upstaging was associated with pT3/T4 (OR 4.1, 95%CI 1.5-11.7, P < 0.01) and pTX (OR 7.1, 95CI 1.6-51.1, P = 0.02). Age, smoking status, HPV status, and LVI were not associated with upstaging. Age (HR 1.03/y, 95%CI 1.01-1.06, P < 0.01) and upstaging (HR 2.8, 95%CI 1.3-5.9, P < 0.01) were associated with worse OS. Upstaged patients had a 5-year OS of 49%, compared with 86% for patients who were not upstaged. CONCLUSION The majority of cN1 pSCC patients harbor a higher-risk disease state than their clinical staging suggests, especially those with higher pT stages. More intensive pre-operative workup may be warranted for these patients to identify upstaging prior to ILND and potentially qualify them for neoadjuvant chemotherapy or clinical trials.

Objective: This study aimed to provide real-world data on the multidisciplinary management of metastatic penile squamous-cell carcinoma (mpSCC) patients and their survival outcomes, particularly those who receive best supportive care (BSC). Methods: A retrospective analysis of 1720 patients, managed via a supra-regional penile-specialist multidisciplinary team was conducted between January 2006 and May 2020. Results: A total of 101 patients (median age 63 years; interquartile range 56–72 years; 73% ECOG 0/1) were included. Of these, 32% (32/101) had previously received adjuvant chemotherapy prior to metastatic recurrence, 58% (59/101) received chemotherapy and 42% (42/101) received BSC. Further, 17% (17/101) received second-line systemic therapy, and 3% (3/101) received third-line systemic therapy. For first-line systemic-therapy, there was a 46% (27/59) clinical benefit rate (CBR), with 9% (5/59) complete response, 15% (9/59) partial response and 22% (13/59) stable disease. Patients receiving second-line therapy ( n=17) had a 29% (5/17) CBR. Median progression-free survival for first- and second-line treatment was 3.2 and 2.2 months, respectively. Median overall survival (mOS) for all patients was 6.2 months. mOS for first-line chemotherapy, second-line chemotherapy and BSC patients was 7.2, 4.5 and 2.0 months, respectively. Conclusions: First-line platinum-based chemotherapy is associated with notable response rates in mpSCC patients. Agents with better response rates are needed urgently potentially in combination with platinum-based chemotherapy. Level of evidence: Level 2b.

Penile cancer is a rare malignancy estimated to affect 26,000 men globally each year. The association with penile cancer, in particular non-invasive disease, and human papilloma virus (HPV) is well known. Ninety-five percent of cases of penile cancer are squamous cell carcinoma (SCC), which are staged using the TNM staging system. Terminology describing the histological appearance of non-invasive penile cancer has changed with all cases grouped under the umbrella term of penile intraepithelial neoplasia (PeIN); either undifferentiated or differentiated. This replaces previous terms such as carcinoma in situ (CIS) and eponymous names such as Bowen's disease. This change is recognised by the World Health Organisation (WHO). The topical treatments most commonly used for PeIN are 5-fluorouracil (5-FU) and imiquimod (IQ). Other treatments such as photodynamic therapy (PDT) are used but to a lesser degree. The evidence for all of these treatments is heterogenous with no randomised data available. Overall up to 57% complete response has been reported with a low number of serious adverse events. In this article, we aim to review the available evidence for the topical treatment of non-invasive penile cancer specifically regarding its efficacy and toxicity.

OBJECTIVE To evaluate the prognostic impact of lymph node yield (LNY) on survival outcomes for penile squamous cell carcinoma (SCC). PATIENTS AND METHODS In all, 532 patients who underwent inguinal LN dissection (ILND) across tertiary referral centres from Europe, China, Brazil and North America were retrospectively evaluated. From this cohort, 198 patients received pelvic LND (PLND).We identified threshold values for ILND and PLND using receiver operating characteristic curves. We tested prognostic value of LNY for recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) using the Kaplan-Meir method and Cox proportional hazard regression models. RESULTS The median (interquartile [IQR]) age was 59 (49-68) years and the median (IQR) follow-up after ILND was 28 (12-68.2) months. Overall, 85% of the patients had bilateral dissections. The median (IQR) number of inguinal LNs removed was 15 (10-22). Of those receiving PLND, The median (IQR) number of LNs was 13 (8-19). A LNY of ≥15 was used for dichotomisation of ILND patients, and a LNY of ≥9 was used in the PLND cohort. Patients with a LNY ≥15 had significantly better 5-year OS vs patients with a LNY

INTRODUCTION AND OBJECTIVES:Currently, penile cancer patients with impalpable inguinal lymph nodes routinely undergo dynamic sentinel node biopsy (DSNB) to diagnose metastatic spread to the inguina...

INTRODUCTION AND OBJECTIVES:Red cell distribution width (RDW) is a measure of size variability in circulating red cells reported as a part of full blood count analysis before initiating systemic th...

INTRODUCTION AND OBJECTIVES:The main prognostic factors for survival among patients with penile squamous cell carcinoma (PSCC) remain the presence and the extent of lymph node metastasis (LNM). Kno...

INTRODUCTION AND OBJECTIVES:Penile cancer incidence increases with age, most commonly being diagnosed in men over the age of 60 years. There is little evidence on the independent risk of age and pr...

INTRODUCTION AND OBJECTIVES:Evidence for best practice follow up of node positive SCC of the penis (SCCp) is scant. Our practice mirrors EAU guidelines; 3 monthly review CT (TAP) for 2 years and 6 ...

INTRODUCTION AND OBJECTIVES:Evidence for adjuvant radiotherapy in the management of node positive squamous cell carcinoma of the penis (SCCp) is scant owing to the rarity of the disease. Our supra-...

The historic international penile cancer trial InPACT is now open and accruing patients in the UK and USA. The trial is geared to answer important questions for patients with evidence of inguinal lymph node disease at presentation. This clinical trial update provides an overview of the study and progress to date.

Penile cancer is a rare malignancy, with wide variation in its global incidence rates and health burden. Multiple risk factors are linked to this debilitating disease and possible preventative strategies are well documented. Circumcision is one such strategy and has been shown to prevent this rare and potentially debilitating disease from occurring due to the improved penile hygiene, lower HPV and HIV transmission rates and reduction of chronic inflammatory conditions such as phimosis and balanitis. Although, whether circumcision should be advocated in all males to harness its multi-faceted benefits is controversial and currently, with no official recommendation, the decision will ultimately lie with parents and/or the patient.

To improve the prognostic allocation of patients with penile squamous-cell carcinoma (PSCC) receiving regional lymph node dissection (LND).An international, multicenter, retrospective study was performed on patients with PSCC who received regional LND, with or without perioperative therapy, from 1980 to 2017. We first used a random forest (RF) method with missing data imputation. Additionally, data were modeled using Cox proportional hazard regression, and a Cox model was also fit including prespecified variables. Based on the latter model, a nomogram for estimating 12-month and 24-month overall survival (OS) was developed.There were 743 patients who received LND at 7 referral centers from Europe, the USA, Brazil, and China. Of these patients, 689 were analyzed: 86 (12.5%) received neoadjuvant chemotherapy (NAC); 171 (24.8%) received adjuvant chemotherapy (AC), and 74 (10.7%) received adjuvant radiotherapy. The variables significantly associated with OS were age (P0.001), the pathologically involved/total removed LN ratio (P0.001), pN stage (overall P0.001), and NAC (P = 0.013). NAC and AC were ineffective in N1-2 patients (clinical and pathological, respectively), whereas they provided OS improvements in N3 patients. Finally, we developed a nomogram predicting 12- and 24-month OS based on prespecified variables (c-index: 0.75). The study is limited by its retrospective nature.We propose a tool that can be offered as an aid to physicians to enhance decision-making, clinical research, and patient counseling whenever LND is needed for PSCC. Administration of NAC and AC should be restricted to clinical and pathological N3 patients, respectively.

5088 Background: PSCC patients (pts) with palpable inguinal lymph node (ILN) disease have a poor overall survival (OS). Multimodal perioperative treatments are usually offered despite the lack of clinically meaningful efficacy. Pending the availability of novel effective systemic therapy, the optimization of conventional treatments in better selected pts is needed. Methods: Within an international, multicenter database of 924 PSCC pts who received ILN dissection from USA, Europe, Brazil and China, 494 had information on HPV, and 52 (10.5%) had HPV+ PSCC, predominantly assessed with immunohistochemistry (53%). Multivariable logistic regression analyses evaluated the association between pt factors and HPV status. Multivariable Cox analyses (MVA) assessed predictors of overall mortality (OM), including HPV status, pathologically-involved ILN ratio (ILNR), extranodal extension, margin status, vascular invasion (VI), perioperative RT (pRT) and perioperative chemotherapy (pCT). Comparisons between HPV status and ILNR were performed using interaction tests. Kaplan-Meier method was used to define the OS benefit related in HPV-stratified sub-groups. Results: Median age at diagnosis was 58yrs. Overall, pCT and pRT were used in 227 (46%) and 50 (10%) pts. The median follow-up was 62 months. Neither clinical factors nor country were associated with HPV status. On MVA, ILNR (HR:1.01, p = 0.01) and extranodal extension (HR: 1.5, p = 0.02) were statistically significantly associated with OM, but HPV was not (p = 0.2). However, in the subgroup of pts who received pRT, HPV status was associated with favorable OM (HR: 0.11, 95%CI: 0.03-0.5, p = 0.004) together with negative VI (p = 0.03), and the use of adjuvant CT (p = 0.04). A significant interaction was found on OM between HPV+ status and increasing ILNR, with a cutoff at 50% (p = 0.05). Results are limited by their retrospective nature and small numbers in each subgroup. Conclusions: In the largest available dataset of ILND for PSCC, we observed that pRT seemed to be more effective in the subgroup of HPV+ PSCC. These results should be considered as hypothesis-generating and may inspire both the future prospective trials or the ongoing InPACT study.

5585 Background: PSCC is a rare tumor and the administration of guidelines-based therapies is still problematic in real-world practice. Survival outcomes remain suboptimal in patients (pts) with ILN involvement. Multinational analyses of real-world patterns are needed. Methods: Within an international, multicenter database of 965 PSCC pts who received ILND from 1980-2019, 630 had complete information for the variables of interest, from USA (N=81), Europe (EU, N=355), South America (SA, N=90), and China (Ch, N=104). Descriptive analyses according to geographical and ethnicity/race distribution were made. Comparisons of outcomes were made with Kaplan-Meier analyses and corresponding logrank tests. Results: Median age at diagnosis was 59 yrs, with no differences worldwide and according to ethnicity/race. Pts from SA presented with more advanced cT-stage (cT3-4: 26.7% vs. 17.3% USA vs. 7.6% EU) while EU pts presented with more advanced cN-stage (cN3: 14.9% vs. 11% USA vs. 7.8% SA vs. 5.8% Ch) as well as pathological (p)N-stage: pN3 pts were 53% in EU, 33.3% in USA, 20% in SA, and 18.3% in Ch. Perioperative chemotherapy (pCT) was more frequently administered in EU (53.8%) vs. USA (34.6%) SA (5.6%) Ch (7.7%). cT-stage was more frequently advanced in black pts (cT3-4: 33.3% vs. 12% Caucasian, 6.2% Hispanic/latino, 0% Asian) and the same was for cN-stage (cN3: 25% in black, 13% in Caucasian, 6.2% in Hispanic/latino, 6% in Asian). Conversely, pN3 pts were more frequently Caucasian (45.6%) vs. black (25%), Hispanic/latino (19%), and Asian (18%). pCT was more frequently administered in Caucasian pts (45%) vs. black (8.3%), Hispanic/latino (0), and Asian (8%). No significant differences in overall survival (OS) were observed according to geographical region or ethnicity/race, in the total pts and in the subgroups according to cT, cN, pN-stages and pCT. Median OS after pCT and ILND was 95 months. Bilateral ILN involvement was equally observed regardless of geographical region and ethnicity/race. In the total population, pCT significantly prolonged OS in pts with bilateral ILN (p=0.04), but not in pts with pelvic LN. Conclusions: Treatment patterns for PSCC undergoing ILND remain heterogeneous worldwide, and adherence to guidelines is seemingly poor. However, long-term outcomes with pCT remain uniformly suboptimal with

INTRODUCTION AND OBJECTIVE:Penile squamous-cell carcinoma (PSCC) patients (pts) with palpable inguinal lymph node disease have a poor overall survival (OS). Thus, they could be optimal candidate fo...

2 Background: PSCC patients (pts) with palpable inguinal lymph node (ILN) disease have a poor overall survival (OS). For them, use of neoadjuvant chemotherapy (NAC) is recommended in guidelines, but limited data are available to inform pt selection. We aim to identify predictors of poor OS in clinically ILN-positive (ILN+) pts to define the optimal candidates for NAC. Methods: Within an international, multicenter database of 924 PSCC pts, we identified 334 ILN+ pts with available data. ILN involvement was defined either with the presence of palpable ILN disease or based on preoperative CT-scan. FDG-PET/CT-scan was performed based on clinical judgment of the treating physician. Univariable and multivariable analyses (MVA) assessed predictors of overall mortality (OM). A regression-tree method for censored data was used to generate a risk stratification tool for prediction of 24m OM after diagnosis of ILN+ PSCC. Kaplan-Meier method was used to define the OS benefit related to the use of NAC according to the regression-tree stratified sub-groups. Results: Median age at diagnosis was 58yrs, and 105 (31.4%) had ECOG≥1. Of all, 120 (35.9%), 152 (45.5%), and 62 (18.6%) harbored cN1, cN2, and cN3 disease. Additionally, 152 (45.5%) and 117 (35%) had monolateral vs bilateral clinical ILN involvement. FDG-PET/CT was adopted in 42 (12.2%) pts, and 16 (4.8%) had pelvic LN uptake. Median OS was 107m, with 24m OS = 66%. At MVA, cN2 (HR: 2.28, p=0.006), cN3 (HR: 2.15, p=0.02), PET/CT scan-detected pelvic and ILN involvement (HR: 2.57, p=0.007) were independently associated with higher OM, whether bilateral clinical ILN+ was only univariably significant (HR: 1.56, p=0.02). At regression-tree analysis (AUC 70%), pts with cN3 and cN2 with PET/CT-detected pelvic and ILN involvement had the higher risk of 24m OM (>54%). NAC was associated with improved 24m OS rates (54 vs. 33%) only in this pt subgroup (p=0.002). Conclusions: NAC improves OS in pts with cN3 or cN2 and pelvic FDG-PET/CT scan-detected disease. Our regression-tree may serve to screen ILN+ pts, to identify the optimal NAC candidates before radical treatments.