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222 Background: Penile cancer is a rare malignancy affecting approximately 400 men per year in the United Kingdom. There are relatively limited data regarding the role of chemotherapy, although it may be considered in the adjuvant setting for high-risk disease and for palliation of metastatic disease. Methods: Patients treated with chemotherapy between June 2002 and March 2010 were identified from our prospectively maintained institutional database. Regimens were recorded and toxicity documented according to the Common Toxicity Criteria version 4.0. Response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 until 2009 and then version 1.1. Results: Twenty patients received chemotherapy either for adjuvant treatment (n=6) or for metastatic disease (n=14). Median age was 59 (range 33-80). Different regimens were used over the time period. In the adjuvant setting 4-6 cycles of chemotherapy were planned and all patients received cisplatin in combination with 5-FU or capecitabine. Five (83%) completed planned treatment with no grade 3 or 4 toxicities. One patient stopped after 2 cycles due to deteriorating renal function. Patients remained disease free at up to 22 months follow-up. In the metastatic setting, 10 patients received cisplatin and capecitabine, 1 cisplatin and 5-FU and 1 carboplatin and capecitabine. Of these 12 patients, 2 (17%) had partial response as their best response, 4 (33%) had stable disease (SD) and 6 (50%) had progressive disease (PD). Three patients (25%) experienced pulmonary embolism, 1 of whom died. Two (17%) developed grade 3 neutropenia. One patient received carboplatin, methotrexate and bleomycin with PD after 3 cycles and developed grade 3 neutropenia, stomatitis, and diarrhea. One patient received 3 cycles of paclitaxel, ifosfamide, and cisplatin with SD and no grade 3 or 4 toxicities. Conclusions: Combination chemotherapy can be delivered with acceptable toxicity in the adjuvant setting. In the metastatic setting response rates were disappointing and treatments were associated with greater toxicity. New treatments are urgently required to improve outcomes in this difficult malignancy. [Table: see text]

OBJECTIVES To identify predictive pathological factors for local recurrence (LR) and to study the impact of LR on survival in patients treated with glansectomy for penile squamous cell carcinoma (pSCC). PATIENTS AND METHODS We retrospectively studied patients treated with glansectomy at international, high-volume reference centres. We analysed histopathological predictors of LR, stratified patients into risk groups based on the number of risk factors present, and studied the impact of LR on survival outcomes using Kaplan-Meier survival analysis and stepwise Cox proportional hazards regression models. Subsequently, we performed sensitivity analyses excluding margin-positive cases, pT3 disease, and cN+ disease, or all of these factors. RESULTS Across nine institutions, 897 patients were included, of whom 94 experienced LR. On multivariable analysis, presence of high-grade disease and pT3 stage were independent predictors of LR. LR-free survival rates significantly differed according to the number of risk factors present, with a hazard ratio (HR) of 1.90 (95% confidence interval [CI] 1.17-3.07; P = 0.01) for the intermediate-risk group (one risk factor) and 6.11 (95% CI 3.47-10.77; P < 0.001) for the high-risk group (two risk factors), using the low-risk group (no risk factors) as reference. Patients who experienced LR had significantly worse overall survival (OS; HR 2.89, 95% CI 2.02-4.14; P < 0.001) and cancer-specific survival (CSS; HR 5.64, 95% CI 3.45-9.22; P < 0.001). LR (HR 3.82, 95% CI 2.14-6.8; P < 0.001), lymphovascular invasion and cN status were significant predictors of decreased CSS. LR remained a strong predictor of both OS and CSS in all sensitivity analyses. CONCLUSIONS Pathological T3 stage and presence of high-grade disease were independent histopathological predictors of LR after glansectomy for primary pSCC, which allowed risk stratification into three groups with significantly different risk of developing LR. Additionally, LR is related to poor OS and CSS, indicating that LR is a manifestation of underlying aggressive disease and clearly challenging the dogma of using organ-sparing surgery whenever possible since survival is unaffected by higher LR rates.

Background Urethral stricture is a common cause of difficulty passing urine in men with prevalence of 0.5 %; about 62,000 men in the UK. The stricture is usually sited in the bulbar part of the urethra causing symptoms such as reduced urine flow. Initial treatment is typically by endoscopic urethrotomy but recurrence occurs in about 60 % of men within 2 years. The best treatment for men with recurrent bulbar stricture is uncertain. Repeat endoscopic urethrotomy opens the narrowing but it usually scars up again within 2 years requiring repeated procedures. The alternative of open urethroplasty involves surgically reconstructing the urethra, which may need an oral mucosal graft. It is a specialist procedure with a longer recovery period but may give lower risk of recurrence. In the absence of firm evidence as to which is best, individual men have to trade off the invasiveness and possible benefit of each option. Their preference will be influenced by individual social circumstances, availability of local expertise and clinician guidance. The open urethroplasty versus endoscopic urethrotomy (OPEN) trial aims to better guide the choice of treatment for men with recurrent urethral strictures by comparing benefit over 2 years in terms of symptom control and need for further treatment. Methods/Design OPEN is a pragmatic, UK multicentre, randomised trial. Men with recurrent bulbar urethral strictures (at least one previous treatment) will be randomised to undergo endoscopic urethrotomy or open urethroplasty. Participants will be followed for 24 months after randomisation, measuring symptoms, flow rate, the need for re-intervention, health-related quality of life, and costs. The primary clinical outcome is the difference in symptom control over 24 months measured by the area under the curve (AUC) of a validated score. The trial has been powered at 90 % with a type I error rate of 5 % to detect a 0.1 difference in AUC measured on a 0–1 scale. The analysis will be based on all participants as randomised (intention-to-treat). The primary economic outcome is the incremental cost per quality-adjusted life year. A qualitative study will assess willingness to be randomised and hence ability to recruit to the trial. Discussion The OPEN Trial seeks to clarify relative benefit of the current options for surgical treatment of recurrent bulbar urethral stricture which differ in their invasiveness and resources required. Our feasibility study identified that participation would be limited by patient preference and differing recruitment styles of general and specialist urologists. We formulated and implemented effective strategies to address these issues in particular by inviting participation as close as possible to diagnosis. In addition re-calculation of sample size as recruitment progressed allowed more efficient design given the limited target population and funding constraints. Recruitment is now to target. Trial registration ISRCTN98009168 Date of registration: 29 November 2012. Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-1120-4) contains supplementary material, which is available to authorized users.