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Background: The incidence of penile cancer in Europe lies in the range of 0.9 to 2.1 cases per 100 000 persons per year. Carcinogenesis is associated with human papilloma virus (HPV) infection and with chronic inflammation. Methods: This review is based on publications (2010-2017) retrieved by a selective search in PubMed and EMBASE and on the guidelines of the European Association of Urology, the European Society of Medical Oncology, the National Comprehensive Cancer Network, and the National Institute for Health and Care Excellence (NICE). Results: 95% of cases of penile cancer are accounted for by squamous cell carcinoma, whose numerous subtypes have different clinical courses. Chronic preputial inflammation due to phimosis or lichen sclerosus is often associated with penile cancer. Circumcision lowers the risk of penile cancer (hazard ratio: 0.33). Maximally organ-preserving surgery with safety margins of no more than a few millimeters is the current therapeutic standard, because a local recurrence, if it arises, can still be treated locally with curative intent. Local radiotherapy can be performed in early stages. Lymphogenic metastasis must be treated with radical lymphadenectomy and adjuvant chemotherapy. Patients with clinically unremarkable inguinal lymph nodes nonetheless need invasive lymph node staging because of the high rate of lymphogenic micrometastasis. Conclusion: Penile cancer is curable in all early stages with the appropriate treatment, but its prognosis depends crucially on the proper management of the regional (i.e., inguinal) lymph nodes. In many countries, the treatment of this rare disease entity has been centralized. [ABSTRACT FROM AUTHOR]

Purpose Penile squamous cell carcinoma is a rare but aggressive cancer. Little is known about pivotal events in tumor pathogenesis and metastasis. Lymph node metastasis is the prevailing prognostic factor while clinical detection in patients remains difficult. Our aim was to identify distinct miRNAs that are differentially expressed in metastatic vs nonmetastatic penile carcinoma, which may serve as diagnostic biomarkers for disease progression. Materials and Methods TaqMan® arrays and quantitative polymerase chain reaction were applied to analyze miRNA profiles in penile squamous cell carcinoma specimens and glans tissue from 24 patients. The prognostic value of deregulated miRNAs was analyzed using the Kaplan-Meier method. The Spearman test was applied to determine a potential linkage between distinctive miRNAs in individual patients. Results Loss of miR-1 (p = 0.0048), miR-101 (p = 0.0001) and miR-204 (p = 0.0004) in metastasizing tumors and associated metastases (p = 0.0151, 0.0019 and 0.0003, respectively) distinguished patients with metastatic and nonmetastatic penile squamous cell carcinoma. These 3 miRNAs showed a coherent expression pattern. Consistently, patients with low levels of all 3 miRNAs had worse survival (p = 0.03). We identified a coordinately regulated miRNA target hub that is over expressed in penile squamous cell carcinoma and associated with lymphovascular invasion. Conclusions Our results provide evidence of a novel multiple miRNA based signature associated with lymph node metastasis and unfavorable prognosis of penile squamous cell carcinoma. The integrated loss of miR-1, miR-101 and miR-204 may predict the formation of metastases in penile cancer at an early stage. [ABSTRACT FROM AUTHOR]

Objectives To assess the potential complications associated with inguinal lymph node dissection ( ILND) across international tertiary care referral centres, and to determine the prognostic factors that best predict the development of these complications. Materials and Methods A retrospective chart review was conducted across four international cancer centres. The study population of 327 patients underwent diagnostic/therapeutic ILND. The endpoint was the overall incidence of complications and their respective severity (major/minor). The Clavien-Dindo classification system was used to standardize the reporting of complications. Results A total of 181 patients (55.4%) had a postoperative complication, with minor complications in 119 cases (65.7%) and major in 62 (34.3%). The total number of lymph nodes removed was an independent predictor of experiencing any complication, while the median number of lymph nodes removed was an independent predictor of major complications. The American Joint Committee on Cancer stage was an independent predictor of all wound infections, while the patient's age, ILND with Sartorius flap transposition, and surgery performed before the year 2008 were independent predictors of major wound infections. Conclusions This is the largest report of complication rates after ILND for squamous cell carcinoma of the penis and it shows that the majority of complications associated with ILND are minor and resolve without prolonged morbidity. Variables pertaining to the extent of disease burden have been found to be prognostic of increased postoperative morbidity. [ABSTRACT FROM AUTHOR]

Summary: Acquired chromosomal aberrations, including gene copy number alterations, are involved in the development and progression of human malignancies. SOX2, a transcription factor–coding gene located at 3q26.33, is known to be recurrently and specifically amplified in squamous cell carcinomas of the lung, the esophagus, and the oral cavity. In these organs, the SOX2 protein plays an important role in tumorigenesis and tumor survival. The aim of this study was to determine whether SOX2 amplification is also found in squamous cell carcinomas in other organs commonly affected by this tumor entity. In addition, we examined a large spectrum of lung cancer entities with neuroendocrine differentiation (ie, small cell cancers, large cell cancers, typical and atypical carcinoids) for SOX2 and TTF1 copy number gains to reveal potential molecular ties to squamous cell carcinomas or adenocarcinomas of the lung. Applying fluorescence in situ hybridization, we assessed squamous cell carcinomas of the cervix uteri (n = 47), the skin (n = 57), and the penis (n = 53) for SOX2 copy number alterations and detected amplifications in 28%, 28%, and 32% of tumors, respectively. Furthermore, we performed immunohistochemical SOX2 staining and found that SOX2 amplification is significantly associated with overexpression of the corresponding protein in squamous cell carcinomas (P < .001). Of the lung cancer entities with neuroendocrine differentiation, only small cell cancers and large cell cancers exhibited SOX2 or TTF1 amplifications at significant frequencies, indicating that at least a subset of these might be dedifferentiated forms of squamous cell carcinomas or adenocarcinomas of the lung. We conclude that SOX2 amplification and consequent SOX2 protein overexpression may represent important mechanisms of tumor initiation and progression in a considerable subset of squamous cell carcinomas. [Copyright &y& Elsevier]

Introduction: Although the trend towards penile sparing therapy is increasing for penile squamous cell carcinoma, outcomes for laser ablation therapy have not been widely reported. We assessed the clinical outcomes of penile cancer patients treated with only laser ablation.Materials and Methods: A retrospective review was performed on 161 patients across 5 multi-center tertiary referral centers from 1985 to 2015. All patients underwent penile sparing surgery with only laser ablation for squamous cell carcinoma of the penis. Laser ablation was performed with neodymium-doped yttrium aluminum garnet or carbon dioxide. Overall and recurrence-free survival was calculated using the Kaplan-Meier method and compared with the log rank test.Results: A total of 161 patients underwent laser ablation for penile cancer. The median age was 62 (IQR: 52-71) years and median follow-up was 57.7 (IQR: 28-90) months. The majority of patients were pTa/Tis (59, 37%) or pT1a (62, 39%). Only 19 (12%) had a poorly differentiated grade. The 5-year recurrence-free survival was 46%. When stratified by stage, the 5-year local recurrence-free survival was pTa/Tis: 50%; pT1a: 41%; pT1b: 38%; and pT2: 52%. The inguinal/pelvic nodal recurrence was pTa/Tis: 2%; pT1a: 5%; pT1b: 18%; and pT2: 22%. There were no differences among stages with respect to recurrence-free survival (P = 0.98) or overall survival (P = 0.20).Conclusion: Laser ablation therapy is safe for appropriately selected patients with penile squamous cell carcinoma. Due to the increased risk of nodal recurrence, laser ablation coupled with diagnostic nodal staging is indicated for patients with pT1b or higher. [ABSTRACT FROM AUTHOR]

Objective: To analyze the recurrence and survival outcomes of glansectomy in patients with penile squamous cell carcinoma.Materials and Methods: We performed a retrospective review of 410 patients across 5 international tertiary referral centers between 1999 and 2016. All patients had tumors involving the glans penis and underwent glansectomy as primary treatment. The Kaplan-Meier method and log-rank test were used to calculate survival and recurrence. Median follow-up was 42 months (interquartile range [IQR] 29-56).Results: The median age was 64 years (IQR 53-72). Median tumor size was 2.2 cm (IQR 1.5-3.0). A total of 240 patients (58.5%) had pT2 disease, whereas only 43 patients (10.5%) had pT3 or pT4 disease. The majority of the cohort had poorly differentiated tumors (43.7%). Most recurrences were local at 7.6% (31 patients). Only 14 patients (3.4%) had regional recurrence and 9 patients (2.2%) had distant recurrence. When stratified by pathologic stage, tumors that were pT2 or higher were (P < .001) and were more likely to be poorly differentiated (P < .001). There were no differences in recurrence location among pathologic stages (P = .15). The 1-, 2-, and 5-year recurrence-free survival were 98%, 94%, and 78%, respectively. There were no differences in overall survival when stratified by stage (P = .67).Conclusion: Glansectomy is an oncologically safe treatment modality for squamous cell carcinoma of the glans in appropriately selected invasive tumors. [ABSTRACT FROM AUTHOR]