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Simple Summary: Squamous cell carcinoma of the penis is a rare yet distressing condition representing less than 1% of cancer diagnoses in the United States annually. It is largely associated with human papillomavirus infection, lack of circumcision, and poor hygiene, among other factors. When detected early, local therapies for penile cancer offer robust response and cure rates, but they can be disfiguring, leading to psychologic, social, and functional distress. Herein, we explore local therapies, including topical drugs, laser therapy, and excisional procedures, and more radical surgeries for squamous cell carcinoma of the penis as well as advanced reconstructive techniques, including skin grafting and the creation of a new penis to maintain functional status and cosmesis. Local therapy for penile cancer provides robust survival and can preserve the penis functionally and cosmetically. Interventions must target the appropriate clinical stage. We reviewed studies regarding the primary therapy in penile cancer, from topical therapy to radical penectomy, and reconstructive techniques. Topical therapy (5-FU or Imiquimod) provides a robust oncologic response in patients with Ta or Tis disease. Multiple laser therapies are available for localized patients and those with low-grade T1 disease. There is a non-trivial risk of progression and nodal metastases in poorly selected patients. Wide local excision provides an oncologically sound option in patient with up to T1 disease; less evidence exists for Mohs microsurgery in the setting of penile cancer. Increasingly aggressive approaches include glansectomy and partial/radical penectomy, which provide 5- and 10-year cancer-specific survival rates of over 80%. Meticulous reconstruction is necessary for the durable function of the remaining penis. Preservation of voiding and sexual function occurs via penile skin grafting, glans resurfacing, creation of a functional penile stump, and phalloplasty with a penile implant. Perineal urethrostomy provides an alternative in pathology demanding extensive partial or radical penectomy, and a durable option for seated voiding. Clinical suspicion and timely diagnosis are paramount in terms of management as less-invasive options for earlier-stage disease develop. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer of the penis is a relatively uncommon cancer that nevertheless can be life threatening when it is at an advanced stage. We summarized the published laboratory results that might lead to new and better treatment approaches, including those that harness the immune system. We identified several opportunities for drug development and corresponding clinical trials that are or will soon be testing these ideas in patients. In conclusion, we outline how these ongoing efforts will hopefully improve outcomes for patients with advanced penile cancer. Discovery of effective systemic therapies for patients with advanced penile cancer has been slow to occur. Comprehensive genomic profiling from several studies shed light on the molecular oncogenesis of penile squamous cell carcinoma (PSCC) and differences between HPV-related and unrelated tumors. While these two subsets of PSCC appear distinct in their biology, there are not yet specific treatment strategies recommended on that basis. Cell surface proteins have been identified that may potentially serve as drug targets for monoclonal antibodies or small molecule inhibitors. Here, we review some of the new biological insights regarding PSCC that could lead to improved therapies, as well as the related clinical trials recently completed or in progress. We conclude that antibody-drug conjugates are especially promising, as are the combinations of immune checkpoint inhibitors with other types of drugs. [ABSTRACT FROM AUTHOR]

Copyright of Die Urologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: Penile cancer is a rare but aggressive squamous cell carcinoma affecting the male genitalia. Accounting for less than 1% of male malignancies in the U.S., it primarily manifests in the sixth decade of life. Penile cancer's psychological impact extends beyond diagnosis, encompassing the consequences of treatment and unique cancer-related distress. Treatment approaches range from organ-sparing techniques to more extensive surgeries, impacting sexual function and quality of life. Providing essential psychosocial support involves recognizing and managing emotional stress without stigmatizing it as pathological. Here we summarize studies assessing post-treatment outcomes, including quality of life, psychosocial effects, urinary symptoms, and sexual function. Patients' voices reveal unmet needs, emphasizing the importance of timely diagnosis, treatment access, and individualized psychosocial support. Treatment of penile cancer (PC) focuses on organ preservation, employing various surgical and non-surgical approaches. These interventions may lead to disfigurement, impacting patients' functional outcomes and psychosocial well-being. We reviewed studies related to penile health and PC up to February 2024, limited to studies published in English. Studies employing health-related quality of life (HRQoL) assessments have identified a detrimental association between aggressive treatment and overall health status, physical functioning, and relationships. In contrast, organ-sparing demonstrates improved measures related to HRQoL and sexual function. Assessment through validated questionnaires reveals diverse voiding outcomes, and varying impacts on QoL and sexual activity, emphasizing the necessity for multidisciplinary personalized care. Studies highlight substantial variations in sexual function, with patients reporting adaptations, reduced satisfaction, and concerns about body image and sexual well-being. Furthermore, unmet needs include challenges in patient–clinician communication, obtaining information, and accessing psychosocial support. Patient experiences underscore the importance of timely diagnosis, treatment access, and addressing psychological consequences. Organ-sparing approaches have higher QoL preservation and sexual function. Individualized support, including sexual therapy, support groups, and family counseling, is essential for post-treatment rehabilitation. Timely diagnosis and comprehensive care are paramount in addressing the multifaceted impact of PC on patients and families. [ABSTRACT FROM AUTHOR]

Copyright of Die Urologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Penile metastases are exceptionally rare and are associated with poor prognosis. Herein, we report the case of a 74-year-old man with previously treated squamous cell carcinoma of the anal canal who was referred with a painless penile lump. Biopsy identified a similar squamous cell carcinoma. Imaging studies excluded other sites of metastases. It was considered a solitary metastasis, and a total penectomy was performed. The patient was free of metastases for four years until the disease progressed, and he is currently under palliative chemotherapy with 5 years of follow-up. This is the second worldwide case of anal canal carcinoma with penile metastasis. [ABSTRACT FROM AUTHOR]

Primary urethral cancer is a rare condition often manifesting in the sixth decade of life and is typically associated with urethral stricture disease. A 65-year-old male, a known case of stricture urethra, underwent perineal urethrostomy 10 years back. He presented with a growth at the urethrostomy site and the biopsy revealed squamous cell carcinoma. Magnetic resonance imaging of the pelvis revealed that the lesion extended into the penile and prostatic urethra with possible involvement of the corpus spongiosum, bulbospongiosus, and the bladder neck. Radical cystectomy, penectomy, scrotectomy, and bilateral orchiectomy with ileal conduit were performed. At 18-months of follow-up, the patient is recurrence-free. [ABSTRACT FROM AUTHOR]

Simple Summary: Penile cancer is a rare but aggressive cancer. After it metastasizes, the median survival time is less than 12 months. The overall response rate to common first-line combination chemotherapy treatments is approximately 50%. There is an urgent need in advanced-penile-cancer treatment to find novel therapies that would generate better response rates than standard chemotherapy thus far and have less toxicity. Partially due to its rarity, there are few animal models and cell lines of penile cancer. We report on the generation of seven penile cancer animal models that were created by directly implanting human tumor tissue into immunocompromised mice. Metastatic penile squamous cell carcinoma (PSCC) has only a 50% response rate to first-line combination chemotherapies and there are currently no targeted-therapy approaches. Therefore, we have an urgent need in advanced-PSCC treatment to find novel therapies. Approximately half of all PSCC cases are positive for high-risk human papillomavirus (HR-HPV). Our objective was to generate HPV-positive (HPV+) and HPV-negative (HPV−) patient-derived xenograft (PDX) models and to determine the biological differences between HPV+ and HPV− disease. We generated four HPV+ and three HPV− PSCC PDX animal models by directly implanting resected patient tumor tissue into immunocompromised mice. PDX tumor tissue was found to be similar to patient tumor tissue (donor tissue) by histology and short tandem repeat fingerprinting. DNA mutations were mostly preserved in PDX tissues and similar APOBEC (apolipoprotein B mRNA editing catalytic polypeptide) mutational fractions in donor tissue and PDX tissues were noted. A higher APOBEC mutational fraction was found in HPV+ versus HPV− PDX tissues (p = 0.044), and significant transcriptomic and proteomic expression differences based on HPV status included p16 (CDKN2A), RRM2, and CDC25C. These models will allow for the direct testing of targeted therapies in PSCC and determine their response in correlation to HPV status. [ABSTRACT FROM AUTHOR]

Introduction: Schwannomas originate from the peripheral nerve sheaths and are mainly detected in the head, neck, or extremities. They are rarely encountered in the penoscrotal region. Case Presentation: Herein, we present a case of a penoscrotal schwannoma diagnosed and successfully treated in our center. A 40-year-old patient with a history of resection of a dorsal penile schwannoma presented with multiple nodular lesions at the scrotum, penile shaft, and radix, which were first noticed 5 years before his current presentation. He complained about penile pain and dyspareunia. Magnetic resonance imaging was performed for preoperative diagnosis. All nodular lesions were resected while preserving the neurovascular structures. The histopathological examination revealed benign lesions. The patient's complaints were resolved, and there was no recurrence during the 1-year follow-up. Conclusion: The primary treatment is surgical excision. The patients need close follow-up regarding the risks of recurrence and malignant transformation. [ABSTRACT FROM AUTHOR]

Sexuality in cancer patients is a complex area. It is estimated that 81% of patients with urological cancer develop problems in their sexual functionality, even from the moment of diagnosis and aggravated during treatment due to direct injury to the genitalia. Currently, there are few avenues of care within the field of urology that address sexual health and quality of sexual life in penile cancer survivors, which causes many of them to lose self‐esteem and have problems with their partners. To review the literature on what are the consequences on the sexual life of penile cancer survivors in terms of their performance, including risk factors associated with penile cancer and what are the alternatives they must recover their sexual life. Most penile cancer survivors develop alterations in sexual performance and functionality, such as loss of sexual interest, dysfunctional ejaculation, and loss of orgasm, increasing the risk of depression and anxiety. Sex therapy is presented as an alternative to improve the quality of life of these patients, proposing sexuality as something more than genitalia and helping to lead a better life. Sex therapy is an alternative and should be contemplated in the therapeutic plan of patients with urological cancer, especially penile cancer, since sexuality is part of an individual's life, and its loss affects the quality of life. [ABSTRACT FROM AUTHOR]

The Italian National Immunization Plan (NIP) states that public health today aims at immunizing adolescents of both sexes for maximum protection against all HPV-related vaccine-preventable diseases. Nowadays, the vaccination offer to primary cohorts is reaffirmed with continued free vaccination up to at least 26 years of age for females and up to at least 18 years of age for males. The Italian NIP 2023–2025 recommends HPV vaccination for at-risk categories, including individuals with HIV, men who have sex with men (MSM), women treated for intermediate- or high-grade lesions, and travelers. Catch-up vaccination is recommended for women at least up to 26 years of age, also using the appropriate occasion of the call for the first screening for the prevention of cervical cancer as an opportunity for vaccination, and for men at least up to and including 18 years of age if they have not been previously vaccinated or have not completed the vaccination cycle. In summary, the Italian vaccination offer has been extended to additional cohorts in order to reduce the burden of HPV-related diseases and to improve vaccination coverage of the Italian population. [ABSTRACT FROM AUTHOR]

Simple Summary: Penile cancer is a rare and aggressive disease. Current treatment options when the cancer is locally advanced are suboptimal and potentially mutilating. Insight into the immune dysregulation necessary for the emergence of penile cancer could suggest innovative ways to manipulate the immune system which have already demonstrated efficacy in other, more common malignancies. In this paper, we use multiplex immunofluorescence, a novel technology, to investigate the immune microenvironment of penile cancer for the first time. We describe a pattern of immune exhaustion as cancer becomes more advanced and identify tumor-associated macrophages as a potential key player in regulating this process. Penile squamous cell carcinoma (PSCC) is a rare and deadly malignancy. Therapeutic advances have been stifled by a poor understanding of disease biology. Specifically, the immune microenvironment is an underexplored component in PSCC and the activity of immune checkpoint inhibitors observed in a subset of patients suggests immune escape may play an important role in tumorigenesis. Herein, we explored for the first time the immune microenvironment of 57 men with PSCC and how it varies with the presence of human papillomavirus (HPV) infection and across tumor stages using multiplex immunofluorescence of key immune cell markers. We observed an increase in the density of immune effector cells in node-negative tumors and a progressive rise in inhibitory immune players such as type 2 macrophages and upregulation of the PD-L1 checkpoint in men with N1 and N2-3 disease. There were no differences in immune cell densities with HPV status. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Penile cancers are a rare subset of carcinomas accounting for <1% of all diagnosed malignancies. There have been recent reports of increasing incidence globally; however, there is limited Canadian literature pertaining to these neoplasms. The province of Newfoundland and Labrador (NL) represents an important entity to study, possessing the highest national incidence of cancer, along with a plethora of relevant risk factors for penile cancer. METHODS: A retrospective chart analysis of all patients with a diagnosis of penile cancer in NL between the years of 2006 and 2018 was conducted. The main outcomes included overall incidence, proportion with metastatic disease, tumor demographics, and overall survival (OS). Incidence among the male population was calculated using Statistics Canada annual reports. RESULTS: An identified 81 cases satisfied the inclusion criteria, with a median age at diagnosis of 65 (interquartile range 20) years. Crude incidence of penile cancer ranged from 1.20–4.27/100 000 males in 2007 and 2010, respectively, while the average age-standardized incidence was 2.34/100 000 males across the study timeframe. Metastatic disease was noted in 17 (21.0%) patients, with a five-year OS of 74% for all penile malignancies, decreasing to 66% in those with invasive squamous cell carcinoma. CONCLUSIONS: The incidence of penile cancer in our population was higher than reported Western jurisdictions and showed frequent rates of metastatic spread. These observations are likely multifactorial, resultant of chronic inflammation paired with high rates of modifiable risk factors and diagnostic delays. An evident need for greater examination and improved reporting of these malignancies in the province was identified. [ABSTRACT FROM AUTHOR]

The article presents questions and answers related to the 2023 collaborative guidelines on penile cancer by the European Association of Urology (EAU) and American Society of Clinical Oncology, including the impact of penile cancer on patients' quality of life and the significance of p16 status.

Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma involving the epidermis and sometimes extends into the dermis. EMPD is most commonly seen in the intraepidermal primary form and rarely it occurs as a secondary form associated with malignancies. EMPD mostly occurs in areas such as vulva, penis, scrotum, perineum and axilla where apocrine glands are located. The most common site of involvement is vulva (65%). EMPD of male genital organs is less common, it accounts for 14% of cases. EMPD is a rare entity with very limited data in the literature and EMPD may occur in association with an underlying malignancy in adjacent organs. The diagnosis of EMPD is often delayed because of its non-specific features, its rarity, as well as the use of various treatments for dermatitis. The diagnosis and clinical management of EMPD is difficult. Biopsy should be taken from genital lesions unresponsive to treatment and histopathological examination, which is the basis of the diagnosis, should be performed. A detailed examination is necessary to detect an associated malignancy after diagnosis. Long-term follow-up of patients for regional lymphadenopathy, distant metastasis, local recurrence and development of internal malignancy form the basis of clinical management. [ABSTRACT FROM AUTHOR]

Background: Penile cancer (PC) is a highly aggressive disease, with a significant tendency for lymphatic spreading and subsequent development of distant metastases. The mutilating nature of PC surgical treatment has profound implications on the patient's body integrity and self-image, sexual life and intimacy, voiding and mental health. The aim of our study was to comprehensively evaluate PC patients' post-treatment quality of life (QoL), sexual activity, self-esteem, fatigue and fear of disease recurrence. (2) Methods: A cross-sectional study was conducted at the Clinic of Urology, University Clinical Centre of Serbia, and included 31 PC patients. Data were collected by means of a questionnaire. (3) Results: The average score on the Global health status scale was 67.2 out of 100 (ranging from 16.7 to 100), and the SD was 22.5. Hierarchical linear regression analysis showed that demographic characteristics, Hospital Anxiety and Depression scale (HADS) anxiety and depression scores, total Multidimensional Fatigue Inventory, Fear of cancer recurrence and Rosenberg scores and erectile function score explained a total of 78.2% of the variance in the global health status/QoL scale of PC patients. (4) Conclusions: Efforts should be made not only to increase the survival of PC patients after surgical treatment but also to enable the best possible level of QoL in the post-operative period. [ABSTRACT FROM AUTHOR]

Simple Summary: Accurate preoperative staging and precise outlining of a tumor's extent are crucial for selecting the most suitable treatment approach and improving outcomes. The current clinical staging of penile cancer is still largely based on physical examination. Multiparametric magnetic resonance imaging (mpMRI) is an important imaging modality that complements physical examination and reduces uncertainties that can easily arise during this examination. However, evidence for the application of MRI in the assessment of penile cancer is scarce; there is no consensus on MRI protocols, and functional MRI techniques have not been widely studied before. This paper focuses on the diagnostic performance of non-erectile mpMRI in evaluating penile cancer, reviewing the use of functional techniques for comprehensive oncological assessments together with the current literature and the latest guidelines. The role of multiparametric magnetic resonance imaging (mpMRI) in assessing penile cancer is not well defined. However, this modality may be successfully applied for preoperative staging and patient selection; postoperative local and regional surveillance; and assessments of treatment response after oncological therapies. Previous studies have been mostly limited to a few small series evaluating the accuracy of MRI for the preoperative staging of penile cancer. This review discusses the principles of non-erectile mpMRI, including functional techniques and their applications in evaluating the male genital region, along with clinical protocols and technical considerations. The latest clinical classifications and guidelines are reviewed, focusing on imaging recommendations and discussing potential gaps and disadvantages. The development of functional MRI techniques and the extraction of quantitative parameters from these sequences enables the noninvasive assessment of phenotypic and genotypic tumor characteristics. The applications of advanced techniques in penile MRI are yet to be defined. There is a need for prospective trials and feasible multicenter trials due to the rarity of the disease, highlighting the importance of minimum technical requirements for MRI protocols, particularly image resolution, and finally determining the role of mpMRI in the assessment of penile cancer [ABSTRACT FROM AUTHOR]

Malignant priapism (MP) is defined as a condition of persistent erection of the penis without sexual stimulation due to the neoplastic process of the cavernous sinus and the efferent veins. The effectiveness of established therapeutic recommendations in priapism was ineffective in MP. Modalities of therapy for MP varied from medication treatment, nonsurgical treatment, surgical treatment, and radiotherapy. Despite aggressive surgical management combined with radiation therapy, chemotherapy, or targeted therapy, the survival rate remains low. Therefore, the treatment is usually palliative, focusing on the patient's quality of life improvement and symptom relief. [ABSTRACT FROM AUTHOR]

Objective: Inguinal lymphadenectomy is essential for staging and disease control. Minimally invasive techniques are recently replacing open techniques to reduce complications. We present our experience and lessons learnt from 21 patients who underwent lateral video endoscopic inguinal lymphadenectomy (L-VEIL) for penile malignancy. Methods: All patients above 18 years of age with histo pathology-confirmed squamous cell carcinoma penis with stages = T1b and T1a with persistent lymphadenopathy who underwent L-VEIL over a period of 2 years (2020-2022) were included. The data were analyzed on the basis of intraoperative and postoperative complications, lymph node yield, hospital stay, and histopathology report. Results: Forty-one lower limbs of 21 patients underwent L-VEIL during the abovementioned period. Median age was 52 years. Mean operative time (on 1 side) was 80 minutes. Median lymph node yield per side was 7.2. Intraoperatively, 1 patient had a vascular injury at the saphenofemoral junction, requiring conversion to open. Postoperative complications were superficial surgical site infection (n = 4), lymphedema (n = 1), and lymphocoele (n = 3), one of which was drained by pigtail catheter. One patient required exploration on the second postoperative day because of vascular injury. Average duration of hospital stay was 3 days. The median time of drain removal was 13 days. Histopathology suggested seminoma in 1 patient and mature teratoma in 1 patient; the rest of the patients' reports were negative for malignancy. Conclusion: The L-VEIL is safe and feasible, and there is a reduction (~30%) in complications; oncological outcomes are also not affected. It has better ergonomics, resulting in ease and comfort for surgeons when compared with classical VEIL. [ABSTRACT FROM AUTHOR]

Simple Summary: The human microbiome has become an increasingly important area of study in recent years, with growing evidence suggesting that it plays a critical role in numerous diseases, including those affecting the urinary tract. However, the specific role of the microbiome in malignant urologic diseases remains largely unknown. Our study aimed to synthesize current evidence regarding the relationship between the microbiome and these urologic conditions, such as prostate, bladder, kidney, penile, and testicular cancer. Our systematic review of 37 studies provides an up-to-date overview of the microbiome's role in urologic health concerns. Using the present study as a guide, future studies have potential for microbiome-focused interventions to offer hope for presently unexplained medical conditions. The microbiome, once considered peripheral, is emerging as a relevant player in the intricate web of factors contributing to cancer development and progression. These often overlooked microorganisms, in the context of urological malignancies, have been investigated primarily focusing on the gut microbiome, while exploration of urogenital microorganisms remains limited. Considering this, our systematic review delves into the complex role of these understudied actors in various neoplastic conditions, including prostate, bladder, kidney, penile, and testicular cancers. Our analysis found a total of 37 studies (prostate cancer 12, bladder cancer 20, kidney cancer 4, penile/testicular cancer 1), revealing distinct associations specific to each condition and hinting at potential therapeutic avenues and future biomarker discoveries. It becomes evident that further research is imperative to unravel the complexities of this domain and provide a more comprehensive understanding. [ABSTRACT FROM AUTHOR]

Simple Summary: To date, no specific analyses focusing on penile-sparing surgery for local tumour recurrence after previous glansectomy or partial penectomy have been reported. We addressed this void and we considered a retrospective series of consecutive patients treated at a single institution. We focused on: (1) treatment feasibility, (2) complications, and (3) oncological outcomes. We tested the feasibility and oncological outcomes after penile-sparing surgery (PSS) for local recurrent penile cancer after a previous glansectomy/partial penectomy. We retrospectively analysed 13 patients (1997–2022) with local recurrence of penile cancer after a previous glansectomy or partial penectomy. All patients underwent PSS: circumcision, excision, or laser ablation. First, technical feasibility, treatment setting, and complications (Clavien–Dindo) were recorded. Second, Kaplan–Meier plots depicted overall and local recurrences over time. Overall, 11 (84.5%) vs. 2 (15.5%) patients were previously treated with glansectomy vs. partial penectomy. The median (IQR) time to disease recurrence was 56 (13–88) months. Six (46%) vs. two (15.5%) vs. five (38.5%) patients were treated with, respectively, local excision vs. local excision + circumcision vs. laser ablation. All procedures, except one, were performed in an outpatient setting. Only one Clavien–Dindo 2 complication was recorded. The median follow-up time was 41 months. Overall, three (23%) vs. four (30.5%) patients experienced local vs. overall recurrence, respectively. All local recurrences were safely treated with salvage surgery. In conclusion, we reported the results of a preliminary analysis testing safety, feasibility, and early oncological outcomes of PSS procedures for patients with local recurrence after previous glansectomy or partial penectomy. Stronger oncological outcomes should be tested in other series to optimise patient selection. [ABSTRACT FROM AUTHOR]

Simple Summary: Sufficient prognostic parameters are still lacking in penile cancer. In this study, we sought to evaluate the current TNM classification in terms of its ability to estimate prognosis and to identify additional independent prognostic parameters. We found that lymph node metastasis—as well as lymphovascular invasion in node-negative patients—had the strongest impact on prognosis, whereas HPV did not show an influence on outcome. Furthermore, the pT1b stage seems questionable, and a revision of the current TNM classification is advised. Background: Advanced penile carcinoma is characterized by poor prognosis. Most data on prognostic factors are based on small study cohorts, and even meta-analyses are limited in patient numbers. Therefore, there is still a lack of evidence for clinical decisions. In addition, the most recent TNM classification is questionable; in line with previous studies, we found that it has not improved prognosis estimation. Methods: We evaluated 297 patients from Germany, Russia, and Portugal. Tissue samples from 233 patients were re-analyzed by two experienced pathologists. HPV status, p16, and histopathological parameters were evaluated for all patients. Results: Advanced lymph node metastases (N2, N3) were highly significantly associated with reductions in metastasis-free (MFS), cancer-specific (CS), and overall survival (OS) rates (p = <0.001), while lymphovascular invasion was a significant parameter for reduced CS and OS (p = 0.005; p = 0.007). Concerning the primary tumor stage, a significant difference in MFS was found only between pT1b and pT1a (p = 0.017), whereas CS and OS did not significantly differ between T categories. In patients without lymph node metastasis at the time of primary diagnosis, lymphovascular invasion was a significant prognostic parameter for lower MFS (p = 0.032). Histological subtypes differed in prognosis, with the worst outcome in basaloid carcinomas, but without statistical significance. HPV status was not associated with prognosis, either in the total cohort or in the usual type alone. Conclusion: Lymphatic involvement has the highest impact on prognosis in penile cancer, whereas HPV status alone is not suitable as a prognostic parameter. The pT1b stage, which includes grading, as well as lymphovascular and perineural invasion in the T stage, seems questionable; a revision of the TNM classification is therefore required. [ABSTRACT FROM AUTHOR]

An 8-year-old boy initially thought to have a penile arteriovenous malformation was later diagnosed with a rare vascular sarcoma, epithelioid hemangioendothelioma (EHE). Despite challenges in diagnosis, he underwent supraselective angioembolization and partial penectomy for oncological clearance. EHE, a low-grade malignancy, requires prompt identification and treatment due to potential systemic involvement. [ABSTRACT FROM AUTHOR]

Simple Summary: Male cancers include common prostate cancer (PC) and the much rarer testicular (TC) and penile cancers. Recent survival data for these cancers are relatively good, but long-term studies are rare. To analyzed relative survival in these cancers, we used the NORDCAN database with information from Denmark, Finland, Norway, and Sweden over a 50-year period (1971–2020). Survival improved early for TC, and 5-year survival reached 90% after 1985. Towards the end of the follow-up, TC patients who had survived the 1st year survived the next 4 years with a comparable probability to the background population. For PC, 90% survival was reached after 2000. For penile cancer, 5-year survival never reached 90%, and the improvements in survival were modest at best. As conclusions, more than 90% of the patients diagnosed with PC and TC are alive 5 years later compared to men in general. For penile cancer, mortality is higher, and early symptoms should be discussed with the doctor. Survival studies are important tools for cancer control, but long-term survival data on high-quality cancer registries are lacking for all cancers, including prostate (PC), testicular (TC), and penile cancers. Using generalized additive models and data from the NORDCAN database, we analyzed 1- and 5-year relative survival for these cancers in Denmark (DK), Finland (FI), Norway (NO), and Sweden (SE) over a 50-year period (1971–2020). We additionally estimated conditional 5/1-year survival for patients who survived the 1st year after diagnosis. Survival improved early for TC, and 5-year survival reached 90% between 1985 (SE) and 2000 (FI). Towards the end of the follow-up, the TC patients who had survived the 1st year survived the next 4 years with comparable probability to the background population. For PC, the 90% landmark was reached between 2000 (FI) and after 2010 (DK). For penile cancer, 5-year survival never reached the 90% landmark, and the improvements in survival were modest at best. For TC, early mortality requires attention, whereas late mortality should be tackled for PC. For penile cancer, the relatively high early mortality may suggest delays in diagnosis and would require more public awareness and encouragement of patients to seek medical opinion. In FI, TC and penile cancer patients showed roughly double risk of dying compared to the other Nordic countries, which warrants further study and clinical attention. [ABSTRACT FROM AUTHOR]

Simple Summary: Vaccination against human papillomavirus (HPV) helps prevent cancer caused by this virus. Determining which viral genotypes should be included is key for developing successful vaccination strategies. Low-risk genotypes, especially HPV6 and HPV11, are associated with benign warts. However, some studies also report their presence in cancers. We reviewed the scientific literature to estimate the proportion of cancers that bear single or dual HPV6/11 infections. HPV6 and HPV11 have been reported in up to 5.5% of penile and 87.5% of laryngeal cancers; however, they have not been reported in vulvar, vaginal or oral cancers. Next, we compared the HPV6/11 genomes with HPV16, the most common high-risk HPV genotype, and observed that the similarities mainly involved the E7 gene, suggesting a limited ability to interfere with the differentiation of the host cells. These findings support the use of HPV vaccines that cover HPV6/11 not only for preventing genital warts but also for preventing specific types of cancers. High-risk human papillomavirus (HPV) is etiologically related to cervical cancer, other anogenital cancers and oropharyngeal carcinomas. Low-risk HPV, especially HPV6 and HPV11, cause genital warts and laryngeal papillomas. However, the accumulating data suggests that HPV6 and HPV11 may cause malignant lesions at non-cervical anatomic sites. This review aims to estimate the proportions of single and dual HPV6/11 infections in multiple cancers reported in the last 10 years in the Cochrane, Embasa and PubMed databases. Secondly, the genomes of HPV6/11 were compared with the most common high-risk genotype, HPV16, to determine the similarities and differences. A total of 11 articles were selected, including between one and 334 HPV+ cancer patients. The frequencies of single or dual HPV6/11 infections ranged between 0–5.5% for penile and 0–87.5% for laryngeal cancers and were null for vulvar, vaginal and oral cancers. The genomic similarities between HPV6/11 and HPV16 mainly involved the E7 gene, indicating a limited ability to block cell differentiation. The presence of single or dual HPV6/11 infections in variable proportions of penile and laryngeal cancers support the vaccination strategies that cover these genotypes, not only for preventing genital warts but also for cancer prevention. Other risk factors and co-carcinogens are likely to participate in epithelial carcinogenesis associated with low-risk HPV. [ABSTRACT FROM AUTHOR]

Brachytherapy for localised prostate, muscle-invasive bladder and penile cancer is well established, providing high tumour dose delivery and minimising normal tissue doses compared with external beam techniques. In prostate cancer, the main impact on quality of life relates to diminished sexual function and irritative or obstructive urinary symptoms, which are seen up to 15 years after treatment. Significant changes in bowel function are rare. Compared with radical prostatectomy or external beam radiotherapy, irritative or obstructive urinary symptoms are more prominent, whereas incontinence is less than after radical prostatectomy and bowel changes are less than after external beam radiotherapy. For muscle-invasive bladder cancer, when compared with radical cystectomy, although no difference is seen for urinary symptoms or fatigue, role and social functioning scores are higher and there is better post-treatment sexual function in both men and women. Compared with surgical treatment for penile cancer, brachytherapy results in better erectile function scores than after glansectomy and partial penectomy and high quality of life scores, with good satisfaction ratings for cosmetic appearance. • Brachytherapy for localised prostate, MIBC and penile cancer delivers high tumour dose and minimising normal tissue doses. • In prostate cancer, compared to radical prostatectomy or EBRT, incontinence is less than after radical prostatectomy and bowel changes are less than after EBRT. • For MIBC, compared with radical cystectomy, role and social functioning scores quality of life are higher and there is better post-treatment sexual function in both men and women. • Compared to surgical treatment for penile cancer, brachytherapy results in better erectile function scores, high quality of life scores and good satisfaction ratings for cosmetic appearance. [ABSTRACT FROM AUTHOR]

Simple Summary: Penile squamous cell carcinoma (PSCC) is a rare and aggressive cancer. About half of all PSCC cases are thought to be related to human papillomavirus (HPV) or have increased expression of p16 by immunohistochemistry (IHC), a surrogate marker for HPV infection. HPV/p16 positivity is generally a marker of better outcomes in more common squamous cell carcinomas, but the studies evaluating its prognostic value in PSCC are conflicting. In this systematic review, we aim to summarize the existing literature on the impact of these biomarkers on PSCC prognosis and determine their potential value in identifying patients with more favorable biology. PSCC is a rare cancer, with approximately half of all cases related to HPV. While HPV and p16 IHC testing have proven their prognostic value for oropharyngeal cancer, this is not yet established for PSCC. The current level of evidence exploring the relation between PSCC and HPV is moderate, so we conducted a systematic review following PRISMA guidelines to evaluate the prognostic role of HPV and p16 IHC in PSCC clinical outcomes. We searched the PubMed, Embase, and Cochrane databases and identified 34 relevant studies that met our inclusion criteria. Of these, 33 were retrospective cohort studies, and one was a cross-sectional study. Nine studies reported that HPV-positive and p16-positive PSCC had better overall survival (OS) and disease-free survival (DFS). This study highlights the need for a meta-analysis to determine the role of routine HPV status or p16 staining testing as part of the initial diagnosis and staging of PSCC patients worldwide. [ABSTRACT FROM AUTHOR]

Simple Summary: Penile cancer is considered a rare disease in most developed countries, yet it represents a significant global oncology challenge. Many patients are faced with substantial psychosocial morbidity from diagnosis and treatment, which is further compounded by a lack of access to novel treatment approaches when the disease becomes resistant to upfront therapies. Proteins on the cell surface, or surfaceome, represent an accessible locale of potential biomarkers and therapeutic targets. This study provides the first description of the surfaceome in penile cancer and evaluates if human papillomavirus infection contributes to surfaceome diversity. Penile squamous cell carcinoma (PSCC) is a rare malignancy in most parts of the world and the underlying mechanisms of this disease have not been fully investigated. About 30–50% of cases are associated with high-risk human papillomavirus (HPV) infection, which may have prognostic value. When PSCC becomes resistant to upfront therapies there are limited options, thus further research is needed in this venue. The extracellular domain-facing protein profile on the cell surface (i.e., the surfaceome) is a key area for biomarker and drug target discovery. This research employs computational methods combined with cell line translatomic (n = 5) and RNA-seq transcriptomic data from patient-derived tumors (n = 18) to characterize the PSCC surfaceome, evaluate the composition dependency on HPV infection, and explore the prognostic impact of identified surfaceome candidates. Immunohistochemistry (IHC) was used to validate the localization of select surfaceome markers. This analysis characterized a diverse surfaceome within patient tumors with 25% and 18% of the surfaceome represented by the functional classes of receptors and transporters, respectively. Significant differences in protein classes were noted by HPV status, with the most change being seen in transporter proteins (25%). IHC confirmed the robust surface expression of select surfaceome targets in the top 85% of expression and a superfamily immunoglobulin protein called BSG/CD147 was prognostic of survival. This study provides the first description of the PSCC surfaceome and its relation to HPV infection and sets a foundation for novel biomarker and drug target discovery in this rare cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Sentinel lymph nodes are the first regional lymph nodes to receive lymph fluid from the primary cancer, sentinel lymph node biopsy (SLNB) can detect occult nodal metastasis. In addition, it may also have a therapeutic effect via regional disease control. SLNB was first introduced in melanoma among skin cancers and is currently used in many types of skin cancers. Previous randomized clinical trials suggested a prognostic benefit from SLNB in melanoma patients. However, whether SLNB affects the prognosis of patients with nonmelanoma skin cancer remains largely unknown, although SLNB may provide important information about nodal status. Since SLNB may be associated with adverse events including infection, lymphedema, and nerve injury, routine application of SLNB for all patients with skin cancer is not recommended. In this review, we summarize the evidence available in the literature regarding the role of SLNB in skin cancer. The sentinel lymph node is the first lymph node from the primary tumor. Sentinel lymph node biopsy (SLNB) is a surgical procedure that can detect occult nodal metastasis with relatively low morbidity. It may also have a therapeutic effect via regional disease control. The Multicenter Selective Lymphadenectomy-I (MSLT-I) trial revealed a prognostic benefit from SLNB in melanoma patients. However, it remains unclear whether there is a prognostic benefit from SLNB in patients with nonmelanoma skin cancer owing to a lack of randomized prospective studies. Nevertheless, SLNB provides important information about nodal status, which is one of the strongest factors to predict prognosis and may guide additional nodal treatment. Currently, SLNB is widely used in the management of not only patients with melanoma but also those with nonmelanoma skin cancer. However, the utilization and outcomes of SLNB differ among skin cancers. In addition, SLNB is not recommended for routine use in all patients with skin cancer. In this review, we provide a summary of the role of SLNB and of the indications for SLNB in each skin cancer based on previously published articles. [ABSTRACT FROM AUTHOR]

The research questions were as follows: How much social support do patients with penile cancer (PC) receive after surgical treatment for the condition; which factors are associated with the social support received; and how do patients with PC describe the social support they receive in terms of emotional support, affirmation and concrete aid? The purpose of this study is to describe the amount and type of social support (that is, emotional support, affirmation or concrete aid) received by patients with PC. In addition, it describes the associations between patients' background variables and their perceived social support. Men affected by PC experience a range of unmet support care needs, of which social support has not previously been thoroughly studied. Emotional support consists of caring for another person, respecting and creating a safe atmosphere for them and providing spiritual support. Affirmation is the reinforcement of knowledge and is especially evident in decision‐making processes through advising or counselling. Concrete aid means the provision of assistance in the form of an activity or service that causes the donor to use time or money for the benefit of another person. A partially mixed concurrent dominant status design was used and included semi‐structured interviews with, or letter responses from, 15 patients and a self‐reported social support score survey of 42 patients with PC. The data were analysed using descriptive statistics, a non‐parametric test and a deductive content analysis. Regarding the self‐reported social support score survey, 42 patients reported the social support as good (mean [SD]; range 4.34 [1.06]; 1–6). The most frequent form of social support was affirmation (mean [SD] 4.65 [1.07]), and the least frequent was emotional support (mean [SD] 4.14 [1.16]). Employment status and primary operation were significantly associated with the social support received. Qualitative data imply that family members are the most important emotional supporters. Emotional support from healthcare professionals was felt to be insufficient. Despite their affirmation, patients felt they received incomplete information about the disease. Patients received concrete aid from family members but felt there was a lack of professional help. Although patients deemed the overall social support received to be good, they received insufficient support from healthcare professionals (emotional support) and had unmet informational needs (affirmation) as well as uncertainties regarding income support (concrete aid). Our results can help nurses provide more holistic care to patients with PC. This information can be utilized in the development of nursing interventions for such patients and their family members. In the future, nurses' and other healthcare professionals' counselling skills should be taken into account in their training. They also need to be supported through consultation and referral resources when they reach the limits of their expertise. [ABSTRACT FROM AUTHOR]

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Background Human papillomavirus (HPV) types 16/18 drive oncogenesis for most patients with cervical, anal, and penile cancers. MEDI0457, a therapeutic DNA vaccine containing plasmids for E6 and E7 HPV-16/18 viral oncogenes and IL-12 adjuvant, is safe and provokes an immune response against E6/E7. We tested MEDI0457 with the anti-PD-L1 antibody durvalumab for patients with HPV-associated cancers. Methods Patients with recurrent/metastatic, treatment-refractory HPV-16/18 cervical cancer, or rare HPV-associated (anal and penile) cancers were eligible. Prior immune checkpoint inhibition was not permitted. Patients received MEDI0457 7 mg intramuscularly (weeks 1, 3, 7, 12, and every 8 weeks thereafter) and durvalumab 1500 mg intravenously every 4 weeks. The primary endpoint was overall response (RECIST 1.1). In this Simon two-stage phase 2 trial (Ho: p  < 0.15; Ha: p  ≥ 0.35), ≥2 responses were needed in both cervical and non-cervical cohorts during the first stage for the trial to proceed to stage 2 with an additional 25 patients (34 total) enrolled. Results Twenty-one patients (12 cervical, 7 anal, and 2 penile) were evaluable for toxicity and 19 for response Overall response rate was 21% (95% CI, 6%-46%) among evaluable patients. Disease control rate was 37% (95% CI, 16%-62%). Median duration of response among responders was 21.8 months (95% CI, 9.7%-not estimable). Median progression-free survival was 4.6 months (95% CI, 2.8%-7.2%). Median overall survival was 17.7 months (95% CI, 7.6%-not estimable). Grades 3-4 treatment-related adverse events occurred in 6 (23%) participants. Conclusions The combination of MEDI0457 and durvalumab demonstrated acceptable safety and tolerability in patients with advanced HPV-16/18 cancers. The low ORR among patients with cervical cancer led to study discontinuation despite a clinically meaningful disease control rate. [ABSTRACT FROM AUTHOR]

Context.--Penile squamous cell carcinomas (PSCCs) are divided into tumors that are human papillomavirus (HPV) associated and those that are non-HPV associated. HPV and non-HPV PSCCs each display unique pathogenic mechanisms, histologic subtypes, and clinical behaviors. Treatment of localized PSCC tumors is linked to significant physical and psychological morbidity, and management of advanced disease is often treatment refractory. The identification of novel actionable mutations is of critical importance so that translational scientists and clinicians alike can pursue additional therapeutic options. Objective.--To provide an update on the molecular pathogenesis associated with PSCC. A special emphasis is placed on next-generation sequencing data and its role in identifying potential therapeutic targets. Data Sources.--A literature review using the PubMed search engine to access peer-reviewed literature published on PSCC. Conclusions.--Our understanding of the genetic and molecular mechanisms that underlie PSCC pathogenesis continues to evolve. PSCC tumorigenesis is mediated by multiple pathways, and mutations of oncogenic significance have been identified that may represent targets for personalized therapy. Preliminary results of treatment with immune checkpoint inhibition and tyrosine kinase inhibitors have produced variable clinical results. Further insight into the pathogenesis of PSCC will help guide clinical trials and develop additional precision medicine approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: Penile squamous cell carcinomas harbouring mutations of TP53 have an increased risk of lymph node metastases and an impaired prognosis, but the mutational analysis of the TP53 gene is not available in many pathology laboratories. Although p53 immunohistochemistry (IHC) has been proposed as an alternative to the molecular analysis, the current method of evaluation of p53 IHC has many inaccuracies. The aim of our study was to determine, in a series of 40 penile tumours, if a recently described pattern-based framework of p53 IHC evaluation correlates better than the classical method with the TP53 mutational status. Our results show that the new method has a very good correlation with TP53 mutations (95% sensitivity; 92% specificity), higher than that of the classical method, and can be considered as a reliable surrogate of the TP53 mutational status. This new framework can help clinicians to better define risk groups and refine treatment strategies. p53 immunohistochemistry (IHC) has been proposed as a surrogate for TP53 mutations in penile squamous cell carcinomas (PSCC). We aimed to evaluate the performance of a pattern-based evaluation of p53 IHC in PSCC. Human papilloma virus (HPV) DNA testing, p16 and p53 IHC, and whole exome sequencing were performed in a series of 40 PSCC. p53 IHC was evaluated following a pattern-based framework and conventional p53 IHC evaluation. Out of 40 PSCC, 12 (30.0%) were HPV-associated, and 28 (70.0%) were HPV-independent. The agreement between the p53 IHC pattern-based evaluation and TP53 mutational status was almost perfect (k = 0.85). The sensitivity and accuracy of the pattern-based framework for identifying TP53 mutations were 95.5% and 92.5%, respectively, which were higher than the values of conventional p53 IHC interpretation (54.5% and 70.0%, respectively), whereas the specificity was the same (88.9%). In conclusions, the pattern-based framework improves the accuracy of detecting TP53 mutations in PSCC compared to the classical p53 IHC evaluation. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Penile carcinomas represent a rare malignancy associated with significant psychosocial impacts that deter afflicted individuals from seeking medical attention, thus, worsening prognosis. Following the dramatic shift in healthcare delivery to virtual platforms, it is suspected that prevalent psychosocial impacts have been further compounded by the COVID-19 pandemic, resulting in several late-stage presentations and engendering poorer outcomes. METHODS: A retrospective chart review of surgically managed cases of penile cancer was conducted from January 2020 to June 2022 to identify patients that may have been unduly impacted by the COVID-19 pandemic. Included cases were analyzed in quantifying diagnostic and treatment delays, along with patient outcomes. Relevant epidemiological and pathological markers were also examined. RESULTS: Ten patients met the inclusion criteria. Average time delay from first complaint of a penile lesion to surgical management was 75 days, with 60% of patients experiencing a time delay of two months or more. The average delay from first complaint to diagnosis was 62 days in 2020 and 18 days in 2021. Advanced-stage disease was present in six (60%) individuals at presentation, while four (40%) patients perished during the study period. CONCLUSIONS: In cases of concern for penile malignancy, virtual care cannot replace the necessity of physical exams in preventing diagnostic and treatment delays. The present study further highlights the necessity of initial physical examination of penile abnormalities in preventing fatal outcomes for those afflicted. Such consideration warrants urgent examination of referred males with genital abnormalities to prevent further exacerbation of delays. [ABSTRACT FROM AUTHOR]

To assess the long-term risks of infectious and thromboembolic events following inguinal (ILND) and pelvic (PLND) lymph node dissection in men with penile cancer. A total of 364 men subjected to ILND with or without PLND for penile cancer between 2000 and 2012 were identified in the Swedish National Penile Cancer Register. Each patient was matched based on age and county of residence with six penile cancer-free men. The Swedish Cancer Register and other population-based registers were used to retrieve information on treatment and hospitalisation for selected infectious and thromboembolic events. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazard models with multiple imputation. The risk of infectious events remained increased for more than five years postoperatively in men with penile cancer compared with matched controls. The palpable nodal disease was the only predictor of these events, with risk increasing with the cN stage. The HR at one, three and five years and six months postoperatively was 8.60 (95% CI 5.16–14.34), 4.02 (95% CI 2.65–6.09) and 1.93 (95% CI 1.11–3.38), respectively. An increased risk of thromboembolic events persisted for three years postoperatively. The HR at one and three years postoperatively was 13.51 (95% CI 6.53–27.93) and 2.12 (95% CI 1.07–4.20). The results correspond well with the over-prescription of anticoagulants observed during this period. An association with bulky disease (cN3) was observed. Lymph node dissection for penile cancer is associated with an increased risk of infectious and thromboembolic events. The findings of this population-based study show that the risks of these events remain increased more than five years for infectious and three years for thromboembolic events. Improved awareness of long-term complications following ILND is of importance both among patients and care givers to ensure early detection and treatment. [ABSTRACT FROM AUTHOR]

Background previous studies have focused on the risk of cardiovascular disease (CVD)-related death in individual cancers, adolescents or all cancers. Objective to evaluate the risk of CVD-related death in older patients with cancer. Methods older patients with cancer (over 65 years) of 16 cancers diagnosed between 1975 and 2018 were screened out from the Surveillance, Epidemiology and End Results program. The proportion of deaths, competing risk regression models, standardized mortality ratios (SMRs) and absolute excess risks (AERs) were used to assess the risk of CVD-related death. Results this study included 1,141,675 older patients (median follow-up: 13.5 years). Of the 16 individual cancers, the risk of CVD death exceeded primary neoplasm death in older patients with cancers of the breast, endometrium, vulva, prostate gland, penis and melanoma of the skin over time (high competing risk group). Compared to the general older population, older patients with cancer had higher SMR and AER of CVD-related death (SMR: 1.58–4.23; AER: 21.16–365.89), heart disease-related death (SMR: 1.14–4.16; AER: 16.29–301.68) and cerebrovascular disease-related death (SMR: 1.11–4.66; AER: 3.02–72.43), with the SMR trend varying with CVD-related death competing risk classifications. The risk of CVD-related death in the high-competing risk group was higher than in the low-competing risk group. Conclusions for older patients with cancer, six of 16 individual cancers, including breast, endometrium, vulva, prostate gland, penis and melanoma of the skin was at high risk of CVD-related death. Management for long-term cardiovascular risk in older patients with cancer is needed. [ABSTRACT FROM AUTHOR]

New tumor biomarkers open the potential for designing personalized therapy for penile squamous cell carcinoma. Despite the initial promising results of some biomarkers, controversy remains due to contradictory studies. Further robust research work is required before incorporating biomarkers in the personalized management of penile cancer. This narrative review aims to highlight some of the most commonly and recently investigated biomarkers of penile cancer and to summarize the ongoing registered clinical trials for the management of penile cancer patients. [ABSTRACT FROM AUTHOR]

To compare differences of operative outcomes, post-operative complications and survival outcomes between open and laparoscopic cases in a multicenter study. This was a retrospective cohort study performed at three European centers from September 2011 to January 2019. The surgeon decision to perform open inguinal lymphadenectomy (OIL) or video endoscopic inguinal lymphadenectomy (VEIL) was done in each hospital after patient counselling. Inclusion criteria regarded a minimum follow-up of 9 months since the inguinal lymphadenectomy. A total of 55 patients with proven squamous cell penile cancer underwent inguinal lymphadenectomy. 26 of them underwent OIL, while 29 patients underwent VEIL. For the OIL and VEIL groups, the mean operative time was 2.5 vs. 3.4 h (p=0.129), respectively. Hospital stays were lower in the VEIL group with 4 vs. 8 days in OIL patients (p=0.053) while number of days requiring drains to remain in situ was 3 vs. 6 days (p=0.024). The VEIL group reported a lower incidence of major complications compared to the OIL group (2 vs. 17%, p=0.0067) while minor complications were comparable in both groups. In a median follow-up period of 60 months, the overall survival was 65.5 and 84.6% in OIL and VEIL groups, respectively (p=0.105). VEIL is comparable to OIL regarding safety, overall survival and post-operative outcomes. [ABSTRACT FROM AUTHOR]

The human papillomavirus (HPV) is the most common sexually transmitted infection in the United States despite most cases being preventable by vaccination. HPV vaccine efficacy varies in relationship to when the vaccine is administered, with greater efficacy obtained if administered prior to sexual debut. Historically, this vaccine was created to protect women from cervical cancer. As scientific knowledge of HPV-related cancers has advanced, it has become evident that HPV vaccination is a priority for both genders. HPV is known to contribute to male cancers of the mouth, throat, anus, and penis, as well as causing genital warts. This article aims to explain the benefits of HPV immunization for the gender the farthest from meeting vaccination goals, boys, and young men. This article expounds on the school nurses' role in promoting vaccination to prevent HPV infection and the sequela of related cancers. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Pathology is the property of Canadian Association of Pathologists and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: To optimize results reporting after penile cancer (PC) surgery, we proposed a Tetrafecta and assessed its ability to predict overall survival (OS) probabilities. Methods: A purpose-built multicenter, multi-national database was queried for stage I–IIIB PC, requiring inguinal lymphadenectomy (ILND), from 2015 onwards. Kaplan–Meier (KM) method assessed differences in OS between patients achieving Tetrafecta or not. Univariable and multivariable regression analyses identified its predictors. Results: A total of 154 patients were included in the analysis. The 45 patients (29%) that achieved the Tetrafecta were younger (59 vs. 62 years; p = 0.01) and presented with fewer comorbidities (ASA score ≥ 3: 0% vs. 24%; p < 0.001). Although indicated, ILND was omitted in 8 cases (5%), while in 16, a modified template was properly used. Although median LNs yield was 17 (IQR: 11–27), 35% of the patients had <7 nodes retrieved from the groin. At Kaplan–Maier analysis, the Tetrafecta cohort displayed significantly higher OS probabilities (Log Rank = 0.01). Uni- and multivariable logistic regression analyses identified age as the only independent predictor of Tetrafecta achievement (OR: 0.97; 95%CI: 0.94–0.99; p = 0.04). Conclusions: Our Tetrafecta is the first combined outcome to comprehensively report results after PC surgery. It is widely applicable, based on standardized and reproducible variables and it predicts all-cause mortality. [ABSTRACT FROM AUTHOR]

Simple Summary: Penile cancer is a rare malignant tumor mainly affecting adult/older men. Given the rarity of this disease, affecting 1/100,000 men every year, risk factors and diagnostic procedures are often inadequately described. This is the first multicenter study to describe the approach to this disease in Spain. The results highlight the need for the institution of referral centers and standardized diagnostic pathways for the optimal management of this disease. Introduction: Penile cancer (PC) is a rare malignancy with an overall incidence in Europe of 1/100,000 males/year. In Europe, few studies report the epidemiology, risk factors, clinical presentation, and treatment of PC. The aim of this study is to present an updated outlook on the aforementioned factors of PC in Spain. Materials and Methods: A multicentric, retrospective, observational epidemiological study was designed, and patients with a new diagnosis of PC in 2015 were included. Patients were anonymously identified from the Register of Specialized Care Activity of the Ministry of Health of Spain. All Spanish hospitals recruiting patients in 2015 were invited to participate in the present study. We have followed a descriptive narration of the observed data. Continuous and categorical data were reported by median (p25th–p75th range) and absolute and relative frequencies, respectively. The incidence map shows differences between Spanish regions. Results: The incidence of PC in Spain in 2015 was 2.55/100,000 males per year. A total of 586 patients were identified, and 228 patients from 61 hospitals were included in the analysis. A total of 54/61 (88.5%) centers reported ≤ 5 new cases. The patients accessed the urologist for visually-assessed penile lesions (60.5%), mainly localized in the glans (63.6%). Local hygiene, smoking habits, sexual habits, HPV exposure, and history of penile lesions were reported in 48.2%, 59.6%, 25%, 13.2%, and 69.7%. HPV-positive lesions were 18.1% (28.6% HPV-16). The majority of PC was squamous carcinoma (95.2%). PC was ≥cT2 in 45.2% (103/228) cases. At final pathology, PC was ≥pT2 in 51% of patients and ≥pN1 in 17% of cases. The most common local treatment was partial penectomy (46.9% cases). A total of 47/55 (85.5%) inguinal lymphadenectomies were open. Patients with ≥pN1 disease were treated with chemotherapy in 12/39 (40.8%) of cases. Conclusions: PC incidence is relatively high in Spain compared to other European countries. The risk factors for PC are usually misreported. The diagnosis and management of PC are suboptimal, encouraging the identification of referral centers for PC management. [ABSTRACT FROM AUTHOR]

Introduction: Penile cancer is a rare malignancy of the genitourinary tract. We aimed to validate the recent changes in the T2 and T3 stages of penile cancer in the American Joint Committee on Cancer (AJCC) 8th edition and to compare its predictive ability with two other modified staging systems for survival outcomes. Methods: This is a retrospective study of patients diagnosed with penile cancer from June 2015 to March 2020. The AJCC 8th edition and two other newly proposed systems by Li et al. and Sali et al. were used for staging the tumor. All variables were categorized and correlated with lymph node (LN) metastases and overall survival (OS). Results: Fifty-four patients were eligible for this study. The mean age was 58 years (range 46–72 years). The tumor stage (P = 0.016), clinical LN stage (P = 0.001), the involvement of the spongiosa (P = 0.015) and the cavernosa (P = 0.002), lymphovascular invasion (LVI) (P = 0.000), and PNI (P = 0.021) were found to be the significant predictors of LN metastases. When the 5 year OS was compared between the T2 and T3 stages of the AJCC 8th edition, Li staging and the Sali staging systems, it was 91% and 50.1% (P = 0.001), 97.5% and 10.3% (P = 0.000), 94.4% and 14.7% (P = 0.000), respectively. The presence of LVI (P = 0.001) was the most significant independent predictor of OS. Conclusions: The recent changes in the AJCC 8th edition pertaining to the T2-T3 stage are relevant, although the other two newly proposed staging systems were more precise in predicting the survival outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Between 2002 and 2020, 31 patients with early penile cancer were treated with high-dose-rate brachytherapy (HDR-BT) at a dose of 18 × 3 Gy twice daily. The technique of the hollow steel needles fixed by the template was used. At a median follow-up of 117.5 months, the probability of local control at 5- and 10-years was 80.7% and 68.3%, respectively, with a probability of penis sparing of 80.6% and 62.1%. Cause-specific suervival was 100%. Only one case of radionecrosis was observed. These results show HDR-BT can achieve results that are comparable to low-dose rate BT while also allowing for organ preservation. Background: Low-dose-rate brachytherapy is an effective organ-sparing treatment for patients with early-stage penile cancer. However, only limited data are available on the role of high-dose-rate brachytherapy (HDR-BT) in this clinical setting. Methods: Between 2002 and 2020, 31 patients with early penile cancer were treated at our center with interstitial HDR BT at a dose of 18 × 3 Gy twice daily. A breast brachytherapy template was used for the fixation of stainless hollow needles. Results: The median follow-up was 117.5 months (range, 5–210). Eight patients (25.8%) developed a recurrence; of these, seven were salvaged by partial amputation. Six patients died of internal comorbidities or a second cancer. The probability of local control at 5 and 10 years was 80.7% (95% CI: 63.7–97.7%) and 68.3% (95% CI: 44.0–92.6%), respectively. Cause-specific survival was 100%. Only one case of radiation-induced necrosis was observed. The probability of penile sparing at 5 and 10 years was 80.6% (95% CI: 63.45–97.7%) and 62.1% (95% CI: 34.8–89.4%), respectively. Conclusions: These results show that HDR-BT for penile cancer can achieve results comparable to LDR-BT with organ sparing. Despite the relatively large patient cohort—the second largest reported to date in this clinical setting—prospective data from larger samples are needed to confirm the role of HDR-BT in penile cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Penile Squamous Cell Carcinoma (PSCC) is a rare but aggressive cancer and approximately 30–50% of cases are associated with high risk human papillomavirus (HR-HPV). HR-HPV infection has been shown to correlate with expression of protein p16INK4a (p16). We wanted to determine if HPV-HR or p16 expression is associated with better outcomes in PSCC patients; therefore, we analyzed 143 patients with a diagnosis of PSCC and available tissue was analyzed for p16INK4a expression and HR-HPV status. Patients with p16+ tumors had a significantly longer median cancer specific survival in comparison to the p16-group (p = 0.004), with respective 5-year cancer specific survival probability of 88% (95% CI; 0.84, 1) versus 58% (95% CI; 0.55, 0.76; p = 0.004). HPV status did not predict survival outcomes. Penile Squamous Cell Carcinoma (PSCC) is associated with high-risk human papillomavirus (HR-HPV). The immunohistochemical (IHC) test for p16INK4a (p16) is highly correlated with HR-HPV expression in other SCCs. To investigate whether the expression of p16 IHC or HR-HPV is associated with survival in PSCC, we conducted a single institution analysis of 143 patients with a diagnosis of PSCC and, available tissue were tested for p16 IHC staining patterns, histological subtype, tumor grade, and lymphovascular invasion (LVI) by an experienced pathologist. HR-HPV status using the Cobas PCR Assay or the RNAScope high-risk HPV in situ hybridization kit were also assessed. Patient characteristics were summarized using descriptive statistics of clinico-pathologic variables. Kaplan–Meier was used to estimate median overall survival (OS), cancer specific survival (CSS) and correlated with HPV, p16, and other study variables. Patients with p16+ tumors had a significantly longer median CSS in comparison to the p16– group (p = 0.004), with respective 5-year CSS probability of 88% (95% CI; 0.84, 1) versus 58% (95% CI; 0.55, 0.76; p = 0.004). HPV status did not predict survival outcomes. Multivariable analysis with respect to OS and CSS, showed that p16+ status was associated with a lower risk of death (HR = 0.36, 95%CI; 0.20–0.67, p = 0.001), and improved CSS (HR = 0.20, 95% CI; 0.07–0.54, p = 0.002) after adjusting for covariates. In conclusion, tumor p16 status via IHC was an easy to perform independent prognostic factor for OS and CSS that correlates with HR-HPV expression. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this article is to describe surgical techniques for the management of localized penile cancer concurrent with adult acquired buried penis. Penile cancer, while rare, invariably impacts quality of life as the primary surgical management ranges from local excision to total penectomy. Penile cancer has recently been linked to adult acquired buried penis (AABP) with the hypothesis that chronic inflammation of the penis contributes to risk of penile malignancy. Buried penis reconstruction is now a well-described procedure involving escutcheonectomy and split thickness skin grafting which has been shown to improve quality of life in individuals with adult acquired buried penis.Technical Considerations: This report describes a patient with AABP requiring partial penectomy and inguinal node dissection who also underwent adult acquired buried penis repair during his procedure. A review of cases of buried penis cases was carried out and four other cases of penile cancer were identified who were managed with penile preserving procedures.Conclusions: This combination of surgical techniques strives to improve quality of life and facilitate cancer surveillance without compromising oncologic outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Penile cancer is a rare malignancy, with a Europeanwide annual incidence rate of 1/100 000 males. Approximately one-third of cases are attributable to human papillomavirus (HPV) infection. p16INK4a is a recognized surrogate marker for HPV infection in penile cancer. University Hospital Waterford (UHW) is the national referral center for penile cancer in Ireland. We report the prevalence of HPV infection and histological characteristics of an Irish penile cancer cohort using p16INK4a as a surrogate marker. Methods: Patients who attended UHW for penile cancer surgery between June 2015 and November 2020 were entered into a prospectively maintained database. Clinical, histopathological, and outcome data were collected. Results: Over the study period, 70 patients with a histological diagnosis of penile squamous cell carcinoma had staining for p16INK4a, of whom 64% were positive. p16INK4a-positive patients were significantly younger at diagnosis, with a mean age of 61±15 years compared to 68±12 (p <0.05). Of note, 97% of tumors with high-risk histology were p16INK4a-positive (p<0.001). p16INK4a positivity was more prevalent among higher-grade tumors (p<0.02). Interestingly, p16INK4a status was not associated with recurrence-free or overall survival. Conclusions: Our data is representative of the Irish landscape in penile cancer over the last five years. Using p16INK4a staining, we demonstrate a high rate of HPV prevalence in penile cancer cases in our patient cohort, which is associated with prognostically worse tumor subtypes. This would suggest that HPV vaccination of adolescent boys is a useful public health intervention in preventing penile cancer in the Irish male population. [ABSTRACT FROM AUTHOR]

Objective: Patients with vaginal, vulvar, penile or anal cancer experience deteriorated psychosocial functioning and decreased Quality of Life (QoL). The aims of this study were to explore (1) the challenges and controversies patients experience in managing vaginal, vulvar, penile or anal cancer; their unmet needs; and how this affects their psychosocial functioning and (2) the gaps health care professionals (HCPs) experience in providing psychosocial support and potential improvements in care. Methods: Semi‐structured interviews with patients with vaginal, vulvar, penile or anal cancer and with HCPs were conducted. All interviews were transcribed verbatim and thematically analysed. Results: Fourteen patients (86% female; mean age 55.5) and 12 HCPs (75% female; mean age 46.4) participated. Four themes were identified: (1) recognisable symptoms but unfamiliar diagnosis, (2) 'double hit' has severe impact on psychosocial functioning, (3) personal and tailored information is important but not guaranteed and (4) all‐encompassing care to improve psychosocial functioning and QoL. Conclusion: Patients with vaginal, vulvar, penile or anal cancer encounter a lack of awareness and knowledge about their rare cancer type, difficulties regarding communication and long‐term changes in body image and sexuality. Awareness of symptoms should be raised and psychosocial care should be offered on a structural basis. [ABSTRACT FROM AUTHOR]