A study protocol for a feasibility randomised controlled trial investigating videoendoscopic radical inguinal lymphadenectomy versus open radical inguinal lymphadenectomy in patients with penile cancer (VELRAD).

BACKGROUND: Penile cancer is a rare male genital malignancy. Surgical excision of the primary tumour is followed by radical inguinal lymphadenectomy if there is metastatic disease detected by biopsy, fine needle aspiration cytology (FNAC) or following sentinel lymph node biopsy in patients with impalpable disease. However, radical inguinal lymphadenectomy is associated with a high morbidity rate, and there is increasing usage of a videoendoscopic approach as an alternative. METHODS: A pragmatic, UK-wide multicentre feasibility randomised controlled trial (RCT), comparing videoendoscopic radical inguinal lymphadenectomy versus open radical inguinal lymphadenectomy. Patients will be identified and recruited from supraregional multi-disciplinary team meetings (sMDT) and must be aged 18 or over requiring inguinal lymphadenectomy, with no contraindications to surgical intervention for their cancer. Participants will be followed up for 6 months following randomisation. The primary outcome is the ability to recruit patients for randomisation across all selected sites and the rate of loss to follow-up. Other outcomes include acceptability of the trial and intervention to patients and healthcare professionals assessed by qualitative research and obtaining resource utilisation information for health economic analysis. DISCUSSION: There are currently no other published RCTs comparing videoendoscopic versus open radical inguinal lymphadenectomy. Ongoing study is required to determine whether randomising patients to either procedure is feasible and acceptable to patients. The results of this study may determine the design of a subsequent trial. TRIAL REGISTRATION: Clinicaltrials.gov PRS registry, registration number NCT05592639. Date of registration: 13th October 2022, retrospectively registered.

Penile carcinoma: A retrospective analysis of 93 patients at a tertiary care center in Jakarta, Indonesia.

OBJECTIVES: Penile carcinoma (PC) is a rare disease with considerable physical and psychological impact. To date, there is no data regarding PC prevalence and characteristics in Indonesia. This study aimed to analyze the characteristics of patients with PC in Indonesia and determine cumulative survival rates and time to disease progression. METHODS: This was a retrospective study of all patients diagnosed with PC at Cipto Mangunkusumo General Hospital from 1995 to 2014, with a minimum of 1 year follow-up. The outcomes of the study were cumulative survival rates and time-to-disease progression. RESULTS: Ninety-three subjects were recruited, with a mean age of 49.44 ± 13.62. Inguinal lymph node dissection (ILND) was performed in 49 (53%) patients. The mean survival in the ILND group was better compared to the non-ILND group (80.7 months vs. 67.1 months; p = 0.032). Time-to-progression in the ILND group was significantly longer than in the non-ILND group (71.7 months vs. 54.3 months; p = 0.022). No significant difference in survival between the total and partial penectomy (PP) groups was observed (p = 0.701). Time-to-progression in total penectomy (TP) was significantly longer than in PP (68 months vs. 56.0 months; p = 0.023). In Cox-regression analysis, after adjustment of other variables, history of ILND, higher stage of cancer, and older age were found to affect the survival of patients. CONCLUSION: ILND in PC led to better survival and reduced disease progression. The type of penectomy is only associated with progression but not survival. TP had a longer time to disease progression compared to PP.

Inguinal Lymphadenectomy for Penile Cancer: An Interim Report from a Trial Comparing Open Versus Videoendoscopic Surgery Using a Within-patient Design.

Background and objective: Nodal metastasis is a major survival and prognostic factor in penile cancer (PeCa). Thus, accurate staging, prognosis, and treatment selection require adequate inguinal lymphadenectomy (ILND). ILND surgery should balance oncologic rigor with morbidity and postoperative complications. Our aim was to compare the feasibility and safety of open ILND (OILND) and videoendoscopic ILND (VEILND) in patients with PeCa. Methods: We conducted a single-center randomized trial with a within-patient design between October 2019 and April 2023. Patients who were undergoing either staging or radical ILND for PeCa were included and randomized to receive either OILND or VEILND on one side, with the other technique then used on the contralateral side. The trial was approved by the local ethics committee and was registered on ClinicalTrials.gov (NCT05887921). The primary outcome was the safety of VEILND. Secondary outcomes included intraoperative and postoperative morbidity rates and surgical outcomes for the two procedures, as well as oncological outcomes according to survival estimates. Key findings and limitations: We included 14 patients in the study. Median follow-up was 12 mo (interquartile range [IQR] 12-17). There were no significant differences in operative time and the number of lymph nodes removed between OILND and VEILND. However, the median time to drain removal was significantly shorter in the VEILND group (15 d, IQR 13-17, 95% confidence interval [CI] 12-17) than in the OILND group (27 d, IQR 20-41, 95% CI 24-31; p = 0.025). No intraoperative complications were observed, but postoperative complications occurred in three cases (21.4%, 95% CI 8.4-37.8%) in the VEILND group and eight (57.1%, 95% CI 18.6-54.3%) in the OILND group (p = 0.032). Conclusions and clinical implications: VEILND represents a safe technique to consider for either staging or curative intent in PeCa and seems to have an advantage over OILND in terms of morbidity. Further high-powered studies are warranted to confirm these preliminary results. Patient summary: We compared the outcomes of two different surgical techniques to remove lymph nodes in patients with penile cancer. We found that a video-assisted keyhole surgery approach seems to result in a lower rate of complications than after open surgery.

Developing and validating a nomogram for penile cancer survival: A comprehensive study based on SEER and Chinese data.

OBJECTIVE: The primary aim of this study was to create a nomogram for predicting survival outcomes in penile cancer patients, utilizing data from the Surveillance, Epidemiology, and End Results (SEER) and a Chinese organization. METHODS: Our study involved a cohort of 5744 patients diagnosed with penile cancer from the SEER database, spanning from 2004 to 2019. In addition, 103 patients with penile cancer from Sun Yat-sen Memorial Hospital of Sun Yat-sen University were included during the same period. Based on the results of regression analysis, a nomogram is constructed and validated internally and externally. The predictive performance of the model was evaluated by concordance index (c-index), area under the curve, decision curve analysis, and calibration curve, in internal and external datasets. Finally, the prediction efficiency is compared with the TNM staging model. RESULTS: A total of 3154 penile patients were randomly divided into the training group and the internal validation group at a ratio of 2:1. Nine independent risk factors were identified, including age, race, marital status, tumor grade, histology, TNM stage, and the surgical approach. Based on these factors, a nomogram was constructed to predict OS. The nomogram demonstrated relatively better consistency, predictive accuracy, and clinical relevance, with a c-index over 0.73 (in the training cohort, the validation cohort, and externally validation cohort.) These evaluation indexes are far better than the TNM staging system. CONCLUSION: Penile cancer, often overlooked in research, has lacked detailed investigative focus and guidelines. This study stands as the first to validate penile cancer prognosis using extensive data from the SEER database, supplemented by data from our own institution. Our findings equip surgeons with an essential tool to predict the prognosis of penile cancer better suited than TNM, thereby enhancing clinical decision-making processes.

Impact of pathologic features on local recurrence in penile squamous cell carcinoma after penectomy.

BACKGROUND: Penile squamous cell carcinoma (PSCC) is a rare malignancy that may be cured in cases of local disease by resection of the primary tumor. Risk factors and patterns of local recurrence (LR) have not been well described in cases requiring partial or radical penectomy. In this study, we evaluated risk factors for LR and the impact of frozen and final margin assessment. MATERIALS AND METHODS: We evaluated 119 patients with PSCC who had undergone partial or radical penectomy from 2007 to 2023. Data regarding clinical and pathologic features were collected by retrospective chart review. The primary outcome of interest was LR. Determinants of LR were analyzed by Student's t, Fisher's exact, chi-square and logistic regression analysis. Predictive statistics of frozen margin status on final margin were assessed and LR rates for subsets of frozen and final margin interaction were defined. Finally, all cases of positive margins and LR were described to highlight patterns of LR and the importance of margin status in these cases. RESULTS: There were 8 (6.7%) cases of local recurrence. There were no significant predictors of LR, although a trend toward increased LR risk was observed among those with a positive final margin. Positive final margins were found in 15 (13%) cases. Frozen margin analysis was utilized in 79 cases, of which 10 (13%) were positive. The sensitivity, specificity, positive predictive value, and negative predictive value of frozen margin status for final margins were 44%, 92%, 40%, and 93%, respectively. There were no LR among cases in which frozen margin was not sent. Analysis of all cases with positive margin and/or LR identified three subsets of patients: CIS or focally positive margin resulting in either no LR or LR managed with minimal local intervention, bulky disease in which survival is determined by response to subsequent therapy rather than local recurrence, and clinically significant local recurrence requiring continued surveillance and intervention despite negative margins. CONCLUSIONS: LR is rare, even in cases of larger, proximal tumors requiring partial or radical penectomy. In this study, no statistically significant risk factors for local recurrence were identified; however, analysis of frozen and final margins provided insight into the importance of margin status and patterns of local recurrence. When feasible, visibly intra-operative negative margins are an excellent predictor of low risk for LR, and, in cases of CIS or focally positive margins, further resection to achieve negative margins is unlikely to reduce the risk of clinically significant LR. Additionally, in cases of bulky disease, the goals of resection should be focused toward palliation and next line therapy.

Phallus preservation and reconstruction: 5-year outcomes of national penile cancer centralisation in the Republic of Ireland.

INTRODUCTION: Penile cancer is a rare urological malignancy with an age-standardised incidence of 0.8 per 100,000 person-years [1]. Given this low incidence it has been suggested that centralised care may improve patient outcomes in relation to phallus sparing surgery and nodal assessment [2]. We aim to assess the outcomes after 5-years of national centralisation of penile cancer care. METHODS: A retrospective analysis of prospectively collected data was performed. All patients undergoing penile cancer surgery from January 2018 to December 2022 following centralisation of care were included. The primary outcome was proportion of phallus sparing procedures performed. Secondary outcomes were patient characteristics, histologic outcomes and procedures performed. RESULTS: 124 patients underwent surgery in the study period. Mean age was 64.49 (±13.87). Overall, 82.3% of patients underwent phallus sparing surgery. This remained stable over the 5-year period from 2018 to 2022 â€‹at 92%, 85%, 76%, 79% and 78% respectively (p â€‹= â€‹0.534). 62.7% had reconstruction performed, including split-thickness skin graft neoglans formation, (57.8% [n â€‹= â€‹37]), preputial flap (32.8% [n â€‹= â€‹21]), glans resurfacing (4.7% [n â€‹= â€‹3]), shaft advancement flap (1.6% [n â€‹= â€‹1]), penile shaft skin graft (1.6% [n â€‹= â€‹1]), and partial penectomy with urethral centralisation (1.6% [n â€‹= â€‹1]). Phallus preservation was not affected by positive nodal status (OR 0.75 [95% CI 0.249-2.266], p â€‹= â€‹0.564) or T-stage ≥1b (OR 0.51 [95% CI 0.153-1.711], p â€‹= â€‹0.276). There has been a significant reduction in Nx nodal status from 64% in 2017 to 15% in 2021 (p â€‹= â€‹0.009). CONCLUSION: Centralisation of treatment for rare malignancies such as penile cancer may improve oncologic outcomes and rates of phallus preservation. This study has shown centralisation to has a high rate of phallus preservation. Further long-term analysis of outcomes in Ireland is required.

Penile Osteosarcoma: A Rare Extraosseous Site.

Primary penile extraosseous osteosarcoma (EOS) ranks the most uncommon amongst the differential penile masses, with only nine cases reported so far. In this report, we share the management of a 67-year-old Hispanic male who presented with a painful mass over his distal penile shaft and glans for the last two months. After initial imaging and complete blood investigations, he underwent partial penectomy. Histology revealed high-grade sarcoma, with osteoid production, favoring high-grade extra-skeletal osteosarcoma, with tumor necrosis involving approximately 5% of the tumor volume. The patient had bilateral palpable inguinal lymphadenopathy, which was seen even on a pre-op CT scan. The patient thus underwent bilateral robotic superficial and deep inguinal standard template lymph node dissection three weeks after his partial penectomy. His pathology was negative for malignancy in all examined lymph nodes. At his last follow-up, five months post his primary surgery, he had been doing well without concerns for recurrence.

Does MRI Have a Role in the Preoperative Staging of Penile Cancer?

Background Penile cancer is a rare malignancy usually requiring surgery to achieve oncological control of the primary tumour but often at the expense of functional length. The presenting stage of the primary is a crucial factor in determining the most appropriate surgical procedure. Accurate preoperative staging is essential, and current modalities include clinical and radiological assessment. Clinical staging can, however, be hampered by patient body habitus and unreliable for more advanced T4 tumours, whereas radiological staging allows for more detailed identification of tissue planes and tumour involvement. There is no clear consensus on the preferred imaging technique, although, in the current European Association of Urology penile cancer guidelines, MRI is recommended with the use of ultrasound when MRI is not available. It was recommended that having the penis in an erect state by the administration of intra-cavernosal prostaglandin gave a more detailed picture enabling a greater predictor of corporal involvement. Recent studies have, however, suggested that there may be no such advantage. Methodology A retrospective review was conducted of all patients who underwent surgery for penile cancer comparing the preoperative MRI stage with the final pathological stage between July 2009 and June 2023. In addition to the MRI, patients were given an intra-cavernosal injection of prostaglandin E1 to induce tumescence unless otherwise indicated. All imaging was reported by a single consultant uro-radiologist with surgery undertaken by a single surgeon and pathology reviewed through the supra-regional penile multidisciplinary team. Results A total of 136 penile cancer patients were included in the review. Within this cohort, 98 patients had an MRI without intra-cavernosal prostaglandin and the number who had Ta, T1, T2, T3 and T4 histopathological stages was 3, 31, 45, 18, and 1, respectively. The preoperative MRI stage had a low agreement with the final histological stage for early tumours, with sensitivities and specificity of 35% and 97% for T1 and 56% and 80% for T2, respectively. Sensitivity and specificity increased for cavernosal involvement at 83% and 95%, respectively. In addition, a further 38 patients had an MRI in conjunction with an injection of prostaglandin E1 which failed to show any diagnostic improvement in sensitivity or specificity in the preoperative MRI stage. Conclusions The use of MRI as a preoperative modality for staging penile cancer performs best for identifying tumour involvement of the cavernosal bodies. Performing the MRI with the penis erect with the use of an intra-cavernosal injection did not offer any additional benefit in accurately staging penile cancer.

"Bone in the penis" or fasciitis ossificans of the penis - a first time description of a pseudo-tumor at an extraordinary site.

BACKGROUND: Fasciitis ossificans is a rare subtype of nodular fasciitis, a benign soft tissue tumor with reactive characteristics. Due to its rapid growth, it is often misdiagnosed as a malignant tumor. While fasciitis ossificans commonly originates from the subcutaneous tissue and can appear throughout the body, it may also arise from extraordinary sites. CASE PRESENTATION: We report the first-ever documented case of fasciitis ossificans arising from the penis in a male patient who presented with a tumor on the glans penis. The tumor was surgically resected due to suspicion of penile cancer. Initial histopathological analysis led to a misdiagnosis of squamous cell carcinoma. However, pathological consultation ultimately confirmed the diagnosis of fasciitis ossificans of the penis originating from the glans penis by demonstrating ossification. CONCLUSION: This case underscores the importance of considering fasciitis ossificans in the differential diagnosis of soft tissue tumors, even in unusual locations such as penile soft tissue.

Structured Literature Review to Identify Human Papillomavirus's Natural History Parameters for Dynamic Population Models of Vaccine Impacts.

Human papillomavirus (HPV) is a common sexually transmitted virus that can cause cervical cancer and other diseases. Dynamic transmission models (DTMs) have been developed to evaluate the health and economic impacts of HPV vaccination. These models typically include many parameters, such as natural history of the disease, transmission, demographic, behavioral, and screening. To ensure the accuracy of DTM projections, it is important to parameterize them with the best available evidence. This study aimed to identify and synthesize data needed to parametrize DTMs on the natural history of HPV infection and related diseases. Parameters describing data of interest were grouped by their anatomical location (genital warts, recurrent respiratory papillomatosis, and cervical, anal, vaginal, vulvar, head and neck, and penile cancers), and natural history (progression, regression, death, cure, recurrence, detection), and were identified through a systematic literature review (SLR) and complementary targeted literature reviews (TLRs). The extracted data were then synthesized by pooling parameter values across publications, and summarized using the range of values across studies reporting each parameter and the median value from the most relevant study. Data were extracted and synthesized from 223 studies identified in the SLR and TLRs. Parameters frequently reported pertained to cervical cancer outcomes, while data for other anatomical locations were less available. The synthesis of the data provides a large volume of parameter values to inform HPV DTMs, such as annual progression rates from cervical intraepithelial neoplasia (CIN) 1 to CIN 2+ (median of highest quality estimate 0.0836), CIN 2 to CIN 3+ (0.0418), carcinoma in situ (CIS) 2 to local cancer+ (0.0396), and regional to distant cancer (0.0474). Our findings suggest that while there is a large body of evidence on cervical cancer, parameter values featured substantial heterogeneity across studies, and further studies are needed to better parametrize the non-cervical components of HPV DTMs.

Fine scalpel surgery: preserving the dartos muscle in a patient with scrotal and perigenital giant Buschke-Löwenstein tumors.

Giant condyloma acuminatum (GCA), alternatively referred to as a Buschke-Löwenstein tumor (BLT), is an uncommon, benign, but locally aggressive form of verrucous carcinoma. The condition usually affects the male population under the age of 50 years; however, there have been rare reports of pediatric cases. Various risk factors such as smoking, diabetes, promiscuous behavior, poor hygiene, immunosuppression, and others are linked to the development of this condition. We present the case of a 26-year-old male patient who came to the dermatology department with primary complaints of 10-year-old verrucous tumor formations located in the perigenital and perianal areas. Serological tests for AIDS, hepatitis B, hepatitis C, Chlamydia trachomatis, and syphilis were negative. The routine blood tests were slightly abnormal. Histological verification of condylomata acuminata of Buschke-Löwenstein was made. Given the sensitive areas, surgery was advised. With several fine undermining scalpel excisions, the lesions in the scrotal and perigenital areas were removed and the dartos muscle was preserved. Electrodissection and shave curettage were not performed. The postoperative period passed without complications and no recurrences in the perigenital area were reported. We believe that our case report represents the first documented surgical approach for scrotal Buschke-Löwenstein tumor using exclusively fine undermining scalpel surgery. A brief literature review of the condition is presented, focusing on the currently available treatment options and highlighting the potential effectiveness of the surgical approach.

Improving Quality of Life and Psychosocial Health for Penile Cancer Survivors: A Narrative Review.

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.

Near-infrared fluorescence-assisted superficial inguinal lymph-node excision for low-risk penile cancer.

OBJECTIVE: Identification of superficial inguinal lymph nodes during low-risk penile cancer surgery using near-infrared (NIR) fluorescence to improve the accuracy of lymph-node dissection and reduce the incidence of missed micrometastases and complications. METHODS: Thirty-two cases were selected, which were under the criteria of < T1, and no lymph-node metastasis was found with magnetic resonance imaging (MRI) detection. Two groups were randomly divided based on the fluorescence technique, the indocyanine green (ICG) group and the non-ICG group. In the ICG group, the ICG preparation was subcutaneously injected into the edge of the penile tumor 10 min before surgery, and the near-infrared fluorescence imager was used for observation. After the lymph nodes were visualized, the superficial inguinal lymph nodes were removed first, and then, the penis surgery was performed. The non-ICG group underwent superficial inguinal lymph-node dissection and penile surgery. RESULTS: Among the 16 patients in the ICG group, we obtained 11 lymph-node specimens using grayscale values of images (4.13 ± 0.72 vs. 3.00 ± 0.82 P = 0.003) along with shorter postoperative healing time (7.31 ± 1.08 vs. 8.88 ± 2.43 P = 0.025), and less lymphatic leakage (0 vs. 5 P = 0.04) than the 16 patients in the non-ICG group. Out of 11, 3 lymph nodes that are excised were further grouped into fluorescent and non-fluorescent regions (G1/G2) and found to be metastasized. CONCLUSION: Near-infrared fluorescence-assisted superficial inguinal lymph-node dissection in penile carcinoma is accurate and effective, and could reduce surgical complications.

Preoperative Albumin-to-Alkaline Phosphatase Ratio as an Independent Predictor of Lymph Node Involvement in Penile Cancer.

Background and Objectives: To investigate the role of preoperative albumin-to-alkaline phosphatase ratio (AAPR) in predicting pathologic node-positive (pN+) disease in penile cancer (PC) patients undergoing inguinal lymph node dissection (ILND). Materials and Methods: Clinical data of patients with squamous cell carcinoma (SCC) PC + ILND at a single high-volume institution between 2016 and 2021 were collected and retrospectively analyzed. An AAPR was obtained from preoperative blood analyses performed within 30 days from their scheduled surgery. A ROC curve analysis was used to assess AAPR cutoff, in addition to the Youden Index. Logistic regression analysis was utilized for an odds ratio (OR), 95% confidence interval (CI) calculations, and an estimate of pN+ disease. A p value < 0.05 was considered to be as statistically significant. Results: Overall, 42 PC patients were included in the study, with a mean age of 63.6 ± 12.9 years. The AAPR cut-off point value was determined to be 0.53. The ROC curve analysis reported an AUC of 0.698. On multivariable logistic regression analysis lymphovascular invasion (OR = 5.38; 95% CI: 1.47-9.93, p = 0.022), clinical node-positive disease (OR = 13.68; 95% CI: 4.37-43.90, p < 0.009), and albumin-to-alkaline phosphatase ratio ≤ 0.53 (OR = 3.61; 95% CI: 1.23-12.71, p = 0.032) were predictors of pN+ involvement. Conclusions: Preoperative AAPR may be a potentially valuable prognostic marker of pN+ disease in patients who underwent surgery for PC.

Clinical Profile and Outcomes of Carcinoma Penis Patients Receiving Systemic Therapy at an Indian tertiary care Center: A Retrospective Observational Study.

BACKGROUND: Penile cancer is a rare malignancy with scant data on the impact of systemic therapy on outcomes. METHODS: Retrospective observational study of patients with a histological diagnosis of carcinoma penis treated with systemic therapy at the Tata Memorial Centre (Mumbai, India) between August 2010 and February 2018. Primary objective was overall survival (OS); secondary objectives included assessment of clinical characteristics, treatment approaches, and toxicity profiles. RESULTS: We included 91 patients with penile carcinoma who received systemic therapy at our center. Intent of therapy was curative in 71 patients (78%), and palliative in 20 (22%). Median age was 57 years (interquartile range [IQR], 50-65.5) for curatively treated patients and 58.5 years (IQR, 44-65.2) for those with advanced disease. Common presenting symptoms were lumps (70%), and pain (57%). Neoadjuvant chemotherapy (NACT) with paclitaxel + platinum was administered to 19 patients (20.9%), of which 7 (37%) attained complete or partial response. Six patients (31.5%) underwent R0 surgery post-NACT. All 71 patients underwent primary surgery; 47 (66.2%) undergoing partial penectomy. Of the 20 patients treated with palliative first-line chemotherapy, 4(20%) attained a partial response. Median OS of patients treated in curative and palliative settings was 33.8 months (95% CI, 17.2-not recorded) and 11.4 months (95% CI, 9.53-23.3), respectively. CONCLUSIONS: Patients with penile cancer treated with systemic therapy have poor outcomes. Little over a third of the patients respond to neoadjuvant chemotherapy and those with advanced disease have poor survival despite systemic therapy, emphasizing the need for early detection and optimum management of primary and nodal disease.

Case report of penile squamous cell carcinoma continuous treatment with BRCA2 mutation.

BACKGROUND: Penile squamous cell carcinoma (PSCC) is a highly aggressive malignancy with a poor prognosis. BRCA1/2 mutations are associated with impaired DNA double-strand break repair and are among the common mutations in penile cancer, potentially paving the way for poly ADP-ribose polymerase inhibitor therapy. CASE PRESENTATION: We report a 65-year-old male with PSCC who progressed to thigh metastasis at 10 months after partial penectomy. Next-generation sequencing showed that the penis primary lesion and metastatic thigh lesion harboured a BRCA2 mutation. Chemotherapy plus immunotherapy was used for treatment, and the thigh metastasis was found to involve no tumour. Progression-free survival (PFS) lasted for 8 months until the appearance of lung metastasis. Afterwards, the patient benefited from second-line therapy of olaparib with pembrolizumab and anlotinib, and his disease was stable for 9 months. The same BRCA2 was identified in the lung biopsy. Given the tumour mutation burden (TMB, 13.97 mutation/Mb), the patient received third-line therapy with nivolumab plus ipilimumab, but PFS only lasted for 3 months, with the appearance of right frontal brain metastasis. Then, the patient was treated with radiation sequential fluzoparib therapy as fourth-line treatment, and the treatment efficacy was evaluated as PR. Currently, this patient is still alive. CONCLUSIONS: This is the first report of penile cancer with BRCA2 mutation, receiving a combination treatment with olaparib and experiencing a benefit for 9 months. This case underscores the pivotal role of BRCA2 in influencing treatment response in PSCC, providing valuable insights into the application of targeted therapies in managing recurrent PSCC with BRCA2 alterations. This elucidation establishes a crucial foundation for further research and clinical considerations in similar cases.

Robotic or open superficial inguinal lymph node dissection as staging procedures for clinically node negative high risk penile cancer.

OBJECTIVE: To evaluate perioperative and oncologic outcomes of a cohort of clinically node negative high-risk penile cancer patients undergoing robotic assisted inguinal lymph node dissection (RAIL) compared to patients undergoing open superficial inguinal lymph node dissection (OSILND). PATIENTS AND METHODS: We retrospectively reviewed the clinical characteristics and outcomes of clinically node negative high-risk penile cancer patients undergoing RAIL at MDACC from 2013-2019. We sought to compare this to a contemporary open cohort of clinically node negative patients treated from 1999 to 2019 at MDACC and Moffit Cancer Center (MCC) with an OSILND. Descriptive statistics were used to characterize the study cohorts. Comparison analysis between operative variables was performed using Fisher's exact test and Wilcoxon's rank-sum test. The Kaplan-Meier method was used to estimate survival endpoints. RESULTS: There were 24 patients in the RAIL cohort, and 35 in the OSILND cohort. Among the surgical variables, operative time (348.5 minutes vs. 239.0 minutes, P < 0.01) and the duration of operative drain (37 vs. 22 days P = 0.017) were both significantly longer in the RAIL cohort. Complication incidences were similar for both cohorts (34.3% for OSILND vs. 33.3% for RAIL), with wound complications making up 33% of all complications for RAIL and 31% of complications for OSILND. No inguinal recurrences were noted in either cohort. The median follow-up was 40 months for RAIL and 33 months for OSILND. CONCLUSIONS: We observed similar complication rates and surgical variable outcomes in our analysis apart from operative time and operative drain duration. Oncological outcomes were similar between the two cohorts. RAIL was a reliable staging and potentially therapeutic procedure among clinically node negative patients with penile squamous cell carcinoma with comparable outcomes to an OSILND cohort.

Neonatal Male Circumcision: Clearly Beneficial for Public Health or an Ethical Dilemma? A Systematic Review.

Contrasting ethical and legal arguments have been made concerning neonatal male circumcision (NMC) that merit the first systematic review on this topic. We performed PRISMA-compliant keyword searches of PubMed, EMBASE, SCOPUS, LexisNexis, and other databases and identified 61 articles that met the inclusion criteria. In the bibliographies of these articles, we identified 58 more relevant articles and 28 internet items. We found high-quality evidence that NMC is a low-risk procedure that provides immediate and lifetime medical and health benefits and only rarely leads to later adverse effects on sexual function or pleasure. Given this evidence, we conclude that discouraging or denying NMC is unethical from the perspective of the United Nations Convention on the Rights of the Child, which emphasizes the right to health. Further, case law supports the legality of NMC. We found, conversely, that the ethical arguments against NMC rely on distortions of the medical evidence. Thus, NMC, by experienced operators using available safety precautions, appears to be both legal and ethical. Consistent with this conclusion, all of the evidence-based pediatric policies that we reviewed describe NMC as low-risk and beneficial to public health. We calculated that a reduction in NMC in the United States from 80% to 10% would substantially increase the cases of adverse medical conditions. The present findings thus support the evidence-based NMC policy statements and are inconsistent with the non-evidence-based policies that discourage NMC. On balance, the arguments and evidence reviewed here indicate that NMC is a medically beneficial and ethical public health intervention early in life because it reduces suffering, deaths, cases, and costs of treating adverse medical conditions throughout the lifetimes of circumcised individuals.

[Lichen sclerosus in clinically relevant phimosis: incidence, risk factors, and association with squamous cell carcinoma of the penis]. / Lichen sclerosus bei klinisch relevanter Phimose: Häufigkeit, Risikofaktoren und Assoziation mit Plattenepithelkarzinomen des Penis.

BACKGROUND: Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory skin disease. It is frequently diagnosed following circumcision. Diabetes mellitus (DM) is a known risk factor in men. Malignant pathology is more common in patients with LSA. Data on LSA in men are very limited. OBJECTIVE: This study investigated the incidence of LSA in men who had undergone circumcision. Risk factors and likelihood of malignancy were captured. MATERIALS AND METHODS: Data of 215 patients were retrospectively analyzed. As potential risk factors, age, body mass index (BMI), DM, coronary heart disease (CHD) and arterial hypertension were identified. Data were analyzed and displayed graphically as spike histograms. Logistic regression was applied. Age and BMI were transformed using cubic spline function. RESULTS: Mean age of patients was 37 years (±â€¯22 years). Mean BMI was 26.4. In all, 24% of the patients had a BMI > 30. Of the patients, 11% had DM, 5.1% had CHD, and 19% had arterial hypertension. Pathology revealed LSA in 47% of patients. Malignant disease was apparent in 3.3% of patients (2.7% without concomitant LSA, 4% with concomitant LSA). Age (55 vs 20 years, odds ratio [OR]: 3.210 [1.421, 7.251]) was a significant risk factor for LSA. BMI (30 vs 22 kg/m2, OR 1.059 [0.614, 1.828]) and DM (OR: 0.42 [0.148, 1.192]) elevated the risk for LSA. CONCLUSION: We saw high rates of LSA in patients had undergone circumcision. Higher age represents a significant risk factor. In 3.3%, final pathology revealed squamous cell carcinoma of the penis. Therefore, pathologic work-up of circumcision specimen is mandatory.

Machine learning-based overall and cancer-specific survival prediction of M0 penile squamous cell carcinoma：A population-based retrospective study.

Background: Penile cancer is a rare tumor and few studies have focused on the prognosis of M0 penile squamous cell carcinoma (PSCC). This retrospective study aimed to identify independent prognostic factors and construct predictive models for the overall survival (OS) and cancer-specific survival (CSS) of patients with M0 PSCC. Methods: Data was extracted from the Surveillance, Epidemiology, and End Results database for patients diagnosed with malignant penile cancer. Eligible patients with M0 PSCC were selected according to predetermined inclusion and exclusion criteria. These patients were then divided into a training set, a validation set, and a test set. Univariate and multivariate COX regression analyses were initially performed to identify independent prognostic factors for OS and CSS in M0 PSCC patients. Subsequently, traditional and machine learning prognostic models, including random survival forest (RSF), COX, gradient boosting, and component-wise gradient boosting modelling, were constructed using the scikit-survival framework. The performance of each model was assessed by calculating time-dependent area under curve (AUC), C-index, and integrated Brier score (IBS), ultimately identifying the model with the highest performance. Finally, the Shapley additive explanation (SHAP) value, feature importance, and cumulative rates analyses were used to further estimate the selected model. Results: A total of 2, 446 patients were included in our study. Cox regression analyses demonstrated that age, N stage, and tumor size were predictors of OS, while the N stage, tumor size, surgery, and residential area were predictors of CSS. The RSF and COX models had a higher time-independent AUC and C-index, and lower IBS value than other models in OS and CSS prediction. Feature importance analysis revealed the N stage as a common significant feature for predicting M0 PSCC patients' survival. The SHAP and cumulative rate analyses demonstrated that the selected models can effectively evaluate the prognosis of M0 PSCC patients. Conclusion: In M0 PSCC patients, age, N stage, and tumor size were predictors of OS. In addition, the N stage, tumor size, surgery, and residential area were predictors of CSS. The machine learning-based RSF and COX models effectively predicted the prognosis of M0 PSCC patients.