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Rectal cancer metastasising to the penis is an exceptionally rare clinical entity, with less than 80 reported cases. Metastasis to the penis is typically identified in conjunction with widespread metastatic disease and as such is usually associated with a very poor prognosis. We report a case of a man who presented with a metastatic deposit in his penis 15 years after the initial diagnosis of rectal cancer. The patient was initially managed with radical penectomy and perineal urethrostomy formation. This was followed by FOLFIRI chemotherapy regimen when further nodules were identified in his lungs on postoperative imaging. At 20months' follow-up, the patient remains alive and disease-free., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Update of the recommendations for the management of penile lesions., Materials and Methods: Comprehensive PubMed review from 2022 of the literature on the diagnosis, treatment and follow-up of penile tumours. The level of evidence of the studies was assessed., Results: A total of 95% of infiltrating penile cancers are squamous cell carcinomas, one-third of which are related to human papillomavirus (HPV) infection. Clinical examination can reveal the size of the lesion, its location, its proximity to the urethral meatus and its infiltration depth. Urinary and sexual function should be assessed. Magnetic resonance imaging (MRI) is the gold standard for local assessment. Penile tumours are classified as low-risk (≤pT1a and well-differentiated G1), intermediate-risk (pT1a G2) or high-risk (≥pT1b, G3, or sarcomatoid contingent). Lymph node assessment in penile cancer is fundamental. The sentinel node technique is recommended for the evaluation of cN0 patients with tumours of intermediate risk or higher. 18FDG PET is recommended for cN+ patients. Surgery is the standard treatment locally and depends on the size, location and grade of the tumour. Topical treatment or brachytherapy may be indicated in some cases. Radical inguinal curettage (RIC) is recommended for stages cN1/cN2. Neoadjuvant chemotherapy is recommended for patients with cN3-stage lesions, combined with RIC in responders. Metastatic forms may be treated with palliative chemotherapy and immunotherapy as part of a clinical trial., Conclusion: The treatment of penile cancer is essentially surgery, with or without chemotherapy in the case of lymph node involvement. The main prognostic factor is lymph node involvement, which justifies early diagnostic and therapeutic management of the inguinal areas., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Penile squamous cell carcinoma (PSCC) is classified into 2 prognostically distinct types: human papillomavirus (HPV)-associated and HPV-independent. However, the impact of p53 status on prognosis remains controversial. We correlated HPV and p53 status with the prognosis of a large series of patients with PSCC. p53 was analyzed according to a recently described immunohistochemical (IHC) pattern-based framework that includes 2 normal and 4 abnormal patterns and closely correlates with TP53 mutational status. A total of 122 patients with surgically treated PSCC in 3 hospitals were included. Based on HPV in situ hybridization and p16 and p53 IHC, the tumors were classified into 3 subtypes: HPV-associated, HPV-independent/p53 normal, and HPV-independent/p53 abnormal. All patients were followed up for at least 22 months (median: 56.9 months). Thirty-six tumors (29%) were HPV-associated, 35 (29%) were HPV-independent/p53 normal, and 51 (42%) were HPV-independent/p53 abnormal. Disease-related deaths were observed in 3/36 (8%), 0/35 (0%) and 14/51 (27%) of the patients, respectively ( P < 0.001). A total of 7/14 deaths in the latter group were patients with tumors showing p53 abnormal patterns not recognized in the classic p53 IHC interpretation (basal, null, and cytoplasmic). According to our multivariate analysis, HPV-independent/p53 abnormal tumors and advanced stage were associated with impaired disease-specific survival (hazard ratio = 23.4, 95% CI = 2.7-3095.3; P = 0.001 and 16.3, 95% CI = 1.8-2151.5; P = 0.008, respectively). In conclusion, compared with patients with HPV-associated and HPV-independent/p53-normal PSCC, patients with HPV-independent/p53 abnormal PSCC have worse clinical outcomes. p53 IHC results define 2 prognostic categories in HPV-independent PSCC: HPV-independent/p53-normal tumors as low-risk tumors, whereas HPV-independent/p53-abnormal tumors as aggressive neoplasms., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Sarcopenia, defined as age-associated loss of skeletal muscle function and muscle mass, is a negative prognostic marker for survival in several tumor entities. However, data evaluating the impact of sarcopenia and fat distribution on penile cancer are rarely described. We performed a retrospective study including 38 patients who were diagnosed with squamous cell carcinoma of the penis. By measuring skeletal muscle mass and fat distribution at axial abdominal computed tomography images at the third lumbar vertebra several body composition parameters including skeletal muscle index (SMI), psoas muscle index (PMI), visceral obesity and visceral-to-subcutaneous fat ratio were determined. Among 38 patients, 26% (n = 10) of the patients with penile cancer were identified as sarcopenic. SMI, age, lymph node metastases, distant metastases and penile cancer of the shaft were identified as significant risk factors for overall survival. PMI and distant metastases were significantly associated with cancer specific survival. None of the analysed adipose tissue parameters could be identified as risk factors for survival in this study. We showed that sarcopenia occurs in a relevant part of patients with penile cancer and is a significant risk factor for overall survival (p = 0.032) and cancer specific survival (p = 0.034) for patients with penile cancer. Regarding fat distribution further studies are needed to evaluate its impact on sarcopenia and survival., (© 2024. The Author(s).)

Objective: Our study tried to evaluate the prognostic utility of preoperative serum cyfra21-1 in patients with penile squamous cell carcinoma (PSCC)., Methods: This retrospective study analyzed data from 94 patients who underwent either partial or radical penectomy accompanied by bilateral inguinal or pelvic lymphadenectomy at our institution from 2010 to 2018. The median duration of follow-up was 66.5 months. Serum cyfra21-1 concentrations were quantified through enzyme-linked immunosorbent assay, with patients classified into two groups based on cyfra21-1 levels (≤ 3.30 ng/ml and > 3.30 ng/ml). The impact of cyfra21-1 levels on clinical outcomes was evaluated., Results: Among the 94 patients, 68 (72.3%) had normal cyfra21-1 levels, while 26 (27.6%) exhibited elevated cyfra21-1 levels. During the follow-up period, 38 patients (40.4%) experienced relapse, and 35 patients (37.2%) died from PSCC. A significantly higher occurrence of advanced pathological grades was observed in the elevated cyfra21-1 group compared to the normal group (P = 0.029). Patients with elevated cyfra21-1 levels had significantly worse disease-free survival (DFS) and disease-specific survival (DSS) than those with normal levels (P < 0.001 and P < 0.001, respectively). In multivariate analysis, cyfra21-1 (HR: 3.938, 95% CI: 1.927-8.049, P < 0.001), lymph node involvement (HR: 8.277, 95% CI: 2.261-30.298, P = 0.001), pathological grade (HR: 2.789, 95% CI: 1.110-7.010, P = 0.029), and ECOG (Eastern Cooperative Oncology Group) performance status (HR: 1.751, 95% CI: 1.028-2.983, P = 0.039) were independent predictors of worse DFS. Similarly, CYFRA 21 - 1 (HR: 3.000, 95% CI: 1.462-6.156, P = 0.003), lymph node involvement (HR: 9.174, 95% CI: 2.010-41.862, P = 0.003), and ECOG performance status (HR: 1.856, 95% CI: 1.053-3.270, P = 0.032) were independent predictors of worse DSS., Conclusions: High preoperative serum cyfra21-1 levels correlate with greater tumor aggressiveness and represent a novel, effective, and convenient prognostic biomarker for PSCC., (© 2024. The Author(s).)

Purpose: Our objective was to investigate the association between programmed death-ligand (PD-L1) immunoexpression measured as a combined positive score and clinical outcomes in penile SqCC., Materials and Methods: We retrospectively reviewed all penile SqCC cases diagnosed in our institution between 2018 and 2023. PD-L1 immunohistochemistry was performed as a qualitative assay. Immunoexpression in both tumor and immune cells equal or superior to 1 was considered positive., Results: A total of 34 patients with conventional penile SqCC were included. Eleven cases were HPV-associated (32.4%). Twelve cases were PD-L1 CPS < 1 and twenty-two were PD-L1 CPS ≥ 1. Nine cases (32.4%) were PD-L1 CPS ≥ 1 and p16 positive, but this did not translate in worse clinicopathological features. Larger tumors (3.0 cm in PD-L1 CPS ≥ 1 vs 2.5 cm in PD-L1 CPS < 1; p = 0.662), vascular invasion (36.4% in PD-L1 CPS ≥ 1 vs. 25.0% in PD-L1 CPS < 1; p = 0.705) and perineural invasion (40.9% in PD-L1 CPS≥1 vs. 16.7% in PD-L1 CPS < 1; p = 0.252) were associated with PD-L1 expression. Among the high-risk features, only lymph node involvement had statistical significance, with 14 out of 22 PD-L1 CPS ≥ 1 patients (63.6%) having lymph node metastases when lymphadenectomy was performed (p = 0.031). With a median follow-up of 16 months (IQR 27.5), PD-L1 CPS ≥ 1 patients had worse overall survival (53.4 months vs 75.9 months), but no statistical significance could be inferred (p = 0.188)., Conclusions: It is noteworthy the clinical significance of lymph node involvement in PD-L1 CPS ≥ 1 cases and a trend towards worse overall survival in this group of patients.

Purpose: Open inguinal lymph node dissection (OILND) plays a crucial role in penile cancer management, but in order to improve patient outcomes, minimally-invasive (MILND) approaches were developed. Our "bottoms-up" MILND is a novel endoscopic technique, changing the way the sequence of dissection is performed. This study aims to compare our approach to the current standard of OILND in terms of oncologic and perioperative outcomes., Materials and Methods: In our database, from 2016 to 2023, 12 patients underwent OILND and 16 had a "bottoms-up" MILND, which is performed with a three port configuration, starting the dissection under the fascia lata, dissecting the femoral vessels in the most distal part of the femoral fossa, followed by dissection of the proximal and superficial lymph nodes at the top of thefemoral triangle., Results: For MILND, median operation time per groin was shorter (58 vs 64 minutes, p=0.34), patients presented shorter hospital stays (10 vs 18 days, p=0.32) and fewer days with drains (14 vs 24 days, p=0.01). Median lymph node yield per groin was higher for MILND (10 vs 9 nodes, p=0.7), but OILND had a higher median of positive lymph nodes (4 vs 3 nodes, p=0.63). MILND patients experienced a lower incidence of major complications (33% vs 58%, p=0.007)., Conclusions: We have proved that our technique of MILND is not inferior to the current standard and we believe that it can further improve patient outcomes with a safer, simplified and easily reproducible approach.

Background: Human papillomavirus (HPV) and Epstein-Barr virus (EBV) are important etiological factors for several cancers. This study aimed to determine the prevalence of HPV and EBV infection in penile cancer., Methods: Forty-three formalin-fixed paraffin-embedded penile cancer tissue samples were analyzed for the HPV-induced p16INK4A protein by immunohistochemistry and Epstein-Barr encoding region in situ hybridization. Demographic data and overall survival were analyzed., Results: The median age of patients was 59 years, ranging from 23 to 91 years old. Most of the tumors (86%) were located at the tip of the penis. HPV infection was positive in 12/43 (27.9%) patients. EBV infection was observed in 2/43 (4.6%) of cases and there was no co-infection detected in this cohort. Patients who had p16INK4A overexpression had a trend toward longer survival compared to those without; the median survival time of 104.4 vs 89 months, the hazard ratio of 0.48 (95% CI: 0.16-1.42, p = 0.173)., Conclusions: One-third of penile cancer patients were positive for HPV-induced p16INK4A expression and there was a trend toward better survival in HPV-positive patients. EBV infection was infrequent in penile cancer in Thailand.

Introduction: Frozen section examination (FSE) of the tumor resection margins is important during penile-preserving surgery (PPS) in penile cancer. The margin status will impact on how much penile or urethral tissue is excised. We aim to evaluate the outcomes of intraoperative FSE of resection margins in PPS., Patients and Methods: A retrospective analysis of patients with penile squamous cell carcinoma (SCC) who underwent a FSE of resection margins between 2010 and 2022 was conducted. FSEs were compared with the final histopathological analysis and the Diagnostic Testing Accuracy (DTA): sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated., Results: Overall, 137 FSE were performed. The median (IQR) age was 65 (53-75) years. 118 (86.1%) patients had negative FSE margins, 16 (11.7%) had positive FSE margins and 3 (2.2%) had equivocal (atypical cells) results. The sensitivity, specificity, PPV, NPV and diagnostic accuracy of penile FSE were 66.7%, 100%, 100%, 93.2% and 94% respectively. 18 patients underwent further resection in the same episode due to a positive or equivocal FSE and 12 (66.7%) achieved negative margins. Limitations include the retrospective nature of the study and lack of control arm to compare with., Conclusions: Intraoperative FSE performed at our center for the assessment of penile SCC margins is 66.7% sensitive and 100% specific. FSE should be considered in PPS, as it's an essential and a reliable diagnostic tool in minimizing over-treatment., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Penile squamous cell carcinoma (PSCC) can develop from human papillomavirus (HPV) infection. This study investigates if the prognostic value of the TNM stage groups or the components tumor stage (pT), grade of differentiation (Grade), lymphovascular invasion (LVI), and nodular stage (pN) depend on HPV status. Also, whether the value of tumor parameters (pT, Grade, and LVI) for predicting node-positive disease depends on HPV status was investigated., Patients and Methods: Stored tumor tissue from 226 patients treated for PSCC in Western Norway between 1973 and 2023 was investigated for HPV DNA. Histopathological variables were reevaluated according to the current TNM classification. Disease course was registered from hospital records. Inclusion of an interaction term between HPV and TNM stage groups in Cox regression enabled analysis of whether cancer-specific survival (CSS) of the stage groups depended on HPV status. This was also done separately for pT, Grade, LVI, and pN. Logistic regression with interaction terms between HPV and the tumor parameters were used to investigate if their predictive value depended on HPV status., Results: HPV DNA was detected in 43% of the tumors. Stratified by HPV status, there was no significant interaction term in the Cox regression between HPV status and TNM stage groups (P = .74). Similar results were found for pT (P = .94), Grade (P = .08), LVI (P = .91) and pN (P = .77). Moreover, there were no significant interaction terms in the logistic regression between HPV status and the tumor parameters pT, Grade, and LVI (all P > .2)., Conclusions: This study found that prognosis of the TNM stage groups and the components pT, Grade, LVI, and pN were not modified by HPV in PSCC. The value of pT, Grade, and LVI for predicting lymph node-positive disease was not affected by HPV status., Competing Interests: Disclosure None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the potential utility of antibody-drug conjugates targeting trophoblast cell surface antigen-2 (TROP-2) in patients with primary penile squamous cell carcinoma (PSCC), patients with recurrence (REC cohort), and patient-matched distant metastases (MET cohort), and to assess the potential use of TROP-2 as a predictive non-invasive biomarker in PSCC., Methods: A cohort comprising a PRIM (n = 37), REC (n = 5) and MET subcohort (n = 7), with MET including lymph node and lung metastases, was analysed using quantitative real-time PCR, ELISA and immunohistochemical staining with evaluation of H-score., Results: TROP-2 mRNA and serum protein levels were significantly increased in primary and recurrent PSCC compared to cancer-free controls (both P < 0.001). Immunohistochemical analysis revealed that most of the PRIM cohort (n = 34/37, median H-score 260, interquartile range [IQR] 210-300), as well as all patients in the REC (median [IQR] H-score 200 [165-290]) and MET cohorts (median [IQR] H-score 280 [260-300]) exhibited moderate to strong membranous TROP-2 expression. Additionally, The H-score (membranous TROP-2 expression) was positively correlated with TROP-2 mRNA (ρ = 0.69, P < 0.0001, R 2 = 0.70) and protein levels (ρ = 0.86, P < 0.0001, R 2 = 0.59), indicating its potential as a non-invasive biomarker in PSCC., Conclusion: In summary, our results support further studies on TROP-2 as a diagnostic and therapeutic target in primary, recurrent and metastatic PSCC., (© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

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 ​at 92%, 85%, 76%, 79% and 78% respectively (p ​= ​0.534). 62.7% had reconstruction performed, including split-thickness skin graft neoglans formation, (57.8% [n ​= ​37]), preputial flap (32.8% [n ​= ​21]), glans resurfacing (4.7% [n ​= ​3]), shaft advancement flap (1.6% [n ​= ​1]), penile shaft skin graft (1.6% [n ​= ​1]), and partial penectomy with urethral centralisation (1.6% [n ​= ​1]). Phallus preservation was not affected by positive nodal status (OR 0.75 [95% CI 0.249-2.266], p ​= ​0.564) or T-stage ≥1b (OR 0.51 [95% CI 0.153-1.711], p ​= ​0.276). There has been a significant reduction in Nx nodal status from 64% in 2017 to 15% in 2021 (p ​= ​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., Competing Interests: Declaration of competing interest The author's declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Background: To evaluate the overall survival (OS) and construct a nomogram to predict the OS of patients with penile squamous cell carcinoma (PSCC)., Methods: This retrospective study analyzed data of patients with PSCC from the First Affiliated Hospital of Soochow University between 2012 and 2022. R software was used to explore factors influencing OS in PSCC. Kaplan-Meier method and log-rank test were employed for OS estimation. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify these factors. A nomogram was created to identify the independent prognostic factors. The model was evaluated by concordance index, receiver operating characteristic (ROC) curves, and calibration plots., Results: A total of 159 patients with T1/T2 PSCC were included in the analysis. Patients with T2/N2 stage, older age, larger tumor size, high preoperative systemic immune-inflammation index (SII), and poor preoperative nutrition had a higher incidence of poor OS. Age, T/N stage, tumor size, and SII were identified as independent prognostic indicators. A prognostic nomogram was formulated, and its predictive accuracy for estimating OS in PSCC patients was validated through ROC curves and calibration plots., Conclusion: The nomograms, based on age, T/N stage, tumor size, and high preoperative SII, provide a valuable tool for predicting 1-, 2-, and 3-year OS in patients with T1/T2 PSCC without distant metastases., Competing Interests: Disclosure We declare that we have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To compare the safety and effectiveness of minimally invasive surgery (MIS) with open inguinal lymph node dissection (O-ILND) in penile cancer., Methods: We performed a systematic reviews and cumulative meta-analyses of primary results of interest according to PRISMA criteria, and quality assessment followed AMSTAR. The system searched five databases, including Zhiwang, Embase, PubMed, Cochrane Library and Web of Science. The search period ranged was from database creation until September 2023. The statistical analysis software used Stata16., Results: A total of 16 studies, including 898 patients. Compared to O-ILND, MIS is superior in length of stay (WMD = -2.96, 95%CI [-4.38, -1.54], P < 0.05), drainage time (WMD = -3.24, 95%CI [-4.70, -1.78], P < 0.05) and estimated blood loss (WMD = -35.70, 95%CI [-46.27, -25.14], P < 0.05), while operation time, recurrence rate and 5-year overall survival rate are the same. The number of lymph nodes dissection between the two groups are not statistically significant. Subgroup analyses found that there are more lymph nodes dissection in robotic-assisted inguinal lymph nodes dissection (WMD = 0.50, 95%CI [0.20, 0.80], P < 0.05). The overall complication rate of MIS was lower (OR = 0.26, 95%CI [0.09, 0.70], P < 0.05)., Conclusion: Minimally invasive inguinal lymph nodes dissection appears to be a better option for penile cancer cases. But more large samples and multicenter studies are needed to further confirm., Competing Interests: Declaration of competing interest There are no conflicts of interest involved in this study., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

PeCa is a rare entity with rising incidence rates due to increased infections with human papillomaviruses (HPV). The distinct subtypes of PeCa with an individual pathogenesis demand biomarkers for a precise patient risk assessment regarding disease progression and therapeutic susceptibility. We recently identified promising candidates associated with an HPV-instructed tumor microenvironment (TME) using HPV-positive PeCa cell lines and tissue microarrays (TMA). The capacity of HPV + p63 + PeCa cells to release neutrophil-attracting CXCL-8 provided a molecular link explaining the infiltration of CD15 + myeloid cells in PeCa specimens. The candidate biomarkers HPV, p63, CD15, DKK1, and CD147 linked a tumor-promoting TME with a higher TNM classification reflecting more aggressive and metastasizing cancers. Based on immune-reactive scores (IRS) from TMA staining for these biomarkers, we calculated correlations and conducted association analyses to assess the degree of relationship between all biomarkers. We then conducted Kaplan-Meier survival estimates and Cox regression analyses to delineate the impact on PeCa patient survival. There is a notable predictive potential regarding the survival of patients with biomarker profiles beyond the potency of the individual biomarker. From all candidate biomarkers and biomarker profiles, the combination of CD147 and infiltrating CD15 + cells linked to an active HPV-driven transformation displayed cancer-immune dynamics with dismal prognosis for patients. After deciphering relevant interdependencies, the HPV + CD147 + CD15 + status was the most potent profile predicting metastasis-free survival of PeCa patients. The results of this report underscore the need for analysis of the TME and the development of multi-parameter composite scores that reflect fundamental cancer-immune relationships to tailor therapeutic interventions based on actual cancer immune dynamics., (© 2024. The Author(s).)

Aim: The primary aim of this study was to validate the reliability, sensitivity and safety profile of novel combination of ICG- methylene blue dye as an SN tracer for PeCa., Methods: This is a validation and non-randomised prospective observational study involving 25 patients (50 inguinal basins) who underwent SLNB where in ICG and methylene blue were used for localisation. The patients with clinically node negative groins were recruited in the study. SNs were identified intraoperatively using near infrared fluorescence imaging (NIRF Imaging system, SPY-PHI, Stryker, Sweden) and blue dye. The numbers of SNs identified by each tracer and the rates of complications and nodal recurrence during the followup., Results: Overall 137 SNs were identified intraoperatively. Among the 137 SNs excised fluorescence, blue dye and Combined (blue + green) identified 57(41.6%), 27 (19.7%), and 51 (37.2%), respectively. The average number of SLNs removed per patient was 5 (range, 1-11) with sentinel lymph nodes detection rate at 94% (47/50). Seven patients had malignancy on SLNB and underwent ipsilateral radical inguinal lymphadenectomy. One patient had false negative SN and positive node in modified inguinal lymphadenectomy specimen. No adverse events were observed in all cases., Conclusion: The Novel combination of ICG fluorescence-Methylene blue dye technique is simple, reliable and safe. Moreover, it demonstrates a high SLN detection rate with a low false-negative rate, and it avoids radiation exposure., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: We conducted this study to summarize the results of studies reporting the role of NLR (neutrophil to lymphocyte ratio) in PSCC (penile squamous cell carcinoma)., Methods: This meta-analysis was conducted using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria. A systematic search was conducted on PubMed, Scopus, and web of science up to March 10, 2023. Fourteen studies were included in the review. The NOS (Newcastle-Ottawa Scale) was used to determine the quality of the included studies. This meta-analysis was conducted on the studies reporting the relationship between NLR and survival using HR (hazard ratio) and 95% CI (confidence interval)., Results: There was a significant association between NLR levels and the prognosis, nodal stage, and anatomical tumor stage of PSCC patients. In the meta-analysis of the association of NLR with survival, NLR level was significantly associated with lower cancer-specific survival (HR = 3.51, 95% CI = 2.07-5.98, p < 0.001) and lower disease-free survival (HR = 2.88, 95% CI = 1.60-5.20, p < 0.001). However, NLR was found to have no association with the stage, grade, location, and size of the tumor., Conclusion: NLR has a significant diagnostic and prognostic value in PSCC., (© 2024. The Author(s).)

Background: Penile cancer is high in some underdeveloped countries. Signal transducer and activator of transcription 3 (STAT3) and CD44, CD24, and SOX2+ are known to be markers of diagnosis and prognosis in other cancers, but without studies in penile cancer., Methods: A cross-sectional study was conducted at the Hospital de Cancer de Pernambuco from March 2015 to December 2017. We performed SOX2, STAT3, CD24, and CD44 analyses in blood and tumor tissue by flow cytometry., Results: High levels of CD44 high CD24 low , CD44 high CD24 low pSTAT3+ and CD44 hig h CD24 low in the blood of patients compared to the controls (p < 0.05). Low of SOX2+ T cells in blood of patients compared to controls. High CD44 high CD24 low levels in patients with perineural invasion (PNI), tumor size > 3 cm, and pT2 stage (p < 0.05). High T cell levels in the blood and tumor tissue of patients with tumor ≤3 cm (p < 0.05). Increased SOX2+ T cells in blood of patients with PNI (-) and pT1 stage (p < 0.05). CD44 high CD24l ow pSTAT3+ (r = 0.669; p = 0.024) and SOX2+T cells (r = 0.404, p = 0.029) correlation were observed between blood and tumor tissue in penile cancer patients., Conclusion: CD44, CD24, and SOX2 molecules were markers of advanced disease associated with the worst prognosis in CaPe. However, pSTAT3 and T cells were associated with a more favorable prognosis in this study., (© 2024 Wiley Periodicals LLC.)

Background: Radiotherapy (RT) represents an alternative treatment option for patients with T1 squamous cell carcinoma of the penis (SCCP), with proven feasibility and tolerability. However, it has never been directly compared with partial penectomy (PP) using cancer-specific mortality (CSM) as an end point., Methods: In the Surveillance, Epidemiology, and End Results database (2000-2020), T1N0M0 SCCP patients treated with RT or PP were identified. This study relied on 1:4 propensity score-matching (PSM) for age at diagnosis, tumor stage, and tumor grade. Subsequently, cumulative incidence plots as well as multivariable competing risks regression (CRR) models addressed CSM. Additionally, the study accounted for the confounding effect of other-cause mortality (OCM)., Results: Of 895 patients with T1N0M0 SCCP, 55 (6.1%) underwent RT and 840 (93.9%) underwent PP. The RT and PP patients had a similar age distribution (median age, 70 vs 70 years) and more frequently harbored grade I or II tumors (67.3% vs 75.8%) as well as T1a-stage disease (67.3% vs 74.3%). After 1:4 PSM, 55 (100%) of the 55 RT patients versus 220 (26.2%) of the 840 PP patients were included in the study. The 10-year CSM derived from the cumulative incidence plots was 25.4% for RT and 14.4% for PP. In the multivariable CRR models, RT independently predicted a higher CSM than PP (hazard ratio, 1.99; 95% confidence interval, 1.05-3.80; p = 0.04)., Conclusion: For the T1N0M0 SCCP patients treated in the community, RT was associated with nearly a twofold higher CSM than PP. Ideally, a validation study based on tertiary care institution data should be conducted to test whether this CSM disadvantage is operational only in the community or not., (© 2024. Society of Surgical Oncology.)

Objective: The aim of this study was to introduce HPV-associated and HPV-independent histologic classifications to analyze prognostic factors and develop a prognostic nomogram for patients with penile squamous cell carcinoma (PSCC)., Methods: Data of 1502 PSCC patients between 2010 and 2020 were accessed from the SEER database, and the patients were randomly divided into a training set and a validation set. Independent risk factors for PSCC patients prognosis were analyzed by using univariate and multivariate COX proportional hazards regression, and was used for the construction of the nomogram, and the predictive performance of the model was evaluated by C-index, calibration curve and ROC curve. Kaplan-Meier analysis was applied to explore the impact of HPV-related factors on patient survival, while propensity score matching (PSM) and inverse probability treatment weighting (IPTW) techniques were used to balance other confounding factors like individual clinical and pathological factors, and to evaluate the differences in overall survival (OS) and cause-specific survival (CSS) between subgroups., Result: The results indicated that histologic type, Grade classification, T/M stage, surgical methods and chemotherapy were independent risk factors affecting OS and CSS in PSCC patients. In addition, age and marital status were significantly associated with OS, while lymph node metastasis was an independent prognostic factor for CSS, the validation results of the model showed that the nomogram had a superior predictive performance compared with the American Joint Committee on Cancer staging system. In addition, subgroup analyses prior to and after IPTW and PSM adjustments showed that HPV-associated group had better OS and CSS than HPV-independent group., Conclusion: Our study developed and validated a nomogram using a novel histologic classification and achieved satisfactory results, which can better help clinicians to predict the prognosis of penile squamous cell carcinoma patients., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: In squamous cell carcinoma of the penis (PeCa), treatment options for primary tumors vary by disease stage and may include surgery, radiation, topical chemotherapy, or laser excision. This review aims to highlight the current evidence on the value of radiotherapy as an organ-preserving strategy in primary PeCa., Material and Methods: Manuscripts on primary PeCa treatment with external beam radiotherapy (EBRT) and brachytherapy were evaluated via Scopus, PubMed/MEDLINE, and Web of Science TM (2013-2023) to assess their efficacy and safety. Animal studies, studies with <5 patients, and case reports were excluded., Results: Radiotherapy offers the potential for organ preservation with tumor control rates comparable to radical surgery, while disease-specific survival rates up to 70 % were experienced with EBRT. Brachytherapy (BT) is the preferred method of irradiation for glans-limited tumors, whereas a higher relapse risk is expected for tumors >4 cm. BT shows 73 % amputation-free survival at 8-10 years and 81 % progression-free survival at 5-10 years. Compared with BT, total amputation significantly improves 5-year disease-free survival rate. BT offers a superior 5-year local control and penile preservation rates compared to EBRT. Common acute toxicities of brachytherapy include radiodermatitis, sterile urethritis, and urethral adhesions. The primary late adverse events of BT are soft tissue necrosis (0-31 %) and meatal stenosis (0-43 %)., Conclusion: BT is a favorable radiation modality, offering an efficient and conservative approach. HDR BT is favored for its enhanced dose distribution and radiation protection. Collaboration between radiation oncologists and urologists is essential in order to provide an optimal patient selection and manage toxicities thus optimizing patient outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: Penile cancer is a rare entity and has a good prognosis in localized stage. Delayed surgical treatment of lymphatic disease is associated with poor overall survival but conventional imaging cannot detect occult lymph node metastasis sufficiently. Imaging cancer related fibroblasts has shown promising results as non-invasive staging tool in various tumor entities but has not yet been evaluated in penile cancer., Methods: In this single-center pilot study, patients planned for surgical treatment for penile cancer underwent preoperatively [ 68 Ga]Ga-FAPI-46 PET/CT. Post-operative histopathology was compared to [ 68 Ga]Ga-FAPI-46 PET/CT results., Results: From January 2022 to June 2022, a total number 11 patients with histopathologically proven penile cancer underwent surgery and received [ 68 Ga]Ga-FAPI-46 PET/CT prior therapy. 8 primary tumor sites and 4 lymph node regions were analyzed. FAPI uptake was increased on primary tumor site (SUV max 16.2 (9.1 - 25.8)). Histopathological proven lymph node regions showed highly increased FAPI uptakes (SUV max 17.9 (16.4 - 23.5) on [ 68 Ga]Ga-FAPI-46 PET/CT., Conclusion: In this first pilot cohort, there were no false-positive FAPI uptake which might allow the detection of occult lymph node metastasis by [ 68 Ga]Ga-FAPI-46 PET/CT and might consequently lead to omitting lymph node regions during surgery that had no increased FAPI uptake pre-operatively., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: Cutaneous sarcomatoid squamous cell carcinoma is well-described with histology resembling pleomorphic undifferentiated sarcoma featuring collagenous or myxoid stroma with or without elements of keratinizing squamous carcinoma. This report presents 2 cases of dedifferentiated squamous cell carcinoma (SCC) composed of sheets of malignant mononuclear cells with malignant osteoclast-like multinucleated giant cells, extravasated blood, and hemosiderin resembling cutaneous giant cell tumor (cGCT). In the first case, an exophytic facial mass of a 96-year-old woman removed by shave showing extensive cGCT-like tumor but with microscopic elements of SCC in situ and positivity for cytokeratin 5/6 in the malignant spindle cells and SCC. The second case involved a 32-year-old man with a pedunculated penile mass removed by shave biopsy, displaying malignant cytology resembling cGCT, focal staining for cytokeratin AE1/AE3 and p63, and CD68 highlighting the osteoclast-like giant cells. Molecular analysis revealed CDKN2A, TP53, and TERT. Upon reexcision, case 2 showed focally invasive keratinizing SCC associated with differentiated penile intraepithelial neoplasia and lichen sclerosus. Skin specimens with an exophytic mass histologically resembling cGCT but with malignant cytology should be meticulously evaluated for elements of SCC. Molecular analysis, detecting mutations like H3F3 or HMGA2-NCOR2 fusion, can aid in distinguishing cutaneous sarcomatoid squamous cell carcinoma from GCT bone or GCT soft tissue., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: We investigated the feasibility of the tertiary lymphoid structure (TLS) as a prognostic marker for penile squamous cell carcinoma(SCC)., Methods: We retrospectively collected data from 83 patients with penile squamous cell carcinoma. H&E-stained slides were reviewed for TLS density. In addition, clinical parameters were analyzed, the prognostic value of these parameters on overall survival (OS) was evaluated using ‒ Kaplan-Meier survival curves, and the prognostic value of influencing factors was evaluated using Cox multifactor design nomogram analysis., Result: BMI, T, N, and M are significant in the survival curve with or without tertiary lymphoid structure. BMI, T, N, M and TLS were used to construct a prognostic model for penile squamous cell carcinoma, and the prediction accuracy reached a consensus of 0.884(0.835-0.932), and the decision consensus reached 0.581(0.508-0.655)., Conclusion: TLS may be a positive prognostic factor for penile squamous cell carcinoma, and the combination of BMI, T, N and M can better evaluate the prognosis of patients., (© 2024. The Author(s).)

Penile cancer with bulky inguinal metastasis has a high probability of harboring pathologically involved lymph nodes best managed in a multidisciplinary care setting. Appropriate staging with cross-sectional imaging and fine-needle aspirate cytology of suspicious nodes guide decision-making for the use of platinum-based neoadjuvant chemotherapy followed by inguinal lymph node dissection. Surgical resection plays an important diagnostic, therapeutic, and guiding role in disease management. Patients with adverse pathologic features, especially those with extranodal disease extension, may derive additional benefit from adjuvant radiotherapy., Competing Interests: Disclosure The authors have no pertinent conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Reproductive problems in cattle are frequent and have an important impact on production. In addition, inflammatory, traumatic and other diseases may be followed by the development of tumours, which are a cause of culling of breeding males. The main types of tumours diagnosed in the bull penis are fibropapilloma and squamous cell carcinoma. The aim of this study was to characterize a case of a tumour in the glans penis of a bull from a dairy farm in Santa Fe, Argentina. The neoplastic tissue was stained with haematoxylin and eosin and then analysed by immunohistochemistry to reveal its characteristic phenotype. Results showed positivity to vimentin, neuron specific enolase, proliferating cell nuclear antigen, S100 and glial fibrillary acidic protein. This suggested that the tumour was a neoplasm of neural origin, classified as neurofibrosarcoma, a peripheral nerve sheath tumour, here reported in the penis of a bull for the first time., Competing Interests: Declaration of competing interests The authors declared no conflicts of interest in relation to the research, authorship of publication of this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Objective: TP53 loss-of-function (TP53LOF) mutations might be a driver of poor prognosis and chemoresistance in both human papillomavirus (HPV)-independent (HPV-) and HPV-associated (HPV+) penile squamous cell carcinoma (PSCC). Here, we aim to describe transcriptomic differences in the PSCC microenvironment stratified by TP53LOF and HPV status., Methods: We used single-cell RNA sequencing (scRNA-seq) and T-cell receptor sequencing to obtain a comprehensive atlas of the cellular architecture of PSCC. TP53LOF and HPV status were determined by targeted next-generation sequencing and sequencing HPV-DNA reads. Six HPV+ TP53 wild type (WT), six HPV- TP53WT, and four TP53LOF PSCC samples and six controls were included. Immunohistochemistry and hematoxylin-eosin confirmed the morphological context of the observed signatures. Prognostic differences between patient groups were validated in 541 PSCC patients using Kaplan-Meier survival estimates., Key Findings and Limitations: Patients with aberrant p53 staining fare much worse than patients with either HPV- or HPV+ tumors and WT p53 expression. Using scRNA-seq, we revealed 65 cell subtypes within 83 682 cells. TP53LOF tumors exhibit a partial epithelial-to-mesenchymal transition, immune-excluded, angiogenic, and morphologically invasive environment, underlying their aggressive phenotype. HPV- TP53WT tumors show stemness and immune exhaustion. HPV+ TP53WT tumors mirror normal epithelial maturation with upregulation of antibody-drug-conjugate targets and activation of innate immunity. Inherent to the scRNA-seq analysis, low sample size is a limitation and validation of signatures in large PSCC cohorts is needed., Conclusions and Clinical Implications: This first scRNA-seq atlas offers unprecedented in-depth insights into PSCC biology underlying prognostic differences based on TP53 and HPV status. Our findings provide clues for testing novel biomarker-driven therapies in PSCC., Patient Summary: Here, we analyzed tissues of penile cancer at the level of individual cells, which helps us understand why patients who harbor a deactivating mutation in the TP53 gene do much worse than patients lacking such a mutation. Such an analysis may help us tailor future therapies based on TP53 gene mutations and human papillomavirus status of these tumors., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Disclosures Dr J.M. Holzbeierlein has no disclosures related to this publication. Dr P.E. Spiess has no financial disclosures and only leadership disclosures as follows: (1) vice chair of the NCCN bladder and penile cancer panel; (2) president of the Global Society of Rare Genitourinary Tumors; (3) member of the ASCO/EAU panel; (4) AUA guidelines committee for the updates in testicular cancer.

Introduction: The European Association of Urology (EAU) and the American Society of Clinical Oncology (ASCO) recently issued updated guidelines on penile cancer, emphasising dynamic sentinel node biopsy (DSNB) as the preferred method for surgical staging among patients with invasive penile tumours and no palpable inguinal lymphadenopathy. This paper outlines the rationale behind this new recommendation and describes remaining challenges, as well as strategies for promoting DSNB worldwide., Main Text: DSNB offers high diagnostic accuracy with the lowest postoperative complications compared to open or minimally invasive inguinal lymph node dissection (ILND), prompting its preference in the new guidelines. Nevertheless, despite its advantages, there are challenges hampering the widespread adoption of DSNB. This includes the false-negative rate associated with DSNB and the potential negative impact on patient outcome. To address this issue, improvements should be made in several areas, including refining the timing and interpretation of the lymphoscintigraphy and the single photon emission computed tomography/computed tomography images. In addition, the quantity of tracer employed and choice of the injection site for the radiopharmaceutical should be optimised. Finally, limiting the removal of nodes without tracer activity during surgery may help minimise complication rates., Conclusion: Over the years, DSNB has evolved significantly, related to the dedicated efforts and innovations in nuclear medicine and subsequent clinical studies validating its efficacy. It is now strongly recommended for surgical staging among selected penile cancer patients. To optimise DSNB further, multidisciplinary collaborative research is required to improve SN identification for better diagnostic accuracy and fewer complications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The landscape of squamous cell carcinoma of the penis (SCC-P) has undergone a significant transformation since the new World Health Organization classification of genitourinary cancers and recent European Association of Urology/American Association of Clinical Oncology guidelines. These changes emphasize the necessity to categorize SCC-P into 2 groups based on its association with human papillomavirus (HPV) infection. This shift has major implications, considering that prior knowledge was derived from a mix of both groups. Given the distinct prognosis, treatment options, and staging systems observed for HPV-associated tumors in other body areas, the question now arises: will similar patterns emerge for SCC-P?, Competing Interests: Disclosure The authors have no relevant conflict of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Penile cancer is a rare malignancy with a poor prognosis. Studies with single-agent immune checkpoint inhibitors (ICIs) have demonstrated efficacy, but response rates are low. Studies combining ICIs with both chemotherapy and targeted therapy are ongoing. Up to 50% of penile cancer cases are associated with human papillomavirus (HPV). HPV-targeting therapies, such as HPV-targeting vaccines and T-cell receptor therapies, are an area of active investigation. Penile cancer cells also express cell surface antigens that may be targeted by the emerging class of antibody-drug conjugates., Competing Interests: Disclosure Nicholas Simon, Saad Atiq, and Andrea Apolo report no disclosures. Guru Sonpavde reports the following disclosures: Advisory Board: EMD Serono, BMS, Merck, Seattle Genetics/Astellas, Janssen, Bicycle Therapeutics, Pfizer, Gilead, Scholar Rock, Eli Lilly/Loxo Oncology, Vial, PrecisCa, Atkis, Kura Oncology, Daiichi-Sankyo.Consultant/Scientific Advisory Board (SAB): Syapse, Merck, Servier, Syncorp.Research Support to institution: EMD Serono, Jazz Therapeutics, BMS.Speaker: Seagen, Gilead, Natera, Exelixis, Janssen, Astellas, Bayer, Aveo, Merck, Pfizer.CME-certified speaking: Research to Practice, PeerView Institute, Ideology Health, IBCU/Grand Rounds in Urology.Data safety monitoring committee (honorarium): Mereo. Employment: Spouse employed by Myriad. Writing/Editor fees: Uptodate, Practice Update, Onviv, DAVA Oncology. Travel: BMS, Astellas., (Published by Elsevier Inc.)

Penile cancer (PC), although rare, poses significant challenges in both diagnosis and treatment. Penile squamous cell carcinoma (PSCC) represents the most common histologic subtype of PC, accounting for approximately 95% of cases. With limited therapeutic options available, systemic therapies have emerged as critical components in the management of advanced PSCC. Recent developments in clinical research have revealed the effectiveness of new therapeutic strategies. By elucidating the mechanism of action and clinical evidence supporting these treatments, we strive to offer insights into optimizing treatment strategies and enhancing the quality of care for patients affected by this complex disease., Competing Interests: Disclosure C. Mercinelli, M. Al Assaad and H. Safai have no conflicts of interest that are directly relevant to the content of this article. J. Chahoud received consultation fees from Pfizer, Aveo, Exelisis, and Mycaregorythm. A. Necchi reports the following: Honoraria: Roche, MSD, AstraZeneca, Janssen, Foundation Medicine, BMS, Astellas; consulting or advisory role: MSD, Roche, Bayer, AstraZeneca, Clovis Oncology, Janssen, Incyte, Seattle Genetics/Astellas, Bristol-Myers Squibb, Rainier Therapeutics, Bycicle Therapeutics, GlaxoSmithKline, Basilea Pharmaceutica, Catalym; research funding (institution): MSD, AstraZeneca, Ipsen, Gilead; and travel, accommodations, and expenses: Roche, MSD, AstraZeneca, Janssen, Rainer Therapeutics, Pfizer. P.E. Spiess reports the following leadership positions: President of Global Society of Rare GU Tumors, NCCN bladder and penile cancer panel, vice-chair, and a member of the American Society of Clinical Oncology/EAU penile cancer panel., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This study aimed to investigate disease-free survival (DFS) outcomes and associated prognostic factors among surgically treated penile cancer patients at Songklanagarind Hospital, Thailand, over a 20-year period., Methods: A retrospective analysis was conducted on 208 primary penile cancer patients treated between January 2001 and December 2022. Disease-free survival was assessed using Kaplan-Meier survival curves, and Cox proportional hazard models were employed for multivariate analysis., Results: All of patients (100%) were squamous cell carcinoma of penis, with 38.9% having T1 tumors, 70.7% well-differentiated tumors, and 32.6% diagnosed at stage III. The recurrence rate was 16.8%, with a mean time to recurrence of 25.9 months. Disease-free survival rates at 1, 3, and 5 years were 82.1%, 72%, and 70.2%, respectively. Median overall survival was 18.2 months, with rates at 1, 3, and 5 years at 68.7%, 44.7%, and 36.4%, respectively. Significant associations were found between disease-free survival and higher T stage, clinical chronic inflammation, delayed onset of symptoms, primary lesion location, groin node metastasis, lymphovascular invasion, and pelvic lymph node metastases. However, multivariate analysis revealed that higher primary tumor stage (T) was the only independent prognostic factor for disease-free survival., Conclusion: This study provides valuable insights into disease-free survival outcomes in penile cancer treatment at a single institution over an extended period. Higher pathologic T stage emerged as the sole independent prognostic factor for disease-free survival. Further validation through large-scale prospective studies is warranted., Competing Interests: Disclosure The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Penile squamous cell carcinomas (SCCs) are common, potentially life-threatening neoplasms of horses. They are well-recognized to be caused by Equus caballus papillomavirus (EcPV) type 2, although EcPV2 cannot be detected in all cases. A 23-year-old standardbred gelding developed multiple penile in situ and invasive SCCs that contained histological evidence of PV infection. By using both consensus and specific PCR primers, these lesions were found to contain EcPV7 DNA, but not DNA from EcPV2 or any other PV type. To determine how frequently EcPV7 is present in equine penile SCCs, specific primers were used to detect EcPV2 and EcPV7 in a series of 20 archived samples. EcPV7 was the only PV detected in one, both EcPV2 and 7 were detected in five, and only EcPV2 was detected in 14 SCCs. EcPV7 DNA was also detected in three of 10 archived oropharyngeal SCCs, although only as a co- infection with EcPV2. This is the first report of EcPV7 causing disease in horses. These results suggest EcPV7 could cause a subset of equine penile SCCs, and this is the first evidence that PV types other than EcPV2 can cause these neoplasms. The detection of EcPV7 in the oropharyngeal SCCs suggests a potential role of this PV type in the development of these SCCs. There were no clinical or histological features that differentiated lesions containing EcPV7 DNA from those containing EcPV2 DNA. If EcPV7 causes a proportion of equine penile SCCs, vaccines to prevent EcPV2 infection may not prevent all equine penile SCCs., Competing Interests: Declaration of Competing Interest None of the authors of this paper has a financial or personal relationship with other people or organisations that could inappropriately influence or bias the content of the paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Human papillomavirus (HPV) infection is a risk factor for the development of penile squamous cell carcinoma (PSCC). It remains inconclusive whether HPV-related PSCC has a different prognosis from non-HPV-related PSCC., Objective: To investigate the relationship between HPV status and survival as well as temporal changes in the proportion of HPV-related PSCC., Design, Setting, and Participants: A retrospective cohort of 277 patients treated in Norway between 1973 and 2022 was investigated for HPV DNA in tumor tissue. Clinicopathological variables and disease course were registered., Outcome Measurements and Statistical Analysis: Kaplan-Meier curves and Cox regression were used to investigate the determinants of cancer-specific survival (CSS). The chi-square test for trend in proportions enabled investigation of temporal changes in the HPV-related proportion of PSCC patients treated in Western Norway (n = 211)., Results and Limitations: HPV DNA was detected in tumor tissue from 131 (47%) patients. Stratified by HPV status, 5-yr CSS did not differ between groups (p = 0.37). When investigating only node-positive patients, however, presence of HPV DNA was an independent predictor of better survival in multivariable Cox regression after adjustment for age, nodal stage, and adjuvant therapy (hazard ratio 0.54, 95% confidence interval: [0.30-0.99], p = 0.04). In cases from Western Norway, an increasing proportion of HPV-related cases over time was found (p = 0.01). The main limitation is the retrospective study design., Conclusions: HPV DNA in tumor tissue was associated with significantly better CSS for node-positive patients. The proportion of HPV DNA-positive PSCC has increased significantly in Western Norway over the past 50 yr., Patient Summary: We investigated the impact of human papillomavirus (HPV) on the survival of penile cancer patients treated over a 50-yr period in Norway. We found that for patients with lymph node metastasis, survival was better for HPV-related cases. We also found that the proportion of cases due to HPV has increased in Western Norway., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the feasibility of fluorescence molecular imaging (FMI), using cetuximab-800CW, as an intraoperative tool to determine surgical margins in penile squamous cell carcinoma (PSCC)., Patients and Methods: A total of 11 patients with PSCC received 75 mg cetuximab followed by 15 mg cetuximab-800CW 2 days before surgery. FMI of the whole excision specimen and tissue slices was performed. Fluorescence visualisation was correlated to histopathology. Based on tumour and healthy tissue regions of interest, mean fluorescence intensity was calculated for each individual patient., Results: Significant differences between tumour and healthy mean fluorescence intensity were found with tumour-to-background ratios of a median (IQR) of 1.51 (0.99) and a mean (SD) of 1.51 (0.32) in the excision specimen and tissue slices, respectively. One patient showed a high relative fluorescence intensity with a signal-to-background ratio of 1.79, corresponding to a tumour-positive margin on fresh frozen sectioning., Conclusion: In this Phase I study we showed that cetuximab-800CW seems suitable to discriminate PSCC from background tissue. The tracer was well tolerated, and no false positive spots were seen., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Objectives: There is a paucity of data on North American cohorts of patients with penile squamous cell carcinoma (pSCC). Herein, we aimed to assess the sensitivity of various modalities to identify human papillomavirus (HPV) status, determine the prevalence of high-risk HPV-positivity, and evaluate the prognostic impact of relevant clinicopathologic variables., Methods: Patients with pSCC (n = 121) consecutively treated with partial/total penectomy (2000-2022) at a single institution were included. HPV status (based on immunohistochemistry [IHC], in situ hybridization [ISH], and panviral metagenomic sequencing [PMS]), histologic features, and outcomes were reviewed. Outcome events included death due to disease and progression., Results: The majority of patients were white (105/121, 86.8%). Thirty-seven (30.6%) were high-risk HPV-positive, and morphologic evaluation had a sensitivity of 97.3% (95% confidence interval [CI], 86.2-99.5) for predicting high-risk HPV status compared to IHC/ISH/PMS. Disease progression was more common among high-risk HPV-negative compared to high-risk HPV-positive patients (HR 2.74, CI 1.12-8.23, P = 0.03). Moreover, among high-risk HPV-negative patients, those with moderate-poorly differentiated tumors had increased disease-specific mortality (32.6%, CI 17.1-48.1) compared to those with well-differentiated tumors (0%). Among high-risk HPV-positive patients, those with basaloid morphology had lower disease-specific mortality (0% vs 14.4%, CI 0.0-33.1)., Conclusions: We demonstrate high-risk HPV-positivity in approximately one-third of patients with pSCC. Morphologic evaluation alone had a high sensitivity in correctly determining HPV status. Our results suggest that high-risk HPV status and morphologic features (differentiation in high-risk HPV-negative, and basaloid subtype in high-risk HPV-positive pSCC) may have prognostic value., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To report outcomes of multicenter series of penile cancer patients undergoing robot-assisted video endoscopic inguinal lymph node dissection (RA-VEIL). Materials and Methods: In this retrospective analysis from 3 tertiary care centers in India, consecutive intermediate-/high-risk carcinoma penis (CaP) patients with nonpalpable inguinal lymphadenopathy and/or nonbulky (<3 cm) mobile inguinal lymphadenopathy undergoing RA-VEIL were included. Patients with matted/bulky (>3 cm) and fixed lymphadenopathy were excluded. Demographic, clinical, and intraoperative data were recorded. Perioperative complications were graded by the Clavien-Dindo classification (CDC). The International Society of Lymphology (ISL) {0-III} grading was used for the assessment of lymphedema. Incidence and pattern of recurrences were assessed on follow-up. Results: From January 1, 2011, to September 30, 2023, 115 patients (230 groins) underwent bilateral RA-VEIL for CaP. The median age of the cohort was 60 (50-69) years. Clinically palpable (either unilateral or bilateral) inguinal lymphadenopathy was seen in 54 patients (47%). The "per groin" median operative time was 120 (100-140) minutes with median lymph node yield of 12 (9-16). No complications were recorded in 87.8% groins operated, with major complications (CDC 3) seen in 2.6% groins. At a median follow-up of 13.5 months, 13 patients had documented recurrences and there were 10 cancer-related deaths. No port-site recurrences were observed. No/minimal lymphedema (ISL 0/I) was seen in 94% legs. Conclusion: RA-VEIL demonstrates safety and oncologic efficacy in penile cancer patients presenting with clinically nonpalpable and/or nonbulky inguinal lymphadenopathy, with favorable functional outcomes.

Background: Inguinal lymph node dissection plays an important role in the management of melanoma, penile and vulval cancer. Inguinal lymph node dissection is associated with various intraoperative and postoperative complications with significant heterogeneity in classification and reporting. This lack of standardization challenges efforts to study and report inguinal lymph node dissection outcomes. The aim of this study was to devise a system to standardize the classification and reporting of inguinal lymph node dissection perioperative complications by creating a worldwide collaborative, the complications and adverse events in lymphadenectomy of the inguinal area (CALI) group., Methods: A modified 3-round Delphi consensus approach surveyed a worldwide group of experts in inguinal lymph node dissection for melanoma, penile and vulval cancer. The group of experts included general surgeons, urologists and oncologists (gynaecological and surgical). The survey assessed expert agreement on inguinal lymph node dissection perioperative complications. Panel interrater agreement and consistency were assessed as the overall percentage agreement and Cronbach's α., Results: Forty-seven experienced consultants were enrolled: 26 (55.3%) urologists, 11 (23.4%) surgical oncologists, 6 (12.8%) general surgeons and 4 (8.5%) gynaecology oncologists. Based on their expertise, 31 (66%), 10 (21.3%) and 22 (46.8%) of the participants treat penile cancer, vulval cancer and melanoma using inguinal lymph node dissection respectively; 89.4% (42 of 47) agreed with the definitions and inclusion as part of the inguinal lymph node dissection intraoperative complication group, while 93.6% (44 of 47) agreed that postoperative complications should be subclassified into five macrocategories. Unanimous agreement (100%, 37 of 37) was achieved with the final standardized classification system for reporting inguinal lymph node dissection complications in melanoma, vulval cancer and penile cancer., Conclusion: The complications and adverse events in lymphadenectomy of the inguinal area classification system has been developed as a tool to standardize the assessment and reporting of complications during inguinal lymph node dissection for the treatment of melanoma, vulval and penile cancer., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Abstract: A 72-year-old man presented with a painless penile mass for 3 months. Contrast-enhanced CT revealed heterogeneous enhancement, whereas 18 F-FDG PET/CT displayed inhomogeneous 18 F-FDG accumulation in the lesion without other abnormal activity. The histopathological examination from biopsied specimen confirmed the diagnosis of a plasmacytoma. However, the subsequent tests, including serum/urine immunofixation electrophoresis, serum/urine free light chain assay, and bone marrow smear/biopsy, did not show any abnormalities. The conclusive diagnosis was a solitary extramedullary plasmacytoma of the penis., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Lymphatic metastasis is the major challenge in the treatment of penile cancer. The prognosis of individuals with lymphatic metastasis is extremely poor. Therefore, early identification of disease progression and lymphatic metastasis is an urgent task for researchers in penile cancer worldwide., Methods: In this study, using single-cell RNA sequencing, an immune landscape was established for the cancer ecosystem based on 46,861 cells from six patients with penile cancer (four with lymphatic metastasis [stage IV] and two without lymphatic metastasis [stage I]). Using bulk RNA sequencing, the discrepancy between the cancers and their respective metastatic lymph nodes was depicted based on seven patients with penile cancer., Results: The interaction between epithelial cells, fibroblasts, and endothelial cells, and the functional cooperation among invasion, epithelial-mesenchymal transition, and angiogenesis were found to be important landscapes in the penile cancer ecosystem, playing important roles in progression of cancer and lymph node metastasis., Conclusions: This study is the first to investigate the altered tumor microenvironment heterogeneity of penile cancer as it evolves from non-lymphatic to lymphatic metastasis and provides insights into the mechanisms underlying malignant progression, the premetastatic niche, and lymphatic metastasis in penile cancer., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)