Inflammation appears to play a crucial role in the development and progression of penile cancer (PeCa). Two molecular pathways of PeCa are currently described: HPV-dependent and HPV-independent. The tumor immune microenvironment (TIME) of PeCa is characterized by the presence of tumor-associated macrophages, cancer-associated fibroblasts, and tumor-infiltrating lymphocytes. The components of the TIME produce pro-inflammatory cytokines and chemokines, which have been found to be overexpressed in PeCa tissues and are associated with tumor progression and unfavorable prognoses. Additionally, the nuclear factor kappa B (NF-κB) pathway and secreted phosphoprotein 1 (SPP1) have been implicated in PeCa pathogenesis. Elevated C-reactive protein (CRP) levels and the neutrophil-to-lymphocyte ratio (NLR) have been identified as potential prognostic biomarkers in PeCa. This overview presents the complex contribution of the inflammatory process and collates projects aimed at modulating TIME in PeCa.

Purpose The study examines the microbial compositions of patients with lichen sclerosus (LS) compared to control group, and individuals with other penile conditions. The aim is to address the critical question regarding the etiology of penile LS and to explore the potential involvement of the microbiome in its pathogenesis. Methods In this prospective single-centre study, 73 uncircumcised male patients undergoing circumcision for phimosis were enrolled between January 2023 and April 2024. Foreskin and urethral swabs were obtained prior to surgery to isolate Candida, aerobic, and anaerobic microorganisms and sexually transmitted pathogens. Patients were categorised into LS (n = 44) and non-LS (n = 29) groups based on histopathological findings. Additionally, a control group, which consisted of patients with healthy foreskin, has been specified to conduct further analysis. Results No statistically significant differences were observed in the prevalence of specific bacterial or viral pathogens between the LS and non-LS groups and between the LS/non-LS and control group. The most common commensal organisms were Staphylococcus coagulase-negative (48% and 34% respectively) and Corynebacterium spp. (27% and 17% respectively), whereas Enterococcus faecalis (14%) and Escherichia coli (16%) were the most frequent pathogens in LS group, and Streptococcus agalactiae (21%) was the most abundant pathogen in non-LS group. HPV was detected in 5% of patients with LS and in 14% of patients without LS. There were no statistically significant differences in CRP levels and BMI. In exploratory multivariable models adjusting for age and BMI, the presence of Streptococcus agalactiae was associated with lower odds of LS (OR 0.19; 95% CI 0.04–0.92; p = 0.04; FDR = 0.07); however, given limited power, these results should be interpreted cautiously. Conclusions Our study demonstrated no significant association between specific microbial or viral profiles and penile lichen sclerosus. However, due the fact that the culture-based approach employed in this study may underestimate the diversity of the penile microbiome, further research is warranted.

Background/Objectives: Penile squamous cell carcinoma (PSCC) is rare but aggressive. Systemic chemotherapy plays a crucial role in the management of node-positive or metastatic cases; however, the supporting evidence predominantly originates from small, non-randomized studies. This review provides a narrative analysis of the cytotoxic classes and regimens employed in PSCC and compares major clinical guidelines to facilitate informed decision-making in practice. Methods: English-language reports were identified in PubMed/Scopus/Google Scholar without date limits. Selection prioritized objective response, survival and toxicity outcomes, and guidance statements across neoadjuvant, adjuvant, and palliative settings. Results: Bleomycin-containing triplet regimens demonstrated efficacy but were associated with unacceptable pulmonary toxicity, leading to their discontinuation in clinical recommendations. Currently, cisplatin/taxane-based combinations remain fundamental in treatment protocols. The paclitaxel–ifosfamide–cisplatin (TIP) regimen achieves approximately 40–50% objective responses in phase II studies and may enable curative surgery, while taxane–cisplatin–5-fluorouracil (TPF) shows comparable efficacy with higher toxicity. For less fit patients, cisplatin–5-fluorouracil (PF) or carboplatin–taxane doublets are pragmatic alternatives. Single-agent taxanes or vinflunine offer modest second-line benefits. Although EAU–ASCO 2023, ESMO–EURACAN 2024, and NCCN v2.2025 are broadly in consensus, recommendations differ regarding eligibility thresholds and regimen preferences. Overall, the quality of the evidence remains low. Conclusions: TIP remains the reference neoadjuvant option for chemotherapy-fit patients with bulky nodal disease; doublets are reasonable when cisplatin fitness is limited; and bleomycin should be avoided. Harmonized eligibility criteria, biomarker-enriched studies, and coordinated multicenter trials are needed to improve outcomes in this rare malignancy.

Penile metastasis is extremely rare. The most common neoplasms that spread to the external male genital area are bladder and prostate cancer. The diagnosis usually begins with the appearance of penile symptoms. Further examination usually reveals metastasis to other organs, which worsens the patient prognosis.

Background/Objectives: Transperineal MRI-fusion prostate biopsy under local anaesthesia is increasingly performed in the outpatient setting, which places greater weight on procedural tolerability. Psychological and anatomical determinants of pain have rarely been compared within a single model, and MRI-derived perineal anatomical parameters have not been evaluated. We aimed to identify factors associated with procedural pain and to determine at which step pain peaks. Methods: In this prospective, pre-registered, single-centre cohort study (OSF: osf.io/pbacu), 182 consecutive men referred for transperineal MRI–ultrasound fusion biopsy under local anaesthesia were assessed for eligibility, and 177 constituted the Full Analysis Set. State anxiety was measured with the STAI-S before and after biopsy. Pain was rated on a Numeric Rating Scale (NRS 0–10) by a nurse not involved in the procedure at four predefined steps: probe insertion, skin infiltration, periprostatic nerve block and core sampling. Midline perineal tissue thickness (MPT) and levator ani thickness were measured on pre-biopsy T2-weighted MRI by a radiologist blinded to outcomes. The primary outcome was the maximum NRS score; ten candidate predictors were entered simultaneously into a multivariable linear regression model. Results: Clinically significant pain (maximum NRS score ≥ 4) was reported by 157 of 177 men (88.7%). Pain differed markedly across steps (F(2.68, 472.39) = 230.51, p < 0.001, partial η² = 0.567) and peaked at the periprostatic nerve block (5.88 ± 2.03), exceeding core sampling by 2.62 points (95% CI 1.85–3.40). In multivariable analysis (R² = 0.192), pre-biopsy anxiety was the strongest independent predictor (standardised β = 0.30, partial R² = 0.094, p < 0.001), followed by prostate volume (β = 0.19, p = 0.014); MPT showed only an exploratory, borderline association (β = 0.17, p = 0.052). Core number, body mass index and levator ani thickness were not associated with pain. Conclusions: Most men undergoing transperineal MRI-fusion biopsy experience clinically significant pain, peaking at administration of the periprostatic block rather than at core sampling. Pre-procedural anxiety and prostate volume, both available beforehand, support simple risk stratification, while the block itself is the most logical target for analgesic improvement.