Penile cancer is a rare malignancy, with an Australian incidence of 0.6 in 100 000 men, with a wide range of clinical presentations, from localised, curable tumours to aggressive forms with high morbidity and mortality. Epidemiological data and management guidelines for penile cancer in Australia are limited. The Australian Penile Cancer Clinical Registry (APCCR) aims to address this gap through a centralised database studying local risk factors, treatment effectiveness, and outcomes. The APCCR is a national, multicentre, prospective clinical quality registry. The primary objective is to map demographic and tumour characteristics, human papillomavirus infection rates, long-term surgical and non-surgical (radiotherapy and chemotherapy) interventions in penile cancer. Secondary objectives include elucidating disparities and interdisciplinary gaps in care and identifying areas for further studies. The registry aims to capture adult men with penile cancer in, utilising retrospective data collection and a prospective cohort design. Retrospective data are extracted from existing medical records, and prospective data are collected at enrolled sites. The registry is built in Research Electronic Data Capture (REDCap) and hosted on BioGrid Australia servers, enabling standardised data collection. Registration with the Australian Register of Clinical Registries is pending approval. The pilot phase of the APCCR is currently operational, with ongoing site recruitment. Five sites in Victoria and New South Wales are currently enrolled in the registry. The APCCR Steering Committee determined reporting and data protocols to ensure accurate data collection. The dataset was developed to comprise relevant clinical metrics on penile cancer diagnosis, disease, intervention, and surveillance. The APCCR is a robust platform for furthering the understanding of penile cancer diagnostic and treatment practices in Australia, aiming to further research and clinical practice changes. This will drive further collaboration and improvements in outcomes for Australian men affected by penile cancer, particularly with ongoing national expansion and improved longitudinal data.

CD47 as a prognostic biomarker and potential immunotherapy target in penile squamous cell carcinoma.

Penile squamous cell carcinoma (PSCC) is rare, but a biologically aggressive malignancy. Recent comprehensive genomic profiling (CPG) efforts revealed the underlying genomic landscape of PSCC, identifying TP53, TERT, CDKN2A, PIK3CA, NOTCH1, and FAT1 as frequently altered genes with potential roles in penile oncogenesis. In addition, recurrent mutations encoded in the GPS1 gene have been observed in 7.4% of cases in a particular PSCC cohort. Functional studies demonstrated loss of function due to GPS1 Exon 9 missense mutations, proposing a possible role for these alterations as oncogenic driver events in PSCC. However, no other study confirmed the occurrence of GPS1 gene mutations in PSCC. To elucidate the biological function of GPS1 exon 9 mutations in PSCC pathogenesis, we utilized a comprehensive in-house cohort of 106 PSCC cases to explore their frequency and occurrence. Albeit, the previously reported GPS1 mutations p.D382H and p.M384I were not observed in this large cohort of PSCC cases; this analysis, however, revealed two novel GPS1 alterations in exon 9 in two (1.9%) of the analyzed cases: p.S372F (c.1115C>T) and p.A375D (c.1124C>A). This observation suggests that GPS1 exon 9 sequence is a target of genetic alteration during PSCC pathogenesis. However, the non-recurrent nature of these alterations indicates that they are unlikely to represent oncogenic drivers in this disease.

Diagnostic and treatment delays in penile cancer: a call to improve awareness and referral.

Patients with penile cancer may be particularly vulnerable to depression, anxiety, and social isolation, yet population-level data on mental health outcomes are limited. We investigated the incidence and predictors of mental health disease (MHD) after penile cancer diagnosis and treatment using nationally representative data sets. We conducted a retrospective analysis of the deidentified MarketScan Commercial Claims (MCCD) and Medicare supplemental (MSD) databases (2009-2023). Eligible patients were 18 years or older with confirmed penile cancer. Those with preexisting MHD were excluded. Treatments were categorized as radical (radical penectomy/perineal urethrostomy), partial (partial penectomy), topical (imiquimod/5-fluorouracil), or local excision. The primary outcome was new-onset MHD (major depressive disorder or generalized anxiety disorder) within 36 months. Multivariable Cox models identified predictors. Among 1633 patients (1044 MCCD; 589 MSD), 151 (14.5%) and 83 (14.1%) developed MHD, respectively. In MCCD, radical penectomy (HR 3.33, 95% CI 1.72-6.47, P < .001), Charlson Comorbidity Index (CCI) 2 (HR 1.74, 95% CI 1.03-2.96, P = .040), and CCI 3+ (HR 2.45, 95% CI 1.54-3.91, P < .001) predicted increased MHD risk compared with local excision and a CCI of 0, respectively, while age in the third quartile was protective (HR 0.47, 95% CI 0.30-0.75, P = .001). These variables did not significantly correlate with MHD in the MSD cohort. Patients with penile cancer face high rates of MHD, particularly after radical surgery, in the presence of comorbidities. This relationship appeared to differ between MSD and MCCD cohorts. Survivorship models should integrate timely mental health support and address access disparities.

13 Background: Penile squamous cell carcinoma (PSCC) is a rare tumor with limited therapeutic options in advanced disease. Given the role of PD-L1 as a prognostic biomarker in many cancer subtypes, assessing its value in PSCC may inform prognosis and guide the use of immune checkpoint inhibitors in metastatic disease. In this systematic review and meta-analysis, we evaluate the prevalence of PD-L1 tumor expression in PSCC and assess its prognostic association with overall survival (OS), cancer-specific survival (CSS), and lymph node metastasis (LNM). Methods: We searched PubMed, Embase and Cochrane for relevant studies. The primary outcomes were OS, CSS, and LNM, analyzed using HRs or ORs, each with 95% CIs. Outcomes were prespecified in the PROSPERO protocol (CRD42019129410). Random-effects meta-analyses (restricted maximum-likelihood estimator) were performed using inverse-variance weighting. Heterogeneity was assessed by Q, τ², and I² statistics. Publication bias was examined by Egger’s test and funnel plots. Results: Fifteen retrospective studies were included (N = 1,445). Overall, 57% of tumors were PD-L1 positive (IQR, 44%–66%). Among 796 patients, PD-L1 expression was significantly higher in HPV-negative than in HPV-positive tumors (42% vs 13.5%). Eight studies (N = 930) evaluated OS, nine studies (N = 1,091) assessed CSS, and five studies (N = 622) investigated LNM. PD-L1 positivity was associated with reduced OS (HR 1.52; 1.12–2.05; I² = 6.8%) and CSS (HR 1.61; 1.16–2.23; I² = 38.3%), and with higher odds of LNM (OR 2.94; 1.28–6.78; I² = 57.3%). In meta-regression, HPV adjustment significantly strengthened CSS associations (QM = 7.13, p = 0.008; HR = 2.06, 1.21–3.51), accounting for all observed heterogeneity. Other moderators (sample size, adjustment status, tumor stage, study location, tumor-cell vs TIL scoring) were non-significant. Conclusions: PD-L1 expression is more frequent in HPV-negative PSCC and is consistently associated with adverse clinical outcomes, including shorter OS, shorter CSS, and higher odds of LNM. These findings support PD-L1 as a potential prognostic biomarker in PSCC and underscore the importance of considering HPV status in prognostic and therapeutic stratification.

Select updates in the pathology of kidney, testis, and penile cancer for 2026: Including FLCN-mutated (kidney) tumors, paratesticular mesothelial tumors, and TP53/HPV status in penile squamous cell carcinoma.

Male genital lichen sclerosis (mGLS) is a chronic progressive inflammatory disease with potential complications including urethral strictures and penile cancer. Despite its clinical significance, the molecular mechanisms underlying mGLS remain poorly understood, and male-specific data are limited. This systematic review consolidates current evidence on tissue-based gene and protein expression in mGLS, aiming to identify commonly investigated biomarkers and highlight gaps in the literature. Using the JBI Sumari interface, our research strategy identified a total of 24 studies with considerable variability in targets and methodologies. Only a small subset of 12 genes and proteins was assessed and only one gene, p16, was assessed across multiple studies, limiting the strength of conclusions. QIAGEN Ingenuity Pathway Analysis was used to explore canonical pathways and disease associations linked to reported biomarkers. While preliminary patterns suggest involvement of inflammatory and fibrotic pathways, further research is needed to validate these findings and assess their diagnostic, prognostic or therapeutic potential. This review provides a foundation for future studies focused on improving molecular understanding and clinical management of mGLS.

P0717 Target-dependent in-vitro efficacy of Sacituzumab govitecan and Enfortumab vedotin in penile cancer

P0714 Transition from open to multi- and single-port robotic inguinal lymphadenectomy for bulky nodal disease in penile cancer: A consecutive series comparison

A0735 Optimizing sentinel node mapping in penile cancer: Triple dye versus dual dye prospective evaluation

A0732 Automated 3D CT-based tumor geometry predicts Nodal risk and survival in penile cancer: 162-Patient Cohort

P0713 BelPen study: Prospective evaluation of MRI with Magtrace for sentinel node biopsy in penile cancer

A0733 Surveillance of clinically negative groins in penile cancer using (18F) FDG PET-CT: Single-centre evaluation of its non-invasive accuracy in identifying early inguinal lymph node metastasis and guiding timely management

A0730 Expression of HER2, EGFR and HDAC6 as potential therapeutic targets in penile cancer

P0134 DEPECA-2 (DEfeating PEnile CAncer 2) – robot-assisted vs. open inguinal lymphadenectomy for penile cancer – a prospective randomized trial with a supporting translational program

ENSG00000270077 as a novel regulator of metastatic behavior in penile cancer with inguinal lymph node metastases

Main Genomic Findings in Penile Cancer: An Update.

Predicting inguinal lymph node metastasis in penile squamous cell carcinoma, from imaging, molecular biomarkers to multimodal AI: a narrative review

A0738 18F-FAPI-42 PET/CT outperforms 18F-FDG PET/CT in detecting inguinal nodal metastasis in penile squamous cell carcinoma: A prospective head-to-head comparison study