Penile Cancer

No standard systemic therapy exists beyond first-line treatment for metastatic or recurrent PSCC. Targeted agents and immune checkpoint inhibitors show encouraging activity in biomarker-selected subgroups. Prospective biomarker-guided trials and international collaborations are needed, while multidisciplinary management and clinical trial enrollment remain essential for optimizing outcomes for this rare malignancy.

P2, N=25, Recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Not yet recruiting --> Recruiting

Testicular/paratesticular updates address diagnostic criteria for mesothelium-derived lesions of the tunica vaginalis, recommended immunohistochemical panels for testicular sex cord-stromal tumors, and recommended nomenclature, specifically the use of "embryonic-type neuroectodermal tumor" rather than primitive neuroectodermal tumor (PNET) in the context of somatic transformation of testicular germ cell tumors. For penile squamous cell carcinoma, the summary emphasizes prognostic biomarkers, notably TP53 alterations and high risk HPV status, and nuances pertaining to pathologic staging.

Thus, the present hypothesis is that virally encoded proteins such as HPV-E6 or SARS-COV-2 Spike may cooperate in suppressing host defenses including tumor suppressor mechanisms involving p53. The hypothesis can be further explored through epidemiologic and laboratory studies.

P2, N=200, Recruiting, Mayo Clinic | Trial completion date: Dec 2025 --> Jan 2027 | Trial primary completion date: Dec 2025 --> Jan 2027

These findings highlight IL-1α, IL-12 and TGF-β1 as promising tissue biomarkers of aggressive PeCa and support a central role for cytokine-driven immune dysregulation in penile cancer. The prognostic value of IL-12 should be considered exploratory and warrants validation in larger, multicentre cohorts.

P1/2, N=55, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Dec 2025 --> Nov 2026

Current chemotherapy treatments, including the TIP (Taxol, Ifosfamide, Cisplatin) regimen, have shown limited effects but strong side effects in advanced Penile squamous cell carcinoma (PSCC) patients. Furthermore, compared with cisplatin, TROP-2 targeted ADC could achieve an equivalent inhibitory effect on the proliferation of PSCC both in vivo and in vitro. TROP-2 promoted PSCC cell proliferation via AKT/PKCα-dependent pathway, and TROP-2-targeted ADC-drug has a gratifying inhibitory effect on PSCC proliferation both in vivo and in vitro.

P2, N=25, Active, not recruiting, University Health Network, Toronto | Recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

Molecular studies excluded hallmark translocations of other vascular or perivascular tumors but confirmed MYC gene amplification, supporting a definitive diagnosis of high-grade epithelioid angiosarcoma. This case highlights the diagnostic complexity of rare penile tumors and emphasizes the critical role of integrated histopathological, immunophenotypic, and molecular analyses in distinguishing aggressive vascular malignancies from their mimics.

Together, these data identify FXR as an immune checkpoint and support repurposing UDCA for ICC immunotherapy.