Management and Treatment of Penile Squamous Cell Carcinoma

Penile squamous cell carcinoma (PSCC) is a rare but aggressive malignancy that accounts for over 95% of penile cancers. Management centres on early detection, risk stratification, and a tailored combination of surgical, systemic and adjuvant therapies. Surgical options range from organ‐preserving techniques such as Mohs micrographic excision and glansectomy with reconstruction, to partial or total penectomy in locally advanced disease. Inguinal lymphadenectomy remains a cornerstone for nodal staging and regional control, with minimally invasive approaches gaining traction for reduced morbidity. Radiotherapy and chemotherapy, notably cisplatin‐based regimens, offer adjunctive benefit in high‐risk or metastatic settings, though chemoresistance poses a significant challenge. Advances in targeted and immunotherapeutic strategies are reshaping the treatment landscape: biomarkers including HPV status, PD‐L1 expression and tumour‐infiltrating immune cells inform prognosis and therapeutic selection. Prophylactic human papillomavirus vaccination and improved penile hygiene are emerging as preventive measures with potential to curb global PSCC incidence. A multidisciplinary approach that integrates surgical innovation, precise molecular profiling and evolving systemic therapies is essential to improve survival, functional outcomes and quality of life for men with PSCC.

Research from Nature Portfolio

Recent preclinical work has established a genetically engineered mouse model of PSCC that recapitulates key molecular drivers and an immunosuppressive tumour microenvironment. Co‐deletion of Smad4 and Apc in the penile epithelium induced tumours enriched for myeloid‐derived suppressor cells. Subsequent studies demonstrated that combining immune checkpoint inhibitors with drugs targeting these suppressor cells, such as cabozantinib or celecoxib, produced synergistic anti‐tumour activity. These findings illuminate mechanisms of cisplatin resistance linked to Pten deficiency and identify candidate therapeutic combinations for clinical evaluation, marking a significant advance in translational PSCC research.

Management and Treatment of Penile Squamous Cell Carcinoma publication trend

The graph below shows the total number of articles in management and treatment of penile squamous cell carcinoma across all publications each year (not limited to Nature Index journals).

Technical terms

Penectomy: Surgical removal of the penis, partial or total.
Inguinal lymphadenectomy: Surgical excision of lymph nodes in the groin to manage nodal metastases.
Immune checkpoint blockade: Therapeutic inhibition of regulatory pathways in T cells to enhance anti‐tumour immunity.
Myeloid‐derived suppressor cells (MDSCs): Immunosuppressive cells that inhibit anti‐tumour immune responses.
Cisplatin resistance: Reduced tumour sensitivity to cisplatin chemotherapy, often mediated by molecular alterations.
Age‐standardised incidence rate (ASIR): Incidence rate adjusted for age distribution, enabling comparison across populations.

References

1. Penile Cancers Attributed to Human Papillomavirus Are Associated with Improved Survival for Node-positive Patients. Findings from a Norwegian Cohort Study Spanning 50 Years. European Urology Oncology (2023).
2. Global Pattern and Trends in Penile Cancer Incidence: Population-Based Study. JMIR Public Health and Surveillance (2022).
3. The Prognostic Value of Immune Factors in the Tumor Microenvironment of Penile Squamous Cell Carcinoma. Frontiers in Immunology (2018).
4. Effective combinatorial immunotherapy for penile squamous cell carcinoma. Nature Communications (2020).
5. Video endoscopic inguinal lymphadenectomy (VEIL): minimally invasive resection of inguinal lymph nodes. International braz j urol (2006).