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Breakthrough Study Reveals Potential for Immunotherapy in Advanced Penile Squamous Cell Carcinoma

In a groundbreaking cohort study, researchers have unveiled new insights into the genomic profiles and clinical outcomes of patients with advanced metastatic penile squamous cell carcinoma (PSCC). The study, which analyzed 397 cases, focused on the role of comprehensive genomic profiling and immunotherapy in treating this rare and deadly disease.

Key Findings:

  • Tumor Mutational Burden (TMB): The study identified that 15% of patients had a TMB of 10 mutations per megabase (mut/Mb) or higher, with 4% having a TMB of 20 mut/Mb or higher.
  • Distinct Genomic Profile: Tumors with higher TMB were characterized by a unique genomic profile, including more frequent PIK3CA and KMT2D genomic alterations and human papillomavirus (HPV) infection.
  • Immunotherapy Potential: The findings suggest that patients with advanced metastatic PSCC, particularly those with high TMB values and specific genomic alterations, may be candidates for immune checkpoint inhibitor (ICI) therapy.

Implications for Clinical Practice:

  • Germline Testing: The study emphasizes the importance of germline testing in the management of selected PSCC cases, with 6.9% of genetic alterations predicted to be germline, including homologous recombination repair genes.
  • Integration of ICI Therapy: The researchers advocate for the integration of comprehensive genomic profiling into the management of advanced PSCC cases, providing a basis for the consideration of ICI-based therapy.


Locally advanced metastatic PSCC is a rare and lethal disease with limited treatment options. The standard treatment involves radical inguinal lymphadenectomy, but the prognosis remains challenging. The study aimed to explore the potential of immunotherapy, specifically immune checkpoint inhibitors, as a novel approach to managing advanced PSCC.


In conclusion, this cohort study sheds light on the genomic landscape of advanced PSCC and its potential implications for treatment strategies. The identification of distinct genomic profiles associated with higher TMB opens avenues for precision medicine, paving the way for personalized and targeted therapies, including immunotherapy. The study’s findings could revolutionize the approach to treating this rare and aggressive form of cancer, offering hope for improved outcomes and prolonged survival in patients with advanced PSCC.

Credit: JAMA Network Open, Andrea Necchi