Journal Article

Molecular characterization of metastatic penile squamous cell carcinoma in developing countries and its impact on clinical outcomes: LACOG 2018 translational study

Gazzola, Antonia A, Silva, Gyl Eanes Barros, Barrios, Pablo M, de Jesus, Rafaela Gomes, Alencar Junior, Antonio Machado, da Trindade, Karine Martins, Spiess, Philippe E, Fay, Andre P, Monteiro, Fernando Sabino Marques, Bellmunt, Joaquim, Teixeira Junior, Antonio Augusto Lima, Maluf, Fernando C, Rebelatto, Taiane Francieli

2025

Overview

Abstract Background Penile squamous cell carcinoma (PSCC) is a rare malignancy. However, in developing countries the incidence rate is higher. The understanding of molecular alterations is essential for evaluating possible targets for more effective systemic therapies. Methods We retrospectively collected clinical data of metastatic PSCC (mPSCC) patients who had received at least one prior systemic treatment from 3 Brazilian hospitals. Tumor samples were evaluated using the next-generation sequencing (NGS) Foundation One DX and immunohistochemistry (IHC). The objective was to identify and describe somatic genomic alterations known to be functional or pathogenic and their association with survival outcomes. Results Twenty-three patients were identified, 22 and 18 patients had tumor samples analyzed by IHC and NGS, respectively. PD-L1 expression (CPS ≥ 1%) was positive in 14 patients (63.6%). Regarding the genomic alterations, 16 patients (88.9%) had some clinically relevant genomic alterations. TP53, TERT, CDKN2A, PIK3CA, NOTCH1, and CDKN2B loss were identified in 66.7%, 50%, 50%, 33.3%, 27.8%, and 22.2% of the patients, respectively. No MSI or TMB high (≥10 mutations/MB) cases were identified. NOTCH1 mutation was identified only in HPV-negative patients and it was associated with worse OS (yes: 5.5 vs no: 12.8 months, P = .049) and progression-free survival (yes: 5.5 vs no: 11.7 months, P = .032). Conclusion This study demonstrated that molecular alterations in mPSCC from developing countries are similar to those from developed countries. Predictive biomarkers for immunotherapy response such as TMB high or MSI were not identified. Specific gene mutations may identify patients with worse prognoses and open new avenues for therapeutic development. Understanding molecular alterations is essential for evaluating possible targets for more effective systemic therapies for the rare malignancy penile squamous cell carcinoma.

• Publisher: Oxford University Press
• Subject: Adult / Aged / Biomarkers, Tumor - genetics / Brazil - epidemiology / Cancer / Carcinoma, Squamous Cell - genetics / Carcinoma, Squamous Cell - pathology / Developing Countries / Development and progression / Diagnosis / Gene mutations / Genetic aspects / Genitourinary Cancer / Humans / Male / Middle Aged / Mutation / Neoplasm Metastasis / Oncology, Experimental / Penile cancer / Penile Neoplasms - genetics / Penile Neoplasms - mortality / Penile Neoplasms - pathology / Prognosis / Retrospective Studies / Squamous cell carcinoma / Translational Research, Biomedical