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.
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.
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).
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.
The oncologist. 2024 Sep 02 [Epub ahead of print]
Fernando Sabino Marques Monteiro, Antonio Machado Alencar Junior, Karine Martins da Trindade, Taiane Francieli Rebelatto, Fernando C Maluf, Antonia A Gazzola, Pablo M Barrios, Joaquim Bellmunt, Rafaela Gomes de Jesus, Gyl Eanes Barros Silva, Antonio Augusto Lima Teixeira Junior, Philippe E Spiess, Andre P Fay
Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil., Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), School of Medicine, Porto Alegre, Brazil., Dana Farber Cancer Institute and IMIM Research Lab, Harvard Medical School, Boston, United States., Hospital Universitário da Universidade Federal do Maranhão, Oncology Department, São Luis, Brazil., Postgraduate Program in Genetics, Ribeirão Preto Medical School, Universisty of São Paulo, Ribeirão Preto, Brazil., Department of GU Oncology, Moffitt Cancer Center, Tampa, United States.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/39222919