Abstract 3408: Molecular profiling in penile cancer in peruvian population: A retrospective analysis of clinical features and its association with molecular characteristics

Abstract

Abstract BACKGROUND: Penile cancer (PC) is a rare malignancy in the developed world. The incidence is higher in less developed countries and is associated with poor survival due to the aggressiveness of the disease and lack of effective systemic therapies. Precision medicine is an emerging approach to more accurately predict which treatment strategy will be optimal. METHODS: PC patients attending at INEN from 2006 to 2016 were included in the study. Tumors were re-staged according to the AJCC 8th. FFPE tumor samples were collected to assessed the presence of high-risk human papillomavirus (HPV) by qPCR. Next Generation Sequencing (NGS) was performed using the Ampliseq for Illumina cancer hotspot panel v2 target 2800 COSMIC mutation from 50 oncogenes and tumor supress genes. Kaplan-Meier estimation curves overall survival (OS) was applied and a p≤0.05 was considered statistically significant. RESULTS: A total of 515 PC cases were diagnosed with a mean age of 60 (23-98) years. Most patients (80.95%) underwent tumor surgical treatment. The most frequent surgical procedure was partial penectomy (60.5%). Lymph node dissection was performed in 59.2% (247/417) of patients. Clinical stages were distributed, in I (6.4%), II (23.6%), III (22.7), IV (37.5). At diagnosis, 36.8% had spread regionally and 5.5% had distant metastases. All tumors were epidermoid histological type. Tumor size was ≤5cm (63.9%). Most tumors were invasive (91.9%) and moderately differentiated (63.8%). Positive lymph node was found in 61.9%; (153/247) and lymph extranodal in 52.9% (81/153). Chemotherapy was administered in 18.6%. The median follow-up period was 47.3 months (37.5-57.2), and 5-years OS was 32 months. Tumor surgical treatment and lymph node dissection were associated to OS (55.1% vs 7%) at 2-years and (46.5% vs 25%) at 5-years (ECIII: 40.7%; ECIV: 21.3%). HPV detection was performed in 327 samples. HPV DNA was detected in 84.1% (HPV16: 203/327; HPV18: 72/327) of PC samples. NGS was performed in 48 PC cases representing the spectrum of pathologic grades, stages, QT responses and HPV status. Nonsynonymous point mutations, stopgains/nonsense mutations, or indels were observed in 68% (34/50) genes. TP53 was mutated in 29 cases (69%) and was the most common genomic alteration. Most frequenly mutated genes were EGFR (28.6%), CDKN2A (30.9%), PI3KCA (59.5%), HRAS (61.2%), FBXW7 (21.4%), KDR (66.7%), SKT11 (42.8%) and SMAD4 (30.9%) of cases. No significant associations were present between mutation status for an individual gene and tumor grade, stage or histology. CONCLUSION: High-risk HPV was associated with high indicence. Adecuate staging and clasification of locally adavanced or unresectable disease patients and comprehensive genomic profiling, findings of frequent mutations in peruvian PC, are necessary to select targets and to design effective personalized treatment options. Note: This abstract was not presented at the meeting. Citation Format: Carolina Belmar-Lopez, Bruno Muñante, Sandro Casavilca, Manuel Chumpitaz, Nelly Polo, Ebert Poquioma, Federico Valdez, Claudio Flores, Joseph Pinto, Henry Gomez. Molecular profiling in penile cancer in peruvian population: A retrospective analysis of clinical features and its association with molecular characteristics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3408.