Association of Genetic Alterations with Tumor Biology and Survival Outcomes in Renal Cell Carcinoma: A Prospective and Retrospective Study

Abstract

Background: Renal cell carcinoma (RCC) is a heterogeneous malignancy arising from renal tubular epithelium and accounts for 2–3% of adult cancers. Although RCC predominantly affects older individuals, its incidence in younger patients has shown a rising trend. Young-onset RCC may differ from conventional RCC in terms of tumor biology, genetic profile, and clinical outcomes, making its evaluation clinically significant. Aim: The present study aimed to evaluate the genetic patterns in young-onset RCC patients (≤46 years) and to correlate these findings with tumor characteristics, histopathological subtypes, recurrence, and survival outcomes. Methodology: This retrospective and prospective observational study was conducted at a tertiary care center between 2013 and 2024. A total of 34 young RCC patients meeting inclusion criteria were analyzed. Clinical, demographic, radiological, histopathological, and treatment-related data were collected. Genetic testing using Next-Generation Sequencing (NGS) with Whole Exome Sequencing (WES) was performed in selected high-risk patients after genetic counseling. Statistical analysis was carried out using SPSS version 25.0. Results: The mean age of patients was 38.2 ± 5.6 years, with male predominance. Clear cell RCC was the most common histological subtype. Most tumors were detected incidentally and presented at an early stage with low histological grade. Pathogenic or likely pathogenic germline variants were detected in a minority of patients, predominantly involving the VHL gene. Recurrence was observed mainly in patients with advanced tumor stage and lymph node involvement. Overall survival outcomes were favorable in early-stage disease. Conclusion: Young-onset RCC is characterized by early-stage presentation, favorable histopathology, low recurrence rates, and improved survival. While RCC-specific germline mutations are uncommon, selective genetic evaluation remains valuable in high-risk patients