Clinicopathological Characteristics and Survival Outcomes in Young-Onset Rectal Cancer Treated with Total Neoadjuvant Therapy: Perspective from a Resource Limited Setting

Introduction: The rising incidence of young-onset rectal cancer (YORC) is a significant concern, particularly in low- and middle-income countries like Pakistan. This study evaluates the clinical characteristics, treatment patterns, and outcomes of YORC patients treated at a specialized cancer center in Pakistan. Methods A retrospective review was conducted on patients under 50 years diagnosed with locally advanced rectal cancer between 2010 and 2020. Comprehensive staging, neoadjuvant chemotherapy, chemoradiation, surgical resection, and follow-up were analyzed. Key outcomes included progression-free survival (PFS), overall survival (OS), and recurrence patterns. Results Among 244 patients (median age 36 years), 67.2% were male. Most presented with advanced disease (89% stage III), with 79.5% having positive circumferential resection margins (CRM). Adenocarcinomas were predominant (75.0%), while mucinous/signet ring histology accounted for 25%. All received neoadjuvant therapy. Of the 175 patients who underwent surgery, 20.0% achieved a complete pathological response. At a median follow-up of four years, five-year OS and PFS were 70.7% and 56.1%, respectively for CRM positive and CRM negative patients. Recurrence occurred in 41.0% of cases, with distant metastases being more common than local relapse. Negative CRM status correlated with improved DFS. Conclusion Young rectal cancer patients in Pakistan often present with aggressive, advanced-stage disease. Despite intensive multimodal treatment, outcomes remain suboptimal, highlighting the need for earlier detection, improved access to care, and tailored treatment strategies. These findings underscore the importance of public awareness, screening programs, and further research into the biological distinctiveness of YORC in resource-limited settings.