Outcomes of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: A Prospective Observational Real-World Cohort in Johannesburg, South Africa

Background: Total neoadjuvant therapy (TNT) is increasingly used for treatment of locally advanced rectal cancer (LARC) to improve treatment compliance, oncological outcomes and opportunities for organ preservation. However, evidence describing its implementation and outcomes in low- and middle-income countries remains limited. This study evaluated the feasibility, treatment delivery, oncological outcomes and organ preservation outcomes of TNT in a real-world South African setting. Methods: This was a retrospective review of a prospective cohort of adults with histologically confirmed, non-metastatic LARC treated with TNT at the Wits Donald Gordon Medical Centre, Johannesburg, between March 2022 and January 2026. Treatment was individualised following multidisciplinary review and included induction and/or consolidation systemic chemotherapy with either long- or short-course radiotherapy. Following TNT, treatment response was assessed clinically, endoscopically and radiologically. Patients with a clinical complete response (cCR) were offered watch-and-wait (WW) surveillance, while those with an incomplete response were recommended for total mesorectal excision (TME). The primary outcome was organ preservation, assessed as TME-free survival. Secondary outcomes included tumour regrowth, disease-free survival (DFS), overall survival (OS), and local recurrence-free survival (LRFS) following TME. Results: Forty-six patients were included; median age was 63 years, 67.4% were male, 82.6% had T3-T4 tumours and 80.4% had node-positive disease. TNT was completed as planned in 95.7% of patients. Grade [≥]3 toxicity occurred in 19.5% during chemotherapy and 8.9% during radiotherapy. Twenty-one patients (45.7%) achieved a cCR and entered WW surveillance. TME-free survival was 46% (95% CI 31-60) at 1-year and 18% (95% CI 8-32) at 3-years. Three-year OS and DFS were 87% (95% CI 64-96) and 76% (95% CI 53-89), respectively. Among patients managed with WW, 3-year regrowth-free survival was 53% (95% CI 26-75). Three-year LRFS following TME was 94% (95% CI 68-99), and all patients undergoing TME or completed salvage surgery achieved an R0 resection. Conclusion: TNT was feasible and well tolerated in this real-world South African cohort, with high treatment completion and favourable medium-term oncological outcomes. Although almost half of patients initially achieved a cCR, declining TME-free and regrowth-free survival demonstrated that durable organ preservation was less frequent, highlighting the importance of structured surveillance and timely access to salvage surgery. These findings support the feasibility of delivering contemporary multimodal rectal cancer care in an appropriately resourced African setting.