Survival Benefit from Total Neo-Adjuvant Therapy in Locally Advanced Rectal Cancer Patients

Abstract Background Preoperative chemoradiation in patients with locally advanced rectal cancer has no impact on overall survival (OS) and distant recurrences. The aim of the study was to evaluate local downstaging, toxicity, patient compliance and long-term outcome (2 year OS and DFS) in patients with locally advanced rectal cancer after induction chemotherapy with 12 weeks of 5 fluorouracil based chemotherapy followed by radiotherapy concomitant with capecitabine before total mesorectal excision (TME). Patients and Methods Between January 2018, and December 2019, we enrolled eligible patients with poor-risk rectal cancer defined by high-resolution MRI (Any cT3 and T4 stage, T2 low lying tumor at or below the levators and node positive tumor) and without metastatic disease Patients were planned for 12 weeks of neoadjuvant capecitabine and oxaliplatin (oxaliplatin 130 mg/m² on day 1 with capecitabine 1000 mg/m² twice daily for 14 days every 3 weeks) followed by chemoradiotherapy (50.4 Gy in a conventional fractionation) with capecitabine (825 mg/m² twice daily), then total mesorectal excision (TME) was carried out 6 weeks after the completion of CRT. Results Of 70 consecutively admitted patients starting induction chemotherapy, 55 patients underwent surgery. R0 resection was seen in 92.7% and pathological downstaging in 72.7%. In the intention-to-treat group, Objective response rates after neoadjuvant chemotherapy and chemoradiotherapy were 51.4% and 48.6%, respectively. Pathological complete response was seen in 15.7 %. Two-year disease-free survival (DFS) and OS were 62.5% and 82.6%, respectively. Grade 3/4 toxicity was seen in 20 %, and only one case died within 2 months of therapy. Conclusion Intensification of systemic therapy with neoadjuvant combination chemotherapy before standard treatment is feasible in poor-risk potentially operable rectal cancer, with acceptable safety and promising long-term outcomes. Future development of this multidisciplinary treatment strategy in randomized trials is warranted.