Metastatic response and short-term survival outcomes in patients with stage IV rectal cancer treated with curative intent in the era of Total Neoadjuvant Therapy

BACKGROUND: While patients with stage IV rectal cancer treated with curative intent have a high risk of distant failure, the benefits of delivering systemic treatment within a TNT setting remain unexplored. We describe the short-term outcomes of stage IV rectal cancer patients treated with curative intent using a personalised TNT (pTNT) approach. METHODS: All rectal cancer patients with resectable metastases were treated with pTNT over a 5-year period and included in a prospective database. The primary outcome of this cohort analysis was grade of metastatic response to pTNT. A subset analysis was performed for patients with a minimum of 36 months follow-up and 3-year progression free and overall survival rates were determined. RESULTS: Of 141 patients diagnosed with stage IV rectal cancer during the study period, 62 were treated with curative intent using a pTNT protocol. On initial restaging, 38.7% demonstrated a complete metastatic response and 33.9% exhibiting partial response. The remaining 27.4% progressed on treatment. A complete clinical response (cCR) in the primary rectal tumour was seen in 32.3% of patients. In the subset analysis of 39 patients with a minimum follow-up of 36 months, the 3-year progression free survival rate was 30.8% (median 20.19 months, 95%CI 12.924-27.456) and 3-year overall survival rate of 61.5% (median 44.52 months, 95%CI 31.527-57.513). CONCLUSION: A pTNT approach to stage IV rectal cancer with curative intent resulted in favourable metastatic and primary tumour response in most patients. These results provide support for pTNT to be given consideration as a primary treatment option for these patients, pending longer term survival data.