Total neoadjuvant therapy in high-risk rectal cancer: organ preservation and survival outcomes in a single-center retrospective cohort.

BACKGROUND

Rectal cancer poses a significant global health burden. Conventional neoadjuvant chemoradiotherapy (nCRT) demonstrates limited efficacy in achieving disease-free survival (DFS) and organ preservation. Total neoadjuvant therapy (TNT), an emerging paradigm integrating systemic chemotherapy with radiotherapy, aims to address these limitations.

OBJECTIVES

To evaluate the short- and long-term oncological outcomes and organ preservation feasibility of TNT in high-risk locally advanced rectal cancer (LARC) patients.

DESIGNS: A retrospective study was conducted to analyze the short-term and long-term results after total nCRT.

METHODS

This retrospective study involved 110 rectal cancer patients with high-risk features treated at the Fudan University Shanghai Cancer Center from 2008 to 2022. Patients underwent comprehensive staging and received nCRT followed by either total mesorectal excision (TME) or a watch and wait (W&W) strategy. The regimen included concurrent chemoradiotherapy with 50 Gy/25 fractions and at least six cycles of induction or consolidation chemotherapy. Both short-term and long-term outcomes were collected and analyzed.

RESULTS

Among the LARC patients, 73.6% were stage III, and 47.3% opted for the W&W strategy. The combined rate of clinical complete response or confirmed pathological complete response (pCR) reached 49.1%. During follow-up, 10% of patients experienced local regrowth. The 3-year DFS and overall survival (OS) rates were 75.7% and 92.4%, respectively. The W&W strategy could achieve superior outcomes than patients without pCR in DFS (p = 0.021) and OS (p = 0.006).

CONCLUSION

TNT demonstrates durable survival outcomes and facilitates organ preservation in over 50% of high-risk LARC patients. Intensive surveillance is critical for the early detection of local regrowth.

TRIAL REGISTRATION: Our study is retrospective in nature, rather than a prospective clinical trial. Therefore, registration was not conducted, and the Clinical Trial Number is not applicable.