Total Neoadjuvant Therapy May Aid Organ Preservation in Early Rectal Cancer

Total neoadjuvant treatment (TNT) may offer a promising alternative to surgery for patients with stage I rectal cancer (S1RC), a small study finds.¹ Among patients treated, TNT achieved a 93.7% complete response rate and preserved organs in 87.5% of cases, with no local recurrences observed over a median 20-month follow-up.

This retrospective analysis study is published in Langenbeck’s Archives of Surgery.

“Our findings suggest that TNT may be a viable organ-preserving alternative for select patients with early-stage rectal cancer, particularly for low-lying tumors where conventional surgery often results in a permanent stoma,” wrote the researchers of the study.

Neoadjuvant therapy plays an increasingly important role in the management of early-stage colorectal cancer, with evolving strategies aimed at improving both local and systemic outcomes.² Traditional approaches, including short-course radiotherapy and long-course chemoradiotherapy, are effective at controlling local disease but have limited impact on systemic relapse. TNT has shown promise in enhancing local response and reducing the risk of distant metastases and may also benefit selected patients with locally advanced colon cancer.

In this study, the researchers analyzed data from patients with S1RC who declined total mesorectal excision (TME) and instead underwent TNT between 2015 and 2023.¹ Participants were divided into 2 groups: those who demonstrated a partial response after initial chemoradiation and proceeded with consolidation chemotherapy, and those who underwent transanal full-thickness local excision of rectal lesions later confirmed as S1RC but declined further surgery.

The primary outcomes assessed were complete clinical response and organ preservation rates. Patient follow-up data, including recurrence and metastasis rates, were collected to evaluate the safety and effectiveness of TNT in this early-stage rectal cancer population.

Among the 11 patients who received TNT following a partial response to chemoradiation, 9 (82%) achieved a complete clinical response. A patient with a near-complete response required endoscopic submucosal dissection, revealing a tubulovillous adenoma, while another with a partial response eventually underwent low anterior resection, with final pathology confirming a complete response.

In the group of patients who received TNT after local excision (n = 5), no local recurrence or distant metastasis was observed over a median (IQR) follow-up of 20 (12) months. Overall, the complete response rate across all 16 patients was 93.7%, and the organ preservation rate was 87.5%, suggesting that selective TNT may offer an effective, less invasive alternative to surgery in early-stage rectal cancer.

However, the researchers acknowledged some limitations, including a small sample size, short follow-up, and its single-center design, which prevented a robust comparative analysis. Additionally, cohort heterogeneity and ambiguous treatment sequencing—particularly in patients who underwent local excision—further complicated the study.

Despite these limitations, the researchers believe the study offers valuable preliminary insights into the selective use of TNT and underscores the need for larger, prospective trials to optimize treatment strategies.

“While our findings suggest that selective utilization of TNT in stage I rectal cancer may facilitate organ preservation, particularly in low rectal tumors, the results should be interpreted with caution,” wrote the researchers. “Reduced-dose TNT may be considered a potential treatment option for early-stage rectal cancer patients in the future. Larger prospective trials with various treatment protocols and extended follow-up periods are essential to validate the efficacy of TNT in patients with stage I rectal cancer.”

References

1. Erozkan K, Erkaya M, Miller JA, et al. Is there a role for total neoadjuvant treatment in early-stage rectal cancer? Langenbecks Arch Surg. 2025;411(1):11. doi: 10.1007/s00423-025-03895-2

2. Smith HG, Nilsson PJ, Shogan BD, et al. Neoadjuvant treatment of colorectal cancer: comprehensive review. BJS Open. 2024;8(3):zrae038. doi:10.1093/bjsopen/zrae03