Total Neoadjuvant Therapy for Rectal Cancer: Why Japan Says “Not Yet”

TL;DR

Total neoadjuvant therapy for rectal cancer is widely accepted globally but not in Japan due to healthcare system and practice differences.

Contribution

Analyzes Japan's unique stance on total neoadjuvant therapy and highlights the need for context-specific implementation strategies.

Findings

Japan's 2024 guidelines weakly recommend against routine use of total neoadjuvant therapy or non-operative management.

The Japanese healthcare system's structure and surgeon practice patterns influence the limited adoption of TNT.

Context-specific trials and tailored implementation are needed to balance oncologic efficacy with local healthcare realities.

Abstract

Total neoadjuvant therapy (TNT) has rapidly gained global acceptance as a standard treatment for locally advanced rectal cancer (LARC). Supported by multiple phase III trials, TNT improves pathological complete response (pCR) rates, enhances systemic control, and expands opportunities for non‐operative management (NOM). These advantages have led to its inclusion in major international guidelines as a core strategy for stage II/III rectal cancer. However, not all regions have embraced TNT. Japan's 2024 colorectal cancer treatment guidelines weakly recommend against the routine use of TNT or NOM—making it one of the few countries to diverge from the global trend. This stance does not reflect a rejection of evidence, but rather the realities of a healthcare system where rectal cancer is often treated in non‐specialized institutions. Unlike consensus guidelines designed for subspecialists, the Japanese guidelines are tailored to general surgeons practicing in a wide range of settings, many of whom manage rectal cancer infrequently. This reflects a broader challenge of limited centralization within Japan's otherwise equitable healthcare system. TNT also presents unresolved concerns, including toxicity, uncertain survival benefit, and increased surgical complexity—issues particularly relevant in resource‐diverse environments. This review examines the global evolution of TNT and Japan's restrained response, analyzing key trials, guideline positions, and barriers to implementation. Japan's approach reflects practical realities rather than opposition, emphasizing the need to tailor TNT to each country's healthcare setting. The future of TNT lies not in universal application, but in thoughtful integration that balances oncologic efficacy with local context and patient‐centered care.

Total neoadjuvant therapy (TNT) improves tumor regression, systemic control, and feasibility of non‐operative management, and is now endorsed by major international guidelines for locally advanced rectal cancer. However, Japan's 2024 guidelines weakly recommend against routine TNT or NOM, reflecting healthcare system constraints, surgical practice patterns, and limited domestic evidence. This review analyzes global and Japanese perspectives, highlighting the need for context‐specific trials and tailored implementation.