Letter to the Editor: Surgical safety of RAPIDO-style total neoadjuvant therapy - reassuring early outcomes with important nuances

Abstract

The increasing adoption of total neoadjuvant therapy (TNT) in the management of locally advanced rectal cancer has raised concerns regarding potential increases in surgical complexity and perioperative morbidity, particularly with Rectal Cancer and Preoperative Induction Therapy Followed by Dedicated Operation (RAPIDO)-style treatment strategies that involve prolonged intervals between radiation and surgery. The study by Jabbar et al, published in the recent issue of the World Journal of Gastrointestinal Oncology, comparing outcomes following induction chemotherapy-based TNT with those observed after standard long-course chemoradiotherapy. Across key oncologic and technical endpoints - including R0 resection rates, completeness of total mesorectal excision, and early postoperative complication rates - no clinically meaningful differences were observed between treatment approaches. Importantly, TNT did not translate into higher surgical difficulty or worse short-term morbidity, despite delayed operative timing. Moreover, certain stoma-related outcomes appeared favorable in patients treated with TNT. Collectively, these findings provide reassurance regarding the surgical safety of RAPIDO-style TNT as it becomes more widely implemented and highlight the importance of future prospective studies incorporating objective and standardized measures of operative complexity.

Key Words: Total neoadjuvant therapy; Rectal cancer; RAPIDO protocol; Surgical outcomes; Chemoradiotherapy

Core Tip: This letter highlights real-world data showing that Rectal Cancer and Preoperative Induction Therapy Followed by Dedicated Operation (RAPIDO)-style total neoadjuvant therapy does not appear to increase surgical difficulty or early postoperative morbidity compared with standard long-course chemoradiotherapy. Despite prolonged intervals before surgery, key oncologic and technical metrics - such as R0 resection, total mesorectal excision completeness, and complication rates - were maintained, while stoma-related outcomes may even improve. These findings offer reassurance as total neoadjuvant therapy becomes increasingly integrated into management of locally advanced rectal cancer and underscore the need for future prospective studies incorporating objective measures of operative complexity.

TO THE EDITOR

We read with great interest the manuscript by Jabbar et al[1], published in the recent issue of the World Journal of Gastrointestinal Oncology, “Comparing early surgical outcomes between total neoadjuvant therapy and standard long course chemoradiotherapy for rectal cancer”. The authors address a very practical question: Whether intensified total neoadjuvant therapy (TNT) using the Rectal Cancer and Preoperative Induction Therapy Followed by Dedicated Operation (RAPIDO) protocol affects short-term surgical outcomes compared with conventional long-course chemoradiotherapy (LCCRT). As TNT is increasingly adopted for high-risk locally advanced rectal cancer, the possibility that prolonged and intensified neoadjuvant treatment might translate into more difficult surgery has become a common concern at multidisciplinary rounds[2]. In this context, the data presented are highly relevant and fill a real gap in the literature. It offers reassuring early data, while also underscoring the need for ongoing evaluation as treatment strategies evolve.

STRENGTHS AND CLINICAL IMPLICATIONS

We commend the authors for providing real-world comparative data collected over a decade of practice. Several points from their study stand out. First, although the TNT-RAPIDO group had a much longer interval from the start of neoadjuvant therapy to surgery - almost 10 weeks more than the LCCRT cohort - there was no apparent increase in operative time, intraoperative complications, conversion to open surgery, or early postoperative morbidity. This is reassuring, particularly in light of the longstanding fear that extended intervals between radiation and surgery would exacerbate pelvic fibrosis and, in turn, jeopardize the quality of the total mesorectal excision (TME)[3].

Second, the pathological outcomes are equally reassuring. R0 resection rates, TME completeness, and pathological complete response rates were similar between the two groups, suggesting that good surgical planes and oncologic quality can still be achieved despite prolonged neoadjuvant treatment. These observations are consistent with reports from other high-volume centers, where minimally invasive techniques - especially robotic TME - appear to help surgeons navigate post-radiation fibrosis and maintain specimen quality.

Third, the difference in stoma-related outcomes is clinically meaningful. Patients in the TNT-RAPIDO cohort had shorter stoma duration and a substantially lower rate of permanent stoma formation. Although several factors are likely contributing, such as selection bias or differences in surgical decision-making independent of tumor response, these findings raise the possibility that deeper tumor downstaging or more favorable pelvic conditions at the time of reconstruction may translate into better functional outcomes. Given the impact of stomas on quality of life, psychosocial well-being, and healthcare use, this signal certainly warrants confirmation in larger series.

LIMITATIONS AND CONFOUNDING FACTORS

There are, however, some points that deserve caution. The retrospective, single-center design and relatively small sample size limit the ability to capture more subtle aspects of surgical difficulty or to draw firm conclusions about long-term oncologic outcomes. Multi-institutional or prospective cohorts are needed to validate these results. In addition, the high proportion of robotic procedures in the TNT-RAPIDO group may itself influence operative precision, conversion rates, and postoperative recovery, potentially confounding comparisons between TNT-RAPIDO and LCCRT.

Although robotic surgery does not reverse the biological effects of radiation-induced pelvic fibrosis, it can mitigate the technical challenges encountered during TME[2]. The enhanced three-dimensional visualization, wristed instrument articulation, and improved stability afforded by robotic platforms allow surgeons to navigate obliterated planes and dense fibrotic tissue with greater precision. As a result, lower conversion rates and more consistent TME quality with robotic approaches in post-radiation settings have been described, suggesting that robotics may help preserve operative performance even when pelvic dissection is rendered more difficult by neoadjuvant therapy. As TNT and surgical technology continue to evolve, prospective studies incorporating surgeon-reported difficulty scores, objective intraoperative metrics (such as blood loss), and standardized pathologic assessments would be extremely informative.

CONCLUSION

Overall, Jabbar et al[1] provide important and reassuring real-world evidence supporting the surgical safety of TNT-RAPIDO. Their findings reinforce the idea that intensifying neoadjuvant therapy to improve systemic control and tumor regression does not necessarily come at the cost of TME quality or early morbidity. As TNT becomes more widely used in locally advanced rectal cancer, studies like this one are essential to guide multidisciplinary decision-making, refine patient selection, and reassure clinicians that more intensive preoperative treatment can be delivered without compromising operative outcomes. We congratulate the authors on their thoughtful study and appreciate their contribution to the ongoing discussion on how best to integrate TNT into rectal cancer care.