Jabbar SAA, Choo ALE, Wong NW, Ngu JCY, Teo NZ. Comparing early surgical outcomes between total neoadjuvant therapy and standard long course chemoradiotherapy for rectal cancer. World J Gastrointest Oncol 2025; 17(11): 111250 [DOI: 10.4251/wjgo.v17.i11.111250]
Corresponding Author of This Article
Nan-Zun Teo, Assistant Professor, Consultant, FRCS (Ed), Department of General Surgery, Changi General Hospital, 2 Simei Street 3, Singapore 529889, Singapore. teo.nan.zun@singhealth.com.sg
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Surgery
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Retrospective Cohort Study
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Nov 15, 2025 (publication date) through Nov 13, 2025
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World Journal of Gastrointestinal Oncology
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Jabbar SAA, Choo ALE, Wong NW, Ngu JCY, Teo NZ. Comparing early surgical outcomes between total neoadjuvant therapy and standard long course chemoradiotherapy for rectal cancer. World J Gastrointest Oncol 2025; 17(11): 111250 [DOI: 10.4251/wjgo.v17.i11.111250]
Salman Ahmed Abdul Jabbar, Amadora Li En Choo, Neng-Wei Wong, James Chi-Yong Ngu, Nan-Zun Teo, Department of General Surgery, Changi General Hospital, Singapore 529889, Singapore
Author contributions: Jabbar SAA prepared and wrote the manuscript; Jabbar SAA, Choo ALE, Wong NW, Ngu JCY, and Teo NZ edited the manuscript; Jabbar SAA, Wong NW, Ngu JCY, and Teo NZ contributed to design and critical revision; Jabbar SAA and Teo NZ were involved in conceptualization; Choo ALE contributed to data collection; Teo NZ contributed to statistical analysis. All authors have read and agreed to the final version of the manuscript.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Changi General Hospital (Approval No. 2023/2390).
Informed consent statement: Informed consent was obtained from all patients participating in the study.
Conflict-of-interest statement: The authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Nan-Zun Teo, Assistant Professor, Consultant, FRCS (Ed), Department of General Surgery, Changi General Hospital, 2 Simei Street 3, Singapore 529889, Singapore. teo.nan.zun@singhealth.com.sg
Received: June 27, 2025 Revised: July 12, 2025 Accepted: October 9, 2025 Published online: November 15, 2025 Processing time: 140 Days and 6.2 Hours
Abstract
BACKGROUND
Total neoadjuvant therapy (TNT) has been proposed as an advancement over standard long-course chemoradiotherapy (LCCRT) for the treatment of locally advanced rectal cancer (LARC). It has been suggested that TNT enhances resectability, improves treatment compliance, increases the rate of pathological complete response, and reduces the risk of systemic recurrence. However, concerns have been raised that the prolonged interval to surgery associated with TNT, particularly in regimens such as the Rectal Cancer and Preoperative Induction Therapy Followed by Dedicated Operation (RAPIDO) protocol, may exacerbate fibrosis, leading to more technically challenging resections and poorer surgical outcomes.
AIM
To compare the early surgical outcomes of LARC patients treated with TNT-RAPIDO vs LCCRT.
METHODS
A single-center, retrospective cohort study was conducted of patients with LARC treated with TNT-RAPIDO or standard LCCRT followed by surgical resection between 2014 and 2024. A total of 99 patients with LARC were analyzed, including 29 treated with TNT-RAPIDO and 70 treated with standard LCCRT. Demographics, clinicopathological characteristics and early post-operative outcomes were compared between both groups.
RESULTS
Both groups were comparable in terms of demographics and clinicopathological characteristics. The median interval from initiation of neoadjuvant therapy to surgery was significantly longer in the TNT group compared to the LCCRT group (29.5 weeks vs 19.5 weeks, P < 0.001). Operative time and intraoperative complications were comparable. While the TNT group had a significantly higher lymph node harvest (40.7 vs 23.4, P < 0.001), the number of positive nodes was not significantly different. R0 resection rates were similar (93.1% vs 90%, P = 0.625). There was no difference in post-operative morbidity and 30-day mortality between both groups. The TNT group had a significantly shorter total stoma duration (27.1 weeks vs 42.5 weeks, P = 0.013) and a lower rate of permanent stoma formation (13.8% vs 35.7%, P = 0.013).
CONCLUSION
Compared with LCCRT, TNT-RAPIDO does not compromise operative time, complication rates, or oncological quality of resection and may confer a shorter total stoma duration and a lower permanent stoma rate.
Core Tip: Rectal cancer and preoperative induction therapy followed by dedicated operation has emerged as a total neoadjuvant therapy strategy with improved oncological and functional outcomes. The impact of total neoadjuvant therapy on operative difficulty and short-term surgical outcomes, compared with long-course chemoradiotherapy, remains an area of ongoing debate. This cohort study of 99 patients demonstrated that the Rectal Cancer and Preoperative Induction Therapy Followed by Dedicated Operation (RAPIDO) protocol does not increase surgical difficulty or compromise early surgical outcomes compared with long-course chemoradiotherapy. It may also confer a shorter total stoma duration and a lower permanent stoma rate.
Citation: Jabbar SAA, Choo ALE, Wong NW, Ngu JCY, Teo NZ. Comparing early surgical outcomes between total neoadjuvant therapy and standard long course chemoradiotherapy for rectal cancer. World J Gastrointest Oncol 2025; 17(11): 111250
The management of locally advanced rectal cancer (LARC) has evolved significantly over the past few decades, with a shift towards multimodal treatment strategies aimed at improving both oncological and functional outcomes[1-3]. Total mesorectal excision (TME) remains the cornerstone of curative-intent surgery, having substantially reduced local recurrence rates[4]. However, distant metastases remain a major clinical challenge, underscoring the need for effective systemic treatment approaches[5,6]. Traditionally, long-course chemoradiotherapy (LCCRT), consisting of preoperative radiotherapy with concurrent fluoropyrimidine-based chemotherapy, followed by surgery with or without adjuvant chemotherapy, has been the standard of care[7,8]. While LCCRT has demonstrated efficacy in tumor downstaging and local disease control, compliance with postoperative chemotherapy is often suboptimal, reported in only 30%-70% of patients, potentially compromising systemic disease control and leading to poorer overall survival[5,9,10].
Total neoadjuvant therapy (TNT) has emerged as an alternative approach, aiming to address both local and distant disease by incorporating early induction or consolidation chemotherapy with chemoradiotherapy before surgery[11]. Recent trials, including the Rectal Cancer and Preoperative Induction Therapy Followed by Dedicated Operation (RAPIDO) and PRODIGE 23, have provided evidence supporting TNT, demonstrating improved pathological complete response rates, compliance, and reduced distant metastases compared with LCCRT[12-14]. With an improved pathological complete response rate compared to traditional neoadjuvant regimes, TNT may also lead to higher rates of non-operative management and organ preservation in select patients[15]. Despite these advantages, concerns have been raised regarding the impact of TNT on short-term surgical outcomes[16]. The extended interval between radiotherapy and surgery (> 22 weeks) in TNT protocols may lead to increased tissue fibrosis, inflammation, and edema, potentially increasing operative difficulty and adversely affecting TME precision and surgical specimen quality[17]. Studies have also reported concerns regarding perioperative and early postoperative morbidity[14,17]. However, the extent to which these factors impact short-term surgical outcomes compared with LCCRT remains an area of ongoing debate.
While TNT is increasingly adopted in clinical practice for its oncological benefits, it remains essential to balance these advantages against treatment-related toxicity and surgical morbidity. Since the publication of the TNT-RAPIDO trial results, there has been a paucity of evidence regarding the early surgical outcomes of TNT. Over the past decade, an increasing number of our patients have been treated with the TNT-RAPIDO protocol followed by curative laparoscopic or robotic assisted laparoscopic (RAL) TME. This study aims to compare early surgical outcomes between neoadjuvant TNT-RAPIDO and conventional LCCRT.
MATERIALS AND METHODS
Study design
This single center, retrospective cohort study used prospectively collected clinical data over a 10-year period between October 2014 and November 2024 at Changi General Hospital, a tertiary referral center. The study was reviewed and approved by the Institutional Review Board of Changi General Hospital (Approval No. 2023/2390). Analysis was limited to patients with histologically confirmed invasive rectal adenocarcinomas, totaling 99 cases. LARC was defined as clinical stage T3 or T4, or any T stage with nodal involvement, in the absence of distant metastases. Patients with LARC who underwent neoadjuvant therapy prior to surgical resection were included. Eligible patients were 18 years or older, had a distal tumor extent less than 15 cm from the anal verge, and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2. Exclusion criteria included the presence of metastatic disease, medical unfitness for surgical or neoadjuvant therapy, upfront surgical resection, short-course radiotherapy without chemotherapy, or failure to undergo surgery within 1 year following neoadjuvant therapy.
Complete staging was performed with rectal magnetic resonance imaging (MRI) and computed tomography (CT) scans of the thorax, abdomen and pelvis. Stage was categorized based on the tumor-node-metastasis classification system (Union for International Cancer Control/American Joint Committee on Cancer 8th). All cases were reviewed at a local multidisciplinary team meeting involving surgeons, medical oncologists, radiation oncologists and radiologists. Patients were stratified into two groups, as depicted in the flowchart in Figure 1.
Figure 1 Treatment Algorithm.
A total of 99 patients were included in the study between October 2014 and November 2024; 29 patients underwent total neoadjuvant therapy with Rectal Cancer and Preoperative Induction Therapy Followed by Dedicated Operation (TNT-RAPIDO). The TNT-RAPIDO protocol consisted of short-course radiotherapy (five fractions of 5 Gy radiotherapy) followed by six cycles of oral capecitabine and intravenous oxaliplatin doublet consolidation chemotherapy. A total of 70 patients received long course chemoradiotherapy with 25 fractions of 45-50 Gy radiotherapy and concurrent chemotherapy with oral capecitabine or 5-fluorouracil. Laparoscopic or robot-assisted laparoscopic total mesorectal excision was subsequently performed. TNT: Total neoadjuvant therapy; RAPIDO: Rectal cancer and preoperative induction therapy followed by dedicated operation; CAPOX: Capecitabine and oxaliplatin; FOLFOX: Folinic acid, fluorouracil, and oxaliplatin; TME: Total mesorectal excision; RAL: Robotic assisted laparoscopic.
Patients who underwent long-course chemoradiotherapy received 25 fractions with concurrent capecitabine or 5-fluorouracil-based chemotherapy. The second group of patients received the RAPIDO protocol, which consisted of short-course radiotherapy (five fractions of 5 Gy radiotherapy) followed by six cycles of oral capecitabine and intravenous oxaliplatin doublet consolidation chemotherapy. Restaging with rectal MRI and CT of the thorax, abdomen and pelvis after neoadjuvant therapy was performed, and each case was rediscussed at the multidisciplinary team meeting prior to definitive surgical resection. TME was subsequently performed for all patients at our institution by 1 of 6 consultant colorectal surgeons, with an experience of more than 300 major colorectal resections each. Patients were counseled regarding laparoscopic or robotic TME, with the approach determined by resource availability and patient preference. During the index surgery, all patients undergoing primary anastomosis were defunctioned if a stoma had not been created prior to the initiation of neoadjuvant therapy.
Clinicopathological characteristics
The following clinicopathological variables were analyzed: Patient demographics including age, sex, body mass index and ECOG PS; tumor characteristics and operative parameters including MRI tumor stage, node stage, extramural venous invasion, circumferential resection margin (CRM), pelvic sidewall lymph nodes, interval to surgery and mode of surgery.
The primary objective of the study was to compare the operative and early surgical outcomes of LCCRT and TNT-RAPIDO. Parameters identified for comparison included operative duration, intraoperative complication rate, and oncologic quality of the resected specimens, assessed by completeness of resection, distal margin status and lymph node yield. Outcome measures included 30-day post-operative complications, stratified according to the Clavien-Dindo classification. Grades I and II were defined as minor complications, grades III and IV as severe and life-threatening, and grade V as mortality. Length of in-patient stay (LOS) and 30-day mortality was also recorded. The pathological complete response rate was also recorded and defined as tumor regression with absence of any remaining cancer cells or positive lymph nodes following neoadjuvant therapy. The duration of stoma following index surgery, along with the rate of permanent stoma formation, were compared as covariates.
Statistical analysis
The IBM SPSS version 25.0 was used for statistical analysis. Categorical variables were presented as numbers and percentages, and comparisons between groups were performed using the Fisher’s exact test or χ2 test. Continuous variables with normal distribution were represented as mean ± SD, and a t-test was used for comparisons between groups. Continuous variables that were not normally distributed were expressed as medians (interquartile ranges), and comparisons were performed using the Mann-Whitney U test. P < 0.05 was considered statistically significant.
RESULTS
Demographics and clinicopathological characteristics
A total of 99 patients with LARC who met the inclusion criteria were enrolled between October 2014 and November 2024, including 29 in the TNT-RAPIDO group and 70 in the LCCRT group. The mean age of the subjects in the two groups were 58.2 years and 64.7 years, respectively. The two groups were comparable for body mass index, sex, ECOG PS, MRI tumor and node stage, CRM, extramural venous invasion, and pelvic sidewall nodes with no significant differences noted between the groups. The median interval from initiation of neoadjuvant therapy to surgery was significantly longer in the TNT-RAPIDO group compared to the LCCRT group (29.9 weeks vs 19 weeks, P < 0.001). Overall treatment compliance was good in the TNT-RAPIDO group; however, three patients had the fifth and sixth cycles of capecitabine and oxaliplatin omitted due to thrombocytopenia. In the same group, the sixth cycle of capecitabine and oxaliplatin was omitted in two patients due to skin complications and neuropathy. All patients in the LCCRT group completed the full course of neoadjuvant therapy. A minimally invasive approach was initially employed for all cases, with four conversions to open surgery in the LCCRT group. Table 1 summarizes the demographic and clinicopathological characteristics of patients in the two treatment groups.
Table 1 Baseline demographic and clinicopathological characteristics of patients treated with rectal cancer and preoperative induction therapy followed by dedicated operation vs standard long course chemoradiotherapy, mean ± SD/n (%).
Surgical outcomes for the TNT-RAPIDO and LCCRT groups are summarized in Table 2. Thirty-day morbidity was comparable between the two groups, 34.5% for TNT-RAPIDO and 40% for LCCRT (P = 0.656), and no postoperative mortality occurred within 30 days in either group. Operative durations were comparable between both groups, averaging 306.5 minutes for TNT-RAPIDO and 372.5 minutes for LCCRT (P = 0.111). The perioperative complication rate was low and equivalent across both cohorts, with one event reported in each group (P = 0.502). In the TNT-RAPIDO group, one patient required ureteric stenting for a diathermy injury, while in the LCCRT group, one patient required bladder repair. Although four patients in the LCCRT group required conversion to open surgery, this difference was not statistically significant compared with the TNT-RAPIDO cohort. A total of six Clavien-Dindo grade III complications were reported. Reoperation for an anastomotic leak was required in two patients from the LCCRT group and one patient from the TNT-RAPIDO group. In addition, one patient in the LCCRT group required thrombectomy for massive pulmonary embolism and two patients in the TNT group required endoscopic hemostasis for staple line bleeding. The distribution of minor complications (Clavien-Dindo grades I-II) was similar between groups, with two and five events in the TNT-RAPIDO group compared to 11 and 14 in the LCCRT group, showing no statistically significant difference in frequency. Minor complications included high stoma output, surgical site infection, chyle leak and ileus.
Table 2 Comparative surgical outcomes: Rectal cancer and preoperative induction therapy followed by dedicated operation vs standard long course chemoradiotherapy, median (interquartile range)/mean ± SD/n (%).
There was no significant difference in LOS between patients who underwent neoadjuvant LCCRT and those who received the TNT-RAPIDO protocol (9.5 vs 7 days, P = 0.279). Surgical specimen quality was consistently high regardless of neoadjuvant protocol: R0 resection was achieved in 93.1% of TNT-RAPIDO cases and 90% of LCCRT cases, while complete TME was recorded in 100% and 94.3%, respectively, differences that did not reach statistical significance. Similarly, distal resection margins were comparable between groups (3.1 cm for TNT-RAPIDO vs 3.0 cm for LCCRT; P = 0.827). Although the total number of lymph nodes harvested was significantly higher in the TNT-RAPIDO group (40.7 vs 23.4, P < 0.001), this did not correspond to an increased number of positive nodes identified (1.8 in both groups; P = 0.973). Pathological complete response was achieved in 13.8% of patients in the TNT-RAPIDO and 10.0% of those in the LCCRT group (P = 0.726). Evaluation of stoma-related outcomes revealed a significantly longer duration with stoma in the LCCRT group compared with the TNT-RAPIDO group (42.5 weeks vs 27.1 weeks, P < 0.013), as well as a higher rate of permanent stoma formation (35.7% vs 13.8%, P = 0.031).
DISCUSSION
LARC presents a persistent challenge in management due to its high risk of local recurrence and distant metastasis. The conventional treatment paradigm of LCCRT followed by TME, with optional adjuvant chemotherapy, has yielded favorable local control[18]. However, this approach has limited impact on distant metastases, which remain an important cause of treatment failure and poor overall survival[7]. In recent years, the concept of TNT, which consolidates systemic chemotherapy and radiotherapy prior to surgery, has emerged as a promising strategy to address the limitations of standard treatment[19,20]. The rationale behind TNT includes improved chemotherapy compliance, earlier eradication of micrometastatic disease, and increased pathological tumor regression, potentially enhancing both oncologic outcomes and organ preservation strategies[12-14].
Pathological complete response
Multiple studies have demonstrated that TNT is associated with reduced disease-related treatment failure and increased rates of pathological complete response rates. The TIMING trial also reported that increasing the number of consolidation chemotherapy cycles following chemoradiation was associated with higher rates of pathological complete response[12,14,21]. Interestingly, Goffredo et al[22] evaluated the impact of TNT vs neoadjuvant chemoradiation followed by adjuvant chemotherapy on overall survival, tumor downstaging, and CRM status in 8548 LARC patients. TNT resulted in higher rates of tumor downstaging but did not improve overall survival or CRM status compared with LCCRT. The pathological complete response rate in our study was 13.8%, which is comparable to previously reported rates ranging from 14%-36%[14,20,23,24]. However, no significant difference was observed between the TNT-RAPIDO and LCCRT groups in our cohort, likely due to the limited sample size.
Surgical difficulty
Despite the increasing adoption of TNT to improve oncological outcomes, uncertainty remains regarding its impact on the technical aspects of rectal surgery. The prolonged interval between radiotherapy and TME characteristic of the TNT-RAPIDO regimen (up to 24 weeks) may exacerbate pelvic fibrosis and edema, thereby complicating mesorectal excision and potentially increasing perioperative morbidity[16,17]. Findings from the GRECCAR-6 trial, the CRONOS analysis and the Timing of Rectal Cancer Response to Chemoradiation Consortium support this concern, indicating that prolonged delays to surgery may be associated with higher rates of incomplete TME specimens and increased morbidity[17,25,26]. Interestingly, updated RAPIDO trial data reported a modest increase in locoregional relapse within the TNT cohort despite improved tumor regression, potentially attributable to inferior specimen quality and increased technical challenges associated with prolonged radiation-to-surgery intervals[22].
Multiple studies have emphasized that surgical specimen quality is a critical determinant of local recurrence rates and, ultimately, overall patient outcomes. In our center’s experience, despite a significantly longer interval from initiation of neoadjuvant therapy to surgery in the TNT-RAPIDO group compared with the LCCRT group, 93.1% of patients achieved clear surgical margins and 100% had complete TME specimens, indicating no compromise in surgical quality. A significant difference in lymph node yield was also observed. TME completeness was also high in the LCCRT group (94.3%), with no significant difference in surgical specimen quality between neoadjuvant treatment strategies. These surgical results are consistent with outcomes reported in recent large series and randomized trials of patients with LARC, including studies using neoadjuvant chemoradiotherapy alone without TNT, suggesting that optimal surgical quality remains achievable despite the technical challenges posed by neoadjuvant therapy[27-31]. In another phase III trial comparing the RAPIDO protocol with LCCRT, no significant increase in perioperative morbidity was observed[32]. The favorable findings in our study may, in part, be attributed to the high proportion of robot-assisted resections (49 of 99 patients), which, as demonstrated in recent meta-analyses, facilitate greater surgical precision, particularly in patients who have received neoadjuvant therapy[33].
Early surgical outcomes
Rates of perioperative complications were similar in patients who underwent LCCRT and those who received TNT-RAPIDO. Xu et al[34] conducted a retrospective cohort study comparing the effects of TNT vs neoadjuvant chemoradiation and reported longer operative times and increased estimated blood loss in the TNT group. In our study, median operative time for the TNT-RAPIDO group was 66 minutes shorter than LCCRT, although the results did not reach statistical significance, likely due to small sample size. The conversion rate was higher in the LCCRT group; however, this was also not statistically significant.
We found that TNT-RAPIDO did not result in differences in early post-operative morbidity or LOS compared with LCCRT, with low rates of minor complications (grade I-II) in both groups and only six Clavien-Dindo grade III complications overall. Our findings are consistent with multiple studies on perioperative complications and interval to surgery from completion of radiotherapy[25,35,36]. The STARRCAT trial did not identify an increase in technical difficulty or morbidity following a 12-week interval after completion of radiotherapy[36]. Although studies like the GRECCAR-6 trial suggested an increased rate of morbidity at 11 weeks based on higher conversion rates, surgeon-reported pelvic fibrosis, and operative time, none of these differences were statistically significant[17]. Interestingly, in our study, surgical specimen quality and early surgical outcomes in the TNT-RAPIDO group were comparable to those of the LCCRT group, despite a substantially longer interval from initiation of radiotherapy to surgery compared with previous studies. This suggests that novel intensive pre-surgical treatment strategies such as TNT-RAPIDO may not significantly increase the technical difficulty of TME resection. Surgical complications have been associated with poorer quality of life, as well as reduced local recurrence-free and overall survival; therefore, balancing these risks against the oncological benefits of intensive TNT protocols is essential[37].
Stoma duration
Our results showed that the TNT-RAPIDO group had a significantly shorter total stoma duration compared with LCCRT (27.1 weeks vs 42.5 weeks, P = 0.013). Some studies support this association with earlier stoma reversal in TNT patients. A retrospective cohort study of 24 patients demonstrated a significant difference in total stoma duration of 3.6 months for the TNT group vs 6.9 months for the traditional sequence group[38]. Early systemic control without the need for adjuvant therapy and improved treatment compliance may allow for shorter total stoma durations[39]. Although beyond the scope of this study, lower stoma duration may improve psychosocial and sexual function and overall patient satisfaction, warranting future larger studies to investigate its true impact.
In the last two decades, neoadjuvant therapy has made it possible for significant downstaging and sphincter preservation for low rectal cancers[1-3]. In this study, permanent stoma rate was significantly higher in the LCCRT group compared with the TNT-RAPIDO group (35.7% vs 13.8%, P = 0.031). TNT may facilitate enhanced tumor downstaging and margin clearance compared with LCCRT with improved permanent stoma rate. However, larger studies are needed to further evaluate this. The choice of minimally invasive technique, particularly the robot-assisted approach, may have contributed to improved permanent stoma rates. In our patient cohort, RAL TME was performed for 65.5% of TNT-RAPIDO cases compared with 42.9% of LCCRT cases. Robot-assisted surgery enables more precise dissection with greater instrument flexibility and facilitates lower anastomoses compared with laparoscopic and open approaches[40]. Burghgraef et al[40] described a significant reduction in permanent stoma rates in RAL TME compared with laparoscopy in a retrospective cohort study of 1198 patients.
Limitations
Although we did not identify any differences in early surgical outcomes between TNT-RAPIDO and LCCRT patients, our study has limitations. This was a single center study design with a limited sample size; hence, further prospective research with larger sample sizes should be conducted. We recognize the possibility of type II error, which limited the statistical power to differentiate the characteristics and outcomes between both groups. The significant difference noted in lymph node yield may have been independent of treatment protocol; we recognize that sample size and study scope may have limited our ability to assess this variable. The retrospective design also poses a risk of selection bias and unobserved confounders, which may have impacted the effect estimates. A further limitation is that we were unable to measure perceived technical difficulty by the surgeon. Rather, this was based on clinicopathological measures such as specimen quality, operative time or complications. Blood loss was not included in our dataset, which could have improved our assessment of technical difficulty. While this study focused on short-term outcomes, longer follow-up with prospective randomized controlled trials in the future are warranted to more accurately assess the differences between TNT-RAPIDO and LCCRT in relation to oncological outcomes.
CONCLUSION
Despite the challenges of neoadjuvant treatment strategies such as TNT-RAPIDO, there does not appear to be an association with increased surgical difficulty compared with traditional LCCRT. The intensification of neoadjuvant protocols to pursue the treatment benefits of early systemic control, tumor downstaging and complete pathological response, does not compromise early surgical outcomes compared with LCCRT. Although multifactorial, TNT may also confer a shorter total stoma duration and lower permanent stoma rate. Further studies are warranted to fully evaluate the impact of TNT-RAPIDO on long-term surgical and oncological outcomes.
ACKNOWLEDGEMENTS
The authors thank all the staff members of our institution.
Footnotes
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Oncology
Country of origin: Singapore
Peer-review report’s classification
Scientific Quality: Grade C
Novelty: Grade B
Creativity or Innovation: Grade B
Scientific Significance: Grade C
P-Reviewer: Cavallaro A, PhD, Professor, Italy S-Editor: Zuo Q L-Editor: Filipodia P-Editor: Xu J
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