Impact of the timing of additional surgery after noncurative endoscopic resection of early colorectal cancer on perioperative and oncological outcomes: a single-center retrospective cohort study

Shuhua Zhuo; Yijuan Liu; Kaiyan Wei; Jiantao Zheng; Lin Zhang

doi:10.3393/ac.2025.01319.0188

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Original Article Colorectal cancer Impact of the timing of additional surgery after noncurative endoscopic resection of early colorectal cancer on perioperative and oncological outcomes: a single-center retrospective cohort study: Shuhua Zhuo^1,2, Yijuan Liu^3,4, Kaiyan Wei^3,4, Jiantao Zheng^1,2, Lin Zhang^1,2; Annals of Coloproctology 2026;42(3):345-354.
DOI: https://doi.org/10.3393/ac.2025.01319.0188
Published online: June 26, 2026

¹Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China

²Department of Gastrointestinal Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China

³Department of Gastroenterology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China

⁴Department of Gastroenterology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China

Correspondence to: Lin Zhang, MMed Department of Gastrointestinal Surgery, First Affiliated Hospital of Fujian Medical University, 20 Chazhong Rd, Fuzhou 350005, China Email: freezhanglin915@163.com

• Received: November 2, 2025 • Revised: December 20, 2025 • Accepted: January 25, 2026

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract
INTRODUCTION
METHODS
RESULTS
DISCUSSION
ARTICLE INFORMATION
SUPPLEMENTARY MATERIALS
REFERENCES

Abstract

Purpose
For early colorectal cancer (CRC) following noncurative endoscopic resection, additional curative surgery is the standard of care, but the optimal timing remains unclear. This study investigated the effect of the interval between procedures on surgical complexity, complications, and oncological outcomes.
Methods
This retrospective study included 112 patients with early CRC who underwent additional laparoscopic surgery after noncurative endoscopic resection between August 2019 and August 2024. Clinical and pathological data were collected, with primary endpoints focused on surgical difficulty (operative duration and intraoperative blood loss). Statistical analyses were performed using multivariate analysis of variance, logistic regression, and receiver operating characteristic curve analysis.
Results
The interval between procedures was not significantly associated with surgical difficulty or lymph node metastasis (P>0.05). Multivariate analysis did not identify an optimal timing point for surgery. However, a longer waiting time was independently associated with an increased risk of residual tumor (odds ratio, 1.09; 95% confidence interval, 1.03–1.16; P=0.004). Furthermore, lymphovascular invasion and elevated preoperative carcinoembryonic antigen levels were identified as independent predictors of lymph node metastasis. A higher preoperative lymphocyte ratio was associated with an increased risk of postoperative intra-abdominal infection (r=0.243, P=0.010).
Conclusion
In the era of laparoscopic surgery, the timing of additional surgery does not appear to be the primary determinant of surgical difficulty in CRC. Clinical decision-making should prioritize high-risk pathological features, such as lymphovascular invasion, rather than rigid adherence to a predetermined waiting period. Strategically delaying surgery may facilitate the selection of patients without residual disease, thereby helping to avoid unnecessary procedures.
Keywords: Colorectal neoplasms; Noncurative endoscopic resection; Additional surgery; Timing of surgery; Lymphatic metastasis

INTRODUCTION

Colorectal cancer (CRC) represents a major global public health challenge and remains among the leading causes of cancer-related morbidity and mortality worldwide. According to the latest epidemiological data from GLOBOCAN, CRC is the third most commonly diagnosed cancer, accounting for approximately 10% of all new cancer cases globally. Furthermore, CRC has the second-highest mortality burden, contributing to 9.4% of global cancer-related deaths. These statistics underscore CRC as a high-incidence, high-mortality malignancy [1]. With the widespread implementation of CRC screening programs and continuous advances in endoscopic technologies, the detection rate of early-stage CRC and precancerous lesions has improved substantially. In this context, endoscopic resection has emerged as the preferred treatment for early-stage CRC and high-grade dysplastic lesions owing to its minimally invasive nature, rapid recovery, short hospital stay, low complication risk, and favorable cost-effectiveness [2, 3]. However, 10% to 20% of cases are classified as "noncurative resections" on postoperative pathological evaluation because of the potential risk of residual tumor or lymph node metastasis, thereby necessitating additional curative surgery.

In the setting of early gastric cancer, numerous studies have explored the importance of timing for additional surgery, suggesting an "optimal time window" that balances surgical difficulty and tumor risk [4, 5]. It is generally accepted that surgery performed too early may increase technical difficulty because of post-endoscopic inflammatory edema and fibrosis, whereas surgery performed too late may allow tumor progression [6, 7]. However, given the fundamental differences between the stomach and colon in embryological origin, anatomical structure, physiological environment, and tissue repair mechanisms, it is inappropriate to extrapolate findings from gastric cancer directly to CRC. At present, high-quality studies examining the timing of additional surgery following noncurative endoscopic resection of CRC are limited, and conclusions remain inconclusive.

Moreover, modern colorectal surgery has entered the era of minimally invasive techniques, with laparoscopy representing a key innovation. The magnified visualization and precision afforded by laparoscopy may alter the effect of tissue edema and adhesions on surgical difficulty. Therefore, it is essential to reassess the role of surgical timing within the contemporary laparoscopic context.

This study aimed to systematically evaluate the relationship between the interval to additional surgery and perioperative outcomes (including surgical difficulty and postoperative complications) as well as oncological outcomes (including residual tumor and lymph node metastasis) following noncurative endoscopic resection of early CRC, based on a single-center retrospective cohort analysis. The findings are intended to provide evidence for optimizing clinical decision-making.

METHODS

Ethics statement

This study was approved by the Ethics Committee of the First Affiliated Hospital of Fujian Medical University (No. [2015]084-3). Written informed consent was obtained from all patients prior to the study.

Study design and patient selection

All CRC patients who underwent endoscopic resection between August 2019 and August 2024 were retrospectively reviewed. The inclusion criteria were as follows: (1) postoperative pathological confirmation of early CRC (pT1); (2) fulfillment of predefined noncurative resection criteria; and (3) subsequent curative laparoscopic surgery. Exclusion criteria included the following: (1) synchronous multiple primary cancers; (2) prior history of colorectal surgery; and (3) missing key data. A total of 112 patients were included in the final analysis. The patient selection process is illustrated in Fig. 1.

Definition of noncurative resection

According to the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines [8] and the Chinese expert consensus [9], noncurative resection is defined by the presence of at least one of the following conditions: (1) positive vertical margin (R1v); (2) submucosal invasion depth ≥1,000 µm; (3) lymphovascular invasion; (4) poorly differentiated adenocarcinoma, signet-ring cell carcinoma, or mucinous adenocarcinoma; (5) tumor budding grade (Bd 2–3); or (6) inability to assess the specimen.

Data collection and variable definition

Surgical difficulty, as a multifaceted concept, was indirectly assessed through surrogate indicators, including operative duration and intraoperative blood loss. By identifying the time points with the largest differences in surgical difficulty, patients were stratified into early and late surgery groups. Perioperative parameters and oncological outcomes were subsequently compared between the 2 groups. To minimize the confounding influence of surgeon-specific variables, all procedures were performed by senior chief surgeons with extensive clinical experience.

The following data were extracted from the electronic medical records: (1) baseline characteristics (age, sex, body mass index [BMI], comorbidities); (2) endoscopic features (resection technique, lesion size, location); (3) surgical variables (surgical interval [defined as the number of days between the endoscopic resection and the additional surgery], operative duration [from skin incision to skin closure], intraoperative estimated blood loss]); (4) pathological outcomes (residual tumor, lymph node metastasis status, high-risk pathological features); and (5) postoperative outcomes (complications [with a particular focus on intra-abdominal infection], recovery indicators [time to first liquid intake and length of postoperative hospital stay], Basel index scores on postoperative days 3 and 8).

Statistical analysis

Categorical variables are presented as frequency (percentage) and were compared between groups using the chi-square test or the Fisher exact test. Normally distributed continuous variables are expressed as mean±standard deviation and were compared using the t-test or one-way analysis of variance (ANOVA). Non-normally distributed variables are presented as median (interquartile range, IQR) and were compared using the Mann-Whitney U-test or Kruskal-Wallis H-test. Pearson or Spearman method was used for correlation analysis. Multivariate ANOVA (MANOVA) and principal component analysis were used to evaluate the combined effect of the surgical interval on surgical difficulty (operative duration and blood loss). Multiple linear regression analysis identified independent factors associated with operative time and blood loss. Univariate (Firth penalized logistic regression) and multivariate logistic regression models were employed to identify risk factors for lymph node metastasis. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff value for predicting the lymphocyte ratio. The robustness of the results was evaluated through sensitivity analysis and permutation test. All statistical analyses were conducted using R ver. 4.5.3 (R Foundation for Statistical Computing), with a 2-sided P-value of <0.05 considered statistically significant.

RESULTS

Baseline and pathological characteristics of patients

A total of 112 patients were included in this study. The mean age was 60.42±8.71 years, with a male predominance (65.2%). Endoscopic submucosal dissection was the predominant endoscopic treatment method (80.4%). Lesions were most commonly located in the rectum (40.2%) and sigmoid colon (39.3%). Post-endoscopic pathological evaluation revealed that the most frequent high-risk factors were deep submucosal invasion (≥1,000 µm; 41.1%), positive vertical margin (27.7%), and lymphovascular invasion (14.3%). All patients successfully underwent subsequent laparoscopic surgery, with a median surgical interval of 20 days (IQR, 15–24.25 days). Following additional surgery, the residual tumor and lymph node metastasis rates were 11.6% (13 of 112) and 10.7% (12 of 112), respectively. Baseline characteristics and surgical outcomes are presented in Table 1.

Surgical timing and surgical difficulty

The mean operative duration for all patients was 165.29±48.19 minutes, with a mean intraoperative blood loss of 55.36±60.98 mL. A weak positive correlation was observed between operative duration and intraoperative blood loss (r=0.183, P=0.053). Principal component analysis was employed to synthesize these 2 variables into a composite "surgical difficulty score." The first principal component explained 59.2% of the total variance (loadings: operative duration, 0.707; intraoperative blood loss, 0.707). Following directional correction, higher scores indicated greater surgical difficulty.

To account for potential confounders, multiple linear regression analysis was performed, adjusting for patient age, BMI, prior abdominal surgeries, primary surgeon, lesion location, and surgical approach. The surgical interval was not significantly associated with the surgical difficulty score (β=0.006; 95% confidence interval [CI], −0.012 to 0.024; P=0.492).

To further validate these findings, MANOVA was conducted, treating operative duration and blood loss as the combined dependent variables. The results indicated that a surgical interval of 15 days had the greatest effect on surgical difficulty; however, this effect was not statistically significant (Pillai trace, 0.031; P=0.182). No "optimal timing point," analogous to those reported in gastric cancer studies, was identified. Fig. 2 illustrates the scatter distribution and fitted trend between surgical interval and difficulty indicators, providing additional support for this finding.

Using the 15-day threshold, which corresponded to the largest difference in surgical difficulty, patients were divided into early and late surgery groups. No statistically significant differences were observed between the 2 groups in age, sex, BMI, comorbidities, postoperative complications, or oncological outcomes (all P>0.05) (Supplementary Table 1). The median follow-up duration for the early surgery group was 28.6 months (range, 2–75 months) and 32.5 months (range, 0–75.8 months) for the late surgery group. The overall median follow-up time was 31 months (range, 0–75.8 months). During the follow-up period, 1 patient (0.9%) experienced distant recurrence, and 2 patients (1.8%) died from postoperative complications. The surgical interval did not significantly affect recurrence-free survival, as illustrated in Fig. 3.

Surgical timing and oncological outcomes

Postoperative pathological analysis following additional surgery revealed a residual tumor rate of 11.6% (13 of 112). Univariable analysis identified significant associations between residual tumor and both surgical interval (P<0.001) and surgical approach (P=0.019). However, no significant differences were found between the 2 groups in age, sex, tumor invasion depth, lymphovascular invasion, neural invasion, tumor differentiation, margin status, or lymph node metastasis (all P>0.05), as detailed in Table 2.

To address small-sample-size bias and complete separation issues, Firth penalized logistic regression was employed for multivariate analysis. After adjusting for age and sex, Firth regression analysis revealed that each additional day of surgical interval was associated with a 9.3% increase in the risk of residual tumor (adjusted odds ratio [OR], 1.09; 95% CI, 1.03–1.16; P=0.004). Sensitivity analyses consistently supported the statistical significance of this association (permutation test P<0.001; bootstrap method 95% CI, 1.031–1.165).

Notably, after adding surgical approach and other potential confounders to the model, the surgical interval remained an independent predictor of residual tumor, and no significant interactions were detected with major pathological features (all P>0.05).

The overall postoperative lymph node metastasis (LNM) rate was 10.7% (12 of 112). Among the 12 patients with LNM, 5 (41.7%) exhibited lymphovascular invasion, compared with 11% of the LNM-negative patients (11 of 100 patients) (Supplementary Table 2). Univariate Firth regression analysis indicated that lymphovascular invasion (OR, 5.71; 95% CI: 1.56–20.27; P=0.010) and preoperative carcinoembryonic antigen (CEA) levels (per 1 standard deviation increase: OR, 1.74; 95% CI, 1.12–2.93; P=0.014) were significantly associated with LNM.

In the multivariate full-variable model, after adjusting for other factors, lymphovascular invasion (adjusted OR, 7.66; 95% CI, 1.94–34.11; P=0.004) and CEA (adjusted OR, 1.73; 95% CI, 1.03–3.61; P=0.039) retained independent predictive value for LNM, as detailed in Table 3.

To explore whether surgical timing affected LNM risk, subgroup analyses were performed based on the presence of high-risk features (positive vertical margin or lymphovascular invasion). As shown in Fig. 4, no significant positive correlations were observed between surgical interval and LNM in any subgroup (P>0.05).

Postoperative complications and recovery

The overall incidence of postoperative complications was 18.8% (n=21), with intra-abdominal infection being the most common (n=11, 9.8%). Univariable analysis showed a positive correlation between the preoperative peripheral blood lymphocyte ratio (lymphocyte count to total white blood cell count) and the risk of postoperative intra-abdominal infection (r=0.243, P=0.010) (Supplementary Table 3). The ROC curve analysis yielded an area under the curve of 0.732 (95% CI, 0.549–0.915) for predicting intra-abdominal infection, with an optimal cutoff value of 37.7%.

Regarding postoperative recovery, no significant differences were observed between the early and late surgery groups in time to first liquid intake, the Barthel index scores on postoperative day 3, or postoperative hospital stay duration (Supplementary Table 4). However, among patients with a waiting period exceeding 28 days, a few cases of poor recovery (severe dependence) were noted on postoperative day 8.

DISCUSSION

This study systematically evaluated the effect of surgical timing on perioperative and oncological outcomes following noncurative endoscopic resection of early CRC. Unlike the widely discussed "optimal surgical window" in early gastric cancer, no significant correlation was observed between the surgical interval and laparoscopic surgical difficulty (operative duration or intraoperative blood loss) or LNM rate. This finding challenges the traditional assumption that early postoperative edema and inflammatory response increase surgical difficulty. Notably, an extended surgical interval emerged as an independent risk factor for residual tumor in patients undergoing additional surgery (adjusted OR, 1.09; 95% CI, 1.03–1.16; P=0.004). Furthermore, lymphovascular invasion (adjusted OR, 7.66; 95% CI, 1.94–34.11; P=0.004) and preoperative CEA levels (adjusted OR, 1.73; 95% CI, 1.03–3.61; P=0.039) were identified as independent predictors of LNM, while a higher preoperative lymphocyte ratio was associated with an increased risk of postoperative intra-abdominal infection.

Gastrointestinal ulcer healing is a complex pathophysiological process involving cellular migration, proliferation, re-epithelialization, angiogenesis, and extracellular matrix remodeling, all regulated by various growth factors, transcription factors, and cytokines [10]. Studies have demonstrated that key genes involved in ulcer healing are activated primarily within 14 days after the injury [11]. Animal experiments have further confirmed that approximately 14 days after endoscopic mucosal resection, inflammation at the mucosal defect site substantially subsides, re-epithelialization is largely complete, crypt structures begin to regenerate, and mucosal folds tend to normalize [12]. These findings suggest that the first 2 weeks following endoscopic resection represent the active phase of tissue repair. However, in this study, even when additional laparoscopic surgery was performed during this early postoperative period (≤15 days), during the phase of most pronounced inflammatory response, no significant increase in surgical difficulty was observed. This finding contrasts with studies on early gastric cancer, and several potential explanations are proposed. First, gastric and colorectal tissues differ fundamentally in embryonic origin, local microenvironment, and repair mechanisms. Gastric mucosa is continuously exposed to a highly acidic and mechanically stressed environment, necessitating proton pump inhibitors and other agents to suppress acid secretion and accelerate healing [13, 14]. In contrast, the colorectal mucosa relies on multiple protective barriers (including the mucus layer, epithelial tight junctions, and mucosal immunity) and involves a more complex interplay of cellular interactions, immune regulation, and microbial balance, resulting in more diffuse and prolonged inflammation and edema [15]. Consequently, a concentrated "inflammatory peak" analogous to that observed in the stomach may not occur in the colon. Second, the widespread adoption of laparoscopic techniques may be a key factor. The magnified view and precise operative capabilities of laparoscopic surgery enable surgeons to clearly identify and safely dissect early edema and adhesions, overcoming the tissue dissection challenges that previously arose during open surgery [16]. All patients in this study successfully underwent laparoscopic procedures, which likely attenuated the effect of surgical timing on technical difficulty.

A noteworthy finding is the association between prolonged surgical waiting time and an increased risk of residual tumor in additional surgical specimens. Although the effects of electrocautery, local ischemia, or subsequent immune responses following endoscopic resection may contribute to the degradation of residual tumor cells [17], extended waiting periods may afford the tumor opportunities for continued growth, infiltration, and micrometastasis. During this time, remaining small lesions may undergo biological behavioral changes that further complicate surgical management. This study also found a higher residual tumor rate following sigmoid colon resection, which may be attributable to the significant positional variation, morphological diversity, and vascular anomalies characteristic of the sigmoid colon. Compared with other sites, laparoscopic radical surgery for sigmoid colon cancer presents unique technical challenges [18]. For these patients, meticulous preoperative tumor localization and careful intraoperative technique are essential.

Consistent with previous studies [19, 20], our findings confirmed that lymphovascular invasion is an independent predictor of LNM. Therefore, clinical decisions should primarily consider the presence of lymphovascular invasion rather than rigid adherence to a fixed surgical interval. Even in high-risk subgroups, such as those with lymphovascular invasion, appropriately delaying surgery was not significantly associated with an increased risk of LNM. This may be related to the overall low incidence of LNM in early CRC (10.7% in our study), which provides a window for comprehensive preoperative preparation and patient counseling [21]. The predictive value of CEA was also evaluated. Consistent with previous reports [22–24], our data demonstrated a significant association between CEA levels and LNM. CEA may serve as a valuable adjunctive marker that, when combined with other high-risk pathological features, can aid in the clinical assessment of LNM risk.

Regarding postoperative complications, a correlation was observed between the preoperative lymphocyte ratio and the risk of intra-abdominal infection. This finding suggests that preoperative immune-inflammatory status may be an important factor in determining postoperative susceptibility to infection. Similar to systemic inflammatory markers (e.g., neutrophil to lymphocyte ratio and platelet to lymphocyte ratio) widely used to predict infectious complications [25, 26], the lymphocyte ratio is a simple and readily available indicator that may help identify high-risk patients before surgery, providing a basis for targeted preventive measures such as enhanced intraoperative irrigation or optimized antibiotic regimens. Changes in lymphocyte count may also be influenced by nutritional status, medication use, and active inflammatory conditions; further exploration of these associations may be warranted. Regarding postoperative recovery, evaluation of patients' activities of daily living using the Barthel index [27] revealed no significant differences in early recovery parameters, including time to first liquid intake and length of postoperative hospitalization, across different surgical timing groups. However, among patients with a waiting period exceeding 28 days, a few cases of poor recovery (manifesting as severe dependency) were observed on postoperative day 8. This phenomenon may be attributable to the psychological stress and physiological deconditioning experienced during prolonged waiting periods, representing an important consideration for clinical management.

Based on these findings, the following clinical practice recommendations are proposed:

(1) Individualized surgical timing decisions: Excessive concern about early postoperative surgical difficulty is unwarranted, particularly in centers with established laparoscopic expertise. Decisions should prioritize high-risk pathological features, especially lymphovascular invasion.

(2) Optimization of preoperative preparation pathways: Surgical protocols should be refined, waiting times reduced, and expedited surgical pathways established to minimize the risk of residual tumor and enhance patient outcomes.

(3) Monitoring of preoperative inflammatory status: Patients with a preoperative lymphocyte ratio >37.7% should be carefully assessed for intra-abdominal infection risk, with enhanced perioperative management.

(4) Psychological and rehabilitation support for patients with prolonged waiting periods: Patients with waiting times exceeding 4 weeks should receive nutritional support and psychological counseling to promote recovery.

Limitations

This study has several limitations. First, the retrospective design may introduce selection and information biases. Second, the number of patients undergoing additional surgery was relatively small, limiting the statistical power, particularly in subgroups such as those with lymphovascular invasion or postoperative intra-abdominal infection. Third, long-term oncological outcomes, such as 5-year overall survival, were not available, precluding evaluation of long-term efficacy. Additionally, missing data in some cases prevented the inclusion of other potential prognostic factors (e.g., immunohistochemistry-based tumor budding grade) in the analysis.

These limitations also suggest directions for future research, including multicenter, prospective cohort studies with larger sample sizes and longer follow-up periods. Such studies could incorporate more comprehensive prognostic factors to further validate the conclusions presented here.

Conclusions

In the era of laparoscopic surgery, for early-stage CRC following noncurative endoscopic resection, the timing of additional surgery does not constitute a key determinant of surgical difficulty or postoperative complications. In fact, prolonged surgical intervals may increase the risk of residual tumor. Clinical decision-making should prioritize risk stratification based on high-risk pathological features, particularly lymphovascular invasion, rather than rigid adherence to fixed waiting periods.

ARTICLE INFORMATION

Conflict of interest

No potential conflict of interest relevant to this article was reported.

Funding

This study was supported by the Natural Science Foundation of Fujian Province (No. 2024J01124033).

Author contributions

Conceptualization: SZ, LZ; Data curation: YL, KW; Formal analysis: JZ; Funding acquisition: LZ; Investigation: SZ, YL; Methodology: Kaiyan Wei, JZ, LZ; Project administration: JZ; Supervision: LZ; Validation: SZ, YL; Visualization: JZ; Writing–original draft: SZ, YL; Writing–review & editing: all authors. All authors read and approved the final manuscript.

SUPPLEMENTARY MATERIALS

Supplementary Table 1.

Baseline characteristics of patients stratified by surgical interval

ac-2025-01319-0188-Supplementary-Table-1.pdf

Supplementary Table 2.

Baseline clinical and pathological characteristics according to LNM presence

ac-2025-01319-0188-Supplementary-Table-2.pdf

Supplementary Table 3.

Univariable analysis of factors associated with postoperative intra-abdominal infection

ac-2025-01319-0188-Supplementary-Table-3.pdf

Supplementary Table 4.

Postoperative recovery outcomes stratified by surgical interval

ac-2025-01319-0188-Supplementary-Table-4.pdf

Supplementary materials are available from https://doi.org/10.3393/ac.2025.01319.0188.

Fig. 1.

Patient recruitment flowchart.

Fig. 2.

The time interval point, at which the operative time and the intraoperative blood loss of the earlier operation group and the later operation group showed the greatest disparities, was evaluated using multivariate analysis of variance.

Fig. 3.

Recurrence-free rate curve according to interval time point, 15 days between endoscopic resection and additional surgery (P=0.287).

Fig. 4.

Relationship between surgical interval time and lymph node metastasis rate. (A) Low-risk group. (B) High-risk group.

Table 1.

Baseline clinicopathological characteristics and surgical outcomes (n=112)

Characteristic	Value
Age (yr)	60.42±8.71
Sex
Male	73 (65.2)
Female	39 (34.8)
Body mass index (kg/m²)	23.84 (22.20–25.73)
Heavy smoking history	21 (18.8)
Long-term alcohol history	7 (6.3)
Diabetes	19 (17.0)
Hypertension	36 (32.1)
Previous abdominal surgery	18 (16.1)
Tumor marker
CEA (ng/mL)	1.87 (1.27–2.7)
AFP (ng/mL)	2.54 (1.84–3.64)
CA19-9 (U/mL)	9.73 (5.94–16.18)
Surgical procedure
Right hemicolectomy	56 (50.0)
Left hemicolectomy	17 (15.2)
Sigmoidectomy	25 (22.3)
Radical proctectomy	14 (12.5)
Stoma creation	19 (17.0)
Surgical interval (day)	20 (15.0–24.25)
Operative time (min)	153.5 (120.0–197.25)
Intraoperative blood loss (mL)	50 (20–50)
Postoperative hospital stay (day)	7 (6–9)
Overall postoperative complication	21 (18.8)
Postoperative intra-abdominal infection	11 (9.8)
Lymphocyte ratio (%)	32.01±7.77
Endoscopic resection method
Endoscopic submucosal dissection	90 (80.4)
Endoscopic mucosal resection	15 (13.4)
Snare polypectomy	7 (6.3)
Lesion location
Ascending colon	12 (10.7)
Transverse colon	7 (6.3)
Descending colon	4 (3.6)
Sigmoid colon	44 (39.3)
Rectum	45 (40.2)
Preoperative localization method
Carbon nanoparticle	78 (69.6)
Titanium clip	30 (26.8)
Indocyanine green	4 (3.6)
Endoscopic resection pathology
Maximum tumor diameter (cm)	1.9 (1.3–2.5)
Lymphovascular invasion	16 (14.3)
Perineural invasion	1 (0.9)
Resection margin status
Positive horizontal margin	12 (10.7)
Positive vertical margin	31 (27.7)
Invasion depth ≥1,000 µm	46 (41.1)
Histological type
Adenocarcinoma	107 (95.5)
Mucinous adenocarcinoma	2 (1.8)
Signet-ring cell carcinoma	1 (0.9)
Neuroendocrine tumor	2 (1.8)
Tumor differentiation
Well	7 (6.3)
Moderate	90 (80.4)
Poor	15 (13.4)
Tumor budding grade 2–3	3 (2.7)
Postoperative pathology
Maximum tumor diameter (cm)	1.5 (1–2)
Residual tumor	13 (11.6)
No. of lymph nodes retrieved	19

Values are presented as mean±standard deviation, median (interquartile range), or number (%), unless otherwise indicated.

CEA, carcinoembryonic antigen; AFP, α-fetoprotein; CA19-9, carbohydrate antigen 19-9.

Table 2.

Association between clinical and pathological variables and residual tumor (n=112)

Variable	Residual tumor		P-value
Variable	No (n=99)	Yes (n=13)	P-value
Endoscopic resection pathology
Depth of invasion			0.473
SM1	56 (56.6)	10 (76.9)
SM2	40 (40.4)	3 (23.1)
SM3	3 (3.0)	0 (0)
Lymphovascular invasion			0.689
No	84 (84.8)	12 (92.3)
Yes	15 (15.2)	1 (7.7)
Tumor differentiation			>0.999
Poor	13 (13.1)	2 (15.4)
Well	7 (7.1)	0 (0)
Moderate	79 (79.8)	11 (84.6)
Horizontal margin positive			0.145
No	90 (90.9)	10 (76.9)
Yes	9 (9.1)	3 (23.1)
Vertical margin positive			0.344
No	73 (73.7)	8 (61.5)
Yes	26 (26.3)	5 (38.5)
Lymph node metastasis			0.145
No	90 (90.9)	10 (76.9)
Yes	9 (9.1)	3 (23.1)
Demographic
Age (yr)	60 (55–66)	60 (55–70)	0.778
Sex			0.059
Male	68 (68.7)	5 (38.5)
Female	31 (31.3)	8 (61.5)
Clinical feature
Body mass index (kg/m²)	24.03 (22.31–25.88)	22.77 (21.88–24.20)	0.099
Diabetes			0.230
No	84 (84.8)	9 (69.2)
Yes	15 (15.2)	4 (30.8)
Hypertension			0.544
No	66 (67.0)	10 (77.0)
Yes	33 (33.3)	3 (23.1)
Previous abdominal surgery			0.219
No	85 (85.9)	9 (69.2)
Yes	14 (14.1)	4 (30.8)
Time to surgery (day)	12 (9–17)	21 (16–25)	<0.001^*
Surgical variable
Operative time (min)	165 (120–199)	145 (130–150)	0.147
Intraoperative blood loss (mL)	50 (20–50)	30 (20–100)	0.888
Stoma creation	17 (17.2)	2 (15.4)	>0.999
Lesion location			0.162
Transverse colon	6 (6.1)	1 (7.7)
Descending colon	4 (4.0)	0 (0)
Ascending colon	9 (9.1)	3 (23.1)
Sigmoid colon	37 (37.4)	7 (53.8)
Rectum	43 (43.4)	2 (15.4)
Type of surgery			0.019^*
Sigmoidectomy	20 (20.2)	5 (38.5)
Right hemicolectomy	13 (13.1)	4 (30.8)
Radical proctectomy	54 (54.5)	2 (15.4)
Left hemicolectomy	12 (12.1)	2 (15.4)

Values are presented as number (%) or median (interquartile range). P-values were derived from the Fisher exact test for categorical variables and the Wilcoxon rank sum test for continuous variables.

SM, submucosal.

^*P<0.05.

Table 3.

Univariate and multivariate Firth penalized regression for LNM prediction

Factor	Univariate analysis		Multivariate analysis
Factor	OR (95% CI)	P-value	aOR (95% CI)	P-value
Lymphovascular invasion
No	1 (Reference)		1 (Reference)
Yes	5.71 (1.56–20.27)	0.010^*	7.66 (1.94–34.11)	0.004^*
Preoperative CEA level (per 1 SD increase)	1.74 (1.12–2.93)	0.014^*	1.73 (1.03–3.61)	0.039^*
Residual tumor
No	1 (Reference)		1 (Reference)
Yes	3.18 (0.71–12.06)	0.123	3.45 (0.48–22.83)	0.204
Positive vertical margin
No	1 (Reference)		1 (Reference)
Yes	2.06 (0.60–6.73)	0.241	1.95 (0.45–8.13)	0.359
Tumor differentiation (per 1 grade decrease^a)	1.75 (0.45–6.23)	0.409	2.81 (0.54–14.91)	0.216
Depth of invasion
SM1	1 (Reference)		1 (Reference)
SM2–SM3	1.05 (0.31–3.37)	0.933	1.28 (0.31–5.55)	0.733
Positive horizontal margin
No	1 (Reference)		1 (Reference)
Yes	1.02 (0.10–4.95)	0.987	0.57 (0.05–3.84)	0.590
Time to surgery (day) (per 1 SD increase)	1.18 (0.65–1.83)	0.521	1.32 (0.74–2.21)	0.292

Analyses used Firth's bias-reduced penalized-likelihood method to account for the low LNM event rate (10.7%). The multivariate full model (n=109) included all listed variables + AFP and CA19-9 (both nonsignificant (Supplementary Table 3).

LNM, lymph node metastasis; OR, odds ratio; CI, confidence interval; aOR, adjusted odds ratio; CEA, carcinoembryonic antigen; SD, standard deviation; SM, submucosal; AFP, α-fetoprotein; CA19-9, carbohydrate antigen 19-9.

^aDifferentiation treated ordinally (well=1, moderate=2, poor=3).

^*P<0.05.

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Impact of the timing of additional surgery after noncurative endoscopic resection of early colorectal cancer on perioperative and oncological outcomes: a single-center retrospective cohort study

Ann Coloproctol. 2026;42(3):345-354. Published online June 26, 2026

DOI: https://doi.org/10.3393/ac.2025.01319.0188

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Impact of the timing of additional surgery after noncurative endoscopic resection of early colorectal cancer on perioperative and oncological outcomes: a single-center retrospective cohort study

Fig. 1. Patient recruitment flowchart.

Fig. 2. The time interval point, at which the operative time and the intraoperative blood loss of the earlier operation group and the later operation group showed the greatest disparities, was evaluated using multivariate analysis of variance.

Fig. 3. Recurrence-free rate curve according to interval time point, 15 days between endoscopic resection and additional surgery (P=0.287).

Fig. 4. Relationship between surgical interval time and lymph node metastasis rate. (A) Low-risk group. (B) High-risk group.

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Impact of the timing of additional surgery after noncurative endoscopic resection of early colorectal cancer on perioperative and oncological outcomes: a single-center retrospective cohort study

Characteristic	Value
Age (yr)	60.42±8.71
Sex
Male	73 (65.2)
Female	39 (34.8)
Body mass index (kg/m²)	23.84 (22.20–25.73)
Heavy smoking history	21 (18.8)
Long-term alcohol history	7 (6.3)
Diabetes	19 (17.0)
Hypertension	36 (32.1)
Previous abdominal surgery	18 (16.1)
Tumor marker
CEA (ng/mL)	1.87 (1.27–2.7)
AFP (ng/mL)	2.54 (1.84–3.64)
CA19-9 (U/mL)	9.73 (5.94–16.18)
Surgical procedure
Right hemicolectomy	56 (50.0)
Left hemicolectomy	17 (15.2)
Sigmoidectomy	25 (22.3)
Radical proctectomy	14 (12.5)
Stoma creation	19 (17.0)
Surgical interval (day)	20 (15.0–24.25)
Operative time (min)	153.5 (120.0–197.25)
Intraoperative blood loss (mL)	50 (20–50)
Postoperative hospital stay (day)	7 (6–9)
Overall postoperative complication	21 (18.8)
Postoperative intra-abdominal infection	11 (9.8)
Lymphocyte ratio (%)	32.01±7.77
Endoscopic resection method
Endoscopic submucosal dissection	90 (80.4)
Endoscopic mucosal resection	15 (13.4)
Snare polypectomy	7 (6.3)
Lesion location
Ascending colon	12 (10.7)
Transverse colon	7 (6.3)
Descending colon	4 (3.6)
Sigmoid colon	44 (39.3)
Rectum	45 (40.2)
Preoperative localization method
Carbon nanoparticle	78 (69.6)
Titanium clip	30 (26.8)
Indocyanine green	4 (3.6)
Endoscopic resection pathology
Maximum tumor diameter (cm)	1.9 (1.3–2.5)
Lymphovascular invasion	16 (14.3)
Perineural invasion	1 (0.9)
Resection margin status
Positive horizontal margin	12 (10.7)
Positive vertical margin	31 (27.7)
Invasion depth ≥1,000 µm	46 (41.1)
Histological type
Adenocarcinoma	107 (95.5)
Mucinous adenocarcinoma	2 (1.8)
Signet-ring cell carcinoma	1 (0.9)
Neuroendocrine tumor	2 (1.8)
Tumor differentiation
Well	7 (6.3)
Moderate	90 (80.4)
Poor	15 (13.4)
Tumor budding grade 2–3	3 (2.7)
Postoperative pathology
Maximum tumor diameter (cm)	1.5 (1–2)
Residual tumor	13 (11.6)
No. of lymph nodes retrieved	19

Variable	Residual tumor		P-value
Variable	No (n=99)	Yes (n=13)	P-value
Endoscopic resection pathology
Depth of invasion			0.473
SM1	56 (56.6)	10 (76.9)
SM2	40 (40.4)	3 (23.1)
SM3	3 (3.0)	0 (0)
Lymphovascular invasion			0.689
No	84 (84.8)	12 (92.3)
Yes	15 (15.2)	1 (7.7)
Tumor differentiation			>0.999
Poor	13 (13.1)	2 (15.4)
Well	7 (7.1)	0 (0)
Moderate	79 (79.8)	11 (84.6)
Horizontal margin positive			0.145
No	90 (90.9)	10 (76.9)
Yes	9 (9.1)	3 (23.1)
Vertical margin positive			0.344
No	73 (73.7)	8 (61.5)
Yes	26 (26.3)	5 (38.5)
Lymph node metastasis			0.145
No	90 (90.9)	10 (76.9)
Yes	9 (9.1)	3 (23.1)
Demographic
Age (yr)	60 (55–66)	60 (55–70)	0.778
Sex			0.059
Male	68 (68.7)	5 (38.5)
Female	31 (31.3)	8 (61.5)
Clinical feature
Body mass index (kg/m²)	24.03 (22.31–25.88)	22.77 (21.88–24.20)	0.099
Diabetes			0.230
No	84 (84.8)	9 (69.2)
Yes	15 (15.2)	4 (30.8)
Hypertension			0.544
No	66 (67.0)	10 (77.0)
Yes	33 (33.3)	3 (23.1)
Previous abdominal surgery			0.219
No	85 (85.9)	9 (69.2)
Yes	14 (14.1)	4 (30.8)
Time to surgery (day)	12 (9–17)	21 (16–25)	<0.001^*
Surgical variable
Operative time (min)	165 (120–199)	145 (130–150)	0.147
Intraoperative blood loss (mL)	50 (20–50)	30 (20–100)	0.888
Stoma creation	17 (17.2)	2 (15.4)	>0.999
Lesion location			0.162
Transverse colon	6 (6.1)	1 (7.7)
Descending colon	4 (4.0)	0 (0)
Ascending colon	9 (9.1)	3 (23.1)
Sigmoid colon	37 (37.4)	7 (53.8)
Rectum	43 (43.4)	2 (15.4)
Type of surgery			0.019^*
Sigmoidectomy	20 (20.2)	5 (38.5)
Right hemicolectomy	13 (13.1)	4 (30.8)
Radical proctectomy	54 (54.5)	2 (15.4)
Left hemicolectomy	12 (12.1)	2 (15.4)

Factor	Univariate analysis		Multivariate analysis
Factor	OR (95% CI)	P-value	aOR (95% CI)	P-value
Lymphovascular invasion
No	1 (Reference)		1 (Reference)
Yes	5.71 (1.56–20.27)	0.010^*	7.66 (1.94–34.11)	0.004^*
Preoperative CEA level (per 1 SD increase)	1.74 (1.12–2.93)	0.014^*	1.73 (1.03–3.61)	0.039^*
Residual tumor
No	1 (Reference)		1 (Reference)
Yes	3.18 (0.71–12.06)	0.123	3.45 (0.48–22.83)	0.204
Positive vertical margin
No	1 (Reference)		1 (Reference)
Yes	2.06 (0.60–6.73)	0.241	1.95 (0.45–8.13)	0.359
Tumor differentiation (per 1 grade decrease^a)	1.75 (0.45–6.23)	0.409	2.81 (0.54–14.91)	0.216
Depth of invasion
SM1	1 (Reference)		1 (Reference)
SM2–SM3	1.05 (0.31–3.37)	0.933	1.28 (0.31–5.55)	0.733
Positive horizontal margin
No	1 (Reference)		1 (Reference)
Yes	1.02 (0.10–4.95)	0.987	0.57 (0.05–3.84)	0.590
Time to surgery (day) (per 1 SD increase)	1.18 (0.65–1.83)	0.521	1.32 (0.74–2.21)	0.292

Table 1. Baseline clinicopathological characteristics and surgical outcomes (n=112)

Values are presented as mean±standard deviation, median (interquartile range), or number (%), unless otherwise indicated.

CEA, carcinoembryonic antigen; AFP, α-fetoprotein; CA19-9, carbohydrate antigen 19-9.

Table 2. Association between clinical and pathological variables and residual tumor (n=112)

Values are presented as number (%) or median (interquartile range). P-values were derived from the Fisher exact test for categorical variables and the Wilcoxon rank sum test for continuous variables.

SM, submucosal.

P<0.05.

Table 3. Univariate and multivariate Firth penalized regression for LNM prediction