Introduction

Recent advances in endoscopic technology have allowed many T1 colorectal carcinomas (CRCs) to be resected endoscopically. After endoscopic resection (ER), we often wonder if we should perform an additional surgical resection (SR) with nodal dissection. At present, the indication of additional SR is based only on the risk of simultaneous lymph node metastasis, with no consideration of prognosis in mind. Although in particular elderly people generally have some complications and are more likely to die from other diseases, it is not clear whether the criteria for additional SR after ER should be the same as for non-elderly patients.

Aims & Methods

The aim of this study is to investigate the overall survival (OS) in patients with T1 CRCs treated by ER alone or SR with nodal dissection. After excluding complications of advanced cancer or hereditary colorectal cancer and so on, we retrospectively analyzed 1461 patients with T1 CRCs resected ER or SR at our center from April 2001 to June 2020, and followed them up over a mean period of 77.1 months. We divided the patents into two groups: ER alone group and SR with lymph node dissection group, and compared the OS using the Kaplan–Meier method and the log-rank test. In addition, the same analysis was conducted by dividing the above subjects into those ≤ 75 years of the age and those > 75 years.

Results

In the overall T1 CRC patients, the OS was significantly shorter in the ER alone group than in the SR group (p < 0.01). Among those ≤ 75 years old, that was also shorter in the ER alone group (p < 0.01), while in those > 75 years, no significant difference was found in the OS (p = 0.08).

Conclusion

Among T1 CRC patients > 80 years of age, there was no difference in the remaining life expectancy, with or without SR with nodal dissection, even if additional SR was indicated after ER based on the current criteria. For elderly patients, T1 CRCs could be initially resected endoscopically, and the indication for additional SR with nodal dissection might be carefully considered.

Disclosure

No

Introduction

Several guidelines, including those from the US, Europe, and Japan, recognize "tumor differentiation" as a risk factor for lymph node metastasis (LNM) in T1 colorectal cancer. Surgical resection with lymph node dissection is recommended if poorly differentiated adenocarcinoma, signet-ring cell carcinoma, or mucinous carcinoma are observed in histological findings from endoscopically resected specimens. Recent reports suggest that moderately differentiated adenocarcinoma (tub2) may also be a risk factor for LNM.

Aims & Methods

This study aims to investigate whether tub2 is a risk factor for LNM. We initially evaluated 1,742 patients with T1 colorectal cancer who underwent surgical resection with lymph node dissection at our institution from April 2001 to April 2024. Lesions were assessed based on the worst grade of differentiation. Exclusions were made for patients with (a) metachronous or synchronous advanced cancer, (b) invasion deeper than the muscularis propria, (c) Lynch syndrome, familial adenomatous polyposis, or ulcerative colitis, (d) preoperative chemotherapy or radiotherapy, (e) missing data, or (f) lesions without surgical resection. In addition, after excluding 177 patients with poorly differentiated, mucinous, or signet-ring cell adenocarcinoma, 881 patients were enrolled for analysis. We investigated the sensitivity, specificity, and area under the receiver operating characteristics (ROC) curve of tub2 for predicting LNM, alongside correlations between pathological factors and LNM using multivariate analysis.

Results

LNM was detected in 9.9% (87/881) of patients. The sensitivity, specificity, and area under the ROC curve for tub2 were 78.2%, 42.2%, and 0.60, respectively. In the univariate analysis, tub2 was associated with LNM (p<0.001). Multivariate analysis identified lymphatic invasion, vascular invasion, and tub2 as significant risk factors for LNM, with odds ratios of 7.49, 1.97, and 1.95 (p < 0.01, < 0.01, and = 0.02, respectively).

Conclusion

Moderately differentiated adenocarcinoma (tub2) is a risk factor for LNM in T1 colorectal cancer.

Disclosure

Conflicts of interest:None

Introduction

According to the European Society of Gastrointestinal Endoscopy (ESGE) guidelines, the curative criteria of endoscopic resection (ER) for T1 colorectal cancer (CRC) are well/moderately differentiated adenocarcinoma or papillary carcinoma, no lympho-vascular invasion, submucosal invasion depth <1000μm, and budding grade (BD) 1. Although an additional surgery is recommended for non-curative ER, the incidence of lymph node metastasis (LNM) is less than 12%. Many reports on lymph node metastasis and recurrence in T1 CRC originate from academic centers, with limited reports of real-world data.

Aims & Methods

The aim of this study was to clarify clinical outcomes in patients with T1 CRC. A total of 686 consecutive patients (Male:447 Female:239) were enrolled from April 2009 to August 2019 at 10 institutions. Exclusion criteria included evidence of familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, or inflammatory bowel disease; presence of active, malignant diseases in any other organs; presence of synchronous or metachronous advanced CRC. Risk factors of LNM and recurrence, and survival were analyzed.

Results

The mean age of patients was 69.3±10.2 years old. The mean tumor size was 20.3±12.4mm. The location of the lesion was 439(64%) and 247(36%) in the colon and rectum, respectively. The histopathological types included 681 cases of differentiated type and 5 cases of undifferentiated type. A number of patients with ER without additional SR (ER alone) were 176(curative resection 86, non-curative resection 90), those with SR (SR alone) were 510, and those with ER and additional SR (ER + additional SR) were 116.
(i) Risk factor of LNM: LNM was found in 13(11.2%) patients with ER + additional SR and in 40(10.6%) patients with SR alone. In multivariate analysis, positive lymphatic invasion and tumor size were significant independent risk factor for LNM (OR 5.9, 95% CI [2.2-16], p<0.01, OR 1.04, 95%CI［1.00-1.07］p=0.028, respectively).
(ii) Recurrence: During the mean observation period of 45.5±34.3 months, recurrence was found in 27(3.9%) patients. No recurrence was found in the ER curative resection group. Although 43% (90/206) patients with ER non-curative resection did not receive additional SR, there was no significant difference in recurrence rate between ER alone with non-curative resection and ER + additional SR groups (5.6% (5/90) vs. 2.6% (3/116), respectively; p=0.3). In the SR alone group, recurrence was found in 4.8% (19/394). The significant independent risk factor for recurrence was tumor size (OR 1.12, 95% CI [1.05-1.2], p<0.01).
(iii) Survival: There were 50 deaths (7.3%, 76.2±6.6 years old) during the observation period of 45.5±34.3 months, but CRC-related death was found in only 6 cases (0.8%); one case was ER alone with non-curative resection and the other cases were SR alone.

Conclusion

This study suggests that the possibility of expanding the indication for ER of T1 CRC, because positive lymphatic invasion and tumor size were the only risk factor for LNM and better long-term outcomes were shown despite including significant number of patients with ER alone with non-curative resection. Fifty cases of death showed a higher average age and fewer deaths from CRC. Therefore, even in cases of non-curative resection for T1 CRC after ER, avoiding additional SR may be considered due to advanced age or comorbidities.

Introduction

T1 colorectal cancer can be managed either by surgery or interventional endoscopy. High-risk features after endoscopic resection (G3, submucosal invasion >1000 µm, lympho-vascular invasion, tumour budding+, or R1 resection) increase the risk of lymphnode metastasis (10-15%), often requiring additional surgery. However, the benefits of surgery versus endoscopic resection alone remain unclear, particularly in elderly or frail patients.

Aims & Methods

The aim of the study is to assess recurrence rate and overall survival in patients underwent surgery, endoscopy or both. Secondary endpoints is to evaluate incidence of adverse events and length of hospital stay
All consecutive patients diagnosed with T1 colorectal cancer from 2018 to 2024 in our institution were enrolled in this retrospective study. We divided this cohort in 3 groups: endoscopic resection plus surgery (ER-S), upfront surgery (SR), or endoscopic resection alone (ER). Demographics data, mortality, cancer recurrence rate, disease free survival and AEs were recorded.

Results

One-hundred and thirty-three patients were enrolled in the study: 34 (72 years±10) in the SR group, 65 (65 years±11) in the ER-S group and 34 (77 years±11) in ER, respectively.
Lesions were similar (p-value 0.30) for dimension: 31±15 mm (ER) vs 23±12 mm (ER-S) vs 30±13 mm (ER) such as follow-up (23 vs 24 vs 21 months) for the three groups (p-value 0.428). Hospital stay after the procedure was significantly lower in the ER group (1 day median) vs SR (median 9 days;p-value 0.0001) and ER-S group (7 days median;p-value 0.003). Cumulative 30 days adverse events were higher in the SR group (62%; p-value 0.0001) and in the ER-S group (22%; p-value 0.001) compared to ER alone (12%). During the study period, no endoscopic/radiological recurrence occurred in the SR group whereas 1 patient in the ER-S group and 2 in the ER group showed recurrence non suitable for further treatments.
Five patients in SR group died after a median of 18 months (1 for early surgical complication); 2 died in the ER-S group after a median of 34 months and 3 died in the ER group after a median of 24 months (1 for rectal cancer progression) (p-value 0.365).
Overall survival was comparable among the three groups with no significant difference (p-value 0.718) with a median of 40 months (SR), 28 (ER-S) and 26 (ER) months.

Conclusion

Endoscopic resection alone appears to be a reasonable option for high-risk T1 CRC patients, especially those with increased surgical risk due to low rate of recurrence, low adverse events and a comparable overall survival in short-mid term.

References

1. Quénéhervé, L.; Pioche, M.; Jacques, J. Curative Criteria for Endoscopic Treatment of Colorectal Cancer. Best Pract. Res. Clin. Gastroenterol. 2024, 101883, doi:10.1016/j.bpg.2024.101883.
2. Chen, Y.; Jing, W.; Chen, M.; Wang, Z.; Wu, J.; Yang, J.; Yang, L.; Deng, K. Long-Term Outcomes of Local Resection versus Surgical Resection for High-Risk T1 Colorectal Cancer: A Systematic Review and Meta-Analysis. Gastrointest. Endosc. 2023, 97, 1016-1030.e14, doi:10.1016/j.gie.2023.02.027.
3. Spadaccini M, Bourke MJ, Maselli R, et al. Clinical outcome of non-curative endoscopic submucosal dissection for early colorectal cancer. Gut. Published online January 20, 2022. doi:10.1136/gutjnl-2020-323897
4. Corre, F.; Albouys, J.; Tran, V.-T.; Lepilliez, V.; Ratone, J.-P.; Coron, E.; Lambin, T.; Rahmi, G.; Karsenti, D.; Canard, J.-M.; et al. Impact of Surgery after Endoscopically Resected High-Risk T1 Colorectal Cancer: Results of an Emulated Target Trial. Gastrointest. Endosc. 2023, S0016-5107(23)02933-4, doi:10.1016/j.gie.2023.09.027.
5. UICC. TNM. Classification of malignant tumours. eighth ed. Wiley; 2016. p. 272

Disclosure

Giuseppe Grande is consultant for Olympus, Boston Scientific, ERBE, Fujifilm

Introduction

Endoscopic submucosal dissection (ESD) is widely recognized as the preferred technique for removing large benign colorectal lesions and those with a risk of submucosal invasive cancer (SMIC), with the goal of achieving en-bloc resection. R0 resection is crucial for enabling organ-preservation strategies, particularly in endoscopically resected T1-colorectal cancer (T1-CRC).

Aims & Methods

This study aims to evaluate R0 resection rates in a large cohort of colorectal ESDs by assessing vertical and lateral margins and identifying predictive factors for vertical margin involvement. Furthermore, the presence of other prognostic risk factors for lymph node metastasis (LNM) will be analyzed in this large cohort of T1-CRC. This is a multicenter prospective cohort study in 13 centers, including all colorectal ESDs between 09/2019 and 09/2024. Procedural and histological outcomes were analyzed using univariate and multivariate analysis.

Results

7495 large colorectal polyps were included, of which 781 were T1-CRCs with a median size of 45 [35-65] mm. En bloc resection occurred in 96.7% and R0 resection in 74.9%. Lateral resection margins were free in 92.5%, with positive margins for adenocarcinoma in only 0.8% (low grade dysplasia in 2.6%, high grade in 1.2%, missing data in 2.6%). Vertical margins were free in 80.3%, and decreased significantly when deep SMIC was present to 75.0%, compared to 95.7% for superficial SMIC. However deep SMIC with up to 2000 µm invasion depth, demonstrated free vertical resection margins in still 80.7%, after which it gradually decreased to 73.1% and 67.7% at an infiltration depth of 2000-3000 µm and >3000 µm respectively. Predictive factors for free vertical resection margins include lesion size >50mm (OR=1.66, [1.01;2.71], p=0.045) and rectal location (OR=1.86, [1.04;3.3], p=0.035). Significant difference was observed in the presence of prognostic risk factors for LNM between superficial and deep SMIC, with lympho-vascular invasion (LVI) being present in 9.6% and high-grade tumor budding (Bd) in 17.1% in superficial SMIC, compared to 25.0% and 30.0% respectively, in deep SMIC. However, absence of LVI, Bd or poor differentiation was noted in 75.9% of superficial and 61.7% of deep T1-CRC. Concerning deep SMIC, no relation was observed in the presence of these risk factors with respect to the depth of infiltration.

Conclusion

Following ESD for T1-CRC, the likelihood of achieving free vertical resection margins decreases significantly when invasion depth exceeds 2000 µm. Careful lesion selection through optical diagnosis is therefore critical. To push organ preservation, intermuscular dissection should be considered for T1-CRC with deeper invasion in the rectum. Achieving R0 resection remains paramount, as additional prognostic factors are present in approximately 38% of cases, irrespective of invasion depth.

Introduction

Accurate prediction of lymph node metastasis (LNM) in submucosal invasive (T1) colorectal cancer (CRC) is essential for determining the need for additional surgery following endoscopic resection. Conventional histopathological assessments, however, are limited by interobserver variability. This study aimed to develop and externally validate a stacking-based artificial intelligence (AI) model integrating histopathological whole slide images (WSIs) and clinical parameters to predict the risk of LNM in T1 CRC.

Aims & Methods

This retrospective study included 1,056 patients with histologically confirmed T1 CRC treated at Showa Medical University Northern Yokohama Hospital. Of these, 593 cases were used for model training and 100 for internal testing. External validation was conducted on 25 cases from two independent institutions.
The proposed stacking ensemble model incorporated the Multiple Instance Self-Training (MIST) score derived from WSIs, patient sex, and tumor location (colon vs. rectum). Base learners included logistic regression, XGBoost, and random forest, with a meta-learner synthesizing their outputs to generate the final LNM prediction. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) in both internal and external cohorts.

Results

LNM was observed in 69 (11.6%) training cases, 15 (15.0%) test cases, and 2 (8.0%) external validation cases. The model achieved an AUC of 0.6965 in the internal test cohort and 0.7500 in the external validation cohort, demonstrating stable and generalizable predictive performance.
A representative case involved a 64-year-old man with a 16-mm type 0-Is lesion in the sigmoid colon resected via endoscopic mucosal resection (EMR). Histopathology showed well-differentiated tubular adenocarcinoma (tub1 > tub2), submucosal invasion depth of 3,300 µm (T1b), tumor budding grade BD1, Ly0, V1a, and negative resection margins (HM0, VM0). Despite guideline-based recommendations prompting additional surgical resection, no LNM was found (N0, 0/16), and the patient remained recurrence-free five years postoperatively—consistent with the AI model’s prediction.

Conclusion

The stacking-based AI model exhibited robust and generalizable performance in predicting LNM in T1 CRC, both internally and across external institutions. This approach offers a complementary tool to conventional pathology and may enhance individualized decision-making regarding the necessity of additional surgical intervention.