Introduction

Information about the distribution characteristics and prognostic significance of lateral lymph nodes (LLNs) on primary computed tomography (CT) scan in rectal cancer patients is lacking.

Aims & Methods

Between January 2013 and December 2016, patients with pathologically-proved rectal cancer and pretreatment abdominal enhanced CT in our department were screened. We firstly redivided LLNs into 7 categories based on their locations. Then, the number and distribution of all measurable LLNs and the characteristics of the largest LLN in each lateral compartment were recorded. Furthermore, we investigated the long-term outcomes in patients with different LLNs characteristics and LLN risk scoring.

Results

A total of 572 patients were enrolled in this study. About 80% of patients had measurable LLNs. Most patients developed measurable LLNs in the obturator cranial compartment and a total of 231 (40.38%) patients and 281 (49.13%) patients had left and right obturator cranial LNs, respectively. The proportion of patients with left and right distal internal iliac LNs was 8.57% and 16.61%, respectively, and patients with left and right extended distal internal iliac LNs was 6.64% and 8.22%, respectively. We found the largest LLN short-axis diameter with 3-5 mm and 5-7 mm accounted for the most in every single compartment. The proportion of patients with the largest LLN short-axis diameter with 3-5 mm and 5-7 mm in the left obturator cranial compartment was 64.5% and 16%, respectively, and in the right obturator cranial compartment was 55.2% and 24.9%, respectively. In the whole cohort, there were 20 (4.4%) patients with >10 mm LLN, 52 (11.3%) patients with 7-10 mm LLN, 158 (34.4%) patients with 5-7 mm LLN, 206 (44.9%) patients with 3-5 mm LLN, 23 (5.0%) patients with 0-3 mm LLN. LLNs in the left proximal internal iliac compartment and the left distal internal iliac compartment had the largest short-axis diameter (5.42 ± 2.94) and long-axis diameter (8.47 ± 11.34), respectively. LLNs in the left obturator caudal compartment had both the shortest short-axis (3.85 ± 2.18) and long-axis diameter (5.47 ± 2.99), respectively. Lateral local recurrence (LLR) was observed in 20 patients, which accounted for 83.3% of the local recurrence (LR). Patients with LLN short-axis diameter > 10 mm had the worst 5-year OS (18.5%), which was comparable with that in patients with simultaneous distant metastasis (SDM, 8.5%). With regard to local recurrence-free survival (LRFS) and lateral local recurrence-free survival (LLRFS), patients with LLN short-axis diameter > 10 mm had the worst 5-year LRFS (35.7%) and LLRFS (35.7%). We used the largest LLN characteristics on CT scan to stratify the risk of LLNM (considering short-axis diameter, morphology, border and appearance). Patients with LLN risk scoring ≥ 2 had a worse prognosis than those with LLN risk scoring < 2, while better than those with SDM.

Conclusion

Our study comprehensively descripted the distribution characteristics and prognostic significance of LLNs. Our results confirmed that LLR is the main locoregional recurrence pattern. In addition, most rectal cancer patients have measurable LLNs. However, these patients with enlarged LLNs still have a significant better prognosis than patients with distant metastasis, which indicated the potential value of locoregional treatment for enlarged LLNs. Well-designed studies with larger sample size are required to prove our results.

References

1. Kim TH, Jeong SY, Choi DH, et al. Lateral lymph node metastasis is a major cause of locoregional recurrence in rectal cancer treated with preoperative chemoradiotherapy and curative resection. Ann Surg Oncol. 2008;15(3):729-737.
2. Ogura A, Konishi T, Cunningham C, et al. Neoadjuvant (Chemo)radiotherapy With Total Mesorectal Excision Only Is Not Sufficient to Prevent Lateral Local Recurrence in Enlarged Nodes: Results of the Multicenter Lateral Node Study of Patients With Low cT3/4 Rectal Cancer. J Clin Oncol. 2019;37(1):33-43.
3. Sammour T, Chang GJ. Lateral pelvic lymph node dissection and radiation treatment for rectal cancer: Mutually exclusive or mutually beneficial?. Ann Gastroenterol Surg. 2018;2(5):348-350.
4. Ogura A, Konishi T, Beets GL, et al. Lateral Nodal Features on Restaging Magnetic Resonance Imaging Associated With Lateral Local Recurrence in Low Rectal Cancer After Neoadjuvant Chemoradiotherapy or Radiotherapy. JAMA Surg. 2019;154(9):e192172.
5. Kroon HM, Dudi-Venkata NN, Bedrikovetski S, et al. Malignant Features in Pretreatment Metastatic Lateral Lymph Nodes in Locally Advanced Low Rectal Cancer Predict Distant Metastases. Ann Surg Oncol. 2022;29(2):1194-1203.

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.

Introduction

Watch-and-Wait is an increasingly recognized non-surgical management option for rectal cancer patients achieving a clinical complete response (cCR) following neoadjuvant therapy. This approach aims to preserve organ function by avoiding surgery, but necessitates vigilant endoscopic surveillance, to detect local tumor regrowth¹ (LTR). The specific endoscopic features associated with regrowth remain incompletely defined.

Aims & Methods

We performed a retrospective analysis of patients monitored under the Watch-and-Wait program at Karolinska University Hospital², focusing on the endoscopic characteristics of LTR. As of December 2023, 145 patients who met the criteria for clinical complete response (cCR) were included.
The neoadjuvant treatment consisted of chemoradiotherapy (CRT) in 16 patients (11%), short course radiotherapy (SCRT) + chemotherapy in 69 patients (47.6%) and SCRT alone (5 x 5 Gy) in 60 patients (41.4%). The median age of the patients was 66 years (range 29-94), with 61.4% being male. The initial tumor stage was T1/T2 in 42 patients (29%) and T3/T4 in 103 patients (71%). The nodal stage was N0 in 35 patients (24%) and N+ in 110 patients (75.9%). The median follow-up period was 29 months (range 3-102 months).
Patients were monitored with rectal digital exams, flexible endoscopy, CEA measurements, and MRI every 3 months for 2 years, and then every 6 months thereafter. During endoscopy, narrow-band imaging (NBI) and NICE classification³ was utilized.

Results

Out of the 145 patients, 28 (19.3%) experienced LTR as of December 2023. The median time from the completion of radiotherapy to regrowth was 9 months (range 3-20 months). Regrowth was detected intraluminally by endoscopy in 23 patients (82.1%), while in 5 patients (17.9%), regrowth was detected on MRI but was not visible intraluminally.
The most common endoscopic features of regrowth included a NICE 3 pattern (n=16) and contact bleeding (n=16). Additional findings included polypoid tissue (n=13), ulceration (n=10), irregular surface (n=9), fibrin cover (n=9), stenosis (n=6), and submucosal nodules (n=5).

Conclusion

As regrowth occurs in at least one of five patients and most commonly with intraluminal findings, this study highlights the importance of meticulous endoscopic follow-up. Contact bleeding and NICE type 3 lesions observed with narrow-band imaging (NBI) were key endoscopic findings in patients with tumor regrowth, while polypoid lesions were observed in less than 50%. Combining endoscopic assessment with other modalities, such as MRI, is essential, as regrowth may be undetectable endoscopically in a proportion of patients.

References

1. Cerdan-Santacruz C, Vailati BB, Sao Juliao GP, Habr-Gama A, Perez RO. Local tumor regrowth after clinical complete response following neoadjuvant therapy for rectal cancer: what happens when organ preservation falls short. Tech Coloproctol 2023;27(1):1-9. DOI: 10.1007/s10151-022-02654-5.
2. Nilsson PJ, Ahlberg M, Kordnejad S, Holm T, Martling A. Organ preservation following short-course radiotherapy for rectal cancer. BJS Open 2021;5(5). DOI: 10.1093/bjsopen/zrab093.
3. Hamada Y, Tanaka K, Katsurahara M, et al. Utility of the narrow-band imaging international colorectal endoscopic classification for optical diagnosis of colorectal polyp histology in clinical practice: a retrospective study. BMC Gastroenterol 2021;21(1):336. DOI: 10.1186/s12876-021-01898-z.

Disclosure

Stephan Haas (SLH) has received speaker's honoraria from Santax Medico, Tillotts Pharma, Lilly, Mediahuset, and Johnson & Johnson.