Abstract
Objectives
This study aimed to identify risk factors for recurrence of rectal neuroendocrine neoplasms, establish a cut‐off size for recurrence prediction, and standardize surveillance guidelines.
Methods
This retrospective study analyzed patients diagnosed with rectal neuroendocrine neoplasm at Samsung Medical Center from January 2007 to July 2021. Tumors were classified according to World Health Organization and European Neuroendocrine Tumor Society guidelines. The primary outcome was to determine the ideal cut‐off size for predicting recurrence.
Results
A total of 1011 patients (median follow‐up: 58 months) were included: 967 with grade (G) I neuroendocrine tumor (NET), 35 with GII NET, and 9 with neuroendocrine carcinoma. Disease‐free and overall survival were significantly better in GI NET than in GII and neuroendocrine carcinoma. For NET G1 patients undergoing endoscopic resection, a 0.7 cm cut‐off (area under the curve = 0.94) showed 100% sensitivity, 79% specificity, and no recurrence. In contrast, for lymphovascular invasion (LVI)‐positive, lymph node–negative NET G1 patients undergoing transanal endoscopic microsurgery/transanal excision or radical resection, an optimal cut‐off of 1.5 cm (area under the curve = 0.92) was identified. NET G2 had a 22.9% lymph node metastasis rate, with recurrence risk increasing with size.
Conclusions
For NET G1 tumors ≤0.7 cm without LVI following endoscopic resection, routine surveillance may not be necessary due to the minimal risk of recurrence. Similarly, for LVI‐positive, lymph node–negative NET G1 tumors that underwent surgical resection, surveillance may not be required if the tumor is ≤1.5 cm. Additionally, NET G2 tumors require regular follow‐up regardless of size to ensure favorable oncologic outcomes. These findings contribute to a risk‐based approach for surveillance, optimizing follow‐up strategies.
Keywords: neuroendocrine neoplasm, rectum, surveillance, survival
INTRODUCTION
Rectal neuroendocrine neoplasm (NEN) represents a rare subset of tumors, accounting for approximately 20–50% of all gastrointestinal NENs and a minority among rectal neoplasms. 1 , 2 , 3 , 4 , 5 These neoplasms originate from enterochromaffin cells known to produce neuroendocrine markers and polypeptide hormones. 5 , 6 , 7 NENs are categorized into well‐differentiated neuroendocrine tumors (NETs), which retain morphological and molecular features of normal neuroendocrine cells, and poorly differentiated neuroendocrine carcinomas (NECs) characterized by severe cellular atypia and disrupted molecular profiles while maintaining some neuroendocrine markers. 6 , 8 , 9 NETs generally have more favorable oncologic outcomes than NECs. 10 , 11
Recently, the incidence of rectal NENs has significantly increased, particularly in the rectum. 12 This increase is attributed to advancements in endoscopic technology known to enable early detection and robust colorectal cancer surveillance programs. 2 , 13 , 14 , 15 , 16 Management of well‐differentiated NETs smaller than 10 mm without muscularis propria invasion typically involves local excision due to their slow growth and low malignancy risk. 17 , 18 , 19 In contrast, tumors 20 mm or larger and those invading the muscularis propria require radical resection due to a higher risk of lymph node metastasis. 18 , 20 , 21
Although some studies have attempted to identify prognostic factors for survival in rectal NENs, existing research is often limited by small sample sizes and low statistical power. Therefore, this study aimed to comprehensively identify risk factors for recurrence and recurrence patterns in rectal NENs, establish a cut‐off size to predict recurrence, and standardize surveillance guidelines.
MATERIALS AND METHODS
Patients diagnosed with rectal NEN at Samsung Medical Center between January 2007 and July 2021 were retrospectively analyzed. Patients with recurrent disease, coexisting rectal adenocarcinoma, or <2 years of follow‐up data were excluded to ensure the reliability of long‐term outcome analysis and to minimize selection bias. This study was approved by the institutional review board of the Samsung Medical Center. The requirement of consent was waived due to the retrospective nature of this study.
Treatment approach
Endoscopic resection was performed for NETs smaller than 10 mm without muscularis propria involvement. For NETs measuring between 10 and 20 mm, endoscopic resection was performed when the tumor was localized, and the patient preferred endoscopic treatment over surgery. The choice of resection method, including endoscopic mucosal resection (using precut, ligation, or cap techniques) and endoscopic submucosal dissection, was determined by an experienced endoscopist based on tumor characteristics. Before resection, lesion lifting was achieved using an injection of normal saline, indigo carmine, and diluted epinephrine (1:10,000). All procedures were performed by an endoscopist with substantial expertise. If endoscopic resection was incomplete or infeasible due to tumor depth or size, local excision was performed. Transanal excision (TAE) and transanal endoscopic microsurgery (TEM) were used for full‐thickness resection of the rectal wall under spinal or general anesthesia. These procedures were performed when lymph node metastasis was not detected on abdominopelvic computed tomography (CT) or rectal magnetic resonance imaging (MRI). Radical surgery, including total mesorectal excision with regional lymph node dissection, was performed for tumors with high‐risk features. These included tumors larger than 2 cm, tumor invasion beyond the submucosa, presence of lymphovascular invasion (LVI), or grade 2 NET. Radical surgery was also indicated when regional lymph node metastasis was detected through imaging studies.
Pathological evaluation
Tissue specimens were prepared by formalin fixation and paraffin embedding, with sections cut to 3 μm thickness, mounted on slides, deparaffinized, and stained with hematoxylin and eosin (H&E). Pathologists conducted a comprehensive examination of the H&E‐stained slides to identify LVI by carefully assessing the presence of tumor cells within vascular spaces, including lymphatic channels and small capillaries. To enhance diagnostic precision, confirmatory immunohistochemical staining was performed using D2‐40 to detect endolymphatic tumor emboli and CD31 to identify vascular invasion. The staining protocol incorporated rigorous quality control measures, including appropriate positive and negative controls, as well as negative reagent controls, to ensure the validity and reliability of the histological findings.
Tumors were classified according to the 2010 World Health Organization classification, with tumor characteristics assessed through two critical parameters: mitotic count and Ki‐67 proliferation index. The mitotic count was determined by systematically counting mitotic figures in 10 high‐power fields (HPFs) under microscopic examination of H&E‐stained sections, with results categorized into specific thresholds: less than 2 mitoses per 10 HPFs for grade 1 NET, 2–20 mitoses per 10 HPFs for grade 2 NET, and more than 20 mitoses per 10 HPFs for NEC. The Ki‐67 index was assessed using immunohistochemical staining with a Ki‐67 antibody to label proliferating cells, calculated as the percentage of Ki‐67–positive cells among the total tumor cell population. The Ki‐67 index thresholds were defined as ≤2% for grade 1 NET, 3–20% for grade 2 NET, and >20% for grade 3 NEC. The lesion size was measured by pathologists based on the macroscopic size. TNM stage was determined using the European Neuroendocrine Tumor Society (ENETS) system. 22 , 23
Follow‐up and surveillance
For patients who underwent endoscopic resection with R0 resection, follow‐up consisted of sigmoidoscopy at 6 months, colonoscopy at 1 year, and then at 2 years postprocedure. In cases of R1 resection, an initial imaging workup, including abdomen‐pelvis CT and chest CT, was performed. If no abnormalities were detected, either local full‐thickness excision under anesthesia was carried out, or patients underwent close surveillance with sigmoidoscopy at 3 months. If sigmoidoscopy findings remained negative, subsequent follow‐up followed the same schedule as for R0 resection cases. For patients who underwent surgical resection, the follow‐up protocol included chest and abdomen‐pelvis CT scans every 6 months for 5 years after the operation. Surveillance colonoscopy was performed at 1 year, followed by colonoscopy at 3 years and 5 years after surgery.
Survival analysis and primary outcome
The survival analysis was performed for disease‐free survival (DFS) and overall survival. Patients with distant metastasis who underwent palliative chemotherapy were excluded from the DFS analysis because they were not disease‐free at the start of the study. The primary outcome of this study was to determine the ideal cut‐off size for rectal NENs to predict recurrence and establish a standard for surveillance.
Statistical methods
All statistical analyses were performed using R version 4.3.0. Categorical variables were analyzed using chi‐square and Fisher's exact tests. Continuous variables were analyzed using Student's t‐test and Wilcoxon rank‐sum test. Survival curves were generated using the Kaplan–Meier method. Log‐rank test was used to assess differences between curves. To determine the optimal threshold, logistic regression analysis was performed to generate predicted values. Receiver operating characteristic (ROC) curves were plotted for various thresholds. The one with the highest area under the curve (AUC) value was selected. Sensitivity and specificity of the chosen threshold were determined to evaluate the predictive performance of the model. Statistical significance was set at P ≤ 0.05.
RESULTS
Baseline clinicopathologic characteristics of study cohort
The selection process of patients is described in Figure 1. Medical records of 1226 patients were initially reviewed and 1011 patients were ultimately included in this study. With a median follow‐up period of 59 months (range, 24–194 months), 967, 35, and nine patients were diagnosed with grade I NET (NET G1), grade II NET (NET G2), and NEC, respectively. Baseline clinicopathologic characteristics are detailed in Table 1. NET G1 patients were significantly younger (P = 0.007) with smaller tumor sizes (P < 0.001), lower TNM stages (P < 0.001), lower pathologic T stage (P < 0.001), lower pathologic N stage (P < 0.001), and negative LVI (P < 0.001) (Table 1).
Figure 1.
Flowchart showing the selection process of patients for this study.
Table 1.
Baseline characteristics of patients with neuroendocrine neoplasm according to grade
| Variable | NET G1 (n = 967) | NET G2 (n = 35) | NEC (n = 9) | P value |
|---|---|---|---|---|
| Age, years | 0.007 | |||
| Median (range) | 47 (19–83) | 51 (26–70) | 56 (38–80) | |
| Sex | 0.507 | |||
| Male | 581 (60.1%) | 19 (54.3%) | 4 (44.4%) | |
| Female | 386 (39.9%) | 16 (45.7%) | 5 (55.6%) | |
| BMI, kg/m2 | 0.976 | |||
| Median (range) | 24.2 (15.5–49.6) | 24 (19–34) | 24 (19.5–34) | |
| No. of lesions | 0.495 | |||
| Solitary | 937 (96.9%) | 35 (100%) | 9 (100%) | |
| Multiple | 30 (3.1%) | 0 (0%) | 0 (0%) | |
| Tumor size | <0.001 | |||
| ≤0.7 cm | 790 (81.7%) | 16 (45.7%) | 1 (11.1%) | |
| 0.7 cm–1 cm | 103 (10.7%) | 9 (25.7%) | 0 (0%) | |
| 1–2 cm | 70 (7.2%) | 9 (25.7%) | 3 (33.3%) | |
| >2 cm | 4 (0.4%) | 1 (2.9%) | 5 (55.6%) | |
| TNM stage | <0.001 | |||
| 1 | 945 (97.7%) | 27 (77.1%) | 2 (22.2%) | |
| 2 | 0 (0%) | 0 (0%) | 1 (11.1%) | |
| 3 | 20 (2.1%) | 7 (20%) | 5 (55.6%) | |
| 4 | 2 (0.2%) | 1 (2.9%) | 1 (11.1%) | |
| T stage | <0.001 | |||
| T1 | 951 (98.6%) | 27 (77.1%) | 2 (22.2%) | |
| T2 | 14 (1.4%) | 8 (22.9%) | 2 (22.2%) | |
| T3 | 2 (0%) | 0 (0%) | 2 (22.2%) | |
| T4 | 0 (0%) | 0 (0%) | 3 (33.3%) | |
| N stage | <0.001 | |||
| Nx | 921 (95.2%) | 24 (68.5%) | 2 (22.2%) | |
| N0 | 18 (1.9%) | 3 (8.6%) | 2 (22.2%) | |
| N+ | 28 (2.9%) | 8 (22.9%) | 5 (55.6%) | |
| LVI | <0.001 | |||
| Negative | 838 (86.7%) | 28 (80.0%) | 1 (11.1%) | |
| Positive | 37 (3.8%) | 6 (17.1%) | 5 (55.6%) | |
| Undescribed | 92 (9.5%) | 1 (2.9%) | 3 (33.3%) |
BMI, body mass index; LVI, lymphovascular invasion; NEC, neuroendocrine carcinoma; NET, neuroendocrine tumor.
Treatment type according to grade
Among 967 NET G1 patients, treatment methods were distributed as follows: 721 (74.6%) received endoscopic treatment, 199 (20.6%) underwent TAE/TEM, 45 (4.6%) had radical surgery, and two (0.2%) received palliative chemotherapy. Reasons for radical surgery in NET G1 patients included: positive LVI (n = 17), large tumors (n = 14), positive resection margins (n = 10), and positive lymph nodes on radiologic examinations (n = 9). Of 35 patients with NET G2, 17 (48.6%) received endoscopic treatment, six (17.1%) underwent local excision, 11 (31.4%) had radical surgery, and one (2.9%) underwent palliative chemotherapy. Reasons for radical surgery in NET G2 patients included positive LVI (n = 2), large tumors (n = 3), positive resection margins (n = 2), positive lymph nodes on radiologic examinations (n = 1), deeper than submucosa on radiologic examinations (n = 3), and Grade 2 NET (n = 3).
Survival and recurrence patterns according to grade
Ten year DFS rate was 99.2% for NET G1, 71.4% for NET G2, and 55.6% for NEC, with NET G1 patients showing significantly higher DFS (P < 0.001; Fig. 2A). Additionally, NET G1 patients had significantly higher overall survival than NET G2 and NEC patients (both P < 0.001; Fig. 2B).
Figure 2.
(A) Disease‐free survival and (B) overall survival of rectal neuroendocrine neoplasm patients based on grade.
In NET G1, local recurrence was predominant, with five (62.5%) cases of local recurrence and three (37.5%) cases of distant metastasis (Table 2). Among local recurrences in NET G1, perirectal lymph node metastasis occurred in four patients and rectal wall recurrence occurred in one patient. In NET G2, distributions of local recurrence and distant metastasis were equal. In all local recurrences, patients were diagnosed with perirectal lymph node metastasis. In NEC patients, distant metastasis was dominant. Across all patients, the liver was the most common site for distant metastasis.
Table 2.
Treatment and recurrence patterns of patients with neuroendocrine neoplasm according to grade
| Variable | NET G1 (n = 967) | NET G2 (n = 35) | NEC (n = 9) | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Local resection (n = 918) | Radical surgery (n = 47) | CTx (n = 2) | Local resection (n = 23) | Radical surgery (n = 11) | CTx (n = 1) | Local resection (n = 0) | Radical surgery (n = 8) | CTx (n = 1) | |
| Treatment type | |||||||||
| Polypectomy | 199 | – | – | 1 | – | – | 0 | – | 0 |
| EMR/ESD | 520 | – | – | 16 | – | – | 0 | – | 0 |
| TAE/TEM | 199 | – | – | 6 | – | – | 0 | – | 0 |
| Radical surgery | – | 45 | – | – | 11 | – | – | 8 | 0 |
| CTx | – | – | 2 | – | – | 1 | – | – | 1 |
| Reason for radical surgery | |||||||||
| Size | – | 14 | – | – | 3 | – | – | – | – |
| LN+ | – | 9 | – | – | 1 | – | – | – | – |
| LVI+ | – | 17 | – | – | 2 | – | – | – | – |
| Resection margin+ | – | 10 | – | – | 2 | – | – | – | – |
| Depth | – | 0 | – | – | 3 | – | – | – | – |
| Grade | – | 0 | – | – | 3 | – | – | – | – |
| Recurrence pattern | |||||||||
| Local recur | 3 | 2 | – | 4 | 1 | – | – | 1 | – |
| Rectum | 1 | 0 | – | 0 | 0 | – | – | 0 | – |
| Perirectal LN | 2 | 2 | – | 3 | 1 | – | – | 1 | – |
| Rectum and LN | 0 | 0 | – | 1 | 0 | – | – | 0 | – |
| Distant metastasis | 1 | 2 | – | 2 | 3 | – | – | 3 | – |
| Liver | 1 | 2 | – | 2 | 3 | – | – | 2 | – |
| Peritoneum | 0 | 1 | – | 0 | 0 | – | – | 1 | – |
| Bone | 0 | 0 | – | 0 | 1 | – | – | 0 | – |
| Lung | 0 | 0 | – | 0 | 0 | – | – | 1 | – |
CTx, chemotherapy; EMR, endoscopic mucosal resection; ESD, endoscopic submucosal dissection; LN, lymph node; LVI, lymphovascular invasion; NEC, neuroendocrine carcinoma; NET, neuroendocrine tumor; TAE, transanal excision; TEM, transanal endoscopic microsurgery.
Subgroup analysis of NET G1
In NET G1, 48 patients diagnosed with positive resection margin after endoscopic resection. Of 48 patients, six underwent surgical resection (three with local excision and three with radical surgery). Among these, four patients had no residual tumor in their surgical specimens. NET G1 patients were divided into four groups based on tumor size: tumors ≤0.7 cm, tumors >0.7 cm and ≤1 cm, tumors >1 cm and ≤2 cm, and tumors >2 cm. For those with NET G1, there were no recurrences in tumors ≤0.7 cm. As tumor size increased, the proportion of surgical resections also increased (P < 0.001; Table 3). Additionally, 99.9% of tumors ≤0.7 cm were limited to the submucosa layer, whereas extension to the muscularis propria was higher with increasing tumor size (P < 0.001; Table 3). Furthermore, the positivity of LVI increased with tumor size (P < 0.001; Table 3). As tumor size increased, DFS significantly decreased in NET G1 (P < 0.001; Fig. 3A). ROC curve analysis identified a 0.7 cm cut‐off with an AUC of 0.94, demonstrating an accuracy of 80%, a sensitivity of 100%, and a specificity of 79% in patients who underwent endoscopic resection without LVI (Fig. 4). In contrast, for patients with LVI‐positive, lymph node (LN)‐negative tumors who underwent TEM/TAE or radical resection, the AUC was 0.92 with an optimal cut‐off value of 1.5 cm, indicating a distinct recurrence risk profile in this subgroup (Fig. 5).
Table 3.
Treatment and pathologic outcomes of patients with grade I neuroendocrine tumor according to tumor size
| Variable | ≤0.7 cm (n = 789) | 0.7–1 cm (n = 103) | 1–2 cm (n = 70) | >2 cm (n = 5) | P‐value | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Treatment type | Local resection (n = 777) | Radical surgery (n = 12) | Local resection (n = 88) | Radical surgery (n = 15) | Local resection (n = 51) | Radical surgery (n = 19) | Local resection (n = 2) | Radical surgery (n = 1) | CTx (n = 2) | |
| T stage | <0.001 | |||||||||
| T1 | 776 | 12 | 87 | 14 | 45 | 15 | 2 | 0 | 0 | |
| T2 | 1 | 0 | 1 | 1 | 6 | 4 | 0 | 1 | 0 | |
| T3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | |
| LVI | <0.001 | |||||||||
| Positive | 2 | 4 | 7 | 8 | 6 | 8 | 0 | 1 | 0 | |
| Number of lesions | 0.330 | |||||||||
| Solitary | 753 | 11 | 84 | 14 | 51 | 19 | 2 | 1 | 2 | |
| Multiple | 24 | 1 | 4 | 1 | 0 | 0 | 0 | 0 | 0 | |
| Recur | <0.001 | |||||||||
| Local recur | 0 | 1 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | |
| Distant metastasis | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | |
Local resection includes transanal excision, transanal endoscopic microsurgery, endoscopic mucosal resection, and endoscopic submucosal dissection.
CTx, chemotherapy; LVI, lymphovascular invasion.
Figure 3.
(A) Disease‐free survival of grade 1 neuroendocrine tumor patients according to tumor size, (B) disease‐free survival of grade 2 neuroendocrine tumor patients according to tumor size.
Figure 4.
Receiver operating characteristic curve for predicting tumor recurrence based on tumor size in neuroendocrine tumor grade 1 patients following endoscopic resection.
Figure 5.
Receiver operating characteristic curve for predicting tumor recurrence based on tumor size in neuroendocrine tumor grade 1 patients with lymphovascular invasion but without lymph node metastasis after surgery.
Subgroup analysis of NET G2
In NET G2, one patient had distant metastasis at the first diagnosis and 22.9% patients had lymph node metastasis. Recurrence according to tumor size was as follows: 12.5% in tumor size ≤0.5 cm, 17.6% in tumors >0.5 cm and ≤1 cm, 75% in tumors >1 cm and ≤2 cm. As tumor size increased, DFS significantly decreased (P = 0.012; Fig. 3B). Of four patients with a positive resection margin after endoscopic resection, two patients underwent radical surgery and two patients underwent TEM. Only one patient had lymph node metastasis with no residual tumor in the removal site. The other three patients had no residual tumor.
DISCUSSION
This study investigated the ideal cut‐off size for rectal NEN to predict recurrence and standardize surveillance guidelines. A cut‐off value of 0.7 cm showed a sensitivity of 100% and a specificity of 79%. All NET G1 tumors ≤0.7 cm had tumor depth confined to the submucosa, showing no recurrence. These findings suggest that NET G1 tumors ≤0.7 cm might not require radiologic examination for lymph node metastasis or regular surveillance for recurrence.
Traditionally, small rectal NETs have been considered low‐risk lesions. 1 , 24 , 25 The National Comprehensive Cancer Network guidelines suggest that additional follow‐up can be omitted for those with rectal NET G1 tumors smaller than 1 cm with complete resection. 26 Similarly, ENETS recommends no follow‐up for those who have undergone R0 resection of rectal NET G1 tumors ≤1 cm with negative LVI. However, abdominopelvic MRI every 6 months and sigmoidoscopy yearly for at least 5 years are recommended for rectal NET G1 tumors ≤1 cm with positive LVI. 27 Previous studies have recommended various cut‐off values for tumor size concerning recurrence risk. Concors et al. have suggested that tumors >1.15 cm are at substantial risk of distant metastasis. 24 Gleeson et al. have described that the clinical behavior of tumors 1.1 cm to 1.9 cm is similar to that of tumors >2 cm and suggested that 1 cm is the value for aggressive staging. 28 Matsuhashi et al. have reported that NETs >1 cm carry a metastasis risk equivalent to that of adenocarcinoma, potentially necessitating further proctectomy with regional lymph node dissection. 29
Although NET G1 tumors ≤1 cm have a low risk of recurrence, our cohort showed that NET G1 tumors between 0.7 cm and 1 cm had a 1.8% recurrence rate. Furthermore, NET G1 tumors ≤1 cm with positive LVI showed no recurrence in this study. However, both National Comprehensive Cancer Network and ENETS guidelines suggest regular surveillance for NET G2 tumors ≤1 cm due to a high risk of recurrence. In this study, NET G2 tumors with sizes as small as 0.5 cm experienced recurrence. Xinyu et al. have evaluated rectal NET G2 and shown a 3‐year cancer‐specific survival rate of 95.7% for tumors ≤1.5 cm. 30 Therefore, we suggest that NET G1 tumors ≤0.7 cm without LVI might not require regular surveillance, particularly in patients undergoing endoscopic resection, as the recurrence risk is minimal. However, in LVI‐positive, LN‐negative patients who underwent TEM/TAE or radical resection, an optimal cut‐off of 1.5 cm was identified for recurrence prediction, suggesting a different risk profile. However, NET G2 tumors need regular surveillance regardless of tumor size.
For R1 resection of rectal NET G1 and G2 tumors ≤1 cm, endoscopy, endoscopic ultrasonography, and MRI every year for at least 5 years are recommended by ENETS guidelines. 27 In this study, 41 patients with R1 resection of NET G1 tumors ≤1 cm showed no recurrence during regular follow‐up. Previous studies have indicated that incomplete resection status without additional resection is oncologically safe for small rectal NETs. 31 , 32 , 33 Therefore, we suggest that surveillance of R1 resection of rectal NET G1 tumors ≤1 cm is sufficient with regular follow‐up.
This study has several limitations. First, it was conducted at a single institution with a retrospective nature. Second, the low recurrence rate observed in our cohort, with only 0.8% of the 967 patients experiencing recurrence of NET of the rectum, may impact the study's findings. Although we determined a statistically significant cut‐off value for recurrence using an ROC curve, the limited number of recurrence events may weaken the statistical power of this analysis. Consequently, the derived cut‐off value may lack generalizability, and its applicability in clinical practice should be interpreted with caution. Third, the NET G2 and NEC groups had very small sample sizes and showed relatively heterogeneous findings. Consequently, it is difficult to draw specific conclusions regarding surveillance for these tumor groups. Fourth, follow‐up surveillance was not uniform across the cohort, which might have affected oncologic outcomes. Fifth, the study period was relatively long. Advancements in endoscopic and surgical techniques might have influenced treatment decisions. Despite these challenges, this study represents the largest single‐center cohort analyzing rectal NEN and evaluating the ideal cut‐off size to predict recurrence and standardize surveillance guidelines. Further multicenter studies are required to solidify our findings.
In conclusion, for NET G1 tumors ≤0.7 cm without LVI following endoscopic resection, routine surveillance may not be necessary due to the minimal risk of recurrence. Similarly, for patients with LVI‐positive, LN‐negative NET G1 tumors who underwent surgical resection, surveillance may not be required if the tumor is ≤1.5 cm. However, larger tumors may warrant continued follow‐up. Additionally, NET G2 tumors require regular follow‐up regardless of size to ensure favorable oncologic outcomes. These findings contribute to a risk‐based approach for post‐treatment surveillance, optimizing follow‐up strategies based on tumor characteristics and treatment modality.
CONFLICT OF INTEREST
Authors declare no conflict of interest for this article.
FUNDING INFORMATION
None.
ETHICS STATEMENT
Approval of the research protocol by an Institutional Reviewer Board: This study was approved by the Institutional Review Board of Samsung Medical Center.
Informed Consent: Informed consent was waived due to the retrospective nature of the study.
Registry and the Registration No. of the study/trial: N/A
Animal Studies: N/A.
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