T1 colorectal cancer (CRC), defined by tumor invasion confined to the submucosa, has historically been managed by surgery. Improved understanding of recurrence and lymph node metastases risk, coupled with advances in endoscopic resection techniques, have led to an increasing capacity for organ-sparing local excision. Minimally invasive management of T1 CRC begins with optical evaluation of the lesion to diagnose invasive disease and quantify depth of invasion, which informs therapeutic decision making. Modality selection between various available endoscopic resection techniques depends upon lesion characteristics, technique risk-benefit profiles, and location-specific implications. Following endoscopic resection, established histopathology features determine the risk of recurrence and subsequent management including surveillance or adjuvant surgical excision. The management of non-operative candidates deviates from conventional recommendations with emerging treatment strategies in select populations.

Choosing an optimal post-polypectomy management strategy of malignant colorectal polyps is challenging, and evidence regarding a surveillance-only strategy is limited.

To evaluate long-term outcomes after endoscopic removal of malignant colorectal polyps.

A single-center retrospective cohort study was conducted to evaluate outcomes after endoscopic removal of malignant colorectal polyps between 2010 and 2020. Residual disease rate and nodal metastases after secondary surgery and local and distant recurrence rate for those with at least 1 year of follow-up were investigated. Event rates for categorical variables and means for continuous variables with 95% confidence intervals were calculated, and Fisher's exact test and Mann-Whitney test were performed. Potential risk factors of adverse outcomes were determined with univariate and multivariate logistic regression models.

In total, 135 lesions (mean size: 22.1 mm; location: 42% rectal) from 129 patients (mean age: 67.7 years; 56% male) were enrolled. The proportion of pedunculated and non-pedunculated lesions was similar, with en bloc resection in 82% and 47% of lesions, respectively. Tumor differentiation, distance from resection margins, depth of submucosal invasion, lymphovascular invasion, and budding were reported at 89.6%, 45.2%, 58.5%, 31.9%, and 25.2%, respectively. Residual tumor was found in 10 patients, and nodal metastasis was found in 4 of 41 patients who underwent secondary surgical resection. Univariate analysis identified piecemeal resection as a risk factor for residual malignancy (odds ratio: 1.74; P = 0.042). At least 1 year of follow-up was available for 117 lesions from 111 patients (mean follow-up period: 5.59 years). Overall, 54%, 30%, 30%, 11%, and 16% of patients presented at the 1-year, 3-year, 5-year, 7-year, and 9-10-year surveillance examinations. Adverse outcomes occurred in 9.0% (local recurrence and dissemination in 4 patients and 9 patients, respectively), with no difference between patients undergoing secondary surgery and surveillance only.

Reporting of histological features and adherence to surveillance colonoscopy needs improvement. Long-term adverse outcome rates might be higher than previously reported, irrespective of whether secondary surgery was performed.

We performed a clinical study comparing early-onset and late-onset conventional colorectal adenomas (CCRAs) since little is known about the differences in their characteristics.

Pearson's chi-square test and the Kruskal‒Wallis test were used to compare basic information. MCAR tests and multiple imputation were performed to complete missing values. Multivariate logistic analysis and propensity score matching were used to identify the risk factors for recurrence.

We included 2793 patients (688 with early-onset CCRAs and 2105 with late-onset CCRAs) from January 2017 to December 2021. Patients with early-onset CCRAs had higher levels of Hb, ALB, and triglycerides but lower HDL levels and N/L ratios. Moreover, we found that more early-onset CCRAs were in the left colon than late-onset CCRAs, and the size of early-onset CCRAs was larger. Early-onset CCRAs tended to lack pedicles compared to late-onset CCRAs. Additionally, the ratio of EMR and APC in early-onset CCRAs was higher than that in late-onset CCRAs, and the ratio of ESD and surgery for late-onset CCRAs was higher. We found that age ≥ 50 years, abnormal vessels, drinking alcohol, and DB and ALB levels may be risk factors for recurrence, while the LDL level may be a protective factor. Finally, analysis of cumulative recurrence rates after PSM showed that patients with late-onset CCRAs exhibited higher recurrence rates (P < 0.05).

Compared with late-onset CCRAs, early-onset CCRAs were associated with higher triglyceride levels, lower HDL levels, and larger tumor volumes. Age ≥ 50 years, abnormal vessels, alcohol consumption, and DB and ALB levels were independent risk factors for recurrence of CCRAs.

Risk evaluation of lymph node metastasis (LNM) in superficial colorectal cancer resected by endoscopic surgery is critical for determining subsequent therapeutic strategies, but the role of existing clinical methods, including computed tomography, remains limited.

Features of the nomogram were determined by logistic regression analysis, and the performance was validated by calibration plots, ROC curves and DCA curves in both the training set and the validation set.

A total of 608 consecutive superficial CRC cases were randomly divided into 426 training and 182 validation cases. Univariate and multivariate logistic regression analyses revealed that age < 50, tumour budding, lymphatic invasion and lower HDL levels were risk factors for LNM. Stepwise regression and the Hosmer‒Lemeshow goodness of fit test showed that the nomogram had good performance and discrimination, which was validated by ROC curves and calibration plots. Internal and external validation demonstrated that the nomogram had a higher C-index (training group, 0.749, validation group, 0.693). DCA and clinical impact curves graphically show that the use of the nomogram to predict LNM had remarkable predictive power. Finally, in comparison with CT diagnosis, the nomogram also visually showed higher superiority, as demonstrated by ROC, DCA and clinical impact curves.

Using common clinicopathologic factors, a noninvasive nomogram for individualized prediction of LNM after endoscopic surgery was conveniently established. Nomograms have great superiority in the risk stratification of LNM compared with traditional CT imaging.

Implementation of population-based colorectal cancer screening programs has led to increases in the incidence of pT1 colorectal cancer. These incipient invasive cancers have a very good prognosis and can be treated locally, but more than half of these cases are treated with surgery due to the presence of histological high-risk criteria. These high-risk criteria are suboptimal, with no consensus among clinical guidelines, heterogeneity in definitions and assessment, and poor concordance in evaluation, and recent evidence suggests that some of these criteria considered high risk might not necessarily affect individual prognosis. Current criteria classify most patients as high risk with an indication for additional surgery, but only 2-10.5% have lymph node metastasis, and the residual tumor is present in less than 20%, leading to overtreatment. Patients with pT1 colorectal cancer have excellent disease-free survival, and recent evidence indicates that the type of treatment, whether endoscopic or surgical, does not significantly impact prognosis. As a result, the protective role of surgery is questionable. Moreover, surgery is a more aggressive treatment option, with the potential for higher morbidity and mortality rates. This article presents a comprehensive review of recent evidence on the clinical management of pT1 colorectal cancer. The review analyzes the limitations of histological evaluation, the prognostic implications of histological risk status and the treatment performed, the adverse effects associated with both endoscopic and surgical treatments, and new advances in endoscopic treatment.

Fecal immunochemical tests (FIT) are among the most commonly used tests for colorectal cancer (CRC) screening programs worldwide. However, no randomised controlled trials have been carried out evaluating the impact of FIT-based screening programs (FIT-progr) on CRC incidence and mortality rates. Italian FIT-progr represent one of the most widespread and established experience worldwide. This paper reviews the evidence on the impact of FIT-progr on CRC incidence, tumor stage at diagnosis, mortality and surgery rates, deriving from Italian routine programs, i.e., outside the research setting. Unfortunately, the application of FIT-progr in Italy can be considered as an unplanned experimental model, due to the differences between Regions, both in health system management and adherence of the target population to the screening programs. The analysis of the manuscripts considered in the review, confirms that FIT-progr are effective in reducing CRC incidence and mortality rates and in improving the rate of endoscopic treatment of early invasive lesions. The review also highlights that FIT-progr are less performing for proximal colon than for distal colon and rectum.

According to current guidelines, more than 70% of patients with invasive submucosal colorectal cancer (T1 CRC) undergo a radical operation with lymph node dissection, even though only ~ 10% have lymph node metastasis (LNM). Hence, there is imperative to develop biomarkers that can help robustly identify LNM-positive patients to prevent such overtreatments. Given the emerging interest in exosomal cargo as a source for biomarker development in cancer, we examined the potential of exosomal miRNAs as LNM prediction biomarkers in T1 CRC.

We analyzed 200 patients with high-risk T1 CRC from two independent cohorts, including a training (n = 58) and a validation cohort (n = 142). Cell-free and exosomal RNAs from pre-operative serum were extracted, followed by quantitative reverse-transcription polymerase chain reactions for a panel of miRNAs.

A panel of four miRNAs (miR-181b, miR-193b, miR-195, and miR-411) exhibited robust ability for detecting LNM in the exosomal vs. cell-free component. We subsequently established a cell-free and exosomal combination signature, successfully validated in two independent clinical cohorts (AUC, 0.84; 95% CI 0.70-0.98). Finally, we developed a risk-stratification model by including key pathological features, which reduced the false positive rates for LNM by 76% without missing any true LNM-positive patients.

Our novel exosomal miRNA-based liquid biopsy signature robustly identifies T1 CRC patients at risk of LNM in a preoperative setting. This could be clinically transformative in reducing the significant overtreatment burden of this malignancy.

Vertical tumor margin-negative T1 colorectal carcinoma (CRC) is an absolute curative condition following complete endoscopic resection (ER). However, the influence on prognosis in relation to vertical tumor margin is unclear. Therefore, we evaluated the influence of the distance from vertical tumor margin to resected specimen edge (vertical margin distance) of ER for T1b (submucosal invasion depth > 1000 μm) CRC on the prognosis of patients undergoing additional surgery after ER.

In total, 215 consecutive patients with T1b CRC who underwent additional surgery after ER at Hiroshima University Hospital between February 1992 and June 2019 were enrolled. We assessed 191 patients without lymph node metastases at the additional surgery. The specimens resected by ER were classified into three groups based on the vertical margin distance: patients with a vertical margin distance of ≥ 500 μm (Group A); patients with a vertical margin distance of < 500 μm (Group B); and patients with a positive vertical tumor margin (Group C). Subsequently, we evaluated the prognosis of the patients in relation to the clinicopathological characteristics among the three groups.

There were no significant differences in clinicopathological characteristics among the three groups. Group A had a significantly higher recurrence-free 5-year survival rate than Groups B and C (100%, 84.5%, and 81.8%, respectively). Similarly, Group A had a significantly higher disease-specific 5-year survival rate than Group C (100% vs. 95.5%).

Complete en bloc resection with sufficient submucosal layer from the invasive front (vertical margin distance > 500 μm) by ER for T1 CRC reduces the risk of metastatic recurrence after additional surgery.

The Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines indicate lymphovascular invasion-evaluated by hematoxylin and eosin (HE) staining-as a surgical requirement after endoscopic submucosal dissection (ESD) in T1 colorectal carcinoma (CRC) patients; however, immunohistochemical evaluation may be superior. This study aimed to clarify the significance of immunohistochemical lymphovascular evaluation as an indicator for additional surgery of T1 CRC after ESD, and assessed the guidelines' adequacy, even when evaluating through immunostaining.

Patients with T1 CRC who underwent ESD were enrolled across three institutions between January 2012 and December 2017. Immunohistochemical lymphovascular evaluation was performed. Clinicopathological features, pathological evaluations, and surgery indications were recorded. Univariate and multivariate logistic regression identified risk factors for lymph node (LN) metastasis of T1 CRC after ESD.

Among 370 patients with T1 CRC, recurrence, 5-year overall survival, and 5-year disease specific survival rates were 1.6%, 94.6%, and 99.5%, respectively. Six patients (1.6%) experienced recurrence, five of whom underwent additional surgery. Those with no risk factors did not exhibit recurrence. A total of 215 (58.1%) patients underwent additional surgery after ESD, 21 (9.7%) of whom exhibited LN metastasis. Among 16 patients who underwent additional surgery due to lymphovascular invasion, three (18.8%) had LN metastasis. Multivariate logistic regression analysis identified lymphatic invasion as a significant risk factor for LN metastasis (odds ratio 3.9, 95% confidence interval 1.0-14.6, P = 0.0421).

The JSCCR guidelines have clinical validity, and immunohistochemical lymphatic evaluation findings potentially predict LN metastasis for T1 CRC after ESD.

The recent description of "invasive" forms of intramucosal carcinoma (IMC) has rekindled interest in studying the characteristics, management, and prognosis of IMCs and comparing them with T1 colorectal cancers (CRCs).

This population-based study included 282 cases of IMC and 207 cases of T1 CRC diagnosed by colonoscopy after a positive fecal blood test through a screening program.

IMC presented mainly in the form of pedunculated polyps (68.4%) located in the distal colon (69.9%) ≥20 mm in size (60.6%). IMCs were resected endoscopically in 227 (80.5%) patients and surgically resected in 55 (19.5%) patients. Surgical patients had more right-sided, more sessile, and larger lesions. There was no sign of lymphovascular invasion. Compared with T1 CRCs, IMCs demonstrated lower rates of sessile polyps (31.6% vs 49.8%, P < .0001), primary and ultimate surgical treatment (19.5% vs 39.1% and 19.9% vs 78.7%, P < .0001, respectively), lymph node metastasis in surgical patients (0% vs 9.5%, P = .041), cancer recurrence and cancer-related mortality (0% vs 5.6% and 0% vs 2.5%, respectively), and bleeding after endoscopic resection (1.8% vs 8.7%, P = .001). By multivariate analysis of the pooled cohort (IMC + T1 CRC, n = 489), the factors significantly associated with first-line surgery were shown to be polyp characteristics and the gastroenterologist who performed the colonoscopy.

IMCs account for a quarter of all screening-detected CRCs. They have an excellent prognosis regardless of whether endoscopic or surgical treatment is performed. IMCs differ significantly from T1 carcinomas in terms of management and prognosis.

The main aim of this study was to examine the management strategies that were used and to determine the outcomes (survival and recurrence rate) of screen-detected T1-CRC.

Medical records from 207 patients with T1-CRC diagnosed through the French national screening programme in one district from 2003 to 2015 were analysed. The 5-year overall, CRC-specific and CRC-free survival were calculated for the whole cohort and for the 3 groups treated by endoscopic resection (ER) alone, ER followed by subsequent surgery (ERSS), and primary surgery (PS).

Of the 207 patients, 81 (39%) underwent PS, and 126 (61%) underwent primary ER, of whom 82 (64%) underwent subsequent surgery. The 5-year overall and cancer-specific survival rates were 95.5% (95% CI, 90.8; 97.9) and 98.8% (95% CI, 95.4; 99.7%), respectively. Long-term cancer-specific mortality and recurrence crude rates were 2.4% and 5.6%, respectively. The 5-year CRC-free survival rate was 96.1% (95% CI, 91.8; 98.1%) and did not differ amongst the 3 groups (ER alone, ERSS and PS).

This study demonstrates the good prognosis of screen-detected T1-CRC, regardless of the treatment strategy used. But, there is a room to improve the screening programme quality with regard to the management of screen-detected CRC.