High-risk Colon Cancer Research Articles

Combining pathological risk factors and T, N staging to optimize the assessment for risk stratification and prognostication in low-risk stage III colon cancer

BackgroundThis study aimed to investigate the combined pathological risk factors (PRFs) to stratify low-risk (pT1-3N1) stage III colon cancer (CC), providing a basis for individualized treatment in the future.Patients and methodsPRFs for low-risk stage III CC were identified using COX model. Low-risk stage III CC was risk-grouped combining with PRFs, and survival analysis were performed using Kaplan–Meier. The Surveillance, Epidemiology, and End Results (SEER) databases was used for external validation.ResultsNine hundred sixty-two stage III CC patients were included with 634 (65.9%) as low risk and 328 (34.1%) as high risk. Poor differentiation (OS: P = 0.048; DFS: P = 0.011), perineural invasion (OS: P = 0.003; DFS: P < 0.001) and tumor deposits (OS: P = 0.012; DFS: P = 0.003) were identified as PRFs. The prognosis of low-risk CC combined with 2 PRFs (OS: HR = 3.871, 95%CI, 2.004–7.479, P < 0.001; DFS: HR = 3.479, 95%CI, 2.158–5.610, P < 0.001) or 3 PRFs (OS: HR = 5.915, 95%CI, 1.953–17.420, P = 0.002; DFS: HR = 5.915, 95%CI, 2.623–13.335, P < 0.001) was similar to that of high-risk CC (OS: HR = 3.927, 95%CI, 2.317–6.656, P < 0.001; DFS: HR = 4.132, 95%CI, 2.858–5.974, P < 0.001). In the SEER database, 18,547 CC patients were enrolled with 10,023 (54.0%) as low risk and 8524 (46.0%) as high risk. Low-risk CC combined with 2 PRFs (OS: HR = 1.857, 95%CI, 1.613–2.139, P < 0.001) was similar to that of high-risk CC without PRFs (HR = 1.876, 95%CI, 1.731–2.033, P < 0.001).ConclusionCombined PRFs improved the risk stratification of low-risk stage III CC, which could reduce the incidence of undertreatment and guide adjuvant chemotherapy.

Risk of Bowel Obstruction in Patients Undergoing Neoadjuvant Chemotherapy for High-risk Colon Cancer: A Nested Case-control-matched Analysis of an International, Multicenter, Randomized Controlled Trial (FOxTROT).

This study aimed to identify risk criteria available before the point of treatment initiation that can be used to stratify the risk of obstruction in patients undergoing neoadjuvant chemotherapy (NAC) for high-risk colon cancer. Global implementation of NAC for colon cancer, informed by the FOxTROT trial, may increase the risk of bowel obstruction. A case-control study, nested within an international randomized controlled trial (FOxTROT; ClinicalTrials.gov: NCT00647530). Patients with high-risk operable colon cancer (radiologically staged T3-4 N0-2 M0) that were randomized to NAC and developed large bowel obstruction were identified. First, clinical outcomes were compared between patients receiving NAC in FOxTROT who did and did not develop obstruction. Second, obstructed patients (cases) were age-matched and sex-matched with patients who did not develop obstruction (controls) in a 1:3 ratio using random sampling. Bayesian conditional mixed-effects logistic regression modeling was used to explore clinical, radiologic, and pathologic features associated with obstruction. The absolute risk of obstruction based on the presence or absence of risk criteria was estimated for all patients receiving NAC. Of 1053 patients randomized in FOxTROT, 699 received NAC, of whom 30 (4.3%) developed obstruction. Patients underwent care in European hospitals including 88 UK, 7 Danish, and 3 Swedish centers. There was more open surgery (65.4% vs 38.0%, P =0.01) and a higher pR1 rate in obstructed patients (12.0% vs 3.8%, P =0.004), but otherwise comparable postoperative outcomes. In the case-control-matched Bayesian model, 2 independent risk criteria were identified: (1) obstructing disease on endoscopy and/or being unable to pass through the tumor [adjusted odds ratio: 9.09, 95% credible interval: 2.34-39.66] and stricturing disease on radiology or endoscopy (odds ratio: 7.18, 95% CI: 1.84-32.34). Three risk groups were defined according to the presence or absence of these criteria: 63.4% (443/698) of patients were at very low risk (<1%), 30.7% (214/698) at low risk (<10%), and 5.9% (41/698) at high risk (>10%). Safe selection for NAC for colon cancer can be informed by using 2 features that are available before treatment initiation and identifying a small number of patients with a high risk of preoperative obstruction.

Impact of the SARS-CoV-2 on the journey of high-risk colon cancer patients within the scope of the Unified Health System in Brazil

BackgroundColon cancer is an important cause of mortality related to cancer. During the COVID-19 pandemic, an important reallotment of assistance resources was necessary to tackle the crisis, directly impacting medical practice all over the globe.ObjectiveTo assess the impact of the Sars-Cov-2 pandemic on the time between diagnosis and the beginning of systemic treatment in patients diagnosed with high-risk colon neoplasia.MethodsThis is a retrospective study based on the analysis of medical records of patients diagnosed with colon neoplasia who required systemic treatment and were treated between March 2019 and March 2022, in a reference Oncology unit of the Brazilian Unified Health System. The study’s population was divided into two groups: (I) Pre-COVID-19: diagnoses made between March 2019 and February 2020, (II) COVID-19: diagnoses made between March 2020 and March 2022.ResultsThe sample consisted of 228 patients, 108 (47.97%) of whom were diagnosed during pre-COVID-19 and 118 (52.21%) diagnosed during the two years-period of COVID-19. Regarding the time between colonoscopy and surgery, the time between surgery and first consultation in clinical oncology, and the time between requesting and beginning of systemic treatment, a statistically significant reduction was observed during the COVID-19 period.ConclusionA decrease in time between diagnosis and systemic treatment of patients with colorectal cancer during the COVID-19 pandemic was observed. Yet, even with this improvement, the time to begin treatment remains greater than the recommended by the current guidelines, regardless of the time of diagnosis (before or after the pandemic), which negatively impacts the disease outcome.

Diagnostic accuracy of CT for local staging of colon cancer: A nationwide study in the Netherlands

ObjectiveTo determine the accuracy of computed tomography (CT)-based staging in selecting high-risk colon cancer patients who would benefit from neoadjuvant chemotherapy while avoiding overtreatment. MethodsData of adult patients diagnosed with non-metastatic primary colon cancer in 2005–2020, who underwent surgical resection without neoadjuvant chemotherapy, were retrospectively collected from the Netherlands Cancer Registry. Agreement between clinical and pathological evaluation for each T and N stage was calculated. Sensitivity and specificity analyses were conducted to predict T3-T4 and N1-N2 stages, with histopathology as the reference standard. ResultsData from 44,471 patients (median age, 71 years, 50% female) were evaluated. We included 38,915 patients with complete T stage and 39,565 patients with complete N stage for analyses. The overall clinical-pathological agreement for T stage was 59% and for N stage 57%. The sensitivity and specificity of CT to detect T3-T4 tumours were 80% (95% confidence interval (CI): 0.79, 0.80) and 76% (95% CI: 0.75, 0.77), respectively, with a positive predictive value (PPV) of 92% (95% CI: 0.92, 0.92). The sensitivity and specificity of CT to detect N1-N2 category were 62% (95% CI: 0.61, 0.63) and 70% (95% CI: 0.69, 0.71), respectively, with PPV 60% (95% CI: 0.59, 0.60). ConclusionCT-based staging shows limited accuracy in selecting colon cancer patients who would benefit from neoadjuvant therapy without risking overtreatment. Detection of lymph node metastases with CT remains unreliable.

Transcriptomic Profiling Reveals an Enhancer RNA Signature for Recurrence Prediction in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most fatal malignancies worldwide, and this is in part due to high rates of tumor recurrence in these patients. Currently, TNM staging remains the gold standard for predicting prognosis and recurrence in CRC patients; however, this approach is inadequate for identifying high-risk patients with the highest likelihood of disease recurrence. Recent evidence has revealed that enhancer RNAs (eRNAs) represent a higher level of cellular regulation, and their expression is frequently dysregulated in several cancers, including CRC. However, the clinical significance of eRNAs as recurrence predictor biomarkers in CRC remains unexplored, which is the primary aim of this study. We performed a systematic analysis of eRNA expression profiles in colon cancer (CC) and rectal cancer (RC) patients from the TCGA dataset. By using rigorous biomarker discovery approaches by splitting the entire dataset into a training and testing cohort, we identified a 22-eRNA panel in CC and a 19-eRNA panel in RC for predicting tumor recurrence. The Kaplan-Meier analysis showed that biomarker panels robustly stratified low and high-risk CC (p = 7.29 × 10-5) and RC (p = 6.81 × 10-3) patients with recurrence. Multivariate and LASSO Cox regression models indicated that both biomarker panels were independent predictors of recurrence and significantly superior to TNM staging in CC (HR = 11.89, p = 9.54 × 10-4) and RC (HR = 3.91, p = 3.52 × 10-2). Notably, the ROC curves demonstrated that both panels exhibited excellent recurrence prediction accuracy in CC (AUC = 0.833; 95% CI: 0.74-0.93) and RC (AUC = 0.834; 95% CI: 0.72-0.92) patients. Subsequently, a combination signature that included the eRNA panels and TNM staging achieved an even greater predictive accuracy in patients with CC (AUC = 0.85). Herein, we report a novel eRNA signature for predicting recurrence in patients with CRC. Further experimental validation in independent clinical cohorts, these biomarkers can potentially improve current risk stratification approaches for guiding precision oncology treatments in patients suffering from this lethal malignancy.

Colon cancer CT staging according to mismatch repair status: Comparison and suggestion of imaging features for high-risk colon cancer

BackgroundNeoadjuvant treatment with either chemotherapy or immunotherapy is gaining momentum in colon cancers (CC). To reduce over-treatment, increasing staging accuracy using computed tomography (CT) is of high importance. PurposeTo assess and compare CT imaging features of CC between mismatch repair-proficient (pMMR) and MMR-deficient (dMMR) tumours and identify CT features that can distinguish high-risk (pT3-4, N+) CC according to MMR status. MethodsPrimary staging CTs of 266 patients who underwent primary surgical resection of a colon tumour were retrospectively and independently evaluated by two radiologists. Logistic regression analysis was performed to identify significant associations between imaging features and positive lymph node status. Receiver operating characteristic (ROC) curves of significantly associated features were assessed and validated in an external cohort of 104 patients. ResultsAmong pT3 tumours only, dMMR CC were significantly larger than pMMR CC in both length and thickness (length 59.39 ± 26.28 mm versus 48.70 ± 23.72, respectively, p = 0.031; thickness 20.54 mm ± 11.17 versus 16.34 ± 8.73, respectively, p = 0.027). For pMMR tumours, nodal internal heterogeneity on CT was significantly associated with a positive lymph node status (odds ratio (OR) = 2.66, p = 0.027), while for dMMR tumours, the largest short diameter of the nodes was associated with lymph node status (OR = 2.01, p = 0.049). The best cut-off value of the largest short diameter of involved nodes was 10.4 mm for dMMR and 7.95 mm for pMMR. In the external validation cohort, AUCs for predicting involved nodes based on the largest short diameter was 0.764 for dMMR tumours using 10 mm size cut-off and 0.624 for pMMR tumours using 7 mm cut-off. ConclusionThese data show that CT imaging features of primary CC differ between dMMR and pMMR tumours, suggesting that the assessment of CT-based CC staging should take MMR status into consideration, especially for lymph node status, and thus may help in selecting patients for neoadjuvant treatment.

Radiomic Cancer Hallmarks to Identify High-Risk Patients in Non-Metastatic Colon Cancer.

Simple SummaryColon cancer is one of the most common cancers in the world, and the therapeutic workflow is dependent on the TNM staging system and the presence of clinical risk factors. However, in the case of patients with non-metastatic disease, evaluating the benefit of adjuvant chemotherapy is a clinical challenge. Radiomics could be seen as a non-invasive novel imaging biomarker able to outline tumor phenotype and to predict patient prognosis by analyzing preoperative medical images. Radiomics might provide decisional support for oncologists with the goal to reduce the number of arbitrary decisions in the emerging era of personalized medicine. To date, much evidence highlights the strengths of radiomics in cancer workup, but several aspects limit the use of radiomics methods as routine.The study was aimed to develop a radiomic model able to identify high-risk colon cancer by analyzing pre-operative CT scans. The study population comprised 148 patients: 108 with non-metastatic colon cancer were retrospectively enrolled from January 2015 to June 2020, and 40 patients were used as the external validation cohort. The population was divided into two groups—High-risk and No-risk—following the presence of at least one high-risk clinical factor. All patients had baseline CT scans, and 3D cancer segmentation was performed on the portal phase by two expert radiologists using open-source software (3DSlicer v4.10.2). Among the 107 radiomic features extracted, stable features were selected to evaluate the inter-class correlation (ICC) (cut-off ICC > 0.8). Stable features were compared between the two groups (T-test or Mann–Whitney), and the significant features were selected for univariate and multivariate logistic regression to build a predictive radiomic model. The radiomic model was then validated with an external cohort. In total, 58/108 were classified as High-risk and 50/108 as No-risk. A total of 35 radiomic features were stable (0.81 ≤ ICC < 0.92). Among these, 28 features were significantly different between the two groups (p < 0.05), and only 9 features were selected to build the radiomic model. The radiomic model yielded an AUC of 0.73 in the internal cohort and 0.75 in the external cohort. In conclusion, the radiomic model could be seen as a performant, non-invasive imaging tool to properly stratify colon cancers with high-risk disease.

Identifying high-risk colon cancer on CT an a radiomics signature improve radiologist's performance for T staging?

To assess the role of radiomics in detection of high-risk (pT3-4) colon cancer and develop a combined model that combines both radiomics and CT staging of colon cancer. We included 292 colon cancer patients who underwent pre-operative CT and primary surgical resection within 2 months. Three-dimensional segmentations and CT staging of primary colon tumors were done. From each 3D segmentation of colon tumor, radiomic features were automatically extracted. Logistic regression analysis was performed to identify associations between radiomic features and high-risk (pT3-4) colon tumors. A combined model that integrated both radiomics and CT staging was developed and their diagnostic performance was compared with that of conventional CT staging. Tenfold cross-validation was used to validate the performance of the model and CT staging. The model that combined radiomic features and CT staging demonstrated a significantly better performance in detection of high-risk colon tumors in training set (AUC = 0.799, 95% CI: 0.720-0.839 for combined model and AUC = 0.697, 95% CI = 0.538-0.756 for CT staging only, p < 0.001 for difference). Cross-validation results also demonstrated significantly better detection performance of combined model (AUC = 0.727, 95% Confidence Interval (CI): 0.621-0.777 for combined model and AUC = 0.628, 95% CI = 0.558-0.689 for CT staging only, Boot CI = 0.099). CT radiomic features of primary colon cancer, combined with CT staging, can improve the detection of high-risk colon cancer patients.

Risk of bowel obstruction in patients undergoing neoadjuvant chemotherapy for high-risk colon cancer: A nested Case-control matched analysis of an international, multi-centre, randomised controlled trial (FOxTROT)

Background: Implementation of neoadjuvant chemotherapy (NAC) for colon cancer may increase patient’s risk of bowel obstruction. This study aims to inform patient selection for NAC using features identifiable before treatment initiation.

389MO Risk of bowel obstruction in patients undergoing neoadjuvant chemotherapy for high-risk colon cancer: A nested case-control matched analysis of an international, multi-centre, randomised controlled trial (FOxTROT)

389MO Risk of bowel obstruction in patients undergoing neoadjuvant chemotherapy for high-risk colon cancer: A nested case-control matched analysis of an international, multi-centre, randomised controlled trial (FOxTROT)

Keep Them on the Table: Outcomes Are Improved After Minimally Invasive Colectomy Despite Longer Operative Times in Patients With High-Risk Colon Cancer.

For high-risk patients, traditional surgical dogma advises open operations, with short operative times, to "get them off the table" instead of longer minimally invasive surgery approaches. The aim of this study was to compare postoperative outcomes in patients with high-risk colon cancer undergoing elective longer minimally invasive surgery operations compared with shorter open operations. Retrospective comparative cohort study. Interventions were performed in hospitals participating in the national surgical database. The National Surgical Quality Improvement Program database was used to identify patients with colon cancer with ASA class 3 to 4 undergoing right and sigmoid colectomy between 2012 and 2017. Thirty-day postoperative outcomes were compared between short open and long minimally invasive groups. A total of 3775 patients were identified as having undergone long minimally invasive right colectomy and short open right colectomy (33% open, 67% minimally invasive surgery), and 1042 patients were identified as having undergone long minimally invasive sigmoid colectomy and short open sigmoid colectomy (36% open, 64% minimally invasive). Patients undergoing long minimally invasive right colectomy had significantly lower rates of overall morbidity, severe adverse events, mortality, superficial surgical site infections, and wound disruptions, as well as discharge to a higher level of care and shorter length of stay ( p < 0.05). Patients undergoing long minimally invasive sigmoid colectomy had decreased rates of overall morbidity, severe adverse events, and length of stay, as well as discharge to a higher level of care compared with the patients undergoing short open sigmoid colectomy ( p < 0.05). This study was limited by the retrospective nature and standardized outcome measures. In high-risk patients undergoing colectomy for colon cancer, outcomes were worse with shorter open compared with longer minimally invasive surgery operations. Focus should shift from getting patients "off the table" faster to longer, but safer, minimally invasive surgery in high-risk patients. See Video Abstract at http://links.lww.com/DCR/B642 . ANTECEDENTES:Para los pacientes de alto riesgo, el dogma quirúrgico tradicional aconseja operaciones abiertas, con tiempos quirúrgicos cortos, con el fin de "sacarlos de la mesa" en lugar de enfoques quirúrgicos mínimamente invasivos más prolongados.OBJETIVO:El objetivo de este estudio fue comparar los resultados posoperatorios en pacientes electivos de cáncer de colon de alto riesgo sometidos a operaciones de cirugía mínimamente invasiva más prolongadas en comparación con operaciones abiertas más cortas.DISEÑO:Los resultados posoperatorios de pacientes con cáncer de colon con clase 3-4 de la Sociedad Americana de Anestesiología sometidos a colectomía derecha o sigmoidea se compararon en un análisis multivariado. Se comparó el grupo de colectomía derecha abierta corta (tiempo operatorio <116 minutos) y colectomía derecha mínimamente invasiva larga (tiempo operatorio> 132 minutos). También se compararon la colectomía sigmoidea abierta corta (tiempo operatorio <127 minutos) y la colectomía sigmoidea mínimamente invasiva larga (tiempo operatorio> 161 minutos).ESCENARIO:Las intervenciones se realizaron en hospitales participantes en la base de datos quirúrgica nacional.PACIENTES:La base de datos del Programa Nacional de Mejoramiento de la Calidad Quirúrgica se utilizó para identificar a los pacientes con cáncer de colon con clase 3-4 de la Sociedad Americana de Anestesiología sometidos a colectomía derecha y sigmoidea entre 2012-2017.PRINCIPALES MEDIDAS DE RESULTADO:Se compararon los resultados posoperatorios a los treinta días entre el grupo de procedimientos abiertos cortos y el de mínimamente invasivos largos.RESULTADOS:Se identificó un total de 3.775 pacientes sometidos a colectomía derecha mínimamente invasiva larga y colectomía derecha abierta corta (33% abierta, 67% cirugía mínimamente invasiva) y se identificaron 1042 pacientes sometidos a colectomía sigmoidea mínimamente invasiva larga y colectomía sigmoidea abierta corta (36% abierta, 64% mínimamente invasiva). Los pacientes con colectomía derecha larga mínimamente invasiva tuvieron significativamente menor morbilidad general, eventos adversos graves, mortalidad, infecciones superficiales del sitio quirúrgico, dehiscencia de herida, alta a un nivel más alto de atención y estadía más corta ( p <0.05). Los pacientes con colectomía sigmoidea mínimamente invasiva prolongada tuvieron menor morbilidad general, eventos adversos graves, duración de la estadía y alta a un nivel más alto de atención en comparación con los pacientes con colectomía sigmoidea abierta corta ( p <0.05).LIMITACIONES:Este estudio estuvo limitado por la naturaleza retrospectiva y las medidas de resultado estandarizadas.CONCLUSIONES:En los pacientes de alto riesgo sometidos a colectomía por cáncer de colon, los resultados fueron peores con operaciones abiertas más cortas en comparación con operaciones mínimamente invasivas más largas. El enfoque debe pasar de hacer que los pacientes "salgan rápido de la mesa quirúrgica" a una cirugía mínimamente invasiva más prolongada pero más segura, en pacientes de alto riesgo. Consulte Video Resumen en http://links.lww.com/DCR/B642 . (Traducción-Dr. Jorge Silva Velazco ).

Abstract 650: Transcriptomic profiling identifies an enhancer RNA signature for recurrence prediction in colorectal cancer

Abstract Background: Colorectal cancer (CRC) is one of the most fatal malignancies worldwide, and this is in part due to high rates of tumor recurrence in these patients. Currently, TNM staging remains the gold standard for predicting prognosis and recurrence in CRC patients; however, this approach is inadequate for the identification of high-risk patients who have the highest likelihood of disease recurrence. Recent evidence has revealed that enhancer RNAs (eRNAs) represent a higher level of cellular regulation and their expression is frequently dysregulated in several cancers including CRC. However, the clinical significance of eRNAs as recurrence predictor biomarkers in CRC remains unexplored; which was the primary aim of the present study. Methods: We performed a systematic analysis of eRNA expression profiles in a cohort of 379 colon cancer (CC) and 140 rectal cancer (RC) patients, from the TCGA dataset. By using rigorous biomarker discovery approaches, by splitting the entire dataset into a training and the testing cohort, we identified an eRNA signature for recurrence prediction in CRC. Kaplan-Meier analysis, multivariate and LASSO Cox regression models were used to evaluate the associations of discovered biomarkers with patient cancer recurrence. The performance of the prioritized biomarker panel was first trained and compared against key clinicopathological factors using receiver operating characteristics (ROC) curves analysis, followed by independent validation in the testing cohort. Results: The genome-wide eRNA profiling resulted in the identification of a 22-eRNA in patients with CC, and a 19-eRNA panel in RC. These biomarker panels performed robustly in stratifying low and high-risk CC (P= 7.29e-05) and RC (P = 6.81e-03) patients with recurrence. Multivariate Cox regression analysis demonstrated that both biomarker panels were independent predictors of recurrence, and significantly superior than TNM staging in CC (HR = 11.89, P = 9.54e-04) and RC (HR = 3.91, P = 3.52e-02). Importantly, ROC analysis revealed that both panels exhibited excellent recurrence prediction accuracy in CC (AUC = 0.83; 95% CI: 0.74-0.93) and RC (AUC = 0.81; 95% CI: 0.72-0.92) patients. Subsequently, a combination signature which included the eRNA panels along with TNM staging achieved an even greater predictive accuracy in patients with CC (AUC=0.85) and RC (AUC=0.83). Conclusions: Herein, we report a novel eRNA signature for predicting recurrence in patients with CRC. Pending validation in independent clinical cohorts, these biomarkers have the potential to improve current risk stratification approaches for guiding precision oncology treatments in patients suffering from this lethal malignancy. Citation Format: Divya Sahu, Ajay Goel. Transcriptomic profiling identifies an enhancer RNA signature for recurrence prediction in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 650.

Perineural invasion and number of retrieved lymph nodes are prognostic factors for T2N0 colon cancer.

The prognosis of pathological T2N0 colon cancer has not been adequately investigated. This study aimed to determine the prognostic factors for pathological T2N0 colon cancer by comparing it with those for pathological T3N0 colon cancer. We retrospectively reviewed patients with primary colon cancer who underwent curative resection between January 2007 and December 2015 and included 889 patients with postoperative pathological T2-3N0M0 disease. The clinicopathological characteristics were analyzed to identify the independent prognostic factors. Pathological T2 (n = 185, 20.8%) and T3 (n = 704, 79.2%) tumors showed no difference in the 5-year disease-free survival (5Y DFS) rate (95.8% vs. 93.2%, p = 0.257) after a median follow-up of 55 months (range, 1-106 months). Multivariate Cox regression analysis showed that perineural invasion (hazard ratio [HR] = 2.041, 95% confidence interval [CI] 1.122-3.712, p = 0.019) and number of retrieved lymph nodes < 12 (HR = 2.994, 95% CI 1.327-6.753, p = 0.008) were independent prognostic factors for DFS. Pathological T2 tumors with poor prognostic factors showed similar 5Y DFS as that of T3 tumors with poor prognostic factors (88.9% vs. 88.6%, p = 0.916), but not with T3 tumors without poor prognostic factors (88.9% vs. 95.0%, p = 0.089). Pathological T2N0 colon cancer showed oncologic outcomes similar to that of T3N0 colon cancer. Therefore, more intensive surveillance is necessary for patients with high-risk T2N0 colon cancer.

Risk of metachronous peritoneal metastases in patients with pT4a versus pT4b colon cancer: An international multicentre cohort study

IntroductionWith evolving treatment strategies aiming at prevention or early detection of metachronous peritoneal metastases (PM), identification of high-risk colon cancer patients becomes increasingly important. This study aimed to evaluate differences between pT4a (peritoneal penetration) and pT4b (invasion of other organs/structures) subcategories regarding risk of PM and other oncological outcomes. Materials and methodsFrom eight databases deriving from four countries, patients who underwent curative intent treatment for pT4N0-2M0 primary colon cancer were included. Primary outcome was the 5-year metachronous PM rate assessed by Kaplan-Meier analysis. Independent predictors for metachronous PM were identified by Cox regression analysis. Secondary endpoints included 5-year local and distant recurrence rates, and 5-year disease free and overall survival (DFS, OS). ResultsIn total, 665 patients with pT4a and 187 patients with pT4b colon cancer were included. Median follow-up was 38 months (IQR 23–60). Five-year PM rate was 24.7% and 12.2% for pT4a and pT4b categories, respectively (p = 0.005). Independent predictors for metachronous PM were female sex, right-sided colon cancer, peritumoral abscess, pT4a, pN2, R1 resection, signet ring cell histology and postoperative surgical site infections. Five-year local recurrence rate was 14% in both pT4a and pT4b cancer (p = 0.138). Corresponding five-year distant metastases rates were 35% and 28% (p = 0.138). Five-year DFS and OS were 54% vs. 62% (p = 0.095) and 63% vs. 68% (p = 0.148) for pT4a vs. pT4b categories, respectively. ConclusionPatients with pT4a colon cancer have a higher risk of metachronous PM than pT4b patients. This observation has important implications for early detection and future adjuvant treatment strategies.

The Landmark Series: Surgical Treatment of Colorectal Cancer Peritoneal Metastases.

Peritoneal metastases (PM) are a form of metastatic spread affecting approximately 5-15% of colon cancer patients. The attitude towards management of peritoneal metastases has evolved from therapeutic nihilism towards a more comprehensive and multidisciplinary approach, in large part due to the development of cytoreductive surgery (CRS), usually coupled with heated intraperitoneal chemotherapy (HIPEC), along with the constant improvement of systemic chemotherapy of colorectal cancer. Several landmark studies, including 5 randomized controlled trials have marked the development and refinement of surgical approaches to treating colorectal cancer peritoneal metastases. This review article focuses on these landmark studies and their influence in 4 key areas: the evidence supporting surgical resection of peritoneal metastases, the identification and standardization of important prognostic variables influencing patient selection, the role of surgery and intraperitoneal chemotherapy in prevention of colorectal PM and the role of intraperitoneal chemotherapy as an adjuvant to surgical resection. These landmark studies indicate that surgical resection of colorectal PM should be considered as a therapeutic option in appropriately selected patients and when adequate surgical expertise is available. Standardized prognostic variables including the Peritoneal Cancer Index and the Completeness of Cytoreduction Score should be used for evaluating both indications and outcomes. Current evidence does not support the use of second look surgery with oxaliplatin HIPEC or prophylactic oxaliplatin HIPEC in patients with high risk colon cancer nor the use of oxaliplatin HIPEC with CRS of colorectal PM.

Completeness and accuracy of the registration of recurrences in the Swedish Colorectal Cancer Registry (SCRCR) and an update of recurrence risk in colon cancer

Background The completeness and accuracy of the registration of synchronous metastases and recurrences in the Swedish Colorectal Cancer Registry has not been investigated. Knowing how accurate these parameters are in the registry is a prerequisite to adequately measure the current recurrence risk. Methods All charts for patients diagnosed with stage I–III colorectal cancer (CRC) in two regions were reviewed. In one of the regions, all registrations of synchronous metastases were similarly investigated. After the database had been corrected, recurrence risk in colon cancer was calculated stratified by risk group as suggested by ESMO in 2020. Results In patients operated upon more than five years ago (N = 1235), there were 20 (1.6%) recurrences not reported. In more recent patients, more recurrences were unreported (4.0%). Few synchronous metastases were wrongly registered (3.6%) and, likewise, few synchronous metastases were not registered (about 1%). The five-year recurrence risk in stage II was 6% for low-risk, 11% for intermediate risk, and 23% for high-risk colon cancer patients. In stage III, it was 25% in low- and 45% in high-risk patients. Incorporation of risk factors in stage III modified the risks substantially even if this is not considered by ESMO. Adjuvant chemotherapy lowered the risk in stage III but not to any relevant extent in stage II. Conclusion The registration of recurrences in the registry after 5 years is accurate to between 1 and 2% but less accurate earlier. A small number of unreported recurrences and falsely reported recurrences were discovered in the chart review. The recurrence risk in this validated and updated patient series matches what has been recently reported, except for the risk of recurrence in stage II low risk colon cancers which seem to be even a few percentage points lower (6 vs. 9%).

Impact of the IDEA Collaboration Study Results on Clinical Practice in France for Patients With Stage III Colon Cancer: A National GERCOR - PRODIGE Survey

BackgroundThe IDEA collaboration showed that the type and duration of adjuvant chemotherapy in stage III colon cancer (CC) could be adjusted according to the schedule of chemotherapy and the level of risk. We aimed at evaluating the implementation of IDEA’s results in real-life practice for stage III CC. Material and MethodsAll clinicians registered in the French oncology cooperative groups GERCOR, FFCD, and UNICANCER GI mailing lists were invited to participate to an online anonymized nationwide survey from January 30, 2019 to March 31, 2019. Proportions were compared using the χ2 test. ResultsA total of 213 physicians answered the survey. Of these, 173 (81%) considered that 3 months of adjuvant chemotherapy was the new standard of care for low-risk (pT1-3/N1) stage III CC, and 99% considered that 6 months remained the standard of care for high-risk (pT4 and/or pN2) stage III CC. In patients under 70 years, capecitabine and oxaliplatin (CAPOX) for 3 months was prescribed by 74% of the participants in low-risk CC, whereas 6 months of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) was preferred for high-risk CC in 94% of cases. For patients over 70 years with good performance status and no comorbidities, 172 (81%) physicians prescribed oxaliplatin-based chemotherapy for low-risk CC (3 months, 144 of 172%; 88%), and 200 (94%) physicians prescribed oxaliplatin-based adjuvant chemotherapy for high-risk CC (6 months, 199 of 200%; 99.5%). ConclusionsThe IDEA results have been practice-changing as French physicians have implemented 3 months of CAPOX for patients with low-risk stage III CC, substituting from 6 months of FOLFOX, which remains the preferred regimen for high-risk patients.

Overall survival with 3 or 6 months of adjuvant chemotherapy in Italian TOSCA phase 3 randomised trial

Oxaliplatin-based adjuvant chemotherapy is the standard treatment of high-risk colon cancer (CC). A shorter duration (3 months) can achieve a similar outcome [in terms of relapse-free survival (RFS)] to a longer duration. This study reports the overall survival (OS) analysis of the three or six colon adjuvant (TOSCA) phase III study. It assessed different adjuvant chemotherapy durations in patients with resected high-risk stage II and stage III CC. TOSCA was an open-label, phase III, multicentre, non-inferiority trial conducted in 130 Italian centres. Patients were randomly assigned, in a 1 : 1 ratio, to receive 3 months of standard doses of FOLFOX/CAPOX, or 6 months of FOLFOX/CAPOX. Patients with histologically confirmed high-risk stage II and III CC were included, with RFS being the primary end point. OS was a secondary end point. From June 2007 to March 2013, 3759 patients were accrued. At a median follow-up of 7 years, the hazard ratio (HR) for RFS of the 3-month versus 6-month arms was 1.13; 95% confidence interval (CI) 0.99-1.29, P for non-inferiority= 0.380, P for superiority= 0.068, crossing the non-inferiority limit of 1.20. This result did not allow us to reject the null hypothesis of the inferiority of the 3-month arm. The HR for OS of the 3-month versus 6-month arms was 1.09 (95% CI 0.93-1.26, P for superiority= 0.288). At the last follow-up analysis, the absolute OS difference between arms was <1%. The present analysis of the TOSCA trial does not indicate any significant difference in OS between the treatment groups. The extra benefit provided by the longer treatment should be balanced against the extra toxicity of more prolonged therapy. The trial is registered with ClinicalTrials.gov, registration number: NCT0064660.

Benefit of adjuvant chemotherapy in high-risk colon cancer: A 17-year population-based analysis of 6131 patients with Union for International Cancer Control stage II T4N0M0 colon cancer

BackgroundThe benefit of adjuvant chemotherapy in Union for International Cancer Control (UICC) stage III colon cancer has been demonstrated in numerous studies. While adjuvant chemotherapy is generally not recommended in stage II patients, its role in high-risk UICC stage II disease (e.g. T4 tumours) remains controversial. MethodsThe present population-based multicenter cohort study investigated the influence of adjuvant chemotherapy on survival and recurrence rates in high-risk UICC stage II T4N0M0 tumours. Based on an anonymised nationwide ADT data set from 31 clinical cancer registries, we identified a total of 6651 patients with a T4 tumour of the colon, of whom 6131 were eligible for survival analysis. A matched-pair analysis based on propensity scores (PSM) was performed with a subset of 3986 patients. ResultsMultivariable analyses demonstrated a significant benefit of adjuvant chemotherapy for overall survival (OS) (hazard ratio [HR]: 0.711, 95% confidence interval [CI]: 0.643–0.785, p < 0.001), cumulative recurrence rate (HR: 0.780, 95% CI: 0.681–0.893, p < 0.001), and recurrence-free survival (HR: 0.715, 95% CI: 0.652–0.785, p < 0.001) further confirmed by the matched-pair cohort. ConclusionThis large and representative study demonstrated a significant advantage of adjuvant chemotherapy for patients with T4 UICC stage II colon cancer in terms of OS, recurrence rate, and relapse-free survival. Based on these results, adjuvant chemotherapy should be recommended for these patients.

Stage II high-risk colon cancer: A retrospective analysis of the benefit of chemotherapy in patient subgroups based on the risk factor.

e16068 Background: Adjuvant chemotherapy is routinely recommended for patients with high risk stage II colon cancer. However the risk conferred by each high risk feature (HRF) may be different. This study was done to analyze the magnitude of benefit of chemotherapy in individual HRF patient subgroups. Methods: Resected stage II colon cancer patients during the period January 2012 to March 2018 were retrospectively analyzed for risk features, chemotherapy treatment and survival. Statistical analysis was done with SPSS 16.0. Results: A total of 41 patients were identified as having pathological stage II colon cancer during the study period - 63.4% were males and 36.6%, females. 68.3% had left sided tumor while 31.7% had right sided tumor. 29.3% had none of the high risk features and received no adjuvant chemotherapy. 70.7% patients had at least one of the high risk features and received adjuvant chemotherapy with fluoropyrimidine ± oxaliplatin. 90.2%, 7.3% and 2.5% had stage IIA, IIB and IIC disease respectively. 36.6%, 43.9% and 19.5% had grade I, II and III tumors respectively. Lymphovascular invasion (LVI) and perineural invasion (PNI) were present in 14.6% and 19.5% patients respectively. 29.3% had inadequate lymph node dissection. 22.0% patients had elevated CEA prior to surgery and 4.9% patients had presented with intestinal obstruction. After a minimum follow up period of 20 months the median disease free survival (DFS) was 26 months for the entire cohort. Left sided tumors had significantly prolonged median DFS compared to the right sided tumors (31 vs 26 months; p = 0.05). Median DFS was 24 months for the high risk group compared to 33 months for the low risk group (p = 0.002). On subset analysis T4 HRF subgroup had superior DFS, while LVI HRF subgroup had inferior DFS both of which were statistically significant. Conclusions: Magnitude of chemotherapy benefit was highest in the T4 subgroup, while it was lowest in the LVI subgroup in resected stage II high risk colon cancer [Table: see text]