Asymptomatic Colorectal Cancer Research Articles

Circulating tumour DNA and risk of recurrence in patients with asymptomatic versus symptomatic colorectal cancer.

Multiple initiatives aim to develop circulating tumour DNA (ctDNA) tests for early cancer detection in asymptomatic individuals. The few studies describing ctDNA-testing in both asymptomatic and symptomatic patients report lower ctDNA detection in the asymptomatic patients. Here, we explore if asymptomatic patients differ from symptomatic patients e.g. by including a 'low-ctDNA-shedding' and 'less-aggressive' subgroup. ctDNA assessment was performed in two independent cohorts of consecutively recruited patients with asymptomatic colorectal cancer (CRC) (Cohort#1: n = 215, Cohort#2: n = 368) and symptomatic CRC (Cohort#1: n = 117, Cohort#2: n = 722). After adjusting for tumour stage and size, the odds of ctDNA detection was significantly lower in asymptomatic patients compared to symptomatic patients (Cohort#1: OR: 0.4, 95%CI: 0.2-0.8, Cohort#2: OR: 0.7, 95%CI: 0.5-0.9). Further, the recurrence risk was lower in asymptomatic patients (Cohort#1: sHR: 0.6, 95%CI: 0.3-1.2, Cohort#2: sHR: 0.6, 95%CI: 0.4-1.0). Notably, ctDNA-negative asymptomatic patients had the lowest recurrence risk compared to the symptomatic patients (Cohort#1: sHR: 0.2, 95%CI: 0.1-0.6, Cohort#2: sHR: 0.3, 95%CI: 0.2-0.6). Our study suggests that asymptomatic patients are enriched for a 'low-ctDNA-shedding-low-recurrence-risk' subgroup. Such insights are needed to guide ctDNA-based early-detection initiatives and should prompt discussions about de-escalation of therapy and follow-up for ctDNA-negative asymptomatic CRC patients.

Pictorial essay: improving diagnostic effectiveness of colorectal cancer at CT.

As the routine use for CT increases, there is an opportunity to increase the detection rate of unsuspected and asymptomatic colorectal cancers. This pictorial essay provides abundant examples of the typical morphologic appearances of colorectal cancer in the unprepared colorectum. Many examples of lesions that were missed in clinical practice are illustrated with lessons on how to avoid these errors. Atypical appearances of colorectal cancer are also illustrated. The overall aim is to increase the detection rate of colorectal cancer at routine CT.

Development and multicenter validation of deep convolutional neural network-based detection of colorectal cancer on abdominal CT.

This study aims to develop computer-aided detection (CAD) for colorectal cancer (CRC) using abdominal CT based on a deep convolutional neural network. This retrospective study included consecutive patients with colorectal adenocarcinoma who underwent abdominal CT before CRC resection surgery (training set = 379, test set = 103). We customized the 3D U-Net of nnU-Net (CUNET) for CRC detection, which was trained with fivefold cross-validation using annotated CT images. CUNET was validated using datasets covering various clinical situations and institutions: an internal test set (n = 103), internal patients with CRC first determined by CT (n = 54) and asymptomatic CRC (n = 51), and an external validation set from two institutions (n = 60). During each validation, data from the healthy population were added (internal = 60; external = 130). CUNET was compared with other deep CNNs: residual U-Net and EfficientDet. The CAD performances were evaluated using per-CRC sensitivity (true positive/all CRCs), free-response receiver operating characteristic (FROC), and jackknife alternative FROC (JAFROC) curves. CUNET showed a higher maximum per-CRC sensitivity than residual U-Net and EfficientDet (internal test set 91.3% vs. 61.2%, and 64.1%). The per-CRC sensitivity of CUNET at false-positive rates of 3.0 was as follows: internal CRC determined by CT, 89.3%; internal asymptomatic CRC, 87.3%; and external validation, 89.6%. CUNET detected 69.2% (9/13) of CRCs missed by radiologists and 89.7% (252/281) of CRCs from all validation sets. CUNET can detect CRC on abdominal CT in patients with various clinical situations and from external institutions. • Customized 3D U-Net of nnU-Net (CUNET) can be applied to the opportunistic detection of colorectal cancer (CRC) in abdominal CT, helping radiologists detect unexpected CRC. • CUNET showed the best performance at false-positive rates ≥ 3.0, and 30.1% of false-positives were in the colorectum. CUNET detected 69.2% (9/13) of CRCs missed by radiologists and 87.3% (48/55) of asymptomatic CRCs. • CUNET detected CRCs in multiple validation sets composed of varying clinical situations and from different institutions, and CUNET detected 89.7% (252/281) of CRCs from all validation sets.

Comparative effectiveness of primary tumor resection versus chemotherapy in patients with asymptomatic unresectable metastatic colorectal cancer: a retrospective cohort study using the target trial emulation framework.

Patients who undergo primary tumor resection (PTR) reportedly have significantly higher overall survival (OS) than those who do not undergo this procedure. However, this result is only evident in past retrospective studies, and clinical trial results did not show the same trend. Thus, it remains unclear whether primary tumor resection effectively increases survival in patients with metastatic colorectal cancer (mCRC) across different study designs. We compared the OS of patients with asymptomatic unresectable mCRC who underwent PTR with that of those who did not. This retrospective cohort study was designed to be a target trial emulation of a randomized controlled trial (RCT) that would have compared the effectiveness of PTR versus non-PTR in patients with asymptomatic unresectable mCRC from 2009 to 2017. A systematic review and meta-analysis were conducted to compare the efficacy of PTR and non-PTR in patients with mCRC, and corresponding results were compared. This cohort included 1,132 patients for a per-protocol analysis. The PTR group had non-significantly longer survival (adjusted hazard ratio: 0.70, 95% confidence interval: 0.62-1.01) than the non-PTR group in our cohort. A meta-analysis including five RCTs (1,016 patients) and our cohort found that the PTR group did not have a significantly lower mortality rate than the non-PTR group. The results of this cohort study and previous RCTs suggest that PTR is not associated with improved survival compared to systemic chemotherapy combined with targeted therapy among asymptomatic unresectable mCRC patients. Therefore, routine PTR is not recommended in these patients.

The impact of palliative primary tumor resection on overall survival in minimally symptomatic (asymptomatic) colorectal cancer and synchronous unresectable metastases vs chemotherapy only: a comparative study of outcomes

Aim: to evaluate the impact of primary tumor resection (PTR) on treatment outcomes in patients with asymptomatic or minimally symptomatic colorectal cancer (CRC) and synchronous unresectable metastases.Patients and Methods: treatment outcomes of patients with minimally symptomatic CRC and synchronous unresectable metastases were retrospectively assessed (2016–2022). Patients with PTR followed by chemotherapy were compared to patients receiving chemotherapy only. Survival was determined by the Kaplan-Meier method and differences were evaluated using the log-rank test and Cox proportional-hazards regression model. To reduce potential selection bias between two groups a propensity score matching (PSM) was performed.Results: no significant differences in 30-day mortality rate (р = 1,00) and the rate of surgical intervention due to complications of first treatment (р = 1,00) between the two groups. Before matching the median survivals were 27,8 and 24 months in the PTR and chemotherapy groups, respectively (р = 0,2). After PSM the overall survival rate at 3 years was 42,1% for the PTR group and 34% for the chemotherapy group (р = 0,47). The median survivals were 27,9 and 24,4 months, respectively. Three-year overall survival rate for patients with stage IVB was significantly higher in the PTR group than in the chemotherapy group (37,8% versus 4,8%; р = 0,02). The median survivals were 36,1 and 17,2 months, respectively. In multivariate analysis radical resection (R0) if unresectable metastases converted into resectable after initial treatment was the only significant prognostic factor for survival (p < 0,001).Conclusions: PTR in patients with asymptomatic or minimally symptomatic CRC and synchronous unresectable metastases is associated with acceptable postoperative morbidity and mortality rates and may improve overall survival for patients with stage IVB comparing to chemotherapy as a treatment of first line. However, randomized controlled trials are needed.

The impact of primary tumor resection for asymptomatic colorectal cancer patients with unresectable metastases: a systematic review and meta-analysis.

Whether patients with asymptomatic primary tumors and unresectable metastases of colorectal cancer (CRC) should undergo primary tumor resection (PTR) remains controversial. This study aims to determine the appropriateness of PTR for these individuals by evaluating a number of outcome measures. A systematic literature search was performed. Outcome measures included overall survival, emergency surgery rates, incidence of postoperative complications, time to initiate chemotherapy, conversion rates, and chemotherapy-related toxicities. Patients who received PTR in addition to chemotherapy had a better overall survival rate than those who only received chemotherapy (HR = 0.62, 95%CI, 0.50-0.78, I2 = 84%, p < 0.00001). In the RCT subgroup, there were no significant differences with a HR of 0.72 (95%CI, 0.45-1.13, I2 = 17%, p = 0.15). More patients in the chemotherapy alone group could be converted to resectable status (OR = 0.47, 95%CI, 0.27-0.82, I2 = 0%, p = 0.008), but the incidence of emergency surgery was 23% (95%CI, 17-29%, I2 = 14%). The risk of chemotherapy-related toxicity was not significantly higher in the PTR group (OR = 1.5, 95%CI, 0.94-2.43, p = 0.09, I2 = 0%), with a 7% incidence of postoperative complications (95%CI, 0-14%, p = 0.05, I2 = 0%). The time to initiate chemotherapy after PTR was approximately 33.06days (95%CI, 25.55-40.58, I2 = 0%). PTR plus chemotherapy may be associated with improved survival in asymptomatic CRC patients with unresectable metastases. However, PTR did not provide a significant survival benefit in the subgroup of RCTs. Additionally, PTR did not result in a significantly increased risk of chemotherapy-related toxicity, with a postoperative complication rate of approximately 7%, and chemotherapy could be initiated at approximately 33.06days after PTR. Compared with the PTR plus chemotherapy, chemotherapy alone could result in a significantly higher conversion rate. However, about 23% of patients receiving chemotherapy alone required emergency surgery for primary tumor-related symptoms. The above results needed to be validated in future larger prospective randomized trials.

Recent Advance in the Surgical Treatment of Metastatic Colorectal Cancer-An English Version.

Stage IV colorectal cancer (CRC) has heterogeneous characteristics in tumor extent and biology. The overall survival of patients with metastatic CRC has improved with the development of multimodal treatments and new chemotherapeutic drugs. Resection of metastatic CRC is performed for liver, lung, or peritoneal metastases. Conversion surgeries to resect oligometastatic lesions have been developed with tumor regression using chemotherapeutic agents. Two-stage hepatectomy has extended the surgical indications for patients with metastatic CRC. Synchronous liver and primary tumor resection can be considered in patients with adequate conditions. Local ablation with radiotherapy can be used to treat lung metastasis. In the treatment of patients with CRC with peritoneal metastasis, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy can be considered. Surgical treatments should be performed in patients with symptomatic primary tumors with unresectable metastasis. However, primary tumor resection in patients with asymptomatic CRC with synchronous, unresectable metastases did not show overall survival benefits in recent studies. Therefore, the treatment of metastatic CRC is challenging due to the variable tumor extent and heterogenous characteristics. Tailored surgical treatments and multidisciplinary approaches may improve survival and the quality of life in patients with metastatic CRC.

Surgical treatment for metastatic colorectal cancer

Background: Stage IV colorectal cancer (CRC) exhibits heterogeneous characteristics in tumor extent and biology. The overall survival of patients with metastatic CRC has improved with the development of multimodal treatments and new chemotherapeutic drugs.Current Concepts: Resection of metastatic CRC is performed for liver, lung, or peritoneal metastases. Conversion surgeries to resect oligometastatic lesions have been developed with tumor regression using chemotherapeutic agents. Two-stage hepatectomy has extended the surgical indications for patients with metastatic CRC. Synchronous liver and primary tumor resection can be considered in patients with adequate conditions. Local ablation with radiotherapy can be used to treat lung metastasis. Meanwhile, for treating patients with CRC with peritoneal metastasis, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy can be considered. Surgical treatments should be performed in patients with symptomatic primary tumors with unresectable metastasis. However, in recent studies, primary tumor resection in patients with asymptomatic CRC with synchronous, unresectable metastases did not show overall survival benefits.Discussion and Conclusion: The treatment of metastatic CRC is challenging because of the variable tumor extent and heterogenous characteristics. Tailored surgical treatments and multidisciplinary approaches may improve the survival and quality of life of patients with metastatic CRC.

Validation of the Asia-Pacific colorectal screening score and its modified versions in predicting colorectal advanced neoplasia in Chinese population

BackgroundColorectal cancer is one of the most common cancers in the world. Several studies suggest using the Asia-Pacific colorectal screening (APCS) score and its modified versions to select high-risk populations for early colonoscopy, but external validation remains rare, and which score should be selected for CRC screening in China is unclear. Validation of multiple scores in the same population might help to choose the best performing score.MethodsWe conducted a cross-sectional study under the framework of Cancer Screening Program in Urban China, data from asymptomatic colorectal cancer screening in Xuzhou was used to validate the APCS score, the colorectal neoplasia predict (CNP) score, the Korean colorectal screening (KCS) score, the Modified APCS score and the 8-point risk score in predicting colorectal advanced neoplasia (CAN).Results1804 subjects were included in the analysis and 112 CAN (6.21%) was detected. In each score, the detection rate of CAN was higher in the high-risk group than in the non-high-risk group (P < 0.05), and the RR (95%C.I.) ranged 2.20 (1.50–3.22) [8-point risk] to 4.00 (2.41–6.65) [Modified APCS]. The c-statistics (95%C.I.) of the scoring systems ranged from 0.58 (0.53–0.62) [8-point risk] to 0.65 (0.61–0.69) [KCS]. The sensitivity (95%C.I.) of these systems ranged from 31.25 (22.83–40.70) [8-point risk] to 84.82 (76.81–90.90) [Modified APCS], while the specificity (95%C.I.) ranged from 43.50 (41.12–45.90) [Modified APCS] to 83.81 (81.96–85.53) [8-point risk]. Using the APCS scoring system as a comparator, the net reclassification improvement (NRI) of each modified version ranged from − 10.34% (95%C.I.: − 22.63 to 1.95%) [8-point risk] to 4.79% (95%C.I.: − 1.50% to 11.08) [KCS]. The colonoscopy resource load (95%C.I.) ranged from 9 [1–3] [8-point risk] to 11 [3–5] [APCS and Modified APCS].ConclusionsThe APCS score and its modified versions have certain ability to predict the risk of advanced neoplasia and reduce the resource load. The modified APCS score and the KCS score seemed the preferable systems to classify high risk subjects based on its high RR, sensitivity and predictive ability in the selected population. Future research could focus on adding risk factors or combining with laboratory test results to improve the predictive power of the scoring system.

Symptomatic Colorectal Cancer Is Associated With Stage IV Diagnosis in Two Disparate Populations.

In the United States, individuals of Black/African Ancestry (AA) have a higher incidence and mortality from colorectal cancer (CRC) compared to individuals of White/European Ancestry (EA). In order to develop an approach towards disentangling the complex effects of associated race and socioeconomic factors on CRC outcome, we have conducted a manual chart review of sporadic CRC pathological diagnoses (total n = 334) at an urban public hospital (UH) and a suburban university hospital (SH). There were significant differences between the SH and UH CRC patients with respect to Black/AA race (4.2% vs. 89.1%, p < 0.0001) and Medicaid/Self-pay insurance status (14.9% vs. 85.0%, p < 0.0001). While a higher proportion of newly diagnosed CRC patients presented with metastatic stage 4 CRC at the UH (21%) than the SH (12.5%), only the presence of symptoms was significantly associated with stage 4 CRC (odds ratio, OR 7.94, 95% confidence interval, CI 1.83- 34.54, p = 0.0057) in a multivariable generalized linear model (GLM). The proportion of asymptomatic CRC patients was ~20% at both institutions, suggesting that the UH has contributed to reducing CRC disparities. Initiation of CRC screening at the recommended age at both institutions could reduce the proportion of CRC patients presenting with metastatic spread.

Abstract 3391: Methylation analysis using TriMeth indicate that asymptomatic colorectal cancers (CRCs) release less circulating tumor DNA (ctDNA) compared to symptomatic cancers

Abstract Background: Early detection of cancer is key to identify tumours at a time when patients can be offered curatively intended treatments and outcomes are superior. Previous studies have presented sensitive methods for detection of ctDNA in early-stage cancer, but very few have been validated in asymptomatic individuals e.g. a true screening setting. Furthermore, many methods rely on expensive sequencing-based approaches that may not be cost-effective for population-based screening. Recently, we developed TriMeth, a simple CRC-specific ctDNA detection test based on three DNA methylation markers, which showed a sensitivity of 85% (stage I: 80%, stage II: 85%, stage III: 89%, stage IV: 88%) and a specificity of 99% when evaluated in CRC patients and controls (n=434). Objective: This study aimed to assess the performance of TriMeth cell-free DNA methylation analysis in asymptomatic individuals. Methods and materials: TriMeth was evaluated in 727 average-risk, asymptomatic individuals from the Danish population-based CRC screening program aged 50-74 years. This cohort included 105 CRC patients (stage I: n=53, stage II: n=24, stage III: n=19, stage IV: n=9) and 622 age and gender-matched controls enriched for comorbidities common to the screening population, such as, diabetes (n=47), arthritis (n=9), hypertension (n=279), arteriosclerosis (n=90), inflammatory bowel disease (n=6), adenomas (n=49), and other cancers (n=91). For comparison, TriMeth was also applied to a cohort of 43 symptomatic CRC patients and 42 cancer-free controls. Results: In the asymptomatic cohort, the specificity was consistently high (99%) despite the enrichment for controls with comorbidities in this cohort. The sensitivity was 36%, and was reduced for all disease stages compared to symptomatic cancers, though most markedly reduced for stage I CRC (stage I: 9%, stage II: 67%, stage III: 53%, stage IV: 78%). For a subset of asymptomatic individuals (n=91), an additional aliquot of plasma was analyzed, revealing a very high reproducibility of TriMeth (Spearman corr.coeff. r=0.95, p=7.6e-14). However, merging data from the paired samples did not significantly increase sensitivity. TriMeth showed consistently high accuracy in the symptomatic cohort (sensitivity: 84% and specificity: 100%). Conclusion: TriMeth is highly specific and not affected by comorbidities commonly found in 50-74 years old individuals invited for CRC screening. TriMeth showed high sensitivity for all stages when evaluated in symptomatic CRC patients, but the sensitivity was significantly decreased in asymptomatic cancers, also when stage-stratified. This indicate that asymptomatic cancers, independent of stage, shed less ctDNA than symptomatic cancers and highlights the importance of evaluating methods for early cancer detection in asymptomatic individuals. Citation Format: Sarah Østrup Jensen, Nadia Øgaard, Mai-britt Worm Ørntoft, Mads Heilskov Rasmussen, Jesper Bertram Bramsen, Christina Therkildsen, Claus Lindbjerg Andersen. Methylation analysis using TriMeth indicate that asymptomatic colorectal cancers (CRCs) release less circulating tumor DNA (ctDNA) compared to symptomatic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3391.

Abstract 6203: Evaluating cost-effectiveness and clinical utility of a blood-based colorectal cancer (CRC) early detection assay, ColonAiQ࣪, through a real-world study in average-risk population (PreC)

Abstract Background: Effective non-invasive colorectal cancer (CRC) screening assays, with high sensitivity and specificity, are desired to increase patient compliance, improve early detection, and reduce CRC mortality. Current stool-based tests suffer with the handling difficulties with specimen, while blood-based tests that rely on single gene methylation have limited sensitivity. We have developed a multi-locus blood-based assay targeting circulating tumor DNA methylation, ColonAiQ, which was demonstrated the ability of early detection for CRC and advanced adenoma (AA) [1]. Study Design: We further organized a real-world cohort aiming for recruiting 120,000 average-risk population to evaluate ColonAiQ’s cost-effectiveness and clinical utility over a 3-year period. This Prospective evaluation of ColonAiQ, PreC study, is organized in Yangzhou city in China being supported by the local government and hospitals. Results: From Jan. 2021 to Aug. 2021, 21,735 apparently healthy volunteers aging from 40 to 80 (median 61.8) were recruited with 10ml blood draw to process with ColonAiQ assay. One thousand six hundred and thirty (7.5%) were tested positive in ColonAiQ, among which 650 were further examined by colonoscopy followed by pathological diagnosis on the biopsy specimen. We successfully identified 330 patients with neoplasm, including 14 (4.3%) asymptomatic CRC, 99 (30%) AA, 184 (43.9%) multi-adenoma or non-advanced adenoma, 33 (10%) polyps, together with 19 patients with non-neoplastic GI disorders. The positive predictive value (PPV) is primarily estimated as 2.2% for CRC and 15.2% for AA (43.5% for adenoma), although these numbers can be largely influenced by the scale of the sample size. Among those 14 identified CRC cases, none of them were tested positive in fecal immunochemical test (FIT), the current screening method locally available. Conclusion: Results from this real-world analysis of ColonAiQ performance, although a preliminary subset, demonstrates the assay robustness, tester compliance, patient adherence to the test result, substantially maximizing its potential benefits for average-risk CRC screening. ColonAiQ significantly increases the detection rate for precancerous adenomas and early-stage CRC when compared to existing molecular screening tests, which could greatly improve preventative care and CRC patient survival. Citation Format: Yanbing Ding, Jun Liu, Yongsheng Li, Cuiping Wang, Huisong Luo, Yang Li, Tingdong Tang, Hui Wang, Wenjun Pan, Huimin Yang, Haipeng Jia, Yunzhi Zhang, Rui Liu. Evaluating cost-effectiveness and clinical utility of a blood-based colorectal cancer (CRC) early detection assay, ColonAiQ࣪, through a real-world study in average-risk population (PreC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6203.

Combined Performance of Fecal Immunochemical Tests and a Genetic Risk Score for Advanced Neoplasia Detection

In our study, combining polygenic risk score with fecal immunochemical test (FIT) did not improve diagnostic accuracy for advanced colorectal neoplasia detection compared with FIT alone. So far, such a combination cannot be recommended because it would come at extra costs and effort despite no relevant gain in neoplasia detection.

Impact of Upfront Chemotherapy on the Effect of Primary Tumour Resection for Asymptomatic Synchronous Colorectal Cancer With Unresectable Metastases: A Propensity-Score-Matched Cohort Analysis.

Background:It is controversial whether primary tumour resection (PTR) and the sequencing of chemotherapy and PTR are associated with the survival of patients with incurable stage IV colorectal cancer. This study aimed to explore the effects of PTR and the sequencing of chemotherapy and PTR on asymptomatic colorectal cancer with synchronous unresectable metastases (asmCRC).Patients and Methods:Patients with asmCRC were retrospectively identified from a single centre and categorised into 3 groups: PTR followed by chemotherapy (POC), upfront chemotherapy followed by PTR (UFC), and palliative chemotherapy (PC). The primary end points included median overall survival (OS) and progression-free survival (PFS). Clinical features were analysed using χ2 test, while survival curves were generated using the Kaplan-Meier test. Propensity-score matching (PSM) was performed when comparing survival between POC and UFC groups.Results:From 2008 to 2014, 255 patients were identified and included into the POC (n = 101), UFC (n = 40), and PC (n = 114) groups. The UFC and POC groups had significantly better median OS compared with the PC group (40.7 vs 16.3 months, P < .0001; 39.7 vs 16.3 months, P < .0001). Before PSM, the UFC group had better median PFS than the POC and PC groups (18.5 vs 9.7 months, P = .038; 18.5 vs 6.1 months, P < .0001). After PSM, UFC has better PFS than POC (P = .038). And the UFC group did not have higher postoperative or preoperative morbidity compared with the POC group (P = .235).Conclusions:Primary tumour resection could improve the survival of patients with asmCRC. Compared with POC or PC, UFC was associated with a better median PFS without significantly increasing preoperative or postoperative morbidity.

Colorectal cancer screening challenges in Saudi Arabia. A comprehensive review article

Colorectal cancer (CRC) is the leading cause of cancer-related deaths in Saudi Arabia and usually presents late in patients, who become symptomatic in advanced stages; thus, most cases of CRC in Saudi Arabia have poor outcomes. Saudi Arabia currently follows published guidelines and recommends screening for CRC because early diagnosis is critical; the Saudi Arabian healthcare system runs a program “Colorecal Cancer Early Detection” that has been rolled out in a gradual fashion. A screening program would aim to find individuals with asymptomatic CRC, educate patients, and streamline the process of screening for medium- and high-risk people. Currently, the Saudi Arabian population present minimal knowledge regarding CRC, the benefits of screening, and the importance of regular screening. The Saudi population is heavily dependent on physician recommendations for CRC screening, but physicians working in primary healthcare rarely recommend screening for CRC even in patients who have risk factors. The screening program for CRC in Saudi Arabia is cost effective. Public education is necessary along with expanded colonoscopy resources to continue enhance citizen participation and overcome the barriers of CRC screening such as physician recommendation and female gender low participation.

Racism Is a Modifiable Risk Factor: Relationships Among Race, Ethnicity, and Colorectal Cancer Outcomes

Racism Is a Modifiable Risk Factor: Relationships Among Race, Ethnicity, and Colorectal Cancer Outcomes

Upfront primary tumour resection and survival in synchronous metastatic colorectal cancer according to primary tumour location and RAS status: Pooled analysis of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

IntroductionRetrospective studies and meta-analyses suggest that upfront primary tumour resection (UPTR) confers a survival benefit in patients with asymptomatic unresectable metastatic colorectal cancer (mCRC) undergoing chemotherapy, however a consensus of its role in routine clinical practice in the current era of targeted therapies is lacking. This retrospective study aimed to analyse the survival benefit of UPTR in terms of tumour location and mutational status, in patients with synchronous mCRC receiving chemotherapy and targeted therapy. Patients and methodsSurvival was analysed in a pooled cohort of synchronous mCRC patients treated with a first-line anti-VEGF or anti-EGFR inhibitor in seven trials of the Spanish TTD group, according to UPTR, tumour-sidedness and mutational profiling. ResultsOf 1334 eligible patients, 642 (48%) had undergone UPTR. UPTR was associated with significantly longer overall survival (OS; 25.0 vs 20.3 months; HR 1.30, 95%CI 1.15–1.48; p < 0.0001). UPTR was associated with significant OS benefit in both left-sided (HR 1.38, 95%CI 1.13–1.69; p = 0.002) and right-sided (HR 1.39, 95%CI 1.00–1.94; p = 0.049) tumours, RASwt (HR 1.29, 95%CI 1.05–1.60; p = 0.016) and BRAFwt (HR 1.49, 95%CI 1.21–1.84; p = 0.0002) tumours, and treatment with anti-EGFRs (HR 1.47, 95%CI 1.13–1.92; p = 0.004) and anti-VEGFs (HR 1.25, 95%CI 1.08–1.44; p = 0.003). Multivariate analysis identified number of metastatic sites, RAS status, primary tumour location and UPTR as independent prognostic factors for OS. ConclusionConsidering the selection bias inherent to this study, our results support UPTR before first-line anti-EGFR or anti-VEGF targeted therapy in right and left-sided asymptomatic unresectable synchronous mCRC patients. RAS/BRAF mutational status may also influence UPTR function.

Primary Tumor Resection and Patients With Asymptomatic Colorectal Cancer and Nonresectable Metastases

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue

Detection of cancers and advanced adenomas in asymptomatic participants in colorectal cancer screening: a cross-sectional study

ObjectivesTo assess detection rates for colorectal cancer (CRC) and advanced adenomas in asymptomatic CRC screening participants and bowel symptoms in association with CRC and advanced adenoma.DesignCross-sectional study.SettingTwo screening centres.Participants42 554...

Multimodal circulating tumor DNA (ctDNA) colorectal neoplasia detection assay for asymptomatic and early-stage colorectal cancer (CRC).

3536 Background: To improve average risk CRC screening compliance, additional options are needed, especially options that address patient and provider reported barriers such as time and convenience. LUNAR-2 is a multimodal blood-based colorectal neoplasia detection assay incorporating ctDNA assessment of somatic mutations and tumor derived methylation and fragmentomic patterns, aimed to maximize sensitivity for early stage CRC detection. We evaluated this test in a large patient cohort with newly diagnosed CRC. Methods: Individuals diagnosed with CRC between 2013-2016 consented to provide blood samples prior to surgical resection. Those treated with neoadjuvant chemotherapy were excluded. Isolated plasma samples (median 3mL from EDTA) from 434 individuals were analyzed with LUNAR-2 (Guardant Health, USA) and included in the analysis. Median age at CRC diagnosis was 63 years (range 28 - 89) and 41% were female. Control samples were from 271 age-matched cancer free individuals. “ctDNA detected” and “ctDNA not detected” results were generated by a model trained on a separate sample set (N=614) from both cancer free individuals and those with CRC. Calling threshold was determined based on this held-out set to target 90% specificity. ctDNA results and clinical characteristics were correlated. Results: Overall CRC sensitivity was 91% (393/434), with high sensitivity across all stages; 88% Stage I/II, 93% Stage III (Table). Specificity was 94% (255/271). There was no difference in sensitivity when excluding those with early (&lt;45 years) or late (&gt;84 years) onset CRC (90% sensitivity; 388/429; p=0.95; 88% Stage I/II, 93% Stage III). There were no differences in sensitivity for asymptomatic CRC (88%) compared to symptomatic CRC (91%; p=0.4; Table). However, higher cell-free DNA tumor fractions were observed in the symptomatic cohort. Sensitivity for detection of right-sided and left-sided CRC was similar (93% vs. 90%; p=0.5; Table). Conclusions: In this large early-stage CRC cohort, multimodal ctDNA assessment has high sensitivity for CRC detection with high specificity. Equivalent sensitivity in the asymptomatic cohort suggests this test will have clinically meaningful performance in an average risk screening population. A prospective registrational study is ongoing to evaluate the test in an average risk CRC screening cohort.[Table: see text]