Current noninvasive tests for colorectal cancer screening: An overview of colorectal cancer screening tests

Colorectal cancer (CRC) has become the third most common cancer in the world. Screening has been shown to be an effective way to identify early CRC and precancerous lesions, and to reduce its morbidity and mortality. Several types of noninvasive tests have been developed for CRC screening, including the fecal occult blood test (FOBT), the fecal immunochemical test (FIT), the fecal-based DNA test and the blood-based DNA test (the SEPT9 assay). FIT has replaced FOBT and become the major screening test due to high sensitivity, specificity and low costs. The fecal DNA test exhibited higher sensitivity than FIT but its current cost is high for a screening assay. The SEPT9 assay showed good compliance while its performance in screening needs further improvements. These tests exhibited distinct sensitivity and specificity in screening for CRC and adenoma. This article will focus on the performance of the current noninvasive in vitro diagnostic tests that have been used for CRC screening. The merits and drawbacks for these screening methods will also be compared regarding the techniques, usage and costs. We hope this review can provide suggestions for both the public and clinicians in choosing the appropriate method for CRC screening.     

Practical considerations for colorectal cancer screening in older adults

Recent guidelines recommend that colorectal cancer (CRC) screening after age 75 be considered on an individualized basis, and discourage screening for people over 85 due to competing causes of mortality. Given the heterogeneity in the health of older individuals, and lack of data within current guidelines for personalized CRC screening approaches, there remains a need for a clearer framework to inform clinical decision-making. A revision of the current approach to CRC screening in older adults is even more compelling given the improvements in CRC treatment, post-treatment survival, and increasing life expectancy in the population. In this review, we aim to examine the personalization of CRC screening cessation based on specific factors influencing life and health expectancy such as comorbidity, frailty, and cognitive status. We will also review screening modalities and endoscopic technique for minimizing risk, the risks of screening unique to older adults, and CRC treatment outcomes in older patients, in order to provide important information to aid CRC screening decisions for this age group. This review article offers a unique approach to this topic from both the gastroenterologist and geriatrician perspective by reviewing the use of specific clinical assessment tools, and addressing technical aspects of screening colonoscopy and periprocedural management to mitigate screening-related complications.     

Fecal DNA testing for colorectal cancer screening: Molecular targets and perspectives

The early detection of colorectal cancer with effective screening is essential for reduction of cancer-specific mortality. The addition of fecal DNA testing in the armamentarium of screening methods already in clinical use launches a new era in the noninvasive part of colorectal cancer screening and emanates from a large number of previous and ongoing clinical investigations and technological advancements. In this review, we discuss the molecular rational and most important genetic alterations hallmarking the early colorectal carcinogenesis process. Also, representative DNA targets-markers and key aspects of their testing at the clinical level in comparison or/and association with other screening methods are described. Finally, a critical view of the strengths and limitations of fecal DNA tests is provided, along with anticipated barriers and suggestions for further exploitation of their use.     

Breast and colorectal cancer screening and associated correlates among Chinese older women

Objective: To explore the participation rates for breast and colorectal cancer screening and identify associatedcorrelates among elderly women. Methods: Logistic regressions were conducted using data collected in 2006from 1,533 elderly women aged 60 years or above who had completed a screening instrument, the MinimumData Set-Home Care, while applying for long-term care services at the first time in Hong Kong. Results: Theparticipation rates for breast and colorectal cancer screening among frail older Chinese women were 3.7% and10.8% respectively. Cognitive status was inversely associated with the likelihood of participation in screening(breast: OR = 0.66, 95%CI = 0.47-0.94; colon: OR = 0.81, 95%CI = 0.66-0.99), as was educational level withthe likelihood of participation in breast cancer screening (no formal education: OR = 0.20, 95%CI = 0.06-0.61,some primary education: OR = 0.31, 95%CI = 0.10-1.00). Conclusion: The delivery of cancer preventive healthservices to frail older women is less than ideal. Cognitive status and educational level were important factorsin cancer screening behaviour. Tailor-made strategic promotion programmes targeting older women with lowcognitive status and educational levels are needed to enhance awareness and acceptance within this vulnerablegroup.     

Molecular methods for colorectal cancer screening: Progress with next-generation sequencing evolution

Currently, colorectal cancer(CRC) represents the third most common malignancy and the second most deadly cancer worldwide, with a higher incidence in developed countries. Like other solid tumors, CRC is a heterogeneous genomic disease in which various alterations, such as point mutations, genomic rearrangements, gene fusions or chromosomal copy number alterations, can contribute to the disease development. However, because of its orderly natural history, easily accessible onset location and high...     

Using the Cancer Risk Management Model to evaluate colorectal cancer screening options for Canada

Background

Several screening methods for colorectal cancer (crc) are available, and some have been shown by randomized trials to be effective. In the present study, we used a well-developed population health simulation model to compare the risks and benefits of a variety of screening scenarios. Tests considered were the fecal occult blood test (fobt), the fecal immunochemical test (fit), flexible sigmoidoscopy, and colonoscopy. Outcomes considered included years of life gained, crc cases and deaths prevented, and direct health system costs.

Methods

A natural history model of crc was implemented and calibrated to specified targets within the framework of the Cancer Risk Management Model (crmm) from the Canadian Partnership Against Cancer. The crmm-crc permits users to enter their own parameter values or to use program-specified base values. For each of 23 screening scenarios, we used the crmm-crc to run 10 million replicate simulations.

Results

Using base parameter values and some user-specified values in the crmm-crc, and comparing our screening scenarios with no screening, all screening scenarios were found to reduce the incidence of and mortality from crc. The fobt was the least effective test; it was not associated with lower net cost. Colonoscopy screening was the most effective test; it had net costs comparable to those for several other strategies considered, but required more than 3 times the colonoscopy resources needed by other approaches. After colonoscopy, strategies based on the fit were predicted to be the most effective. In sensitivity analyses performed for the fobt and fit screening strategies, fobt parameter values associated with high-sensitivity formulations were associated with a substantial increase in test effectiveness. The fit was more cost-effective at the 50 ng/mL threshold than at the 100 ng/mL threshold.

Conclusions

The crmm-crc provides a sophisticated and flexible environment in which to evaluate crc control options. All screening scenarios considered in this study effectively reduced crc mortality, although sensitivity analyses demonstrated some uncertainty in the magnitude of the improvements. Where possible, local data should be used to reduce uncertainty in the parameters.     

Expected long-term impact of the German screening colonoscopy programme on colorectal cancer prevention: Analyses based on 4,407,971 screening colonoscopies

AimEndoscopy based screening programmes for colorectal cancer (CRC) are being implemented in an increasing number of countries. In Germany, screening colonoscopy at age 55 or older has been offered since the end of 2002. We aimed to estimate the long-term impact of this offer on CRC prevention.MethodsWe estimated numbers of prevented CRC cases by expected age and year of their (prevented) occurrence over four decades (2005–2045) by four state Markov models (non-advanced adenoma, advanced adenoma, preclinical CRC, clinically manifest CRC). Estimates are based on screening colonoscopies reported to the German screening colonoscopy registry in 2003–2012 (N = 4,407,971), transition rates between the four states and general population mortality rates.ResultsNumbers of prevented clinically manifest CRC cases are projected to increase from <100 in 2005 to approximately 6500 in 2015, 12,600 in 2025, 15,400 in 2035 and 16,000 in 2045, compared to approximately 58,000 incident cases observed in 2003. The annual number of prevented cases is expected to be higher among men than among women and to strongly vary by age. The vast majority of prevented cases would have occurred at age 75 or older.ConclusionsDespite modest participation rates, the German screening colonoscopy programme will lead to substantial reductions in the CRC burden. The reductions will be fully disclosed in the long run only and predominantly affect numbers of incident cases above 75 years of age. Screening offers would need to start at younger ages in order to achieve more effective CRC prevention at younger ages.     

Screening endoscopy and risk of colorectal cancer in United States men

Objectives: The purpose of this study was to describe the effect of screening endoscopy (sigmoidoscopy or colonoscopy) on colorectal cancer incidence and mortality. Methods: We used data from a prospective cohort study of 24,744 men aged 40 to 75 years in 1986, free from cancer and colon polyps, followed until 1994. The outcomes are diagnosis of colorectal cancer and death from colorectal cancer. Results: Screening endoscopy in 1986-87 was associated with a lower risk of all colorectal cancer (multivariate relative risk [RR]=0.58, 95 percent confidence interval [CI]=0.36-0.96); cancer in the distal colon or rectum (multivariate RR=0.40, CI=0.19-0.84); Dukes stage A&B (multivariate RR=0.66, CI=0.35-1.25); and Dukes stage C&D (multivariate RR=0.50, CI=0.20-1.26) colorectal cancer; and death from colorectal cancer (multivariate RR=0.56, CI=0.20-1.60), after adjusting for age and a wide range of colon cancer risk factors. Screening endoscopy in 1988-87 appeared to provide strong protection against distal stage C&D cancers (age-adjusted RR=0.16, CI=0.02-1.23) but no protection against proximal stage C&D cancers (age-adjusted RR=0.96, CI=0.32-2.91). Conclusions: This study provides strong evidence for a protective effect of screening sigmoidoscopy on colorectal cancer incidence and mortality and supports recommendations for screening sigmoidoscopy as an approach to colon cancer prevention.     

Profiles of circulating inflammatory cytokines in colorectal cancer (CRC), high cancer risk conditions,and health are distinct. Possible implications for CRC screening and surveillance

Alternate colorectal cancer (CRC) screening and surveillance strategies are needed to pre-select candidates for invasive methods. We compared systemic inflammatory profiles in CRC (n = 99), health (n = 98), high CRC-risk conditions (n = 48) and overt inflammation (n = 69) by multiplexed analysis of IL-1β, IL-6, IL-8, FGF-2, G-CSF, GM-CSF, MCP-1, MIP-1α, TNF-α, VEGF-A, and PDGF-B and CEA. Cytokines corresponded with CRC advancement. FGF2, GM-CSF, IL-1β, IL-6, MIP-1α, PDGF-BB, TNF-α, and VEGF-A were higher than in controls already in stage I CRC with FGF2, IL1-β, and MIP-1α higher than in high CRC-risk individuals as well. Cytokine panels devised to differentiate early CRC from controls, adenomas, or inflammatory bowel disease patients (IBD) had good accuracy but only IBD panel had promising specificity at 95% sensitivity.     

Outcome of surgical treatment for bone metastases caused by colorectal cancer

BackgroundCancer of the lower intestinal tract, although relatively common, rarely metastasizes to the skeleton. The treatment of metastatic bone disease due to colorectal cancer has thus been poorly described and treatment decisions are therefore difficult. The aim of this study was to describe the outcome of orthopedic surgery in patients with pathological fractures from colorectal cancer and investigate factors that correlate with patient survival, since it influences treatment decisions.MethodsRetrospective review of data collected in a prospectively collected database. 36 patients (38 fractures) who underwent surgery between 2000 and 2019 for metastatic bone disease caused by colorectal cancer were included.ResultsMost metastases were localized in the axial skeleton and 33/36 patients already had visceral metastases. Patients with pathological fractures from colorectal cancer had poor prognosis, with only 5/36 surviving more than 1 year, median survival being 3 months. Patients presenting with a single skeletal metastasis had a superior overall survival (P≤0.001). Post-operative complications were common, noted in 11 patients, and the surgical failure rate was considerable.ConclusionsAlthough relatively rare, bone metastases should be suspected in patients with colorectal cancer presenting with signs and symptoms of spinal cord compression or skeletal pain. In this case, the presence of a solitary skeletal lesion is a favorable prognostic sign. Awareness for local complications after surgery should be high.     

Specialists' perceptions of hereditary colorectal cancer screening in Newfoundland and Labrador

Purpose

Colorectal cancer (crc) screening is particularly valuable in Newfoundland and Labrador (NL), where a substantial proportion of crc cases have a hereditary link. We examined the perceptions of gastroenterologists and general surgeons with respect to screening practices for patients with hereditary crc.

Methods

We surveyed all gastroenterologists and general surgeons in NL to determine demographic and professional practice characteristics and screening knowledge, practices, and attitudes for four groups of patients with hereditary crc.

Results

Of the 43 eligible physicians, 36 (83.7%) responded. Most of the physicians surveyed knew the correct age to start screening, preferred screening by colonoscopy, had a systematic means in their own practice of prioritizing patients for screening, and felt that family doctors or patients (or both) should be responsible for monitoring screening compliance. Most physicians reported that patients with hereditary nonpolyposis crc and familial adenomatous polyposis waited 3 months for screening; patients with a family history of crc or adenomatous polyp waited 6 months or longer. Although respondents agreed on the need for a province-wide crc registry [4.36 on a 5-point Likert scale (1 = strongly disagree; 5 = strongly agree)], they disagreed that wait times were reasonable (2.81) and that other health professionals should perform colonoscopies (2.86). They were equivocal about the need for centralized bookings (3.25) and about whether genetic testing is useful for prioritizing patients (3.25).

Conclusions

Gastroenterologists and general surgeons in NL were knowledgeable about screening, but had varying opinions about individual roles in screening, wait times, and the means for prioritizing and providing screening for patients with hereditary crc.     

Preoperative ultrasonography screening for liver metastases of patients with colorectal cancer

The clinical value of preoperative ultrasonography in screening for synchronous liver metastases was prospectively evaluated in 338 patients with colorectal cancer. Synchronous liver metastases were observed at laparotomy in 11.5% (39/338) of the patients. The liver metastases had been found by preoperative ultrasonography in 30 patients and missed in nine. The overall accuracy rate, sensitivity and specificity, and the positive and negative predictive values of this modality were 0.970, 0.769, 0.997, 0.968 and 0.971, respectively. In detecting liver metastases, the results were superior to those of biochemical blood tests and measurements of carcinoembryonic antigen serum levels. The accuracy of the ultrasonography was also superior to that of these other tests combined. The results indicate ultrasonography to be an indispensable preoperative examination for patients with colorectal cancer.     

Knowledge and attitude of colorectal cancer screening among moderate risk patients in West Malaysia

Colorectal cancer is the commonest cancer among males and the third commonest cancer among women in Malaysia. However, almost 80% of patients sought treatment for cancer only when they were already in late stage due to lack of awareness. Hence, the objectives of this study were to determine the knowledge and attitude of colorectal cancer screening among moderate risk patients. A cross-sectional study was conducted between August 2009 till April 2010 in 44 health clinics with Family Medicine Specialists in West Malaysia. Stratified multistage random sampling was applied and a validated Malay version of the questionnaire with the Cronbach' alpha of 0.65 to 0.82 was used. Data were entered using SPSS 12.0 and analysed with STATA 8.0. A total of 1,905 (93.8%) patients responded. The mean (SD) knowledge and attitude score among moderate risk patients were 69.5 (6.11%) and 66.5 (7.07%), whereas, the percentages for good knowledge and attitude were 4.1% and 3.3% respectively. Less than 1% had undergone colorectal cancer screening and the main reasons were not bothered, busy and embarrassment. The majority of patients who had moderate risk for colorectal cancer had extremely low knowledge and attitude towards colorectal cancer screening. As a result, the majority did not undergo any form of colorectal cancer screening.     

Quality measures improving endoscopic screening of colorectal cancer: a review of the literature

Introduction: Colorectal cancer (CRC) is a major health-care problem all over the world and CRC screening is effective in reducing mortality and increasing the 5-year survival. Colonoscopy has a central role in CRC screening. It can be performed as a primary test, as a recall policy after a positive result of another screening test, and for surveillance. Since effectiveness of endoscopic screening depends on adequate detection and removal of colonic polyps, consistent quality measures, which are useful in enhancing the diagnostic yield of examination, are essential.

Areas covered: The aim of this review is to analyze current evidence from literature supporting quality measures able to refine endoscopic screening of colorectal cancer.

Expert commentary: Quality measures namely a) time slot allotted to colonoscopy, b) assessment of indication, c) bowel preparation, d) Cecal intubation, e) withdrawal time, f) adenoma detection rate, g) proper management of lesions (polypectomy technique, polyps retrieval rate and tattooing of resection sites), and h) adequate follow-up intervals play a key role in identifying malignant and at-risk lesions and improving the outcome of screening. Adherence to these quality measures is critical to maximize the effectiveness of CRC screening, as well as, a proper technique of colonoscopy and a quality report of the procedure. Among all recommended measures, adenoma detection rate is the most important and must be kept above the recommended quality threshold by all physicians practicing in the setting of screening.     

Association between robot-assisted surgery and resection quality in patients with colorectal cancer

Background

Resection quality after robot-assisted surgery for colorectal cancer have not previously been investigated in a nationwide study. The aim of the study was to examine the resection quality in robot-assisted versus laparoscopic surgery for colorectal cancer. Furthermore, 30-day mortality, postoperative complications, and conversion to open surgery were investigated.

Outcome of surgery for colorectal cancer in the presence of peritoneal carcinomatosis

Aim

The detection of peritoneal carcinomatosis (PC) in colorectal cancer patients frequently results in a dilemma with regard to the optimal treatment strategy, especially when PC is encountered unexpectedly during surgery. The aim of this study was to evaluate outcomes of patients undergoing surgery for colorectal carcinoma in the presence of synchronous PC.

Methods

Patients diagnosed with primary colorectal cancer and synchronous PC in three community hospitals were selected from the Eindhoven Cancer Registry database. Outcomes of postoperative complications, in-hospital mortality and overall survival were collected and analyzed according to the type of intervention performed.

Results

Between 1995 and 2009, 169 colorectal cancer patients were diagnosed with synchronous PC, most of them unexpectedly during surgery (n = 130). 142 patients underwent surgery: primary tumor resection (n = 91), palliative procedure (n = 46) or exploration only (n = 5). In-hospital mortality was 41% after palliative surgery and 14% after primary tumor resection. Median survival was 12 weeks after palliative surgery or exploration as opposed to 55 weeks after primary tumor resection.

Conclusion

PC is most often encountered unexpectedly during surgery for colorectal cancer. Results of palliative procedures are very poor with a high in-hospital mortality rate and short survival. Resection of the primary tumor can be performed safely with relatively good outcomes but some patients could have benefited from an even more radical approach when the presence of PC would have been diagnosed at an earlier stage. Improvement of imaging techniques to detect PC prior to surgery is therefore urgently needed. Until this is the case, a high index of suspicion is required when subtle signs of PC are encountered. Keywords: Colorectal cancer, Metastasis, Peritoneal carcinomatosis, Surgery     

Breast and cervical cancer screening behaviours among colorectal cancer survivors in Nova Scotia

Purpose

We analyzed patterns and factors associated with receipt of breast and cervical cancer screening in a cohort of colorectal cancer survivors.

Methods

Individuals diagnosed with colorectal cancer in Nova Scotia between January 2001 and December 2005 were eligible for inclusion. Receipt of breast and cervical cancer screening was determined using administrative data. General-population age restrictions were used in the analysis (breast: 40–69 years; cervical: 21–75 years). Kaplan–Meier and Cox proportional hazards models were used to assess time to first screen.

Results

Of 318 and 443 colorectal cancer survivors eligible for the breast and cervical cancer screening analysis respectively, 30.1% [95% confidence interval (ci): 21.2% to 39.0%] never received screening mammography, and 47.9% (95% ci: 37.8% to 58.0%) never received cervical cancer screening during the study period. Receipt of screening before the colorectal cancer diagnosis was strongly associated with receipt of screening after diagnosis (hazard ratio for breast cancer screening: 4.71; 95% ci: 3.42 to 6.51; hazard ratio for cervical cancer screening: 6.83; 95% ci: 4.58 to 10.16).

Conclusions

Many colorectal cancer survivors within general-population screening age recommendations did not receive breast and cervical cancer screening. Future research should focus on survivors who meet age recommendations for population-based cancer screening.     

How the COVID-19 pandemic has affected the colorectal cancer screening in Italy: A minireview

The coronavirus disease 2019 (COVID-19) pandemic has caused detrimental effects on many aspects of healthcare practice. Screening programs for the commonest malignancies, namely colorectal cancer (CRC), breast cancer and cervical cancer have been discontinued or interrupted since the beginning of restriction measures aimed to limit transmission of the new coronavirus infection. Robust evidence exists in favour of the role of screening campaigns in reducing mortality from CRC. In fact, the majority of pre-malignant lesions of the colon and rectum can be diagnosed with colonoscopy and treated by endoscopic or surgical resection. Besides, colonoscopy screening allows the diagnosis of CRCs in their pre-clinical stage. Italy was one of the first European countries where a high level of COVID-19 infections and deaths was observed, and one of the first where lockdowns and strict measures were adopted to reduce the risk of COVID-19 diffusion among the population. A systematic review of the literature was performed, including the PubMed, Scopus, Web of Sciences, and Reference Citation Analysis databases, with the aim of critically evaluating the impact of the COVID-19 pandemic on CRC screening in Italy. We found that reduction of CRC screening activity surpassed 50% in most endoscopic units, with almost 600000 fewer CRC screening exams conducted in the first 5 mo of 2020 vs the same period of 2019. While the consequences of the discontinuation of endoscopy screening for the prognosis and mortality of CRC will be evident in the next few years, recent data confirm that CRC is currently treated at a more advanced stage than in the pre-COVID-19 era. Since delays in CRC prevention and early diagnosis may translate to increased CRC-specific mortality, world healthcare systems should adopt strategies to maintain the regularity of CRC screening during subsequent peaks of the COVID-19 pandemic, or future events that might hamper screening programs.     

Primary care patients' understanding of colorectal cancer screening

PURPOSE: To determine the current level of awareness and understanding about colorectal cancer (CRC) and colorectal cancer screening (CRCS) among primary care patients in order to develop interventions to educate patients about options for CRCS, help them identify CRCS preferences and make informed choices about CRCS options. METHODS: During the spring of 2001 and 2003, two sets of focus groups with primary care patients were conducted at a large multi-specialty group practice in Houston, Texas. RESULTS: Participants (n = 42) in both sets of focus groups had low knowledge about CRC and expressed fear and embarrassment about CRC and CRCS. Attitudes towards the fecal occult blood test (FOBT) were mixed, with some participants considering it difficult to finish and others preferring the privacy it afforded. Some participants initially failed to recognize the difference between sigmoidoscopy (SIG) and colonoscopy (COL), and several endoscopy-specific barriers were identified such as fear of pain, embarrassment/humiliation, and dislike or fear of test preparation. Some participants felt that endoscopy was likely to be more effective than FOBT, and others clearly preferred COL to SIG. System-specific barriers to endoscopy (e.g. difficulty scheduling appointments and insurance coverage) were also identified. We found little change in the barriers reported by primary care patients, despite a two-year difference between focus groups. Participants also provided suggestions for improving CRCS including telephone, letters and/or email reminders from the clinic, videotapes and websites. CONCLUSIONS: Future interventions focused on improving informed decision-making by educating primary care patients about the risks and benefits of specific test options and about the importance of early detection of CRC could prove to be effective for increasing CRCS.