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One in three adenomas could be missed by white-light colonoscopy - findings from a systematic review and meta-analysis.
Background: White light (conventional) colonoscopy (WLC) is widely used for colorectal cancer screening, diagnosis and surveillance but endoscopists may fail to detect adenomas. Our goal was to assess and synthesize overall and subgroup-specific adenoma miss rates (AMR) of WLC in daily practice. Methods: We conducted a systematic review in MEDLINE, EMBASE, Cochrane Library, and grey literature on studies evaluating diagnostic WLC accuracy in tandem studies with novel-colonoscopic technologies (NCT) in subjects undergoing screening, diagnostic or surveillance colonoscopy. Information on study design, AMR overall and specific for adenoma size, histology, location, morphology and further outcomes were extracted and reported in standardized evidence tables. Study quality was assessed using the QUADAS-2 tool. Random-effects meta-analyses and meta-regression were performed to estimate pooled estimates for AMR with 95% confidence intervals (95% CI) and to explain heterogeneity. Results: Out of 5,963 identified studies, we included sixteen studies with 4,101 individuals in our meta-analysis. One in three adenomas (34%; 95% CI: 30-38%) was missed by WLC in daily practice individuals. Subgroup analyses showed significant AMR differences by size (36%, adenomas 1-5 mm; 27%, adenomas 6-9 mm; 12%, adenomas ≥ 10 mm), histology (non-advanced: 42%, advanced: 21%), morphology (flat: 50%, polypoid: 27%), but not by location (distal: 36%, proximal: 36%). Conclusions: Based on our meta-analysis, one in three adenomas could be missed by WLC. This may significantly contribute to interval cancers. Our results should be considered in health technology assessment when interpreting sensitivity of fecal occult blood or other screening tests derived from studies using WLC as "gold standard".
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Economic evaluations of radioembolization with yttrium-90 microspheres in liver metastases of colorectal cancer: a systematic review
BackgroundTransarterial radioembolization with yttrium-90 (Y-90 TARE) microspheres therapy has demonstrated positive clinical benefits for the treatment of liver metastases from colorectal cancer (lmCRC). This study aims to conduct a systematic review of the available economic evaluations of Y-90 TARE for lmCRC.MethodsEnglish and Spanish publications were identified from PubMed, Embase, Cochrane, MEDES health technology assessment agencies, and scientific congress databases published up to May 2021. The inclusion criteria considered only economic evaluations; thus, other types of studies were excluded. Purchasing-power-parity exchange rates for the year 2020 ($US PPP) were applied for cost harmonisation.ResultsFrom 423 records screened, seven economic evaluations (2 cost-analyses [CA] and 5 cost-utility-analyses [CUA]) were included (6 European and 1 USA). All included studies (n = 7) were evaluated from a payer and the social perspective (n = 1). Included studies evaluated patients with unresectable liver-predominant metastases of CRC, refractory to chemotherapy (n = 6), or chemotherapy-naive (n = 1). Y-90 TARE was compared to best supportive care (BSC) (n = 4), an association of folinic acid, fluorouracil and oxaliplatin (FOLFOX) (n = 1), and hepatic artery infusion (HAI) (n = 2). Y-90 TARE increased life-years gained (LYG) versus BSC (1.12 and 1.35 LYG) and versus HAI (0.37 LYG). Y-90 TARE increased the quality-adjusted-life-year (QALY) versus BSC (0.81 and 0.83 QALY) and versus HAI (0.35 QALY). When considering a lifetime horizon, Y-90 TARE reported incremental cost compared to BSC (range 19,225 to 25,320 $US PPP) and versus HAI (14,307 $US PPP). Y-90 TARE reported incremental cost-utility ratios (ICURs) between 23,875 $US PPP/QALY to 31,185 $US PPP/QALY. The probability of Y-90 TARE being cost-effective at pound 30,000/QALY threshold was between 56% and 57%.ConclusionsOur review highlights that Y-90 TARE could be a cost-effective therapy either as a monotherapy or when combined with systemic therapy for treating ImCRC. However, despite the current clinical evidence on Y-90 TARE in the treatment of ImCRC, the global economic evaluation reported for Y-90 TARE in ImCRC is limited (n = 7), therefore, we recommend future economic evaluations on Y-90 TARE versus alternative options in treating ImCRC from the societal perspective.
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Cost-effectiveness of colorectal cancer screening strategies - A systematic review
BACKGROUND & AIMS: Widespread screening for colorectal cancer (CRC) has reduced its incidence and mortality. Previous studies investigated the economic effects of CRC screening. We performed a systematic review to provide up to date evidence of the cost effectiveness of CRC screening strategies by answering 3 research questions. METHODS: We searched PubMed, NHS EED, SSCI, EconLit, and 3 supplemental databases for original articles published in English from January 2010 through December 2017. All monetary values were converted to United States (US) dollars (year 2016). For all research questions, we extracted, or calculated (if necessary), per-person costs and life years (LY) and/or quality-adjusted LYs (QALY), as well as the incremental costs per LY gained or QALY gained compared to the baseline strategy. A cost-saving strategy is defined as one that was less costly and equally or more effective than the baseline strategy. Net monetary benefit approach was used to answer research question 2. RESULTS: Our review comprised 33 studies (17 from Europe, 11 from North America, 4 from Asia, and 1 from Australia). Annual and biennial guaiac-based fecal occult blood tests, annual and biennial fecal immunochemical tests, colonoscopy every 10 years, and flexible sigmoidoscopy every 5 years were cost-effective (even cost saving in most US models) compared with no screening. Additionally, colonoscopy every 10 years was less costly and/or more effective than other common strategies in the US. Newer strategies such as computed tomographic colonography, every 5 or 10 years, were cost-effective compared to no screening. CONCLUSION: In an updated review, we found that common CRC screening strategies and computed tomographic colonography continued to be cost-effective compared to no screening. There were discrepancies among studies from different regions, which could be associated with the model types or model assumptions.
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A systematic review and meta-analysis on the effectiveness of web-based psychosocial interventions among patients with colorectal cancer
AIMS: To synthesize the effectiveness of web-based psychosocial interventions on self-efficacy, anxiety, depression, quality of life (QoL), non-specific psychological and cancer-specific distress among patients with colorectal cancer (CRC). DESIGN: A systematic review and meta-analysis. DATA SOURCES: Six databases (PubMed, PsycINFO, Embase, Scopus, CINAHL and CNKI) were searched from inception to December 2021. REVIEW METHODS: Experimental/quasi-experimental studies involving patients with CRC for the improvement of aforementioned outcomes were included. Two reviewers screened and extracted the data, and assessed studies' methodological quality using risk of bias tools. Meta-analyses and narrative syntheses were performed. RESULTS: Nineteen studies consisting of 1386 participants were identified. Cognitive-behavioural therapy delivered online was the most common trialled web-based psychosocial intervention. Meta-analyses revealed no positive effect for self-efficacy (standardized mean difference 0.93, 95% CI: 0.52 to 1.35, p < .01) and minimal benefit for QoL (mean difference [MD] 2.83, 95% CI: -0.31 to 5.98, p = .08) but significant positive effects for anxiety (MD -2.23, 95% CI: -3.31 to -1.14, p < .01) and depression (MD -2.84, 95% CI: -4.09 to -1.59, p < .01) among CRC survivors in the intervention group as compared with the control group. Narrative synthesis suggested possible benefits in reducing distress. CONCLUSION: Web-based psychosocial interventions are promising alternatives to conventional delivery methods in reducing patients' anxiety, depression and distress. However, evidence on self-efficacy and QoL remains inconsistent. More adequately powered, well-designed trials with targeted and theory-based interventions are required to ascertain findings. IMPACT: By highlighting the potential of web-based psychosocial interventions in reducing anxiety and depression among CRC survivors, this review has put forth beneficial information supporting the use and acceptance of web-based care delivery in light of COVID-19 restrictions and nationwide lockdowns. Meanwhile, the paucity of empirical support reflects the necessity of more extensive research to test and improve other health outcomes.
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Efficacy and safety of intraoperative radiotherapy in rectal cancer: A systematic review and meta-analysis
BACKGROUND In recent years, intraoperative radiotherapy (IORT) has been increasingly used for the treatment of rectal cancer. However, the efficacy and safety of IORT for the treatment of rectal cancer are still controversial. AIM To evaluate the value of IORT for patients with rectal cancer. METHODS We searched PubMed, Embase, Cochrane Library, Web of Science databases, and conference abstracts and included randomized controlled trials and observational studies on IORT vs non-IORT for rectal cancer. Dichotomous variables were evaluated by odds ratio (OR) and 95% confidence interval (CI), hazard ratio (HR) and 95%CI was used as a summary statistic of survival outcomes. Statistical analyses were performed using Stata V.15.0 and Review Manager 5.3 software. RESULTS In this study, 3 randomized controlled studies and 12 observational studies were included with a total of 1460 patients, who are mainly residents of Europe, the United States, and Asia. Our results did not show significant differences in 5-year overall survival (HR = 0.80, 95%CI = 0.60-1.06; P = 0.126); 5-year disease-free survival (HR = 0.94, 95%CI = 0.73-1.22; P = 0.650); abscess (OR = 1.10, 95%CI = 0.67-1.80; P = 0.713), fistulae (OR = 0.79, 95%CI = 0.33-1.89; P = 0.600); wound complication (OR = 1.21, 95%CI = 0.62-2.36; P = 0.575); anastomotic leakage (OR = 1.09, 95%CI = 0.59-2.02; P = 0.775); and neurogenic bladder dysfunction (OR = 0.69, 95%CI = 0.31-1.55; P = 0.369). However, the meta-analysis of 5-year local control was significantly different (OR = 3.07, 95%CI = 1.66-5.66; P = 0.000). CONCLUSION The advantage of IORT is mainly reflected in 5-year local control, but it is not statistically significant for 5-year overall survival, 5-year disease-free survival, and complications.
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The efficacy and safety of lateral lymph node dissection for patients with rectal cancer: A systematic review and meta-analysis
Lateral lymph node metastasis in rectal cancer was first reported in the 1950s, since then, there has been an on-going debate about the value of lateral lymph node dis (LLND) in the management of rectal cancer. We carried out a systematic review and meta-analysis to evaluate the value of LLND for the patients with rectal cancer. To collect clinical studies for the comparison of LLND and non-LLND in patients with rectal cancer, PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar databases were searched from inception to 2019. A total of 26 studies, including 6865 patients were enrolled. Data processing and statistical analyses were performed using Stata V.15.0 software and Review Manager 5.3 software. Outcome measures included the 5-year survival rate, recurrence rate, perioperative outcomes, urinary function, and male sexual function. Regarding efficacy, our meta-analysis results showed no difference in 5-year disease-free survival rate and local recurrences between the two groups, the Hazard Ratio (HR) and 95% confidence interval (CI) was 1.07 and 0.89 to 1.28 (P = 0.496), and the Odds Ratio(OR) and 95% CI were 0.90 and 0.76 to 1.06 (P = 0.208), respectively. Concerning safety, the incidence of urinary dysfunction and male sexual dysfunction was significantly increased in the LLND group (OR = 2.14, 95%CI = 1.21-3.79, P = 0.009), and (OR = 4.19, 95%CI = 1.55-11.33, P = 0.005), respectively. In conclusion, LLND did not improve the long-term prognosis of patients with rectal cancer, and was associated with increased urinary dysfunction and male sexual dysfunction.
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Population health interventions to improve colorectal cancer screening by fecal immunochemical tests: A systematic review
Despite clear evidence that colorectal cancer (CRC) screening reduces mortality, screening, including fecal immunochemical tests (FIT), is underutilized. We conducted a systematic review to determine the evidence of efficacy of interventions to improve FIT completion that could be scaled and utilized in population health management. We systematically searched publication databases for studies evaluating provider- or system-level interventions to improve CRC screening by FIT between 1 January 1996 and 13 December 2017 without language restrictions. Twenty articles describing 25 studies were included, 23 were randomized controlled trials with 1 quasi-experimental and 1 observational study. Ten studies discussed mailed FIT outreach, 4 pre-FIT patient reminders, 3 tailored patient messages, 2 post-FIT reminders, 2 paired FIT with influenza vaccinations, 2 provider alerts and 1 study each described the use of high-quality small media and patient financial incentives. Mailed FIT outreach was consistently effective with median improvement in CRC screening of 21.5% (interquartile range (IQR) 13.6%-29.0%). FIT paired with vaccinations led to a median 15.9% (IQR 15.6%-16.3%) improvement, while pre-FIT and post-FIT reminders demonstrated modest efficacy with median 4.1% (IQR 3.6%-6.7%) and 3.1% (IQR 2.9%-3.3%) improvement in CRC screening, respectively. More than half the studies were at high or unclear risk of bias; heterogeneous study designs and characteristics precluded meta-analysis. FIT-based CRC screening programs utilizing multilevel interventions (e.g. mailed FIT outreach, FIT paired with other preventative services, and provider alerts) have the potential to significantly increase screening participation. However, such programs must also follow-up patients with abnormal FIT results.
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Patient education interventions for colorectal cancer patients with stoma: A systematic review
OBJECTIVES: To describe the various types of patient education interventions for colorectal cancer patients with stoma and to examine their effects on quality of life, psychosocial skills and self-management skills. METHODS: A systematic review was performed. Six electronic databases were searched. Inclusion criteria were: studies about patient education applying quantitative methods including digestive stoma adults with colorectal cancer. The primary outcome was quality of life. Secondary outcomes were psychosocial and self-management skills. RESULTS: Thirteen studies were identified and included. Five studies examined quality of life and three reported improvements. Patient education improved some psychosocial and self-management skills. Contrasting findings were reported for specific-disease quality of life, emotional distress, length of hospital stay, stoma complications and readmission rate. CONCLUSIONS: Patient education has a positive impact on some psychosocial and self-management skills, indicating that this area should be developed. Contrasting findings were reported for quality of life. Methodologies are heterogeneous making it difficult to produce evidence-based guidelines. This article proposes tools to carry out further studies on this subject and to improve understanding. PRACTICE IMPLICATION: Further education intervention for stoma patients with colorectal cancer should be standardized in terms of intervention, duration and outcome measures to compare intervention and determine best practice.
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DNA mismatch repair deficiency tumour testing for patients with colorectal cancer: a health technology assessment
Excerpt Testing tumours for deficient DNA mismatch repair (dMMR) has been identified as a practice that is potentially over-utilized. According to clinical experts, dMMR tumour testing appears to be transitioning from an approach aimed at identifying patients and families with Lynch syndrome (LS) into a tumour phenotyping procedure that can be used to predict the prognosis of colorectal cancer (CRC) and to guide for adjuvant chemotherapy decisions. The use of a test with a prognostic and predictive value falls under the realm of “personalized medicine.” According to oncology and pathology experts, this recent application of dMMR tumour testing is the major driver of new test requisitions. This transition has led to an increased demand for the test, with unclear benefits for the patient or family members. In general, there is a lack of clarity regarding when the tests should be ordered and the impact of tumour dMMR status on CRC outcomes in the current era of oxaliplatin- and irinotecan-based chemotherapy. The central question, however, is whether universal dMMR tumour testing of CRC tumours is a viable and desirable option, given the known limitations of LS pre-selection criteria based on age, history, and pathology, and recognizing the potential utility of tumour dMMR status for personalizing cancer therapy. Missed cases of LS resulting from a targeted tumour dMMR testing strategy that is restricted to pre-selected high-risk individuals (e.g., selected based on the rBG) can be problematic and costly for the system, which would potentially support broader (universal) dMMR tumour testing of all CRC tumours. Alternatively, universal tumour testing carries with it additional costs associated with testing all CRC patients, most of whom will not have LS. In summary, there is uncertainty regarding: Optimal eligibility criteria for dMMR tumour testing in:CRC patients to identify new families with LSCRC patients to inform prognosis or prediction of response to chemotherapy. The cost-effectiveness of tumour screening strategies and algorithms in:CRC patients to identify new families with LSCRC patients to inform prognosis or prediction of response to chemotherapy.
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Risk of grade 3-4 diarrhea and mucositis in colorectal cancer patients receiving anti-EGFR monoclonal antibodies regimens: A meta-analysis of 18 randomized controlled clinical trials
The anti-Epidermal Growth Factor Receptor monoclonal antibodies (anti-EGFR MoAbs) are beneficial in the treatment of wild type (WT) KRAS colorectal cancer, but are burdened by serious toxicities. We conducted a systematic review and meta-analysis to determine incidence and relative risk (RR) of severe and life-threatening diarrhoea and mucositis in colorectal cancer patients and WT-KRAS subpopulation. PubMed and Embase were searched for trials comparing the same therapeutic regimens with or without anti-EGFR for colorectal cancer. Data on severe and life-threatening diarrhoea and mucositis were extracted from 18 studies involving 13,382 patients. Statistical analyses calculated incidence of AEs, RRs and 95% confidence intervals by using either random or fixed effects models. Patients receiving anti-EGFR MoAbs showed an increased risk of diarrhoea (RR: 1.66, CI 1.52-1.80) and mucositis (RR: 3.44, CI 2.66-4.44). The risk was similar among WT-KRAS patients. Prevention and risk reduction strategies of these AEs are mandatory to optimize clinical outcomes
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Vascular endothelial growth factor receptor tyrosine kinase inhibitors versus bevacizumab in metastatic colorectal cancer: A systematic review and meta-analysis
Bevacizumab has demonstrated a survival benefit in patients with metastatic colorectal cancer (mCRC) when combined with chemotherapy. Several randomized clinical trials comparing the efficacy and toxicity of vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) against bevacizumab have been reported. The present meta-analysis was conducted to identify the potentially significant benefit of the combined treatment regimens in patients with mCRC. PubMed, Embase and Cochrane Library databases were searched for the randomized controlled trials published on or before September 2014, which compared the efficacy and toxicity of VEGFR TKIs with bevacizumab in combination with chemotherapy in patients with mCRC. The primary endpoints included progression-free survival (PFS), overall survival (OS) and overall response rate (ORR), and secondary endpoints were the toxicity profiles. Relative risks (RRs) with 95% confidence intervals (CIs) for response rate and adverse events (AEs) were calculated, as well as hazard ratios (HRs) for PFS and OS. The final analysis included 4 studies comprising a total of 1,929 intent-to-treat patients with mCRC, which compared VEGFR TKIs (cediranib and axitinib) plus chemotherapy with bevacizumab plus chemotherapy. Results demonstrated that VEGFR TKIs plus chemotherapy significantly resulted in a modest but significantly shorter PFS [hazard ratio (HR), 1.12; 95% CI, 1.00-1.25; P=0.05] compared with that of bevacizumab plus chemotherapy but not in OS (HR, 1.10; 95% CI, 0.88-1.17; P=0.87) and ORR (RR, 0.95; 95% CI, 0.85-1.05; P=0.30). VEGFR TKIs treatment showed a less favorable AE profile compared with bevacizumab, with higher rates of grade-III/IV diarrhea, fatigue, hypertension, neutropenia and thrombocytopenia, whereas a higher incidence of peripheral neuropathy associated with the bevacizumab group was observed. In conclusion, the addition of VEGFR TKIs to chemotherapy resulted in a modest but significantly shorter PFS but not in OS and ORR compared with bevacizumab. The VEGFR TKIs group showed a less favorable AE profile with higher rates of diarrhea, fatigue, hypertension, neutropenia and thrombocytopenia, whereas a higher incidence of peripheral neuropathy associated with the bevacizumab was observed
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Interventions to improve care related to colorectal cancer among racial and ethnic minorities: A systematic review
OBJECTIVE: To systematically review the literature to identify interventions that improve minority health related to colorectal cancer care. DATA SOURCES: MEDLINE, PsycINFO, CINAHL, and Cochrane databases, from 1950 to 2010. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: Interventions in US populations eligible for colorectal cancer screening, and composed of ≥50 % racial/ethnic minorities (or that included a specific sub-analysis by race/ethnicity). All included studies were linked to an identifiable healthcare source. The three authors independently reviewed the abstracts of all the articles and a final list was determined by consensus. All papers were independently reviewed and quality scores were calculated and assigned using the Downs and Black checklist. RESULTS: Thirty-three studies were included in our final analysis. Patient education involving phone or in-person contact combined with navigation can lead to modest improvements, on the order of 15 percentage points, in colorectal cancer screening rates in minority populations. Provider-directed multi-modal interventions composed of education sessions and reminders, as well as pure educational interventions were found to be effective in raising colorectal cancer screening rates, also on the order of 10 to 15 percentage points. No relevant interventions focusing on post-screening follow up, treatment adherence and survivorship were identified. LIMITATIONS: This review excluded any intervention studies that were not tied to an identifiable healthcare source. The minority populations in most studies reviewed were predominantly Hispanic and African American, limiting generalizability to other ethnic and minority populations. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Tailored patient education combined with patient navigation services, and physician training in communicating with patients of low health literacy, can modestly improve adherence to CRC screening. The onus is now on researchers to continue to evaluate and refine these interventions and begin to expand them to the entire colon cancer care continuum.
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Impact of surgeon volume on outcomes of rectal cancer surgery: A systematic review and meta-analysis
AIM: To clarify the relationship between surgeon caseload and patient outcomes for patients undergoing rectal cancer surgery in order to inform debate about organisation of services. METHODS: We searched Medline and Embase for articles published up to March 2010, and included studies examining surgeon caseload and outcomes in rectal cancer patients treated after 1990. Outcomes considered were 30-day mortality, overall survival, anastomotic leak, local recurrence, permanent stoma and abdominoperineal excision rates. We assessed the risk of bias in included studies and performed random effects meta-analyses based on both unadjusted and casemix adjusted data. RESULTS: Eleven included studies enrolled 18,301 rectal cancer patients undergoing resective surgery. Unadjusted meta-analysis showed a statistically significant benefit in favour of high volume surgeons for 30-day postoperative mortality (OR = 0.57, 95% CI: 0.43-0.77; based on three studies, 4809 patients) and overall survival (HR = 0.76, 95% CI 0.63-0.90; based on two studies, 1376 patients), although the former relationship was attenuated and non-significant when based on two studies (9685 patients) that adjusted for casemix (OR = 0.79, 95% CI: 0.59-1.06). Pooling of three studies (2202 patients) showed no significant relationship between surgeon volume and anastomotic leak rate. Permanent stoma formation was less likely for high volume surgeons (adjusted OR = 0.75, 95% CI: 0.64 to 0.88; based on two studies, 9685 patients) and APER rates were lower for high volume surgeons (unadjusted OR = 0.58, 95% CI: 0.45 to 0.76); based on six studies, 3921 participants. CONCLUSIONS: This review gives evidence that higher surgeon volume is associated with better overall survival, lower permanent stoma and APER rates.
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The implementation of colorectal cancer screening interventions in low-and middle-income countries: A scoping review
BACKGROUND: Low- and middle-income countries (LMICs) experienced increasing rates of colorectal cancer (CRC) incidence in the last decade and lower 5-year survival rates compared to high-income countries (HICs) where the implementation of screening and treatment services have advanced. This review scoped and mapped the literature regarding the content, implementation and uptake of CRC screening interventions as well as opportunities and challenges for the implementation of CRC screening interventions in LMICs. METHODS: We systematically followed a five-step scoping review framework to identify and review relevant literature about CRC screening in LMICs, written in the English language before February 2020. We searched Medline, Embase, Web of Science and Google Scholar for studies targeting the general, asymptomatic, at-risk adult population. The TIDieR tool and an implementation checklist were used to extract data from empirical studies; and we extracted data-informed insights from policy reviews and commentaries. RESULTS: CRC screening interventions (n = 24 studies) were implemented in nine middle-income countries. Population-based screening programmes (n = 11) as well as small-scale screening interventions (n = 13) utilised various recruitment strategies. Interventions that recruited participants face-to-face (alone or in combination with other recruitment strategies) (10/15), opportunistic clinic-based screening interventions (5/6) and educational interventions combined with screening (3/4), seemed to be the strategies that consistently achieved an uptake of > 65% in LMICs. FOBT/FIT and colonoscopy uptake ranged between 14 and 100%. The most commonly reported implementation indicator was 'uptake/reach'. There was an absence of detail regarding implementation indicators and there is a need to improve reporting practice in order to disseminate learning about how to implement programmes. CONCLUSION: Opportunities and challenges for the implementation of CRC screening programmes were related to the reporting of CRC cases and screening, cost-effective screening methods, knowledge about CRC and screening, staff resources and training, infrastructure of the health care system, financial resources, public health campaigns, policy commitment from governments, patient navigation, planning of screening programmes and quality assurance.
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