Colorectal cancer

Colorectal cancer | NICE guideline [NG151] | January 2020

This guideline covers managing colorectal (bowel) cancer in people aged 18 and over. It aims to improve quality of life and survival for adults with colorectal cancer through management of local disease and management of secondary tumours (metastatic disease).

Recommendations

This guideline includes recommendations on:

See also: Colorectal cancer (Quality Standard 20, updated from Aug 2012)

Robotic surgery for rectal cancer produces similar results to keyhole surgery

NIHR Signal | December 2019 |Robotic surgery for rectal cancer produces similar results to keyhole surgery

Robotic rectal cancer surgery does not appear technically easier than standard keyhole surgery. The researchers, in this trial, judged this by measuring the need to ‘convert’ a keyhole procedure to open surgery when operating. This NIHR-funded trial also found that robotic surgery produced similar clinical results to standard laparoscopic (keyhole) surgery in treating rectal cancer.

In the trial, 28 out of 230 patients (12%) who received keyhole surgery were converted to open surgery, compared with 19 out of 236 (8%) who received robotic surgery. This difference did not achieve statistical significance. There were also no differences in the likelihood of removing the whole tumour, surgery-related complications and bladder or sexual function. Longer-term outcomes such as three-year recurrence and overall survival were also similar.

These results suggest robotic rectal surgery, which costs £1,000 more than laparoscopic surgery due to ongoing equipment costs and longer operating time, may not be cost-effective (Source: NIHR).

The full details of the trial are available from the NIHR 

Full reference:

Jayne, D. | 2019| Robotic-assisted Surgery Compared With Laparoscopic Resection Surgery for Rectal Cancer: The ROLARR RCT | Efficacy and Mechanism Evaluation | DOI: 10.3310/eme06100

Abstract

Background

Robotic rectal cancer surgery is gaining popularity, but there are limited data about its safety and efficacy. Objective To undertake an evaluation of robotic compared with laparoscopic rectal cancer surgery to determine its safety, efficacy and cost-effectiveness.

Design

This was a multicentre, randomised trial comparing robotic with laparoscopic rectal resection in patients with rectal adenocarcinoma.

Setting

The study was conducted at 26 sites across 10 countries and involved 40 surgeons. Participants The study involved 471 patients with rectal adenocarcinoma. Recruitment took place from 7 January 2011 to 30 September 2014 with final follow-up on 16 June 2015. Interventions Robotic and laparoscopic rectal cancer resections were performed by high anterior resection, low anterior resection or abdominoperineal resection. There were 237 patients randomised to robotic and 234 to laparoscopic surgery. Follow-up was at 30 days, at 6 months and annually until 3 years after surgery.

Main outcome measures The primary outcome was conversion to laparotomy. Secondary end points included intra- and postoperative complications, pathological outcomes, quality of life (QoL) [measured using the Short Form questionnaire-36 items version 2 (SF-36v2) and the Multidimensional Fatigue Inventory-20 (MFI-20)], bladder and sexual dysfunction [measured using the International Prostatic Symptom Score (I-PSS), the International Index of Erectile Function (IIEF) and the Female Sexual Function Index (FSFI)], and oncological outcomes. An economic evaluation considered the costs of robotic and laparoscopic surgery, including primary and secondary care costs up to 6 months post operation.

Results Among 471 randomised patients [mean age 64.9 years, standard deviation (SD) 11.0 years; 320 (67.9%) men], 466 (98.9%) patients completed the study. Data were analysed on an intention-to-treat basis. The overall rate of conversion to laparotomy was 10.1% and occurred in 19 (8.1%) patients in the robotic-assisted group and in 28 (12.2%) patients in the conventional laparoscopic group. Of the nine prespecified secondary end points, including circumferential resection margin positivity, intraoperative complications, postoperative complications, plane of surgery, 30-day mortality and bladder and sexual dysfunction, none showed a statistically significant difference between the groups. No difference between the treatment groups was observed for longer-term outcomes, disease-free and overall survival (OS). Males were at a greater risk of local recurrence than females and had worse OS rates. The costs of robotic and laparoscopic surgery, excluding capital costs, were £11,853 (SD £2940) and £10,874 (SD £2676) respectively.

Conclusions

There is insufficient evidence to conclude that robotic rectal surgery compared with laparoscopic rectal surgery reduces the risk of conversion to laparotomy. There were no statistically significant differences in resection margin positivity, complication rates or QoL at 6 months between the treatment groups. Robotic rectal cancer surgery was on average £980 more expensive than laparoscopic surgery, even when the acquisition and maintenance costs for the robot were excluded. Future work The lower rate of conversion to laparotomy in males undergoing robotic rectal cancer surgery deserves further investigation. The introduction of new robotic systems into the market may alter the cost-effectiveness of robotic rectal cancer surgery.

The full article is available from PubMed

Leeds’ findings: Bowel cancer rates after colonoscopy vary by provider

University of Leeds | November 2019 | Bowel cancer rates after colonoscopy vary by provider

New research led by the University of Leeds looked at the number of patients whose colonoscopy found no evidence of bowel cancer, but who were subsequently diagnosed with the disease.

They found that overall the rate of these post-colonoscopy bowel cancers decreased in England. However, they found that the rates of these potentially missed cancers were lower for colonoscopies performed by the NHS than those performed by independent providers on behalf of the NHS.

Co-author Professor Eva Morris, from the University of Leeds’ School of Medicine and the Leeds Institute for Data Analytics, said: “Overall we found the proportion of people whose bowel cancer is being missed by a colonoscopy procedure has declined, meaning that our diagnostic services are getting more and more accurate.

“However, this study reveals wide variation in the accuracy of colonoscopy tests depending on the provider, meaning that some cancers are still being missed. This urgently needs to be addressed to ensure we are detecting cancer cases as early as possible.”

Amongst people diagnosed with bowel cancer who had a colonoscopy within the NHS Bowel Cancer Screening Programme, 3.6% could potentially have been diagnosed at an earlier time point. In contrast, if a person’s colonoscopy was undertaken by an NHS commissioned independent provider 9.3% could potentially have been diagnosed sooner.

The researchers say that if the lower rate had been achieved over the entire nine-year study period, more than 3,900 cases of colorectal cancer could have been prevented or diagnosed earlier (Source: University of Leeds).

Read the news release from the University of Leeds in full here

The study’s findings have now been published in the BMJ 

Burr, N.E., et al. | 2019| Variation in post-colonoscopy colorectal cancer across colonoscopy providers in English National Health Service: population based cohort study| 

Abstract

Objectives To quantify post-colonoscopy colorectal cancer (PCCRC) rates in England by using recent World Endoscopy Organisation guidelines, compare incidence among colonoscopy providers, and explore associated factors that could benefit from quality improvement initiatives.

 

Design Population based cohort study.

Setting National Health Service in England between 2005 and 2013.

Population All people undergoing colonoscopy and subsequently diagnosed as having colorectal cancer up to three years after their investigation (PCCRC-3yr).

 

Main outcome measures National trends in incidence of PCCRC (within 6-36 months of colonoscopy), univariable and multivariable analyses to explore factors associated with occurrence, and funnel plots to measure variation among providers.

Results The overall unadjusted PCCRC-3yr rate was 7.4% (9317/126 152), which decreased from 9.0% in 2005 to 6.5% in 2013 (P<0.01). Rates were lower for colonoscopies performed under the NHS bowel cancer screening programme (593/16 640, 3.6%), while they were higher for those conducted by non-NHS providers (187/2009, 9.3%). Rates were higher in women, in older age groups, and in people with inflammatory bowel disease or diverticular disease, in those with higher comorbidity scores, and in people with previous cancers. Substantial variation in rates among colonoscopy providers remained after adjustment for case mix.

Conclusions Wide variation exists in PCCRC-3yr rates across NHS colonoscopy providers in England. The lowest incidence was seen in colonoscopies performed under the NHS bowel cancer screening programme. Quality improvement initiatives are needed to address this variation in rates and prevent colorectal cancer by enabling earlier diagnosis, removing premalignant polyps, and therefore improving outcomes.

The full article is available from The BMJ 

Visual abstract 

 

 

Case study: ADENOMA – impact case study

NIHR | September 2019 | Case study: ADENOMA – impact case study

NIHR has produced an impact case study on adenoma, a polyp that grows in the bowel that has become cancerous.  Currently, a colonoscopy is regarded as the ‘gold standard’ treatment for adenoma.

Although experienced endoscopists perform the colonoscopies, polyps can get missed for various reasons including the size, shape and location of the lesions, and many colorectal cancer screening programmes have been proposed to improve adenoma detection rate (ADR). Improving the ADR and cancer detection through increased colonoscopy performance brings patient benefits, and earlier diagnosis of cancer is also associated with lower healthcare costs (Cancer Research UK 2014).

The study recruited 1800 participants from across seven sites, with patients being referred to the trial because of symptoms, surveillance or following a positive faecal occult blood test as part of the Bowel Cancer Screening Programme.

These patients were randomized across two arms of the trial: with one group having treatment as usual (the colonoscopy) and the other having the Endocuff Vision arm

The researchers report that the participants in the Endocuff Vision arm of the trial, had a higher Adenoma Detection Rate, increased globally from 36.2 per cent to 40.9 per cent (P=0.02). the increase was driven by a 10.8 per cent increase in FOBt-positive screening patients (50.9 per cent vs 61.7 per cent, P less than 0.001).

The research team conclude that the ADENOMA trial showed that Endocuff Vision significantly improved ADR in bowel cancer screening patients and should be used to improve colonoscopic detection.

The success of the trial led to NHS England announcing Endocuff Vision as one of only four technologies to be fast-tracked into use through NHS England’s Innovation and Technology Payment programme in April 2018.

NICE updated its guidelines for use in June 2019 and NHS trusts across England have significantly increased use of the product.
The Endocuff Vision device has also been adopted internationally and there has been a large rise in the use of the device over the last four years (Source: NIHR).

Read the full story from NIHR

 

Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years

Vuik, F.E., et al | 2019| Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years| 

Research published in the journal Gut analyses trends in the incidence of colorectal cancer (CRC) and mortality in subjects under the age of 50. The experts used data on over 143 million people across European countries to explore . While the researchers observed that CRC incidence continues to rise among young adults in Europe; they indicate further research is necessary to find out the reasons for this trend need to be discovered and if the trend continues, screening guidelines may need to be reconsidered.

The full article is available from the journal Gut

Abstract

Objective The incidence of colorectal cancer (CRC) declines among subjects aged 50 years and above. An opposite trend appears among younger adults. In Europe, data on CRC incidence among younger adults are lacking. We therefore aimed to analyse European trends in CRC incidence and mortality in subjects younger than 50 years.

 

Design Data on age-related CRC incidence and mortality between 1990 and 2016 were retrieved from national and regional cancer registries. Trends were analysed by Joinpoint regression and expressed as annual percent change.

 

Results We retrieved data on 143.7 million people aged 20–49 years from 20 European countries. Of them, 187 918 (0.13%) were diagnosed with CRC. On average, CRC incidence increased with 7.9% per year among subjects aged 20–29 years from 2004 to 2016. The increase in the age group of 30–39 years was 4.9% per year from 2005 to 2016, the increase in the age group of 40–49 years was 1.6% per year from 2004 to 2016. This increase started earliest in subjects aged 20–29 years, and 10–20 years later in those aged 30–39 and 40–49 years. This is consistent with an age-cohort phenomenon. Although in most European countries the CRC incidence had risen, some heterogeneity was found between countries. CRC mortality did not significantly change among the youngest adults, but decreased with 1.1%per year between 1990 and 2016 and 2.4% per year between 1990 and 2009 among those aged 30–39 years and 40–49 years, respectively.

 

Conclusion CRC incidence rises among young adults in Europe. The cause for this trend needs to be elucidated. Clinicians should be aware of this trend. If the trend continues, screening guidelines may need to be reconsidered.

Full article available from the BMJ

 

See also:

Reuters Colorectal cancer becoming more common at younger ages

Cancer Research UK Bowel cancer rates are rising in young adults, but do we know what’s behind the increase?

Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989–2012: a matched case–control study

Zhang, J.Haines, C.Watson, A.J.M., et al | 2019| 
Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989–2012: a matched case–control study | 

 

Researchers behind a population-based study of oral antibiotic exposure and risk   looked at the association between oral antibiotic use and (colorectal cancer) CRC risk have published their findings in the BMJ Journal Gut. 

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Abstract

Background Microbiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of oral antibiotic exposure and risk patterns is lacking.

Objective To assess the association between oral antibiotic use and CRC risk.

Design A matched case–control study (incident CRC cases and up to five matched controls) was performed using the Clinical Practice Research Datalink from 1989 to 2012.

Results 28 980 CRC cases and 137 077 controls were identified. Oral antibiotic use was associated with CRC risk, but effects differed by anatomical location. Antibiotic use increased the risk of colon cancer in a dose-dependent fashion. The risk was observed after minimal use, and was greatest in the proximal colon and with antibiotics with anti-anaerobic activity. In contrast, an inverse association was detected between antibiotic use and rectal cancers, particularly with length of antibiotic exposure more than 60 days as compared with no antibiotic exposure. Penicillins, particularly ampicillin/amoxicillin increased the risk of colon cancer, whereas tetracyclines reduced the risk of rectal cancer. Significant interactions were detected between antibiotic use and tumour location. The antibiotic–cancer association was found for antibiotic exposure occurring more than 10 years before diagnosis.

Conclusion Oral antibiotic use is associated with an increased risk of colon cancer but a reduced risk of rectal cancer. This effect heterogeneity may suggest differences in gut microbiota and carcinogenesis mechanisms along the lower intestinal tract. (Source: Zhang et al, 2019)

The full article is available from BMJ Gut 

In the news:

OnMedica Oral antibiotic use linked to heightened bowel cancer risk

NIHR: Whole-body MRI is effective for identifying metastatic disease in colorectal cancer patients

NIHR| July 2019 |Whole-body MRI is effective for identifying metastatic disease in colorectal cancer patients

A new NIHR Signal showcases the findings of annitial investigation which includes whole-body magnetic resonance imaging (MRI) is as good as standard pathways for detecting metastatic disease in adults with newly diagnosed colorectal cancer. This NIHR-funded study also found that whole-body MRI reduces the number of investigations needed, the length of the staging process, and costs less than standard pathways.

The treatment options for colorectal cancer depend on the stage of the cancer. For example, if a patient has metastatic disease (secondary tumours in other parts of the body), the aims of surgery and chemotherapy can be different. So, an accurate staging process is very important.

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Current NICE guidance recommends a sequence of investigations for staging, with MRI only recommended after biopsies and other imaging investigations. This study suggests that MRI could be used earlier in the process, instead of the currently recommended investigations. However, any changes to guidance would need to take into account the availability of this resource (Source: NIHR).

Summary

Background

Whole-body MRI (WB-MRI) could be an alternative to multimodality staging of colorectal cancer, but its diagnostic accuracy, effect on staging times, number of tests needed, cost, and effect on treatment decisions are unknown. We aimed to prospectively compare the diagnostic accuracy and efficiency of WB-MRI-based staging pathways with standard pathways in colorectal cancer.


Methods

The Streamline C trial was a prospective, multicentre trial done in 16 hospitals in England. Eligible patients were 18 years or older, with newly diagnosed colorectal cancer. Exclusion criteria were severe systemic disease, pregnancy, contraindications to MRI, or polyp cancer. Patients underwent WB-MRI, the result of which was withheld until standard staging investigations were complete and the first treatment decision made. The multidisciplinary team recorded its treatment decision based on standard investigations, then on the WB-MRI staging pathway (WB-MRI plus additional tests generated), and finally on all tests. The primary outcome was difference in per-patient sensitivity for metastases between standard and WB-MRI staging pathways against a consensus reference standard at 12 months, in the per-protocol population. Secondary outcomes were difference in per-patient specificity for metastatic disease detection between standard and WB-MRI staging pathways, differences in treatment decisions, staging efficiency (time taken, test number, and costs), and per-organ sensitivity and specificity for metastases and per-patient agreement for local T and N stage. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN43958015, and is complete.

 

Findings

Between March 26, 2013, and Aug 19, 2016, 1020 patients were screened for eligibility. 370 patients were recruited, 299 of whom completed the trial; 68 (23%) had metastasis at baseline. Pathway sensitivity was 67% (95% CI 56 to 78) for WB-MRI and 63% (51 to 74) for standard pathways, a difference in sensitivity of 4% (−5 to 13, p=0·51). No adverse events related to imaging were reported. Specificity did not differ between WB-MRI (95% [95% CI 92–97]) and standard pathways (93% [90–96], p=0·48). Agreement with the multidisciplinary team’s final treatment decision was 96% for WB-MRI and 95% for the standard pathway. Time to complete staging was shorter for WB-MRI (median, 8 days [IQR 6–9]) than for the standard pathway (13 days [11–15]); a 5-day (3–7) difference. WB-MRI required fewer tests (median, one [95% CI 1 to 1]) than did standard pathways (two [2 to 2]), a difference of one (1 to 1). Mean per-patient staging costs were £216 (95% CI 211–221) for WB-MRI and £285 (260–310) for standard pathways.

 

Interpretation

WB-MRI staging pathways have similar accuracy to standard pathways and reduce the number of tests needed, staging time, and cost.

 

NIHR Whole-body MRI is effective for identifying metastatic disease in colorectal cancer patients

Read the full journal article from The Lancet Gastroenterology & Hepatology 

Article 

Taylor, S.A . et al | 2019| Diagnostic accuracy of whole-body MRI versus standard imaging pathways for metastatic disease in newly diagnosed colorectal cancer: the prospective Streamline C trial | The Lancet Gastroenterology & Hepatology | DOI:https://doi.org/10.1016/S2468-1253(19)30056-1

Diet and colorectal cancer in UK Biobank: a prospective study

Bradbury, K.E.,  Murphy, N., Key, T. | 2019| Diet and colorectal cancer in UK Biobank: a prospective study|  International Journal of Epidemiology| dyz064| https://doi.org/10.1093/ije/dyz064

A research team behind a study into diet and the impact of diet on colorectal cancer used data from the UK Biobank research project in conjunction with  questionnaires to learn about the dietary habits of men and women aged between 40- 69 years and their potential risk of developing colorectal cancer. 

At follow up five years later the participants who had consumed (on average) 76g of red meat, compared to 21g, had a higher risk of developing cancer than other participants.

Participants who ate red meat on four or more occasions a week had a fifth increased risk of developing colorectal cancer compared with subjects who ate red meat twice weekly. 
Subjects who consumed the most wholegrains had a 14% lower risk of developing  colorectal cancer.
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Key Messages
  • Previous studies have found an increased risk of colorectal cancer in those with high intakes of red and processed meat. Most previous studies collected information on dietary intakes during the 1990s or earlier and patterns in meat consumption have since changed.
  • In addition, few studies have used re-measured intakes to reduce the impact of measurement error, and to quantify the amount of red and processed meat that is associated with an increased risk. Measurement error generally biases the associations towards the null value; the associations observed in previous studies that did not re-measure intakes may be underestimated.
  • Our study found that people who were consuming red and processed meat four or more times per week, had a 20% increased risk of colorectal cancer compared with those who were consuming red and processed meat less than twice a week.

Abstract

Background

Most of the previous studies on diet and colorectal cancer were based on diets consumed during the 1990s.

Methods

We used Cox-regression models to estimate adjusted hazard ratios for colorectal cancer by dietary factors in the UK Biobank study. Men and women aged 40–69 years at recruitment (2006–10) reported their diet on a short food-frequency questionnaire (n = 475 581). Dietary intakes were re-measured in a large sub-sample (n = 175 402) who completed an online 24-hour dietary assessment during follow-up. Trends in risk across the baseline categories were calculated by assigning re-measured intakes to allow for measurement error and changes in intake over time.

Results

During an average of 5.7 years of follow-up, 2609 cases of colorectal cancer occurred. Participants who reported consuming an average of 76 g/day of red and processed meat compared with 21 g/day had a 20% higher risk of colorectal cancer. Participants in the highest fifth of intake of fibre from bread and breakfast cereals had a 14% lower risk of colorectal cancer. Alcohol was associated with an 8% higher risk per 10 g/day higher intake. Fish, poultry, cheese, fruit, vegetables, tea and coffee were not associated with colorectal-cancer risk.

Conclusions

Consumption of red and processed meat at an average level of 76 g/d that meets the current UK government recommendation (less than or equal to 90 g/day) was associated with an increased risk of colorectal cancer. Alcohol was also associated with an increased risk of colorectal cancer, whereas fibre from bread and breakfast cereals was associated with a reduced risk.

 

The article is available to read in full in the International Journal of Epidemiology 

In the news:

The Independent Even government guideline amounts of red meat and bacon increase risk of bowel cancer, study finds 

The Guardian Even moderate intake of red meat raises cancer risk, study finds

BBC News A rasher of bacon a day ‘ups cancer risk’ 

Familial colorectal cancer risk in half siblings and siblings: nationwide cohort study

Tian, Y.  et al. | 2019|  Familial colorectal cancer risk in half siblings and siblings: nationwide cohort study | 

The BMJ has published a cohort study that looked at relatives with colorectal cancer, unlike previous research this study also focused on second-degree relatives half siblings. The research identifies that second- degree relatives, for example half siblings, also had an association with colorectal cancer risk similar to that in first-degree relatives such as siblings or parents. 

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Abstract

Objective To explore the risk of colorectal cancer in family members of patients with colorectal cancer, with an emphasis on subtypes of second degree relatives, especially half siblings, which were lacking in the literature.

Design Ambidirectional cohort study.

Setting Nationwide Swedish Family Cancer Data (record linkage).

Participants All people residing in Sweden and born after 1931, with their biological parents, totalling more than 16 million individuals (follow-up: 1958-2015); of those with clear genealogy, 173 796 developed colorectal cancer.

Main outcome measures Lifetime (0-79 years) cumulative risk and standardised incidence ratio of colorectal cancer among first degree relatives and second degree relatives.

Results The overall lifetime cumulative risk of colorectal cancer in siblings of patients was 7%, which represents a 1.7-fold  (n=2089) increase over the risk in those without any family history of colorectal cancer. A similarly increased lifetime cumulative risk (6%) was found among half siblings. The risk in people with colorectal cancer in both a parent and a half sibling (n=32) was close to the risk in those with both an affected parent and an affected sibling (n=396). Family history of colorectal cancer in only one second degree relative other than a half sibling (without any affected first degree relatives), such as a grandparent, uncle, or aunt, showed minor association with the risk of colorectal cancer.

Conclusion Family history of colorectal cancer in half siblings is similarly associated with colorectal cancer risk to that in siblings. The increase in risk of colorectal cancer among people with one affected second degree relative was negligible, except for half siblings, but the risk was substantially increased for a combination of family history in one affected second degree relative and an affected first degree relative (or even another second degree relative). These evidence based findings provide novel information to help to identify people at high risk with a family history of colorectal cancer that can potentially be used for risk adapted screening.

Full abstract available from the BMJ

Read and download the full article online from the BMJ

Rapid cancer diagnostic and assessment pathways

NHS England has published three rapid cancer diagnostic and assessment pathways.  These documents set out how diagnosis within 14 days and diagnosis within 28 days can be achieved for the colorectal, lung, and prostate cancer pathways:

Implementing a timed colorectal cancer diagnostic pathway:

This handbook sets out how the 28 day standard can be achieved in colorectal cancer patients, in preparation for full monitoring against the standard from April 2020.

Implementing a timed lung cancer diagnostic pathway:

This handbook sets out how the 28 day standard can be achieved for lung cancer patients, in preparation for full monitoring against the standard from April 2020.

Implementing a timed prostate cancer diagnostic pathway:

This handbook sets out how the 28 day standard can be achieved for prostate cancer patients, in preparation for full monitoring against the standard from April 2020.