Trends of CRC Incidence and Mortality Rates

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Examine the trends of CRC incidence and mortality rates in the WA population since 1982 to 2014 overall and by demographic with impact of National Bowel Cancer Screening Program (NBCSP): WACRC Study

1.Introduction:

  1. Colorectal cancer:

A close up of a map

Description generated with high confidence
Colorectal cancer is the third most frequent form of cancer occurring globally and in the fourth place to cause the cancer mortality.1 Colorectal cancer has an estimated worldwide annual incidence of 1.4 million cases2 and nearly 700,000 deaths in 2012 as per WHO report. About two thirds of colorectal cancer incidence occurs in countries with high level or very high level human development index.3 In Australia, colorectal cancer was the third most commonly detected cancer in 2013 and it will end up being the second most in 2017.4 Colorectal cancer is the second most commonly detected cancer in both men and women in Western Australia with more prevalence in people over the age of 50 years.5Colorectal cancer also known as bowel cancer arising from the large intestinal mucosa (inner lining of bowel wall) and mostly followed by a polyp, if unobserved it will become an invasive cancer.6 This is also known as colon, rectosigmoid or rectal cancer (collectively colorectal cancer) depending on the sites where the growth originates.6

Figure 1: Colorectal cancer sites

 

  1. Etiology

 

Around two thirds of new cases of colorectal cancer acquire sporadically, and the necessitous genetic changes appear to rise de novo, steered by etiologic factors that can include environmental exposures, and lifestyle factors.7,8 Approximately one third of cases may have a hereditary predisposition tend to cluster in families as there is greater occurrence in families or the cancer appears at young age. However, a precise inherent cause is identified in less than 5% of the cases.7

1.2.1 Sporadic colorectal cancer:

 

The vast majority of colorectal cancers arise sporadically through the adenoma-carcinoma sequence.9 This model put forward by Vogelstein states that through a combination of genetic mutations adenomatous polyps develop and progress from low-grade to high-grade dysplasia changes to invasive malignancy.10 It is estimated that around a quarter of polyps greater than 10mm will develop into cancer over 20 years. Features in keeping with an increased risk of malignant transformation in adenomas include size, sessile morphology and villous architecture.11

 

1.2.2 Non-sporadic colorectal cancer:

 

Approximately 30% of colorectal cancers arise through non-sporadic routes either via inherited conditions or systemic diseases that predispose individuals to the development of colorectal malignancy.11 The occurrence risk is two times higher if the first-degree relative suffers from CRC and it will become four times when the incidence age is below 45 years.12

Hereditary Non-Polyposis Colon Cancer, also known as Lynch syndrome, is an autosomal dominant genetic condition that is the most common of the inherited colorectal cancer conditions.13,14 Its incidence is approximately 1 in 3000 in the general population, accounts for approximately 1-2% of all colorectal cancer diagnoses and has an average age of onset of 45 years.14

Familial adenomatous polyposis syndrome  is an autosomal dominant condition characterised by the development of multiple adenomas across the colon and rectum.15 The incidence in the general population is about 1 in 14 000 individuals and accounts for less than 1% of all colorectal cancers.15

It is widely accepted that patients with inflammatory bowel disease, namely Ulcerative Colitis  and colonic Crohn’s disease have an increased risk of developing colorectal cancer.6 The risk is associated with severity and duration of symptoms with figures derived from meta-analyses estimating risk in Crohn’s disease at 3% at ten years, and in Ulcerative colitis at 2%, 8% and 18% after 10, 20 and 30 years respectively after the disease detection.16 It is hypothesised that chronic inflammation results in genetic alterations leading to the development of colonic dysplasia, which in turn can develop into invasive malignancy.16

1.3 Epidemiology:

Colorectal Cancer presently constitutes 9.67% of the total 14.1 million new cancer cases universally.17 In 2035, the colorectal cancer incidence is anticipated to increase by 80%, around 2.4 million cases and will cause 1.3 million deaths worldwide.17 However, the burden of this disease differs widely across populations, varying with geography, age, gender, and socio-economic status.18 There is wide geographical variation in colorectal cancer incidence due to its association with socio-economic status,  affluent lifestyle factors such as smoking, alcohol consumption, obesity and high meat diets.19 The colorectal cancer burden diverges extensively worldwide, however, two-thirds of incidence and 60% of deaths occurring in industrialized and developed countries.2 Thehighest incidence rates are in North America, Australia, New Zealand, Europe, and Japan,with lowest rates in Africa and South central Asia (American Cancer Society 2011).

1.3.1 Colorectal Cancer Incidence and Mortality rates in Australia:

In Australia, colorectal cancer contributes around 12.9% nearly 15 000 of all new cancers detected in 2014.20 It is the second most common cancer detected next to the prostate cancer, and the second foremost cause of death, around 4071 deaths in 2014, after the lung cancer.21 The overall incidence for colorectal cancer in Australia remains one of the highest in the world.21 Colorectal cancer is associated with advancing age, the rapid rises in occurrence are seen from age 50 years and above.22 The average age of colorectal cancer at diagnosis in Australia is around 69 years for both sexes shared.23 The colorectal cancer detection rate in Australia is expanding due to the increase in population and population  aging, however, the actual rates of both incidence and mortality have showed constancy or small declines.24  One in 13 people is at risk of developing CRC by 85 years of age, and it is assessed that the death risk due to colorectal cancer by the age of 85 years will be 1 in 54 (1 in 63 females and 1 in 47
males) in 2017 25.

Figure 2 Age standardised CRC incidence and mortality rates in Australia

In Western Australia, CRC is the third most common cancer affecting men and second most common in women. Around 1229 people were detected with bowel cancer (739 women, 560 men) In 2014.26 A study conducted in Western Australia among people with aged 15-39 years showed an increased trend in the CRC incidence rate for the past two decades.27

1.4 Risk factors

Even though the primary cause of colorectal cancer is idiopathic, environmental factors and inheritance play a significant role in the development of colorectal cancer.28 There have been a variety of both modifiable and non-modifiable risk factors identified as being associated with an increased risk and will be discussed below.

1.4.1 Patient demographics:

There are clear associations noted between patient age and sex and the development of colorectal cancer. In the Australia alone, males have a lifetime risk of 1 in 11 of developing the disease and females a risk of 1 in 15.29 Increases in colorectal cancer incidence rates have been detected among Australian Indigenous people in recent years and may be due to unhealthy diet, in specific a deficiency of fresh vegetables and fruits, physical inactivity, and obesity.30

Socioeconomic deprivation is a global term used to describe an individual or group relative to the local community or wider society with regards to a variety of factors such as income, housing and education31. There is evidence that those who are more deprived have higher rates of colorectal cancer, although more recently this has been shown to be a phenomenon that appears only to affect males31.

1.4.2 Dietary and Lifestyle factors:

There is evidence for a variety of both dietary and lifestyle factors to affect an individuals

risk of colorectal cancer.32 Individual lifestyle factors which may increase the bowel cancer risk consists of less physical activity, high-calorie diets with less fruit and vegetable intake, excess weight and obesity, smoking, alcohol intake increase the risk factor.15

 

1.5 Screening for colorectal cancer

The latest WHO fact sheet on cancer states that around 30–50% of cancers can be prevented by avoiding the common risk factors and executing current evidence-based prevention approaches.

1.5.1 Survival benefit of screening:

Early diagnosis and elimination of risk factors can lessen the colorectal cancer occurrence and mortality rates and also leads minimal invasive treatment, with reduced morbidity, mortality, and treatment expense.33 There are several key elements underlying population screening : it must be targeted at an important health issue; the screening procedure should be simple, safe, precise and validated; early stage treatment should be more beneficial than late stage treatment; there should be evidence that screening reduces mortality/morbidity; the benefits should outweigh the harm; the process should be economically viable; the program should be audited against set standards; and screening participants should be fully informed of the implications of participation.34

In addition to this, colorectal cancer also has the apparent advantage of developing from a precursor lesion with what is considered to be a relatively long average interval from the precursor to the development of invasive disease.35 Around 90% of colorectal cancers are adenocarcinomas and are thought to develop from dysplastic polyps, with around 8% of polyps greater than 10mm developing into cancer at ten years.36 It is considered that targeting these adenomas with endoscopic resection should prevent them developing into tumors.36 As the majority of polyps are symptomless, then a screening tool to identify them should potentially lead to a reduction in colorectal cancer incidence and ultimately improve outcomes.37

1.5.2 Screening programs:

The CRC screening program implementation involves various strategic determinants, mostly the choice of testing methods, which can be an invasive test or a non-invasive test.

Faecal occult blood tests:

The guaiac faecal occult blood test (gFOBT), and faecal immunochemical test (FIT) are the more common noninvasive stool tests used to detect the colorectal cancer and are relatively inexpensive.38 The gFOBT uses a biochemical to detect the haeme, a constituent of blood haemoglobin, whereas, the FIT uses antibodies to identify the human haemoglobin protein distinctively.38 FITs have a higher sensitivity for adenoma even with a single faecal sample and has higher detection and participation rates compared with gFOBT screening.39

The gFOBT is less sensitive (63.3% versus 79.1%) and less specific (90.1% versus 96.9%) than the FIT  for the detection of colorectal cancer.38 However, the faecal occult blood test based screening programs are less invasive and have higher compliance rates than endoscopic programmes, which have higher sensitivity and specificity.38 The annual or biennial FOBT screening did not affect the colorectal incidence rate, but, it decrease the colorectal cancer related mortality around16%.40

Colonoscopy:

The universal gold standard screening test to the detect the colorectal cancer is colonoscopy, and it aided the reduction in colorectal cancer mortality rate in longterm41. The use of colonoscopy for screening colorectal cancer was associated with a reduction in the incidence rate (67%) and mortality rate (65%).42 A flexible fiberoptic tube is passed per rectum to the caecum allowing for direct luminal visualisation and biopsy of any lesions identified. It is, however, an invasive test with a complication rate of colonic perforation of approximately 0.05%.42 There are also resource and cost issues in instigating this as an initial screening tool and the public acceptance of undergoing endoscopic evaluation of the large bowel is at present thought to be limited.43

Some screening programs use the colonoscopy as the principal screening test, and other programs choose a two-step method, initially use noninvasive screening tests and use the colonoscopy for diagnostic confirmation.44 The two-step approach has higher screening participant compliance and reduces the colonoscopy rates which needs more resources.44

Other tests consider for screening:

Flexible sigmoidoscopy, CT colonography are also used as a screening test. Less-invasive tests include blood and stool examination to detect RNA, DNA and protein biomarker are recently evolved and get more attention.45

Risks of colorectal cancer screening:

 

The potential barriers to colorectal cancer screening are numerous and include fear of invasive tests, aversion to the bowel preparation, and lack of insurance coverage or access to care.

Complications of endoscopic procedures:

The major advantage of stool-based tests is that they are non-invasive. However, a proportion of patients will undergo colonoscopy following a positive test, and this is a procedure that is not without risk. Notably, there is a risk of perforation and significant hemorrhage.46

The psychological impact of screening:

In addition to the physical harm that can be caused by an endoscopic procedure, there are further psychological impacts on the individual. For example, it has been suggested that the stress of a false positive result can adversely affect an individual. The issue with FOBT is that of false negatives that may falsely reassure a person that colorectal cancer is not present.47

Global CRC screening programs:

A systematic screening program with noninvasive stool test is used in most Europe countries and earlier days they executed gFOBT based test, and now they replaced it with FIT.48 The U.S. Preventive Services Task Force recommends colorectal cancer screening in the USA and up to 65% of US adults were undergone colorectal cancer screening in 2012, which commonly used the colonoscopy as a screening test.49 In Central and South American countries, there will be the national level guidelines for colorectal cancer screening. However, only a few countries implement the colorectal cancer screening programs.50 In Middle East countries, Abu Dhabi is the only country which implements colorectal cancer screening program.51 The Asia Pacific Colorectal Cancer Working Group  suggests colorectal cancer screening in regions with higher incidence rates (>30 per 100 000). Population-based screening programs were established in Asia Pacific regions.50A 4-year national bowel cancer screening pilot program was started in New Zealand in 2011 to assess the need for the countrywide screening program.52

NBCSP in Australia:

Australia is one of the highest colorectal cancer incidence rates in the world.53 The Australian Health Technology Advisory Committee directed a systematic analysis of the substantiation for colorectal cancer screening and established that screening with faecal occult blood testing was effectual.54 It recommended that a nationwide population based bowel cancer screening program be introduced, subject to pilot and feasibility testing.55 In 2000-01, the Australian Government funded a four-year pilot bowel cancer screening program to advance information about early finding of bowel cancer.

The pilot phase of National Bowel Cancer Screening Programme (NBCSP) was introduced in November 2002 and extended up to June 2004 in three different Australian states (Victoria, Queensland and South Australia) with 56,907 randomly selected population.56 In late 2006, the core NBCSP was announced in Australia and is administered by the Department of Health in partnership with state and territory governments, proposing free immunochemical fecal occult blood testing for Australian population with age 55 years and 65 years in 2006.57


Figure 3:  The start dates of each NBCSP phase and eligible ages

Source: www.bowelcanceraustralia.org/national-bowel-cancer-screening-program

The goal of the NBCSP is to decrease the CRC mortality and morbidity by implementing the screening program effectively among the target population for early diagnosis or disease prevention. During the year 2012-2013, more than 321 000 people (33% of those invited) participated in the NBCSP.58 Australian Indigenous people are reportedly less likely to participate in the population-based bowel screening program.59

Colonoscopy in Australia:

The per capita colonoscopy rate is highest in Australia when compared to the other countries in the world.60 In Australia, increasing utilisation of colonoscopy has been observed for the past two decades.61 In Western Australia, during 2008/0 more than 60,000 colonoscopies were performed, whereas 9% done in public tertiary hospitals and an additional 27% done in secondary and regional public hospitals.62 The remaining two thirds of colonoscopy performed in the private sector. The colonoscopy involves effectively in cancer prevention by detection and removal of polyps/adenomas.63 However, some studies telling that there are  90% reductions60 in CRC incidence rate while others argued that it has only marginal benefits.64

 

2. Study aim and objectives:

This project aims to investigate the trends in incidence and mortality rates of CRC in the Western Australian (WA) population from 1982 to 2014 overall and by age, sex family history with impact of National Bowel Cancer Screening Program (NBCSP).

2.1 Objectives:

The study was formulated with the following objectives to achieve the overall aim:

  • To quantify the overall incidence and mortality rates of CRC in Western Australia from 1982 to 2014. Analyses will be stratified by age (<50 years vs. ≥50 years), sex (males vs. females) and family history (present vs. absent)
  • To analyze the impact of NBCSP in the Western Australian population with incidence and mortality rates before and after implementation of this program.
  • To examine any change in trends in colonoscopy rates with the introduction of the NBCSP and compare rates in private and public hospitals.

2.2 Significance of this study

Cancer incidence and mortality statistics are a means of quantifying the effectiveness of early detection strategies and treatment regimens at the population level. They are used as comparative measures between different people with age, sex, demographic, family history and these comparisons help to identify the possible reasons for the differences and suggest goals for enhancement and continuous monitoring. Due to the massive impact of cancer on the health care system and the escalating cost of health care, strategies for cancer screening programs are becoming more important.

Only a small number of CRC incidence and mortality studies and the impact of National Bowel Cancer Screening Program on these rates have been conducted in various states of Australia, and no such studies have been carried out in Western Australia. Therefore, results of this study will support the crucial need to understand the burden of CRC in Western Australia better, thus contributing to the implementation of the national efforts of cancer prevention and control.

Colonoscopy is widely available in Australian public and private hospitals and the increase in colonoscopy utilisation rate occur due to rise in ageing and overall population. The higher incidence of colorectal cancer in Australia combined with the implementation of National Bowel Cancer Screening Program surge the colonoscopy demand. This study will evaluate the changing trend in colonoscopy rates in public and private sectors and provide the essential information for the future guidelines for screening colonoscopy in Western Australia.

 

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