Colorectal cancer screening from 45 years of age: Thesis, antithesis and synthesis

Table 1 Model-estimated benefits and burden of colorectal cancer screening starting at age 45 vs 50 per 1000 screened over a lifetime[27]

Screening test	Age of start and stop	Life years gained	Number of colonoscopies	Recommendable?
Colonoscopy every 10 yr	45-75	429	5646	Yes
	50-75	404	4836	No
CTC every 5 yr	45-75	390	2666	Yes
	50-75	368	2430	No
Flexible sigmoidoscopy every 5 yr	45-75	403	3761	Yes
	50-75	380	3426	No
FIT every year	45-75	403	2698	Yes
	50-75	377	2402	No
HSgFOBT every year	45-75	403	3364	No
	50-75	377	2956	No
mt-sDNA every 3 yr	45-75	376	2640	No
	50-75	350	2331	No

The model predicted better suitability for fecal immunochemical testing over high sensitivity guaiac fecal occult blood testing (HSgFOBT) because the latter has higher false positive rates (nonsteroidal anti-inflammatory drugs causing upper gastrointestinal bleeding, red meat, dietary peroxidases contained in fruits and vegetables). Thus, it increases the number of unnecessary colonoscopies. However, HSgFOBT is less expensive, making it an attractive option in low-resource settings. Colonoscopy every 10 years from the age of 45 to 75 years provides the greatest reduction of mortality and incidence, as well as more life-years gained and deaths averted, with twice as many colonoscopies as stool-based tests. CTC: Computed tomography colonoscopy; FIT: Fecal immunochemical testing; HSgFOBT: High sensitivity guaiac fecal occult blood testing; mt-sDNA: Multitarget stool DNA.

Table 2 Reasons in favor of and against colorectal cancer screening from 45 years of age

Reasons favoring earlier screening	Reasons against earlier screening
Burden of disease
The incidence of eoCRC is increasing, and metastatic diseases are increasing faster. 11% and 10% of all males’ and females’ CRC cases occur before the age of 50; of all years of potential life lost from CRC, 10% were from the 45-49 age group	The absolute risk of eoCRC is still considerably smaller than the older counterpart; incidence reaches 34 vs 60:100000, respectively
Expected benefits
In the absence of data from randomized controlled studies, three computational models predicted a benefit from lowering the age of screening	Computational models have several limits. They assume an unrealistic 100% adherence rate; they failed to consider CRC as a multifactorial disease where other risk factors influence one’s risk (i.e., sex, diabetes, diet, lifestyle and others)
Sustainability
Earlier screening is economically feasible in the United States, and it might be similarly feasible in most European countries; some European countries have also reported a shortage of gastroenterologists	Earlier screening will create care costs that may not balance the reduced incidence and mortality; implementing earlier screening might produce resource diversion. Enhancing compliance rates to colorectal screening is an equally important task that might be overlooked if excessive emphasis is placed on earlier screening
Society guidelines
The ACS recommends screening from 45 years of age. ACG and ASGE support screening from 45 years of age for African Americans, whose incidence of eoCRC is superimposable on Caucasians	USPSTF, USMSTF and ECCSGWG support screening from 50 years of age

eoCRC: Early-onset colorectal cancer; CRC: Colorectal cancer; ACS:American Cancer Society; ACG: American College of Gastroenterology; ASGE: American Society of Gastrointestinal Endoscopy; USPSTF: United States Preventive Service Task Force; USMSTF: United States Multi-Society Task Force on colorectal cancer; ECCSGWG: European Colorectal Cancer Screening Guidelines Working Group.