In the USA, screening for CRC has been promoted since the mid-1970s but the tools that are currently used for screening have a much longer history. Although the Corpus Hippocraticum, dating back to the fourth and fifth centuries BC, recorded the first rudimentary attempt at endoscopy with a rectal speculum, most historians credit Philipp Bozzini (Fig. 2.2a) as the creator of the first “modern” endoscope in 1806—the Lichtleiter or light conductor (Fig. 2.2b). The device was constructed with double aluminum tubes (to be inserted in the body orifice being examined) and angled mirrors to project internal structures to the human eye, employing a single candle as a light source [7]. Rigid sigmoidoscopes have long been used diagnostically and screening sigmoidoscopy was developed in the 1950s [8].

Fecal occult blood testing (FOBT) also has a long history. In the 1850s, Christian Friedrich Schonbein first recognized the chemical reaction causing rapid bluing of guaiac (a resin from the West Indian gouyaca plant) when exposed to ozonized air [9]. Guaiac contains a phenolic compound that is oxidized to a quinone by hydrogen peroxide in a reaction catalyzed by peroxidases including hemoglobin. Von Deen developed a guaiac-based test for occult blood in 1863 [10]. Greegor stimulated widespread interest in FOBT when he reported, in 1967, that asymptomatic CRC could be detected by the presence of blood in the stool [11]. The immunologic tests to detect human hemoglobin were introduced in the 1970s [12], commercialized in the 1980s, and are now considered preferable to standard guaiac-based FOBT because of better performance characteristics (see below). Several FIT tests have now been approved by the US Food and Drug Administration (US-FDA).

As early as 1977, the American Cancer Society (ACS) recommended CRC screening with digital rectal exam and rigid proctoscopy as part of a cancer-related health checkup [13]. The rationale for screening was largely based on observations that patients with screen-detected CRCs had earlier stage disease and longer survival than those with symptomatic CRCs. Compelling evidence of the effectiveness of CRC screening emerged with the completion of large randomized screening trials beginning in the 1990s. On the basis of these trials, the US Preventive Services Task Force (USPSTF) initially recommended CRC screening with annual FOBT and/or sigmoidoscopy in 1995 with a grade B recommendation citing fair evidence of effectiveness [14]. In 2002, the USPSTF upgraded CRC screening to a grade A recommendation stating that the USPSTF “strongly recommends that clinicians screen men and women aged 50 and older who are at average risk for colorectal cancer.”In 2004,CRC screening became a Healthcare Effectiveness Data and Information Set (HEDIS) performance measure, essentially establishing that CRC screening is an accepted standard of care in the USA (HEDIS measures are used by more than 90 % of US health plans to measure performance). CRC screening guidelines in the USA have evolved over time (Fig. 2.3), largely based on the results of the trials that are described in this chapter.

Current CRC screening options can be categorized into stool-based testing and structural radiographic or endoscopic imaging. Stool-based tests detect the consequences of colonic neoplasia (bleeding or shedding of neoplastic cells into the stool) and, as a one-time test, are better at detecting cancers than precancerous colonic polyps, while imaging modalities (endoscopy, radiology) can directly visualize both colonic polyps and cancers. The advantages, disadvantages, and performance characteristics of these tests are compared in Table 2.1.