LAUSR

Simple Summary Since the 70s, a variety of colorectal cancer (CRC) screening programs have been adopted throughout the world with the aim of reducing the mortality rate of one of the leading cancer-related causes of death in the world. However, currently employed techniques present numerous shortcomings that negatively affect early-stage CRC detection, thus urging us to consider new and improved alternatives. Among the cited shortcomings are invasiveness and cultural stigma surrounding certain sample collection techniques, both of which negatively affect screening compliance. For this reason, many of the viable alternatives collected and described in this review aim to achieve good diagnostic performance while minimizing patient stress and discomfort. This text should serve as a guiding light for healthcare providers specialized in preventive medicine in the continuous pursuit of improved patient care. Abstract Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Since the 70s, many countries have adopted different CRC screening programs, which has resulted in a decrease in mortality. However, current screening test options still present downsides. The commercialized stool-based tests present high false-positive rates and low sensitivity, which negatively affects the detection of early stage carcinogenesis. The gold standard colonoscopy has low uptake due to its invasiveness and the perception of discomfort and embarrassment that the procedure may bring. In this review, we collected and described the latest data about alternative CRC screening techniques that can overcome these disadvantages. Web of Science and PubMed were employed as search engines for studies reporting on CRC screening tests and future perspectives. The searches generated 555 articles, of which 93 titles were selected. Finally, a total of 50 studies, describing 14 different CRC alternative tests, were included. Among the investigated techniques, the main feature that could have an impact on CRC screening perception and uptake was the ease of sample collection. Urine, exhaled breath, and blood-based tests promise to achieve good diagnostic performance (sensitivity of 63–100%, 90–95%, and 47–97%, respectively) while minimizing stress and discomfort for the patient.