The toll of not screening for colorectal cancer

Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer mortality worldwide. Each year, 1.4 million people are diagnosed with CRC, representing 10% of the total global cancer incidence, and 700,000 people die as a result of the disease [1]. Although more cases continue to occur in highincome countries, CRC incidence has been rising rapidly in many less developed countries, such as Brazil, Philippines, and Bulgaria [2]. A large proportion of these cancers, however, develop slowly from removable colorectal adenomas over many years [3], and when detected and treated at early stages, the disease is mostly curable. Patients with CRC detected in a localized stage have a 5-year survival rate exceeding 90%, whereas 5-year survival still hardly exceeds 10% for patients with metastatic CRC [4]. These features make CRC a most suitable target for screening. Through early detection and removal of nonmalignant precancerous lesions and early cancers, screening tests can effectively reduce the incidence of advanced carcinoma and thus lead to a reduction in CRC mortality. A growing body of joint evidence from randomized controlled trials (RCTs) and observational studies have well established the effectiveness of screening by fecal occult blood test (FOBT), sigmoidoscopy, and colonoscopy in the prevention of CRC occurrence and deaths [5,6]. Population-based epidemiological analyses showed that recent colonoscopy use among around onethird of the screening-eligible population in the USA had avoided approximately 10,000 CRC deaths in 1 year, and about twice as many deaths could theoretically have been prevented if perfect adherence (100%) were achieved [7]. The considerable declines in CRC incidence and mortality observed in the USA over the past decade, in fact, are believed to be largely attributed to the increased awareness about the disease and the relatively high adherence to screening, especially colonoscopy screening [8]. Likewise, in Germany, a substantial and accelerating decrease in CRC incidence and mortality was observed between 2003 and 2012, the first 10 years since the implementation of screening colonoscopy. This decrease was selectively observed in the age groups for whom screening colonoscopy is offered (55+) [9]. Although CRC screening requires initial investments, modeling studies have consistently shown that CRC screening is cost-effective (if not cost-saving) in the long run, and comparable effectiveness and cost-effectiveness can be achieved through different strategies, such as annual FOBT, sigmoidoscopy every 5 years with annual FOBT, and colonoscopy every 10 years [10]. Because of the large potential in reducing disease burden, CRC screening has been recommended in many guidelines for average-risk persons aged over 50 years. However, only a few countries currently have screening programs in place or are in the process of implementation, and screening programs are essentially restricted to some of the more developed countries in North America, Europe, and Asia [11]. Even in countries where screening tests are routinely offered, such offers often do not reach the entire population and uptake rates often remain suboptimal, leaving much of the potential impact of screening programs unutilized. Most population-based organized screening programs employ a two-step approach, starting with a noninvasive stool test, usually guaiac-based FOBT (gFOBT) or (increasingly) fecal immunochemical test (FIT), and following up with colonoscopy for those with positive results. Due to the need for repeated testing annually or biennially, one of the challenges these programs face is how to keep up the good compliance among initially screened persons in the following rounds of screening [12]. Sustained participation is essential for screening efficacy and should be an equally important indicator for program evaluation. Experience from the Netherlands and Finland shows that sustained high participation rates can be achieved by well-organized screening programs [13,14]. In some affluent countries where CRC screening is mostly opportunistic and delivered through physician recommendation, such as the USA, the predominantly used strategy is screening colonoscopy every 10 years. Seemingly more flexible for the target population, such strategy also has adherence that falls below the desirable levels – about one-third of age-eligible US residents were not up to date with screening in 2012 [15]. Multiple factors from individual, healthcare provider and organizational levels have been reported to be associated with screening compliance, such as patient socioeconomic status and knowledge of CRC screening, physician