The American Cancer Society estimates that colorectal cancer (CRC) will be the third most common
cause of cancer death for both men and women in the U.S. in 2013. The natural history of the
disease suggests that longer delays in CRC diagnosis will negatively influence stage at diagnosis and
long-term survival. CRC may be diagnosed by screening asymptomatic patients or by evaluation of
symptomatic patients. Previous studies investigating the influence of delays on survival or cancer
stage at diagnosis have primarily focused on the evaluation of time from first symptom development
in symptomatic patients and have demonstrated inconsistent results. For example, among 13 studies
published between 1977 and 2006 included in a 2007 systematic review by Ramos and colleagues,
10 found no association between the symptom-to-diagnosis interval (SDI) and survival and the
other three found that increased delays resulted in better chances of survival. As for the relationship
between SDI and tumor stage, among 18 studies, 11 found no association, four found that shorter
delays were associated with an earlier stage at diagnosis and three paradoxically found that a greater
delay was associated with an earlier stage at diagnosis. As noted by Ramos et al., the SDI risk
function is likely nonlinear and multifaceted, reflecting a complex interaction between tumor biology
and location, the clinical course, patient behavior, and the functioning of the healthcare system, and
the studies have varied in their methods for adjusting for these confounding factors. These findings
highlight the importance of detecting colorectal cancer through screening, before symptoms appear.
Key Question 1: How does variation in time to colonoscopy affect colorectal cancer-related
outcomes in patients referred for diagnostic colonoscopy?
Key Question 2: What are the clinical factors (e.g., reason for referral, positive FOBT or
symptoms; type and duration of symptoms; etc.) that moderate the relationship between time to
colonoscopy and harm?