Our study reviewed patterns of presentation, diagnostic delays, and outcomes in EoCRC. Multiple studies have shown early-onset patients experience diagnostic delays and diagnosis at more advanced stages of CRC(8, 16, 17). As individuals < 50 fall outside screening programs in most countries, it is imperative to understand the constellation of symptoms they present with. Our study demonstrates that EoCRCs present at more advanced stages, have more symptoms at diagnosis, and experience diagnostic delays, however in our dataset these delays did not result in worse survival. Furthermore, the number of symptoms at presentation plays a role in determining the survival of all individuals with CRC, but to a much greater extent in EoCRC. This persists after controlling for confounding variables with multivariate analysis.
The pattern of symptoms at presentation is similar between EoCRC and LoCRC. The three most common symptoms are bloody stools, abdominal pain and change in bowel habits, consistent with prior studies(18–20). Several prospective studies(21, 22) and a systematic review(23) to determine the positive predictive value of CRC-type symptoms found that these three symptoms individually and in combination are effective at predicting CRC. While it is important to recognize that these three symptoms may be indicative of other benign diseases, placing CRC on the differential is imperative, especially in younger individuals.
Our group found EoCRC has improved survival compared to LoCRC, similar to the work of others(10, 24–26). Despite this, the interval duration from symptom onset to diagnosis was longer in EoCRC, in accordance with multiple studies(27, 28). Multiple reasons for this have been postulated, including lack of recognition of symptom significance and denial on both the part of the clinician and patient(4, 29). We have also shown in this study, that duration of symptoms does not impact survival significantly, which is a key finding. In this case, what is driving this survival advantage in EoCRC? We found a strong predictor of survival is the symptom burden at diagnosis and noted that young patients presented with more symptoms. This may be a reflection of a more aggressive tumor causing rapid growth for patients with symptoms, while other young patients may have slower growing tumors and their pre-morbid health may be protective and improve the median survival of the overall cohort.
Our study has important limitations. First, symptoms were collected through retrospective chart review of a pre-defined list of symptoms, some of which may not have been documented, and therefore our analysis may under-represent symptom burden. Second, the duration of symptoms is subject to recall bias as this information was collected from documents at the time of diagnosis, limiting the interpretation of the absolute median days from symptom onset to diagnosis. Thirdly, we found that LoCRC had a rate of 20% detection of cancer through screening. The uptake in BC’s Colon Screening Program in 2019 shows a participation rate of 30–39% depending on age and a recent randomized study suggested uptake in a clinical trial was only 42%(1). Overall, uptake in screening programs is low, and with this study we demonstrate the benefit to survival of identifying CRC prior to development of symptoms.
In conclusion, we demonstrate the importance of recognizing symptoms associated with CRC. While symptom burden was associated with survival, we did not note delays in CRC diagnosis as a predictor of survival or complications during initial presentation. With the rising incidence of EoCRC, more work is needed to understand how best to identify these patients early so they have the best chance of cure.