Time to diagnosis and treatment in younger adults with colorectal cancer: A systematic review

Abstract

Background The incidence of colorectal cancer is rising in adults <50 years of age. As a primarily unscreened population, they may have clinically important delays to diagnosis and treatment. This study aimed to review the literature on delay intervals in patients <50 years with colorectal cancer (CRC), and explore associations between longer intervals and outcomes. Methods MEDLINE, Embase, and LILACS were searched until December 2, 2021. We included studies published after 1990 reporting any delay interval in adults <50 with CRC. Interval measures and associations with stage at presentation or survival were synthesized and described in a narrative fashion. Risk of bias was assessed using the Newcastle-Ottawa Scale, Institute of Health Economics Case Series Quality Appraisal Checklist, and the Aarhus Checklist for cancer delay studies. Results 55 studies representing 188,530 younger CRC patients were included. Most studies used primary data collection (64%), and 47% reported a single center. Sixteen unique intervals were measured. The most common interval was symptom onset to diagnosis (21 studies; N = 2,107). By sample size, diagnosis to treatment start was the most reported interval (12 studies; N = 170,463). Four studies examined symptoms onset to treatment start (total interval). The shortest was a mean of 99.5 days and the longest was a median of 217 days. There was substantial heterogeneity in the measurement of intervals, and quality of reporting. Higher-quality studies were more likely to use cancer registries, and be population-based. In four studies reporting the relationship between intervals and cancer stage or survival, there were no clear associations between longer intervals and adverse outcomes. Discussion Adults <50 with CRC may have intervals between symptom onset to treatment start greater than 6 months. Studies reporting intervals among younger patients are limited by inconsistent results and heterogeneous reporting. There is insufficient evidence to determine if longer intervals are associated with advanced stage or worse survival. Other This study’s protocol was registered with the Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42020179707).

Analysis of Time to Treatment and Survival Among Adults Younger Than 50 Years of Age With Colorectal Cancer in Canada

“…Advanced and metastatic disease was strongly associated with shorter time to treatment, likely explaining why younger patients with CRC with overall intervals less than 100 days had worse outcomes, particularly those with intervals less than 6 weeks (overall mortality: HR, 1.73 [95% CI, 1.46-2.06]). Among a subset of 2548 patients with lower-urgency presentations and nonmetastatic disease, the analysis reached similar conclusions: longer time to treatment was not associated with worse OS or CSS.To our knowledge, there are few studies examining the association between delay intervals and survival specifically in adults younger than 50 years with CRC 10. Di Girolamo et al11 performed a Figure shows restricted cubic spline regression data for entire cohort (A) and stratified by stage of colorectal cancer (B).…”

“…in comparison with the literature, 10 and is also unlikely to be applicable to the Ontario setting. Our study greatly adds to this limited literature in younger adults.…”

“…11,[40][41][42][43][44][45] In a meta-analysis of 93 655 patients, 40 there was no difference in disease stage for those attending the TWW program's lower GI pathway vs standard referral. Our results suggest time to treatment is closely tied to disease stage at presentation and subsequent triage by physicians, and efforts to shorten this interval further are unlikely to result in meaningful improvements in survival for younger patients with CRC at the 46 While there are other benefits of timely treatment, including health care costs, efficient use of resources, and patient distress, 47 our study (and much of the existing literature 10,13,14 ) does not implicate postpresentation delay as a driver of worse outcomes for patients younger than 50 years with CRC.…”

“…To our knowledge, there are few studies examining the association between delay intervals and survival specifically in adults younger than 50 years with CRC . Di Girolamo et al performed a population-based analysis in the UK, examining cancer waiting time targets and survival, which included 3542 younger patients with CRC (aged 15-44 years).…”

“…The literature specifically examining adults younger than age 50 years is sparse. In a systematic review of 55 studies 10 reporting delay intervals in this population, only 2 examined survival in young people and 1 found worse outcomes with longer delay. 11,12 These 2 studies have limitations; the first 12 is a single-center analysis, and the second 11 did not assess survival beyond 1 year.…”