This register-based nationwide study included more than 140,000 cancers and demonstrated that the probability of getting diagnosed through a specific RtD varied by the age of the patients (in both case-mix adjusted analyses and analyses adjusting for socio-economic characteristics and comorbidity). Among patients diagnosed with cancer outside screening programs, our study showed that patients aged 80 years or older were more likely to get diagnosed by DCO or by an unplanned admission, and less likely to get diagnosed after a CPP referral from primary care compared to patients aged 50–79 years. The pattern was even more profound for patients aged 90 years or more. Patients below 50 years were also less likely to get diagnosed after a CPP referral from primary care, yet more likely to be diagnosed after CPP referral from secondary care compared to patients aged 50–79 years.
Among screen-detected cancers, the probability of having a screen-detected cervical cancer was higher among the youngest age groups (aged 23–49) compared to patients aged 50–59, while for patients with breast cancer the probability of being diagnosed after screening was higher among patients aged 60–69 than among patients aged 50–59.
Comparison with other literature
Despite this being the first large scale study to report the associations between age and RtD in a Nordic healthcare system, our findings still bear similarities with findings from other countries and smaller studies [4, 6, 32,33,34].
In parallel with findings from England, while CPP with referral from primary care was the most frequent RtD across all age groups, the oldest patients were less likely to get diagnosed via this route compared to younger age groups [4, 6]. A smaller study from Denmark contradicts our findings of older patients being less likely to get diagnosed after CPP referral from primary care, as Jensen and colleagues reported no age differences [32]. However, this discrepancy may be due to selection and information bias in the former study, as the study was based on questionnaire data [32].
A study from Norway showed that older patients were less likely to complete a CPP than younger patients [15]. Although the Norwegian study did not account for other RtD, the findings in conjunction with ours indicates that older patients are less likely to get diagnosed after CPP referral from primary care – especially as the organization of CPPs in Norway is similar to the Danish [14, 15].
Elliss-Brookes et al. also reported that older patients constituted a larger proportion of patients diagnosed by DCO or after an emergency admission compared to younger patients with cancer in England [4]. This is in line with our findings. Especially emergency presentation, which relates to unplanned admission investigated in our study, has been shown to be associated with older age [6, 34].
Our finding of the youngest patients being less likely to get diagnosed after CPP referral from primary care contrasts the reporting from both England [4] and a smaller Danish survey [32]. In England, the proportion of younger patients diagnosed by two-week-wait referral was similar or slightly higher than the proportion of patients from 50 to 69 years of age [4]. The reasons for this discrepancy is unknown, whereas the discrepancy with the Danish survey study may be due to the higher number of young patients in the present study [32].
Interestingly, screening programs detected a large share of the cervix cancers among the youngest women, even though the participation rates in the national screening program in Denmark is lower within this age group compared to older age groups [35]. Participation rates in breast cancer screening are fairly even across the invited age groups while we find that screening detected a slightly higher share of patients aged 60–69 compared to 50–59 [36, 37].
Methodological considerations
Major strengths of the study are the high quality of data that cover the entire Danish cancer population, and that Danish national registers are reliable and have a high degree of completeness [20]. We facilitated the analyses by excluding relatively few observations, but this is unlikely to substantially to have impacted the results. Arguably, using registry data, registration errors should be acknowledge, but such registration errors are unlikely to systematically bias the results. Also, our methods were robust, as the results were similar in sensitivity analyses.
Some limitations, however, also relates to the data. The RtDs were defined in line with most related studies in the field by using a contextual definition, in contrast to a clinical definition, which relates to the patient’s medical condition [7]. Despite, the definition being contextual, increased adverse prognosis among unplanned admissions supports the use of a contextual definition as a marker of clinical severity [4, 7, 18]. An additional limitation is that the registers do not contain data that allow adjustment for important covariates such as body mass index, smoking or alcohol consumption.
Interpretation and implications
Patients with cancer aged 50–79 years were most likely to get diagnosed after CPP referral from primary care in symptomatic patients. Along with screening, this RtD may, from a prognostic view, be seen as the most optimal RtD for a given patient [38], as these two RtDs are associated with the best prognosis and highest level of patient satisfaction [4, 6, 33, 39].
Despite symptomatic patients aged 50–79 years were most likely to get diagnosed after CPP referral from primary care, more than four out of ten symptomatic patients with cancer in this age range were still diagnosed via an RtD associated with a worse prognosis. This emphasizes that there may be room for improvement in the diagnosis of cancer among mid-aged patients.
We found that patients younger than 50 years were less likely to get diagnosed after referral from primary care to a CPP. General practitioners not suspecting cancer as the cause of young patients’ symptoms may explain this [32, 40]. Yet, patients with cancer aged 50 years or younger comprise 16% of all patients with cancer in Denmark [41], indicating that cancer diagnoses could be missed initially in this age group. Thus, although relatively uncommon in patients below 50 years, cancer remains a potential differential diagnosis whenever a patient presents to healthcare, now or in the future, as the incidence of cancer in patients aged 20–50 years are increasing [41].
Despite patients aged 70 years or older constitute almost half of all patients with cancer in Denmark [42], our study shows that the oldest patients are less likely to get diagnosed after CPP referral from primary care. This may be related to the higher prevalence of comorbidity in older patients for two reasons: The existence of other morbidities may mislead clinicians to contribute signs and symptoms to the already existing morbidity rather than an underlying cancer [43]. Consequently, the patients may not be referred to CPP, and despite displaying symptoms, the cancer is not discovered until the patient interacts with the healthcare system in relation to other comorbidities or presents urgently with severe symptoms. This argument is substantiated by studies reporting that the suspicion of cancer is lowest among patients with a high customary use of primary care, and that these patients often have multiple morbidities [40]. However, having another disease may also bring the cancer forward at an earlier point in time – potentially even before the cancer symptoms become apparent. For instance, clinicians may discover hepatocellular carcinoma when surveilling patients with cirrhosis [44].
Recently more emphasis has been put on frailty rather than comorbidity to explain why older patients seem to be disadvantaged in healthcare, as two persons with same level of comorbidity may have substantially different level of health [45]. Frailty may be defined as an increased vulnerability and risk of adverse effects caused by reduced organ reserve capacity in a person, and is often measured by geriatrics using a comprehensive geriatric assessment (CGA) tool [45]. Using CGA have shown potential to improve prognosis in older patients with cancer [46], why a broader use of CGA (e.g. in primary care) may be useful. However, as current comprehensive geriatric assessment needs to be undertaken by an interdisciplinary team [46], a simpler and easier to use screening tool that could identify the patients most in need of a full CGA at a hospital could be useful.
While comorbidities and frailty are probable contributors to the age discrepancy in RtD, it is also possible that older patients are more likely to decline urgent referrals. Indeed, research suggests that while most old patients with cancer accept treatment, these patients are more likely to refuse invasive treatment compared to younger patients [47, 48]. Yet, we cannot rule out that some of the age discrepancy in RtD may also reflect a lower inclination among clinicians to offer speedy diagnostics to older patients with potential cancer.