Six out of 10 patients presenting to primary care with a high-risk feature of possible cancer did not receive an urgent referral in the 14 days after presentation, despite this being a guideline-recommended action. Urgent referral frequency varied by feature, with patients with breast lump receiving the highest percentage of referrals and patients with dysphagia the lowest. Younger patients, and those with comorbidities were less likely to receive an urgent referral. Associations between patient characteristics and urgent referrals differed by feature. More deprived women with breast lump, and patients with anaemia, breast lump, or haematuria and multi-morbidity were less likely to receive a referral; 3.6% of patients who did not receive an urgent referral were diagnosed with cancer within 1 year, this percentage varying between 2.8% for rectal bleeding and 9.5% for iron-deficiency anaemia.

We used a large, longitudinal, validated linked dataset which has been used extensively for cancer diagnostic studies,10 50 51 enabling important insights into patients’ journeys through the healthcare system. However, there are limitations. First, as an urgently referred patient would usually be investigated in an outpatient setting, the HES dataset comprised outpatient hospital data. Consequently, patients referred and admitted to hospital or directed to an emergency department will not have been identified even though timely action was taken. However, the number of such patients is likely small for the studied presenting features, especially given the substantial decrease in the number of cancers diagnosed following emergency GP referrals in the last decade.13 Second, identification of index consultations with one of the six features was based on medical codes in patient records. Some patients may have been missed because the feature was only recorded in inaccessible ‘free text’ (which is not available to researchers to avoid de-anonymisation) or because the feature was not recorded at all. However, CPRD studies of free-text data suggest it usually only confirms coded entries.52 Consequently, some patients with features of interest may not have been included in the study. However, those who were included almost certainly had the feature, and thus a Two Week Wait referral would have been recommended. Third, inclusion of patients was limited to 2014 and 2015 as cancer registry data were only available up to and including 2016 at the time of data extraction. However, it is unlikely that this will have affected results, as the guidelines had been in use for a number of years, and analyses were restricted to patients where an urgent referral would have been recommended in both the 2005 and 2015 guidance. Fourth, we excluded patients with haematuria who were treated for possible urinary tract infection (unless it was not the last visit or a third consultation within 6 months) on the basis of prescriptions for two of the most common first-line antibiotics for urinary tract infection. A small number of patients will have been prescribed different antibiotics and been included in error. Fifth, although the study showed that many patients were diagnosed with cancer after not receiving an urgent referral after presenting with a suspected cancer feature, we were unable to give insight into the potential impact of non-referral on cancer stage. Finally, we note that although for three features we exceeded our planned sample size, the number of patients presenting with iron-deficiency anaemia or post-menopausal bleeding was significantly less than planned.

Previous studies have reported that the number of GP consultations before referral varied by cancer type.53 It appears that GPs are less likely to suspect cancer for some features compared with others. This may be partially explained by the greater likelihood of some features being caused by other explanations than cancer. However, the risk of cancer with all these features is always low in absolute terms, with iron-deficiency anaemia having the highest positive predictive value of the six for cancer (for men over 60 years with a haemoglobin <11 g/dL and features of iron deficiency, the positive predictive value is 13%54). The decision to refer may be influenced by factors other than guidelines, such as GPs’ symptom interpretation,55 additional presenting features supporting a different diagnosis, and clinical intuition,56 but also by how local health services are organised.20 Variation in referral has been shown to be partly attributable to Clinical Commissioning Groups (CCGs) and Acute Hospital Trusts.20 This is supported by qualitative research suggesting that GPs are hesitant to refer or even feel pressured by CCGs to not refer due to resource pressures.57 Additionally, although probably only responsible for a small proportion of non-referrals, there are a number of other factors which may affect whether a referral was made or recorded (box 1). Regardless of the GPs’ reasons for referral or non-referral, our study shows that GPs often made the right decision regarding referral for their patients. Given the proportion of patients going on to be diagnosed with cancer was considerably higher in those receiving an urgent referral than those who did not, we can conclude that GP referral decision-making is not without value. However, given the number of patients diagnosed with cancer after non-referral, we may question whether clinical judgement is good enough: 5.5% of patients with anaemia not receiving an urgent referral were diagnosed with colorectal cancer within 1 year, 3.5% of women presenting with breast lump who did not receive a referral were diagnosed with breast cancer, and 2.9% who presented with post-menopausal bleeding were diagnosed with uterine cancer. In these patients it can be argued that guideline-discordant decision-making may have resulted in a missed opportunity to diagnose early. Better adherence to the guidelines may therefore be important in order to increase detection rate, even for alarm features with already high urgent referral rates.

Although we expect that it only affects a small number of patients, there are a number of mechanisms besides GP referral decision-making which may potentially influence whether an urgent referral was made or recorded:

Patients were admitted to hospital via emergency admission

The referral was not accepted by the hospital. (This should be captured by the sensitivity analysis including Clinical Practice Research Datalink (CPRD) referrals)

The patient refused to be referred

A downgrade of the urgency level of the referral was requested by the hospital. (This should still be captured in the CPRD sensitivity analysis)

Index consultation took place with out-of-hours practice services

Variations in local guidelines for referral. (For most patients this should be captured in either the sensitivity analysis including CPRD referrals or the sensitivity analysis including referrals made up to 90 days after presentation)

The patient received a related referral before first presentation, which affected the decision to refer

Our finding that younger patients were less likely to receive an urgent referral reflects earlier research reporting that younger patients typically experience longer diagnostic timelines.53 The present study also offers new insights into how multi-morbidity may affect diagnostic timeliness. Although there are suggestions that more contact with health services can shorten diagnostic intervals, a growing body of evidence suggests that multi-morbidity can also prolong diagnostic intervals.15 58–61 Given our findings, it may be these prolonged intervals arise, in part, due to a lower likelihood of receiving an urgent referral. Additionally, research suggests that multi-morbidity is associated with decreased use of specialist investigations.62 This may explain the strong multi-morbidity gradient observed for patients with anaemia where urgent referral would lead to an invasive test. Future research investigating how multi-morbidity affects GP referral decision-making for potential cancer features may help target improvement efforts.

Although, on average, deprivation was not associated with urgent referrals, more deprived patients with haematuria, rectal or post-menopausal bleeding were more likely to receive a referral. Although we can only speculate, this finding could be explained by earlier research suggesting that deprived patients are more likely to delay presentation,63 64 resulting in more serious potential cancer features, increasing the chance of an urgent referral. On the other hand, more deprived women presenting with breast lump were less likely to receive an urgent referral. As few women with breast cancer delay presentation,63 the association between deprivation and referral is likely to reflect differences post-presentation. Patients with a higher socioeconomic status tend to be more effectively able to communicate their symptoms and concerns,65 66 while GPs’ communication tends to be more patient-centred with less deprived patients.67 This may potentially result in closer alignment in perceptions of symptom significance68 and influence GPs’ decision to refer.

We have identified patient groups who may be at risk of longer diagnostic timelines. GPs may be less likely to refer patients when their age,69 or alternative medical explanations, suggest a lower risk of cancer. However, guidelines incorporate patient age and thus recommended action is still appropriate for those age groups.

Clinical practice guidelines have been shown to improve treatment quality for a range of conditions and could also help to improve the quality of the diagnostic process. However, our study shows that recommendations for the assessment of patients with features of possible cancer are not always followed. Stricter adherence to the guidelines and increased awareness of patient groups especially at risk of long diagnostic timelines may help improve early diagnosis and ultimately cancer survival rates. Due to the potential impact of regional health services, interventions to reduce guideline discordant behaviour may have more impact if they do not just focus on GPs and individual practices, but also on local diagnostic service provision.