Research

Association between use of urgent suspected cancer referral and mortality and stage at diagnosis: a 5-year national cohort study

Thomas Round, Carolynn Gildea, Mark Ashworth and Henrik Møller
British Journal of General Practice 2020; 70 (695): e389-e398. DOI: https://doi.org/10.3399/bjgp20X709433

Abstract

Background There is considerable variation between GP practices in England in their use of urgent referral pathways for suspected cancer.

Aim To determine the association between practice use of urgent referral and cancer stage at diagnosis and cancer patient mortality, for all cancers and the most common types of cancer (colorectal, lung, breast, and prostate).

Design and setting National cohort study of 1.4 million patients diagnosed with cancer in England between 2011 and 2015.

Method The cohort was stratified according to quintiles of urgent referral metrics. Cox proportional hazards regression was used to quantify risk of death, and logistic regression to calculate odds of late-stage (III/IV) versus early-stage (I/II) cancers in relation to referral quintiles and cancer type.

Results Cancer patients from the highest referring practices had a lower hazard of death (hazard ratio [HR] = 0.96; 95% confidence interval [CI] = 0.95 to 0.97), with similar patterns for individual cancers: colorectal (HR = 0.95; CI = 0.93 to 0.97); lung (HR = 0.95; CI = 0.94 to 0.97); breast (HR = 0.96; CI = 0.93 to 0.99); and prostate (HR = 0.88; CI = 0.85 to 0.91). Similarly, for cancer patients from these practices, there were lower odds of late-stage diagnosis for individual cancer types, except for colorectal cancer.

Conclusion Higher practice use of referrals for suspected cancer is associated with lower mortality for the four most common types of cancer. A significant proportion of the observed mortality reduction is likely due to earlier stage at diagnosis, except for colorectal cancer. This adds to evidence supporting the lowering of referral thresholds and consequent increased use of urgent referral for suspected cancer.

INTRODUCTION

Late diagnosis contributes to relatively worse cancer survival rates in the UK,1,2 with longer diagnostic intervals associated with higher mortality.3,4 Although most of those with cancer present symptomatically to primary care,5,6 diagnosis of cancer is not straightforward.7,8 Patient-, doctor-, and system-related factors can all contribute to longer cancer diagnostic intervals.9–13 Concerns about potential diagnostic delays led to the implementation of urgent suspected cancer referral pathways,14,15 based on referral criteria defined by the National Institute for Health and Care Excellence (NICE). These pathways enable rapid access to a specialist opinion or diagnostic test (2-week wait [2WW] in England) for patients with specified symptoms. Evidence shows time to diagnosis and start of treatment is shorter for patients referred urgently,16,17 whereas longer diagnostic intervals are associated with more advanced cancers at diagnosis.18 The NICE suspected cancer referral guidelines were updated in June 2015,19 lowering the risk threshold for referral. Referrals have been increasing by approximately 10% year on year, with >2 million referrals in England in 2018. As a result, more patients are being diagnosed with cancer following GP referrals, with significant reductions in those diagnosed via emergency routes.20 There is significant variation between practices in their use of urgent suspected cancer referrals,21–23 which has been a cause for concern.24 Use of urgent referrals varies by cancer site, with referral less likely for cancers characterised by non-specific presenting symptoms and patients belonging to low-cancer-incidence demographic groups.25

From financial year 2009/2010 a set of yearly suspected cancer referral metrics for every practice in England became available, produced by Public Health England (PHE).26 Previously published evidence that higher practice use of urgent referral is associated with lower cancer patient mortality27 was based on a single year (2009) cohort.

A more detailed analysis has been called for to understand variation in use of urgent referral pathways.14,23,28 This includes whether the association with cancer patient mortality can be replicated over a longer time period, is consistent across the main cancer types (colorectal, lung, breast, and prostate) — which make up approximately half of all cancer cases, and the association with stage at diagnosis.27

METHOD

In this study, cancer registration data were extracted for all patients diagnosed with cancer (ICD-10 codes C00–C97, excluding non-melanoma skin cancer [C44]) between 2011 and 2015 in England from PHE’s National Cancer Registration and Analysis Service (NCRAS).29 Demographic data included sex, deprivation, age at diagnosis, and vital status. For each tumour, data included diagnosis date, cancer type, stage at diagnosis, mortality, and the associated GP practice code.

There is considerable variation in use of urgent referral for suspected cancer between general practices. This study shows a significant association between higher practice use of urgent referral for suspected cancer and lower cancer patient mortality (2011–2015), for all cancers combined and for the most common types of cancer (colorectal, lung, breast, and prostate). A significant proportion of this reduction in mortality is likely due to earlier stage at diagnosis for all cancers, except colorectal. This study supports the observed increased use of urgent referral for suspected cancer in primary care following the updated National Institute for Health and Care Excellence guidelines.

How this fits in

These tumours were linked to GP practice metrics on urgent referrals for suspected cancer, derived from the English national Cancer Waiting Times (CWT) database.30 These metrics were based on patients with a date of first hospital appointment or treatment recorded in financial years April 2011 to March 2016, relating to approximately 6.9 million urgent referrals for suspected cancer from >9000 English general practices. Those with missing practice-level referral metrics were analysed separately.

Three practice-level referral metrics26 were used:

  • practice referral ratio (RR) — indirectly standardised number of urgent referrals for suspected cancer, standardised according to the general practice’s registered list, and age–sex distributions (mean value 1);

  • practice detection rate (DR) — proportion of CWT-recorded cancers resulting from an urgent referral for suspected cancer (that is, the sensitivity of the selection of patients for urgent referral in the general practice); and,

  • practice conversion rate (CR) — proportion of urgent referrals for suspected cancer that result in a diagnosis of cancer (that is, the positive predictive value [PPV] for cancer among the patients selected for urgent referral).

Five-year aggregated practice referral metrics were used for all cancers, and metrics were separately calculated for each of the four most common types of cancer (colorectal, lung, breast, and prostate). Similar methods were used to those previously reported,27,31 with referral metrics data analysed as categorical variables by converting rates into quintiles (that is, five groups of equal population).

Cox proportional hazards regression was used to quantify the hazard of death from any cause in relation to referral metric quintiles, including for the four main cancer types. All analyses were adjusted for the age, sex, and socioeconomic status of the individual patients. The main analysis used a 5-year time window of follow-up from diagnosis to death, ending at the earliest of 5 years or the study end date in 2017.

Logistic regression was used to calculate the odds of late-stage (III/IV) versus early-stage (I/II) cancer at diagnosis in relation to referral quintiles. A further Cox proportional hazards regression was undertaken, in which stage at diagnosis (I to IV and missing) was taken into account. This was used to determine how much of the observed changes in mortality could potentially be related to stage at diagnosis (see Figure 1, with stage as a potential mediator between referral and mortality).

Figure 1.
Figure 1.

Possible associations between practice use of urgent referral and mortality, in the presence of a mediator (stage).

Stratified and sensitivity analyses were pursued to assess the consistency and internal validity of the findings, including a shared frailty random effects model32,33 to accommodate the multilevel structure of data where groups of patients with cancer belong to the same general practice list. All analyses were carried out with Stata 13 and 14.

RESULTS

Of 1 469 160 new cancer registrations between 2011 and 2015 (Figure 2), 57 registrations were excluded because of a negative duration of follow-up (that is, they were reported as having died before their cancer was registered). During follow-up 660 606 deaths occurred (45.0%) (for the increase in urgent referrals for suspected cancer from 2009/2010 to 2016/2017, and the impact on detection and conversion rates in England, see Supplementary Figure S1).

Figure 2.
Figure 2.

Flow diagram of study population with inclusions and exclusions.

Cohort characteristics

Table 1 reports demographic and tumour-related characteristics of the 1 469 103 cancer registrations included.

View this table:
Table 1.

Characteristics of the study cohort

The four most common types of cancer were identified. They were: colorectal (n = 173 293; 11.8%), lung (n = 186 018; 12.7%), breast (n = 221 695; 15.1%), and prostate (n = 196 745; 13.4%), together accounting for 52.9% of the cohort. One-third (32.9%) of the cohort had missing stage data, with variation by cancer type. Separate analysis was done of the 51 640 (3.5%) cancer registrations with missing 5-year GP referral data (see Supplementary Table S1 for details). Analysis of the cohort showed that approximately 1% of cancer patients changed practice within 4 months of referral, and approximately 2.5% changed practice within 4 months of diagnosis.

Distributions of referral metrics

Table 2 reports values for the three practice referral metrics. For all cancers combined, RR medians varied from 0.67 to 1.36, DR medians from 0.38 to 0.56, and CR medians from 0.06 to 0.13. Practices in the highest referral ratio quintile utilised the urgent referral pathway approximately twice as much as those in the lowest quintile.

View this table:
Table 2.

Quintiles of practice referral metrics (RR/DR/CR) for all cancers combined and specific cancer type

Mortality and stage analysis

All cancers

Table 3 shows 5-year all-cause mortality, odds of late- versus early-stage cancer at diagnosis, and mortality taking stage into account, in relation to quintiles of practice referral metrics.

View this table:
Table 3.

Analysis of mortality and stage for all cancers in relation to quintiles of referral metrics

Higher RR and DR quintiles were both significantly associated (P<0.001) with lower hazard of death for all cancer patients (Table 3a), with four and five percentage point reductions in mortality, respectively. Moving from lowest to highest quintiles for RR and DR showed a consistent significant trend in the association with lower mortality. CR was not significantly associated with mortality (P = 0.872).

Higher practice referral (RR/DR/CR) quintiles were all significantly associated with lower odds of late-stage versus early-stage cancer at diagnosis (P<0.001) (Table 3b). For the highest compared with lowest quintiles of RR and DR this equates to a two or three percentage point decrease in late-stage cancers at diagnosis.

After adjustment for stage at diagnosis, hazard ratios for the highest quintiles of RR and DR were attenuated (Table 3c compared with Table 3a), suggesting approximately half of the relative reductions in mortality for higher use of referral are potentially due to reductions in late-stage cancers at diagnosis. When stage was taken into account, higher CR quintiles were associated with a larger hazard of death (HR = 1.05; CI = 1.04 to 1.06) for highest CR quintile.

The patterns of association were consistent for sensitivity analyses, including 1-year mortality, and from a shared frailty random effects model accounting for clustering in GP practices.

Main cancer subtypes

See Supplementary Tables S2 to S4 for a report of colorectal, lung, breast, and prostate cancer cohorts in relation to quintiles of their specific referral indices.

For the four most common cancer subtypes, similar significant associations were also found between higher RRs and lower hazard of death over 5 years (P-values of <0.001, except for breast cancer [P = 0.005]).

Higher RRs were associated with lower odds of late- versus early-stage cancers at diagnosis (Supplementary Tables S2b to S5b) for all cancer types except for colorectal cancers.

When cancer stage was taken into account, hazard ratios for increasing RR were attenuated for all cancer types, except colorectal.

Table 4 summarises the percentage point difference from lowest to highest quintile of referral metrics (RR/DR/CR) for all cancers combined and most common types of cancer in relation to (a) 5-year mortality; (b) odds of late- versus early-stage cancers at diagnosis; and (c) 5-year mortality, taking stage into account. This demonstrates that a higher practice RR is significantly associated with lower cancer patient mortality and reduced late-stage diagnoses. This was found for all cancers and the most common types, except for late stage diagnosis for colorectal cancer. DR, and particularly CR, demonstrated less consistent associations.

View this table:
Table 4.

Percentage point difference between lowest (Q1) to highest (Q5) quintiles of referral metrics for all cancers and the most common types of cancer

Missing GP referral data

Of the total number of cases, 51 640 (3.5%) did not have GP referral data available (see Supplementary Table 1b for characteristics). Although those cohorts with missing GP referral data were of similar age distribution to the total cohort, they had lower white population (75.4% white in the missing referral data group versus 89.9% in total cohort) and showed higher rates of social deprivation (21.3% from the most deprived quintile in the missing referral data group versus 16.8% in the overall cohort). The missing referral data group also had lower rates of cancer diagnosis following urgent referral (28.2% versus 35.3%), and higher rates of unknown stage at diagnosis (40.6% versus 32.9%) compared with the overall cohort. Of the total, 44 852 cases (86.9%) had a registered practice code but the practice did not have a full 5 years of referral data, primarily due to practice changes (for example, closure) or small list size (<1000). Cases numbering 6795 (13.2%) were without practice code, including those who were unregistered with a GP practice and those for whom NCRAS could not determine the registered practice.

Those with missing GP referral data were found to have an overall higher hazard of death over 5 years compared with those with practice referral data (HR = 1.15; CI = 1.14 to 1.17; P<0.001).

DISCUSSION

Summary

This analysis of >1.4 million patients diagnosed with cancer in England between 2011 and 2015 shows that a greater propensity to use referrals for suspected cancer was associated with lower mortality for all cancers combined and for the most common types of cancer. Significant reductions in late-stage cancers at diagnosis were found for patients from practices with higher RRs, including for the most common types of cancer, except for colorectal cancer, where there was not a significant association.

Overall, the accuracy in case selection for urgent referral (CR) was not significantly associated with mortality or stage at diagnosis. But when stage was taken into account there was an increase in mortality with the highest CR quintiles.

A large proportion (one-third to half) of the observed reduction in mortality with higher use of urgent referral is likely to be explained by earlier stage at diagnosis — except for colorectal cancer, where lead time or other confounders may play a more important role.

Cancer patients with missing GP referral data (due to their practice not having 5-years’ referral data or not having an identifiable practice) showed significantly higher mortality.

This study has demonstrated that lower mortality and a reduction in late-stage cancers at diagnosis are associated with higher referral use. This supports the hypothesis that increased primary care use of urgent suspected cancer referrals and associated diagnostic testing may reduce late-stage diagnoses and mortality of patients with cancer.34,35

Strengths and limitations

The analysis was based on the complete national population of England, using all CWT records and population-based cancer registrations for 2011–2015. This reduces biases that can arise from the waiting times paradox,16,36 where patients with short and long times to treatment are compared.37 Also, direct comparison of urgently referred and non-referred patients is subject to selection bias and confounding by indication.38,39

As effects on mortality were estimated by time to event (death), lead time may contribute to the observed effect. Lead-time research has been focused primarily on screening,40,41 and in particular breast42,43 and prostate cancers,44 with relatively little mention in early symptomatic diagnosis literature.27,45,46

The most likely causes of case-mix variation between the general practices were adjusted for.25,47,48 Similar associations were found in sensitivity analyses accounting for cancer patient clustering at a practice level33 and for both 1-year and 5-year mortality, suggesting robust results. However, as in any observational study, the possibility of confounding remains.38,49

With >4% of patients changing practice in the study cohort, this suggests that the registered GP practice referral metrics give an accurate indication of referral patterns for the majority of patients.

At a practice level, urgent referral metrics for a single year can be based on relatively small numbers of referrals and cancer cases, meaning they exhibit year-on-year random variation,28 with differences in case-mix50 and in referral selection accuracy and thresholds.51 By using 5-year aggregated metrics, year-on-year random variation is reduced (although not completely excluded) and reliability should be improved. Even for 1-year metrics, process measures such as referral rate were shown to demonstrate acceptable reliability,28 although longer time-intervals are likely required for cancer-specific referral metrics and outcome measures such as conversion and detection rates.

Outcome measures included all-cause mortality and late versus early stage at diagnosis, and then mortality analysis taking stage into account (I to IV and missing) (see Table 4a to 4c and Supplementary Tables S2 to S5 for details) to understand the potential impact of stage on observed mortality (Figure 1). Although approximately one-third of the cohort having missing stage means the subsequent mortality analysis is potentially less robust, over time stage is increasingly better recorded within cancer registration data.

Comparison with existing literature

This study confirms the association between higher overall practice utilisation of suspected cancer referral pathways and lower patient mortality for all cancers,27 previously found for a single-year (2009) cohort study.23 It is also consistent with a previous study that showed an association between lower levels of referral from English general practices for gastroscopy (2006–2008) and worse patient outcomes for oesophageal-gastric cancers.52

In a study using data from 2012 on referral and cancer stage,53 higher use of urgent referral of patients with suspected cancer was associated with a smaller proportion of patients having advanced cancer. To the authors’ knowledge, this study for the first time included mortality, stage at diagnosis, and the impact of stage on mortality for all cancers and the most common types of cancer.

As noted, there have been studies investigating the reliability of these routinely collected practice measures28,50,51 and around practice and GP characteristics associated with their use.47,54

Higher practice CRs were associated with higher mortality when stage was taken into account for all cancers, suggesting worse outcomes. This could be due to a high threshold for referral by some GPs, with research showing an association between CRs and individual GP decision making.55

Although this study focused on primary care and GP referrals for suspected cancer, there is clearly potential variation once patients are referred, including in the clinical practice of individual specialists, treatments offered, and in the wider healthcare system31 that are important to consider.56

Implications for research and practice

The significant reduction in mortality between lower and higher use of urgent referral of between four and five percentage points approaches the magnitude of known and important differences between England and comparable countries.57,58 The number of referrals did increase over the period of the study and have continued to do so, with an associated increase in the number of cancer patients diagnosed following GP referral and a decrease in the proportion of cancer patients diagnosed via emergency routes, in whom there are worse outcomes,39 from 25% to 20%.20

Further investigations are warranted into the different scale of impact on mortality and stage at diagnosis for other specific cancer-site referral pathways, including the effect of lead time41,46 in symptomatic diagnosis — which is under-researched — and other potential mediators. In particular, there is a need to understand reasons for the observed lack of mortality reduction when stage is taken into account for colorectal cancer patients. This could include the impact of colorectal screening programmes, or, more recently, the use of Faecal Immunochemical Testing (FIT) in both screening and symptomatic presentation. Further work is needed to understand the factors associated with variation in referral including at individual GP,55 practice,47 and wider healthcare organisation levels.56

Although this study focuses on symptomatic urgent referral pathways for all cancers combined and the four most common cancer types, cancers characterised by lower-risk non-specific presenting symptoms (for example, multiple myeloma or pancreas) are likely to have multiple GP consultations prior to referral59 and pose diagnostic challenges.25 Further development and implementation of evidence-based clinical decision tools,34,60 including addressing issues around clinician cognitive error61,62 and the potential of future novel biomarkers60,63 are needed to aid earlier cancer detection — especially for difficult-to-diagnose cancer types.

This research adds to evidence supporting the policy of lowering referral thresholds from primary care and subsequent increased use of suspected cancer referral pathways.19 Recommendations supporting higher 2WW referral rates need to be tempered by an understanding of the healthcare system. Also, the health economic implications need to be further explored,34 especially given finite staff and resources,64 and the risks of overdiagnosis.64,65 With referrals in England (and other countries) increasing year on year, additional risk assessment and triage testing in primary care before referral for certain cancers, such as colorectal,60,63 may be indicated.

Acknowledgments

This study uses data provided by patients and collected by the NHS as part of its care and support. Data for this study are based on patient-level information collected by the NHS, as part of the care and support of cancer patients. The data are collated, maintained, and quality assured by the NCRAS, which is part of PHE. The authors would like to thank their patient and public involvement steering group, which provided input to this programme of research (NIHR-funded DRF).

Notes

Funding

Thomas Round is funded by a National Institute for Health Research (NIHR) Doctoral Research Fellowship (DRF) (ref: DRF-2016-09-054) for this research project, and was previously supported by a Royal Marsden Partners (RMP) Research Fellowship. The views expressed are those of the authors and not necessarily those of the NIHR, NHS, RMP, Public Health England (PHE), or the Department of Health and Social Care.

Ethical approval

Ethics committee approval is not required for research based on routine data. Approval according to section 251 of the NHS Act 2006 applies to cancer registration and cancer intelligence in PHE.

Provenance

Freely submitted; externally peer reviewed.

Competing interests

Henrik Møller has an honorary contract with National Cancer Registration and Analysis Service (NCRAS) PHE, and Carolynn Gildea is employed by NCRAS PHE. There are no other relationships or activities that could appear to have influenced the submitted work.

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  • Received October 30, 2019.
  • Revision requested November 7, 2019.
  • Accepted December 16, 2019.

REFERENCES

  1. 1.↵
    1. Department of Health
    Cancer reform strategy2007https://www.nhs.uk/NHSEngland/NSF/Documents/Cancer%20Reform%20Strategy.pdf (accessed 2 Apr 2020).
  2. 2.↵
    1. Abdel-Rahman M,
    2. Stockdon D,
    3. Rachet B,
    4. et al.
    What if cancer survival in Britain were the same as in Europe: how many deaths are avoidable?Br J Cancer2009101S2S115S124
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Tørring ML,
    2. Frydenberg M,
    3. Hamilton W,
    4. et al.
    Diagnostic interval and mortality in colorectal cancer: U-shaped association demonstrated for three different datasetsJ Clin Epidemiol2012656669678
    OpenUrlCrossRefPubMed
  4. 4.↵
    1. Tørring ML,
    2. Frydenberg M,
    3. Hansen RP,
    4. et al.
    Evidence of increasing mortality with longer diagnostic intervals for five common cancers: a cohort study in primary careEur J Cancer201349921872198
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Royal College of General Practitioners
    National audit of cancer diagnosis in primary care2018https://www.rcgp.org.uk/policy/rcgp-policy-areas/national-audit-of-cancer-diagnosis-in-primary-care.aspx (accessed 2 Apr 2020).
  6. 6.↵
    1. Hamilton W
    Five misconceptions in cancer diagnosisBr J Gen Pract2009https://doi.org/10.3399/bjgp09X420860.
  7. 7.↵
    1. Hamilton W,
    2. Sharp D
    Diagnosis of colorectal cancer in primary care: the evidence base for guidelinesFam Pract200421199106
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Lyratzopoulos G,
    2. Wardle J,
    3. Rubin G
    Rethinking diagnostic delay in cancer: how difficult is the diagnosis?BMJ2014349g7400
    OpenUrlFREE Full Text
  9. 9.↵
    1. Hansen RP,
    2. Olesen F,
    3. Sørensen HT,
    4. et al.
    Socioeconomic patient characteristics predict delay in cancer diagnosis: a Danish cohort studyBMC Health Serv Res20088149
    OpenUrlCrossRefPubMed
  10. 10.
    1. Scott S,
    2. Walter F,
    3. Webster A,
    4. et al.
    The model of pathways to treatment: conceptualization and integration with existing theoryBr J Health Psychol20131814565
    OpenUrlCrossRefPubMed
  11. 11.
    1. Walter F,
    2. Webster A,
    3. Scott S,
    4. et al.
    The Andersen Model of Total Patient Delay: a systematic review of its application in cancer diagnosisJ Health Serv Res Policy2012172110118
    OpenUrlCrossRefPubMed
  12. 12.
    1. Round T,
    2. Steed L,
    3. Shankleman J,
    4. et al.
    Primary care delays in diagnosing cancer: what is causing them and what can we do about them?J R Soc Med201310611437440
    OpenUrlCrossRefPubMed
  13. 13.↵
    1. Vested P,
    2. Olesen F
    Are the serious problems in cancer survival partly rooted in gatekeeper principles? An ecologic studyBr J Gen Pract2011https://doi.org/10.3399/bjgp11X588484.
  14. 14.↵
    1. Emery JD,
    2. Shaw K,
    3. Williams B,
    4. et al.
    The role of primary care in early detection and follow-up of cancerNat Rev Clin Oncol20141113848
    OpenUrlCrossRefPubMed
  15. 15.↵
    1. Department of Health
    HSC, 2000/013: referral guidelines for suspected cancer2000http://webarchive.nationalarchives.gov.uk/+/www.dh.gov.uk/en/Publicationsandstatistics/Lettersandcirculars/Healthservicecirculars/DH_4004320 (accessed 2 Apr 2020).
  16. 16.↵
    1. Neal R,
    2. Din N,
    3. Hamilton W,
    4. et al.
    Comparison of cancer diagnostic intervals before and after implementation of NICE guidelines: analysis of data from the UK General Practice Research DatabaseBr J Cancer20131103584592
    OpenUrlPubMed
  17. 17.↵
    1. Olesen F,
    2. Hansen RP,
    3. Vedsted P
    Delay in diagnosis: the experience in DenmarkBr J Cancer2009101Suppl 2S5S8
    OpenUrlCrossRefPubMed
  18. 18.↵
    1. Tørring ML,
    2. Murchie P,
    3. Hamilton W,
    4. et al.
    Evidence of advanced stage colorectal cancer with longer diagnostic intervals: a pooled analysis of seven primary care cohorts comprising 11 720 patients in five countriesBr J Cancer20171176888
    OpenUrl
  19. 19.↵
    1. National Institute for Health and Care Excellence
    Suspected cancer: recognition and referral NG122015https://www.nice.org.uk/guidance/ng12/resources/suspected-cancer-recognition-and-referral-pdf-1837268071621 (accessed 2 Apr 2020).
  20. 20.↵
    1. Herbert A,
    2. Abel GA,
    3. Winters S,
    4. et al.
    Cancer diagnoses after emergency GP referral or A&E attendance in England: determinants and time trends in Routes to Diagnosis data, 2006–2015Br J Gen Pract2019https://doi.org/10.3399/bjgp19X705473.
  21. 21.↵
    1. Baughan P,
    2. Keatings J,
    3. O’Neill B
    Urgent suspected cancer referrals from general practice: audit of compliance with guidelines and referral outcomesBr J Gen Pract2011https://doi.org/10.3399/bjgp11X606591.
  22. 22.
    1. Lewis JD,
    2. Brown A,
    3. Localio AR,
    4. Schwartz JS
    Initial evaluation of rectal bleeding in young persons: a cost-effectiveness analysisAnn Intern Med2002136299110
    OpenUrlPubMed
  23. 23.↵
    1. Meechan D,
    2. Gildea C,
    3. Hollingworth L,
    4. et al.
    Variation in use of the 2-week referral pathway for suspected cancer: a cross-sectional analysisBr J Gen Pract2012https://doi.org/10.3399/bjgp12X654551.
  24. 24.↵
    1. Department of Health, NHS England, Public Health England
    Progress in improving cancer services and outcomes in England2015https://www.nao.org.uk/wp-content/uploads/2015/01/Progress-improving-cancer-services-and-outcomes-in-England.pdf (accessed 2 Apr 2020).
  25. 25.↵
    1. Zhou Y,
    2. Mendonca S,
    3. Abel G,
    4. et al.
    Variation in ‘fast-track’ referrals for suspected cancer by patient characteristic and cancer diagnosis: evidence from 670 000 patients with cancers of 35 different sitesBr J Cancer2018118124
    OpenUrl
  26. 26.↵
    1. Public Health England
    Cancer serviceshttps://fingertips.phe.org.uk/profile/cancerservices (accessed 2 Apr 2020).
  27. 27.↵
    1. Møller H,
    2. Gildea C,
    3. Meechan D,
    4. et al.
    Use of the English urgent referral pathway for suspected cancer and mortality in patients with cancer: cohort studyBMJ2015351h5102
    OpenUrlAbstract/FREE Full Text
  28. 28.↵
    1. Abel G,
    2. Saunders CL,
    3. Mendonca SC,
    4. et al.
    Variation and statistical reliability of publicly reported primary care diagnostic activity indicators for cancer: a cross-sectional ecological study of routine dataBMJ Qual Saf20182712130
    OpenUrlAbstract/FREE Full Text
  29. 29.↵
    1. Henson KE,
    2. Elliss-Brookes L,
    3. Coupland VH,
    4. et al.
    Data resource profile: National Cancer Registration Dataset in EnglandInt J Epidemiol2019https://doi.org/10.1093/ije/dyz076.
  30. 30.↵
  31. 31.↵
    1. Møller H,
    2. Coupland VH,
    3. Tataru D,
    4. et al.
    Geographical variations in the use of cancer treatments are associated with survival of lung cancer patientsThorax2018736530537
    OpenUrlAbstract/FREE Full Text
  32. 32.↵
    1. Gutierrez RG
    Parametric frailty and shared frailty survival modelsStata Journal2002212244
    OpenUrl
  33. 33.↵
    1. Hougaard P
    Frailty models for survival dataLifetime Data Anal199513255273
    OpenUrlCrossRefPubMed
  34. 34.↵
    1. Hamilton W,
    2. Walter FM,
    3. Rubin G,
    4. Neal RD
    Improving early diagnosis of symptomatic cancerNat Rev Clin Oncol20161312740749
    OpenUrlCrossRef
  35. 35.↵
    1. Hamilton W
    Diagnosing symptomatic cancer in the NHSBMJ2015351h311
    OpenUrl
  36. 36.↵
    1. Tørring ML,
    2. Frydenberg M,
    3. Hansen RP,
    4. et al.
    Time to diagnosis and mortality in colorectal cancer: a cohort study in primary careBr J Cancer20111046934
    OpenUrlCrossRefPubMed
  37. 37.↵
    1. Di Girolamo C,
    2. Walters S,
    3. Gildea C,
    4. et al.
    Can we assess Cancer Waiting Time targets with cancer survival? A population-based study of individually linked data from the National Cancer Waiting Times monitoring dataset in England, 2009–2013PloS One2018138e0201288
    OpenUrl
  38. 38.↵
    1. Nørgaard M,
    2. Ehrenstein V,
    3. Vandenbroucke JP
    Confounding in observational studies based on large health care databases: problems and potential solutions — a primer for the clinicianClin Epidemiol20179185
    OpenUrlCrossRefPubMed
  39. 39.↵
    1. Elliss-Brookes L,
    2. McPhail S,
    3. Ives A,
    4. et al.
    Routes to diagnosis for cancer — determining the patient journey using multiple routine data setsBr J Cancer2012107812201226
    OpenUrlCrossRefPubMed
  40. 40.↵
    1. Zahl P,
    2. Jørgensen KJ,
    3. Gøtzsche P
    Overestimated lead times in cancer screening has led to substantial underestimation of overdiagnosisBr J Cancer201310972014
    OpenUrlCrossRefPubMed
  41. 41.↵
    1. Duffy SW,
    2. Nagtegaal ID,
    3. Wallis M,
    4. et al.
    Correcting for lead time and length bias in estimating the effect of screen detection on cancer survivalAm J Epidemiol2008168198104
    OpenUrlCrossRefPubMed
  42. 42.↵
    1. Puliti D,
    2. Duffy S,
    3. Miccinesi G,
    4. et al.
    Methodology and estimate of overdiagnosis in breast cancer service screening: a review of the European studiesJ Med Screen201219S14254
    OpenUrlCrossRefPubMed
  43. 43.↵
    1. Duffy SW,
    2. Parmar D
    Overdiagnosis in breast cancer screening: the importance of length of observation period and lead timeBreast Cancer Res2013153R41
    OpenUrlCrossRefPubMed
  44. 44.↵
    1. Draisma G,
    2. Etzioni R,
    3. Tsodikov A,
    4. et al.
    Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and contextJ Natl Cancer Inst20091016374383
    OpenUrlCrossRefPubMed
  45. 45.↵
    1. Biswas M,
    2. Ades A,
    3. Hamilton W
    Symptom lead times in lung and colorectal cancers: what are the benefits of symptom-based approaches to early diagnosis?Br J Cancer20151122271
    OpenUrlCrossRefPubMed
  46. 46.↵
    1. Ades AE,
    2. Biswas M,
    3. Welton NJ,
    4. et al.
    Symptom lead time distribution in lung cancer: natural history and prospects for early diagnosisInt J Epidemiol201443618651873
    OpenUrlCrossRefPubMed
  47. 47.↵
    1. Mendonca SC,
    2. Abel GA,
    3. Gildea C,
    4. et al.
    Associations between general practice characteristics with use of urgent referrals for suspected cancer and endoscopies: a cross-sectional ecological studyFam Pract2018365573580
    OpenUrl
  48. 48.↵
    1. Murchie P,
    2. Chowdhury A,
    3. Smith S,
    4. et al.
    General practice performance in referral for suspected cancer: influence of number of cases and case-mix on publicly reported dataBr J Cancer20151121117911798
    OpenUrlCrossRefPubMed
  49. 49.↵
    1. Bosco JL,
    2. Silliman RA,
    3. Thwin SS,
    4. et al.
    A most stubborn bias: no adjustment method fully resolves confounding by indication in observational studiesJ Clin Epidemiol20106316474
    OpenUrlCrossRefPubMed
  50. 50.↵
    1. Murchie P,
    2. Chowdhury A,
    3. Smith S,
    4. et al.
    General practice performance in referral for suspected cancer: influence of number of cases and case-mix on publicly reported dataBr J Cancer2015112111791
    OpenUrlCrossRefPubMed
  51. 51.↵
    1. Burton CD,
    2. McLernon DJ,
    3. Lee AJ,
    4. et al.
    Distinguishing variation in referral accuracy from referral threshold: analysis of a national dataset of referrals for suspected cancerBMJ Open201778e016439
    OpenUrlAbstract/FREE Full Text
  52. 52.↵
    1. Shawihdi M,
    2. Thompson E,
    3. Kapoor N,
    4. et al.
    Variation in gastroscopy rate in English general practice and outcome for oesophagogastric cancer: retrospective analysis of Hospital Episode StatisticsGut2014632250261
    OpenUrlAbstract/FREE Full Text
  53. 53.↵
    1. Maclean R,
    2. Jeffreys M,
    3. Ives A,
    4. et al.
    Primary care characteristics and stage of cancer at diagnosis using data from the National Cancer Registration Service, Quality Outcomes Framework and general practice informationBMC Cancer20151511
    OpenUrlCrossRefPubMed
  54. 54.↵
    1. Lyratzopoulos G,
    2. Mendonca SC,
    3. Gildea C,
    4. et al.
    Associations between diagnostic activity and measures of patient experience in primary care: a cross-sectional ecological study of English general practicesBr J Gen Pract2018https://doi.org/10.3399/bjgp17X694097.
  55. 55.↵
    1. Kostopoulou O,
    2. Nurek M,
    3. Cantarella S,
    4. et al.
    Referral decision making of general practitioners: a signal detection studyMed Decis Making20193912131
    OpenUrl
  56. 56.↵
    1. Burton C,
    2. O’Neill L,
    3. Oliver P,
    4. Murchie P
    Contribution of primary care organisation and specialist care provider to variation in GP referrals for suspected cancer: ecological analysis of national dataBMJ Qual Saf2019doi:10.1136/bmjqs-2019-009469.
    OpenUrlCrossRef
  57. 57.↵
    1. Morris EJ,
    2. Sandin F,
    3. Lambert PC,
    4. et al.
    A population-based comparison of the survival of patients with colorectal cancer in England, Norway and Sweden between 1996 and 2004Gut201160810871093
    OpenUrlAbstract/FREE Full Text
  58. 58.↵
    1. Coleman M,
    2. Forman D,
    3. Bryant H,
    4. et al.
    Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995–2007 (the International Cancer Benchmarking Partnership): an analysis of population-based cancer registry dataLancet20113779760127138
    OpenUrlCrossRefPubMed
  59. 59.↵
    1. Lyratzopoulos G,
    2. Neal RD,
    3. Barbiere JM,
    4. et al.
    Variation in number of general practitioner consultations before hospital referral for cancer: findings from the 2010 National Cancer Patient Experience Survey in EnglandLancet Oncol2012134353365
    OpenUrlCrossRefPubMed
  60. 60.↵
    1. Rubin G,
    2. Berendsen A,
    3. Crawford SM,
    4. et al.
    The expanding role of primary care in cancer controlLancet Oncol2015161212311272
    OpenUrlCrossRefPubMed
  61. 61.↵
    1. Kostopoulou O,
    2. Rosen A,
    3. Round T,
    4. et al.
    Early diagnostic suggestions improve accuracy of GPs: a randomised controlled trial using computer-simulated patientsBr J Gen Pract2015https://doi.org/10.3399/bjgp15X683161.
  62. 62.↵
    1. Kostopoulou O,
    2. Sirota M,
    3. Round T,
    4. et al.
    The role of physicians’ first impressions in the diagnosis of possible cancers without alarm symptomsMed Decis Making2017371916
    OpenUrlCrossRefPubMed
  63. 63.↵
    1. Rubin G,
    2. Walter F,
    3. Emery J,
    4. et al.
    Reimagining the diagnostic pathway for gastrointestinal cancerNat Rev Gastroenterol Hepatol2018153181
    OpenUrl
  64. 64.↵
    1. Round T
    Primary care and cancer: facing the challenge of early diagnosis and survivorshipEur J Cancer Care2017263e12703
    OpenUrl
  65. 65.↵
    1. Nicholson B
    Detecting cancer in primary care: where does early diagnosis stop and overdiagnosis begin?Eur J Cancer Care2017263e12692
    OpenUrl
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British Journal of General Practice: 70 (695)
British Journal of General Practice
Vol. 70, Issue 695
June 2020
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Association between use of urgent suspected cancer referral and mortality and stage at diagnosis: a 5-year national cohort study
Thomas Round, Carolynn Gildea, Mark Ashworth, Henrik Møller
British Journal of General Practice 2020; 70 (695): e389-e398. DOI: 10.3399/bjgp20X709433
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British Journal of General Practice