Marie Louise Tørring

Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes? Systematic review

Background:It is unclear whether more timely cancer diagnosis brings favourable outcomes, with much of the previous evidence, in some cancers, being equivocal. We set out to determine whether there is an association between time to diagnosis, treatment and clinical outcomes, across all cancers for symptomatic presentations.Methods:Systematic review of the literature and narrative synthesis.Results:We included 177 articles reporting 209 studies. These studies varied in study design, the time intervals assessed and the outcomes reported. Study quality was variable, with a small number of higher-quality studies. Heterogeneity precluded definitive findings. The cancers with more reports of an association between shorter times to diagnosis and more favourable outcomes were breast, colorectal, head and neck, testicular and melanoma.Conclusions:This is the first review encompassing many cancer types, and we have demonstrated those cancers in which more evidence of an association between shorter times to diagnosis and more favourable outcomes exists, and where it is lacking. We believe that it is reasonable to assume that efforts to expedite the diagnosis of symptomatic cancer are likely to have benefits for patients in terms of improved survival, earlier-stage diagnosis and improved quality of life, although these benefits vary between cancers.

Time to diagnosis and mortality in colorectal cancer: a cohort study in primary care

Background:The relationship between the diagnostic interval and mortality from colorectal cancer (CRC) is unclear. This association was examined by taking account of important confounding factors at the time of first presentation of symptoms in primary care.Methods:A total of 268 patients with CRC were included in a prospective, population-based study in a Danish county. The diagnostic interval was defined as the time from first presentation of symptoms until diagnosis. We analysed patients separately according to the general practitioners interpretation of symptoms. Logistic regression was used to estimate 3-year mortality odds ratios as a function of the diagnostic interval using restricted cubic splines and adjusting for tumour site, comorbidity, age, and sex.Results:In patients presenting with symptoms suggestive of cancer or any other serious illness, the risk of dying within 3 years decreased with diagnostic intervals up to 5 weeks and then increased (P=0.002). In patients presenting with vague symptoms, the association was reverse, although not statistically significant.Conclusion:Detecting cancer in primary care is two sided: aimed at expediting ill patients while preventing healthy people from going to hospital. This likely explains the counterintuitive findings; but it does not explain the increasing mortality with longer diagnostic intervals. Thus, this study provides evidence for the hypothesis that the length of the diagnostic interval affects mortality in CRC patients.

Evidence of increasing mortality with longer diagnostic intervals for five common cancers: a cohort study in primary care.

BACKGROUND Early diagnosis is considered a key factor in improving the outcomes in cancer therapy; it remains unclear, however, whether long pre-diagnostic patient pathways influence clinical outcomes negatively. The aim of this study was to assess the association between the length of the diagnostic interval and the five-year mortality for the five most common cancers in Denmark while addressing known biases. METHODS A total of 1128 patients with colorectal, lung, melanoma skin, breast or prostate cancer were included in a prospective, population-based study in a Danish county. The diagnostic interval was defined as the time from the first presentation of symptoms in primary care till the date of diagnosis. Each type of cancer was analysed separately and combined, and all analyses were stratified according to the general practitioners (GPs) interpretation of the presenting symptoms. We used conditional logistic regression to estimate five-year mortality odds ratios as a function of the diagnostic interval using restricted cubic splines and adjusting for comorbidity, age, sex and type of cancer. RESULTS We found increasing mortality with longer diagnostic intervals among the approximately 40% of the patients who presented in primary care with symptoms suggestive of cancer or any other serious illness. In the same group, very short diagnostic intervals were also associated with increased mortality. Patients presenting with vague symptoms not directly related to cancer or any other serious illness had longer diagnostic intervals and the same survival probability as those who presented with cancer suspicious/serious symptoms. For the former, we found no statistically significant association between the length of the diagnostic interval and mortality. CONCLUSION In full coherence with clinical logic, the healthcare system instigates prompt investigation of seriously ill patients. This likely explains the counter-intuitive findings of high mortality with short diagnostic intervals; but it does not explain the increasing mortality with longer diagnostic intervals. Thus, the study provides further evidence for the hypothesis that the length of the diagnostic interval affects mortality negatively.

Diagnostic interval and mortality in colorectal cancer: U-shaped association demonstrated for three different datasets.

OBJECTIVE To test the theory of a U-shaped association between time from the first presentation of symptoms in primary care to the diagnosis (the diagnostic interval) and mortality after diagnosis of colorectal cancer (CRC). STUDY DESIGN AND SETTING Three population-based studies in Denmark and the United Kingdom using data from general practitioners questionnaires, interviewer-administered patient questionnaires, and primary care records, respectively. RESULTS Despite variations in the potential selection and information bias when using different methods of identifying the date of first presentation, the association between the length of the diagnostic interval and 5-year mortality rate after the diagnosis of CRC was the same for all three types of data: displaying a U-shaped association with decreasing and subsequently increasing mortality with longer diagnostic intervals. CONCLUSION Unknown confounding and in particular confounding by indication is likely to explain the counterintuitive findings of higher mortality among patients with very short diagnostic intervals, but cannot explain the increasing mortality with longer diagnostic intervals. The results support the theory that longer diagnostic intervals cause higher mortality in patients with CRC.

Cancer suspicion in general practice, urgent referral and time to diagnosis: a population-based GP survey and registry study

BackgroundMany countries have implemented standardised cancer patient pathways (CPPs) to ensure fast diagnosis of patients suspected of having cancer. Yet, studies are sparse on the impact of such CPPs, and few have distinguished between referral routes. For incident cancer patients, we aimed to determine how often GPs suspected cancer at the time of first presentation of symptoms in general practice and to describe the routes of referral for further investigation. In addition, we aimed to analyse if the GP’s suspicion of cancer could predict the choice of referral to a CPP. Finally, we aimed to analyse associations between not only cancer suspicion and time to cancer diagnosis, but also between choice of referral route and time to cancer diagnosis.MethodsWe conducted a population-based, cross-sectional study of incident cancer patients in Denmark who had attended general practice prior to their diagnosis of cancer. Data were collected from GP questionnaires and national registers. We estimated the patients’ chance of being referred to a CPP (prevalence ratio (PR)) using Poisson regression. Associations between the GP’s symptom interpretation, use of CPP and time to diagnosis were estimated using quantile regression.Results5,581 questionnaires were returned (response rate: 73.8%). A GP was involved in diagnosing the cancer in 4,101 (73.5%) cases (3,823 cases analysed). In 48.2% of these cases, the GP interpreted the patient’s symptoms as ‘alarm’ symptoms suggestive of cancer. The GP used CPPs in 1,426 (37.3%) cases. Patients, who had symptoms interpreted as ‘vague’ had a lower chance of being referred to a CPP than when interpreted as ‘alarm’ symptoms (PR = 0.53 (95%CI: 0.48;0.60)). Patients with ‘vague’ symptoms had a 34 (95% CI: 28;41) days longer median time to diagnosis than patients with ‘alarm’ symptoms.ConclusionsGPs suspect cancer more often than they initiate a CPP, and patients were less likely to be referred to a CPP when their symptoms were not interpreted as alarm symptoms of cancer. The GP’s choice of referral route was a strong predictor of the duration of the diagnostic interval, but the GP’s symptom interpretation was approximately twice as strong an indicator of a longer diagnostic interval.

Diagnostic intervals before and after implementation of cancer patient pathways – a GP survey and registry based comparison of three cohorts of cancer patients

BackgroundFrom 2008, Danish general practitioners could refer patients suspected of having cancer to standardised cancer patient pathways (CPPs).We aimed to compare the length of the diagnostic interval in 2010 with the length of the diagnostic interval before (2004/05) and during (2007/08) the implementation of CPPs in Denmark for all incident cancer patients who attended general practice prior to the cancer diagnosis.MethodsGeneral practitioner questionnaires and register data on 12,558 patients were used to compare adjusted diagnostic interval across time by quantile regression.ResultsThe median diagnostic interval was 14 (95% CI: 11;16) days shorter during and 17 (95% CI: 15;19) days shorter after the implementation of CPPs than before. The diagnostic interval was 15 (95% CI: 12;17) days shorter for patients referred to a CPP in 2010 than during the implementation, whereas patients not referred to a CPP in 2010 had a 4 (95% CI: 1;7) days longer median diagnostic interval; the pattern was similar, but larger at the 75th and 90th percentiles.ConclusionThe diagnostic interval was significantly lower after CPP implementation. Yet, patients not referred to a CPP in 2010 tended to have a longer diagnostic interval compared to during the implementation. CPPs may thus only seem to expedite the diagnostic process for some cancer patients.

Impact of COPD on Outcome Among Patients With Complicated Peptic Ulcer

BACKGROUND COPD is associated with an increased risk of peptic ulcer disease, but limited data exist on whether COPD influences short-term mortality among patients with bleeding and a perforated peptic ulcer. We examined the association between COPD and 30-day mortality following bleeding and perforation of a peptic ulcer. METHODS We identified all patients who had been hospitalized with a first-time diagnosis of peptic ulcer perforation (n = 2,033) or bleeding (n = 7,486) in northern Denmark between 1991 and 2004. Information on COPD, comorbidities, and filled prescriptions was obtained from medical databases. Mortality was ascertained using the Danish Civil Registration System. We computed the cumulative 30-day mortality rates for ulcer patients with COPD and for other ulcer patients, and used regression analysis to obtain the 30-day mortality rate ratios (MRRs), controlling for potential confounding factors. RESULTS Among patients who were hospitalized with perforated peptic ulcers, 218 (10.7%) had previously been hospitalized with COPD. The 30-day mortality rate was 44.0% among perforated ulcer patients with COPD vs 25.5% among other ulcer patients (adjusted MRR, 1.48; 95% confidence interval [CI], 1.18 to 1.85). Among patients hospitalized with a bleeding peptic ulcer, 759 (10.1%) had previously been hospitalized with COPD. The 30-day mortality rate was 16.5% among bleeding peptic ulcer patients with COPD vs 10.8% among other ulcer patients (adjusted MRR, 1.38; 95% CI, 1.14 to 1.68). The use of oral glucocorticoids among COPD patients was associated with higher MRRs for both perforated and bleeding peptic ulcers. CONCLUSIONS COPD substantially increased 30-day mortality among patients with bleeding and perforated peptic ulcers.

Existing data sources for clinical epidemiology: Danish Cancer in Primary Care cohort

Background In this paper, we describe the settings, content, and possibilities of the Danish Cancer in Primary Care (CaP) cohort as well as some of the key findings so far. Further, we describe the future potential of the cohort as an international resource for epidemiological and health services research studies. Methods The CaP cohort comprises information from three Danish subcohorts set up in 2004–2005, 2007–2008, and 2010 on newly diagnosed cancer patients aged 18 years or older. General practitioner (GP)-reported and patient-reported data from six questionnaires generated information on causes and consequences of delayed diagnosis of cancer, and these data were supplemented with complete information on, eg, death, migration, health care utilization, medication use, and socioeconomic data from Denmark’s comprehensive health and administrative registers. The cohort is followed up in terms of emigration, death, hospitalization, medication, and socioeconomics, and data are updated regularly. Results In total, we identified 22,169 verified incident cancer cases. Completed GP questionnaires were returned for 17,566 (79%) of the verified cases, and patient questionnaires were completed by 8,937 (40%) respondents. Patients with participating GPs did not differ from patients with nonparticipating GPs in regard to one-year survival, comorbidity, or educational level. However, compared with nonparticipating GPs, patients listed with participating GPs were more likely to be women, younger, to have a higher disposable income, to have more regional or distant spread of tumors, were also more likely to have breast cancer, and were less likely to have prostate cancer. Responding patients were more likely to be women, aged 45–74 years, and diagnosed with breast cancer or malignant melanoma, and have higher one-year survival rates, more localized tumors, higher educational background, and higher disposable income. Conclusion The cohort is an international resource for epidemiological and health service research, and data are accessible for well defined and approved collaborative studies.

Evidence of advanced stage colorectal cancer with longer diagnostic intervals: a pooled analysis of seven primary care cohorts comprising 11 720 patients in five countries

Background:The benefits from expedited diagnosis of symptomatic cancer are uncertain. We aimed to analyse the relationship between stage of colorectal cancer (CRC) and the primary and specialist care components of the diagnostic interval.Methods:We identified seven independent data sets from population-based studies in Scotland, England, Canada, Denmark and Spain during 1997–2010 with a total of 11 720 newly diagnosed CRC patients, who had initially presented with symptoms to a primary care physician. Data were extracted from patient records, registries, audits and questionnaires, respectively. Data sets were required to hold information on dates in the diagnostic interval (defined as the time from the first presentation of symptoms in primary care until the date of diagnosis), symptoms at first presentation in primary care, route of referral, gender, age and histologically confirmed stage. We carried out reanalysis of all individual data sets and, using the same method, analysed a pooled individual patient data set.Results:The association between intervals and stage was similar in the individual and combined data set. There was a statistically significant convex (∩-shaped) association between primary care interval and diagnosis of advanced (i.e., distant or regional) rather than localised CRC (P=0.004), with odds beginning to increase from the first day on and peaking at 90 days. For specialist care, we saw an opposite and statistically significant concave (∪-shaped) association, with a trough at 60 days, between the interval and diagnosis of advanced CRC (P<0.001).Conclusions:This study provides evidence that longer diagnostic intervals are associated with more advanced CRC. Furthermore, the study cannot define a specific ‘safe’ waiting time as the length of the primary care interval appears to have negative impact from day one.

Global Health Care–seeking Discourses Facing Local Clinical Realities: Exploring the Case of Cancer

Using cancer as an example and drawing on Pierre Bourdieus concepts of field and on prolonged fieldwork in Danish general medical practice settings, we examine how discourses about what counts as legitimate help-seeking practices are negotiated in local clinical encounters. Overall, we identify competition between two discourses on help-seeking practices. This competition is present most when people seek help with unspecific, vague, or diffuse illness complaints, voicing uncertainty as to what counts as signs of illness, characteristic of proactive discourses emanating from global, scientific biomedicine. Such indistinct help-seeking conflicts with the dominant discourse in the local clinical setting and is characterized by an overt focus on identification of the chief complaint. The analysis illustrates how competing discourses may result in conflicting expectations to the clinical encounter and prove counterproductive to ensuring early diagnosis of cancer.