The elusive diagnosis of cancer: testing times

Nicholson, Brian D; Perera, Rafael; Thompson, Matthew

doi:10.3399/bjgp18x699461

Cited by 7 publications

(6 citation statements)

References 18 publications

(16 reference statements)

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“…The evidence base informed the National Institute for Health and Care Excellence guidance on suspected cancer, which recommended further investigations for patients with a positive predictive value (PPV) for cancer exceeding 3% 10. Studies have investigated unexpected WL together with other symptoms and signs occurring over a one to two year period preceding the cancer diagnosis without acknowledging that the predictive value of individual symptoms will vary during different periods 51112. In this context, predictive values could have been reported for pairs of clinical features that occurred months or years apart, potentially with different causes unrelated to the eventual cancer diagnosis.…”

Section: Introductionmentioning

confidence: 99%

“…10 Studies have investigated unexpected WL together with other symptoms and signs occurring over a one to two year period preceding the cancer diagnosis without acknowledging that the predictive value of individual symptoms will vary during different periods. 5 11 12 In this context, predictive values could have been reported for pairs of clinical features that occurred months or years apart, potentially with different causes unrelated to the eventual cancer diagnosis.…”

Section: Introductionmentioning

confidence: 99%

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Prioritising primary care patients with unexpected weight loss for cancer investigation: diagnostic accuracy study

Nicholson

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et al. 2020

BMJ

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Objective To quantify the predictive value of unexpected weight loss (WL) for cancer according to patient’s age, sex, smoking status, and concurrent clinical features (symptoms, signs, and abnormal blood test results). Design Diagnostic accuracy study. Setting Clinical Practice Research Datalink electronic health records data linked to the National Cancer Registration and Analysis Service in primary care, England. Participants 63 973 adults (≥18 years) with a code for unexpected WL from 1 January 2000 to 31 December 2012. Main outcome measures Cancer diagnosis in the six months after the earliest weight loss code (index date). Codes for additional clinical features were identified in the three months before to one month after the index date. Diagnostic accuracy measures included positive and negative likelihood ratios, positive predictive values, and diagnostic odds ratios. Results Of 63 973 adults with unexpected WL, 37 215 (58.2%) were women, 33 167 (51.8%) were aged 60 years or older, and 16 793 (26.3%) were ever smokers. 908 (1.4%) had a diagnosis of cancer within six months of the index date, of whom 882 (97.1%) were aged 50 years or older. The positive predictive value for cancer was above the 3% threshold recommended by the National Institute for Health and Care Excellence for urgent investigation in male ever smokers aged 50 years or older, but not in women at any age. 10 additional clinical features were associated with cancer in men with unexpected WL, and 11 in women. Positive likelihood ratios in men ranged from 1.86 (95% confidence interval 1.32 to 2.62) for non-cardiac chest pain to 6.10 (3.44 to 10.79) for abdominal mass, and in women from 1.62 (1.15 to 2.29) for back pain to 20.9 (10.7 to 40.9) for jaundice. Abnormal blood test results associated with cancer included low albumin levels (4.67, 4.14 to 5.27) and raised values for platelets (4.57, 3.88 to 5.38), calcium (4.28, 3.05 to 6.02), total white cell count (3.76, 3.30 to 4.28), and C reactive protein (3.59, 3.31 to 3.89). However, no normal blood test result in isolation ruled out cancer. Clinical features co-occurring with unexpected WL were associated with multiple cancer sites. Conclusion The risk of cancer in adults with unexpected WL presenting to primary care is 2% or less and does not merit investigation under current UK guidelines. However, in male ever smokers aged 50 years or older and in patients with concurrent clinical features, the risk of cancer warrants referral for invasive investigation. Clinical features typically associated with specific cancer sites are markers of several cancer types when they occur with unexpected WL.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prioritising primary care patients with unexpected weight loss for cancer investigation: diagnostic accuracy study

Nicholson

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Price

et al. 2020

BMJ

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“…Focus in Northern Europe has shifted to the role of multidisciplinary diagnostic centres (MDCs) to achieve this. 12,14,43,44 Emerging evidence from MDC pilot sites in the UK show that unexpected weight loss is the most common reason for referral. 14,44 Insights gained from the ongoing evaluation of MDCs may inform the optimal diagnostic process for patients referred with unexpected weight loss.…”

Section: Implications For Research and Practicementioning

confidence: 99%

The association between unexpected weight loss and cancer diagnosis in primary care: a matched cohort analysis of 65,000 presentations

et al. 2020

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Background We aimed to understand the time period of cancer diagnosis and the cancer types detected in primary care patients with unexpected weight loss (UWL) to inform cancer guidelines. Methods This retrospective matched cohort study used cancer registry linked electronic health records from the UK’s Clinical Practice Research Datalink from between 2000 and 2014. Univariable and multivariable time-to-event analyses examined the association between UWL, and all cancers combined, cancer site and stage. Results In all, 63,973 patients had UWL recorded, of whom 1375 (2.2%) were diagnosed with cancer within 2 years (days-to-diagnosis: mean 181; median 80). Men with UWL (HR 3.28 (2.88–3.73)) and women (1.87 (1.68–2.08)) were more likely than comparators to be diagnosed with cancer within 3 months. The association was greatest in men aged ≥50 years and women ≥70 years. The commonest cancers were pancreas, cancer of unknown primary, gastro-oesophageal, lymphoma, hepatobiliary, lung, bowel and renal-tract. The majority were late-stage, but there was some evidence of association with stage II and stage III cancers. In the 3–24 months after presenting with UWL, cancer diagnosis was less likely than in comparators. Conclusion UWL recorded in primary care is associated with a broad range of cancer sites of early and late-stage.

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“…There is little guidance on how clinicians should interpret these blood tests in combination or which are most relevant for use in clinical practice [ 1 , 6 ]. When baseline investigations are normal, a watchful waiting approach may be preferable to invasive testing [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Combining simple blood tests to identify primary care patients with unexpected weight loss for cancer investigation: Clinical risk score development, internal validation, and net benefit analysis

et al. 2021

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Background Unexpected weight loss (UWL) is a presenting feature of cancer in primary care. Existing research proposes simple combinations of clinical features (risk factors, symptoms, signs, and blood test data) that, when present, warrant cancer investigation. More complex combinations may modify cancer risk to sufficiently rule-out the need for investigation. We aimed to identify which clinical features can be used together to stratify patients with UWL based on their risk of cancer. Methods and findings We used data from 63,973 adults (age: mean 59 years, standard deviation 21 years; 42% male) to predict cancer in patients with UWL recorded in a large representative United Kingdom primary care electronic health record between January 1, 2000 and December 31, 2012. We derived 3 clinical prediction models using logistic regression and backwards stepwise covariate selection: Sm, symptoms-only model; STm, symptoms and tests model; Tm, tests-only model. Fifty imputations replaced missing data. Estimates of discrimination and calibration were derived using 10-fold internal cross-validation. Simple clinical risk scores are presented for models with the greatest clinical utility in decision curve analysis. The STm and Tm showed improved discrimination (area under the curve ≥ 0.91), calibration, and greater clinical utility than the Sm. The Tm was simplest including age-group, sex, albumin, alkaline phosphatase, liver enzymes, C-reactive protein, haemoglobin, platelets, and total white cell count. A Tm score of 5 balanced ruling-in (sensitivity 84.0%, positive likelihood ratio 5.36) and ruling-out (specificity 84.3%, negative likelihood ratio 0.19) further cancer investigation. A Tm score of 1 prioritised ruling-out (sensitivity 97.5%). At this threshold, 35 people presenting with UWL in primary care would be referred for investigation for each person with cancer referred, and 1,730 people would be spared referral for each person with cancer not referred. Study limitations include using a retrospective routinely collected dataset, a reliance on coding to identify UWL, and missing data for some predictors. Conclusions Our findings suggest that combinations of simple blood test abnormalities could be used to identify patients with UWL who warrant referral for investigation, while people with combinations of normal results could be exempted from referral.

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The elusive diagnosis of cancer: testing times

Cited by 7 publications

References 18 publications

Prioritising primary care patients with unexpected weight loss for cancer investigation: diagnostic accuracy study

Prioritising primary care patients with unexpected weight loss for cancer investigation: diagnostic accuracy study

The association between unexpected weight loss and cancer diagnosis in primary care: a matched cohort analysis of 65,000 presentations

Combining simple blood tests to identify primary care patients with unexpected weight loss for cancer investigation: Clinical risk score development, internal validation, and net benefit analysis

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