Subsequent Cancer Diagnosis After No Diagnosis With Urgent Suspected Cancer Referral

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In a national cohort study in England reported in The Lancet Oncology, Scott et al found a high rate of subsequent cancer diagnosis in persons with an urgent suspected cancer referral that did not result in cancer diagnosis.

As noted by the investigators, “Following referral for investigation of urgent suspected cancer within the English National Health Service referral system, 7% of referred individuals are diagnosed with cancer. This study aimed to investigate the risk of cancer occurrence within 1 to 5 years of finding no cancer following an urgent suspected cancer referral.”

Study Details

The study used data for the eight most common urgent suspected cancer referral pathways (breast, gynecologic, head and neck, lower and upper gastrointestinal, lung, skin, and urologic) from April 2013 to March 2014, with 5-year follow-up for individuals with no cancer diagnosis within 1 year of referral. The objective was to determine incidence of subsequent cancer in years 1 to 5 after initial referral that led to no cancer diagnosis. Rates of subsequent cancers were compared with expected cancer incidence in years 1 to 5 after referral using standardized incidence ratios based on matched age and gender distributions of expected cancer incidence in England for the same time period.

Key Findings

Of 1.18 million referrals without cancer diagnosis in years 0 to 1, 63,112 subsequent cancers were diagnosed 1 to 5 years after referral.  The absolute rate of 1,338 cancers per 100,000 referrals per year was higher than the expected rate of 1,054 (standardized incidence ratio [SIR] = 1.27, 95% confidence interval [CI] = 1.26–1.28). Rates per 100,000 referrals per year were 1,038 among females and 1,888 among males.

The absolute rate per 100,000 referrals per year for any subsequent cancer diagnosis was lowest for breast cancer referral (746) and gynecologic referral (996), and highest for urologic referral (2,110) and lung referral (1,835). The highest relative risks vs expected rates were for urologic cancer (SIR = 1.49, 95% CI = 1.47–1.52) and lung cancer (SIR = 1.35, 95% CI = 1.30–1.40).

For diagnosis of the same cancer as the initial referral pathway, the lowest absolute rates per 100,000 referrals per year were for skin cancer (113) and head and neck cancer (135), and the highest rates were for urologic cancer (1,011) and lung cancer (638). The highest relative risks vs expected rates were for head and neck cancer (SIR = 3.49, 95% CI = 3.22–3.78) and lung cancer (SIR = 3.00, 95% CI = 2.82–3.20).

The investigators concluded, “Cancer risk was higher than expected in the 5 years following an urgent suspected cancer referral. The potential for targeted interventions, such as proactive monitoring, safety netting, and cancer awareness or risk reduction initiatives, should be investigated.”

Suzanne E. Scott, PhD, of the Wolfson Institute of Population Health, Queen Mary University of London, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Cancer Research UK. For full disclosures of the study authors, visit

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