Future cancer risk after urgent suspected cancer referral in England when cancer is not found: a national cohort study

Background: 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 1–5 years of finding no cancer following an urgent suspected cancer referral. Methods: This national cohort study used urgent suspected cancer referral data for England from the Cancer Waiting Times dataset and linked it with cancer diagnosis data from the National Cancer Registration dataset. Data were extracted for the eight most commonly referred to urgent suspected cancer referral pathways (breast, gynaecological, head and neck, lower and upper gastrointestinal, lung, skin, and urological) for the period April 1, 2013, to March 31, 2014, with 5-year follow-up for individuals with no cancer diagnosis within 1 year of referral. The primary objective was to investigate the occurrence and type of subsequent cancer in years 1–5 following an urgent suspected cancer referral when no cancer was initially found, both overall and for each of the eight referral pathways. The numbers of subsequent cancers were compared with expected cancer incidence in years 1–5 following referral, using standardised incidence ratios (SIRs) based on matched age-gender distributions of expected cancer incidence in England for the same time period. The analysis was repeated, stratifying by referral group, and by calculating the absolute and expected rate of all cancers and of the same individual cancer as the initial referral. Findings: Among 1·18 million referrals without a cancer diagnosis in years 0–1, there were 63 112 subsequent cancers diagnosed 1–5 years post-referral, giving an absolute rate of 1338 (95% CI 1327–1348) cancers per 100 000 referrals per year (1038 [1027–1050] in females, 1888 [1867–1909] in males), compared with an expected rate of 1054 (1045–1064) cancers per 100 000 referrals per year (SIR 1·27 [95% CI 1·26–1·28]). The absolute rate of any subsequent cancer diagnosis 1–5 years after referral was lowest following suspected breast cancer referral (746 [728–763] cancers per 100 000 referrals per year) and highest following suspected urological (2110 [2070–2150]) or lung cancer (1835 [1767–1906]) referral. For diagnosis of the same cancer as the initial referral pathway, the highest absolute rates were for the urological and lung pathways (1011 [984–1039] and 638 [598–680] cancers per 100 000 referrals per year, respectively). The highest relative risks of subsequent diagnosis of the same cancer as the initial referral pathway were for the head and neck pathway (SIR 3·49 [95% CI 3·22–3·78]) and lung pathway (3·00 [2·82–3·20]). Interpretation: 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. Funding: Cancer Research UK.