Identifying early symptoms associated with a diagnosis of childhood, adolescent and young adult cancers: a population-based nested case-control study.

Background: Childhood, teenage and young adult (CTYA, 0-24 years) cancers are rare and diverse, making timely diagnosis challenging. We aim to explore symptoms and symptom combinations associated with a subsequent cancer diagnosis and to establish their timeframe.

Methods: Using the QResearch Database, we carried out a matched nested case-control study. Associations between pre-specified symptoms encountered in primary care and a subsequent diagnosis of any cancer were explored using conditional logistic regression. Median diagnostic intervals were used to split symptoms into "late" and "early" timeframes to identify relevant early symptoms.

Results: 3186 cases and 50,576 controls were identified from a cohort of 3,424,771 CTYA. We identified 12 novel associations, of which hemiparesis [OR 90.9 (95%CI 24.7-335.1), PPV = 1.6%], testicular swelling [OR 186.7 (95%CI 86.1-404.8), PPV = 2.4%] and organomegaly [OR 221.6 (95%CI 28.3-1735.9), PPV = 5.4%] had significant positive predictive values (PPV). Limb pain, a known marker of serious illness in children, was a recurrent early symptom across cancer subtypes. Similar clinical presentations were observed across childhood and TYA cancers.

Discussion: Using the largest cohort to date, we provide novel information on the time-varying predictive utility of symptoms in the diagnosis of CTYA cancers. Our findings will help to raise clinical and public awareness of symptoms, stratify those at higher-risk and ultimately aid earlier diagnosis.