Diagnostic timeliness of cancer in adolescents and young adults

A prompt diagnosis of cancer is thought to be associated with an increased prospect of cure. Good evidence exists for some cancers that are prevalent in adults, such as carcinoma of the breast, and has led to strenuous efforts to improve diagnostic timeliness.1Lyratzopoulos G Markers and measures of timeliness of cancer diagnosis after symptom onset: a conceptual framework and its implications.Cancer Epidemiol. 2014; 38: 211-213Crossref PubMed Scopus (7) Google Scholar Otherwise known as lag time, this is the interval from the onset of symptoms, usually an imprecise starting point, to the date of definitive diagnosis. In children, the relationship between diagnostic timeliness and survival is much less clear and is affected in large measure by the biology of the non-carcinomas, mainly embryonal tumours, that predominate in childhood. This relationship has been little studied in the intervening age group—adolescents and young adults. Because the incidence of cancer in young people is much lower than that in older adults, general practitioners (GPs; ie, family physicians) have much less exposure to malignant disease in patients younger than 40 years. The BRIGHTLIGHT programme of research holds considerable promise of important findings in the care of young people with cancer, especially with respect to the return on investment in specialist services. In The Lancet Child & Adolescent Health, Annie Herbert and colleagues2Herbert A Lyratzopoulos G Whelan J et al.Diagnostic timeliness in adolescents and young adults with cancer: a multicentre, cross-sectional analysis of the BRIGHTLIGHT cohort.Lancet Child Adolesc Health. 2018; (published online Jan 29.)http://dx.doi.org/10.1016/S2352-4642(18)30004-XSummary Full Text Full Text PDF Scopus (29) Google Scholar report a cross-sectional analysis of the BRIGHTLIGHT cohort, which included 830 young people aged 12–24 years with a new primary cancer diagnosis in England. Diagnostic timeliness was assessed through structured, face-to-face interviews, supplemented with data from case report forms and the national cancer registry. One of the most striking observations was that the median symptom onset-to-diagnosis interval in female adolescents and young adults was 24 (95% CI 11–37) days longer than that in males. Whether this disparity varies by the type of cancer is unknown. This finding is noteworthy because females were more likely to have had three or more GP consultations before referral to specialist services than were males (adjusted odds ratio 1·6 [95% CI 1·1–2·3], p=0·0093). As the authors point out, female adolescents and young adults should be a high-priority target for improvement in diagnostic timeliness, and innovative solutions are needed, even if only to reduce the burden of anxious uncertainty. The cancers associated with the highest proportion of three or more prereferral GP consultations—lymphomas and bone tumours—were those with clinical presentations that are frequent and common in young people, cervical lymphadenopathy and bone pain, respectively. By contrast, patients with melanoma, leukaemia, and germ-cell tumours (such as in the testis) commanded prompt attention and referral by GPs. These findings are consistent with a systematic review,3Brasme JF Morfouace M Grill I et al.Delays in diagnosis of paediatric cancers: a systematic review and comparison with expert testimony in lawsuits.Lancet Oncol. 2012; 13: e445-e459Summary Full Text Full Text PDF PubMed Scopus (122) Google Scholar which additionally reported that presentation to emergency rooms, presumably with more dramatic symptoms and signs, is associated with expeditious referral to specialist services. As the authors acknowledge, comparability and benchmarking are limited by the age range of the participants (12–24 years). In the context of cancer, childhood is commonly defined as younger than 15 years and adolescence as 15–19 years. Young adulthood starts at 20 years, with the upper limit adopted in North America,4Department of Health and Human ServicesNational Institutes of HealthNational Cancer InstituteLivestrong Young Adult AllianceClosing the gap: research and care imperatives for adolescents and young adults with cancer. Report of the Adolescent and Young Adult Oncology Progress Review Group. National Institutes of Health, Bethesda, MD2006Google Scholar and more recently in Europe,5Saloustros E Stark DP Michailidou K et al.The care of adolescents and young adults with cancer: results of the ESMO/SIOPE survey.ESMO Open. 2017; 2: e000252Crossref PubMed Scopus (35) Google Scholar being 39 years. Nonetheless, the evolving discipline of adolescent and young adult oncology6Barr RD Ferrari A Ries L Whelan J Bleyer WA Cancer in adolescents and young adults. A narrative review of the current status and a view of the future.JAMA Pediatr. 2016; 170: 495-501Crossref PubMed Scopus (256) Google Scholar focuses attention, in purpose-designed clinical programmes, on a narrow age range encompassing those aged 13–24 years, as exemplified by Teenage Cancer Trust, which now have more than 25 operational units in the UK. Because of the unique biology of cancers in young people, it is preferable to categorise these diseases by systems that are not primarily topographical (ie, by anatomical site). The International Classification of Diseases in Oncology (ICD-O) is dominated by carcinomas, the epithelial tumours that account for the majority of malignant neoplasms in older adults. By contrast, most tumours in children, adolescents, and young adults are not carcinomas, and the classification systems for cancers in these age groups take a primarily histological approach.7Steliarova-Foucher E Stiller C Lacour B Kaatsch P International classification of childhood cancer, third edition.Cancer. 2005; 103: 1457-1467Crossref PubMed Scopus (1028) Google Scholar, 8Barr RD Holowaty EJ Birch JM Classification schemes for tumors diagnosed in adolescents and young adults.Cancer. 2006; 106: 1425-1430Crossref PubMed Scopus (99) Google Scholar This is not a semantic matter: half the participants in the BRIGHTLIGHT cohort had lymphomas and germ-cell tumours. Taking a histological approach encourages emphasis to be placed on the biology of cancers, which is important because 60% of the relationship between diagnostic timeliness and survival is explained by the biological characteristics of diseases.9Barr RD “Delays” in diagnosis: a misleading concept, yet providing opportunities for advancing clinical care.J Pediatr Hematol Oncol. 2014; 36: 169-172Crossref PubMed Scopus (28) Google Scholar Brasme and colleagues' systematic review,3Brasme JF Morfouace M Grill I et al.Delays in diagnosis of paediatric cancers: a systematic review and comparison with expert testimony in lawsuits.Lancet Oncol. 2012; 13: e445-e459Summary Full Text Full Text PDF PubMed Scopus (122) Google Scholar which included more than 22 000 paediatric patients, illustrates not only how diagnostic intervals vary considerably by disease, as confirmed in the Herbert and colleagues' study,2Herbert A Lyratzopoulos G Whelan J et al.Diagnostic timeliness in adolescents and young adults with cancer: a multicentre, cross-sectional analysis of the BRIGHTLIGHT cohort.Lancet Child Adolesc Health. 2018; (published online Jan 29.)http://dx.doi.org/10.1016/S2352-4642(18)30004-XSummary Full Text Full Text PDF Scopus (29) Google Scholar but also how the length of these intervals has a complex relationship with important clinical outcomes such as survival. For example, shorter lag times are associated with longer survival in patients with Wilms' tumour, soft tissue sarcomas, and retinoblastoma, but with shorter survival in children with medulloblastoma and brain stem gliomas.3Brasme JF Morfouace M Grill I et al.Delays in diagnosis of paediatric cancers: a systematic review and comparison with expert testimony in lawsuits.Lancet Oncol. 2012; 13: e445-e459Summary Full Text Full Text PDF PubMed Scopus (122) Google Scholar, 9Barr RD “Delays” in diagnosis: a misleading concept, yet providing opportunities for advancing clinical care.J Pediatr Hematol Oncol. 2014; 36: 169-172Crossref PubMed Scopus (28) Google Scholar In another study,10Brasme JF Chalumeau M Oberlin O Valteau-Couanet D Gaspar N Time to diagnosis of Ewing tumors in children and adolescents is not associated with metastasis or survival: a prospective multicenter study of 436 patients.J Clin Oncol. 2014; 32: 1935-1940Crossref PubMed Scopus (48) Google Scholar time to diagnosis was unrelated to metastasis or survival in 436 young people (<21 years old) with Ewing's sarcoma. Although it might be premature to expect such data from the BRIGHTLIGHT cohort, it should be possible to determine whether the symptom onset-to-diagnosis intervals are associated with the stage of lymphomas and the presence of metastatic disease with extracranial solid tumours at the time of diagnosis. Further reports from the BRIGHTLIGHT investigators are eagerly awaited, as these will shed more light on the facets at the core of adolescent and young adult oncology. I declare no competing interests. Diagnostic timeliness in adolescents and young adults with cancer: a cross-sectional analysis of the BRIGHTLIGHT cohortThe findings provide a benchmark for diagnostic timeliness in young people with cancer and help to identify subgroups at higher risk of a prolonged diagnostic journey. Further research is needed to understand reasons for these findings and to prioritise and stratify early diagnosis initiatives for AYAs. Full-Text PDF Open Access

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