Symptom Signatures and Diagnostic Timeliness in Cancer Patients: A Review of Current Evidence.

Early diagnosis is an important aspect of contemporary cancer prevention and control strategies, as the majority of patients are diagnosed following symptomatic presentation. The nature of presenting symptoms can critically influence the length of the diagnostic intervals from symptom onset to presentation (the patient interval), and from first presentation to specialist referral (the primary care interval). Understanding which symptoms are associated with longer diagnostic intervals to help the targeting of early diagnosis initiatives is an area of emerging research. In this Review, we consider the methodological challenges in studying the presenting symptoms and intervals to diagnosis of cancer patients, and summarize current evidence on presenting symptoms associated with a range of common and rarer cancer sites. We propose a taxonomy of cancer sites considering their symptom signature and the predictive value of common presenting symptoms. Finally, we consider evidence on associations between symptomatic presentations and intervals to diagnosis before discussing implications for the design, implementation, and evaluation of public health or health system interventions to achieve the earlier detection of cancer

Stage–specific incidence trends of renal cancers in the East of England, 1999–2016

Objectives: To determine stage-specific time-trends in renal cancer incidence. Methods: We used population-based East Anglia data 1999−2016 (population ∼2 million) on 5,456 primary renal cancer diagnoses, estimating stage-specific annual incidence using Poisson regression, allowing for changing time-trends, and adjusting for sex, age, and socioeconomic deprivation. Results: Renal cancer incidence increased from 9.8–16.4 cases per 100,000 during 1999−2016. Incidence of Stage I, II, and III cases increased over time, most steeply for Stage I, with annual Incidence Rate Ratio [IRR] for Stage I of 1.09 (95 % CI 1.07–1.12) during 1999−2010; and 1.03 (1.00–1.05) during 2011−2016. In contrast, the annual incidence of Stage IV renal cancer decreased during most years, IRR of 0.99 (0.98–1.00) during 2003−2016. Conclusion: The findings are consistent with both earlier detection of symptomatic renal cancer and increasing identification of asymptomatic lesions. However, the decreasing incidence of late-stage disease suggests genuine shifts towards earlier diagnosis

Associations between diagnostic time intervals and health-related quality of life, clinical anxiety and depression in adolescents and young adults with cancer:cross-sectional analysis of the BRIGHTLIGHT cohort

The association of diagnostic intervals and outcomes is poorly understood in adolescents and young adults with cancer (AYA). We investigated associations between diagnostic intervals and health-related quality of life (HRQoL), anxiety and depression in a large AYA cohort.Participants aged 12-24 completed interviews post-diagnosis, providing data on diagnostic experiences and the patient-reported outcomes (PROs) HRQoL, anxiety and depression. Demographic and cancer information were obtained from clinical and national records. Six diagnostic intervals were considered. Relationships between intervals and PROs were examined using regression models.Eight hundred and thirty participants completed interviews. In adjusted models, across 28 of 30 associations, longer intervals were associated with poorer PROs. Patient intervals (symptom onset to first seeing a GP) of ≥1 month were associated with greater depression (adjusted odds ratio (aOR):1.7, 95% Confidence Interval (CI):1.1-2.5) compared to <1 month. ≥3 pre-referral GP consultations were associated with greater anxiety (aOR:1.6, CI:1.1-2.3) compared to 1-2 consultations. Symptom onset to first oncology appointment intervals of ≥2 months was associated with impaired HRQoL (aOR:1.8, CI:1.2-2.5) compared to <2 months.Prolonged diagnostic intervals in AYA are associated with an increased risk of impaired HRQoL, anxiety and depression. Identifying and delivering interventions for this high-risk group is a priority

Association of Self-reported Presenting Symptoms With Timeliness of Help-Seeking Among Adolescents and Young Adults With Cancer in the BRIGHTLIGHT Study

Importance: Evidence regarding the presenting symptoms of cancer in adolescents and young adults can support the development of early diagnosis interventions. / Objective: To examine common presenting symptoms in adolescents and young adults aged 12 to 24 years who subsequently received a diagnosis of cancer and potential variation in time to help-seeking by presenting symptom. / Design, Setting, and Participants: This multicenter study is a cross-sectional analysis of the BRIGHTLIGHT cohort study, which was conducted across hospitals in England. Participants included adolescents and young adults aged 12 to 24 years with cancer. Information on 17 prespecified presenting symptoms and the interval between symptom onset and help-seeking (the patient interval) was collected through structured face-to-face interviews and was linked to national cancer registry data. Data analysis was performed from January 2018 to August 2019. / Exposures: Self-reported presenting symptoms. / Main Outcomes and Measures: The main outcomes were frequencies of presenting symptoms and associated symptom signatures by cancer group and the proportion of patients with each presenting symptom whose patient interval was longer than 1 month. / Results: The study population consisted of 803 adolescents and young adults with valid symptom information (443 male [55%]; 509 [63%] aged 19-24 years; 705 [88%] White). The number of symptoms varied by cancer group: for example, 88 patients with leukemia (86%) presented with 2 or more symptoms, whereas only 9 patients with melanoma (31%) presented with multiple symptoms. In total, 352 unique symptom combinations were reported, with the 10 most frequent combinations accounting for 304 patients (38%). Lump or swelling was reported by more than one-half the patients (419 patients [52%; 95% CI, 49%-56%]). Other common presenting symptoms across all cancers were extreme tiredness (308 patients [38%; 95% CI, 35%-42%]), unexplained pain (281 patients [35%; 95% CI, 32%-38%]), night sweats (192 patients [24%; 95% CI, 21%-27%]), lymphadenopathy (191 patients [24%; 95% CI, 21%-27%]), and weight loss (190 patients [24%; 95% CI, 21%-27%]). The relative frequencies of presenting symptoms also varied by cancer group; some symptoms (such as lump or swelling) were highly prevalent across several cancer groups (seen in >50% of patients with lymphomas, germ cell cancers, carcinomas, bone tumors, and soft-tissue sarcomas). More than 1 in 4 patients (27%) reported a patient interval longer than 1 month; this varied from 6% (1 patient) for fits and seizures to 43% (18 patients) for recurrent infections. / Conclusions and Relevance: Adolescents and young adults with cancer present with a broad spectrum of symptoms, some of which are shared across cancer types. These findings point to discordant presenting symptom prevalence estimates when information is obtained from patient report vs health records and indicate the need for further symptom epidemiology research in this population

Conceptual Framework to Guide Early Diagnosis Programs for Symptomatic Cancer as Part of Global Cancer Control.

Diagnosing cancer earlier can enable timely treatment and optimize outcomes. Worldwide, national cancer control plans increasingly encompass early diagnosis programs for symptomatic patients, commonly comprising awareness campaigns to encourage prompt help-seeking for possible cancer symptoms and health system policies to support prompt diagnostic assessment and access to treatment. By their nature, early diagnosis programs involve complex public health interventions aiming to address unmet health needs by acting on patient, clinical, and system factors. However, there is uncertainty regarding how to optimize the design and evaluation of such interventions. We propose that decisions about early diagnosis programs should consider four interrelated components: first, the conduct of a needs assessment (based on cancer-site-specific statistics) to identify the cancers that may benefit most from early diagnosis in the target population; second, the consideration of symptom epidemiology to inform prioritization within an intervention; third, the identification of factors influencing prompt help-seeking at individual and system level to support the design and evaluation of interventions; and finally, the evaluation of factors influencing the health systems' capacity to promptly assess patients. This conceptual framework can be used by public health researchers and policy makers to identify the greatest evidence gaps and guide the design and evaluation of local early diagnosis programs as part of broader cancer control strategies

Conceptual Framework to Guide Early Diagnosis Programs for Symptomatic Cancer as Part of Global Cancer Control

ACKNOWLEDGMENT This research arises from the CanTest Collaborative, which is funded by Cancer Research UK (C8640/A23385), of which MMK and NC are Postdoctoral Researchers, GL is Associate Director, GPR is Chair and FMW is Director. GL is supported by Cancer Research UK Clinician Advanced Scientist Fellowship (grant number: C18081/A18180). The funder has had no role in the study, writing of the report, or decision to submit the paper for publication.Peer reviewedPublisher PD

Associations between diagnostic time intervals and health related quality of life, clinical anxiety and depression in adolescents and young adults with cancer: cross-sectional analysis of the BRIGHTLIGHT cohort

Background:The association of diagnostic intervals and outcomes is poorly understood in adolescents and young adults with cancer (AYA). We investigated associations between diagnostic intervals and health-related quality of life (HRQoL), anxiety and depression in a large AYA cohort.Methods:Participants aged 13-24 completed interviews post-diagnosis, providing data on diagnostic experiences and the patient-reported outcomes (PROs) HRQoL, anxiety and depression. Demographic and cancer information were obtained from clinical and national records. Six diagnostic intervals were considered. Relationships between intervals and PROs were examined using regression models.Results:830 participants completed interviews. In adjusted models, across 28 of 30 associations, longer intervals were associated with poorer PROs. Patient intervals (symptom onset to first seeing a GP) of ≥1 month were associated with greater depression (adjusted odds ratio (aOR):17, 95% Confidence Interval (CI):11-25) compared to <1 month. ≥3 pre-referral GP consultations were associated with greater anxiety (aOR:16, CI:11-23) compared to 1-2 consultations. Symptom onset to first oncology appointment intervals of ≥2 months were associated with impaired HRQoL (aOR:18, CI:12-25) compared to <2 months.Conclusions:Prolonged diagnostic intervals in AYA are associated with an increased risk of impaired HRQoL, anxiety and depression. Identifying and delivering interventions for this high-risk group is a priority

Stage-specific incidence trends of melanoma in an English region, 1996-2015: longitudinal analyses of population-based data.

The aim of this study was to examine temporal trends in overall and stage-specific incidence of melanoma. Using population-based data on patients diagnosed with melanoma in East Anglia, England, 1996-2015, we estimated age-standardized time trends in annual incidence rates for each stage at diagnosis. Negative binomial regression was used to model trends over time adjusted for sex, age group and deprivation, and to subsequently examine variation in stage-specific trends by sex and age group. The age-standardized incidence increased from 14 to 29 cases/100 000 persons (i.e. 4% annually). Increasing incidence was apparent across all stages but was steepest for stage I [adjusted annual increase: 5%, 95% confidence interval (CI): 5-6%, and more gradual for stage II-IV disease (stage II: 3%, 95% CI: 2-4%; stage III/IV: 2%, 95% CI: 1-3%)]. Stage II-IV increase was apparent in men across age groups and in women aged 50 years or older. Increases in incidence were steeper in those aged 70 years or older, and in men. The findings suggest that both a genuine increase in the incidence of consequential illness and a degree of overdiagnosis may be responsible for the observed increasing incidence trends in melanoma in our population during the study period. They also suggest the potentially lower effectiveness of public health awareness campaigns in men and older people.CRUK C18081/A1818

Association of self-reported presenting symptoms and timeliness of help-seeking among adolescents and young adults with cancer

Importance: Evidence relating to the presenting symptoms of adolescent and young adults with cancer can support the development of early diagnosis interventions. Objective: To examine common presenting symptoms in adolescents and young adults aged 12–24 years subsequently diagnosed with cancer and potential variation in time to help-seeking by presenting symptom. Design: Cross-sectional analysis of the BRIGHTLIGHT cohort. Information on 17 pre-specified presenting symptoms and the symptom-onset-to-help-seeking interval (patient interval) was collected through structured face-to-face interviews and linked to national cancer registry data. Setting: Multi-centre study across English hospitals. Exposures: Self-reported presenting symptoms. Main Outcomes and Measures: Frequencies of presenting symptoms and associated ‘symptom signatures’ by cancer group. Proportion of patients with each presenting symptom whose patient interval was greater than one month. Results: The study population consisted of 803 adolescents and young adults with valid symptom information (55% male, 63% aged 19–24 years, and 88% white ethnicity). The number of symptoms varied by cancer group: for example, 86% of leukaemia patients presented with two or more symptoms while only 31% of melanoma patients presented with multiple symptoms. In total, 352 unique symptom combinations were reported, with the 10 most frequent combinations accounting for 38% of patients. Lump or swelling was reported by over half the patients (prevalence (95% CI): 52% (49–56%)). Other common presenting symptoms across all cancers were extreme tiredness (38% (35–42%)), unexplained pain (35% (32–38%)), night sweats (24% (21–27%)), lymphadenopathy (24% (21–27%)), and weight loss (24% (21–27%)). The relative frequencies of presenting symptoms also varied by cancer group; some symptoms (such as lump/swelling) were highly prevalent across several cancer groups (seen in >50% of patients diagnosed with lymphomas, germ cell tumours, carcinomas, bone tumours, and soft-tissue sarcomas). Over one in four patients (27%) reported a patient interval longer than one month: this varied from 6% (fits/seizures) to 43% (recurrent infections). Conclusions and Relevance: Adolescents and young adults with cancer present with a broad spectrum of symptoms, some of which are shared across cancer types. The findings point to discordant presenting symptom prevalence estimates when information is obtained from patient report versus health records