Increasing melanoma incidence with unchanged mortality: more sunshine, better treatment, increased diagnostic activity, overdiagnosis or lowered diagnostic threshold?

BACKGROUND: Increasing melanoma incidence with less increasing mortality is observed in several countries. This discrepancy is not well understood. OBJECTIVES: In this study, our aim was to discuss factors [ultraviolet radiation (UVR) exposure, melanoma treatment, diagnostic activity, overdiagnosis, pathologists' diagnostic threshold and clinicians' propensity to remove suspect skin lesions] that might influence melanoma incidence and mortality in Denmark. METHODS: This was a register study with the number of melanocyte-related lesions and melanoma mortality based on comprehensive national pathology and mortality databases for the period 1999-2019. We investigated melanocyte-related diagnoses and mortality in a population of 5.5 million with a national healthcare system. Age-adjusted melanoma mortality and age-adjusted incidence of benign naevi, atypical lesion, or melanoma in situ and of invasive melanoma were computed for data analysis. RESULTS: In total, 1 434 798 biopsies were taken from 704 682 individuals (65% female). The mean age at biopsy was 39.8 years in males and 37.6 in females. In males and females, the incidence of invasive melanoma increased by 87% during the period 1999-2011. During the subsequent period it increased by 9% in males but remained unchanged in females. The incidence of melanoma in situ increased by 476% in males and 357% in females during the study period, while the increases for atypical melanocytic lesions were 1928% and 1686%, respectively. Biopsy rates increased by 153% in males and 118% in females from 1999 through 2011 but fell by 20% in males and 22% in females during the subsequent period. Mortality varied slightly from year to year without any significant time trend for males or females. We identified no evidence of increased UVR exposure over the latest 30 years in Denmark. Immunotherapy of advanced melanoma was introduced in Denmark in 2010 and came into general use in 2014. CONCLUSIONS: Comprehensive national data demonstrate increasing melanoma incidence correlated with increasing biopsy rates, but with no change in mortality. Previously suggested explanations for such a trend are a lowered threshold of melanoma diagnosis among pathologists, increased diagnostic activity in the presence of overdiagnosis and improved melanoma treatment. Because the study is observational and we have more explanatory factors than outcomes, the findings do not warrant conclusions about causal relationships.

Rates of melanoma have been increasing across several countries, with less increasing mortality. However, information is lacking surrounding which factors might be influencing this. This study aimed to discuss factors (e.g. ultraviolet radiation exposure, melanoma treatment, diagnostic activity, overdiagnosis, pathologists' diagnostic threshold and clinicians' propensity to remove suspect skin lesions) that might influence melanoma incidence and mortality in Denmark. The data demonstrated that increasing melanoma incidence was related to increasing biopsy rates, but with no change in mortality. Our findings suggest increased diagnostic activity, particularly in population groups with the lowest melanoma risk. The rapid increase in atypical/in situ in relation to melanoma could be associated with changes in pathologists' threshold for specifying these diagnoses. It is conceivable that the threshold for atypical/in situ as well as for melanoma have declined because of increased melanoma awareness. Overall, the present study indicates that changes in melanoma incidence may be explained by the interaction among sun exposure, the propensity to remove suspected melanoma lesions, lowered diagnostic thresholds and overdiagnosis.

Is Myocardial Infarction Overdiagnosed?

This Viewpoint examines whether overdiagnosis rather than underdiagnosis may now be the dominant form of myocardial infarction misdiagnosis.

Ecological study estimating melanoma overdiagnosis in the USA using the lifetime risk method.

OBJECTIVES: To quantify the proportion of melanoma diagnoses (invasive and in situ) in the USA that might be overdiagnosed. DESIGN: In this ecological study, incidence and mortality data were collected from the Surveillance, Epidemiology and End Results 9 registries database. DevCan software was used to calculate the cumulative lifetime risk of being diagnosed with melanoma between 1975 and 2018, with adjustments made for changes in longevity and risk factors over the study period. SETTING: USA. PARTICIPANTS: White American men and women (1975-2018). MAIN OUTCOME MEASURES: The primary outcome was excess lifetime risk of melanoma diagnosis between 1976 and 2018 (adjusted for year 2018 competing mortality and changes in risk factors), which was inferred as likely overdiagnosis. The secondary outcome was an excess lifetime risk of melanoma diagnosis in each year between 1976 and 2018 (adjusted and unadjusted). RESULTS: Between 1975 and 2018 the adjusted lifetime risk of being diagnosed with melanoma (invasive and in situ) increased from 3.2% (1 in 31) to 6.4% (1 in 16) among white men, and from 1.6% (1 in 63) to 4.5% (1 in 22) among white women. Over the same period, the adjusted lifetime risk of being diagnosed with melanoma in situ increased from 0.17% (1 in 588) to 2.7% (1 in 37) in white men and 0.08% (1 in 1250) to 2.0% (1 in 50) in white women. An estimated 49.7% of melanomas diagnosed in white men and 64.6% in white women were overdiagnosed in 2018. Among people diagnosed with melanomas in situ, 89.4% of white men and 85.4% of white women were likely overdiagnosed in 2018. CONCLUSIONS: Melanoma overdiagnosis among white Americans is significant and increasing over time with an estimated 44 000 overdiagnosed in men and 39 000 in women in 2018. A large proportion of overdiagnosed melanomas are in situ cancers, pointing to a potential focus for intervention.

Discriminative capacity of guideline recommendations in the assessment of patients with asymptomatic microhematuria.

BACKGROUND & OBJECTIVE: Asymptomatic microhematuria (aMh) remains a diagnostic challenge in urological practice: while aMh is a risk factor of urothelial carcinoma (UC), prevalence of aMh is high. Guidelines were developed to permit risk stratification and reduce diagnostic workload. This study investigates the efficacy of several recommendations. MATERIAL & METHODS: Sixty hundred eight patients with newly diagnosed aMh without previous UC from an academic referral center (A; n = 320) and a private outpatient clinic (B; n = 288) were included. All patients underwent clinical workup including medical history, urine cytology, upper tract imaging and cystoscopy. Eleven former and current guidelines were applied to each patient individually; every patient was classified as either low risk (no further workup recommended) or high risk. Furthermore, a recently developed nomogram for hematuria assessment was included. RESULTS: The cohort comprised 142 females and 466 males (mean age 62 [range 18-92] years). Sixty-one patients (10.0%) were diagnosed with UC. Excluding the Swedish and recent NICE guideline generally advising against urologic workup, application of 9 other recommendations would have diagnosed all UCs and saved 1.6% to 16.1% of patients from workup. For the 2020 US guideline, solely applied to cohort B, 10.6% of patients were classified as low risk. The use of the nomogram would have saved 17.1% to 25% of patients from workup. CONCLUSIONS: Practical relevance of current guidelines is limited as they do not sufficiently identify patients not requiring clinical work up. Thus, guideline adherence may trigger overdiagnosis and even overtreatment. New ways of risk stratification are needed to improve aMh assessment.

QT prolongation is over-estimated by Bazett compared to Friderica in Japanese child and adolescent inpatients.

Recent researches suggested that the risk of drug-induced QTc prolongation is low in child and adolescent psychiatry setting. However, these cohorts enrolled mainly of Caucasian background. We aimed to assess the prevalence of QTc prolongation and its association with antipsychotic use in Japanese youth. The medical records of inpatients were reviewed. Two different definitions of QT prolongation, Bazett's corrected QT interval (QTcB) >450 msec and Fridericia's corrected QT interval (QTcF) >450 msec, were adopted. In 220 participants [age: 13.4 ± 2.3 years, antipsychotics according to the chlorpromazine equivalence: 50 (25th-75th percentiles; 0-150) mg/day], the prevalence of QTcB and QTcF prolongation was 13.6 and 2.3%, respectively. Patients with QTcB >450 msec had a significantly higher heart rate than those with QTcB ≤450 msec (91.2 ± 20.6 bpm vs. 76.1 ± 15.2 bpm; P < 0.001). The other variables, except potassium level (4.1 ± 0.4 mEq/L vs. 4.2 ± 0.3 mEq/L; P = 0.030), showed no significant difference. Clinically meaningful QTc prolongation was rare even in this Japanese cohort. This study also suggested that if QTcB is used, clinicians should be aware of possible overdiagnosis of QTc prolongation due to accelerated heart rate.

Overdiagnosis of Malaria Illness in an Endemic Setting: A Facility-Based Surveillance Study in Malawi.

In endemic settings where asymptomatic malaria infections are common, malaria infection can complicate fever diagnosis. Factors influencing fever misdiagnosis, including accuracy of malaria rapid diagnostic tests (mRDTs) and the malaria-attributable fraction of fevers (MAF), require further investigation. We conducted facility-based surveillance in Malawi, from January 2012 through December 2013 in settings of high perennial (Chikhwawa), high seasonal (Thoylo), and moderate seasonal (Ndirande) malaria transmission. Consecutive patients presenting to outpatient departments were screened; those with suspected malaria illness were tested by mRDT or routine thick-smear microscopy. Test positivity rates (TPRs), positive predictive value (PPVs) of mRDTs, and MAFs were calculated by site, age, and season. Of 41,471 patients, 10,052 (24.2%) tested positive for malaria. The TPR was significantly greater in Chikhwawa (29.9%; 95% CI, 28.6-30.0) compared with Thyolo (13.2%; 95% CI, 12.5-13.7) and Ndirande (13.1%; 95% CI, 12.2-14.4). The overall PPV was 77.8% (95% CI, 76.8-78.7); it was lowest among infants (69.9%; 95% CI, 65.5-74.2) and highest among school-age children (81.9%; 95% CI, 80.3-83.4). Malaria infection accounted for about 50% of fevers in children younger than 5 years old with microscopy-confirmed Plasmodium falciparum infection, and less than 20% of such fevers in school-age children. Outpatient settings in Malawi had a high burden of malaria illness, but also possible overdiagnosis of malaria illness. Interventions to reduce malaria transmission and rapid testing for other common febrile illness may improve diagnostic clarity among outpatients in malaria endemic settings.