Total-Body Examination Vs Lesion-Directed Skin Cancer Screening

Research

Original Investigation Total-Body Examination vs Lesion-Directed Skin Cancer Screening

Isabelle Hoorens, MD; Katrien Vossaert, MD; Lore Pil; Barbara Boone, MD, PhD; Sofie De Schepper, MD, PhD; Katia Ongenae, MD, PhD; Lieven Annemans, MD, PhD; Ines Chevolet, MD; Lieve Brochez, MD, PhD

Editorial page 19

IMPORTANCE Skin cancer is the most frequent cancer type. It remains unknown if and how CME Quiz at screening programs can be organized in a cost-effective manner. jamanetworkcme.com and CME Questions page 120 OBJECTIVE To compare the 2 screening strategies of systematic total-body examination (TBE) and lesion-directed screening (LDS), with a focus on the participation rate, detection rate, anxiety, and cost.

DESIGN, SETTING, AND PARTICIPANTS Population-based cross-sectional screenings by a team of 6 dermatologists were organized in 2 sociodemographically similar regions. The TBE was organized in a community of 9325 inhabitants 18 years and older (Wichelen, East Flanders, Belgium) during a 5-day screening (March 14-18, 2014). The LDS was organized in a sociodemographically comparable community (Nevele, East Flanders, Belgium) of 9484 adult inhabitants during a 4-day screening (April 22 and 25-27, 2014). The first population received a personal invitation for a standard TBE. In the second population, individuals were invited for an LDS if they had a lesion meeting 1 or more of the following criteria: ABCD rule (A, asymmetry; B, borders; C, colors; and D, differential structures), ugly duckling sign, new lesion lasting longer than 4 weeks, or red nonhealing lesions.

MAIN OUTCOMES AND MEASURES In total, 1982 individuals were screened, and 47 skin cancers (2.4%) were histologically confirmed, including 9 melanomas (0.5%), 37 basal cell carcinomas (1.9%), and 1 squamous cell carcinoma or Bowen disease (0.1%).

RESULTS The positive predictive value for all suspicious lesions was 56.6% (47 of 83). The participation rate was 17.9% (1668 of 9325) in the TBE group vs 3.3% (314 of 9484) in the LDS group (P < .01). The skin cancer detection rate per 100 participants did not differ significantly between the 2 groups, with rates of 2.3% (39 of 1668) in the TBE group vs 3.2% (8 of 248) in the LDS group (P = .40). The operational effectiveness per 100 invitees was 0.4% (39 of 9325) in the TBE group vs 0.1% (8 of 9484) in the LDS group (P < .01). In addition, LDS was 5.6 times less time consuming than TBE. Participants in the LDS group had significantly higher baseline anxiety levels compared with participants in the TBE group (3.7 vs 3.3 points on a visual analog scale, P < .01). In screenees without a suspicious lesion, anxiety levels significantly dropped after screening.

CONCLUSIONS AND RELEVANCE Total-body examination yielded a higher absolute number of skin cancers. Lesion-directed screening had a similar detection rate of 3.2% (8 of 248) but was 5.6 times less time consuming. When performed by dermatologists, LDS is an acceptable alternative screening method in health care systems with limited budgets or long waiting lists. Author Affiliations: Department of Dermatology, University Hospital Ghent, Ghent, Belgium (Hoorens, Boone, De Schepper, Ongenae, Chevolet, Brochez); private practice, Maldegem, Belgium (Vossaert); Department of Public Health, University Ghent, Ghent, Belgium (Pil, Annemans). Corresponding Author: Lieve Brochez, MD, PhD, Department of Dermatology, University Hospital Ghent, 185 De Pintelaan, 9000 JAMA Dermatol. 2016;152(1):27-34. doi:10.1001/jamadermatol.2015.2680 Ghent, Belgium (lieve.brochez Published online October 14, 2015. @ugent.be).

(Reprinted) 27

Downloaded From: https://jamanetwork.com/ on 09/28/2021 Research Original Investigation Total-Body Examination vs Lesion-Directed Skin Cancer Screening

he incidence of melanoma and nonmelanoma skin cancer (NMSC) has been rising dramatically worldwide, and Methods T this increase is expected to continue with aging of the population.1,2 The cumulative lifetime risk of developing basal Patients and Screening cell carcinoma (BCC) in the Netherlands is estimated to range Population-based cross-sectional skin cancer screenings were from 1 in 5 to 1 in 6 persons.3 In the United Kingdom, the life- performed without randomization. The TBE was organized in time risk of developing malignant melanoma is 1 in 55 for men a community of 9325 inhabitants (Wichelen, East Flanders, Bel- and 1 in 56 for women.4 Early detection is believed to result in gium) during a 5-day screening (March 14-18, 2014). All inhab- better cure rates and subsequently more cost-effective itants 18 years and older received a personal invitation 5 weeks treatment.5,6 Because skin examination is a simple, noninva- in advance for a free-of-charge TBE, including a message that sive technique, several early detection initiatives exist, most of skin cancer incidence is an increasing health care problem. which focus on melanoma only. However, most skin cancers are The LDS was organized in a comparable community in NMSC, and these neoplasms represent the greatest direct cost terms of genetic background, socioeconomic status, culture, to public health.7-9 Population-based screening by means of and geographic area (Nevele, East Flanders, Belgium) during total-body examination (TBE) in asymptomatic persons has not a 4-day screening (April 22 and 25-27, 2014). The 9484 inhab- been proven cost-effective,10,11 although experience in Ger- itants were also invited by a personal letter 5 weeks in ad- many suggests that such screening is feasible and can reduce vance for a free-of-charge skin cancer check if they had a le- skin cancer burden.5,12 Most screening initiatives focus on spe- sion meeting 1 or more of the following listed criteria: ABCD cific high-risk groups,13-15 missing many skin cancers that oc- rule (A, asymmetry; B, borders; C, colors; and D, differential cur outside of this high-risk setting. A reliable and acceptable structures), ugly duckling sign, new lesion lasting longer than test is an important tool in skin cancer screening. Dermoscopy 4 weeks, or red nonhealing lesions. A TBE was offered to all has been shown to increase diagnostic accuracy for melanoma LDS participants at the end of the lesion screening. over naked-eye examination in experienced users.16,17 Individuals were asked to preregister to obtain an esti- Because evidence for the cost-effectiveness of skin can- mate of the number of participants and to organize the screen- cer screening by TBE is lacking, we aimed to test a lesion- ing team. All aspects of the sensitization campaign and regis- directed screening (LDS) approach. With this method, screen- tration process were similar in the 2 groups. Only the specific ees are seen with only a specific lesion of concern meeting message to the populations differed. certain preset criteria. We hypothesized that LDS would in- The screenings were organized in a public place of the mu- crease the a priori probability of skin cancer detection and be nicipality. All participants were randomized to 1 of 6 derma- time saving for the physician. tologists (including K.V., B.B., S.D.S., K.O., or L.B.) with simi- In a pilot study evaluating LDS in 199 persons, 25 suspi- lar expertise in skin cancer and dermoscopy. The screening was cious lesions (12.6%) were detected, and individuals were re- performed using both naked-eye inspection and dermos- ferred to their general practitioner (GP) or to a dermatologist copy. In the case of a suspicious lesion, a second opinion was for further care. When only BCC (which can be diagnosed clini- obtained to reduce interobserver variability. Suspicious le- cally) and 2 histologically confirmed melanomas were in- sions were photographed, and the patient received a referral cluded, the pilot study had a detection rate of at least 8.5%. letter for his or her GP or a dermatologist. This percentage is 10-fold higher than the detection rate of a The study was approved by the Flemish government and systematic skin cancer screening program in the German state by the medical ethics committee of the University Hospital of Schleswig-Holstein, in which skin cancers were detected in Ghent, Ghent, Belgium. All participants provided written 0.8% of the population, including 0.5% BCCs, 0.1% squa- informed consent. mous cell carcinomas (SCCs), and 0.2% melanomas.5 Based on estimated incidence rates in Belgium, the expected skin can- Data Collection cer yield would be less than 0.2% of the population. There- Participants were interviewed using a standard question- fore, screening individuals for selected lesions meeting pre- naire to collect information on demographics and risk fac- defined criteria could give a higher yield of relevant lesions tors. Anxiety about skin cancer was evaluated using a VAS rang- than promoting systematic whole-body screening. This con- ing from 0 (no fear) to 10 (highest possible fear) before and cept is new in skin cancer screening. Based on these data, we immediately after screening, irrespective of the outcome. decided to perform a comparative effectiveness study.18 During the clinical examination, the following features We compared dermatologist-conducted LDS with stan- were recorded: skin type according to Fitzpatrick,23 solar len- dard TBE screening in 2 sociodemographically similar re- tigines, actinic keratosis, the number of nevi, and the pres- gions, with a focus on the participation rate, detection rate, ence of atypical nevi. All melanocytic lesions on exposed skin anxiety level, and cost. Because screening may cause anxiety (except genitalia) were counted, and atypical melanocytic nevi and depression,19,20 a visual analog scale (VAS) to measure were defined as previously described by Garbe et al.24,25 The anxiety levels was included in the protocol. Such a scale is an duration of the clinical examination was noted. This period was accepted tool used in dental practice and in the measure- defined as the time needed for the patient to get fully un- ment of perioperative anxiety.21,22 The VAS corresponds well dressed (for TBE) or to show the specific lesion (for LDS), plus with the Spielberger State-Trait Anxiety Inventory, a vali- the time needed for the dermatologist to examine the body (for dated test quantifying anxiety.22 TBE) or the lesion (for LDS) via naked eye and dermoscopy.

28 JAMA Dermatology January 2016 Volume 152, Number 1 (Reprinted) jamadermatology.com

Downloaded From: https://jamanetwork.com/ on 09/28/2021 Total-Body Examination vs Lesion-Directed Skin Cancer Screening Original Investigation Research

Table 1. Demographics, Participation Rate, Motivation to Participate, and Previous Skin Checks Among 1982 Participants, Including 869 Men and 1113 Womena

TBE LDS Variable (n = 1668) (n = 314) P Valueb Age, mean (SD), y 50.7 (15.5) 52.2 (15.7) .11c Sex, No. (%) .93 Male 732 (43.9) 137 (43.6) Female 936 (56.1) 177 (56.4) Participation rate, No./total No. (%) 1668/9325 (17.9) 314/9484 (3.3) <.01 Educational level, No. (%) (n = 1654) (n = 306) <.01 Primary school 208 (12.6) 37 (12.1) High school 757 (45.8) 119 (38.9) Higher education 526 (31.8) 101 (33.0) University degree 163 (9.9) 49 (16.0) History of skin cancer, No. (%) Personal 40 (2.4) 6 (2.0) .84 Familial 179 (10.7) 41 (13.1) .17 Motivation to participate, No. (%) (n = 1655) I just wanted to be checked 1280 (77.3) 56 (17.8) <.01 Abbreviations: LDS, lesion-directed I have many moles 131 (7.9) 1 (0.3) <.01 screening; TBE, total-body I have 1 or more suspicious skin lesions 109 (6.6) 238 (75.8) <.01 examination. A family member or friend advised me 5 (0.3) 4 (1.3) .06 a Some totals differ from heading A physician advised me 59 (3.6) 2 (0.6) .01 totals because of missing data. b Pearson χ2 test unless otherwise Other 71 (4.3) 13 (4.1) .99 stated. At least 1 previous skin check, No. (%) 634 (38.3) 123 (39.2) .29 c Wilcoxon rank sum test.

When a suspicious lesion was detected during one of Statistical Analysis the screenings, the patient was referred to his or her GP or All categorical variables were compared using Pearson χ2 test to a dermatologist for biopsy or excision and treatment. The or Fisher exact test if the conditions for Pearson χ2 test were clinical suspicion rate was defined as the number of refer- not met. Independent-sample or paired-sample t test was used rals divided by the number of participants. The pathological for continuous variables. Differences are expressed with 95% outcome of the lesion was retrieved and considered the CIs. All statistical tests were 2 tailed, and P < .05 was consid- final diagnosis and yield. ered statistically significant. The analyses were conducted using statistical software (SPSS, version 21.0; IBM). Sample size Outcomes calculation of the number of invitees was based on the par- Four primary outcomes were evaluated. First was the participation rate and effect size of published data and the pilot ticipation rate, defined as the total number of participants study. Power analysis was also conducted using a computer divided by the total number of invited inhabitants. Second program (SPSS SamplePower, version 3.0; IBM). was the detection rate, defined as the number of histologically confirmed skin cancers among the total number of participants, as well as the operational effectiveness, defined as Results the overall yield in the invited population. Third, the effect of the screening on anxiety was evaluated by comparing the Participation VAS scores before and after screening. Fourth, the cost, In total, 1982 individuals were screened in this study. The par- expressed as the direct cost per detected lesion, was calcu- ticipation rate was 17.9% (1668 of 9325) in the TBE group vs lated for the 2 screening methods. For calculation of the 3.3% (314 of 9484) in the LDS group (P < .01) (Table 1). The sex cost, the measurement and valuation were consistent with distribution was comparable, with a modest female predomi- the perspective of the Belgian health care budget and in nance of 56.2% (1113 of 1982) overall. There was no difference accordance with the 2014 National Institute for Health reim- between groups in the median age. Educational level was bursement guidelines in Belgium. For these costs of the higher in the LDS group, with 16.0% (49 of 306) having a uni- screening program, subsequent treatment and indirect costs versity degree compared with 9.9% (163 of 1654) in the TBE were not taken into account. In addition, the time spent per group (P < .01). screening was assessed to better understand the screening Regarding their motivation to participate, 77.3% (1280 of capacity of both methods. Mortality was not included as an 1655) in the TBE group wanted to obtain a total-body skin end point. check, whereas 75.8% (238 of 314) in the LDS group consulted

jamadermatology.com (Reprinted) JAMA Dermatology January 2016 Volume 152, Number 1 29

Downloaded From: https://jamanetwork.com/ on 09/28/2021 Research Original Investigation Total-Body Examination vs Lesion-Directed Skin Cancer Screening

Table 2. Clinical Findings and Risk Factors Among Participantsa

No. (%) Overall TBE LDS Variable (N = 1982) (n = 1668) (n = 314) P Valueb Fitzpatrick skin type (n = 1936) (n = 1653) (n = 283) .23c I 123 (6.4) 107 (6.5) 16 (5.7) II 1143 (59.0) 965 (58.4) 178 (62.9) III 637 (32.9) 551 (33.3) 86 (30.4) IV 26 (1.3) 24 (1.5) 2 (0.7) V 6 (0.3) 6 (0.4) 0 VI 1 (0.1) 0 1 (0.4) Nevus count (n = 1935) (n = 1652) (n = 283) .96 <25 1108 (57.3) 944 (57.1) 164 (58.0) 25 to <50 567 (29.3) 483 (29.2) 84 (29.7) 50 to <100 194 (10.0) 168 (10.2) 26 (9.2) ≥100 66 (3.4) 57 (3.5) 9 (3.2) Presence of (n = 1935) (n = 1652) (n = 283) Abbreviations: AK, actinic keratosis; AK 152 (7.8) 130 (7.9) 22 (7.8) .90 BCC, basal cell carcinoma; Solar lentigines 1264 (65.3) 1051 (63.6) 213 (75.3) <.01 LDS, lesion-directed screening; Atypical nevi 298 (15.4) 249 (15.1) 49 (17.3) .33 SCC, squamous cell carcinoma; TBE, total-body examination. Screenees (n = 1982) (n = 1668) (n = 314) .66 a Some totals differ from heading With suspected skin cancer of any type 83 (4.2) 73 (4.4) 10 (3.2) totals because of missing data. With suspected melanoma 10 (0.5) 9 (0.5) 1 (0.3) b Pearson χ2 test unless otherwise With atypical nevi referred for excision 17 (0.9) 17 (1.0) 0 stated. With suspected BCC 47 (2.4) 40 (2.4) 7 (2.2) c Fisher exact test was used because the conditions for Pearson χ2 test With suspected SCC or Bowen disease 8 (0.4) 6 (0.4) 2 (0.6) were not met. With other suspected skin cancerd 1 (0.1) 1 (0.1) 0 d Merkel cell carcinoma.

for a specific lesion. However, 6.6% (109 of 1655) in the TBE matology office for biopsy. In the TBE group, 1 participant died group consulted because of concern about a specific lesion, and before referral, 4 participants chose not to have an excision or 17.8% (56 of 314) in the LDS group had no specific lesion of con- biopsy, and 7 participants postponed excision or biopsy be- cern but consulted for a TBE. In total, 90.1% (283 of 314) of scre- cause of other health problems. enees in the LDS group agreed to a total-body skin check. In total, 1982 individuals were screened, and 47 skin cancers (2.4%) were histologically confirmed. No suspicious le- Clinical Findings sions were found in screenees younger than 35 years, and the The clinical findings are summarized in Table 2. Participants skin cancer detection rate in the age group 35 years and older in the 2 groups did not differ significantly regarding Fitzpat- was 3.0% (47 of 1548). Melanoma was detected in 0.5% (9 of rick skin type, total nevus count, and the presence of actinic 47), 1.9% (37 of 47) had confirmed BCC, and 0.1% (1 of 47) mani- keratosis or atypical nevi. A positive personal or family his- fested SCC or Bowen disease. The positive predictive value tory of skin cancer and the number of participants who had (PPV) for melanoma was 50.0% (95% CI, 0.24-0.76), while received at least 1 previous skin check was similar in both the PPV for BCC was 72.3% (95% CI, 0.58-0.83) (Table 3). groups at 38.3% (634 of 1655) in the TBE group and 39.2% (123 The PPV for SCC or Bowen disease was only 12.5% (95% CI, of 314) in the LDS group. 0.01-0.49). The overall PPV for skin cancer was 56.6% (95% The clinical suspicion rate was 4.4% (73 of 1668) in the TBE CI, 0.46-0.67). group vs 3.2% (10 of 314) in the LDS group (P = .66). The most Skin cancer detection rates between the 2 screening meth- frequent clinical diagnosis was BCC. Some screenees had more ods did not differ significantly at 2.3% (39 of 1668) for TBE vs than 1 clinically suspicious lesion, especially multiple BCCs (1 3.2% (8 of 248) for LDS (P = .40). However, in the population individual each had 3, 9, and 10 lesions, while 6 individuals invited for TBE, significantly more skin cancers were de- had 2 lesions) and Bowen disease lesions (1 individual had 3 tected given the higher participation rate of 0.4% (39 of 9325) lesions, while 3 individuals had 2 lesions). for TBE vs 0.1% (8 of 9484) for LDS (P <.01)(Table 4). In total, 283 of 314 participants in the LDS group (90.1%) Skin Cancer Detection Rate agreed to have a total-body skin check. Among individuals in The histological diagnoses of 1 participant in the LDS group and whom the initial index lesion was not suspicious, only one skin 12 participants in the TBE group could not be retrieved. In the cancer at another site was detected. In a subgroup of 10 par- LDS group, a lesion suspicious for Bowen disease had re- ticipants in whom the presented lesion was suspicious, addi- solved spontaneously when the participant came to the der- tional malignant lesions were revealed by total-body skin check

30 JAMA Dermatology January 2016 Volume 152, Number 1 (Reprinted) jamadermatology.com

Downloaded From: https://jamanetwork.com/ on 09/28/2021 Total-Body Examination vs Lesion-Directed Skin Cancer Screening Original Investigation Research

Table 3. Histological Findings

No./Total No. (%) Overall TBE LDS Variable (N = 1982) (n = 1668) (n = 248)a P Valueb TBE Minus LDS, % (95% CI) Skin cancer detection rate 47 (2.4) 39 (2.3) 8 (3.2) .40 −0.89 (−3.96 to 0.90) Melanoma Detection rate 9 (0.5) 8 (0.5)c 1 (0.4) .87 0.08 (−1.78 to 0.65) PPV 5/10 (50.0) 4/9 (44.4)c 1/1 (100) .99d NA BCC Detection rate 37 (1.9) 30 (1.8)e,f 7 (2.8)g .28 −1.02 (−3.96 to 0.61) PPV 34/47 (72.3) 28/40 (70.0)e,f 6/7 (85.7)g .69 NA SCC or Bowen disease Detection rate 1 (0.1) 1 (0.1)f 0.99d 0.06 (−1.47 to 0.34) PPV 1/8 (12.5) 1/6 (16.7)f 0/2 NA NA Missing histology reports 13 12 1 NA NA Abbreviations: BCC, basal cell carcinoma; LDS, lesion-directed screening; NA, referred for excision of a lesion suspicious for melanoma. not applicable; PPV, positive predictive value; SCC, squamous cell carcinoma; d Fisher exact test was used because the conditions for Pearson χ2 test were not TBE, total-body examination. met. a In total, 248 participants in the LDS group consulted for a specific lesion. e Two BCCs were detected among participants with a lesion suspicious for Participants undergoing a standard skin check were not included in the total Bowen disease. number. f For calculation of the detection rate and PPV, only the first BCC and Bowen b 2 Pearson χ test unless otherwise stated. disease lesion were taken in account. c Four melanomas were detected among participants referred for excision of an g One BCC was detected in a patient with a lesion suspicious for SCC. atypical nevus. Four melanomas were also detected among participants

Table 4. Skin Cancer Detection Rate and Operational Effectiveness

TBE Minus LDS, % Variable No. (%) P Valuea (95% CI) Skin Cancer Detection Rate TBE LDS (n = 1668) (n = 248) Skin cancer 39 (2.3) 8 (3.2) .40 −0.89 (−3.96 to 0.90) Melanoma 8 (0.5) 1 (0.4) .87 0.08 (−1.78 to 0.65) BCC 30 (1.8) 7 (2.8) .28 −1.02 (−3.96 to 0.61) Abbreviations: BCC, basal cell carcinoma; LDS, lesion-directed b SCC or Bowen disease 1 (0.1) 0 .99 0.06 (−1.47 to 0.34) screening; SCC, squamous cell Operational Effectiveness TBE LDS carcinoma; TBE, total-body (n = 9325) (n = 9484) examination. Skin cancer 39 (0.4) 8 (0.1) <.01 0.33 (0.19 to 0.49) a Pearson χ2 test unless otherwise Melanoma 8 (0.1) 1 (0.0) .02 0.08 (0.01 to 0.16) stated. BCC 30 (0.3) 7 (0.1) <.01 0.25 (0.12 to 0.39) b Fisher exact test was used because the conditions for Pearson χ2 test SCC or Bowen disease 1 (0) 0 .99b 0.01 (−0.03 to 0.06) were not met.

in 3 persons (confirmed BCC in 2 and confirmed Bowen dis- Time and Cost ease in 1). Among 66 participants in the LDS group who did not The mean (SD) duration of the complete skin cancer exami- consult for a specific lesion, only one skin cancer (a con- nation was 232.0 (70.1) seconds in the TBE compared with 40.9 firmed BCC) was detected in her total-body check. (67.1) seconds in the LDS (P < .01) group. Therefore, LDS was 5.6 times less time consuming than TBE. Analysis of the time Anxiety needed to perform only the clinical examination, without con- Participants in the LDS group had significantly higher base- sidering the time to undress, revealed similar mean (SD) re- line anxiety scores (3.7 points) compared with the TBE group sults of 171.6 (62.7) seconds for TBE and 24.2 (31.8) seconds (3.3 points) as measured by the VAS (P < .01) (Table 5). Among for LDS. individuals in whom no suspicious lesion was detected by Reimbursement for the clinical examination, excision, and screening, a similar reduction in anxiety level of 1.3 points on pathological analysis was in accordance with the 2014 Na- the VAS was observed in both groups (P < .01). In screenees who tional Institute for Health reimbursement guidelines in Bel- were diagnosed as having a suspicious lesion, a small rise in gium. The total estimated costs of screening per detected skin the level of anxiety of 0.3 points was seen, but this change was cancer were €931 (US $1008) for LDS and €1012 (US $1096) for not statistically significant. TBE. In future work, a Markov model will be designed to de-

jamadermatology.com (Reprinted) JAMA Dermatology January 2016 Volume 152, Number 1 31

Downloaded From: https://jamanetwork.com/ on 09/28/2021 Research Original Investigation Total-Body Examination vs Lesion-Directed Skin Cancer Screening

Table 5. Anxiety Levelsa

Mean (SD) Variable TBE LDS P Valueb Anxiety levels on the VAS Before screening 3.3 (2.5) 3.7 (2.8) <.01c After screening 2.1 (2.2) 2.5 (2.6) .01c c Difference in anxiety levels before and after screening −1.2 (2.2) −1.2 (2.4) .69 Abbreviations: AK, actinic keratosis; Paired difference in anxiety levels for TBE outcomes LDS, lesion-directed screening; No suspicious lesion −1.3 (2.1) NA <.01 NA, not applicable; TBE, total-body examination; VAS, visual analog scale. Diagnosis of AK −0.1 (2.8) NA .57 a Difference in anxiety levels Diagnosis of suspicious lesion 0.3 (2.5) NA .28 represents the VAS score after Paired difference in anxiety levels for LDS outcomes screening minus the VAS score No suspicious lesion NA −1.3 (2.2) <.01 before screening. b Paired-sample t test unless Diagnosis of AK NA −0.2 (3.1) .80 otherwise stated. Diagnosis of suspicious lesion NA −0.5 (3.4) .57 c Independent-sample t test.

termine the incremental cost-effectiveness ratio comparing the Data from the Euromelanoma campaigns rarely report TBE and LDS methods vs no screening. complete histological follow-up for NMSC. The yield for histologically confirmed melanoma varies among different Eu- ropean countries. In the 2009 and 2010 campaigns, the total 27 Discussion detection rate was 0.35% among all participating countries. Only one campaign in Switzerland included NMSC histologi- In this article, we present the results of a study comparing 2 cal findings, resulting in detection rates of 0.38% for BCC and different screening methods for skin cancer by dermatolo- 0.15% for SCC.27-29 During the 2009 Euromelanoma cam- gists in 2 similar populations. The participation rate, detec- paign in Belgium, 2652 participants were screened, and 12 tion rate, anxiety level, and cost were compared. melanomas were found, resulting in a detection rate of 0.45%, Overall, 1982 individuals were screened by this initiative, which is similar to our findings.27 Their PPV for melanoma was and 47 skin cancers (2.4%) were histologically confirmed, 22.2% compared with 50.0% in our study, although dermos- including 9 melanomas (0.5%), 37 BCCs (1.9%), and 1 SCC or copy was used in 94.4% of their examinations. Bowen disease (0.1%). No skin cancers were detected Compared with TBE, LDS had a lower operational effec- among 434 individuals in the age group younger than 35 tiveness, with TBE detecting 5 times more skin cancers in the years while the detection rate was 3.0% (47 of 1548) in those population. However, the detection rates were not signifi- 35 years and older. In addition, the PPV for all suspicious cantly different between the 2 screening methods (2.3% [39 lesions was 56.6%. Definitive histological diagnoses were of 1668] for TBE vs 3.2% [8 of 2480] for LDS, P = .40). Further- missing for 13 lesions. Therefore, the rate of false-positive more, LDS was 5.6 times less time consuming than TBE and findings, an important adverse effect of screening, ranged resulted in lower costs per detected skin cancer. The opera- between 27.7% and 44.6%. tional effectiveness of LDS can be increased if whole-body These detection rates and PPVs were high compared with screening is offered to individuals in whom the initial index other screening initiatives. The largest European study to date lesion that was the reason for participation was not suspi- is the screening in the German state of Schleswig-Holstein, cious on clinical examination. A large 2-step screening study30 which reported a histological yield of 0.8% malignant lesions offered a TBE after dermatologists performed an inspection of (0.5% BCC, 0.1% SCC, and 0.2% melanoma) and a false- the problem area. The researchers found that, if a skin tumor positive rate of 74.3%.5,26 The use of dermoscopy could have was the reason for consultation (odds ratio, 3.8; 95% CI, 2.0- led to a higher diagnostic accuracy in the present study. The 4.8) or if a suspicious lesion was found at the problem area odds for detecting melanoma have been shown to increase by (odds ratio, 6.8; 95% CI, 5.2-9.0), the risk of missing a skin can- at least 9 times with dermoscopy compared with naked-eye cer significantly increased when no additional TBE was per- examination.17 However, some of this difference could also be formed. A large proportion of patients with BCC develop mul- explained by study design variation. In the screening de- tiple BCCs over time, and some of these patients are seen with scribed herein, a team of dermatologists highly experienced synchronous BCCs.31 In our study, 3 of 10 patients had a sec- in skin cancer and dermoscopy was involved, whereas in Ger- ond confirmed BCC or Bowen disease after being seen with a many nondermatologists may participate in screening after an confirmed malignant lesion on LDS. Total-body examination 8-hour course on clinical detection of skin cancer. Therefore, seems to be the most complete skin cancer screening that can it is possible that the false-negative rate was high in the Ger- be offered to a population. However, because of budgetary and man study because some patients with suspicious lesions medical staff challenges that health care systems face today may not have been correctly referred to a dermatologist, and that result in waiting lists to see a dermatologist, LDS might resulting in an overall lower yield of malignant lesions. be a viable alternative.

32 JAMA Dermatology January 2016 Volume 152, Number 1 (Reprinted) jamadermatology.com

Downloaded From: https://jamanetwork.com/ on 09/28/2021 Total-Body Examination vs Lesion-Directed Skin Cancer Screening Original Investigation Research

The participation rate in the TBE group herein was com- ing 45 on the State-Trait Anxiety Inventory.36 This definition parable to the participation rate of 19.1% in the German SCREEN correlates with a VAS score cutoff of greater than 2 points, with (Skin Cancer Research to Provide Evidence for Effectiveness a sensitivity of 76.7% and a specificity of 64.9%.22 Our results of Screening in Northern Germany) project.32 The almost 5 show that the mean anxiety level dropped significantly in both times lower participation rate in the LDS group herein can likely groups by 1.2 points after a negative screening result (P < .01). be explained by the specific message on the invitation or the In the case of a positive screening result, anxiety level did not stated conditions to participate because all other aspects of the increase significantly. It is possible that anxiety was induced sensitization campaign were similar and because the 2 par- by the personal invitations sent out 5 weeks in advance, re- ticipating areas were socioeconomically comparable accord- sulting in a subsequent return to baseline levels. An anxiety ing to official statistics. In the TBE group, 109 of 1655 partici- measurement obtained before sending out the invitation would pants (6.6%) attended the screening because they were worried provide a more accurate effect of the intervention. Anxiety level about 1 or more lesions compared with 238 of 314 partici- prescreening was 0.4 points higher in the LDS group com- pants in the LDS group (75.8%). Therefore, the message on the pared with the TBE group (P < .01). This effect is likely be- invitation was correctly interpreted by most individuals in the cause of the perceived alarming nature of the information re- LDS group, probably resulting in a general lower participa- garding skin cancer on the LDS invitation. The anxiety level tion rate. In screening, higher educational levels lead to greater of 109 participants having a specific lesion of concern in the participation. Our data showed a significantly higher educa- TBE group was comparable to the prescreening level of anxi- tional level in the LDS group, with 49.0% (150 of 306) of par- ety in the LDS group (mean 3.7, P = .95). Therefore, it is not only ticipants having a higher education or a university degree the specific message on the invitation but also the invitee’s rea- compared with 41.7% (689 of 1654) of participants in the TBE son for participation that influences an individual’s anxiety group. This finding could be related to the more complex about having skin cancer. and selective message communicated to the LDS group and deserves attention because lower socioeconomic class is an important risk factor for nonparticipation in health care Conclusions programs and for more advanced cancers at diagnosis.33,34 Efforts to increase the participation rate in the LDS group by In general, this study obtained a high skin cancer detection rate means of sensitization campaigns using television, social and PPV compared with other screening initiatives. There was media, and extra reminders should be examined to fully also high male participation relative to other screenings. Im- exploit the benefits of the LDS method and raise its overall portant factors in establishing skin cancer screening are com- yield. Introduction of a preventive health care pathway munity-based sensitization campaigns and personal invita- managed by GPs could benefit the current socioeconomic tions to participate, as well as screening teams with discrimination in screening campaigns. dermatologists experienced in using dermoscopy. Melanoma is one of the most aggressive of all skin can- Total-body examination yielded a higher absolute num- cers. However, the screening cost per melanoma detected in ber of skin cancers in the invited population. Lesion-directed our study was high, raising the question whether it can be cost- screening had a similar detection rate of 3.2% but was 5.6 times effective to focus only on melanoma. In this study, the screen- less time consuming. When performed by dermatologists, LDS ing cost per melanoma detected varied between €4631 (US is an acceptable alternative screening method, especially in $5015) and €7449 (US $8067). Nonmelanoma skin cancers rep- health care systems with limited budgets or long waiting lists. resent a higher direct cost in the health care budget. Their early The effectiveness of skin cancer screening by nondermatolo- detection can help to reduce this cost because when applied gists warrants further study. It is important to increase the par- to early-stage disease the treatment options are less costly and ticipation rate in LDS and thus the absolute number of skin can- more effective.35 cers detected, noting any differences in screenees’ educational To our knowledge, no studies evaluating anxiety in skin levels and skin cancer awareness. Among participants herein cancer screening have been published to date, and this ad- in whom the initial index lesion was not suspicious, only one verse effect is frequently used as an argument against screen- skin cancer at another site was detected. This finding sug- ing. The literature suggests that a high-anxiety state should be gests that a TBE would primarily be indicated if an individual defined at 1 SD above the normative mean, or a value exceed- is seen with a suspicious lesion.

ARTICLE INFORMATION Drafting of the manuscript: Hoorens, Vossaert, Pil, fellowship from the Clinical Research Foundation of Accepted for Publication: June 24, 2015. Chevolet, Brochez. University Hospital Ghent. Dr Chevolet is supported Critical revision of the manuscript for important by a doctoral fellowship from the Research Published Online: October 14, 2015. intellectual content: All authors. Foundation, Flanders, Belgium. doi:10.1001/jamadermatol.2015.2680. Statistical analysis: Hoorens, Chevolet. Role of the Funder/Sponsor: The funding sources Author Contributions: Drs Hoorens and Brochez Obtained funding: Hoorens, Chevolet. or sponsors of the study had no access to the data had full access to all the data in the study and take Study supervision: Hoorens, Brochez. and no role in study design, data collection, responsibility for the integrity of the data and the Conflict of Interest Disclosures: None reported. analysis, or interpretation of the data. accuracy of the data analysis. Study concept and design: All authors. Funding/Support: The skin cancer screening was Additional Contributions: Sven Lanssens, MD Acquisition, analysis, or interpretation of data: All supported by a research grant from the LEO (with the Department of Dermatology, University authors. Foundation. Dr Hoorens is supported by a doctoral

jamadermatology.com (Reprinted) JAMA Dermatology January 2016 Volume 152, Number 1 33

Downloaded From: https://jamanetwork.com/ on 09/28/2021 Research Original Investigation Total-Body Examination vs Lesion-Directed Skin Cancer Screening

Hospital Ghent, at the time of the study) 13. Osborne JE. Skin cancer screening and study of the Central Malignant Melanoma Registry participated on the screening team. surveillance. Br J Dermatol. 2002;146(5):745-754. of the German Dermatological Society. JInvest 14. Girgis A, Clarke P, Burton RC, Sanson-Fisher RW. Dermatol. 1994;102(5):695-699. REFERENCES Screening for melanoma by primary health care 26. Waldmann A, Nolte S, Geller AC, et al. 1. Lomas A, Leonardi-Bee J, Bath-Hextall F. physicians: a cost-effectiveness analysis. J Med Frequency of excisions and yields of malignant skin A systematic review of worldwide incidence of Screen. 1996;3(1):47-53. tumors in a population-based screening nonmelanoma skin cancer. Br J Dermatol. 2012;166 15. Losina E, Walensky RP, Geller A, et al. Visual intervention of 360,288 whole-body examinations. (5):1069-1080. screening for malignant melanoma: Arch Dermatol. 2012;148(8):903-910. 2. de Vries E, van de Poll-Franse LV, Louwman WJ, a cost-effectiveness analysis. Arch Dermatol.2007; 27. van der Leest RJ, de Vries E, Bulliard JL, et al. de Gruijl FR, Coebergh JW. Predictions of skin 143(1):21-28. The Euromelanoma skin cancer prevention cancer incidence in the Netherlands up to 2015. Br J 16. Kittler H, Pehamberger H, Wolff K, Binder M. campaign in Europe: characteristics and results of Dermatol. 2005;152(3):481-488. Diagnostic accuracy of dermoscopy. Lancet Oncol. 2009 and 2010. J Eur Acad Dermatol Venereol. 3. Flohil SC, de Vries E, Neumann HA, Coebergh 2002;3(3):159-165. 2011;25(12):1455-1465. JW, Nijsten T. Incidence, prevalence and future 17. Vestergaard ME, Macaskill P, Holt PE, Menzies 28. Bulliard JL, Maspoli M, Panizzon RG, Hohl D, trends of primary basal cell carcinoma in the SW. Dermoscopy compared with naked eye Gueissaz F, Levi F. Evaluation of the Euromelanoma Netherlands. Acta Derm Venereol. 2011;91(1):24-30. examination for the diagnosis of primary skin cancer screening campaign: the Swiss 4. Statistical Information Team, Cancer Research melanoma: a meta-analysis of studies performed in experience. J Eur Acad Dermatol Venereol. 2008;22 UK. United Kingdom Cancer Registry. Published 2012. a clinical setting. Br J Dermatol. 2008;159(3):669- (3):365-366. http://www.cancerresearchuk.org. Accessed July 19, 676. 29. Stratigos A, Nikolaou V, Kedicoglou S, et al. 2015. 18. Peppercorn J, Zafar SY, Houck K, Ubel P, Melanoma/skin cancer screening in a 5. Breitbart EW, Waldmann A, Nolte S, et al. Meropol NJ. Does comparative effectiveness Mediterranean country: results of the Systematic skin cancer screening in Northern research promote rationing of cancer care? Lancet Euromelanoma Screening Day Campaign in Greece. Germany. J Am Acad Dermatol. 2012;66(2):201-211. Oncol. 2014;15(3):e132-e138. doi:10.1016/S1470 J Eur Acad Dermatol Venereol. 2007;21(1):56-62. 6. Katalinic A, Waldmann A, Weinstock MA, et al. -2045(13)70597-7. 30. Argenziano G, Zalaudek I, Hofmann-Wellenhof Does skin cancer screening save lives? an 19. Korfage IJ, Essink-Bot ML, Westenberg SM, R, et al. Total body skin examination for skin cancer observational study comparing trends in melanoma Helmerhorst T, Habbema JD, van Ballegooijen M. screening in patients with focused symptoms. JAm mortality in regions with and without screening. How distressing is referral to colposcopy in cervical Acad Dermatol. 2012;66(2):212-219. Cancer. 2012;118(21):5395-5402. cancer screening? a prospective quality of life study. 31. Kiiski V, de Vries E, Flohil SC, et al. Risk factors 7. Tinghög G, Carlsson P, Synnerstad I, Rosdahl I. Gynecol Oncol. 2014;132(1):142-148. for single and multiple basal cell carcinomas. Arch Societal cost of skin cancer in Sweden in 2005. Acta 20. Keyzer-Dekker CM, De Vries J, van Esch L, et al. Dermatol. 2010;146(8):848-855. Derm Venereol. 2008;88(5):467-473. Anxiety after an abnormal screening mammogram 32. Anders MP, Nolte S, Waldmann A, et al. The 8. Stang A, Stausberg J, Boedeker W, is a serious problem. Breast. 2012;21(1):83-88. German SCREEN project: design and evaluation of Kerek-Bodden H, Jöckel KH. Nationwide 21. Facco E, Zanette G, Favero L, et al. Toward the the communication strategy. Eur J Public Health. hospitalization costs of skin melanoma and validation of Visual Analogue Scale for Anxiety. 2014. non-melanoma skin cancer in Germany. J Eur Acad Anesth Prog. 2011;58(1):8-13. 33. Kristensson JH, Sander BB, von Euler-Chelpin Dermatol Venereol. 2008;22(1):65-72. 22. Kindler CH, Harms C, Amsler F, Ihde-Scholl T, M, Lynge E. Predictors of non-participation in 9. Vallejo-Torres L, Morris S, Kinge JM, Poirier V, Scheidegger D. The visual analog scale allows cervical screening in Denmark. Cancer Epidemiol. Verne J. Measuring current and future cost of skin effective measurement of preoperative anxiety and 2014;38(2):174-180. cancer in England. J Public Health (Oxf). 2014;36(1): detection of patients’ anesthetic concerns. Anesth 34. von Euler-Chelpin M, Olsen AH, Njor S, et al. 140-148. Analg. 2000;90(3):706-712. Does educational level determine screening 10. Bigby M. Why the evidence for skin cancer 23. Fitzpatrick TB. The validity and practicality of participation? Eur J Cancer Prev. 2008;17(3):273-278. screening is insufficient: lessons from prostate sun-reactive skin types I through VI. Arch Dermatol. 35. Rogers HW, Coldiron BM. A relative value cancer screening. Arch Dermatol. 2010;146(3):322- 1988;124(6):869-871. unit–based cost comparison of treatment 324. 24. Garbe C, Büttner P, Weiss J, et al. Associated modalities for nonmelanoma skin cancer: effect of 11. Gordon LG, Rowell D. Health system costs of factors in the prevalence of more than 50 common the loss of the Mohs multiple surgery reduction skin cancer and cost-effectiveness of skin cancer melanocytic nevi, atypical melanocytic nevi, and exemption. J Am Acad Dermatol. 2009;61(1):96-103. prevention and screening: a systematic review. Eur actinic lentigines: multicenter case-control study of 36. Millar K, Jelicic M, Bonke B, Asbury AJ. J Cancer Prev. 2015;24(2):141-149. Medline: the Central Malignant Melanoma Registry of the Assessment of preoperative anxiety: comparison of 12. Waldmann A, Nolte S, Weinstock MA, et al. Skin German Dermatological Society. J Invest Dermatol. measures in patients awaiting surgery for breast cancer screening participation and impact on 1994;102(5):700-705. cancer. Br J Anaesth. 1995;74(2):180-183. melanoma incidence in Germany: an observational 25. Garbe C, Büttner P, Weiss J, et al. Risk factors study on incidence trends in regions with and for developing cutaneous melanoma and criteria for without population-based screening. Br J Cancer. identifying persons at risk: multicenter case-control 2012;106(5):970-974.

34 JAMA Dermatology January 2016 Volume 152, Number 1 (Reprinted) jamadermatology.com

Downloaded From: https://jamanetwork.com/ on 09/28/2021