Cimu-al and Exptrmental Dermatology 1992; 17: 307-312.
Original Articles
Fundamentals of skin cancer/melanoma screening campaigns F.H.J.RAMPEN, II.A.M.NEUMANN* AND T..A.I..M.KlKMENEYt Departments of Derma lolo^y. Stnt Anna Hospital, Oss. and "^Elkcrhek Hospital, HelmondjDeurne and •]• Comprehensive Canfcr Center IKO, hHjme;j;en, the Netherlands Accepted for puhluation 1 October 1991
Summar\
Since 1985, the American Academy of Dermatology (AAD) has been sponsoring free, volunteer, nationwide There is increased world-wide concern about rhe rising skin-cancer/melanoma screening clinics. These clinics incidence of melanoma and non-melanoma ^kin cancer. target persons at high risk. Screenees attend on the basis Screening theoretically reduces dearh and morbidity of self-selection. So far, the results are encouraging with from skin cancer/melanoma. Visual examiniition of the yields of clinically positive screens for melanoma and skin is a rapid, safe and inexpensive screening tool. In this non-melanomaskincancerrangingfrom9 5 to 15-3')o.''^"'" review the fundamentals of early disease detection before Biro and Price tried to verify clinical diagnoses and found implementation of a public-health screening programme that 33 of 232 screened people had a biopsy-confirmed are critically analysed with reference to the ^kin cancer/ melanoma, epidemic. It is concluded that frkin cancer/ malignancy {14-2%).'•' During the first 6 years of the AAD programme, an melanoma fulfils, for the most part, the criteria enunestimated 358 805 people have bet^n screened nationwide, ciated by Wilson and Jungner in 1968. However, inforresulting in 31 268 suspected skin cancers, including 2516 mation ahout the effect of screening on reducing incimelanomas.'"' l'>om these campaigns it appears that skin dence and mortalitv is still lacking. I'^uture research cancer/melanoma may be a suitable target for screening. should focus on methods of improving compliance and on Howe\er, many questions have fo be addressed before the costs and benefits of such screening programmes. Vull implementation of a screening programme. Earlv disease detection or secondary prevention by means of screenings is aimed at discovering cancer at a There is increasing concern about the need for early stage at which people do not seek medical care spontadetection of skin cancer and melanoma. The incidence of neously. People at risk are deliberately sought for disease cutaneous melanoma is rising sharply among communipresentation at an early or pre-symptomatic stage outside ties with a predominantly white complexion in temperate ot the traditonal medical circuit. Planning screening or sunny climates. Puhlic education campaigns' and free requires several prerequisites and guidelines. Emphasis is cancer-screening clinics- may enhance public awareness placed on detecting those people with previously unreof skin cancer and theoretically could reduce morhidity cognized (symptom-free) cancer and the avoidance of and mortality, cspeciaily of melanoma. Skin cancer is having those without cancer. The basic principles of susceptible to early detection. Precursor lesions and early screening for disease have been delineated comprehensiinvasive carcinomas/melanomas are relatively easy to vely by Wilson and Jungner.'' The following is an detect hy visual inspection of the skin. attempt to outline the prerequisites of skin cancer/ The history of skin cancer screening goes back to 1969 melanoma screening activities according to these princiwhen Weary conducted screening on 548 farmers and ples. It is emphasized that Wilson and Jungner presented ranchers.* He found 23 lesions suspected as cancer, all their criteria for strictly defined large-scale screening hasal cell carcinomas (4-2'';,). Other attempts to establish programmes aiming at examining every person from a skin-cancer detection clinics in the 1970s have also target population. However, these criteria can also be yielded promising results, the proportion of suspected used for evaluating programmes based on self-selection. skin cancers ranging from 1-7 to 9-3%.^ ' In a recent survey of persons who voluntarily attended the AAD screening locations in Massachusetts, Koh el al. Correspondence: Dr F.H.J.Rampen, Sint Anna Hospital, |. Zwij- found that attendees were indeed, for the most part, at risk for skin cancer."' scniaan 121, 5342 BT Oss, The Netherlands, 307
308
F.H.J.RAMPEN, H.A.M.NEUMANN AND L.A.L.M.KIRMENEY
Screening criteria l'^ach ofthe basic principles of disease screening elaborated by Wilson and Jungner will be discvissed in relation to the skin cancer/melanoma epidemic. As the major objective of screening is to reduce morbidity and mortality from melanoma, we may apply the principles of screening principally to this tumour. Where appropriate, we will discuss the criteria in relation to non-melanoma skin cancer as well.
lesions should also theoretically reduce morbidity and mortality of melanoma. There is an accepted clinical practice for the management and follow-up of patients with the dysplastic naevus syndrome and congenital naevi.-''^"^ Treatment of solar keratoses is more controversial; only a tiny proportion evolve into squamous cell carcinomas.^'' Facililies for diagnosis and treatment should be available
Diagnostic and treatment services for positive screens arc readily available. Most types of skin cancer/melanoma 'I'he morbidity and mortality from skin Cancer/melanoma can be managed by simple office procedures. Hospital arc considerable. In the United States an estimated admission is necessary in only a minority of cases. In rare 600 000 people arc diagnosed each year \vith skin cancer/ instances, treatment in specialized centres is required. melanoma.'' Non-melanoma skin cancer is the most However, it needs emphasizing here that screening common type of cancer in western countries. It can lead activities for other types of cancer are continuous to substantial morbidity. Mortality rates are low. How- processes; the workload generated by such programmes is ever, annual mortality rates for non~mclanoma skin spread over the year. Screening for skin cancer/melanoma cancer among whites in the United States are increas- according to the A.AD model involves a once yearly ing.'^''' The non-melanoma skin cancer mortality rates educational campaign coupled with screening services. have increased from 0 94 per 100000 population in 1980 This may cause dramatic increases in referrals to the to 1-34 in 1986 among men and from 0-32 to 0 35 among dermatologist during the weeks following the campaign. women.'"' Obviously, advances in early and appropriate In countries with a low dermatologist to patient ratio (e.g. treatment are not keeping pace with the rising incidence United Kingdom) this especially may lead to a chaotic (on the assumption that there have not been marked situation. I'^ine tuning the aims and scope of skin cancer/ secular trends in the diagnosis of such tumours). 1'hc melanoma screening campaigns to the available services is incidence of melanoma is doubling every decade.-""' a sine qua non. Any screening programme should quantify Mortality rates of melanoma are also increasing and about the level of care required, both for the screening itself and 20% of melanoma patients will eventually die from their for the diagnosis and treatment of positive screenees, disease. Annual mortality from melanoma in the United before embarking upon national programmes. States is now 6300.'" For comparison, the estimated death rate for cancer of the cervix uteri is 6000.'' Finally, mortality from skin cancer/melanoma ranks second There should be a recognizable latent or early symptomatic among males aged 15-34 years (after leukaemia) and third stage among those aged 35-54 years (after lung cancer and Basal cell carcinoma, squamous cell carcinoma, and colorectal cancer).'' Nearly all the fatal cases are melano- melanoma have recognizable early stages. Nearly all cases mas, which makes this tumour a serious cause of death, of skin cancer/melanoma can be detected at a stage at especially in young people with many potential working which metastasis or gross tissue destruction have not yet years remaining. In Europe the situation is more or less occurred. Moreover, precursor lesions such as congenital identical though reliable statistics arc lacking in many naevi, actinic keratoses, and to a lesser extent, dysplastic countries. naevi are easily detectable to the experienced eye. The condition sought should be an tmportunt health problem
There should be an accepted treatment for patients with recognized disease
There should be a suitable test or examination
Although clearly defined estimations of validity parameters are not available, in our opinion visual inspection Treatment for skin cancer/melanoma is inexpensive and effective. Surgery, radiotherapy, cryotherapy, and elcc- of the skin by the dermatologist is a reliable screening trocautery arc accepted modalities because of their tool. Based on the records of a university dermatological simplicity and ready application. I'h^oretically, early setting Kopf ^? al. calculatetl the diagnostic accuracy for treatment produces a better prognosi*; than when the melanoma as follows: sensitivity 77%, specificity 99 7% condition is treated at a later stage. Thi^ holds especially and positive predictive value 80%.^^ However, these data true for melanoma. Survival rates of patients with thin do not pertain to screening itself. Thus, no pronouncemelanomas according to Breslow are superior to those of ments as to the validity c>f a visual examination by patients with thick melanomas.'^ Treatrnent of precursor dermatologists as a screening tool can be deduced from
SKIN CANCER/MF.LANOMA SCREENING them. The accuracy in clinically evaluating dysplastic naevi is relatively low.-'' Exact sensitivity and specificity values based on screening activitie.s cannot be calculated because of lack of follow-up in persons with 'negative' screens. According to Koh et al., the validity of a visual examination by dermatologists as a cancer st-reening tool in terms of sensitivity ranges from 89^!;, for sclLiamous cell carcinoma, to 94% for basal cell carcinoma ^nd 97*'() for melanoma.'' These data are derived from the 1986 and 1987 free skin-cancer screening clinics in Massachusetts. Assuming that the figures represent cogent estimates of sensitivities based on incident cases, tht^y compare favourably with sensitivities for screening tests used in hreast, colon, and cervical cancer.'- Bolognia et al.
309
studies by Clark'' and Breslow^- on histological prognostic factors for melanoma, our knov\ledge of the natural history of this tumour has increased enormously. Accurate prognostication of outcome for melanoma is possible. Thin melanomas, still in their radial growth phase, have an excellent progri'isis, whereas signs of vertical growth extension herald a dismal outcome.'^ For melanoma it is vital to establish diagnosis in its earh radial growth phase. Precursor lesions may progress to invasive cancer (though not in all cases). As already mentioned, solar keratoses often exhibit spontaneous regression or do not evolve into squamous cell carcinoj^^j. 2xi5,.,4 yi^g proportion that show malignant transformation is small. Large congenital naevi have an estimated maVignant potential of 3 2t>'o, t'he smaller ones 1 5%." " The life-time risk of developing melanoma in patients w ith the dysplastic naevus syndrome ranges from 5 to 100%, according to the personal and family histories of dysplastic naevi and/or melanoma.''^ The true value of finding and treating people with pre-malignant lesions is subject to dispute.
tive skin cancer was only 34%." We found that the positive predictive value for skin cancer in two screening settings in The Netherlands was 50-60%.'^ The low value reported by Bolognia and co-authors may be due to overdiagnosi.s of borderline cases. I'ear of lawsuits may betray screening physicians into acts of 'defensive medicine'. This is a great problem in the United States, less so in Europe. Finally, it is emphasized that the consequences of talse-positive visual screens for skin cancer/ There should he an agreed policy (in whom to treat melanoma are limited (punch or excisional biopsy) Screenees with invasi\e skin cancer/melanoma should he compared to false-positive screens for other types of treated, irrespecti\e of the t>pe of cancer. A possible cancer. Furthermore, many persons with tiilse-positive exception is the very elderly piitient with a hasal cell screens would have attended their physician in any case carcinoma, though such persons will not usually present because their benign skin lesions gave concern or for voluntary screening. Whether all precursor lesions discomfort. The accuracy of clinical examination of the di.scovcred at screening should be treated or not, is a skin in detecting skin cancer/melanoma differs with the matter for argument. In our view, 'border-line' cases are p-ft^eiaW^^ \\Sx imtreatccl. This group comprises patients with minor solar keratoses, with non-familial dyspiastic better than non-dermatologists.^''-'" naevi exhibiting only scant clinical expression of the syndrome, and with small congenital naevi in which The test should be acceptable to the population simple excision cannot be easily performed. Depending on definitions and criteria used, the 'border-line' group A visual skin examination is rapid, painless, non-invasive may be greater than the 'diseased' group. Therefore, it is and has no side-effects. Its acceptance to screenees is important to have a clearly defined policy about 'borderhigh. One impediment to screening is that people may be embarrassed to take off their clothes. Thut*, total skin line' screenees. examination may be slightly more embarrassing than partial examination. On the other hand, complete cutaneous examination may result in better melanoma yields '1 he cost of screening (including diagnosis and treatment of patients diagnosed) should be economically balanced m than partial examination.^ relation to possible expenditure on medical care as a whole
The natural history of the condttion. including development from latent to declared disease, should he adequately understood
Non-melanoma skin malignancies evolve slowly to destructive lesions. Advanced disease may cau^c considerable discomfort (bleeding, pain). Certain locations are notorious for their relatively poor prognosis, such as scalp and nasolabial folds for basal cell carcinoma and lower lip for squamous cell carcinoma. Since the pioneering
Screening for skin cancer/melanoma is inexpensive.''^ We have conducted pilot screening projects in Oss and Arnhem, The Netherlands, in \9S9 and 1990; expenses Nv^i":^ Wss \^h'av^ £\.SttptT scTccnee'^ TVitse estimates are not true co.sts. Much of the work was done by volunteer physicians and the cost of treatment of detected malignancies has not been included. On the other hand, it is emphasized that the reassurance of negative screenees may save costs. On the whole, total costs of screening, diagnosing, and treating people for skin cancer/melanoma
310
F.H.J.RAMPEN, ILA.M.NEUMANN AND L.A.L.M.KIEMENKY
is relatively inexpensive when compared with the costs of similar procedures for other types of cancer. So far, no studies have addressed the problem of Cost-effectiveness of skin cancer/melanoma screening clinics in detail; assessing efficacy of such screening is very difficult. The most fundamental parameter is the reduction of mortality. No case-control or other studies have tested this end point. An intermediate end-point is the Breslow thickness of primar\ melanomas.^^ An increasing proportion of thin melanomas following screening may suggest future reduced mortality. Publicity campaigns in the United Kingdom have been followed by an increase in the proportion of" thin, good prognosis melanomas.'-''' •*' At present^ jDo.sui"h iji/orjuatjon is available with regard to the efficacy of screening programmes. Screening should be a continuing process and not a 'once atid for air project
In the 1970s skin cancer/melanoma screening in the United States had the form of single-occasion 'fairs'.'""' The full use of the organization thus created is only served b> a continuing process. Such regular examinations have been promoted since 1985 by the AAD on a nationwide and voluntary basis.^ '' It seems likely that annual, free skin-cancer clinics will be established in other countries as well. Periodic screening has the advantage of covering more and more of the population at risk. Finally, regular screening programmes have a definite educational impact. These advantages do pertain not only to population-based screening; situations, but also to screening interventions on the basis of selfselection. Discussion Because of its accessibility, the skin is rriore amenable to screening intervention than any other or^ran. Skin cancer/ melanoma fulfils, on the whole, all the criteria for screening for disease set out by Wilson and Jungner.''' This docs not necessarily mean that screening is effective, or cost-effective. So far, improved survival rates as the appropriate end-point for the efficacy of screening intervention has not been quantitated. Yet, the recent AAD annual, free skin-cancer clinics indicate that yields are substantial, costs are moderate and acceptance by the public is satisfactory. However, many crucial questions remain unresolved.^ Screening for skin cancer/melanoma implies selective screening, not mass screening. Mass screening based on population registries would be too expensive. An annual 'Skin-Scan"*- for everybody is most probably not costeffective. The profile of groups at risk for skin cancer in general and melanoma in particular is better understood than the risk profile for any of the major types of cancer
amenable to screening activities (breast, colon, uterine cervix).'"'"^^ To this end, skin cancer/melanoma detecting campaigns serve an important educational purpose. Concomitant public education should encourage highrisk persons to attend screening facilities: those with changes in 'funny-looking' moles, those with more than average mole counts, those with a family history of skin cancer/melanoma, those with outdoor work and over 50 years of age, and those with a fair skin complexion. A recent study indicates that people who voluntarily attend free skin-cancer screenings are, for the most part, at risk for the disease."^ Some ethical issues merit consideration. Not all persons will benefit from screening and some may even be adversely affected (false-positive and, to a lesser extent, false-negative screens). In order to avoid undue concern (or lawsuits for clinical misinterpretation) it is advocated that only dermatologists should screen. It has also heen suggested that people who attend for screening should give informed consent."^ The limitations of the screen should be properly explained to the screenee. Ethical guidelines pertinent to screening activities have been established and published by the Michigan Dermatological Society.'' Skin cancer detection clinics should not be undertaken for the benefit of the physician but of the patient-participant. It may be argued whether screening should be held in private or hospital offices or in public premises such as libraries, schools, sport accommodations, etc. It is also pertinent to mention the 'borderline' problem. Are persons with minimal 'disease' to be directed into the medical circuit? In our view, only attendants with unequivocal malignancies or precursor states should be referred to their physician. There is no case for alerting 'border-lint;' cases, such as those with minimal actinic keratoses oy scant atypical pigmented lesions, by screening campaigns. The ethical point also relates to the follow-up of those with positive screens. Provision for adequate follow-up and treatment is vitally important. First of all, the yield of screening needs to be evaluated in terms of histologicalh verified malignancies in ordt^r to justify continuation of the project. Secondly, inadequate follow-up may cause considerable harm to individual positive screenees. Information on compliance with referral or biopsy results is lacking in nearly ail early studies. Zagula-Mafly et al. reported that after 1 year only 17 of 43 positive screenees had visited their physician (40'^,,,).'' Systematic follow--up of positive screenees proved also to be relatively poor in the recent series reported by K'oh et af, foffow-up information with histology was available in only 63H,, of suspected cancer cases.'^ Bolognia et al. reported 78% clinical and histological follt)w-up for persons with positive screens for skin Cancer." Follow-up in our campaigns was more complete at 90%.^^ Other opportunities for tarly skin cancer/melanoma
SKIN CANCER/MELANOMA SCREENING
31
detection are public and professional education camscreening: A local cxpericnct:. Journal of the American Academy of paigns. This type of approach has been accomplished in Dermatology 1987; 16: 637 641. several areas in the United Kingdom, with dramatic 11. Hoiognia JL, Berwick M, Fine JA. Complete follow-up and evaluation of a skin cancer screening in Conniicticm. Journal of the effects on the number of persons referred for assessment of suspected skin cancer.^""" However, effects on pre- 12. American Academy of Dermatology 1990; 23: iO98 1106. Koh HK, C:aruso A, Gage 1 el al. Evaluation of melanoma/skin existing trends in thickness distribution of melanoma cancer screening in Massachusetts: Preliminary results. Cancer varied; whereas Doherty and MacKie claimed a signifi1990; 65: 375 379. cant rise in the proportion of thin melanomas,-^'* other 13. Biro L, Price E, Skin cancer; Screening in urban conmmnity. .\e!P York Slate Journal of Medtcine 1978; 78: 7.S3- 755, authors have been less enthusiastic.'•^'^•^' 14. Kob HK, Miller DR, Geller AC, Lew RA, Rampen FHJ. The This commentary does not address the subject of promise of screening for melanoma and other skin cancers. Clinics practicability of skin cancer/melanoma screening clinics. in Dermatology 1992 (in press), Advice about the setting up of screening programmes will 15. Wilson JMG, Jungner G, The principles and practice of screening for disease. Puhlir Health Papers, f^o. 34 Gcneva" depend on the infrastructure of the health system in a particular country and on the public, professional, and U). WlIO, 1968. Koh HK, Geller AC, Miller DR, Caruso A, Gage I, Lew RA, governmental attitudes towards screening for cancer. Will) is being screened for melanoma/skin cancer? Characteristics I'uture planning and evaluation of screening activities of persons screened in Massachusetts. Journal of the American necessitate close co-operation with epidemiologists with Academy ol Dermatology 1991; 24: 271- 277, 17, Silverberg E, Boring CX; Squires TS. Cancer stali.lics 1990 CA experience in this field. Skin cancer/melanoma is an important health problem. 18. 1990; 40: 9 26. Glass ACi, \ loover R \ . The emerging epidemic of melanoma and Incidence figures arc rising steeply.'^^^'''^ Theoretically, squamous cell skin VAncer. JAM A 1989; 262: 2097 2100. public and professional education and screening efforts 19. \\'einsti>ck MA. The epidemic of squamous cell carcinoma would result in a substantial reduction of the mortality of JAMA 1989; 262:2138-2140. cutaneous meianoma.^--^-"^ The AAD initiative to promote 20, Kopf A, Rigel D, Friedman R, The rising incidence and mortality rates of malignant melanoma. Journal of Dermalologie .Suri;ery and free skin-cancer screening clinics through the United Oncology 1982; 8: 760 761. States generates much puhlic and professional interest. 21. 0sterljnd A, Jensen OM. Trends in incidence of malignant Similar clinics may prove worthwhile in other countries melanoma of the sLm in Denmark 1943 1982. In: Ciallagher RP, as well, especially those with a predominantly white ed. r.pidemuilo!{y ojniali^nanl melanoma. Heidelberg- Springer\crlag, 1986: 8 17. population and with a high skin cancer/melanoma inciBreslow \. Thickness, cross-sectional area, and depth of invasion dence. Some knowledge of the principles of skin cancer/ in the prognosis of cutaneous melanoma. Annah ofSui-gery 1970melanoma screening should form part of the knowledge 172:902-908. base of all dermatologists. 23. Anonymous. Precursors to malignant melanoma: Consensus conference. 7_/4;.-f 1984; 251: !86^-1866. 24. Rhodes AR. Cjmgenital ne\i: Sbould these be excised- 74M 4 1989; 262: 1696.
References
1^. Marks R, Rennie (i, Selwood TS. Malignant transformation of solar keratoses to squamous cell carcinoma. I.ancei 1988- i- 7951. Graham-Brown RAC, Osborne JE, London SP et al. The initial 797. effects on workload and outcome of a public education campaign 26. Kopf AW, Mintzis M, Bart RS. Diagnostic accuracy in malignant on early diagnosis and treatment of malignant melanoma in melanoma. Archives of Dermatology 1975; HI: 1291- 1292, Leicestershire. British Journal of Dcrmatoiogy 1990; 122: 53 59. 27. Curlev RK, Cook M(i, I'allowficid ME, Marsden RA. Accuracy 2. Koh HK, Lew RA, Prout M \ . Screening for melanoma/skin in clinically evaluating pigmented lesions. British Medical louriial cancer: Theoretic and practical considerations. Journal of ihe 1989; 299: 16-18. American Academy of Dermatology 1989; 20: 159 -172. 28. Rampen FHJ, van Huystee BKWL, Kiemenc> LALM. Mela3. Weary PE. A 2-year experience with a series of rural skin and oral noma/skin cancer screening clinics: experiences in rhe Nethercancer detection dmks.JAMA 1971; 217: 1862-1863. lands. Journal of the American Academy of Dermatology 1991; 25: 4. Lynch H, Lynch J, Kraft C. A new approach to cancer screening 776 777. and education. Geriatrics 1973; 28: 152 157. 29. Cassileth Br, CJark WH, Lusk l^J, I'rederick BI', Thompson C], 5. Kanof EP. Experience with a skin cancer detection clinic at a state Walsh WP. How well do physicians recognize melanoma and fair. North Carolina .Medical Journal 1974; 35: 159 161. otber problem lesions? Journal of the American -Icaderny of 6. Zagula-Mally ZW, Rosenberg EW, Kashgarian M. Frequency nf Dermalology 1986; 14: 555 560. skm cancer and solar keratoses in a rural southern county as 30. Rampen I'l IJ, Rumke P. Referral pattern and accuracy of clinical determined b> papuLitton sampling. Cancer 1974; 34: .345-349. diagnosis of cuianeou,s melanoma. Ai:ta Dermato-Venereoloi^ua 7. Loetfel ED, Watson W. Screening for skin cancer at a county fair. (Stockholm! 1988; 68: 61 64, Western Journal of Medicine 1975; 122: 123-126. 31, C:iark \\ II, I'rom L, Bernardino ICA, Mihm MC. The histogene8 Rigtil DS, Friedman RJ, Kopf AW et al. Importance of complete sis and biological behaviour of primary human malignant melanocutaneous examination for the detection of malignant melanoma. mas of the skin. Cancer Research 1969; 29: 705-726. Journal of the American Academy of Dermatotosy 1986- 14' 857 - 32. Cox KB, V'ollmer RT, Seigler I IF. Melanoma in the Soutbeastern 860. ' • " United States: Experience at the Duke Medical Centre. In: Balch 9. T'ield SI. A-lelanoma/skin cancer screening in Michigan. Journal of CM, Milton GW, eds. Cutaneous melanoma; Clinical Management the Atnericun Academy of Dermatology 1987; 16: 578-583. and Treatment Results World-wide. Philadelphia: Lippincott 10 Olsen TG, I'eeser TA, Conte KT, Schroeter AL. Skin cancer C:ompany, 1985; 407 418.
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3.1 Marks F, I'oley P, Goodman G, Hage BH, Selwood TS. 39. Spontaneous remission of solar keratoses: The case of conservative management. British Journal of Dermatology 1986; 115: 649 655. 40. 34. Harve> I, Shalom D, Marks RM, Frankel SJ. Non-melanoma skin cancer: Distribution and natural course are siili open questions, British Medical Journal 1989; 299: 1118-1120. 41. 35. Rhodes AR, Sober .\J, ].>a> CL et al. The malignant potential of small congenital nevocellular ncvi: An estimate of association based on a histologic study of 234 primary cutaneous melanomas. Journal of ihc American Academy ofDermatology 1982; 6: 230-241.42. 36. Ulig L, Weidner F, I Iundeiker M et at. Congenital nevi < 10 cm as precursors to melanoma: 52 cases, a review, and a new 43. conception. Archives of Dermatology 1985; l2I: 1274 1281. 37. Rhodes AR, Weinstock MA, Fitzpatrick TH. Mihm MC, Sober 44. ,'\|. Risk factors for cutaneous melanoma: A practical method of
Doherty VR, MacKie RM. Experience of a public education programme on early detection of cutaneous malignant melanoma. British Medical Journal 1988; 297: 388-391, Wbitchead SM, Wroughton M.'\, Elwood JM, Davi.son J, Stewart M. Effects of a health education campaign for the earlier diagnosis of melanoma. British Journal of Cancer 1989; 60: 421-425. Williams HC^, Smith D, du Vivier AWT. Kvaluation of public education campaigns in cutaneous melanoma; The King's C^ollegc Hospital experience, British Journal of Dermatology V)9^:, 123: 8592. Kopf AW. Prevention and early detection of skin cancer/ melanoma. Cancer 1988; 62: 179i 1795. MacKie RM, Freudenberger T^ Aitcbison TCI Personal riskfactor chart for cutaneous melanoma. Lancet 1989; ii: 487 490. Gallagher RP, Ma B, McLean DI et al. Trends in basal cell carcinoma, squamous eel! carcinoma, and melanoma of the skin from J973 thrmsgh VW. Jnurn/j} qf ihe American Academy nxv;gim-,vfg' i7,-cdkiT
Original Articles
Fundamentals of skin cancer/melanoma screening campaigns F.H.J.RAMPEN, II.A.M.NEUMANN* AND T..A.I..M.KlKMENEYt Departments of Derma lolo^y. Stnt Anna Hospital, Oss. and "^Elkcrhek Hospital, HelmondjDeurne and •]• Comprehensive Canfcr Center IKO, hHjme;j;en, the Netherlands Accepted for puhluation 1 October 1991
Summar\
Since 1985, the American Academy of Dermatology (AAD) has been sponsoring free, volunteer, nationwide There is increased world-wide concern about rhe rising skin-cancer/melanoma screening clinics. These clinics incidence of melanoma and non-melanoma ^kin cancer. target persons at high risk. Screenees attend on the basis Screening theoretically reduces dearh and morbidity of self-selection. So far, the results are encouraging with from skin cancer/melanoma. Visual examiniition of the yields of clinically positive screens for melanoma and skin is a rapid, safe and inexpensive screening tool. In this non-melanomaskincancerrangingfrom9 5 to 15-3')o.''^"'" review the fundamentals of early disease detection before Biro and Price tried to verify clinical diagnoses and found implementation of a public-health screening programme that 33 of 232 screened people had a biopsy-confirmed are critically analysed with reference to the ^kin cancer/ melanoma, epidemic. It is concluded that frkin cancer/ malignancy {14-2%).'•' During the first 6 years of the AAD programme, an melanoma fulfils, for the most part, the criteria enunestimated 358 805 people have bet^n screened nationwide, ciated by Wilson and Jungner in 1968. However, inforresulting in 31 268 suspected skin cancers, including 2516 mation ahout the effect of screening on reducing incimelanomas.'"' l'>om these campaigns it appears that skin dence and mortalitv is still lacking. I'^uture research cancer/melanoma may be a suitable target for screening. should focus on methods of improving compliance and on Howe\er, many questions have fo be addressed before the costs and benefits of such screening programmes. Vull implementation of a screening programme. Earlv disease detection or secondary prevention by means of screenings is aimed at discovering cancer at a There is increasing concern about the need for early stage at which people do not seek medical care spontadetection of skin cancer and melanoma. The incidence of neously. People at risk are deliberately sought for disease cutaneous melanoma is rising sharply among communipresentation at an early or pre-symptomatic stage outside ties with a predominantly white complexion in temperate ot the traditonal medical circuit. Planning screening or sunny climates. Puhlic education campaigns' and free requires several prerequisites and guidelines. Emphasis is cancer-screening clinics- may enhance public awareness placed on detecting those people with previously unreof skin cancer and theoretically could reduce morhidity cognized (symptom-free) cancer and the avoidance of and mortality, cspeciaily of melanoma. Skin cancer is having those without cancer. The basic principles of susceptible to early detection. Precursor lesions and early screening for disease have been delineated comprehensiinvasive carcinomas/melanomas are relatively easy to vely by Wilson and Jungner.'' The following is an detect hy visual inspection of the skin. attempt to outline the prerequisites of skin cancer/ The history of skin cancer screening goes back to 1969 melanoma screening activities according to these princiwhen Weary conducted screening on 548 farmers and ples. It is emphasized that Wilson and Jungner presented ranchers.* He found 23 lesions suspected as cancer, all their criteria for strictly defined large-scale screening hasal cell carcinomas (4-2'';,). Other attempts to establish programmes aiming at examining every person from a skin-cancer detection clinics in the 1970s have also target population. However, these criteria can also be yielded promising results, the proportion of suspected used for evaluating programmes based on self-selection. skin cancers ranging from 1-7 to 9-3%.^ ' In a recent survey of persons who voluntarily attended the AAD screening locations in Massachusetts, Koh el al. Correspondence: Dr F.H.J.Rampen, Sint Anna Hospital, |. Zwij- found that attendees were indeed, for the most part, at risk for skin cancer."' scniaan 121, 5342 BT Oss, The Netherlands, 307
308
F.H.J.RAMPEN, H.A.M.NEUMANN AND L.A.L.M.KIRMENEY
Screening criteria l'^ach ofthe basic principles of disease screening elaborated by Wilson and Jungner will be discvissed in relation to the skin cancer/melanoma epidemic. As the major objective of screening is to reduce morbidity and mortality from melanoma, we may apply the principles of screening principally to this tumour. Where appropriate, we will discuss the criteria in relation to non-melanoma skin cancer as well.
lesions should also theoretically reduce morbidity and mortality of melanoma. There is an accepted clinical practice for the management and follow-up of patients with the dysplastic naevus syndrome and congenital naevi.-''^"^ Treatment of solar keratoses is more controversial; only a tiny proportion evolve into squamous cell carcinomas.^'' Facililies for diagnosis and treatment should be available
Diagnostic and treatment services for positive screens arc readily available. Most types of skin cancer/melanoma 'I'he morbidity and mortality from skin Cancer/melanoma can be managed by simple office procedures. Hospital arc considerable. In the United States an estimated admission is necessary in only a minority of cases. In rare 600 000 people arc diagnosed each year \vith skin cancer/ instances, treatment in specialized centres is required. melanoma.'' Non-melanoma skin cancer is the most However, it needs emphasizing here that screening common type of cancer in western countries. It can lead activities for other types of cancer are continuous to substantial morbidity. Mortality rates are low. How- processes; the workload generated by such programmes is ever, annual mortality rates for non~mclanoma skin spread over the year. Screening for skin cancer/melanoma cancer among whites in the United States are increas- according to the A.AD model involves a once yearly ing.'^''' The non-melanoma skin cancer mortality rates educational campaign coupled with screening services. have increased from 0 94 per 100000 population in 1980 This may cause dramatic increases in referrals to the to 1-34 in 1986 among men and from 0-32 to 0 35 among dermatologist during the weeks following the campaign. women.'"' Obviously, advances in early and appropriate In countries with a low dermatologist to patient ratio (e.g. treatment are not keeping pace with the rising incidence United Kingdom) this especially may lead to a chaotic (on the assumption that there have not been marked situation. I'^ine tuning the aims and scope of skin cancer/ secular trends in the diagnosis of such tumours). 1'hc melanoma screening campaigns to the available services is incidence of melanoma is doubling every decade.-""' a sine qua non. Any screening programme should quantify Mortality rates of melanoma are also increasing and about the level of care required, both for the screening itself and 20% of melanoma patients will eventually die from their for the diagnosis and treatment of positive screenees, disease. Annual mortality from melanoma in the United before embarking upon national programmes. States is now 6300.'" For comparison, the estimated death rate for cancer of the cervix uteri is 6000.'' Finally, mortality from skin cancer/melanoma ranks second There should be a recognizable latent or early symptomatic among males aged 15-34 years (after leukaemia) and third stage among those aged 35-54 years (after lung cancer and Basal cell carcinoma, squamous cell carcinoma, and colorectal cancer).'' Nearly all the fatal cases are melano- melanoma have recognizable early stages. Nearly all cases mas, which makes this tumour a serious cause of death, of skin cancer/melanoma can be detected at a stage at especially in young people with many potential working which metastasis or gross tissue destruction have not yet years remaining. In Europe the situation is more or less occurred. Moreover, precursor lesions such as congenital identical though reliable statistics arc lacking in many naevi, actinic keratoses, and to a lesser extent, dysplastic countries. naevi are easily detectable to the experienced eye. The condition sought should be an tmportunt health problem
There should be an accepted treatment for patients with recognized disease
There should be a suitable test or examination
Although clearly defined estimations of validity parameters are not available, in our opinion visual inspection Treatment for skin cancer/melanoma is inexpensive and effective. Surgery, radiotherapy, cryotherapy, and elcc- of the skin by the dermatologist is a reliable screening trocautery arc accepted modalities because of their tool. Based on the records of a university dermatological simplicity and ready application. I'h^oretically, early setting Kopf ^? al. calculatetl the diagnostic accuracy for treatment produces a better prognosi*; than when the melanoma as follows: sensitivity 77%, specificity 99 7% condition is treated at a later stage. Thi^ holds especially and positive predictive value 80%.^^ However, these data true for melanoma. Survival rates of patients with thin do not pertain to screening itself. Thus, no pronouncemelanomas according to Breslow are superior to those of ments as to the validity c>f a visual examination by patients with thick melanomas.'^ Treatrnent of precursor dermatologists as a screening tool can be deduced from
SKIN CANCER/MF.LANOMA SCREENING them. The accuracy in clinically evaluating dysplastic naevi is relatively low.-'' Exact sensitivity and specificity values based on screening activitie.s cannot be calculated because of lack of follow-up in persons with 'negative' screens. According to Koh et al., the validity of a visual examination by dermatologists as a cancer st-reening tool in terms of sensitivity ranges from 89^!;, for sclLiamous cell carcinoma, to 94% for basal cell carcinoma ^nd 97*'() for melanoma.'' These data are derived from the 1986 and 1987 free skin-cancer screening clinics in Massachusetts. Assuming that the figures represent cogent estimates of sensitivities based on incident cases, tht^y compare favourably with sensitivities for screening tests used in hreast, colon, and cervical cancer.'- Bolognia et al.
309
studies by Clark'' and Breslow^- on histological prognostic factors for melanoma, our knov\ledge of the natural history of this tumour has increased enormously. Accurate prognostication of outcome for melanoma is possible. Thin melanomas, still in their radial growth phase, have an excellent progri'isis, whereas signs of vertical growth extension herald a dismal outcome.'^ For melanoma it is vital to establish diagnosis in its earh radial growth phase. Precursor lesions may progress to invasive cancer (though not in all cases). As already mentioned, solar keratoses often exhibit spontaneous regression or do not evolve into squamous cell carcinoj^^j. 2xi5,.,4 yi^g proportion that show malignant transformation is small. Large congenital naevi have an estimated maVignant potential of 3 2t>'o, t'he smaller ones 1 5%." " The life-time risk of developing melanoma in patients w ith the dysplastic naevus syndrome ranges from 5 to 100%, according to the personal and family histories of dysplastic naevi and/or melanoma.''^ The true value of finding and treating people with pre-malignant lesions is subject to dispute.
tive skin cancer was only 34%." We found that the positive predictive value for skin cancer in two screening settings in The Netherlands was 50-60%.'^ The low value reported by Bolognia and co-authors may be due to overdiagnosi.s of borderline cases. I'ear of lawsuits may betray screening physicians into acts of 'defensive medicine'. This is a great problem in the United States, less so in Europe. Finally, it is emphasized that the consequences of talse-positive visual screens for skin cancer/ There should he an agreed policy (in whom to treat melanoma are limited (punch or excisional biopsy) Screenees with invasi\e skin cancer/melanoma should he compared to false-positive screens for other types of treated, irrespecti\e of the t>pe of cancer. A possible cancer. Furthermore, many persons with tiilse-positive exception is the very elderly piitient with a hasal cell screens would have attended their physician in any case carcinoma, though such persons will not usually present because their benign skin lesions gave concern or for voluntary screening. Whether all precursor lesions discomfort. The accuracy of clinical examination of the di.scovcred at screening should be treated or not, is a skin in detecting skin cancer/melanoma differs with the matter for argument. In our view, 'border-line' cases are p-ft^eiaW^^ \\Sx imtreatccl. This group comprises patients with minor solar keratoses, with non-familial dyspiastic better than non-dermatologists.^''-'" naevi exhibiting only scant clinical expression of the syndrome, and with small congenital naevi in which The test should be acceptable to the population simple excision cannot be easily performed. Depending on definitions and criteria used, the 'border-line' group A visual skin examination is rapid, painless, non-invasive may be greater than the 'diseased' group. Therefore, it is and has no side-effects. Its acceptance to screenees is important to have a clearly defined policy about 'borderhigh. One impediment to screening is that people may be embarrassed to take off their clothes. Thut*, total skin line' screenees. examination may be slightly more embarrassing than partial examination. On the other hand, complete cutaneous examination may result in better melanoma yields '1 he cost of screening (including diagnosis and treatment of patients diagnosed) should be economically balanced m than partial examination.^ relation to possible expenditure on medical care as a whole
The natural history of the condttion. including development from latent to declared disease, should he adequately understood
Non-melanoma skin malignancies evolve slowly to destructive lesions. Advanced disease may cau^c considerable discomfort (bleeding, pain). Certain locations are notorious for their relatively poor prognosis, such as scalp and nasolabial folds for basal cell carcinoma and lower lip for squamous cell carcinoma. Since the pioneering
Screening for skin cancer/melanoma is inexpensive.''^ We have conducted pilot screening projects in Oss and Arnhem, The Netherlands, in \9S9 and 1990; expenses Nv^i":^ Wss \^h'av^ £\.SttptT scTccnee'^ TVitse estimates are not true co.sts. Much of the work was done by volunteer physicians and the cost of treatment of detected malignancies has not been included. On the other hand, it is emphasized that the reassurance of negative screenees may save costs. On the whole, total costs of screening, diagnosing, and treating people for skin cancer/melanoma
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F.H.J.RAMPEN, ILA.M.NEUMANN AND L.A.L.M.KIEMENKY
is relatively inexpensive when compared with the costs of similar procedures for other types of cancer. So far, no studies have addressed the problem of Cost-effectiveness of skin cancer/melanoma screening clinics in detail; assessing efficacy of such screening is very difficult. The most fundamental parameter is the reduction of mortality. No case-control or other studies have tested this end point. An intermediate end-point is the Breslow thickness of primar\ melanomas.^^ An increasing proportion of thin melanomas following screening may suggest future reduced mortality. Publicity campaigns in the United Kingdom have been followed by an increase in the proportion of" thin, good prognosis melanomas.'-''' •*' At present^ jDo.sui"h iji/orjuatjon is available with regard to the efficacy of screening programmes. Screening should be a continuing process and not a 'once atid for air project
In the 1970s skin cancer/melanoma screening in the United States had the form of single-occasion 'fairs'.'""' The full use of the organization thus created is only served b> a continuing process. Such regular examinations have been promoted since 1985 by the AAD on a nationwide and voluntary basis.^ '' It seems likely that annual, free skin-cancer clinics will be established in other countries as well. Periodic screening has the advantage of covering more and more of the population at risk. Finally, regular screening programmes have a definite educational impact. These advantages do pertain not only to population-based screening; situations, but also to screening interventions on the basis of selfselection. Discussion Because of its accessibility, the skin is rriore amenable to screening intervention than any other or^ran. Skin cancer/ melanoma fulfils, on the whole, all the criteria for screening for disease set out by Wilson and Jungner.''' This docs not necessarily mean that screening is effective, or cost-effective. So far, improved survival rates as the appropriate end-point for the efficacy of screening intervention has not been quantitated. Yet, the recent AAD annual, free skin-cancer clinics indicate that yields are substantial, costs are moderate and acceptance by the public is satisfactory. However, many crucial questions remain unresolved.^ Screening for skin cancer/melanoma implies selective screening, not mass screening. Mass screening based on population registries would be too expensive. An annual 'Skin-Scan"*- for everybody is most probably not costeffective. The profile of groups at risk for skin cancer in general and melanoma in particular is better understood than the risk profile for any of the major types of cancer
amenable to screening activities (breast, colon, uterine cervix).'"'"^^ To this end, skin cancer/melanoma detecting campaigns serve an important educational purpose. Concomitant public education should encourage highrisk persons to attend screening facilities: those with changes in 'funny-looking' moles, those with more than average mole counts, those with a family history of skin cancer/melanoma, those with outdoor work and over 50 years of age, and those with a fair skin complexion. A recent study indicates that people who voluntarily attend free skin-cancer screenings are, for the most part, at risk for the disease."^ Some ethical issues merit consideration. Not all persons will benefit from screening and some may even be adversely affected (false-positive and, to a lesser extent, false-negative screens). In order to avoid undue concern (or lawsuits for clinical misinterpretation) it is advocated that only dermatologists should screen. It has also heen suggested that people who attend for screening should give informed consent."^ The limitations of the screen should be properly explained to the screenee. Ethical guidelines pertinent to screening activities have been established and published by the Michigan Dermatological Society.'' Skin cancer detection clinics should not be undertaken for the benefit of the physician but of the patient-participant. It may be argued whether screening should be held in private or hospital offices or in public premises such as libraries, schools, sport accommodations, etc. It is also pertinent to mention the 'borderline' problem. Are persons with minimal 'disease' to be directed into the medical circuit? In our view, only attendants with unequivocal malignancies or precursor states should be referred to their physician. There is no case for alerting 'border-lint;' cases, such as those with minimal actinic keratoses oy scant atypical pigmented lesions, by screening campaigns. The ethical point also relates to the follow-up of those with positive screens. Provision for adequate follow-up and treatment is vitally important. First of all, the yield of screening needs to be evaluated in terms of histologicalh verified malignancies in ordt^r to justify continuation of the project. Secondly, inadequate follow-up may cause considerable harm to individual positive screenees. Information on compliance with referral or biopsy results is lacking in nearly ail early studies. Zagula-Mafly et al. reported that after 1 year only 17 of 43 positive screenees had visited their physician (40'^,,,).'' Systematic follow--up of positive screenees proved also to be relatively poor in the recent series reported by K'oh et af, foffow-up information with histology was available in only 63H,, of suspected cancer cases.'^ Bolognia et al. reported 78% clinical and histological follt)w-up for persons with positive screens for skin Cancer." Follow-up in our campaigns was more complete at 90%.^^ Other opportunities for tarly skin cancer/melanoma
SKIN CANCER/MELANOMA SCREENING
31
detection are public and professional education camscreening: A local cxpericnct:. Journal of the American Academy of paigns. This type of approach has been accomplished in Dermatology 1987; 16: 637 641. several areas in the United Kingdom, with dramatic 11. Hoiognia JL, Berwick M, Fine JA. Complete follow-up and evaluation of a skin cancer screening in Conniicticm. Journal of the effects on the number of persons referred for assessment of suspected skin cancer.^""" However, effects on pre- 12. American Academy of Dermatology 1990; 23: iO98 1106. Koh HK, C:aruso A, Gage 1 el al. Evaluation of melanoma/skin existing trends in thickness distribution of melanoma cancer screening in Massachusetts: Preliminary results. Cancer varied; whereas Doherty and MacKie claimed a signifi1990; 65: 375 379. cant rise in the proportion of thin melanomas,-^'* other 13. Biro L, Price E, Skin cancer; Screening in urban conmmnity. .\e!P York Slate Journal of Medtcine 1978; 78: 7.S3- 755, authors have been less enthusiastic.'•^'^•^' 14. Kob HK, Miller DR, Geller AC, Lew RA, Rampen FHJ. The This commentary does not address the subject of promise of screening for melanoma and other skin cancers. Clinics practicability of skin cancer/melanoma screening clinics. in Dermatology 1992 (in press), Advice about the setting up of screening programmes will 15. Wilson JMG, Jungner G, The principles and practice of screening for disease. Puhlir Health Papers, f^o. 34 Gcneva" depend on the infrastructure of the health system in a particular country and on the public, professional, and U). WlIO, 1968. Koh HK, Geller AC, Miller DR, Caruso A, Gage I, Lew RA, governmental attitudes towards screening for cancer. Will) is being screened for melanoma/skin cancer? Characteristics I'uture planning and evaluation of screening activities of persons screened in Massachusetts. Journal of the American necessitate close co-operation with epidemiologists with Academy ol Dermatology 1991; 24: 271- 277, 17, Silverberg E, Boring CX; Squires TS. Cancer stali.lics 1990 CA experience in this field. Skin cancer/melanoma is an important health problem. 18. 1990; 40: 9 26. Glass ACi, \ loover R \ . The emerging epidemic of melanoma and Incidence figures arc rising steeply.'^^^'''^ Theoretically, squamous cell skin VAncer. JAM A 1989; 262: 2097 2100. public and professional education and screening efforts 19. \\'einsti>ck MA. The epidemic of squamous cell carcinoma would result in a substantial reduction of the mortality of JAMA 1989; 262:2138-2140. cutaneous meianoma.^--^-"^ The AAD initiative to promote 20, Kopf A, Rigel D, Friedman R, The rising incidence and mortality rates of malignant melanoma. Journal of Dermalologie .Suri;ery and free skin-cancer screening clinics through the United Oncology 1982; 8: 760 761. States generates much puhlic and professional interest. 21. 0sterljnd A, Jensen OM. Trends in incidence of malignant Similar clinics may prove worthwhile in other countries melanoma of the sLm in Denmark 1943 1982. In: Ciallagher RP, as well, especially those with a predominantly white ed. r.pidemuilo!{y ojniali^nanl melanoma. Heidelberg- Springer\crlag, 1986: 8 17. population and with a high skin cancer/melanoma inciBreslow \. Thickness, cross-sectional area, and depth of invasion dence. Some knowledge of the principles of skin cancer/ in the prognosis of cutaneous melanoma. Annah ofSui-gery 1970melanoma screening should form part of the knowledge 172:902-908. base of all dermatologists. 23. Anonymous. Precursors to malignant melanoma: Consensus conference. 7_/4;.-f 1984; 251: !86^-1866. 24. Rhodes AR. Cjmgenital ne\i: Sbould these be excised- 74M 4 1989; 262: 1696.
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