Malignant Melanoma: Incidence Issues and Their Effect on Diagnosis and Treatment in the 1990s

The incidence of melanoma is increasing at a rate faster than that for any other cancer in the United States and worldwide. Several factors show that this increase in incidence is real and not due to artifact. The rapid increase is not attributable to better overall counting of the cases of cancer (because the incidence of other cancers is decreasing). Furthermore, it is not due to changes in histologie criteria. Finally, the mortality rate from melanoma continues to increase at a time when survival rates are also increasing. This apparent paradox can be true only if the actual incidence is increasing at an even faster rate than the death rate. This dramatic increase in the incidence of melanoma highlights the need for improved methods of prevention, diagnosis, and treatment as melanoma becomes increasingly important as a public health issue. The incidence of melanoma is increasing at a rate faster than that for any other cancer in the United States and worldwide. Several factors show that this increase in incidence is real and not due to artifact. The rapid increase is not attributable to better overall counting of the cases of cancer (because the incidence of other cancers is decreasing). Furthermore, it is not due to changes in histologie criteria. Finally, the mortality rate from melanoma continues to increase at a time when survival rates are also increasing. This apparent paradox can be true only if the actual incidence is increasing at an even faster rate than the death rate. This dramatic increase in the incidence of melanoma highlights the need for improved methods of prevention, diagnosis, and treatment as melanoma becomes increasingly important as a public health issue. Increasingly, malignant melanoma is becoming a more important public health problem in the United States and worldwide. Investigators have estimated that, in 1997 alone, compiled statistics will show 40,300 new invasive cases of this tumor in the United States’ and another 30,000 to 50,000 diagnoses of in situ lesions.2Salopek TG Marghoob AA Slade JM Rao B Rigel DS Kopf AW et al.An estimate of the incidence of malignant melanoma in the United States: based on a survey of members of the American Academy of Dermatology.Dermatol Surg. 1995; 21: 301-305Crossref PubMed Scopus (37) Google Scholar Currently, malignant melanoma is the fifth most frequently occurring cancer in the United States. Of more importance, 7,300 deaths from this cancer were predicted to occur in US citizens during 1997.1Parker SL Tong T Bolden S Wingo PA Cancer statistics, 1996.CA Cancer J Clin. 1996; 46: 5-27Crossref PubMed Scopus (1971) Google Scholar The incidence for melanoma is increasing faster than for any other cancer in the United States.3Rigel DS Friedman RJ Kopf AW The incidence of malignant melanoma in the United States: issues as we approach the 21st century.J Am Acad Dermatol. 1996; 34: 839-847Abstract Full Text PDF PubMed Scopus (332) Google Scholar In 1980, the risk for development of melanoma was estimated at 1 in every 250 US citizens during their lifetime (increased from 1 in 1,500 in 1935).4Kopf AW Rigel DS Friedman RJ The rising incidence and mortality rate of malignant melanoma.J Dermatol Surg Oncol. 1982; 8: 760-761Crossref PubMed Scopus (102) Google Scholar That risk increased to 1 in 150 by 19855Rigel DS Kopf AW Friedman RJ The rate of malignant melanoma in the United States: are we making an impact?.J Am Acad Dermatol. 1987; 17: 1050-1053Abstract Full Text PDF PubMed Scopus (131) Google Scholar and reached 1 in 87 in 1996 (Fig. 1).3Rigel DS Friedman RJ Kopf AW The incidence of malignant melanoma in the United States: issues as we approach the 21st century.J Am Acad Dermatol. 1996; 34: 839-847Abstract Full Text PDF PubMed Scopus (332) Google Scholar The 1997 estimated lifetime risk for development of melanoma among Americans is 1 in 84. The risk in the highest race- and sex-specific group, white males, is now at 1 in 70.3Rigel DS Friedman RJ Kopf AW The incidence of malignant melanoma in the United States: issues as we approach the 21st century.J Am Acad Dermatol. 1996; 34: 839-847Abstract Full Text PDF PubMed Scopus (332) Google Scholar A review of melanoma incidence and mortality data since the 1950s shows a consistent 6% annual increase in incidence and a 2% annual increase in mortality (Fig. 2).Fig. 2Incidence and mortality rate of melanoma in the United States, 1950 through 1996.View Large Image Figure ViewerDownload (PPT) Several factors clearly demonstrate that this increase in incidence is, in fact, real and not due to exogenous or endogenous artifact. 1.The rapid increase in incidence is not due to improved awareness and surveillance. The public's knowlege of the problem of melanoma in the United States has increased dramatically. This enhanced awareness has occurred especially during the past decade in conjunction with programs such as the skin cancer screenings conducted by the American Academy of Dermatology. If, however, this increase was merely due to earlier diagnosis and the actual number of cases was not increasing, a subsequent decrease in incidence would be expected as these cases were removed from the population pool. In fact, no such decrease has occurred.2.Better methods of counting cases of cancer, in general, are not causing an increase in incidence. Melanoma is one of the few major cancers not classified as a reportable condition in most jurisdictions.6Melia J Frost T Graham-Brown R Hunter J Marsden A du Vivier A et al.Problems with registration of cutaneous malignant melanoma in England.BrJ Cancer. 1995; 72: 224-228Crossref PubMed Scopus (35) Google Scholar Consequently, the actual incidence of melanoma is probably greater than that reported.2Salopek TG Marghoob AA Slade JM Rao B Rigel DS Kopf AW et al.An estimate of the incidence of malignant melanoma in the United States: based on a survey of members of the American Academy of Dermatology.Dermatol Surg. 1995; 21: 301-305Crossref PubMed Scopus (37) Google Scholar, 7Roberts DL Accuracy of local data on skin cancer: skin cancer registry data may greatly underestimate cases [letter].BMJ. 1995; 310: 1327Crossref PubMed Scopus (3) Google Scholar Because hospital tumor registries are the primary source of cancer statistics, the fact that an increasing number of melanomas are being treated in an outpatient setting (and biopsy specimens are not being sent to a hospital-based pathology laboratory) will result in an even greater magnitude of undercounting of this tumor in the future.8Koh HK Clapp RW Barnett JM Nannery WM Tahan SR Geller AC et al.Systematic underreporting of cutaneous malignant melanoma in Massachusetts: possible impücations for national incidence figures.J Am Acad Dermatol. 1991; 24: 545-550Abstract Full Text PDF PubMed Scopus (52) Google Scholar If better cancer counting methods, in general, were causing the increased number of melanomas, an increased number of all cancers would be expected. The incidence of melanoma is increasing faster than that for any other cancer (highest in men and second only to lung cancer in women) at a time when the incidence of many other cancers, such as stomach, gallbladder, and cervical cancer, is decreasing.9Devesa SS Silverman DT Young Jr, JL Pollack ES Brown CC Horm JW et al.Cancer incidence and mortality trends among whites in the United States, 1947-84.J Nati Cancer Inst. 1987; 79: 701-770PubMed Google Scholar 3. Changing histologie criteria are not causing an artificial increase in incidence. The histopathologic criteria for diagnosing melanoma have evolved over time. Despite this, studies that have reviewed pigmented lesions histologically diagnosed in the past have shown that the effects of these alterations in criteria are minimal and cannot explain the current increase in the incidence of melanoma.10Wender RC Barriers to effective skin cancer detection.Cancer. 1995; 75: 691-698Crossref PubMed Scopus (41) Google Scholar, 11van der Esch EP Muir CS Nectoux J Macfarlane G Maisonneuve P Bharucha H et al.Temporal change in diagnostic criteria as a cause of the increase of malignant melanoma over time is unlikely.Int J Cancer. 1991; 47: 483-489Crossref PubMed Scopus (90) Google Scholar 4. The death rate from melanoma continues to increase. A decreasing mean thickness of melanomas at the time of diagnosis12Balch CM Soong JS Shaw HM Urist MM McCarthy WH An analysis of prognostic factors in 8500 patients with cutaneous melanoma.in: Balch CM Houghton AN Milton GW Sober AJ Soong SJ Cutaneous Melanoma. 2nd ed. Lippincott, Philadelphia1992: 165-187Google Scholar has resulted in an overall increased survival for persons with localized melanoma—from 50% in the 1950s to almost 90% today.1Parker SL Tong T Bolden S Wingo PA Cancer statistics, 1996.CA Cancer J Clin. 1996; 46: 5-27Crossref PubMed Scopus (1971) Google Scholar This trend has also led some investigators to suggest that the increasing incidence of melanoma could be explained by the diagnosis of more very thin “non-lethal” melanomas that, in the past, would not have manifested as early in their progression; thus, the associated risk of mortality may be less. In fact, the absolute number of thicker melanomas is also increasing.13Herd RM Cooper EJ Hunter JA McLaren K Chetty U Watson AC et al.Cutaneous malignant melanoma: publicity, screening clinics and survival-the Edinburgh experience 1982-90.BrJDermatol. 1995; 132: 563-570Google Scholar, 14Burton RC Coates MS Hersey P Roberts G Chetty MP Chen S et al.An analysis of a melanoma epidemic.Int J Cancer. 1993; 55: 765-770Crossref PubMed Scopus (103) Google Scholar Despite the improved survival percentage, the mortality rate from melanoma also continues to increase. The only explanation for an increasing death rate from melanoma (especially in light of diagnosis of an increasing percentage of lesions associated with a more favorable prognosis) is an even faster paced increasing incidence (Fig. 2).3Rigel DS Friedman RJ Kopf AW The incidence of malignant melanoma in the United States: issues as we approach the 21st century.J Am Acad Dermatol. 1996; 34: 839-847Abstract Full Text PDF PubMed Scopus (332) Google Scholar The increasing incidence of melanoma has major implications for the diagnosis and management of this tumor. Identification of a high-risk subset of the population helps to focus educational messages and to increase the awareness of physicians for lesions in persons likely to be at risk. Numerous factors have been suggested to influence the risk of development of malignant melanoma. In an analysis of 43 potential risk factors in 200 patients with malignant melanoma in comparison with control subjects,15Rigel DS Identification of those at highest risk for development of malignant melanoma.Adv Dermatol. 1995; 10: 151-170PubMed Google Scholar 6 key factors were noted to influence the risk of melanoma: (1) red or blond hair, (2) family history of malignant melanoma, (3) actinic kératoses, (4) considerable freckling on the upper back area, (5) three or more blistering sunburns before the age of 20 years, and (6) 3 or more years of outdoor summer jobs during the teenage years. The presence of any one or two of these factors increased a person's risk for the development of malignant melanoma 3- to 4-fold, and three or more of these factors increased the risk almost 20-fold. With this model, a high-risk subset of the population can easily be identified clinically so that educational and surveillance efforts can be directed effectively. The cornerstone of management of malignant melanoma is early diagnosis, which leads to treatment at a curable stage. Thus, currently, diagnostic efforts are focused on early diagnosis. With that in mind, in 1984, the New York University Melanoma Cooperative Group16Friedman RJ Rigel DS Silverman MK Kopf AW Vossaert KA Malignant melanoma in the 1990s: the continued importance of early detection and the role of physician examination and self-examination of the skin.CA Cancer J Clin. 1991; 41: 201-226Crossref PubMed Scopus (187) Google Scholar developed the A, B, C, and D rules for recognition of early malignant melanoma (Table 1).Table 1A, B, C, and D Guidelines for Recognition of Early Malignant Melanoma*Established by the New York University Melanoma Cooperative Group.16FactorDescriptionAsymmetryOne side of the lesion differs from the other sideBorder irregularityThe border of the lesion is irregular or indistinctColor variegationThe lesion has variegated shades of brownDiameterThe diameter of the lesion is >6 mm (¼ in)* Established by the New York University Melanoma Cooperative Group.16Friedman RJ Rigel DS Silverman MK Kopf AW Vossaert KA Malignant melanoma in the 1990s: the continued importance of early detection and the role of physician examination and self-examination of the skin.CA Cancer J Clin. 1991; 41: 201-226Crossref PubMed Scopus (187) Google Scholar Open table in a new tab Diagnostic methods that involve inspection alone are about 60 to 80% effective in identifying malignant melanoma. Several other techniques can be used to augment these results. A baseline full-body photographic series for follow-up of patients with atypical moles (persons who are at higher risk for malignant melanoma) is helpful.17Slue W Kopf AW Rivers JK Total-body photographs of dysplastic nevi.Arch Dermatol. 1988; 124: 1239-1243Crossref PubMed Scopus (82) Google Scholar In a patient with many pigmented lesions, epiluminescence microscopy (dermoscopy) may be useful for identifying the most likely suspicious lesion for biopsy and histopathologic evaluation.18Binder M Schwarz M Winkler A Steiner A Kaider A Wolff K et al.Epiluminescence microscopy: a useful tool for the diagnosis of pigmented skin lesions for formally trained dermatologists.Arch Dermatol. 1995; 131: 286-291Crossref PubMed Scopus (445) Google Scholar In addition, new computer-based image analysis algorithms have the potential for substantially improving diagnostic accuracy.19Green A Martin N Pfitzner J O'Rourke M Knight N Computer image analysis in the diagnosis of melanoma.J Am Acad Dermatol. 1994; 31: 958-964Abstract Full Text PDF PubMed Scopus (149) Google Scholar Malignant melanoma is a potentially lethal cancer, but it is not uniformly fatal. The factor that best predicts survival in patients with malignant melanoma is the thickness of the primary lesion. Almost all persons with lesions less than 0.75 mm thick survive, whereas only 50% of those with lesions thicker than 3 mm survive.16Friedman RJ Rigel DS Silverman MK Kopf AW Vossaert KA Malignant melanoma in the 1990s: the continued importance of early detection and the role of physician examination and self-examination of the skin.CA Cancer J Clin. 1991; 41: 201-226Crossref PubMed Scopus (187) Google Scholar Multivariate analysis indicates that other factors, including clinical stage, anatomic site, and ulcération, have prognostic significance.20Rigel DS Rogers GS Friedman RJ Prognosis of malignant melanoma.Dermatol Clin. 1985 Apr; 3: 309-314PubMed Google Scholar Other studies have suggested that age, sex, level of invasion, and mitotic activity influence survival. Newer data suggest that immunologie factors21Clark Jr, WH Elder DE Guerry IV, D Braitman LE Trock BJ Schultz D et al.Model predicting survival in stage I melanoma based on tumor progression.J Nati Cancer Inst. 1989; 81: 1893-1904Crossref PubMed Scopus (1026) Google Scholar and tumor volume22Friedman RJ Rigel DS Kopf AW Grin CM Heilman E Bart RS et al.Volume of malignant melanoma is superior to thickness as a prognostic indicator: preliminary observation.Dermatol Clin. 1991 Oct; 9: 643-648PubMed Google Scholar may be better predictors of survival than the aforementioned variables. Initially, treatment of melanoma relies on biopsy and histopathologic evaluation of the suspicious lesion.23Salopek TG Slade JM Marghoob AA Rigel DS Kopf AW Bart RS et al.Management of cutaneous malignant melanoma by dermatologists of the American Academy of Dermatology. I. Survey of biopsy practices of pigmented lesions suspected as melanoma.J Am Acad Dermatol. 1995; 33: 441-450Abstract Full Text PDF PubMed Scopus (30) Google Scholar Although transection of a pigmented lesion at the time of biopsy has been shown not to affect survival adversely,24Lederman JS Sober AJ Does wide excision as the initial diagnostic procedure improve prognosis in patients with cutaneous melanoma?.J Dermatol Surg Oncol. 1986; 12: 697-699Crossref PubMed Scopus (20) Google Scholar removal by conservative excision for histopathologic evaluation is still the method of choice. Excisional biopsy allows comprehensive pathologic review of the important histologie factors, such as thickness and ulcération, that directly affect prognosis. After the diagnosis of melanoma has been confirmed, the lesion is removed with a definitive surgical excision. The most appropriate margins for effective removal of this cancer have been a controversial issue. The 1992 National Institutes of Health consensus conference report on early melanoma25NIH Consensus Development Panel on Early Melanoma Diagnosis and treatment of early melanoma.JAMA. 1992; 268: 1314-1319Crossref PubMed Scopus (319) Google Scholar recommended that in situ melanoma be removed with clinical margins of 0.5 cm. Invasive lesions up to 1 mm in depth should be removed with clinical margins of 1 cm.26Veronesi U Cascinelli N Narrow excision (1-cm margin): a safe procedure for thin cutaneous melanoma.Arch Surg. 1991; 126: 438-441Crossref PubMed Scopus (417) Google Scholar Surgical margins for excision of more advanced melanoma are also intended to minimize the chance of local recurrence and to maximize the probability of effective removal. Although the approach may vary somewhat, margins of 2 to 3 cm are usually recommended for lesions more than 1 mm thick. Lymph node dissection for patients with melanoma is also a controversial issue.27Lyons III, JH Cockerell CJ Elective lymph node dissection for melanoma.J Am Acad Dermatol. 1994; 30: 467-480Abstract Full Text PDF PubMed Scopus (15) Google Scholar The rationale for this procedure is that with expeditious removal, spread of the melanoma can be curtailed at the lymph nodes. Patients with clinically palpable regional nodes should undergo a therapeutic node dissection, even though their prognosis is poor (5-year survival, less than 20%). The efficacy of elective regional lymph node dissection (ERLND) is also questioned.27Lyons III, JH Cockerell CJ Elective lymph node dissection for melanoma.J Am Acad Dermatol. 1994; 30: 467-480Abstract Full Text PDF PubMed Scopus (15) Google Scholar In addition to limiting spread of the melanoma, ERLND can provide staging and may improve survival in patients with lesions of the however, can cause with and can increase and may not improve survival. In a New York University series of patients with melanomas to mm thick who ERLND nodes histologically for tumor. In addition, the of is not better of is G D R et and of melanoma regional invasive for the diagnosis of Surg. 1995; Google Scholar This that is the of the melanoma. This through the to the can also be with this the of the node biopsy has been JL et role of in the management of patients with malignant melanoma.Dermatol Surg. 1995; 21: Google Scholar The node can be identified by of a at the of the melanoma. The is up by the and through to the regional nodes. The initial node that becomes removed for Early studies have shown that if no tumor is in the dissection may not be DL R A and cervical for melanomas of the and 1993; Google Scholar Newer studies suggest that the can be with a to that used in for better of the Currently, no is effective as a consistent for melanoma that has spread the regional nodes. of and have been in patients with advanced melanoma, and the best rates have been less than GS for malignant 1995; PubMed Scopus Google Scholar, Jr, RJ et of in high-risk cutaneous melanoma: a Nati Cancer Inst. 1995; PubMed Scopus Google Scholar, M G et for in malignant J Surg. 1995; PubMed Scopus Google Scholar Of these the most The is to a melanoma to the initial of the tumor in high-risk activity of a melanoma Cancer 1995; PubMed Scopus Google Scholar treatment for melanoma are in Guidelines for by thickness margins lymph node with with with with with with Open table in a new tab The risk of recurrence of melanoma is a of tumor thickness and other prognostic variables. a second primary melanoma in of patients who have an initial melanoma. this lifetime follow-up of patients with melanoma is CM Kopf AW Bart RS for patients with stage I malignant melanoma.J Dermatol Surg Oncol. 1994; PubMed Scopus (35) Google Scholar suggested follow-up are in of for Patients With by CM Kopf AW Bart RS for patients with stage I malignant melanoma.J Dermatol Surg Oncol. 1994; PubMed Scopus (35) Google thickness of follow-up in of follow-up in Open table in a new tab The most important of a follow-up is a cutaneous and lymph node are in patients with melanomas more than 1 mm Consensus Development Panel on Early Melanoma Diagnosis and treatment of early melanoma.JAMA. 1992; 268: 1314-1319Crossref PubMed Scopus (319) Google Scholar for are in for Patients With by thickness of 6 for and Open table in a new tab The rapid increase in the incidence of melanoma has major implications in of the enhanced clinical that will be for management of this cancer in the in and new for the management of will increasingly be a for advanced melanoma, however, early diagnosis and treatment will to be the cornerstone for this