Skin biopsy rates and incidence of melanoma: population based ecologic
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《英国医生杂志》
1 VA Outcomes Group, Department of Veterans Affairs Medical Center, White River Junction, VT 05009, USA
Correspondence to: H Gilbert Welch, Center for the Evaluative Clinical Sciences, Dartmouth Medical School, Hanover, NH 03755-1404, USA H.Gilbert.Welch@dartmouth.edu
Objectives To describe changes in skin biopsy rates and to determine their relation with changes in the incidence of melanoma.
Design Population based ecological study.
Setting Nine geographical areas of the United States.
Participants Participants of the Surveillance Epidemiology and End Results (SEER) programme aged 65 and older.
Main outcome measures For the period 1986 to 2001, annual skin biopsy rates for each surveillance area from Medicare claims and incidence rates for melanoma for the same population.
Results Between 1986 and 2001 the average biopsy rate across the nine participating areas increased 2.5-fold among people aged 65 and older (2847 to 7222 per 100 000 population). Over the same period the average incidence of melanoma increased 2.4-fold (45 to 108 per 100 000 population). Assuming that the occurrence of true disease was constant, the extra number of melanoma cases that were diagnosed after carrying out 1000 additional biopsies was 12.6 (95% confidence interval 11.2 to 14.0). After controlling for a potential increase in the true occurrence of disease, 1000 additional biopsies were still associated with 6.9 (3.1 to 10.8) extra melanoma cases diagnosed. Stage specific analyses suggested that 1000 biopsies were associated with 4.4 (2.1 to 6.8) extra cases of in situ melanoma diagnosed and 2.3 (0.0 to 4.6) extra cases of local melanoma, but not with the incidence of advanced melanoma. Mortality from melanoma changed little during the period.
Conclusion The incidence of melanoma is associated with biopsy rates. That the extra cases diagnosed were confined to early stage cancer while mortality remained stable suggests overdiagnosis—the increased incidence being largely the result of increased diagnostic scrutiny and not an increase in the incidence of disease.
The incidence of melanoma of the skin is rising faster than any other major cancer in the United States. In 2002—the most recent year of data—the incidence was about six times that in 1950.
Some dermatologists suggest that this rising incidence may be more apparent than real1–3 and acknowledge that diagnosis on the basis of histology is malleable; studies have shown that pathologists examining the same skin biopsy samples often disagree on the diagnosis of melanoma.4–6 Dermatologists argue that some lesions that appear malignant to pathologists are biologically benign—an idea supported by data showing that most of the increased incidence is confined to early stage disease.1 3 7 Finally, whenever physicians look more closely for melanoma, they find more cases.7–10
Population based data have not been reported on skin biopsies, the critical end point of surveillance. We examined data from Medicare, a nationwide health insurance for older Americans, to determine whether changes in the biopsy rate relate to the incidence of melanoma.
Methods
We used Medicare claims to obtain annual population based rates of skin biopsy for patients aged 65 and older in each of the nine geographical areas included in the US National Cancer Institute's Surveillance Epidemiology and End Results (SEER) programme from 1986 to 2001. We calculated the biopsy rates for each of 14 years (claims were unavailable for 1991 and 1992). To obtain the annual incidence of melanoma for the same population, we used the programme's statistical software (SEER*Stat, version 5.3.0).11 We obtained stage specific incidence rates using the surveillance programme's four histological disease stages (in situ, local, regional, and distant) and summed them to produce an incidence rate for all stages combined. Using SEER*Stat's incidence based mortality method we also calculated melanoma incidence and disease specific mortality for all nine geographical areas combined.
Analysis
We used multiple linear regression to explore the relation between biopsy rate (independent variable) and melanoma rate (dependent variable). The unit of analysis was the surveillance programme's area in an individual year (nine areas, 14 years, 126 observations). To control for regional differences that may affect incidence (for example, latitude, racial composition, practice style) we included an indicator variable for area in all analyses. Our baseline analysis predicts the effect of 1000 additional biopsies on the number of melanoma diagnoses. The implicit assumption is that the true occurrence of disease may differ across areas but that it does not change over time. Our second analysis predicts the effect of biopsy assuming the true occurrence of disease has increased. To do this we used interaction terms for year and area, which allow the incidence of melanoma in each area to increase independently—that is, to have its own slope. Finally, we carried out four stage specific regressions using the same interaction terms when the dependent variable was the incidence of a specific disease stage. All analyses were carried out using Stata 7.0 (see bmj.com for detailed model outputs).
Results
The incidence of melanoma in older people ( 65 years) in nine geographical areas of the US National Cancer Institute's Surveillance Epidemiology and End Results programme showed a steady, striking increase between 1986 and 2001 (fig 1). Most of the increase was in early stage disease (in situ and local) and not late stage disease (regional and distant). Mortality from melanoma changed little during the period.
Fig 1 Incidence of melanoma and mortality in population aged 65 and older residing in one of nine US areas participating in Surveillance Epidemiology and End Results programme, 1986-2001. Early stage refers to in situ and local disease; late stage refers to regional and distant disease
Relation between biopsy and incidence
Between 1986 and 2001 the average biopsy rate across the nine areas increased 2.5-fold, from 2847 to 7222 per 100 000 population. Over this time the average incidence of melanoma increased 2.4-fold, from 45 to 108 per 100 000 population. Figure 2 shows the annual skin biopsy rate and incidence of melanoma for each area during the 14 years, illustrating a positive linear relation.
Fig 2 Scatterplot of annual rate of skin biopsy and incidence of melanoma for residents age 65 and older in each of nine US areas participating in Surveillance Epidemiology and End Results programme, 1986-2001
Table 1 provides estimates for the extra number of cases of melanoma diagnosed in association with an additional 1000 biopsies. Assuming no change in the true occurrence of disease, an additional 1000 biopsies resulted in 12.6 (95% confidence interval 11.2 to 14.0) number of cases of melanoma. Assuming the true occurrence of disease increased, 1000 additional biopsies were associated with an extra 6.9 (3.1 to 10.8) cases of melanoma. Stage specific analyses suggested that 1000 biopsies were associated with 4.4 (2.1 to 6.8) extra cases of in situ melanoma and 2.3 (0.0 to 4.6) extra cases of local melanoma, but not with the incidence of advanced melanoma.
Table 1 Estimate of extra cases of melanoma diagnosed per 1000 additional biopsies by stage of disease
Discussion
Swerlick RA, Chen S. The melanoma epidemic: more apparent than real? Mayo Clin Proc 1997;72: 559-64.
Florez A, Cruces M. Melanoma epidemic: true or false? Int J Dermatol 2004;43: 405-7.
Beddingfield FC. The melanoma epidemic: res ipsa loquitur. Oncologist 2003;8: 459-65.
Farmer ER, Gonin R, Hanna MP. Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists. Hum Pathol 1996;27: 528-31.
Corona R, Mele A, Amini M, De Rosa G, Coppola G, Piccardi P, et al. Interobserver variability on the histopathologic diagnosis of cutaneous melanoma and other pigmented skin lesions. J Clin Oncol 1996;14: 1218-23.
Weinstock MA, Barnhill RL, Rhodes AR, Brodsky GL. Reliability of the histopathologic diagnosis of melanocytic dysplasia. Arch Dermatol 1997;133: 953-8.
Burton RC, Armstrong BK. Recent incidence trends imply a nonmetastasizing form of invasive melanoma. Melanoma Res 1994;4: 107-13.
Hiatt RA, Fireman B. The possible effect of increased surveillance on the incidence of malignant melanoma. Prev Med 1986;15: 652-60.
Burton RC, Coates MS, Hersey P, Roberts G, Chetty MP, Chen S, et al. An analysis of a melanoma epidemic. Int J Cancer 1993;55: 765-70.
Swerlick RA, Chen S. The melanoma epidemic. Is increased surveillance the solution or the problem? Arch Dermatol 1996;132: 881-4.
Surveillance research program. National Cancer Institute SEER*Stat software, version 5.3.0. www.seer.cancer.gov/seerstat (accessed 31 Aug 2004).
Sone S, Takashima S, Li F, Yang Z, Honda T, Maruyama Y, et al. Mass screening for lung cancer with mobile spiral computed tomography scanner. Lancet 1998;351: 1242-5.
Zahl PH, Strand BH, Maehlen J. Incidence of breast cancer in Norway and Sweden during introduction of nationwide screening: prospective cohort study. BMJ 2004;328: 921-4.
Spouge AR, Wilson SR, Wooley B. Abdominal sonography in asymptomatic executives: prevalence of pathologic findings, potential benefits, and problems. J Ultrasound Med 1996;15: 763-7.
Woods WG, Gao RN, Shuster JJ, Robison LL, Bernstein M, Weitzman S, et al. Screening of infants and mortality due to neuroblastoma. N Engl J Med 2002;346: 1041-6.
Schilling FH, Spix C, Berthold F, Erttmann R, Fehse N, Hero B, et al. Neuroblastoma screening at one year of age. N Engl J Med 2002;346: 1047-53.
Eskew LA, Bare RL, McCullough DL. Systematic 5 region prostate biopsy is superior to sextant method for diagnosing carcinoma of the prostate. J Urol 1997;157: 199-202.
Babaian RJ, Toi A, Kamoi K, Troncoso P, Sweet J, Evans R, et al. A comparative analysis of sextant and an extended 11-core multisite directed biopsy strategy. J Urol 2000;163: 152-7.
Arnold PM, Niemann TH, Bahnson RR. Extended sector biopsy for detection of carcinoma of the prostate. Urol Oncol 2001;6: 91-3.
Durkan GC, Sheikh N, Johnson P, Hildreth AJ, Greene DR. Improving prostate cancer detection with an extended-core transrectal ultrasonography-guided prostate biopsy protocol. Br J Urol Int 2002;89: 33-9.
Fleshner N, Klotz L. Role of "saturation biopsy" in the detection of prostate cancer among difficult diagnostic cases. Urology 2002;60: 93-7.(H Gilbert Welch, professor of medicine1,)
Correspondence to: H Gilbert Welch, Center for the Evaluative Clinical Sciences, Dartmouth Medical School, Hanover, NH 03755-1404, USA H.Gilbert.Welch@dartmouth.edu
Objectives To describe changes in skin biopsy rates and to determine their relation with changes in the incidence of melanoma.
Design Population based ecological study.
Setting Nine geographical areas of the United States.
Participants Participants of the Surveillance Epidemiology and End Results (SEER) programme aged 65 and older.
Main outcome measures For the period 1986 to 2001, annual skin biopsy rates for each surveillance area from Medicare claims and incidence rates for melanoma for the same population.
Results Between 1986 and 2001 the average biopsy rate across the nine participating areas increased 2.5-fold among people aged 65 and older (2847 to 7222 per 100 000 population). Over the same period the average incidence of melanoma increased 2.4-fold (45 to 108 per 100 000 population). Assuming that the occurrence of true disease was constant, the extra number of melanoma cases that were diagnosed after carrying out 1000 additional biopsies was 12.6 (95% confidence interval 11.2 to 14.0). After controlling for a potential increase in the true occurrence of disease, 1000 additional biopsies were still associated with 6.9 (3.1 to 10.8) extra melanoma cases diagnosed. Stage specific analyses suggested that 1000 biopsies were associated with 4.4 (2.1 to 6.8) extra cases of in situ melanoma diagnosed and 2.3 (0.0 to 4.6) extra cases of local melanoma, but not with the incidence of advanced melanoma. Mortality from melanoma changed little during the period.
Conclusion The incidence of melanoma is associated with biopsy rates. That the extra cases diagnosed were confined to early stage cancer while mortality remained stable suggests overdiagnosis—the increased incidence being largely the result of increased diagnostic scrutiny and not an increase in the incidence of disease.
The incidence of melanoma of the skin is rising faster than any other major cancer in the United States. In 2002—the most recent year of data—the incidence was about six times that in 1950.
Some dermatologists suggest that this rising incidence may be more apparent than real1–3 and acknowledge that diagnosis on the basis of histology is malleable; studies have shown that pathologists examining the same skin biopsy samples often disagree on the diagnosis of melanoma.4–6 Dermatologists argue that some lesions that appear malignant to pathologists are biologically benign—an idea supported by data showing that most of the increased incidence is confined to early stage disease.1 3 7 Finally, whenever physicians look more closely for melanoma, they find more cases.7–10
Population based data have not been reported on skin biopsies, the critical end point of surveillance. We examined data from Medicare, a nationwide health insurance for older Americans, to determine whether changes in the biopsy rate relate to the incidence of melanoma.
Methods
We used Medicare claims to obtain annual population based rates of skin biopsy for patients aged 65 and older in each of the nine geographical areas included in the US National Cancer Institute's Surveillance Epidemiology and End Results (SEER) programme from 1986 to 2001. We calculated the biopsy rates for each of 14 years (claims were unavailable for 1991 and 1992). To obtain the annual incidence of melanoma for the same population, we used the programme's statistical software (SEER*Stat, version 5.3.0).11 We obtained stage specific incidence rates using the surveillance programme's four histological disease stages (in situ, local, regional, and distant) and summed them to produce an incidence rate for all stages combined. Using SEER*Stat's incidence based mortality method we also calculated melanoma incidence and disease specific mortality for all nine geographical areas combined.
Analysis
We used multiple linear regression to explore the relation between biopsy rate (independent variable) and melanoma rate (dependent variable). The unit of analysis was the surveillance programme's area in an individual year (nine areas, 14 years, 126 observations). To control for regional differences that may affect incidence (for example, latitude, racial composition, practice style) we included an indicator variable for area in all analyses. Our baseline analysis predicts the effect of 1000 additional biopsies on the number of melanoma diagnoses. The implicit assumption is that the true occurrence of disease may differ across areas but that it does not change over time. Our second analysis predicts the effect of biopsy assuming the true occurrence of disease has increased. To do this we used interaction terms for year and area, which allow the incidence of melanoma in each area to increase independently—that is, to have its own slope. Finally, we carried out four stage specific regressions using the same interaction terms when the dependent variable was the incidence of a specific disease stage. All analyses were carried out using Stata 7.0 (see bmj.com for detailed model outputs).
Results
The incidence of melanoma in older people ( 65 years) in nine geographical areas of the US National Cancer Institute's Surveillance Epidemiology and End Results programme showed a steady, striking increase between 1986 and 2001 (fig 1). Most of the increase was in early stage disease (in situ and local) and not late stage disease (regional and distant). Mortality from melanoma changed little during the period.
Fig 1 Incidence of melanoma and mortality in population aged 65 and older residing in one of nine US areas participating in Surveillance Epidemiology and End Results programme, 1986-2001. Early stage refers to in situ and local disease; late stage refers to regional and distant disease
Relation between biopsy and incidence
Between 1986 and 2001 the average biopsy rate across the nine areas increased 2.5-fold, from 2847 to 7222 per 100 000 population. Over this time the average incidence of melanoma increased 2.4-fold, from 45 to 108 per 100 000 population. Figure 2 shows the annual skin biopsy rate and incidence of melanoma for each area during the 14 years, illustrating a positive linear relation.
Fig 2 Scatterplot of annual rate of skin biopsy and incidence of melanoma for residents age 65 and older in each of nine US areas participating in Surveillance Epidemiology and End Results programme, 1986-2001
Table 1 provides estimates for the extra number of cases of melanoma diagnosed in association with an additional 1000 biopsies. Assuming no change in the true occurrence of disease, an additional 1000 biopsies resulted in 12.6 (95% confidence interval 11.2 to 14.0) number of cases of melanoma. Assuming the true occurrence of disease increased, 1000 additional biopsies were associated with an extra 6.9 (3.1 to 10.8) cases of melanoma. Stage specific analyses suggested that 1000 biopsies were associated with 4.4 (2.1 to 6.8) extra cases of in situ melanoma and 2.3 (0.0 to 4.6) extra cases of local melanoma, but not with the incidence of advanced melanoma.
Table 1 Estimate of extra cases of melanoma diagnosed per 1000 additional biopsies by stage of disease
Discussion
Swerlick RA, Chen S. The melanoma epidemic: more apparent than real? Mayo Clin Proc 1997;72: 559-64.
Florez A, Cruces M. Melanoma epidemic: true or false? Int J Dermatol 2004;43: 405-7.
Beddingfield FC. The melanoma epidemic: res ipsa loquitur. Oncologist 2003;8: 459-65.
Farmer ER, Gonin R, Hanna MP. Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists. Hum Pathol 1996;27: 528-31.
Corona R, Mele A, Amini M, De Rosa G, Coppola G, Piccardi P, et al. Interobserver variability on the histopathologic diagnosis of cutaneous melanoma and other pigmented skin lesions. J Clin Oncol 1996;14: 1218-23.
Weinstock MA, Barnhill RL, Rhodes AR, Brodsky GL. Reliability of the histopathologic diagnosis of melanocytic dysplasia. Arch Dermatol 1997;133: 953-8.
Burton RC, Armstrong BK. Recent incidence trends imply a nonmetastasizing form of invasive melanoma. Melanoma Res 1994;4: 107-13.
Hiatt RA, Fireman B. The possible effect of increased surveillance on the incidence of malignant melanoma. Prev Med 1986;15: 652-60.
Burton RC, Coates MS, Hersey P, Roberts G, Chetty MP, Chen S, et al. An analysis of a melanoma epidemic. Int J Cancer 1993;55: 765-70.
Swerlick RA, Chen S. The melanoma epidemic. Is increased surveillance the solution or the problem? Arch Dermatol 1996;132: 881-4.
Surveillance research program. National Cancer Institute SEER*Stat software, version 5.3.0. www.seer.cancer.gov/seerstat (accessed 31 Aug 2004).
Sone S, Takashima S, Li F, Yang Z, Honda T, Maruyama Y, et al. Mass screening for lung cancer with mobile spiral computed tomography scanner. Lancet 1998;351: 1242-5.
Zahl PH, Strand BH, Maehlen J. Incidence of breast cancer in Norway and Sweden during introduction of nationwide screening: prospective cohort study. BMJ 2004;328: 921-4.
Spouge AR, Wilson SR, Wooley B. Abdominal sonography in asymptomatic executives: prevalence of pathologic findings, potential benefits, and problems. J Ultrasound Med 1996;15: 763-7.
Woods WG, Gao RN, Shuster JJ, Robison LL, Bernstein M, Weitzman S, et al. Screening of infants and mortality due to neuroblastoma. N Engl J Med 2002;346: 1041-6.
Schilling FH, Spix C, Berthold F, Erttmann R, Fehse N, Hero B, et al. Neuroblastoma screening at one year of age. N Engl J Med 2002;346: 1047-53.
Eskew LA, Bare RL, McCullough DL. Systematic 5 region prostate biopsy is superior to sextant method for diagnosing carcinoma of the prostate. J Urol 1997;157: 199-202.
Babaian RJ, Toi A, Kamoi K, Troncoso P, Sweet J, Evans R, et al. A comparative analysis of sextant and an extended 11-core multisite directed biopsy strategy. J Urol 2000;163: 152-7.
Arnold PM, Niemann TH, Bahnson RR. Extended sector biopsy for detection of carcinoma of the prostate. Urol Oncol 2001;6: 91-3.
Durkan GC, Sheikh N, Johnson P, Hildreth AJ, Greene DR. Improving prostate cancer detection with an extended-core transrectal ultrasonography-guided prostate biopsy protocol. Br J Urol Int 2002;89: 33-9.
Fleshner N, Klotz L. Role of "saturation biopsy" in the detection of prostate cancer among difficult diagnostic cases. Urology 2002;60: 93-7.(H Gilbert Welch, professor of medicine1,)