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  Vol. 281 No. 17, May 5, 1999 TABLE OF CONTENTS
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Rising Incidence of Renal Cell Cancer in the United States

Wong-Ho Chow, PhD; Susan S. Devesa, PhD; Joan L. Warren, PhD; Joseph F. Fraumeni, Jr, MD

JAMA. 1999;281:1628-1631.

ABSTRACT

Context  Clinical surveys have revealed that incidental detection of renal cell carcinoma is rising because of increased use of imaging procedures.

Objective  To examine incidence, mortality, and survival trends of renal cell and renal pelvis cancers by age, sex, race, and tumor stage at diagnosis.

Design  Calculation of age-adjusted incidence and mortality rates, along with 5-year relative survival rates, using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program.

Setting and Participants  Patients diagnosed as having kidney cancer from 1975 through 1995 in the 9 geographic areas covered by tumor registries in the SEER program, which represent about 10% of the US population.

Main Outcome Measures  Incidence, mortality, and 5-year relative survival rates by time periods.

Results  The age-adjusted incidence rates for renal cell carcinoma between 1975 and 1995 for white men, white women, black men, and black women were 9.6, 4.4, 11.1, and 4.9 per 100,000 person-years, respectively. The corresponding rates for renal pelvis cancer were 1.5, 0.7, 0.8, and 0.5 per 100,000 person-years. Renal cell cancer incidence rates increased steadily between 1975 and 1995, by 2.3% annually among white men, 3.1% among white women, 3.9% among black men, and 4.3% among black women. Increases were greatest for localized tumors but were also seen for more advanced and unstaged tumors. In contrast, the incidence rates for renal pelvis cancer declined among white men and remained stable among white women and blacks. Although 5-year relative survival rates for patients with renal cell cancer improved among whites but not among blacks, kidney cancer mortality rates increased in all race and sex groups.

Conclusions  Increasing detection of presymptomatic tumors by imaging procedures, such as ultrasonography, computed tomography, and magnetic resonance imaging, does not fully explain the upward incidence trends of renal cell carcinoma. Other factors may be contributing to the rapidly increasing incidence of renal cell cancer in the United States, particularly among blacks.



INTRODUCTION
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Malignant tumors of the kidney account for more than 2% of cancer incidence and mortality in the United States, with nearly 30,000 new cases and 12,000 deaths estimated for 1998.1 More than 80% of kidney cancers arise in the renal parenchyma, with the remainder in the renal pelvis.2 Nearly all kidney cancers originating in the renal parenchyma are adenocarcinomas (renal cell carcinomas), whereas the vast majority of renal pelvis cancers are transitional cell carcinomas.

Recent clinical surveys have revealed that incidental detection of renal cell carcinomas is rising, partly because of increased use of imaging procedures, such as ultrasonography, computed tomography, and magnetic resonance imaging (MRI).3-5 This observation is consistent with epidemiological data from the United States and other countries suggesting that renal cell cancer may be on the rise.2, 6 To further clarify these trends, we examined the incidence, mortality, and survival data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. For comparison, we also analyzed trends for renal pelvis cancer.


METHODS
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Persons diagnosed as having kidney cancer from 1975 through 1995 were identified from 9 population-based cancer registries in the SEER program.7 The registries, accounting for approximately 10% of the US population, are located in the states of Connecticut, Hawaii, Iowa, New Mexico, and Utah, as well as the San Francisco–Oakland, Calif, Seattle–Puget Sound, Wash, Detroit, Mich, and Atlanta, Ga, metropolitan areas.

The study included microscopically confirmed cases of invasive cancers of the kidney parenchyma or kidney, not otherwise specified (International Classification of Diseases for Oncology, Second Edition8 [ICDO-2] site code C64.9) and renal pelvis (ICDO-2 site code C65.9), excluding nonepithelial tumors (ie, melanomas, sarcomas, and lymphomas). The proportion of cases microscopically confirmed was more than 90% and varied little during the study period. Cases with racial origin other than black or white were excluded because their numbers were too small for detailed analysis.

For analysis, cancer cases with anatomical site coded as kidney, not otherwise specified, and histological codes of transitional cell, squamous cell, or other papillary carcinomas (ICDO-2 morphology codes 8050-8130) were recoded to renal pelvis cancer. The cases were classified by age (in 5-year age groups up to >85 years), sex, and race. Incidence rates were calculated by summing the number of cases diagnosed during each 3-year period from 1975-1977 to 1993-1995, dividing by the sum of the corresponding midyear population estimates provided by SEER, and multiplying by 100,000 (ie, per 100,000 person-years). Rates were age-adjusted to the 1970 US population using direct adjustment. Trends in incidence rates were evaluated for the seven 3-year periods, along with annual US mortality rates from 1975 to 1995. Figures were prepared by plotting the rates at the midpoint of each 3-year interval on the x-axis and using a logarithm scale for the y-axis so rates of change could be compared visually.9


RESULTS
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From 1975 to 1995, there were 31,105 invasive cancers of the renal parenchyma and/or kidney, not otherwise specified, and 4985 cancers of the renal pelvis diagnosed among whites and blacks in the 9 SEER study areas. During the study period, the age-adjusted incidence rates for renal cell cancer among white men and women were lower than those among black men and women, with rates of 9.6, 4.4, 11.1, and 4.9 per 100,000 person-years, respectively. The corresponding rates per 100,000 person-years were 1.5, 0.7, 0.8, and 0.5 for renal pelvis cancer, respectively. In contrast with renal cell cancer, incidence rates for renal pelvis cancer were higher among whites than blacks.

Renal cell cancer incidence rates increased between 1975-1977 and 1993-1995 by 2.3% annually among white men, 3.1% among white women, 3.9% among black men, and 4.3% among black women (Figure 1). Since the mid-1980s, the incidence rates for blacks have surpassed those for whites in both sexes. The increases in renal cell cancer incidence have occurred in all age groups (data not shown). In contrast, the incidence rate for renal pelvis cancer has declined slightly among white men and remained stable among white women. The numbers of renal pelvis cancer among blacks were too small for stable estimates of trends.



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Figure 1. Age-Adjusted (1970 US Standard) Incidence Rates for Renal Cell Carcinoma and Renal Pelvis Carcinoma Per 100,000 Person-Years by Sex and Race—SEER, 1975-1977 to 1993-1995

SEER indicates Surveillance, Epidemiology, and End Results program.


The greatest increase in renal cell cancer incidence rates occurred for localized tumors, rising annually by 3.8% among white men, 4.7% among white women, 5.0% among black men, and 5.6% among black women (Figure 2). However, rates for more advanced tumors, including those with regional extension and distant metastasis, as well as unstaged tumors, also showed increases in all race and sex groups.



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Figure 2. Age-Adjusted (1970 US Standard) Incidence Rates Per 100,000 Person-Years for Renal Cell Carcinoma by Sex, Race, and Tumor Stage at Diagnosis—SEER, 1975-1977 to 1993-1995

SEER indicates Surveillance, Epidemiology, and End Results program.


In addition, mortality rates for kidney cancer (subsite specification unavailable) rose between 1975 and 1995 (Figure 3). The increases were more rapid among blacks than whites, consistent with the upward incidence trends and the lack of improvement in survival rates for renal cell cancer among blacks (Table 1). In contrast, the 5-year relative survival rates for whites generally improved over time. For renal pelvis cancer, the 5-year relative survival rate declined slightly over time among whites, while the survival trend among blacks was unstable due to small numbers.



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Figure 3. Age-Adjusted (1970 US Standard) Kidney Cancer Mortality Rates by Sex and Race—United States, 1975-1995



View this table:
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Table. Relative 5-Year Survival Percentage Rate for Patients With Renal Cell Carcinoma or Renal Pelvis Carcinoma by Sex, Race, and Time Period—SEER, 1975-1995*



COMMENT
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It has been shown that incidental detection of renal cell carcinoma has risen with increased use of imaging procedures, such as ultrasonography, computed tomography, and MRI.3-5 Based on our analysis of unpublished data from the Health Care Financing Administration, the use of abdominal or pelvic computed tomography scans or MRI increased steadily from 2622 to 4536 per 100,000 Medicare beneficiaries between 1986 and 1994, a 73% rise during this period. The incidence trends by tumor stage suggest an effect of early detection because the increases in renal cell cancer were most pronounced for localized tumors. However, upward trends were also apparent for more advanced and unstaged tumors. This pattern, along with an increase in the mortality rates for kidney cancer, suggests that the detection of presymptomatic tumors cannot fully explain the rising incidence of renal cell carcinoma.

We considered the possibility that improvements in subsite specification for kidney cancers may have contributed to the rising incidence of renal cell cancer. This explanation seems unlikely because renal pelvis cancer declined only among white men and the magnitude of change could not have compensated for the increase in renal cell cancer in all race and sex groups. Furthermore, tumor classification also was based on histology, and microscopic confirmation surpassed 90% and changed little over time.

Reasons for the racial disparity in incidence and mortality trends, with more rapid increases among blacks than whites, are not entirely clear. Obesity and hypertension are established risk factors for renal cell cancer10-12 and are more prevalent among blacks than whites in the United States.13-14 However, the upward trends in the prevalence of obesity have varied little among race and sex groups.13 In addition, the prevalence of hypertension has remained stable since the 1960s,14 although the number and variety of antihypertensive prescriptions have risen steadily in recent decades.15-16 While black-white differences exist in the incidence and prognosis of hypertension and patterns and effectiveness of therapy,17-20 there are few data available by race on trends in the use of diuretics and other antihypertensive drugs, which has been related in some studies to the risk of renal cell cancer.10 Smoking is also an established risk factor for renal cell cancer, but the prevalence of smoking has declined since the mid-1960s.21 However, given the long latency of tumor development and the possibility of difference in smoking behavior for those who have not quit, the upward smoking prevalence in earlier decades might have contributed to the continuing increases in renal cell cancer, particularly at older ages.

The declining incidence of renal pelvis cancer among white men and relatively stable trends among white women and blacks may be explained in part by the decreasing prevalence of 2 major risk factors, cigarette smoking and the use of phenacetin-containing analgesics.10 The diverse incidence trends for renal pelvis and renal cell cancers underscore the importance of distinguishing between these types of tumors in future descriptive and analytical epidemiological studies.

In summary, the rapidly rising incidence of renal cell cancer in the United States may be due in part to the increasing detection of presymptomatic tumors, but a real increase is suggested by the upward incidence trend for more advanced tumors and by a corresponding increase in kidney cancer mortality. The increases in incidence and mortality have been greater among blacks than whites, providing clues for further research into the causes and prevention of these tumors.


AUTHOR INFORMATION
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Acknowledgment: The authors appreciate the sustained high-quality registry operations of the SEER program participants, the dedication of the National Cancer Institute SEER staff, and the computer programming and figure development by John Lahey of IMS Inc, Rockville, Md.

Corresponding Author: Wong-Ho Chow, PhD, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, EPS 8100, Bethesda, MD 20892-7240 (e-mail: choww{at}exchange.nih.gov).

Author Affiliations: Division of Cancer Epidemiology and Genetics (Drs Chow, Devesa, and Fraumeni), and the Division of Cancer Control and Population Sciences (Dr Warren), National Cancer Institute, Bethesda, Md.


REFERENCES
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1. Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1998. CA Cancer J Clin. 1998;48:6-29. ABSTRACT
2. Devesa SS, Silverman DT, McLaughlin JK, Brown CC, Connelly RR, Fraumeni JF Jr. Comparison of the descriptive epidemiology of urinary tract cancers. Cancer Causes Control. 1990;1:1133-1141.
3. Bretheau D, Lechevallier E, Eghazarian C, Grisoni V, Coulange C. Prognostic significance of incidental renal cell carcinoma. Eur Urol. 1995;5:319-323.
4. Homma Y, Kawabe K, Kitamura T, et al. Increased incidental detection and reduced mortality in renal cancer: recent retrospective analysis at eight institutions. Int J Urol. 1995;2:77-80. FULL TEXT | PUBMED
5. Jayson M, Sanders H. Increased incidence of serendipitously discovered renal cell carcinoma. Urology. 1998;51:203-205. FULL TEXT | ISI | PUBMED
6. McCredie M. Bladder and kidney cancers. Cancer Surv. 1994;19:343-368.
7. Ries LAG, Kosary CL, Hankey BF, et al. SEER Cancer Statistics Review, 1973-1995. Bethesda, Md: National Cancer Institute; 1998.
8. Percy C, Van Holten V, Muir C. International Classification of Diseases for Oncology, Second Edition. Geneva, Switzerland: World Health Organization; 1990.
9. Devesa SS, Donaldson J, Fears T. Graphical presentation of trends in rates. Am J Epidemiol. 1995;141:300-304. FREE FULL TEXT
10. McLaughlin JK, Blot WJ, Devesa SS, Fraumeni JF Jr. Renal cancer. In: Schottenfeld D, Fraumeni JF Jr, eds. Cancer Epidemiology and Prevention. 2nd ed. New York, NY: Oxford University Press; 1996:1142-1155.
11. Benichou J, Chow W-H, McLaughlin JK, Mandel JS, Fraumeni JF Jr. Population attributable risk of renal cell cancer in Minnesota. Am J Epidemiol. 1998;148:424-430. FREE FULL TEXT
12. Yuan J-M, Castelao JE, Gago-Dominguez M, Ross RK, Yu MC. Hypertension, obesity and their medications in relation to renal cell carcinoma. Br J Cancer. 1998;77:1508-1513. ISI | PUBMED
13. Flegal KM, Carroll MD, Kuczmarski RJ, Johnson CL. Overweight and obesity in the United States: prevalence and trends, 1960-1994. Int J Obesity. 1998;22:39-47. FULL TEXT | ISI | PUBMED
14. Federation of American Societies for Experimental Biology, Life Sciences Research Office. Third Report on Nutrition Monitoring in the United States: Volume 1. Washington, DC: Interagency Board for Nutrition Monitoring and Related Research; 1995:ES9-ES11.
15. Gross TP, Wise RP, Knapp DE. Antihypertensive drug use: trends in the United States from 1973 to 1985. Hypertension. 1989;13(suppl I):I113-I118.
16. van Zwieten PA. Development and trends in the drug treatment of essential hypertension. J Hypertens. 1992;10(suppl 7):S1-S12.
17. Eisner GM. Hypertension: racial differences. Am J Kidney Dis. 1990;16(suppl 1):35-40.
18. Materson BJ, Reda DJ, Cushman WC, et al. Single-drug therapy for hypertension in men. N Engl J Med. 1993;328:914-921. FREE FULL TEXT
19. Espeland MA, Kumanyika S, Kostis JB, et al. Antihypertensive medication use among recruits for the Trial of Nonpharmacologic Interventions in the Elderly (TONE). J Am Geriatr Soc. 1996;44:1183-1189. ISI | PUBMED
20. Weir MR, Chrysant SG, McCarron DA, et al. Influence of race and dietary salt on the antihypertensive efficacy of an angiotensin-converting enzyme inhibitor or a calcium channel antagonist in salt-sensitive hypertensives. Hypertension. 1998;31:1088-1096. FREE FULL TEXT
21. National Center for Health Statistics. Health, United States, 1996-97, and Injury Chartbook. Hyattsville, Md: National Center for Health Statistics; 1997:182-183.


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J. Am. Soc. Nephrol. 2002;13:1847-1854.
ABSTRACT | FULL TEXT  

Temporal Change in Risk of Metachronous Contralateral Renal Cell Carcinoma: Influence of Tumor Characteristics and Demographic Factors
Rabbani et al.
JCO 2002;20:2370-2375.
ABSTRACT | FULL TEXT  

Radio-frequency Ablation of Renal Cell Carcinoma: Early Clinical Experience
Gervais et al.
Radiology 2000;217:665-672.
ABSTRACT | FULL TEXT  

Obesity, Hypertension, and the Risk of Kidney Cancer in Men
Chow et al.
NEJM 2000;343:1305-1311.
ABSTRACT | FULL TEXT  

Increasing Incidence of Renal Cell Cancer
Katner et al.
JAMA 1999;282:2119-2121.
FULL TEXT  





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