American Journal of EpKtermotogy Vo! 134, No 8 Copyright C 1991 by The Johns Hopkrts Uruversfty School of Hygiene and Put*: Health Printed in US A AS rights reserved A BRIEF ORIGINAL CONTRIBUTION Incidence of Surgically Treated Benign Prostatic Hypertrophy and of Prostate Cancer among s and s in a Prepaid Health Care Plan Stephen Sidney, 1 Charles P. Quesenberry, Jr., 1 Marianne C Sadler, 1 Harry A. Guess, : Eva G. Lydick, and Eugene V. Cattolica 3 The incidence of surgically treated benign prostatic hypertrophy and of prostate cancer was examined to December 1987 in 14,897 men (2,175 blacks and 12,722 whites) who received multiphasic health checkups dunng 1971-1972 while members of the Kaiser Permanente Medical Care Program (San Francisco-Oakland, California). Prostate cancer incidence was higher in blacks than in whites for all age groups (ageadjusted relative risk (RR) = 1.8, 95% confidence interval (Cl) 1.4-2.3). The incidence of benign prostatic hypertrophy was somewhat higher in blacks than in whites until age 65 years, after which it was higher in whites. In contrast to the risk of prostate cancer, the age-adjusted risk of benign prostatic hypertrophy was the same for blacks as for whites (RR = 1.0, 95% Cl 0.8-1.2). Am J Epidemiol 1991,134:825-9. blacks; prostatic hypertrophy; prostate neoplasms; whites Surgical treatment for benign prostatic hypertrophy is the most commonly performed operation in men in the United States (1). Little is known about racial differences in the incidence of surgically treated benign prostatic hypertrophy. Because of this, we examined the incidence of surgically treated benign prostatic hypertrophy for blacks and whites in a cohort of nearly 15,000 Kaiser Permanente Medical Care Program mem- Received foe publication October 15, 1990, and in final form June 20,1991 Abbreviations CAMUS, California Automated Mortality Linkage and Information System, Q, confidence interval, SEER, Surveillance, Epidemiology, and End Results 1 Division of Research, Kaiser Permanente Medical Care Program, Oakland, CA 2 Merck Sharp and Dohme Research Laboratories, West Point, PA. 3 Kaiser Permanente Medical Center, Oakland, CA Reprint requests to Dr Stephen Sidney, Division of Research, Kaiser Permanente Medical Care Program, 3451 Piedmont Avenue, Oakland, CA 94611 This research was supported by a grant from Merck Sharp and Dohme Research Laboratories bers. We also examined the incidence of prostate cancer in this cohort to determine if previous findings of higher incidence rates of this disorder in blacks would be confirmed (2) and to determine the proportion of prostate cancer cases that were incidentally detected as a result of surgery for benign prostatic hypertrophy. MATERIALS AND METHODS Study population The study population consisted of 14,897 men (2,175 blacks and 12,722 whites) at least 40 years old who received multiphasic health checkups during 1971 and 1972 in San Francisco or Oakland, California, while members of the Kaiser Permanente Medical Care Program, a prepaid health care program that serves about one quarter of the San Francisco Bay Area population. Excluded from the study population were 646 multiphasic health checkup examinees with 825
826 Sidney et al. a prior history of prostate surgery, prostate cancer, or bladder cancer or treatment to the prostate gland within the 6-month period prior to the multiphasic health checkup. Follow-up Follow-up was carried out for benign prostatic hypertrophy to the date of the earliest of the following: surgery for benign prostatic hypertrophy (n = 973); incidence of prostate cancer (n = 315), bladder cancer («= 117), or both (n = 10); prostate surgery for a reason other than benign prostatic hypertrophy or cancer (n = 4); death {n = 2,370); membership termination (n = 3,870); or December 31, 1987 (n = 7,238). Bladder cancer was included as a criterion for termination of follow-up because surgical treatment of bladder cancer may involve the removal of prostatic tissue, resulting in a potential ascertainment bias for prostatic disease. Follow-up was carried out for prostate cancer to the date of the earliest of the following: incidence of prostate cancer (n = 403), bladder cancer (n = 117), or both (n = 6); death (n = 2,542); membership termination (n = 3,935); or December 31, 1987 (n = 7,894). The mean length of follow-up was 11.8 years for benign prostatic hypertrophy and 12.2 years for prostate cancer. Source of follow-up data Membership termination data. Annual membership status was determined in June of each year by examination of computerized files and microfiche. The membership termination date was estimated to be December 31 of the year in which the person last appeared in the June membership file, because that date represents the midpoint of the time period between successive June membership updates. Determination of benign prostatic hypertrophy cases. Surgical treatment of benign prostatic hypertrophy was determined from a computerized file of all overnight hospitalizations in Northern California Kaiser Permanente medical centers. Discharge diagnoses and surgical codes were recorded, at first using International Classification of Diseases, Eighth Edition, codes and then, starting in 1979, using International Classification of Diseases, Ninth Edition, codes. Surgically treated benign prostatic hypertrophy was defined as 1) a discharge diagnosis of benign prostatic hypertrophy (diagnosis code 600) in combination with a surgical code for prostatectomy (except for radical prostatectomy) or 2) a surgical code for prostatectomy (except for radical prostatectomy) in the absence of a discharge diagnosis of all of the following: benign prostatic hypertrophy (diagnosis code 600), prostate cancer (diagnosis code 185), bladder cancer (diagnosis code 188), or other prostatic disease (diagnosis code 601 or 602). This second criterion was included because a review of the medical records of 14 randomly selected cases which met this criterion revealed that pathologic evidence of benign prostatic hypertrophy was invariably present in the surgically treated prostate gland. Altogether, medical record review of 95 randomly selected cases confirmed that surgical treatment of benign prostatic hypertrophy was performed in 93 (98 percent) of the reviewed cases. Determination of prostate cancer cases. Incident prostate cancer cases were determined from a summary file of first occurrences of cancer in the Kaiser Permanente Medical Care Program which has been maintained since 1972. The main source of cases for this file was the Resource for Cancer Epidemiology, a California state-run and federally supported population-based registry of cancer incidence in the five San Francisco Bay Area counties including Oakland and San Francisco. (The administration changed in 1986 to the Northern California Cancer Center, and the registry is now known as the Bay Area Resource for Cancer Control.) The file also includes cancer cases from the Kaiser Permanente hospitalization file. Of the 403 incident prostate cancer cases, 374 (93 percent) were verified by medical record review. Mortality. Mortality was ascertained through 1987 by computer-matching the members of the study cohort with the Kaiser
Prostate Disease Incidence in s and s 827 Permanente Medical Care Program membership file as of 1989 and extracting a list of subjects who were no longer members. From the list we accepted as confirmed deaths those ascertained in previous studies performed at the Kaiser Permanente Division of Research. The mortality status of the remaining study subjects who were no longer members was ascertained by computermatching names with the California death file using the California Automated Mortality Linkage and Information System (CAMUS) (3). CAMLIS has been shown to have a sensitivity nearly identical to that of the National Death Index in a study of Kaiser Permanente members (3). Data analysis -specific rates were calculated by allocating follow-up time and incident cases of benign prostatic hypertrophy and prostate cancer to the appropriate age intervals. We calculated age-adjusted rates as summary measures to compare data across race, using the direct method and the 1980 US Census age distribution as the standard. Mantel- Haenszel estimates of relative risks for benign prostatic hypertrophy and prostate cancer associated with race were calculated, adjusting for age. Confidence intervals for these relative risk estimates were formed using Breslow's variance estimator (4). In addition, chi-square tests for homogeneity in the relative risks associated with race across age strata were examined. RESULTS Benign prostatic hypertrophy The mean age at the time of the multiphasic health checkup was 51.6 years for blacks and 54.2 years for whites. The incidence of benign prostatic hypertrophy was somewhat higher in blacks than in whites through the age of 64, after which it became higher in whites than in blacks (table 1 and figure 1). The overall age-adjusted incidence (per 100,000 person-years) of benign prostatic hypertrophy was 181 in blacks and 192 in whites. The estimated relative risk of benign prostatic hypertrophy associated with race was 1.0 for blacks as compared with whites (95 percent confidence interval (CI) 0.8-1.2). There was no statistically significant heterogeneity in relative risk by age for benign prostatic hypertrophy associated with race (p = 0.42, chi-square test for homogeneity). Nonetheless, given the apparent crossover in the incidence rates, the relative risk (age-adjusted) for blacks as compared with whites was 1.2 (95 percent CI 0.9-1.6) for ages 40-64 years and 0.8 (95 percent CI 0.6-1.1) for ages 65 years or more. Prostate cancer The incidence of prostate cancer was higher in blacks than in whites in all age groups (table 2 and figure 2). The overall age-adjusted incidence (per 100,000 personyears) of prostate cancer was 113 in blacks and 73 in whites. The estimated relative risk of prostate cancer associated with race was 1.8 for blacks as compared with whites (95 percent CI 1.4-2.3). Simultaneous diagnosis of benign prostatic hypertrophy and prostate cancer There were 41 men (31 white and 10 black) in whom benign prostatic hypertrophy and prostate cancer were diagnosed nearly simultaneously; i.e., the prostate cancer was diagnosed within 10 days before or TABLE 1. Incidence of surgically treated benign prostatic hypertrophy, by age and race, in Kaiser Permanente Medical Care Program murtiphasic examinees, San Francisco-Oakland, California (years) 40-54 55-59 60-64 65-69 70-74 2:75 No. of cases 7 14 34 25 19 19 16 62 161 202 196 218 Person-years of fotow-up 9,534 6,181 5,187 3.433 1,853 1,158 42,480 28,654 27,762 21,860 15,031 12.793 Incidence rate per 100,000 person-years 73 227 655 728 1,025 1,641 38 216 580 924 1,304 1,704
828 Sidney et al Incidence Rate 2000 Incidence Rate 1000 1600 800 - eoo 1000-400 500 40-64 Race FIGURE 1. Incidence (per 100,000 person-years) of benign prostatic hypertrophy, by race and age, in Kaiser Permanente Medical Care Program multiphasic examinees, San Francisco-Oakland, California TABLE 2. Incidence of prostate cancer, by age and race, In Kaiser Permanente Medical Care Program multiphasic examinees, San Francisco- Oakland, California (years) No of cases Incidence Person-years of rate per fobow-up 100,000 person-years Hack Write 40-54 4 8 9,552 42,506 42 19 55-59 10 19 6,237 28,851 160 66 60-64 21 52 5,291 28,351 397 183 65-69 16 57 3,600 22,946 444 248 70-74 17 64 1,994 16,237 853 394 75 12 123 1,303 14,663 921 839 30 days after surgery for benign prostatic hypertrophy. The medical records of 34 of these individuals were reviewed (seven were unavailable) to determine which of these diagnoses was suspected before surgical treatment was performed. Benign prostatic hypertrophy was suspected in 88 percent of these cases (30 of 34). If the same percentage were applicable to the seven cases that were unavailable for review, then 36 of the prostate cancers were incidentally discovered as a result of surgery that was performed for 200-40-64 66-59 60-64 66-69 70-74 Race ~- -+- FIGURE 2. Incidence (per 100,000 person-years) of prostate cancer, by race and age, in Kaiser Permanente Medical Care Program multiphasic examinees, San Francisco-Oakland, California benign prostatic hypertrophy. Therefore, the incidental discovery of prostate cancer occurred in nearly 4 percent (36 of 973) of subjects who underwent surgery for benign prostatic hypertrophy and represented 9 percent of the total number of prostate cancers that occurred in this cohort. DISCUSSION The overall risk of surgically treated benign prostatic hypertrophy was nearly the same in blacks and whites. We are not aware of any previously published data examining the relation of race to surgically treated benign prostatic hypertrophy. As other studies have shown (2), blacks had a substantially higher risk of prostate cancer than did whites. The findings regarding the incidental discovery of prostate cancer during surgery for benign prostatic hypertrophy indicate that a relatively small (9 percent) proportion of prostate cancers were detected in this way. Benign prostatic hypertrophy and prostate cancer are generally found in different regions of the prostate gland, making it un-
Prostate Disease Incidence in s and s 829 likely that benign prostatic hypertrophy is a precursor lesion to prostate cancer (5). Histologic evidence of prostatic cancer is quite common with advancing age, with a prevalence rate greater than 40 percent in autopsy studies of men over the age of 80 years (5). Because of this, the simultaneous finding of benign prostatic hypertrophy and prostate cancer is probably due to chance. The finding of different rates for prostatic cancer but similar rates for benign prostatic hypertrophy in the two races in this study also suggests that these two conditions are etiologically distinct. Two other studies which have examined the relation of benign prostatic hypertrophy to prostate cancer yielded conflicting findings. Armenian et al. (6) found that prostate cancer risk was elevated in men with benign prostatic hypertrophy, but Greenwald et al. (7) did not. It is possible that benign prostatic hypertrophy and prostate cancer may share similar risk factors. In this regard, it is noteworthy that castration is protective against both benign prostatic hypertrophy and prostate cancer (5), suggesting a role of androgens in the etiology of both disorders. Ascertainment bias could potentially exist if substantial numbers of cases were surgically treated outside of the Kaiser Permanente system, since they would not be detected in the computerized case files. While there are no populations with which the incidence data for benign prostatic hypertrophy can be compared, the incidence rates of prostate cancer in blacks and whites in this study cohort were overall slightly lower than those for the San Francisco-Alameda County region of the Surveillance, Epidemiology, and End Results (SEER) program (8) for the years 1973-1981. In the directly comparable 55-59, 60-64, 65-69, and 70-74 year age groupings, the Kaiser Permanente incidence rates of prostate cancer for whites were 0.1 percent higher, 3.6 percent higher, 22.5 percent lower, and 23.1 percent lower, respectively, than the SEER rates, while for blacks they were 8.5 percent lower, 18.2 percent higher, 22.4 percent lower, and 9.7 percent lower. The similarity in the comparison of Kaiser Permanente and SEER data in blacks and whites suggests that differences in risk are not likely to be due to differential ascertainment of cases in the two races. The Kaiser Permanente Medical Care Program membership is sociodemographically diverse but more educated on average than the local general population, with underrepresentation of persons of very high income and low income (9). We do not know whether these results can be generalized to the overall US population. However, the overall rinding of little difference between blacks and whites in the incidence of surgically treated benign prostatic hypertrophy is strengthened by the racial difference in prostate cancer incidence, a finding which is consistent with the results of other studies (2). REFERENCES 1. Carter HB, Coffey DS. The prostate, an increasing medical problem. Prostate 1990; 16:39-48. 2. Mandel JS, Schuman LM. Epidemiology of cancer of the prostate. In: Iilienfeld AM, ed. Reviews in cancer epidemiology. Vol 1. New York: Elsevier/ North-Holland Publishing Company, 1980:20-3. 3. Arellano MG, Petersen GR, Petitti DB, et al. The California Automated Mortality Linkage System. Am J Public Health 1984;74:1324-30. 4. Breslow NE, Day NE, eds. Statistical methods in cancer research. Vol 2. The design and analysis of cohort studies. Lyon, France: International ncy for Research on Cancer, 1987. (IARC scientific publication no. 82). 5. Meikle AW, Smith JA Jr. Epidemiology of prostate cancer. Urol Chn North Am 1990,17:709-18. 6. Armenian HK, Lilienfeld AM, Diamond EL, et al. Relation between benign prostatic hyperplasia and cancer of the prostate: a prospective and retrospective study. Lancet 1974^:115-17. 7. Greenwald P, Kirmss V, Polan AK, et al. Cancer of the prostate among men with benign prostatic hyperplasia. J Natl Cancer Inst 1974;53:335-40. 8. SEER program: cancer incidence and mortality in the United States, 1973-81. Bethesda, MD: National Cancer Institute, 1985. (N1H publication no. 85-1837). 9. Hiatt RA, Friedman GD. The frequency of kidney and urinary tract diseases in a defined population. Kidney Int 1982^22:63-8.