NATURAL HISTORY OF BENIGN PROSTATIC HYPERPLASIA AND RISK OF PROSTATECTOMY The Baltimore Longitudinal Study of Aging H. M I C H A E L A R R I G H I , M.S. E. J E F F R E Y M E T T E R , M.D. H A R R Y A. GUESS, M . D . , PH.D. J A M E S L. F O Z Z A R D , PH.D.
F r o m the D e p a r t m e n t of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, N o r t h Carolina; Merck Sharp & D o h m e Research Laboratories, West Point, Pennsylvania; and Gerontology Research Center, National Institute on Aging, Baltimore, M a r y l a n d
ABSTRACT--The natural history of prostatism (clinically diagnosed benign prostatic hyperplasia) is examined based on symptom questionnaires and digital rectal examinations administered periodically to 1,057 men followed prospectively for up to thirty years in the Baltimore Longitudinal Study of Aging (BLSA). Benign prostatic hyperplasia (BPH) was clinically diagnosed in 527 men, 110 had a prostatectomy for BPH, and in 21 prostate cancer developed. Among men aged sixty or older with prostatic enlargement and obstructive symptoms, the twenty-year probability of surgery was 39 percent; for men aged fifty to fifty-nine years this probability was 24 percent; and]or men aged forty to forty-nine years, the probability was 13 percent. The age-specific prevalence of clinically diagnosed BPH agreed closely at all ages with the age-specific autopsy prevalence of pathologically defined BPH from a published international compilation of 5 independent autopsy studies involving 1,075 prostates.
Benign prostatic hyperplasia (BPH) refers to prostatic cellular proliferation leading to an increase in prostate size. In this purely anatomic sense the relationship of BPH to age has been most clearly described. Berry et al. 1 analyzed data from 10 published studies providing estimates of the age-specific prevalence of histologically recognizable BPH. About 50 percent of men were estimated to have pathologic BPH in the sixth decade of life. However, as Birkhoff2 has noted, the incidence and natural history of clinically diagnosed BPH are at least as important as the anatomic progression, for it is the symptoms and sequelae of BPH that affect patients rather than simply the physical presence of an enlarged prostate. Quantitative epidemiologic information on the clinical course of BPH is lacking.
4
We have analyzed data prospectiv over thirty years in periodic medical performed on over 1,000 men in tl Longitudinal Study of Aging (BLSA) tc ditional information on how clinicall BPH relates to anatomically diagnose g0al of this investigation is to seek etiology of BPH and how symptomatob surgical outcome. Material and Methods The Baltimore Longitudinal Study of A established in 1958 and has been descri where2 Healthy, adult volunteers are enr~ continuous process, with new participants cruited to replace those who leave the st~
SUPPLEMENTTO UROLOGY / JULY1991 / VOLUMEXXXVIII,
December 1988, 1,371 male volunteers have been enrolled. Subjects are followed by study physicians with uniform, periodic, standardized medical histories and physical examinations, which include digital rectal examinations. The medical examinations are performed approximately every two years. Siudy physicians record clinical diagnoses, including BPH, which is diagnosed on the basis of clinical judgment, taking into account the medical history arid digital rectal examination. The medical history includes information on symptoms, surgical proce(d~es, and hospitalizations. The diagnosis of BPH in the BLSA has been made entirely on the basis of a d physical examination, without benefit of ;d urologic procedures. The reported of BPH actually corresponds to the clinical of prostatism. alysis is based on all 1,057 men in the study ot have a history of prostatectomy or pros~r on entry into the study and who had at follow-up visit beyond the baseline visit, 5 men with incomplete medical records. pecific cumulative prevalence of prostai i ~ (clinically diagnosed BPH) at a given age is dei~ned as the percentage of all men of that age in ~ m a clinical diagnosis of BPH had been made on ~:' ~hy study examination up through that time. The '~e;specific point prevalence of prostatism at a ~iVen age was defined as the percentage of all men ~f that age in whom a clinical diagnosis of BPH was ~ d e at that ase. ted the age-specific point prevaltic enlargement on digital rectal at age, and (2) prostatic enlargeobstructive symptoms (hesitancy, orce of the urinary stream, sensaemptying, or terminal dribbling) symptoms are reported by the pa• general symptom questionnaire medical examination. 4 sequent surgery was determined ps of men. One grou p had an Jn digital rectal examination with ~bstructive symptoms. The secorid nly an enlarged prostate and did my of the obstructive symptoms. not have an enlarged prostate nor with any obstructive symptoms. bility of surgery was determined Kaplan-Meier. s autopsy prevalences of BPH and dard errors are those published by e basis of a combined analysis of ~m 5 independent autopsy studies dies), Austria, Norway, and In-
100 z
80
60 z~
40 ,0 0
40-49
50-59
60-69
70-79
80+
AGE IN YEARS /
Enlarged Prostate
/
Clinical ~ Prevalence
Autopsy Prevalence
FIGURE 1. Benign prostatic hyperplasia: clinical prevalence and autopsy prevalence.
dia. 6-1° The age-specific prevalence of prostatic enlargement is based on a cross-sectional survey of 6,975 men undergoing physical examinations for life insurance in the United States. n Prostate enlargement was estimated by digital rectal examination. Results Figure 1 shows the findings of prostatic enlargement and clinically diagnosed BPH reported from the BLSA and the autopsy review of 5 surveys. The age-specific prevalence rates of the clinical diagnosis of BPH from the BLSA was within one standard error of the autopsy prevalence of histologically defined BPH 1 at each of the 5 decades. The prevalence of prostatic enlargement from the BLSA exhibits lower age-specific prevalence rates for all age categories when compared with the BLSA clinical diagnosis of BPH and when compared with the autopsy diagnosis of BPH. Prostatic enlargement by digital rectal examination from BLSA and 6,975 men undergoing examinations for life insurance are displayed in Figure 2.
lOO Z
'"
80
i,
o
60
I--
z
40
"' a.
20
w 0 n-
o
10-19
20-29
30-39
40-49
50-59
60-69
70-79
AGE G R O U P I
6975 LIFE INSUR. EXAMS
~
BLSA (n- 1057)
FIGURE 2. Prevalence of enlarged prostate: comparison of two populations.
g~'EMENT TO UROLOGY / JULY1991 / VOLUMEXXXVIII, NUMBER 1
5
C
100 80 60 40 O O L. a.
20 0 40
45
50
55 Age
60 in
Diagnosis of BPH
65
70
75
80
Years • • • ' Prostatic Enlargement
Benign prostatic hyperplasia prevalence: Baltimore Longitudinal Study of Aging.
FIGUtqE 3.
o E >, ¢0
.=
100 80 60 40
enlarged prostates by digital rectal examination a r e experiencing at least one obstructive symptom. Figure 5 shows the probability of BPH surgery among men with an enlarged prostate and any of~ the obstructive symptoms. The probability of even- i! tual surgery for BPH increases with increasing age'j For a forty to forty-nine-year-old man the probabil, i,i ity of BPH surgery after ten years is 3 percent, and after twenty years it is 13 percent. For a fifty t o fifty-nine-year-old man the probability of BPH sur,' gery after ten years is 7 percent, and after twenty years it is 24 percent. Among men aged sixty to sixtynine years, the ten- and twenty-year probabilities for BPH surgery are 16 percent and 39 percent, re-~ spectively. For men aged seventy years or more, the ten- and twenty-year probabilities for surgery are 34 percent and 41 percent, respectively. Figure 6 shows the probabilities of BPH surgery among men without an enlarged prostate and without any of the obstructive symptoms. The probi ability of BPH surgery among men aged forty ti
20 o.
0 40
i
I
i
i
45
50
55
60
Age Men with Dx of BPH
p
65
i
i
70
75
80
o Q
50 40
in Y e a r s
-
O)
m,,,, Men wl Prost Enlargement
Prevalence o] obstructive symptoms in BPH: Baltimore Longitudinal Study o] Aging. FIGURE 4.
5'i
30 20
o
10
..,,,.,~
5
o
There is an observed similarity in both the magnitude and slope of point estimates from these two populations. The BLSA does exhibit slightly higher estimates of prostatic enlargement at all age intervals, except the youngest category, ages ten to nineteen years. Figure 3 shows the age-specific prevalence rates of BPH and prostatic enlargement from the BLSA. This shows a clear age-related progression for the clinical diagnosis of BPH and prostate enlargement by digital rectal examination. By age sixty, nearly 60 percent of men have clinically diagnosable BPH. However, by age seventy, only 50 percent of men have an enlarged prostate on digital rectal examination. Figure 4 shows the prevalence of obstructive symptoms among men with a clinical diagnosis of BPH and among men with an enlarged prostate. Among men aged sixty years and more, the majority of men with clinically diagnosable BPH have obstructive symptoms (changes in size or force of the urinary stream, a feeling of incomplete voiding, hesitancy, or terminal dribbling). Also, among men aged sixty years and more, the majority of men with
6
~ ~ -.,,..
-
-
_
oJ Years I
70 ÷ Years
IIII
10 of 00-69 Years
15
Follow-Up BImlIB 4 0 - 4 9 Years
BBIIIBBI 5 0 - 5 5 Years
:
FIGURE 5. Probability o/BPH surgery among me~ with prostatic enlargement and with any obstructi~i symptoms.
5O Q
40 =
30 2O 10 0
0
5 Years
m
70 + Years
|II|!
10 of 60-69 Years
15 ~
Follow-Up mllm
50-59 Years
mm
40-49 years ~
Probability o/BPH surgery among m 4 without prostatic enlargement and without any ob~ structive symptoms. FIGURE 6.
SUPPLEMENTTO UROLOGY / JULY1991 / VOLUMEXXXVIII, NUMBI~!~
forty-nine years at ten and twenty years are 2 pericent and 4 percent, respectively. Among men aged ':'fifty to fifty-nine years, the respective ten- and twenty-year probabilities are 2 percent and 9 percent, For men aged sixty to sixty-nine, the ten-year p~0bability of surgery is 9 percent, and at twenty 'i ~ s it is 22 percent. The ten-year probability is 13 percent, for men aged seventy years or more. !
+,
i
i
Comment
i
MoSt information on the clinical course of BPH i hai come from relatively small series of patients fol~;ib~ed in urology clinics for symptoms of prosta-
!it~ir applicability to the general male population or !:even to a primary eare setting is limited by the seitNed nature of the patients. Ball, Feneley, and iAbrams 15 conducted a follow-up study of patients i~ho presented with symptoms of prostatie obstrue;i~n in whom prostatectomy was not elinieally indicare& They eoneluded that urinary flow rate i measurements provided a good screening test to de;fg;~ine which patients were at risk of elinical deterioration suffieient to require surgery. Birkhoff e t al. 14 eompared 10 patients who preinfed in acute urinary retention to 26 other patients ~ith prostatie symptoms and eoneluded that those )h0 experienced urinary retention were not neees!inY the most symptomatic. Powell e t a l . ! 6 eon[~ded that Pressure-flow studies alone were also int h o s e patients at highest risk of eommenting on the acute retena "near absolute" indieation for ~ersen e t al. t7 eoneluded that the acute retention implies a meehat eulmination of the progression ~1a study in whieh evidenee of was found in 85 pereent of pa:or acute retention but in only 3 who had BPH but not retenhowever, that this study did not ity that the infaretion may have cent, rather than a cause of the zondueted a follow-up study of ;ented to their general practi¢ symptoms and in whom prossubsequently diagnosed. Of the ith acute urinary retention, 57.5 p r o s t a t e c t o m y within three 13.5 percent of the 123 who did ate retention came to prostatecmonths. A life-table analysis
showed that i0 percent of those not presenting with acute retention might be expected to develop it in seven years, if they did not have a prostatectorny. A multivariate analysis of the patients not presenting with acute retention showed that no combination of presenting symptoms was predictive of subsequent prostatectomy. This result and other findings suggesting the lack of prognostic significance of symptoms (other than acute retention) and their lack of association with manually determined prostate size may be at least partly a consequence of the small numbers of patients studied. To examine prospectively the relationship of urologic symptoms, prostatic size by digital rectal examination, and subsequent prostatectomy for BPH, Arrighi e t al. 4 analyzed symptom questionnaire and physical examination data on 1,057 men followed for up to thirty years in the BLSA study. 3 This is the first study to quantify the extent to which urologic symptoms and digital prostate examination results can identify men most likely to require prostatectomy for BPH. Men with prostate enlargement and obstructive symptoms (especially those of diminished size and force of the urinary stream and a sensation of incomplete emptying) were found to be about five to eight times more likely to require prostatectomy within the next few years than those of the same age who did not. This result contrasts with the lack of association between prostatic symptoms and prostatectomy found in earlier, smaller studies. Among men with a clinical diagnosis of BPH, there is an increasing prevalence of obstructive symptoms with increasing age. Among men with prostatic enlargement, there is a similar relationship between obstructive symptoms and age. This is indicative of the interaction between age, prostatic enlargement, obstructive symptoms, and a clinical diagnosis of BPH. This steady increase in age-specific prevalence of obstructive symptoms on a population basis is in contrast to what is seen in serial responses from individual patients. Spontaneous reversions are common. 4,17 For example in the BLSA, of 502 men aged fifty and older reporting hesitancy for the first time, 27.1 percent did not report in on the next examination two years later. 4 Of 360 men aged fifty and older who reported hesitancy on two successive examinations approximately two years apart, 18.6 percent did not report it on the subsequent examination. Of interest is that the 50 percent prevalence of clinically diagnosed BPH seen in the middle of the sixth decade is the same as the autopsy prevalence of pathologically defined BPH reported by Berry e t al.1 for men of comparable age, based on a review of a number of studies. These two findings suggest that
__,-)LOGY / JULY1991 / VOLUMEXXXVIII, NUMBER1
7
by age sixty most men are likely to have histologic or clinical evidence of BPH. There is a critical difference in the protocol between the BLSA and the comparison studies. The observations in the BLSA are not independent. In the BLSA, study participants are examined at multiple intervals, and a single participant may contribute information at multiple age categories. The comparison studies are all cross sections, each observation represents a different individual. In the BLSA, the study physicians have access to the complete medical records and symptom history. Past clinical impressions undoubtedly will influence current clinical impressions; this is particularly true of chronic conditions such as BPH that is thought to be progressive with age. These past clinical records m a y influence subsequent results and interpretations. The repeated examinations m a y allow for an accurate diagnosis of BPH due to the availability of baseline information. Glynn e t al. 2° studied the development of BPH among men in the Normative Aging Study (NAS), a prospective study of h u m a n aging by the Boston Veterans Administration. In this study 2,036 male volunteers were followed for up to t w e n t y years with periodic health questionnaires and physical examinations. For a forty-year-old man, their estimate of the forty-year probability for surgery is 29.2 percent. In the BLSA, the estimate of twenty-year probability for BPH surgery is 26 percent, among men aged forty to forty-nine years with an enlarged prostate and exhibiting at least one obstructive symptom. The twenty-year probability of BPH surgery is only 7 percent among men aged forty to forty-nine years without an enlarged prostate and no history of obstructive symptoms. This present study provides a basis for estimating risk of BPH surgery among men with and without prostatic enlargement and obstructive symptoms. The probability of subsequent surgery is not only an age-related function but also a function of obstructive symptoms, prostatic enlargement, and their interaction. While these findings m a y not be directly applied to making treatment decisions on individual patients, these findings are indicative that there are factors other than age that m a y play a role in the development of BPH. Continued clinical observa-
8
tion of patients diagnosed with BPH and undergoing: treatment may provide critical clues to its etiology and the development of a successful prevention ii strategy. Department of Epidemiology ii School of Public Health, CB-7400~! MeGavran-Greenberg Building University of North Carolina':} Chapel Hill, North Carolina 27599-7400 !i (DR. GUESS):!i References 1. Berry SJ, et al: The developmentof human benign prostatic; hyperplasia with age, J Urol 132:474 (1984). 2. BirkhoffJD: Natural history of benign prostatic hypertrophy, in Hinman F Jr (Ed): Benign Prostatic Hypertrophy, New York; Springer-Verlag, 1983, p 5. 3. National Institutes of Health, Normal Human Aging: The Baltimore Longitudinal Study of Aging, NOvember 1984; Washington, DC, US GPO (NIH Publication No. 84-2450). 4. Arrighi HM, et al: Symptomsand signs of prostatism as rise factors for prostateetomy,Prostate 16:253 (1990). ii . . . 5. Kaplan EL, and Memr P: .Nonparametrm estmaatlon from) incomplete observations, J Am Stat Assoc 53:457 (1978). 6. SwyerGIM: Post-natal growth changes in the human pros! tate, J Anat 78:130 (1944). 7. MooreRA: Benign hypertrophy of the prostate, a morphC logical study, J Urol 50:680 (1943). 8. Franks LM: Benign nodular hypertrophy of the prostatel review, Ann R Coil Surg 14:92 (1954). 9. Harbitz TB, and Haugen OA: Histology of the prostate i~ elderly men, a study in an autopsy series, Aeta Pathol Mierobi01 Scand 80(A): 756 (1972). 10. 'Pradhan BK, and Chandra K: Morphogenesisof nodul~ hyperplasia, prostate, J urol 113:210 (1975). 11. Lytton B: Interracial incidence of bemgn prostatic hy~ pertrophy, in Hinman F Jr (Ed): Benign Prostatic Hypertrophyi New York, Springer-Verlag, 1983, p 22. 12. Abrams PH, and Feneley RCL: The significance of symptoms associated with bladder outflow obstruction, Urol i~:~ 33:171 (1978). 13. AndersenJT, Nordling J, and Walter S: Prostatism: I. T correlation between symptoms, cystometric and urodynan findings, Scand J Urol Nephrol 13:229 (1980). 14. Birkhoff l D, et al: Natural history of benign prostatic pertrophy and acute urinary retention, Urology 7:48 (1976). 15. Ball AJ, Feneley RCL, and Abrams PH: The natural 1 tory of untreated prostatism, Br ] Urol 53:613 (1982). 16, Powell PH, et al: The identification of patients at risk ff acute retention, Br l Urol 52:520 (1980). 17 Graversen PH et al: Controversiesabout indications transurethral resection of the prostate, J Urol 141:475 (1989):~ 18. Spiro LH, Labay G, and Orkin LA: Prostatic infarcti, role in acute urinary retention, Urology 3:345 (1974). 19. Craigen AA et al: Natural history of prostatic obstructi, J R Coil Gen Praet 18:226 (1969). i~ 20. Glynn RJ, et al: The development of benign prostatici~:! perplasia among volunteers in the Normative Aging Study, Epidemiol 121:78 (1985).
SUPPLEMENT TO UROLOGY / JULY 1991 / VOLUMEXXXVIII, NUMBI~
F r o m the D e p a r t m e n t of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, N o r t h Carolina; Merck Sharp & D o h m e Research Laboratories, West Point, Pennsylvania; and Gerontology Research Center, National Institute on Aging, Baltimore, M a r y l a n d
ABSTRACT--The natural history of prostatism (clinically diagnosed benign prostatic hyperplasia) is examined based on symptom questionnaires and digital rectal examinations administered periodically to 1,057 men followed prospectively for up to thirty years in the Baltimore Longitudinal Study of Aging (BLSA). Benign prostatic hyperplasia (BPH) was clinically diagnosed in 527 men, 110 had a prostatectomy for BPH, and in 21 prostate cancer developed. Among men aged sixty or older with prostatic enlargement and obstructive symptoms, the twenty-year probability of surgery was 39 percent; for men aged fifty to fifty-nine years this probability was 24 percent; and]or men aged forty to forty-nine years, the probability was 13 percent. The age-specific prevalence of clinically diagnosed BPH agreed closely at all ages with the age-specific autopsy prevalence of pathologically defined BPH from a published international compilation of 5 independent autopsy studies involving 1,075 prostates.
Benign prostatic hyperplasia (BPH) refers to prostatic cellular proliferation leading to an increase in prostate size. In this purely anatomic sense the relationship of BPH to age has been most clearly described. Berry et al. 1 analyzed data from 10 published studies providing estimates of the age-specific prevalence of histologically recognizable BPH. About 50 percent of men were estimated to have pathologic BPH in the sixth decade of life. However, as Birkhoff2 has noted, the incidence and natural history of clinically diagnosed BPH are at least as important as the anatomic progression, for it is the symptoms and sequelae of BPH that affect patients rather than simply the physical presence of an enlarged prostate. Quantitative epidemiologic information on the clinical course of BPH is lacking.
4
We have analyzed data prospectiv over thirty years in periodic medical performed on over 1,000 men in tl Longitudinal Study of Aging (BLSA) tc ditional information on how clinicall BPH relates to anatomically diagnose g0al of this investigation is to seek etiology of BPH and how symptomatob surgical outcome. Material and Methods The Baltimore Longitudinal Study of A established in 1958 and has been descri where2 Healthy, adult volunteers are enr~ continuous process, with new participants cruited to replace those who leave the st~
SUPPLEMENTTO UROLOGY / JULY1991 / VOLUMEXXXVIII,
December 1988, 1,371 male volunteers have been enrolled. Subjects are followed by study physicians with uniform, periodic, standardized medical histories and physical examinations, which include digital rectal examinations. The medical examinations are performed approximately every two years. Siudy physicians record clinical diagnoses, including BPH, which is diagnosed on the basis of clinical judgment, taking into account the medical history arid digital rectal examination. The medical history includes information on symptoms, surgical proce(d~es, and hospitalizations. The diagnosis of BPH in the BLSA has been made entirely on the basis of a d physical examination, without benefit of ;d urologic procedures. The reported of BPH actually corresponds to the clinical of prostatism. alysis is based on all 1,057 men in the study ot have a history of prostatectomy or pros~r on entry into the study and who had at follow-up visit beyond the baseline visit, 5 men with incomplete medical records. pecific cumulative prevalence of prostai i ~ (clinically diagnosed BPH) at a given age is dei~ned as the percentage of all men of that age in ~ m a clinical diagnosis of BPH had been made on ~:' ~hy study examination up through that time. The '~e;specific point prevalence of prostatism at a ~iVen age was defined as the percentage of all men ~f that age in whom a clinical diagnosis of BPH was ~ d e at that ase. ted the age-specific point prevaltic enlargement on digital rectal at age, and (2) prostatic enlargeobstructive symptoms (hesitancy, orce of the urinary stream, sensaemptying, or terminal dribbling) symptoms are reported by the pa• general symptom questionnaire medical examination. 4 sequent surgery was determined ps of men. One grou p had an Jn digital rectal examination with ~bstructive symptoms. The secorid nly an enlarged prostate and did my of the obstructive symptoms. not have an enlarged prostate nor with any obstructive symptoms. bility of surgery was determined Kaplan-Meier. s autopsy prevalences of BPH and dard errors are those published by e basis of a combined analysis of ~m 5 independent autopsy studies dies), Austria, Norway, and In-
100 z
80
60 z~
40 ,0 0
40-49
50-59
60-69
70-79
80+
AGE IN YEARS /
Enlarged Prostate
/
Clinical ~ Prevalence
Autopsy Prevalence
FIGURE 1. Benign prostatic hyperplasia: clinical prevalence and autopsy prevalence.
dia. 6-1° The age-specific prevalence of prostatic enlargement is based on a cross-sectional survey of 6,975 men undergoing physical examinations for life insurance in the United States. n Prostate enlargement was estimated by digital rectal examination. Results Figure 1 shows the findings of prostatic enlargement and clinically diagnosed BPH reported from the BLSA and the autopsy review of 5 surveys. The age-specific prevalence rates of the clinical diagnosis of BPH from the BLSA was within one standard error of the autopsy prevalence of histologically defined BPH 1 at each of the 5 decades. The prevalence of prostatic enlargement from the BLSA exhibits lower age-specific prevalence rates for all age categories when compared with the BLSA clinical diagnosis of BPH and when compared with the autopsy diagnosis of BPH. Prostatic enlargement by digital rectal examination from BLSA and 6,975 men undergoing examinations for life insurance are displayed in Figure 2.
lOO Z
'"
80
i,
o
60
I--
z
40
"' a.
20
w 0 n-
o
10-19
20-29
30-39
40-49
50-59
60-69
70-79
AGE G R O U P I
6975 LIFE INSUR. EXAMS
~
BLSA (n- 1057)
FIGURE 2. Prevalence of enlarged prostate: comparison of two populations.
g~'EMENT TO UROLOGY / JULY1991 / VOLUMEXXXVIII, NUMBER 1
5
C
100 80 60 40 O O L. a.
20 0 40
45
50
55 Age
60 in
Diagnosis of BPH
65
70
75
80
Years • • • ' Prostatic Enlargement
Benign prostatic hyperplasia prevalence: Baltimore Longitudinal Study of Aging.
FIGUtqE 3.
o E >, ¢0
.=
100 80 60 40
enlarged prostates by digital rectal examination a r e experiencing at least one obstructive symptom. Figure 5 shows the probability of BPH surgery among men with an enlarged prostate and any of~ the obstructive symptoms. The probability of even- i! tual surgery for BPH increases with increasing age'j For a forty to forty-nine-year-old man the probabil, i,i ity of BPH surgery after ten years is 3 percent, and after twenty years it is 13 percent. For a fifty t o fifty-nine-year-old man the probability of BPH sur,' gery after ten years is 7 percent, and after twenty years it is 24 percent. Among men aged sixty to sixtynine years, the ten- and twenty-year probabilities for BPH surgery are 16 percent and 39 percent, re-~ spectively. For men aged seventy years or more, the ten- and twenty-year probabilities for surgery are 34 percent and 41 percent, respectively. Figure 6 shows the probabilities of BPH surgery among men without an enlarged prostate and without any of the obstructive symptoms. The probi ability of BPH surgery among men aged forty ti
20 o.
0 40
i
I
i
i
45
50
55
60
Age Men with Dx of BPH
p
65
i
i
70
75
80
o Q
50 40
in Y e a r s
-
O)
m,,,, Men wl Prost Enlargement
Prevalence o] obstructive symptoms in BPH: Baltimore Longitudinal Study o] Aging. FIGURE 4.
5'i
30 20
o
10
..,,,.,~
5
o
There is an observed similarity in both the magnitude and slope of point estimates from these two populations. The BLSA does exhibit slightly higher estimates of prostatic enlargement at all age intervals, except the youngest category, ages ten to nineteen years. Figure 3 shows the age-specific prevalence rates of BPH and prostatic enlargement from the BLSA. This shows a clear age-related progression for the clinical diagnosis of BPH and prostate enlargement by digital rectal examination. By age sixty, nearly 60 percent of men have clinically diagnosable BPH. However, by age seventy, only 50 percent of men have an enlarged prostate on digital rectal examination. Figure 4 shows the prevalence of obstructive symptoms among men with a clinical diagnosis of BPH and among men with an enlarged prostate. Among men aged sixty years and more, the majority of men with clinically diagnosable BPH have obstructive symptoms (changes in size or force of the urinary stream, a feeling of incomplete voiding, hesitancy, or terminal dribbling). Also, among men aged sixty years and more, the majority of men with
6
~ ~ -.,,..
-
-
_
oJ Years I
70 ÷ Years
IIII
10 of 00-69 Years
15
Follow-Up BImlIB 4 0 - 4 9 Years
BBIIIBBI 5 0 - 5 5 Years
:
FIGURE 5. Probability o/BPH surgery among me~ with prostatic enlargement and with any obstructi~i symptoms.
5O Q
40 =
30 2O 10 0
0
5 Years
m
70 + Years
|II|!
10 of 60-69 Years
15 ~
Follow-Up mllm
50-59 Years
mm
40-49 years ~
Probability o/BPH surgery among m 4 without prostatic enlargement and without any ob~ structive symptoms. FIGURE 6.
SUPPLEMENTTO UROLOGY / JULY1991 / VOLUMEXXXVIII, NUMBI~!~
forty-nine years at ten and twenty years are 2 pericent and 4 percent, respectively. Among men aged ':'fifty to fifty-nine years, the respective ten- and twenty-year probabilities are 2 percent and 9 percent, For men aged sixty to sixty-nine, the ten-year p~0bability of surgery is 9 percent, and at twenty 'i ~ s it is 22 percent. The ten-year probability is 13 percent, for men aged seventy years or more. !
+,
i
i
Comment
i
MoSt information on the clinical course of BPH i hai come from relatively small series of patients fol~;ib~ed in urology clinics for symptoms of prosta-
!it~ir applicability to the general male population or !:even to a primary eare setting is limited by the seitNed nature of the patients. Ball, Feneley, and iAbrams 15 conducted a follow-up study of patients i~ho presented with symptoms of prostatie obstrue;i~n in whom prostatectomy was not elinieally indicare& They eoneluded that urinary flow rate i measurements provided a good screening test to de;fg;~ine which patients were at risk of elinical deterioration suffieient to require surgery. Birkhoff e t al. 14 eompared 10 patients who preinfed in acute urinary retention to 26 other patients ~ith prostatie symptoms and eoneluded that those )h0 experienced urinary retention were not neees!inY the most symptomatic. Powell e t a l . ! 6 eon[~ded that Pressure-flow studies alone were also int h o s e patients at highest risk of eommenting on the acute retena "near absolute" indieation for ~ersen e t al. t7 eoneluded that the acute retention implies a meehat eulmination of the progression ~1a study in whieh evidenee of was found in 85 pereent of pa:or acute retention but in only 3 who had BPH but not retenhowever, that this study did not ity that the infaretion may have cent, rather than a cause of the zondueted a follow-up study of ;ented to their general practi¢ symptoms and in whom prossubsequently diagnosed. Of the ith acute urinary retention, 57.5 p r o s t a t e c t o m y within three 13.5 percent of the 123 who did ate retention came to prostatecmonths. A life-table analysis
showed that i0 percent of those not presenting with acute retention might be expected to develop it in seven years, if they did not have a prostatectorny. A multivariate analysis of the patients not presenting with acute retention showed that no combination of presenting symptoms was predictive of subsequent prostatectomy. This result and other findings suggesting the lack of prognostic significance of symptoms (other than acute retention) and their lack of association with manually determined prostate size may be at least partly a consequence of the small numbers of patients studied. To examine prospectively the relationship of urologic symptoms, prostatic size by digital rectal examination, and subsequent prostatectomy for BPH, Arrighi e t al. 4 analyzed symptom questionnaire and physical examination data on 1,057 men followed for up to thirty years in the BLSA study. 3 This is the first study to quantify the extent to which urologic symptoms and digital prostate examination results can identify men most likely to require prostatectomy for BPH. Men with prostate enlargement and obstructive symptoms (especially those of diminished size and force of the urinary stream and a sensation of incomplete emptying) were found to be about five to eight times more likely to require prostatectomy within the next few years than those of the same age who did not. This result contrasts with the lack of association between prostatic symptoms and prostatectomy found in earlier, smaller studies. Among men with a clinical diagnosis of BPH, there is an increasing prevalence of obstructive symptoms with increasing age. Among men with prostatic enlargement, there is a similar relationship between obstructive symptoms and age. This is indicative of the interaction between age, prostatic enlargement, obstructive symptoms, and a clinical diagnosis of BPH. This steady increase in age-specific prevalence of obstructive symptoms on a population basis is in contrast to what is seen in serial responses from individual patients. Spontaneous reversions are common. 4,17 For example in the BLSA, of 502 men aged fifty and older reporting hesitancy for the first time, 27.1 percent did not report in on the next examination two years later. 4 Of 360 men aged fifty and older who reported hesitancy on two successive examinations approximately two years apart, 18.6 percent did not report it on the subsequent examination. Of interest is that the 50 percent prevalence of clinically diagnosed BPH seen in the middle of the sixth decade is the same as the autopsy prevalence of pathologically defined BPH reported by Berry e t al.1 for men of comparable age, based on a review of a number of studies. These two findings suggest that
__,-)LOGY / JULY1991 / VOLUMEXXXVIII, NUMBER1
7
by age sixty most men are likely to have histologic or clinical evidence of BPH. There is a critical difference in the protocol between the BLSA and the comparison studies. The observations in the BLSA are not independent. In the BLSA, study participants are examined at multiple intervals, and a single participant may contribute information at multiple age categories. The comparison studies are all cross sections, each observation represents a different individual. In the BLSA, the study physicians have access to the complete medical records and symptom history. Past clinical impressions undoubtedly will influence current clinical impressions; this is particularly true of chronic conditions such as BPH that is thought to be progressive with age. These past clinical records m a y influence subsequent results and interpretations. The repeated examinations m a y allow for an accurate diagnosis of BPH due to the availability of baseline information. Glynn e t al. 2° studied the development of BPH among men in the Normative Aging Study (NAS), a prospective study of h u m a n aging by the Boston Veterans Administration. In this study 2,036 male volunteers were followed for up to t w e n t y years with periodic health questionnaires and physical examinations. For a forty-year-old man, their estimate of the forty-year probability for surgery is 29.2 percent. In the BLSA, the estimate of twenty-year probability for BPH surgery is 26 percent, among men aged forty to forty-nine years with an enlarged prostate and exhibiting at least one obstructive symptom. The twenty-year probability of BPH surgery is only 7 percent among men aged forty to forty-nine years without an enlarged prostate and no history of obstructive symptoms. This present study provides a basis for estimating risk of BPH surgery among men with and without prostatic enlargement and obstructive symptoms. The probability of subsequent surgery is not only an age-related function but also a function of obstructive symptoms, prostatic enlargement, and their interaction. While these findings m a y not be directly applied to making treatment decisions on individual patients, these findings are indicative that there are factors other than age that m a y play a role in the development of BPH. Continued clinical observa-
8
tion of patients diagnosed with BPH and undergoing: treatment may provide critical clues to its etiology and the development of a successful prevention ii strategy. Department of Epidemiology ii School of Public Health, CB-7400~! MeGavran-Greenberg Building University of North Carolina':} Chapel Hill, North Carolina 27599-7400 !i (DR. GUESS):!i References 1. Berry SJ, et al: The developmentof human benign prostatic; hyperplasia with age, J Urol 132:474 (1984). 2. BirkhoffJD: Natural history of benign prostatic hypertrophy, in Hinman F Jr (Ed): Benign Prostatic Hypertrophy, New York; Springer-Verlag, 1983, p 5. 3. National Institutes of Health, Normal Human Aging: The Baltimore Longitudinal Study of Aging, NOvember 1984; Washington, DC, US GPO (NIH Publication No. 84-2450). 4. Arrighi HM, et al: Symptomsand signs of prostatism as rise factors for prostateetomy,Prostate 16:253 (1990). ii . . . 5. Kaplan EL, and Memr P: .Nonparametrm estmaatlon from) incomplete observations, J Am Stat Assoc 53:457 (1978). 6. SwyerGIM: Post-natal growth changes in the human pros! tate, J Anat 78:130 (1944). 7. MooreRA: Benign hypertrophy of the prostate, a morphC logical study, J Urol 50:680 (1943). 8. Franks LM: Benign nodular hypertrophy of the prostatel review, Ann R Coil Surg 14:92 (1954). 9. Harbitz TB, and Haugen OA: Histology of the prostate i~ elderly men, a study in an autopsy series, Aeta Pathol Mierobi01 Scand 80(A): 756 (1972). 10. 'Pradhan BK, and Chandra K: Morphogenesisof nodul~ hyperplasia, prostate, J urol 113:210 (1975). 11. Lytton B: Interracial incidence of bemgn prostatic hy~ pertrophy, in Hinman F Jr (Ed): Benign Prostatic Hypertrophyi New York, Springer-Verlag, 1983, p 22. 12. Abrams PH, and Feneley RCL: The significance of symptoms associated with bladder outflow obstruction, Urol i~:~ 33:171 (1978). 13. AndersenJT, Nordling J, and Walter S: Prostatism: I. T correlation between symptoms, cystometric and urodynan findings, Scand J Urol Nephrol 13:229 (1980). 14. Birkhoff l D, et al: Natural history of benign prostatic pertrophy and acute urinary retention, Urology 7:48 (1976). 15. Ball AJ, Feneley RCL, and Abrams PH: The natural 1 tory of untreated prostatism, Br ] Urol 53:613 (1982). 16, Powell PH, et al: The identification of patients at risk ff acute retention, Br l Urol 52:520 (1980). 17 Graversen PH et al: Controversiesabout indications transurethral resection of the prostate, J Urol 141:475 (1989):~ 18. Spiro LH, Labay G, and Orkin LA: Prostatic infarcti, role in acute urinary retention, Urology 3:345 (1974). 19. Craigen AA et al: Natural history of prostatic obstructi, J R Coil Gen Praet 18:226 (1969). i~ 20. Glynn RJ, et al: The development of benign prostatici~:! perplasia among volunteers in the Normative Aging Study, Epidemiol 121:78 (1985).
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