Full text of DOI:10.1016/S0022-5347(05)67454-X

0022-5347/00/1641-0081/0
®
THE JOURNAL OF UROLOGY
Vol. 164, 81–88, July 2000
Copyright © 2000 by AMERICAN UROLOGICAL ASSOCIATION, INC.®
Printed in U.S.A.
PATTERNS OF TREATMENT OF PATIENTS WITH PROSTATE CANCER
INITIALLY MANAGED WITH SURVEILLANCE: RESULTS FROM THE
CaPSURE DATABASE
THERESA M. KOPPIE, GARY D. GROSSFELD, DAVID MILLER,* JENNY YU,† DAVID STIER,*
JEANETTE M. BROERING, DEBORAH LUBECK,* JAMES M. HENNING, SCOTT C. FLANDERS* AND
PETER R. CARROLL‡
From the Department of Urology, Center for Urologic Outcomes, University of California-San Francisco, University of California-San
Francisco-Mt. Zion Cancer Center and Lewin TAG, San Francisco, California, and TAP Holdings, Deerfield, Illinois
ABSTRACT
Purpose: We determined the demographic and clinical profile of men who elect surveillance as
the initial management of prostate cancer as well as the incidence and predictors of secondary
treatment of these patients.
Materials and Methods: The Cancer of the Prostate Strategic Urological Research Endeavor
(CaPSURE) is a national disease registry of patients with various stages and treatments of
prostate cancer. Using this database of 4,458 men we identified 329 (8.2%) who elected surveil-
lance as the initial management of prostate cancer. Patients choosing watchful waiting were
compared to other CaPSURE participants using the chi-square test. The likelihood of treatment
initiation in the watchful waiting group was calculated using the Kaplan-Meier method. After
adjusting for patient age, race, prostate specific antigen (PSA) at diagnosis, clinical T stage and
total Gleason score the Cox proportional hazards regression model was used to determine
significant predictors of treatment initiation.
Results: Compared with others in the database, patients on watchful waiting were more likely
to be 75 years old or older (51% versus 16%, p Ͻ0.001), white (93% versus 85%, p Ͻ0.001), and
have lower serum PSA (p Ͻ0.001), organ confined disease (97% versus 88%, p Ͻ0.001) and a total
Gleason score of 7 or less (97% versus 88%, p Ͻ0.001). In the watchful waiting group there was
a 52% likelihood of treatment initiation within 5 years of the diagnosis. Significant predictors of
secondary treatment were age younger than 65 years and elevated serum PSA at diagnosis.
Neither race, extraprostatic stage cT3 disease nor higher total Gleason score was a significant
predictor of treatment.
Conclusions: Men who elect initial watchful waiting for prostate cancer tend to be older, have
lower serum PSA and more favorable disease characteristics than those who seek treatment. PSA
at diagnosis is the dominant factor for predicting secondary treatment.
KEY WORDS: prostate, prostate-specific antigen, prostatic neoplasms
Prostate cancer is the most commonly diagnosed cancer in
To date information on the outcome of patients electing
American men and the second leading cause of cancer related watchful waiting is limited since it has generally been derived
death.1 The optimal management of prostate cancer remains from experiences at single institutions.5 We describe national
controversial. To date no consensus exists on the best form of trends in the use of watchful waiting as primary therapy for
treatment for any disease stage.
prostate cancer. Specifically the demographic and clinical pro-
Given the protracted natural history of prostate cancer and file of men who elected surveillance as the initial management
the advanced age at diagnosis in many patients, initial sur- of prostate cancer was assessed, as were the incidence and
veillance or watchful waiting remains an important treat- predictors of secondary prostate cancer treatment.
ment option for those newly diagnosed with the disease.
Retrospective series indicate that watchful waiting may
MATERIALS AND METHODS
achieve a long-term survival outcome similar to that of other
We analyzed data on patients with prostate cancer en-
treatment modalities, especially in older men with well or
rolled in the Cancer of the Prostate Strategic Urological
moderately differentiated, low stage prostate cancer. More-
Research Endeavor (CaPSURE) database who elected watch-
over, such a favorable outcome may be achieved without any
ful waiting as the initial form of therapy. CaPSURE is a
longitudinal, observational database of patients with pros-
tate cancer recruited through a network of urologists at 29
community and academic urology practice sites distributed
regionally throughout the United States. At each practice
site men with biopsy proved prostate cancer are invited to
join the study in a consecutive fashion as they present for
outpatient care. Subjects may be enrolled in the database
despite a considerable interval since the initial diagnosis.
At enrollment extensive clinical and demographic informa-
tion is recorded based on the existing medical record. These
associated treatment related morbidity.2–4 With widespread
prostate specific antigen (PSA) screening in all age groups
considerable stage migration has occurred and increased
numbers of patients may be candidates for watchful waiting
as the primary therapy for prostate cancer.
Accepted for publication January 28, 2000.
* Financial interest and/or other relationship with TAP Holdings.
† Financial interest and/or other relationship with Lewin Group.
‡ Financial interest and/or other relationship with TAP Holdings,
Anthra, Alza, National Institutes of Health, National Cancer Insti-
tute, Swob and EDAP-Technomed.
81

82
PATTERNS OF PROSTATE CANCER TREATMENT
TABLE 1. Comparison of patients who elected watchful waiting and those who underwent immediate treatment
No. Immediate
No. Pts.
No. Watchful Waiting (%)
329
p Value (chi-square test)
Treatment (%)
Total No.
4,129
Age (mean 73.7, median 75.1):
0.001
Younger than 65
65–74
75 or Older
38 (11.6)
125 (38.0)
166 (50.5)
1,499 (36.7)
1,937 (47.4)
651 (15.9)
Race:
0.001
0.001
0.001
White
302 (92.6)
19 (5.8)
3,478 (84.6)
484 (11.8)
151 (3.7)
4,098 (1994)
Black
Other
5
(1.5)
Median yr. diagnosis
Clinical T stage at diagnosis:
329 (1994)
cTX
2
(1.6)
107 (2.6)
864 (20.9)
2,750 (66.6)
409 (9.9)
cT1
143 (43.6)
170 (53.8)
13 (4.0)
cT2
cT3–cT4
PSA at diagnosis (mean 12.3, median 7.4):
0.0–4.0
53 (18.6)
139 (48.8)
62 (21.8)
31 (10.9)
363 (9.8)
1,654 (44.6)
861 (23.2)
823 (22.4)
4.1–10.0
10.1–20.0
20.1 or Greater
Gleason score at diagnosis (mean 4.8, median 5):
0.001
0.001
0.003*
2–6
7
249 (86.2)
31 (10.7)
2,514 (67.2)
771 (20.6)
454 (12.1)
8–10
Risk of disease:
Low
Intermediate
High
Death:
9
(3.1)
67 (20.4)
177 (54.0)
84 (25.6)
23
296 (7.3)
1,836 (45.3)
1,917 (47.4)
230
60 (26.1)
24 (10.4)
83 (36.1)
63 (27.4)
Related to prostate Ca
Related to other Ca
Other causes
Unknown causes
3 (13.0)
1
(4.3)
16 (69.6)
3 (13.0)
* Other causes versus remaining 3 groups.
FIG. 1. Kaplan-Meier event-free treatment survival curve stratified by disease risk

PATTERNS OF PROSTATE CANCER TREATMENT
83
FIG. 2. Kaplan-Meier event-free survival curve stratified by T stage at diagnosis
data include the type of primary treatment given as well as nosis, clinical T stage and total Gleason score, the multivar-
patient age, cancer stage, tumor grade and initial serum iate Cox proportional hazards regression model was used to
PSA. Additional data are recorded prospectively at each of- assess the predictors of treatment initiation in the watchful
fice visit after the baseline visit, including new procedures, waiting group. A time dependent Cox model was also con-
treatments and diagnostic tests. Hospital discharge summa- structed to model the time dependent covariates of PSA be-
ries are obtained for all hospitalizations reported, and all fore treatment and change in PSA or clinical stage during
international classification of diseases, version 9 diagnoses watchful waiting.
and procedures are abstracted. Patients are followed in the
database until death or study withdrawal. Institutional re-
RESULTS
view board approval for the study is obtained at each clinical
site and patient informed consent for participation is re-
Of 4,459 patients enrolled in the CaPSURE database 471
quired for data collection. Additional details of the project (10.6%) elected watchful waiting as the initial form of cancer
methodology have been published previously.6
treatment. Mean and median followup in these cases was
Men who elected watchful waiting as the initial treatment 3.06 and 2.25 years, respectively (range 0 to 25) after diag-
option are the subjects of our study. Patients were excluded nosis. Of the 471 men 79 started therapy within 9 months of
from analysis if they started therapy within 9 months of the diagnosis, while an additional 63 elected watchful waiting 9
prostate cancer diagnosis or elected watchful waiting more months or more after the initial diagnosis. Such patients
than 9 months after the diagnosis. Demographics and clinical were excluded from current analysis because the former
characteristics of the watchful waiting group were compared group likely included those who simply deferred initial treat-
to those of all others with prostate cancer in the CaPSURE ment and the latter likely included those who were indecisive
database using the chi-square test statistic. To define the regarding any form of therapy for prostate cancer. Since we
risk profiles of patients in the database high, intermediate or evaluated only cases in which the clinical course most closely
low disease risk categories were assigned based on clinical T represented the natural history of watchful waiting, 329
stage, serum PSA at diagnosis and biopsy Gleason score. (8.2% of the overall CaPSURE cohort) form the basis of our
High risk tumors were defined as Gleason score 7 or greater, study.
serum PSA greater than 15 ng./ml. or stage T3 or greater
Mean and median age of these patients was 73.6 and 75.08
disease. Low risk cancer was defined as stage T1 or years, respectively (range 44.16 to 87.17). PSA at diagnosis
T2aN0M0 disease, Gleason score 6 or less with no Gleason 4 was recorded in 285 of the 329 cases (87%) at enrollment.
or 5 components and serum PSA less than 5 ng./ml. The Mean and median serum PSA was 12.29 and 7.4 ng./ml.,
intermediate risk category included all remaining cases.
respectively. Mean and median Gleason score documented in
Freedom from event (treatment) curves in the watchful 289 cases (88%) was 4.8 and 5, respectively. Disease was
waiting group were calculated using the Kaplan-Meier clinical stage T1 in 143 patients (43.9%), stage T2 in 170
method. After adjusting for patient age, race, PSA at diag- (52.1%) and stage T3 to T4 in 13 (4%). Of the patients 92.6%

84
PATTERNS OF PROSTATE CANCER TREATMENT
FIG. 3. Kaplan-Meier event-free survival curve stratified by clinical Gleason score at diagnosis
were white and 5.8% black. Disease was low, moderate and than 65 years. In addition, men with clinical stage T2 dis-
high risk in 20.4%, 54% and 25.6%, respectively, of those for ease were more likely to undergo secondary treatment than
whom complete information was available on serum PSA, those with clinical stage T1 disease (p ϭ 0.0153). Neither
clinical T stage and Gleason score. There were significant race, extraprostatic stage cT3 disease extension nor higher
differences in CaPSURE patients who elected initial surveil- total Gleason score was a significant predictor of secondary
lance and those who underwent other forms of prostate can- treatment.
cer treatment (table 1). Men who elected watchful waiting
We also performed a Cox regression analysis of time de-
were significantly older, had significantly lower stage and pendent covariates, including PSA before treatment and
grade disease, and significantly lower serum PSA values at change in PSA or disease stage during watchful waiting.
diagnosis than other patients.
Since patients were enrolled in the database prospectively at
According to death certificate data 23 men (7%) on watch- diagnosis as well as after diagnosis and treatment, time
ful waiting died during the study period. Prostate cancer was dependent data were not complete for each patient. For in-
the cause of death in only 3 of the 23 patients (13%). Of the stance, a baseline serum PSA and at least 1 followup value
3 men 2 who had been assigned to the high risk disease were available in 163 of the 329 cases analyzed. Median
category due to a PSA of greater than 20 ng./ml. at diagnosis increase in PSA in patients who received secondary treat-
died of prostate cancer, and 1 who was considered at inter- ment was 6.2 ng./ml. and median ratio (final/initial PSA) was
mediate risk died 15 years after diagnosis.
1.82 ng./ml. In those who remained on watchful waiting
Of the patients on watchful waiting 39% received second- serum PSA was stable (median change 0 ng./ml.). Up staging
ary cancer treatment during followup. Figures 1 to 5 show was uncommon, occurring in only 3% of treated patients and
Kaplan-Meier estimates of freedom from treatment. The risk 4% of those who remained on watchful waiting.
of secondary treatment 5 years after diagnosis in the watch-
The ratio of increasing serum PSA from baseline was a
ful waiting cohort was 52.5%. The risk of secondary treat- significant predictor of secondary treatment by the Cox re-
ment after definitive local therapy in the CaPSURE database gression model. The hazards ratio for the change in serum
has been previously reported.7
PSA was 1.99 (confidence interval 1.18 to 3.35). Therefore,
Univariate analysis demonstrated that PSA at diagnosis for each factor serum PSA increased from baseline, the risk of
was the dominant factor for predicting secondary treatment treatment approximately doubled compared to when serum
(fig. 4 and table 2). Table 3 shows the multivariate Cox PSA remained stable with time. For example, a ratio of 2,
proportional hazards model assessing predictors of secondary calculated as the most recent/baseline PSA, indicates almost
treatment. As in univariate analysis, PSA at diagnosis was 2-fold (1.99) the risk of treatment compared to a ratio of 1.
the most important factor for predicting initiation of second- Furthermore, a ratio of 3 indicates a 1.99-fold greater risk
ary treatment (table 3). In addition, patient age was an than a ratio of 2. Of the 128 patients with secondary treat-
important predictor of secondary treatment in the multivar- ment 86 (67%) underwent androgen deprivation therapy
iate model since patients older than 65 years were less likely with nilutamide, bicalutamide, diethylstilbestrol, flutamide,
to receive secondary treatment compared to those younger leuprolide, finasteride and goserelin (table 4). External beam

PATTERNS OF PROSTATE CANCER TREATMENT
85
FIG. 4. Kaplan-Meier event-free survival curve stratified by PSA at diagnosis
radiation therapy, radical prostatectomy, orchiectomy and diate and delayed treatment groups, and only 11% of patients
cryosurgery were done in 22 (17%), 14 (11%), 4 (3%) and 2 died of prostate cancer. Men with poorly differentiated dis-
(1.5%) cases, respectively.
ease had the highest death rate from prostate cancer (56%)
compared to those with well (7%) or moderately (16%) differ-
entiated disease. Similarly, Albertsen et al evaluated 451
men with clinically localized prostate cancer identified from
the Connecticut tumor registry.4 Patients received no treat-
ment, or immediate or delayed androgen deprivation therapy
at disease progression and were followed an average of 15.5
years after diagnosis. Albertsen et al observed that age ad-
justed survival of men with Gleason score 2 to 4 tumors was
similar to that of the general population. However, those
with Gleason score 5 to 7 and 8 to 10 tumors had a 4 to 5 and
6 to 8-year loss of life expectancy, respectively, compared to
that of the general population without prostate cancer. In a
more recent series of the Connecticut tumor registry Albert-
sen et al evaluated the probability of death within 15 years of
diagnosis in men 55 to 74 years old treated conservatively for
clinically localized prostate cancer.10 As in previous studies,
tumor grade was the most important predictor of death from
prostate cancer in patients treated with initial surveillance.
In contrast to previous studies of men on watchful waiting,
we determined the demographic and clinical profiles of those
who elected watchful waiting as the initial management of
prostate cancer. Moreover, we determined the incidence and
predictors of secondary treatment in these patients. The
cases analyzed in our series represent a large national sam-
ple of prostate cancer cases recruited from various urology
practice sites distributed throughout the United States. Clin-
ical sites were selected to represent a wide variety of practice
settings, including managed care, fee for service practices
DISCUSSION
The optimal management of prostate cancer remains con-
troversial because no consensus yet exists on the best form of
treatment for any stage disease. Steinberg et al proposed
that watchful waiting is the best treatment option in men
with well or moderately differentiated, low volume prostate
cancer and a life expectancy of less than 10 years.8 However,
to our knowledge little information is available on the out-
come, such as secondary treatment and cause specific mor-
tality, of contemporary patients treated in this fashion in the
United States and no randomized trials have been done di-
rectly comparing observation to any definitive local treat-
ment modality available for those with prostate cancer.
While the prostate cancer versus observation trial comparing
radical prostatectomy with expectant management is ran-
domized, the results of this trial will not be available for some
time.9 Until such information becomes available physicians
seeking data on watchful waiting must rely on nonrandom-
ized retrospective studies, of which most were performed
outside of the United States.
Many previous series of watchful waiting analyzed the
overall survival rate of patients electing such treatment.
Johansson et al reported the disease specific outcome of 642
patients diagnosed with prostate cancer in Sweden.2 Of the
300 men with localized prostate cancer 223 received no initial
therapy, followed by delayed treatment for symptomatic pro-
gression. A total of 77 patients received initial external beam
radiation, androgen deprivation or radical prostatectomy. and university based teaching hospitals. Broad geographic
The corrected 15-year survival rate was similar in the imme- representation is included. Thus, the CaPSURE database

86
PATTERNS OF PROSTATE CANCER TREATMENT
FIG. 5. Kaplan-Meier event-free survival curve stratified by patient age
TABLE 2. Kaplan-Meier estimates of the risk of secondary treatment
Freedom From Secondary Treatment
p Value (log rank test)
No. Pts.
329
% 2 Yrs. Ϯ SE
% 5 Yrs. Ϯ SE
All watchful waiting pts.
76.1 Ϯ 2.6
47.5 Ϯ 3.9
Age:
Younger than 65
65–74
75 or Older
Race:
White
Black
38
125
166
66.1 Ϯ 8.8
80.1 Ϯ 3.9
75.1 Ϯ 3.8
40.6 Ϯ 10.0
50.6 Ϯ 6.7
46.8 Ϯ 5.4
0.5484 vs. younger than 65
0.9075 vs. younger than 65
0.4416
302
19
75.6 Ϯ 2.7
83.3 Ϯ 10.8
47.5 Ϯ 4.0
33.3 Ϯ 18.8
Clinical T stage at diagnosis:
CT1
CT2
CT3–T4
143
170
13
85.9 Ϯ 3.2
67.9 Ϯ 4.0
64.9 Ϯ 16.7
61.6 Ϯ 5.4
37.6 Ϯ 5.5
16.2 Ϯ 14.7
0.0001 vs. pT1
0.0657 vs. pT1
PSA at diagnosis (ng./ml.):
0–4.0
53
139
62
85.8 Ϯ 5.9
75.5 Ϯ 4.1
66.4 Ϯ 7.2
55.2 Ϯ 9.3
69.9 Ϯ 8.9
44.9 Ϯ 7.1
37.4 Ϯ 9.1
16.2 Ϯ 8.0
4.1–10.0
0.016 vs. 0–4.0
0.0028 vs. 0–4.0
0.0001 vs. 0–4.0
10.1–20.0
20.1 and Greater
31
Clinical Gleason score at diagnosis:
2–6
7
8–10
249
31
9
77.7 Ϯ 2.9
75.2 Ϯ 8.8
51.4 Ϯ 20.4
50.0 Ϯ 4.6
37.6 Ϯ 12.0
0.1898 vs. 2–6
0.0850 vs. 2–6
Risk of disease:
Low
Intermediate
High
67
177
84
89.4 Ϯ 4.5
77.7 Ϯ 3.4
62.8 Ϯ 5.8
79.4 Ϯ 7.1
50.6 Ϯ 4.9
23.3 Ϯ 6.5
0.0032 vs. low
0.0001 vs. low
may provide a realistic view of how prostate cancer is man- cer than of other causes. Such an outcome may have been
aged nationwide, providing important information with re- expected since the majority of patients who elected watchful
spect to disease specific outcomes associated with various waiting had favorable disease characteristics and were older
forms of prostate cancer treatment.
at diagnosis. Of our study population 39% underwent second-
We noted that men who elected watchful waiting tended to ary cancer treatment within the followup period with the
be older, and have lower baseline PSA and more favorable likelihood of secondary cancer treatment reaching 52.5% at 5
disease characteristics than those who chose definitive ther- years after prostate cancer diagnosis.
apy. Compared to others in the CaPSURE database fewer
This rate of secondary cancer treatment is somewhat
patients in the watchful waiting group died of prostate can- higher than previously reported in patients treated with

PATTERNS OF PROSTATE CANCER TREATMENT
87
TABLE 3. Cox proportional hazards model for predictors of secondary treatment
Unadjusted Estimates
Adjusted Estimates
Risk of Secondary Treatment
No. Pts.
329
Hazards
Ratio
Hazards
Ratio
95% CI
p Value
95% CI
p Value
Age:
65–74 vs. younger than 65
75 or Older vs. younger than 65
Clinical T stage at diagnosis:
cT2 vs. cT1
0.866
1.041
0.493–1.519
0.607–1.786
0.6148
0.8834
0.374
0.336
0.179–0.784
0.166–0.679
0.0091
0.0024
326
285
2.222
2.305
1.520–3.248
0.982–5.410
0.0001
0.0550
1.833
1.149
1.123–2.992
0.440–3.002
0.0153
0.7769
cT3–cT4 vs. cT1
PSA at diagnosis (ng./ml.):
4.1–10.0 vs. 0–4.0
2.400
3.122
4.693
1.172–4.916
1.448–6.730
2.178–10.112
0.0167
0.0037
0.0001
3.064
3.680
6.864
1.352–6.944
1.544–8.769
2.587–18.202
0.0073
0.0033
0.0001
10.1–20.0 vs. 0–4.0
20.1 or Greater vs. 0–4.0
Clinical Gleason score at diagnosis:
7 vs. 2–6
289
328
326
1.438
2.459
0.831–2.488
0.898–6.735
0.1946
0.0800
1.082
1.179
0.570–2.053
0.395–3.515
0.8090
0.7681
8–10 vs. 2–6
Risk of disease:
Intermediate vs. low
High vs. low
19 Black vs. 302 white ϩ 5 other pts.
2.749
5.335
1.353
1.372–5.508
2.612–10.895
0.630–2.907
0.0043
0.0001
0.4385
1.220
0.451–3.302
0.6948
strongest factor influencing the decision. Older patients in
their study were significantly more likely to prefer observa-
tion rather than surgical intervention. Overall health status
was not significantly associated with patient preference.
Physician preference may also be important for determin-
ing which patients are offered watchful waiting and how
patients perceive treatment options. The finding that those
who elected watchful waiting in our series had more favor-
able disease characteristics is to be expected because the
literature supports watchful waiting in such patients.3, 4 In
addition, co-morbidity may have had an impact on such de-
cisions. The recent national survey of urologists and primary
care physicians of Fowler et al revealed that two-thirds of
physicians considered watchful waiting appropriate in pa-
tients with less than 10 years of life expectancy.16
While we did not assess why patients underwent secondary
cancer treatment, it is notable that such treatment was given
more frequently to those with higher serum PSA and those
who were younger at diagnosis. Moreover, patients in whom
serum PSA changed with time were more likely to undergo
secondary treatment compared to those in whom serum PSA
remained stable. Such results may reflect the tendency to-
ward definitive treatment of younger patients with prostate
cancer as well as the impact of serial PSA testing on medical
resource use. McLaren et al evaluated the predictive value of
initial PSA and PSA doubling time on clinical behavior in
cases of early untreated prostate cancer.12 They demon-
strated that while PSA doubling time was a strong predictor
of clinical tumor progression by digital rectal examination,
initial PSA was the only significant predictor of time to
secondary treatment. It is also interesting that cancer stage
was not associated with secondary treatment in our study
and migration to higher stage disease was uncommon, occur-
ring in only 3% of those who received secondary treatment. In
addition, tumor grade was not associated with secondary
treatment, although grade appears to be the most important
predictor of cause specific survival in patients on watchful
waiting.10 Thus, our data suggest that for patients on watch-
ful waiting physicians rely on serum PSA as a surrogate
marker of disease progression in a similar fashion to that
after definitive local treatment with radical prostatectomy or
radiation therapy.
TABLE 4. Type of secondary treatment
No. Pts. (%)
Androgen deprivation therapy
86 (67.2)
22 (17.2)
14 (10.9)
External beam radiation therapy
Radical prostatectomy
Orchiectomy
4
2
(3.1)
(1.6)
Cryosurgery
Total
128 (100)
watchful waiting.11, 12 It is also higher than that reported
after definitive local therapy. Grossfeld et al provided rates of
secondary treatment after definitive local therapy using sim-
ilar data from the CaPSURE database.7 Of 1,894 CaPSURE
patients treated with radical prostatectomy, external beam
radiation or cryosurgery 22% underwent secondary cancer
treatment within a mean of 3 years after the initial therapy.
Lu-Yao13 and Fowler14 et al also reported rates of secondary
treatment after radical prostatectomy, including 16% within
2 years, 22% within 3 years and up to 35% within 5 years of
surgery.
It was also interesting that the most common form of
secondary treatment in our series was androgen deprivation
therapy followed by external beam radiation therapy. Pa-
tients were much less likely (16%) to choose surgical inter-
vention as secondary treatment. This finding may be due to
the advanced age of the population that initially elected
watchful waiting, limited life expectancy due to competing
co-morbid conditions or patient preference against surgical
intervention.
While we did not determine why patients in the database
elected watchful waiting, it is likely that a number of factors
influenced this decision, including patient preference and
physician recommendation. McLaren et al followed 113 men
who chose watchful waiting after referral to the British Co-
lumbia Cancer Agency.12 Reasons for choosing watchful waiting
included patient preference in 37% of cases, physician recom-
mendation in 42%, decreased life expectancy in 19% and con-
traindication to radiotherapy in 2%. Mazur and Hickman
counseled 140 veterans at an outpatient medical clinic re-
garding radical prostatectomy and watchful waiting as treat-
ment options for prostate cancer.15 Patients were then asked
which option they would prefer if they were diagnosed with
prostate cancer and why they elected that specific treatment
option. Of the patients interviewed 53% stated that they
would prefer surgical treatment over watchful waiting, in-
cluding 92% who reported that the possibility of complete
tumor removal was the strongest factor influencing the deci-
sion. In contrast, 42% of the men stated that they would
Our study has limitations. Although the database repre-
sents a national population of patients from various practice
settings, serial PSA data were available for only 163 of the
329 patients (49.5%) studied. Since men were enrolled in the
database prospectively at diagnosis, and after diagnosis and
treatment, time dependent information was incomplete for
prefer observation as the initial disease treatment, of whom many patients. Those with similar disease characteristics
80% reported that the possibility of complications was the were not randomized to other treatment options, making it

88
PATTERNS OF PROSTATE CANCER TREATMENT
impossible to compare disease specific outcomes in watchful 13. Lu-Yao, G. L., Potosky, A. L., Albertsen, P. C. et al: Follow-up
prostate cancer treatments after radical prostatectomy: a
population-based study. J Natl Cancer Inst, 88: 166, 1996
14. Fowler, F. J., Jr., Barry, M. J., Lu-Yao, G. L. et al: Patient-
reported complications and follow-up treatment after radical
prostatectomy. The national Medicare experience: 1988–1990
(updated June 1993). Urology, 42: 622, 1993
15. Mazur, D. J. and Hickam, D. H.: Patient preferences for man-
agement of localized prostate cancer. West J Med, 165: 26,
1996
waiting versus other forms of initial treatment. In addition,
the rationale for the initial election of watchful waiting and
secondary treatment was not known. Nevertheless, our study
provides considerable insight into the natural history of pa-
tients selected for watchful waiting in this country. Such
information may be important to patients, physicians and
other health care professionals who counsel patients on the
various treatment options available for prostate cancer.
16. Fowler, F. J., Jr., Bin, L., Collins, M. M. et al: Prostate cancer
screening and beliefs about treatment efficacy: a national sur-
vey of primary care physicians and urologists. Am J Med, 104:
526, 1998
CONCLUSIONS
Men who elect initial watchful waiting for prostate cancer
tend to be older, and have lower serum PSA and more favor-
able disease characteristics than those who seek definitive
local therapy. A low percent of such men died of prostate
cancer in our study. Eventual treatment was given in 52% of
cases within 5 years of prostate cancer diagnosis. Patients
who were younger and had higher serum PSA at diagnosis
were significantly more likely to undergo secondary treat-
ment, as were those in whom serum PSA increased during
observation. The most common form of secondary treatment
was androgen deprivation therapy, followed by external
beam radiation therapy and radical prostatectomy.
EDITORIAL COMMENT
The appropriate treatment of newly diagnosed prostate cancer
continues to pose a dilemma for patients and clinicians. In younger
patients with high grade disease the risk of disease progression and
possible death from prostate cancer are sufficiently high to justify
the potential risk of complications associated with radical surgery or
radiation therapy. These men rarely elect watchful waiting. Older
men, especially those with relatively low grade disease, have a much
more difficult decision. Are the risks associated with treatment bal-
anced by the potential gain in longevity or quality of life? In the
absence of data from randomized trials patients must turn to case
series reports.
REFERENCES
These authors provide us with new information concerning this
important group of men. Using information available from the
CaPSURE database they convincingly demonstrated that men
electing watchful waiting are older than those seeking treatment
after the diagnosis of prostate cancer. While median followup is only
2.3 years, 23 patients died of various causes but only 3 died of
prostate cancer. At least 2 patients had serum PSA that many would
regard as too high to reflect localized disease. The remaining patient
was diagnosed more than 15 years ago and before the advent of PSA
1. Landis, S. H., Murray, T., Bolden, S. et al: Cancer statistics,
1998. CA Cancer J Clin, 48: 6, 1998
2. Johansson, J. E., Holmberg, L., Johansson, S. et al: Fifteen-year
survival in prostate cancer. A prospective, population-based
study in Sweden. JAMA, 277: 467, 1997
3. Chodak, G. W., Thisted, R. A., Gerber, G. S. et al: Results of
conservative management of clinically localized prostate can-
cer. New Engl J Med, 330: 242, 1994
4. Albertsen, P. C., Fryback, D. G., Storer, B. E. et al: Long-term
survival among men with conservatively treated localized testing. None of these patients would likely have benefited from
prostate cancer. JAMA, 274: 626, 1995
aggressive local therapy. Thus, we may assume that they made the
correct decision regarding treatment selection.
5. Adolfsson, J., Carstensen, J. and Lowhagen, T.: Deferred treat-
ment in clinically localized prostatic carcinoma. Br J Urol, 69:
183, 1992
A surprising 39% of these men underwent secondary cancer ther-
apy because of increasing serum PSA or concern regarding disease
progression. Will these secondary treatments improve clinical out-
comes? In the absence of randomized trials we will probably not
know. Physicians are usually quick to recommend treatment for
cancer. No matter what the outcome they claim a benefit for the
patient. If disease progresses, they have done everything possible. If
it does not progress, they assume that they have cured the patient.
6. Lubeck, D. P., Litwin, M. S., Henning, J. M. et al: The CaPSURE
database: a methodology for clinical practice and research in
prostate cancer. CaPSURE Research Panel, Cancer of the
Prostate Strategic Urologic Research Endeavor. Urology, 48:
773, 1996
7. Grossfeld, G. D., Stier, D. M., Flanders, S. C. et al: Use of second
treatment following definitive local therapy for prostate can-
cer: data from the CaPSURE database. J Urol, 160: 1398, 1998
8. Steinberg, G. D., Bales, G. T. and Brendler, C. B.: An analysis of
watchful waiting for clinically localized prostate cancer.
J Urol, 159: 1431, 1998
9. Wilt, T. J. and Brawer, M. K.: The Prostate Cancer Intervention
Versus Observation Trial (PIVOT). Oncology, 11: 1133, 1997
10. Albertsen, P. C., Hanley, J. A., Gleason, D. F. et al: Competing
risk analysis of men aged 55 to 74 years at diagnosis managed
conservatively for clinically localized prostate cancer. JAMA,
280: 975, 1998
11. Johansson, J. E.: Expectant management of early stage prostatic
cancer: Swedish experience. J Urol, part 2, 152: 1753, 1994
12. McLaren, D. B., McKenzie, M., Duncan, G. et al: Watchful wait-
ing or watchful progression? Prostate specific antigen doubling
times and clinical behavior in patients with early untreated
prostate carcinoma. Cancer, 82: 342, 1998
Simply watching
a patient is much more difficult. If disease
progresses, the physician has failed regardless of whether the tumor
was curable. If the disease does not progress, the patient assumes
that he did not need physician input.
The true value of this patient cohort will become evident during
the next several years. Although we may not be able to control for the
differences between men who seek secondary therapy and those who
do not, we will determine whether they fare as well as patients who
elect radical surgery or radiation therapy. With more information
concerning clinical outcomes, especially in men who choose to forgo
treatment, we will be better able to guide our patients to select a
clinical course that is most appropriate for their particular condition.
Peter C. Albertsen
Department of Urology
University of Connecticut Health Center
Farmington, Connecticut