Impact of Age at Diagnosis on Prostate Cancer Treatment and Survival

Article (PDF Available)inJournal of Clinical Oncology 29(2):235-41 · January 2011with35 Reads
DOI: 10.1200/JCO.2010.30.2075 · Source: PubMed
Abstract
Older men are more likely to be diagnosed with high-risk prostate cancer and to have lower overall survival. As a result, age often plays a role in treatment choice. However, the relationships among age, disease risk, and prostate cancer-specific survival have not been well established. We studied men in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database with complete risk, treatment, and follow-up information. High-risk patients were identified by using the validated Cancer of the Prostate Risk Assessment (CAPRA) score. Competing risks regression was used to identify the independent impact of age on cancer-specific survival. We also analyzed the effect of local treatment on survival among older men with high-risk disease. In all, 26% of men age ≥ 75 years presented with high-risk disease (CAPRA score 6 to 10). Treatment varied markedly with age across risk strata; older men were more likely to receive androgen deprivation monotherapy. Controlling for treatment modality alone, or for treatment and risk, age did not independently predict cancer-specific survival. Furthermore, controlling for age, comorbidity, and risk, older men with high-risk tumors receiving local therapy had a 46% reduction in mortality compared with those treated conservatively. Older patients are more likely to have high-risk prostate cancer at diagnosis and less likely to receive local therapy. Indeed, underuse of potentially curative local therapy among older men with high-risk disease may in part explain observed differences in cancer-specific survival across age strata. These findings support making decisions regarding treatment on the basis of disease risk and life expectancy rather than on chronologic age.

Full-text (PDF)

Available from: Matthew R Cooperberg
Impact of Age at Diagnosis on Prostate Cancer Treatment
and Survival
Seth K. Bechis, Peter R. Carroll, and Matthew R. Cooperberg
From the Helen Diller Family Comprehen-
sive Cancer Center, University of California-
San Francisco, San Francisco, CA.
Submitted April 29, 2010; accepted
October 7, 2010; published online
ahead of print at www.jco.org on
December 6, 2010.
CaPSURE is supported by Abbott Labo-
ratories, Chicago, IL, and by Grant No.
P50CA89520 from the National Insti-
tutes of Health/National Cancer Insti-
tute University of California-San
Francisco Special Program of Research
Excellence.
Authors’ disclosures of potential con-
flicts of interest and author contribu-
tions are found at the end of this
article.
Corresponding author: Matthew R.
Cooperberg, MD, MPH, University of
California, San Francisco, Box 1695,
1600 Divisadero St, A-607, San Fran-
cisco, CA 94143-1695; e-mail:
mcooperberg@urology.ucsf.edu.
© 2010 by American Society of Clinical
Oncology
0732-183X/11/2902-235/$20.00
DOI: 10.1200/JCO.2010.30.2075
ABSTRACT
Purpose
Older men are more likely to be diagnosed with high-risk prostate cancer and to have lower overall
survival. As a result, age often plays a role in treatment choice. However, the relationships among
age, disease risk, and prostate cancer–specific survival have not been well established.
Patients and Methods
We studied men in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE)
database with complete risk, treatment, and follow-up information. High-risk patients were
identified by using the validated Cancer of the Prostate Risk Assessment (CAPRA) score.
Competing risks regression was used to identify the independent impact of age on cancer-specific
survival. We also analyzed the effect of local treatment on survival among older men with
high-risk disease.
Results
In all, 26% of men age 75 years presented with high-risk disease (CAPRA score 6 to 10).
Treatment varied markedly with age across risk strata; older men were more likely to receive
androgen deprivation monotherapy. Controlling for treatment modality alone, or for treatment and
risk, age did not independently predict cancer-specific survival. Furthermore, controlling for age,
comorbidity, and risk, older men with high-risk tumors receiving local therapy had a 46% reduction
in mortality compared with those treated conservatively.
Conclusion
Older patients are more likely to have high-risk prostate cancer at diagnosis and less likely to
receive local therapy. Indeed, underuse of potentially curative local therapy among older men with
high-risk disease may in part explain observed differences in cancer-specific survival across age
strata. These findings support making decisions regarding treatment on the basis of disease risk
and life expectancy rather than on chronologic age.
J Clin Oncol 29:235-241. © 2010 by American Society of Clinical Oncology
INTRODUCTION
By 2030, almost 20% of men in the United States will
be older than age 65 years compared with 12% in
2000.
1
Overall life expectancy continues to improve,
with the average life expectancy of a 70-year-old
man now reaching 13 years.
2
Prostate cancer inci-
dence increases with advancing age; thus, it can be
anticipated that the prevalence of prostate cancer in
men older than age 65 years will continue to in-
crease. Prostate cancer already is the most common
malignancy among older men
3
; 64% of new prostate
cancer cases in the United States were diagnosed in
men older than age 65 years, and 23% in men older
than age 75 years.
4
Despite the predicted increase in prevalence of
disease in the elderly, most studies investigating op-
timal treatment regimens have focused on men
younger than 75 years of age. Ongoing prospective
studies investigating the utility of prostate cancer
screening exclude patients older than age 75 years.
5,6
Likewise, the US Preventive Services Task Force
(USPSTF) explicitly recommends against screening
men age 75 years or older—yet this statement is
based in large part on extrapolations from studies of
patients younger than age 75 years and does not
account for health status or comorbidities.
7
Fur-
thermore, nomograms predicting outcomes after
prostatectomy are principally derived from data-
sets with a median age 65 years.
8
Reports of
treatment trends have found high prevalence
of both overtreatment
9
and undertreatment
10
of
older men diagnosed with prostate cancer. Patient
age is thus a frequent source of disparity both in
treatment practice and in clinical trial recruit-
ment and participation.
11,12
Older men in the United States are more likely
to be diagnosed with high-risk prostate cancer and
JOURNAL OF CLINICAL ONCOLOGY ORIGINAL REPORT
VOLUME 29 NUMBER 2 JANUARY 10 2011
© 2010 by American Society of Clinical Oncology 235
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to have lower overall and cancer-specific survival.
8,12-14
However, the
evolution and progression of cancer of a given grade and stage should
be expected to occur independent of chronologic age. Therefore, vari-
ation in lead-time at diagnosis and in management may explain, at
least in part, observed differences in cancer-specific survival. Indeed,
patient age is known to strongly influence treatment decision making,
with older men less likely to receive potentially curative therapy.
15
However, the independent impact of age on prostate cancer–specific
survival has not been well established.
Recent studies
8,16
have shown that with careful patient selection,
older men up to age 75 years with Gleason score 5 to 7 prostate cancer
and up to age 80 years with Gleason score 8 to 10 disease who undergo
radical prostatectomy or radiotherapy have gains in life expectancy
and quality-adjusted life expectancy comparable with those of younger
men, raising the question of whether age per se drives outcomes and,
in turn, whether it should drive treatment selection. We therefore
sought to understand whether age plays a role in disease risk and
prostate cancer–specific survival in a large, prospective patient cohort.
Table 1. Baseline Study Sample Characteristics
Characteristic
Age Group (years)
Total55 56-65 66-75 75
No. % No. % No. % No. % No. %
Race/ethnicity
Latino 26 2 74 2 82 2 13 1 195 2
African American 200 14 508 13 429 9 79 5 1,216 10
White 1,158 82 3,336 83 4,083 87 1,585 93 10,162 86
Other 27 2 87 2 73 2 30 2 217 2
Comorbidities
0 308 22 646 16 528 11 142 8 1,624 14
1 352 25 895 22 931 20 264 15 2,442 21
2 220 16 740 18 995 21 362 21 2,317 20
3 102 7 437 11 708 15 295 17 1,542 13
3 51 4 340 8 574 12 276 16 1,241 11
Missing 378 27 947 24 931 20 368 22 2,624 22
PSA at diagnosis, ng/mL
0-10 1,121 79 2,908 73 3,056 65 864 51 7,949 67
10-20 136 10 513 13 818 18 425 25 1,892 16
20-30 19 1 105 3 209 4 113 7 446 4
30 44 3 178 4 243 5 177 10 642 5
Missing 91 6 301 7 341 7 128 8 861 7
Gleason score
2-6 1,011 72 2,623 65 2,813 60 805 47 7,252 62
34 213 15 613 15 732 16 318 19 1,876 16
43 71 5 278 7 406 9 188 11 943 8
8-10 67 5 272 7 413 9 262 15 1,014 9
Missing 49 3 219 5 303 6 134 8 705 6
Clinical stage
T1 744 53 1,959 49 2,034 44 630 37 5,367 46
T2a/b 357 25 1,090 27 1,404 30 536 31 3,387 29
T2c 231 16 673 17 857 18 406 24 2,167 18
T3a 16 1 69 2 132 3 60 4 277 2
Missing 64 4 214 5 240 5 75 4 592 5
Percent positive biopsy
10 156 11 424 11 514 11 159 9 1,253 11
11-33 514 36 1,364 34 1,534 33 494 29 3,906 33
34-50 386 27 980 24 1,111 24 411 24 2,888 25
51-75 114 8 368 9 418 9 155 9 1,055 9
75 128 9 432 11 504 11 220 13 1,284 11
Missing 113 8 437 11 586 13 268 16 1,404 12
Treatment
RP 1,197 85 2,801 70 1,810 39 47 3 5,855 50
Cryotherapy 15 1 129 3 263 6 51 3 458 4
Brachytherapy 81 6 441 11 789 17 241 14 1,552 13
EBRT 45 3 290 7 804 17 350 21 1,489 13
PADT 49 3 232 6 661 14 696 41 1,638 14
WW 24 2 112 3 340 7 322 19 798 7
Total 1,411 4,005 4,667 1,707 11,790
Abbreviations: PSA, prostate-specific antigen; RP, radical prostatectomy; EBRT, external-beam radiation therapy; PADT, primary androgen deprivation therapy; WW,
watchful waiting.
Bechis, Carroll, and Cooperberg
236 © 2010 by American Society of Clinical Oncology JOURNAL OF CLINICAL ONCOLOGY
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Copyright © 2011 American Society of Clinical Oncology. All rights reserved.
We hypothesized that with adequate control for disease risk charac-
teristics and treatment, the impact of age on cancer-specific survival
may attenuate, and furthermore that variation in treatment driven by
age rather than risk may explain observed survival differences.
PATIENTS AND METHODS
Disease Registry
Data for analysis were abstracted from the Cancer of the Prostate Strate-
gic Urologic Research Endeavor (CaPSURE), a longitudinal, observational
disease registry of men with biopsy-proven prostate cancer, recruited from 40
community-based and academic urology practices throughout the United
States. The database includes demographic, clinical, treatment, and follow-up
outcome data on 13,805 patients as of July 2008. Comorbidities were recorded
at baseline and follow-up, and a comorbidity score based on the Charlson
index was recorded.
17
Informed consent was obtained from each patient
under institutional review board approval, and patients were followed until
death or withdrawal from the study. Clinicians reported mortality events,
copies of state death certificates were obtained, and the National Death Index
was queried annually to identify date and cause of death for men lost to
follow-up or whose certificates were not available. Detailed descriptions of the
CaPSURE project methods can be found elsewhere.
18-20
Study Design
Patients included in the analysis had localized disease (clinical stage up to
T3aN0M0); complete risk, treatment, and age data available; comorbidity and
ethnicity information available; and at least 6 months of follow-up after treat-
ment. To determine whether age impacts disease severity, patient age was
categorized as 55, 56 to 65, 66 to 75, and 75 years at the time of diagnosis.
Risk was determined by the Kattan preoperative nomogram
21
and the Uni-
versity of California-San Francisco Cancer of the Prostate Risk Assessment
(CAPRA) score.
22
CAPRA scores of 0 to 2, 3 to 5, and 6 to 10 defined low-,
intermediate-, and high-risk groups, respectively, as previously validated.
22
Treatment modalities included radical prostatectomy (RP), cryotherapy,
brachytherapy, electron beam radiation therapy (EBRT), primary androgen depri-
vation therapy (PADT), and watchful waiting/active surveillance (WW/AS).
Statistical Analysis
Logistic regression was used to determine the likelihood of receiving any
local treatment (RP, EBRT, brachytherapy, or cryotherapy) by age at diagnosis,
controlling for CAPRA score and year of treatment. The Pearson
2
test was
used to compare risk stratification and treatment patterns among men of
various age groups. We assessed the relationships between age and both
cancer-specific survival and overall survival via univariate Kaplan-Meier sur-
vival analysis. Fine and Gray’s competing risks regression
23
was performed to
identify independent predictors of prostate cancer–specific survival while ad-
justing for age, year of treatment, treatment modality, and risk as determined
by the CAPRA or Kattan score. Subhazard ratios (SHRs) were calculated with
their 95% CIs.
We further analyzed the impact of local treatment on cancer-specific
survival and overall survival among older men (defined as either 70 or 75
years old) with high-risk disease (CAPRA score of 6 to 10). We used competing
risks regression for cancer-specific survival and standard Cox proportional
hazards analysis for overall survival. Both analyses were adjusted for prostate-
specific antigen (PSA), Gleason score, percent of biopsy cores positive, clinical
stage, and year of treatment; the all-cause mortality analysis was additionally
adjusted for comorbidity. All statistical tests were two-sided, and analyses were
performed by using STATA version 11 (STATA, College Station, TX).
RESULTS
In our analysis, of the 13,805 men in CaPSURE, 12,286 had known
primary treatment and at least 6 months of subsequent follow-up; of
these, 496 had nonlocalized disease and were excluded, leaving 11,790.
Baseline characteristics of the study sample are provided in Table 1.
There was no consistent association between age and likelihood of
missing data (11.4%, 20.0%, 10.1%, and 11.9% for men age 55, 56
to 65, 66 to 75, and 75 years, respectively). Mean standard deviation
age in the overall cohort was 66.2 8.6 years, and median age was 66
years. Of these men 1,411 (12.0%) were age 55 years at the time of
treatment, 4,005 (34.0%) were age 56 to 65, 4,667 (39.6%) were age 66 to
75, and 1,707 (14.5%) were older than age 75 years. The likelihood of
high-risk disease by CAPRA classification increased significantly
with increasing age cohort (P.001 by Mantel-Haenszel
2
; Fig 1).
We observed substantial variation in treatment based on patient
age and disease risk (Fig 2); in general, treatment varied to a greater
extent with age at diagnosis than with cancer risk. Older men in
particular were more likely to be treated with PADT than their
CAPRA 0−2 CAPRA 3−5 CAPRA 6−10
Age Group (years)
Percentage of Patients
100
80
60
40
20
0
< 55 55−59 60−64 65−69 70−74 75−79 80
68.5
25.6
5.8
60.9
30.6
8.5
55.3
33.7
11.0
49.9
37.8
12.3
42.5
43.3
14.2
36.0
42.6
21.4
24.9
41.6
33.4
Fig 1. Distribution of disease risk by age at diagnosis. Proportion of patients in each
risk category are given by age stratum; risk is defined by validated groupings of the
Cancer of the Prostate Risk Assessment (CAPRA) scores 0 to 2, 3 to 5, or 6 to 10.
2
89
61
1
2
1
87
62
2
2
0
63
3
13
3
18
3
75
14
3
2
2
1
73
9
8
3
6
1
46
8
17
6
21
10
41
23
11
5
10
4
42
16
18
7
13
1
25
11
29
8
26
24
2
26
17
4
27
15
3
17
22
3
40
8
2
7
21
3
60
0−2CAPRA Score 3−5 6−10 0−2 3−5 6−10 0−2 3−5 6−10 0−2 3−5 6−10
WW RP Brachy EBRT Cryo PADT
Percentage of Patients
100
80
60
40
20
0
55 56−65 66–75 > 75
Age Group (years)
Fig 2. Distribution of treatment modality by Cancer of the Prostate Risk
Assessment (CAPRA) risk score and by age cohort. For patients in each age
stratum within each risk group (defined by CAPRA scores 0 to 2, 3 to 5, or 6 to
10), distribution among treatments is given. WW, watchful waiting; RP, radical
prostatectomy; Brachy, brachytherapy; EBRT, external-beam radiation therapy;
Cryo, cryotherapy; PADT, primary androgen deprivation therapy.
Age Does Not Predict Prostate Cancer–Specific Survival
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younger counterparts, regardless of their risk score. Furthermore, men
with high-risk disease were more likely to receive PADT than their
age-matched low-risk counterparts. Men with increasing age were less
likely to receive local therapy in general, and surgical treatment in
particular, regardless of disease risk. Compared with men age 55
years, and adjusting for CAPRA score and year of treatment, the odds
ratios for receiving local treatment were 0.59 (95% CI, 0.43 to 0.81),
0.21 (95% CI, 0.15 to 0.28), and 0.04 (95% CI, 0.03 to 0.06) for men
age 56 to 65, 66 to 75, and 75 years, respectively.
Age at diagnosis was a univariate predictor of both overall and
prostate cancer–specific mortality; unadjusted Kaplan-Meier survival
curves showed decreasing survival rates among men with increasing
age (log-rank P.001; Fig 3). On competing risks analysis controlling
only for year of treatment, age as a continuous variable was a predictor
of cancer-specific mortality (SHR, 1.02; 95% CI, 1.01 to 1.03; P.01).
When age was analyzed as a categorical variable, there was a consistent
trend toward increased cancer-specific mortality with increasing age,
but this did not reach statistical significance until men older than age
75 years were compared with those age 55 years (Table 2).
On multivariable competing risks analysis, however, controlling
either for treatment modality alone or for treatment modality and
disease risk, age was no longer a predictor of prostate cancer–specific
survival (Table 3). When controlling for treatment modality alone, all
four age cohorts shared equal outcomes in terms of survival despite
differences among specific treatments. When further adjusting for risk
as well as year and treatment, the impact of age on prostate cancer–
specific survival was further reduced. Of note, both CAPRA and Kat-
tan risk scores were continuous predictors of mortality (hazard ratio
[HR], 1.39; 95% CI, 1.32 to 1.47 and HR, 0.98; 95% CI, 0.97 to 0.98,
respectively; both P.001).
Among 629 men 70 years old with high-risk (CAPRA score 6
to 10) disease, 275 (44%) died during follow-up at a median of 5.7
years; 57 (21% of decedents) died of prostate cancer. Among 392
men 75 years old with high-risk disease, 183 (47%) died during
follow-up at a median of 5.3 years; 36 (20% of decedents) died of
prostate cancer. Receipt of local therapy among older men with high-
risk tumors was strongly associated with decreased mortality,
although the association was not statistically significant for cancer-
specific mortality among men older than age 75 years. After con-
trolling for tumor risk and year of treatment, the SHR for cancer-
specific mortality was 0.54 (95% CI, 0.32 to 0.92) for men age 70
years and 0.61 (95% CI, 0.30 to 1.25) for men age 75 years. After
controlling for these variables in addition to comorbidity, the HR for
all-cause mortality after local therapy was 0.54 (95% CI, 0.41 to 0.72)
for men age 70 years and 0.58 (95% CI, 0.40 to 0.84) for men age
75 years. There were no differences in survival between men receiv-
ing PADT and those receiving WW/AS in any analysis.
DISCUSSION
With increasing age, men are significantly more likely to have high-
risk prostate cancer. There is common use of PADT and WW/AS
among these older men and less local therapy, particularly RP, com-
pared with younger men. On univariate analysis, age predicted overall
AB
0
55
56−65
66−75
> 75
Cancer-Specific Survival (proportion)
Follow-Up Time (years)
No. at risk
Age 55 1,410 905 429 178 108
Age 56−65 4,004 2,730 1,398 712 429
Age 66−75 4,666 3,415 2,005 1,058 666
Age 75 1,706 1,188 672 324 169
1.0
0.8
0.6
0.4
0.2
2.5 5.0 7. 5 10.0 0
55
56−65
66−75
> 75
Overall Survival (proportion)
Follow-Up Time (years)
No. at risk
Age 55 1,410 905 429 178 108
Age 56−65 4,004 2,730 1,398 712 429
Age 66−75 4,666 3,415 2,005 1,058 666
Age 75 1,706 1,188 672 324 169
1.0
0.8
0.6
0.4
0.2
2.5 5.0 7. 5 10.0
Fig 3. Unadjusted Kaplan-Meier plots of cancer-specific and overall survival by age stratum.
Table 2. Prostate Cancer–Specific Mortality by Age: Univariate Analysis
Age (years)
Competing Risks Regression
Hazard Ratio 95% CI P
55 Reference
56-65 1.36 0.86 to 2.13 .19
66-75 1.43 0.92 to 2.21 .11
75 1.86 1.17 to 2.97 .009
Bechis, Carroll, and Cooperberg
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Copyright © 2011 American Society of Clinical Oncology. All rights reserved.
and prostate cancer–specific survival. However, when controlling for
either treatment modality alone or treatment modality and risk, age
was not an independent predictor of mortality from prostate cancer.
These findings suggest that under-use of potentially curative local
therapy among older men with high-risk disease may in part explain
higher cancer-specific mortality rates observed with increasing age.
Overall survival is of course lower in patients of increasing age,
reflecting the impact of other variables including comorbidities, in-
creased susceptibility to major illness, and decreased immune re-
sponse. However, our data support the hypothesis that prostate cancer
evolution, and hence mortality, occurs not on the basis of patient age
but instead on the basis of cellular mechanisms whose malignant
potential can be categorized by established disease risk features. There-
fore, older patients with clinically localized, high-risk disease, and a
noncancer life expectancy of 10 years should be considered for
surgical treatment and/or radiation therapy. Recent studies have
shown that with careful patient selection, gains in life expectancy in
men older than age 70 years following radical or laparoscopic prosta-
tectomy are comparable to those in younger men.
8,16
Indeed, comor-
bidity has been found to be a more important predictor of surgical
complications than age.
24
Another recent report
20
found that among
men with higher-risk disease, mortality outcomes are improved fol-
lowing RP with either EBRT or PADT, findings that held with adjust-
ment for age.
Our findings suggest a serious discrepancy among older patients
between actual treatment practices and optimal treatment. Optimal
treatment should be based primarily on disease risk and other clinical
factors rather than chronologic age, yet actual treatment practices
appear to reflect variation driven rather by physician practice style and
patient age. In our analysis, the relatively few older men with high-risk
disease who received local therapy had nearly a 50% reduction in
risk-adjusted mortality compared with those in the same age cohort
who received PADT or WW/AS. However, most older men were more
likely to receive PADT, regardless of disease risk category, although the
benefit of hormonal therapy in localized cancer is unclear
4,25
and
PADT is associated with potential musculoskeletal, cardiovascular,
and other adverse effects.
26,27
Multiple previous studies have similarly reported that older men
were less likely to undergo the potentially curative treatments of RP or
radiotherapy, regardless of disease risk and comorbidities.
12,28-30
Men
younger than 60 years of age are 25 times more likely to receive RP
than men older than 70 years of age, likely due in part to physician
tendencies to avoid surgery in older men.
31,32
Indeed, individual
physician preferences have been shown to play a significant role in
determining whether patients receive PADT or any potentially life-
prolonging treatment.
31-34
Prior reports found that more than 15% of
men older than age 75 years with high-risk disease were undertreated,
and a majority never received curative therapy for their prostate can-
cer.
10,35
Our results further suggest that prostate cancer survival dif-
ferences across age strata are influenced by treatment decisions, which
are themselves driven by age, not disease risk.
An earlier analysis
12
of more than 2,000 men older than age 75
years in CaPSURE found that patient comorbidities and tumor-risk
characteristics did not play a substantial role in treatment decision
making. Similarly, in a study of PSA screening rates in US Veterans
Affairs patients,
36
among men older than age 85 years, those in the best
health were screened less frequently than their counterparts in the
worst health. The USPSTF recommendation against screening all men
older than age 75 years also fails to consider comorbidity; such a broad
statement could potentially harm older men in otherwise good health
by missing treatable high-risk tumors.
37
We found that within 5 years
of follow-up of high-grade disease among men older than age 75 years,
cancer-specific mortality reaches 20%; similar findings from other
databases have been reported elsewhere.
38
The estimation of life expectancy remains a difficult task, with
both individual clinicians and life-table nomograms suffering from
suboptimal accuracy.
39,40
However, comorbidity and risk assessment
remain critical to determining appropriate disease management to
minimize both overtreatment of low-risk disease and undertreatment
of high-risk disease. Overestimation of life expectancy can lead to
overtreatment of lower-risk prostate cancer, especially in elderly
men.
14,34
Conversely, our data suggest that undertreatment, or unnec-
essary treatment with suboptimal therapy, is an equally important
problem. The use of PADT increases dramatically with age despite a
lack of evidence to support its efficacy as a monotherapy for localized
disease.
4,9
Developing more stringent criteria to help guide treatment
in elderly men may enable a more uniform standard of care that could
decrease morbidity and prevent unnecessary therapy.
The limitations of our study deserve mention. Comorbidity re-
porting is based on self-report and may not completely reflect the
impact of comorbid illness on overall survival for each patient. How-
ever, the concordance of the proportional hazards and competing
risks analyses is reassuring in this regard. Identifying cancer-specific
mortality as determined by review of death certificates is limited by the
thoroughness of information documented on the certificates, which
in turn relies on the individual physician’s knowledge of each patient’s
history. As a result, the database may underestimate mortality from
prostate cancer because of the presence of other comorbidities and/or
Table 3. Multivariate Competing Risks Regression Analysis Controlling for Treatment Modality Alone or Treatment Modality and Cancer Risk by Age Cohort
(CAPRA or Kattan)
Age (years)
Age, Year Age, Year, Treatment
Age, Year, Treatment,
CAPRA Score
Age, Year, Treatment,
Kattan Score
SHR 95% CI PSHR 95% CI PSHR 95% CI PSHR 95% CI P
55 Ref Ref Ref Ref
56-65 1.36 0.86 to 2.13 .19 1.29 0.82 to 2.03 .27 1.19 0.66 to 2.14 .57 0.99 0.96 to 1.02 .50
66-75 1.44 0.93 to 2.23 .10 1.10 0.69 to 1.74 .70 0.93 0.51 to 1.71 .82 1.06 0.58 to 1.95 .85
75 1.91 1.20 to 3.05 .01 1.01 0.60 to 1.70 .98 0.81 0.41 to 1.62 .56 1.03 0.56 to 1.91 .91
Abbreviations: CAPRA, Cancer of the Prostate Risk Assessment; SHR, subhazard ratio; Ref, reference.
Age Does Not Predict Prostate Cancer–Specific Survival
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Copyright © 2011 American Society of Clinical Oncology. All rights reserved.
toxicities of treatment. It is important to consider why a given tumor
was detected relatively late in life: a tumor detected in the context of a
slowly rising PSA and prior negative biopsies may be quite different
biologically from one detected in an older man who had never been
screened previously. However, the focus of the CaPSURE registry is on
management, not screening, so the database includes a variable depth
of information on prediagnosis PSA values. Therefore, the impact of
the intensity of prior screening on disease risk at diagnosis cannot be
ascertained by using this database.
CaPSURE comprises data from community-based and academic
urology practice sites across the country, but these sites were not
chosen at random and the population cannot be assumed to represent
a statistically valid sample of the US prostate cancer population. Afri-
can Americans, for example, are moderately represented in the data-
base, but other ethnic groups are underrepresented compared with
the larger population. In addition, CaPSURE patients tend to have a
higher socioeconomic status on average compared with the overall
population.
22
A total of 1,519 patients (11%) were excluded because of
incomplete treatment and/or follow-up data. These gaps in the data are
attributable to variability among the large number of physicians at multi-
ple sites submitting data to the registry. There is no indication that the
missing data are nonrandomly distributed across the age strata.
When diagnosed with prostate cancer, older men are more likely
to have high-risk disease and are more likely to be treated with PADT
rather than potentially curative local therapy. Older men also have
lower overall survival. However, when controlling for treatment mo-
dality alone, or treatment modality and cancer risk category, age is not
an independent predictor of prostate cancer–specific survival. These
results may be due in part to differences in treatment by age group;
older men are more likely to be treated by PADT or WW/AS. Those
with high-risk tumors who receive local therapy have a 46% reduction
in risk-adjusted mortality compared with men managed conserva-
tively. These findings highlight the importance of making treatment
decisions guided by disease risk and life expectancy rather than chro-
nologic age. Most older men with low-risk disease are candidates for
active surveillance, but selected patients with more aggressive tumors
should not be denied the opportunity for potentially curative lo-
cal therapy.
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS
OF INTEREST
Although all authors completed the disclosure declaration, the following
author(s) indicated a financial or other interest that is relevant to the subject
matter under consideration in this article. Certain relationships marked
with a “U” are those for which no compensation was received; those
relationships marked with a “C” were compensated. For a detailed
description of the disclosure categories, or for more information about
ASCO’s conflict of interest policy, please refer to the Author Disclosure
Declaration and the Disclosures of Potential Conflicts of Interest section in
Information for Contributors.
Employment or Leadership Position: None Consultant or Advisory
Role: None Stock Ownership: None Honoraria: Peter R. Carroll,
Takeda Pharmaceuticals; Matthew R. Cooperberg, Takeda
Pharmaceuticals, Abbott Laboratories Research Funding: None Expert
Testimony: None Other Remuneration: None
AUTHOR CONTRIBUTIONS
Conception and design: Peter R. Carroll, Matthew R. Cooperberg
Financial support: Peter R. Carroll
Administrative support: Peter R. Carroll
Provision of study materials or patients: Peter R. Carroll
Data analysis and interpretation: Seth K. Bechis,
Matthew R. Cooperberg
Manuscript writing: Seth K. Bechis, Peter R. Carroll,
Matthew R. Cooperberg
Final approval of manuscript: Seth K. Bechis, Peter R. Carroll,
Matthew R. Cooperberg
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Age Does Not Predict Prostate Cancer–Specific Survival
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    • "The significantly lower prevalence of advanced prostate cancer, especially lower prevalence of GS 8–10 in the S group, was considered to be associated with higher cancerspecific survival. Older patients are more likely to have high-risk prostate cancer at diagnosis [12, 21]. The difference in the median age between the two groups was only 2 years; however, this difference might be responsible for the significantly lower prevalence of GS 8–10 prostate cancer in the S group. "
    Chapter · Sep 2016 · Journal of Population Economics
    • "Older men with prostate cancer more often have larger, higher-grade tumors than younger men, but only a minority with high-risk localized disease receive treatment with curative intent [1][2][3][4][5]. Furthermore, older patients with advanced disease may be denied survival-extending treatments such as chemotherapy because of toxicity concerns [6,7]. "
    [Show abstract] [Hide abstract] ABSTRACT: Aims: To compare the efficacy and tolerability of taxane and nontaxane therapy in senior adults with chemonaïve metastatic castration-resistant prostate cancer (mCRPC), and examine the effect of patient health status on outcomes. Patients and methods: Between 2009 and 2011, 333 patients aged≥70 years with mCRPC were enrolled in a prospective international registry. Patients were categorized as having received taxane-based or nontaxane therapy, and classified as fit, vulnerable, frail, or terminal, according to investigator judgement or International Society of Geriatric Oncology guidelines. Efficacy measures included overall survival (OS) and progression-free survival. Grade 3/4 toxicities were recorded. Predictors of OS were identified using multivariate Cox regression. Results: The proportions of fit/vulnerable/frail patients were 65%/14%/17% (International Society of Geriatric Oncology), and 39%/43%/17% (investigator). In single-factor analyses, taxane therapy improved OS (hazard ratio [95%CI] = 0.53 [0.30-0.93]; P = 0.027) and progression-free survival (hazard ratio [95% CI] = 0.55 [0.40-0.76]; P<0.001) vs. nontaxane therapy. Patients with frailty also benefited from taxane therapy (adapted regimen in 52%). In multivariate analysis, taxanes improved OS even with poor prognostic factors present (P = 0.017); age was unrelated to prognosis. Taxane therapy was well tolerated; most common grade 3/4 toxicities (taxane vs. nontaxane) were fatigue (17% vs. 4%), nausea/vomiting (14% vs. 5%) and neutropenia (10% vs. 1%). Conclusions: The results of this nonrandomized, observational study suggest that first-line taxane therapy may benefit senior adults with mCRPC more than alternative therapies. Treatment decisions should not be based on chronological age.
    Full-text · Article · Jan 2016
    • "! 20! of age (Early Breast Cancer Trialists' Collaborative Group 2005; Wilcken, Horbuckle, and Ghersi 2003; Bechis, Carroll, and Cooperberg 2011). While new cancer drugs tend to diffuse more rapidly in the United States, some research suggests the overall availability of expensive cancer drugs in the two countries may be similar, at least in recent years (Faden et al. 2009). "
    [Show abstract] [Hide abstract] ABSTRACT: The effectiveness of cancer screening is a salient health policy issue that remains unresolved. This article sheds new light on the benefits of population-wide cancer screening. We investigate changes in mortality after the introduction of screening guidelines for breast and prostate cancers in the USA and UK. We use differences in the timing of guideline adoption, differences in ages recommended for screening, and differences in which cancers are detectable by screening to identify the effect of cancer screening guidelines. Our quadruple-differencing strategy finds a moderately sized mortality benefit from mammography and prostate-specific antigen (PSA) screening guidelines among recommended age groups and little change in mortality rates among age groups not recommended to receive screening. As a falsification test, we verify that prostate cancer rates among men did not fall after the introduction of mammography screening and breast cancer rates among women did not fall after the introduction of the PSA test.
    Full-text · Article · Oct 2015
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