Economic Evaluation of Treatment Strategies for Benign Prostatic Hyperplasia—Is Medical Therapy More Costly in the Long Run? Christopher S. Saigal,* Mehran Movassaghi, Jennifer Pace, Geoffrey Joyce and the Urologic Diseases in America Project From the Department of Urology, University of California-Los Angeles Medical Center, Los Angeles, California Purpose: Although medical therapy for newly diagnosed benign prostatic hyperplasia is initially less expensive than surgery, to our knowledge the long-term costs of these treatments are unknown. We defined longer term costs of these treatment strategies. Materials and Methods: We examined spending on benign prostatic hyperplasia related services by examining health care claims for a 5-year period subsequent to a new benign prostatic hyperplasia diagnosis. Expenditures for subjects treated initially with surgery were compared to expenditures for those with initial medical treatment. Expenditures were projected during longer periods and the net current value of these expenditures was calculated. Results: Of the 970 subjects identified who received benign prostatic hyperplasia treatment 913 (94.1%) relied on medical therapy as initial treatment. Of those subjects 832 (91.1%) were on ␣-blockers. The secondary treatment rates for surgery far exceeded those for medical therapy (37% vs 8%). Average total expenditures were higher for subjects who initially received surgery ($12,699, 95% CI 9,865–15,533) than for those initially treated with medication ($2,193, 95% CI 1,959 –2,428). If future streams of spending were discounted at standard rates (3%), the costs of initial medical therapy as a treatment strategy would always be lower than those of initial surgical therapy even at 40 years. Conclusions: In a cohort of privately insured men with newly diagnosed benign prostatic hyperplasia monotherapy with ␣-blockers was the most common initial treatment. Surgical therapy was associated with higher treatment failure rates and higher costs during 5 years. Increased expenditures related to initial surgical therapy were consistent when projected over long time frames. Key Words: prostate, prostatic hyperplasia, outcome assessment (health care), health expenditures
Beforetheadventofeffectivemedicaltherapysurgery edgedataoncomplicationratesandlong-termexpenditures
for BPH was the mainstay of treatment. However,
associated with BPH treatment have not been reported. To
␣-adrenergic antagonist medications (␣-blockers),
gain insight into the costs of differing initial treatment strat-
which were introduced in the 1990s, have largely supplanted
egies for BPH we evaluated the costs of initial medical or
surgical therapy as first line treatment for BPH, as evi-
surgical therapy for BPH in a cohort of privately insured
denced by the rapidly decreasing rate of BPH related sur-
men followed for 5 years. Our primary hypothesis was that
The number of prostatectomies performed in Medi-
for younger men with BPH initial surgical treatment would
care beneficiaries decreased from 250,000 in 1987 to 88,000
be less expensive than lifelong medical therapy after ac-
in This 65% decrease in TURP occurred despite a
counting for treatment failure rates.
sustained increase in the number of male beneficiaries andit coincided with a dramatic increase in office visits forThis change in the national treatment paradigm for
MATERIALS AND METHODS
BPH occurred with only limited analysis of the implications
Data Source
We examined spending on BPH related services for noneld-
Although initial surgical treatment is more costly than
erly patients with employer provided insurance. The data
initial medical therapy in the short term, to our knowledge
included enrollment files as well as medical and pharmacy
the longer term costs associated with these treatment strat-
claims for 25 large employers in the United States covering
egies are unknown, especially the costs associated with med-
40,895 male beneficiaries 40 years and older who were con-
ical and surgical failures. Studies of this topic examined this
tinuously enrolled in their employer provided plan from
question using computer models, relying on various assump-
1997 to 2002. Claims files captured all health care claims
tions drawn from experts and clinical To our knowl-
and encounters, including prescription drugs. Medical claimsincluded date of service, diagnosis and procedure codes, andexpenditures, including billed charges, negotiated discounts,
Submitted for publication July 12, 2006.
excluded expenses, deductibles, co-payments, payments made
* Correspondence: Department of Urology, Center for Health Sci-
by the employer and employee, and other third party coverage.
ences, University of California-Los Angeles Medical Center, Box
Drug claims included information on drug type, place of pur-
951738, 10833 Le Conte Ave., Los Angeles, California 90095 (tele-phone: 310-206-8183; FAX: 310-206-5343; e-mail: csaigal@ucla.edu).
chase and expenditures. The enrollment files allowed us to
Copyright 2007 by AMERICAN UROLOGICAL ASSOCIATION
DOI:10.1016/j.juro.2006.11.083
ECONOMIC EVALUATION OF BENIGN PROSTATIC HYPERPLASIA TREATMENT STRATEGIES
track who was eligible for services as well as basic demograph-
ics, such as patient age, gender, marital status and relation-ship to the sponsoring employee. Cohort Identification
We identified patients receiving treatment for BPH based on
diagnostic codes (International Classification of Disease, 9th
edition), procedure codes (Common Procedural Terminol-
ogy), and National Drug Codes for BPH and BPH related
medications (see Appendix). Subjects were initially selected
based on primary or secondary International Classification
of Disease, 9th edition diagnosis codes for BPH. Men whohad a claim as described in 1997 were excluded to create acohort of incident cases of BPH in 1998. Subjects were fur-
were for generic formulations of the drugs. A total of 71 men
ther stratified according to the type of medical intervention
(7.8%) who were initially on medical therapy underwent a
(␣-blocker alone, 5␣-reductase inhibitor alone or combina-
surgical procedure at a later date. Of these men 92% initially
tion therapy) using medication claims. These patients were
used ␣-blocker monotherapy, 7% initially used 5␣-reductase
then followed through their claims to determine the need for
inhibitors and 1% initially used combination therapy. Of the
continued or additional therapy as well as related expendi-
subjects 57 had surgical intervention as their index event,
tures during the 5 years of observation.
including transurethral prostatectomy in 56 and open pros-
To accomplish this, subjects were stratified into 2 cohorts
tatectomy in 1 (cohort 2). Seven of those men (12%) under-
according to their initial BPH treatment selection. Cohort 1
went a second procedure and 14 (25%) received subsequent
was composed of subjects who initially chose medical therapy
with an ␣-blocker medication, a 5␣-reductase inhibitor medi-
For subjects choosing initial medical therapy who did not
cation or a combination of the 2 medications. We also examined
undergo subsequent surgery average time on medical ther-
costs in the subgroup composed of subjects who initially were
apy was 3.2 years. Of these subjects 10% filled only 1 pre-
treated using medication but who later underwent a procedure
scription and excluding them increased average duration to
to treat BPH (medication failure). Cohort 2 includes individu-
3.5 years. The mean time of medical therapy for subjects
als who selected a BPH procedure for initial therapy. We also
who started with medical therapy but subsequently under-
examined costs in the subgroup of subjects who subsequently
received medical therapy for BPH after initial surgical therapy
lists expenditures for each cohort. In inflation
and the subgroup of those who subsequently underwent repeat
adjusted 2002 dollars average total expenditures during the
5 study years were higher for subjects who initially under-
Annual medical and pharmacy expenditures were calcu-
went surgery ($12,699, 95% CI 9,865–15,533) than for those
lated for each cohort and subcohort. Expenditures consisted of
initially treated with medication ($2,193, 95% CI 1,959 –
total annual payments made by the enrollee (co-payments,
2,428). At 5 years therapy with ␣-blocker medication was
deductibles and excluded expenses) and by all third party
less expensive than therapy with 5␣-reductase inhibitor (ex-
payers (primary and secondary coverage, and net of negoti-
cluding subjects on combination therapy $1,397 vs $2,175, p
ated discounts) for BPH related medical services and pre-
Ͻ0.001). also lists expenditures by specific treat-
scription drug claims. Expenditures were tabulated for each
ment paths. A total of 71 subjects initially chose medical
group during the 5 years and a direct comparison was made.
therapy but underwent surgical therapy at some point in the
To determine total expenditures the expenditures for all
next 5 years, which increased average total expenditures to
BPH related office visits, inpatient stays, drugs and proce-
$9,012 (95% CI 6,753–11,271). A total of 11 subjects under-
dures were summed annually and after 5 years. Addition-
went surgery initially but were subsequently placed on med-
ally, we calculated the net current value of initial medical vs
ical therapy, which resulted in 5-year average total expen-
surgical treatment for 5, 10, 20 and 40-year horizons. A
ditures of $11,745 (95% CI 6,857–16,634).
discount rate of 3% was applied to these calculations and we
If future streams of spending were discounted at stan-
assumed that prices were fixed in constant dollars.
dard rates (3%), the costs of initial medical therapy wouldalways be lower than initial surgical therapy. Even at 40
years the net current value of the initial medication strategywas $7,816, while the net current value of the initial surgical
shows the age distribution of the sample. Of the
subjects 1,952 had a new BPH diagnosis code in 1998 but noassociated claim for medical or surgical therapy. DISCUSSION
Of the 970 subjects identified who received BPH treat-
ment 913 (94.1%) relied on medical therapy as initial treat-
Our study has several significant findings. First, expendi-
ment (cohort 1). Of those subjects 832 (91.1%) were on
tures in a 5-year period were higher in the cohort of subjects
␣-blockers, 62 (6.8%) were on 5␣-reductase inhibitor therapy
initially choosing surgery and they continued to be higher in
and 19 (2.1%) were on combination therapy with the 2 types
future time frames. Contrary to our hypothesis, there was no
of medication Because of the small number of
time frame at which surgical therapy was cumulatively less
individuals on combination therapy, this group was ana-
expensive than medical therapy in current value dollars.
lyzed with the cohort initially placed on 5 ␣-reductase inhib-
Total average expenditures during 5 years were signifi-
itors. Of total terazosin and doxazosin prescriptions 37%
cantly higher for subjects undergoing surgery as an initial
ECONOMIC EVALUATION OF BENIGN PROSTATIC HYPERPLASIA TREATMENT STRATEGIES
TABLE 2. Initial and subsequent BPH treatments
treatment strategy. The dramatically higher expenditures
this sample of men with private insurance. This finding is
associated with a surgical procedure during the initial study
consistent with trends documented The num-
year were not significantly mitigated by lower medication
bers of subjects treated with 5␣-reductase inhibitor or sur-
costs. Our results are consistent with computer model based
gery was similar and far smaller than the number treated
economic analyses of the direct treatment costs of ␣-blockers
with ␣-blockers. Treatment with combination medical ther-
vs 5␣-reductase inhibitors vs Using a 2-year time
apy was relatively rare. During the study period sparse data
frame Lowe et al found that costs for terazosin were about
supported the effectiveness of 5␣-reductase inhibitors as
38% of costs for TURP based on costs in a privately insured
monotherapy or combination therapy in most men with
population, which is higher than our corresponding 11%
BPH. However, subsequent publication of the MTOPS trial,
This difference may be due to our longer time frame for
which showed a significant decrease in the risk of BPH
analysis (capturing more treatment failures) or differences in
progression in men on combination may have in-
the assumptions made in the model used by Lowe et al.
creased the initial use of combination therapy in men diag-
It is interesting to note that, although medical therapy
nosed with BPH in 2003 and later. Surprisingly only 33% of
for BPH with ␣-blockers may be considered lifelong therapy,
men with a new BPH diagnosis were treated in year 1 of
the average duration of treatment in this study was shorter
diagnosis, a finding similar to the 23% active treatment rate
than the 5 years of available observation even when exclud-
in year 1 of diagnosis documented by Black et al in a pro-
ing subjects who only filled 1 prescription. This phenomenon
prietary claims This finding may be partially the
contributed to lower expenditures in the cohort treated ini-
result of artifact since a physician claim for an office visit
tially with medication. Expenditures for medical therapy in
may include a diagnosis code for BPH if BPH is suspected as
our study are smaller than those reported previously. Lowe
the reason for patient complaints. This diagnosis may later
et al performed a trial in men randomized to terazosin or
change, obviating the need for BPH treatment. Our bias is
placebo and reported health care costs from the perspective
that this clinical scenario is not common enough to explain
of the health care plan at 1 Expenditures were calcu-
the high proportion of men on watchful waiting. We believe
lated using a private insurance health care claims database.
that these data support the thesis that many patient/physi-
Annual expenditures were $2,932 in the terazosin group.
cian dyads select watchful waiting as initial therapy. To our
However, in that study all health care use was recorded. Our
knowledge the true appropriate active treatment rate for
data are specific to BPH related services. Medication costs in
men with BPH is undefined. In practice the active treatment
the terazosin group for year 1 were $327 more than in the
rate may be influenced by several variables, including the
placebo group, similar to annual costs in our ␣-blocker
structure of patient health care benefits.
group. Given the results of the MTOPS trial, which showed
Third, the secondary treatment rates for surgery far ex-
that therapy with 5␣-reductase inhibitor decreased the need
ceeded those for medical therapy. Approximately 8% of sub-
for subsequent surgical therapy (or the medical therapy
jects on medical therapy required subsequent surgical inter-
failure rate) by medical therapy may be even more
vention, while 25% undergoing surgery subsequently required
favored from a cost perspective if combination medical ther-
medical therapy. Additionally, 12% of the surgery cohort re-
quired second surgery, including 5% who required second sur-
Second, for those who were treated ␣-blocker medication
was overwhelmingly the most common initial treatment in
TABLE 4. Net current value of expenditures related toinitial medical or surgical therapy projected over various
TABLE 3. Five-year expenditures per individual by initial cohort
ECONOMIC EVALUATION OF BENIGN PROSTATIC HYPERPLASIA TREATMENT STRATEGIES
gery and received subsequent medical therapy, for a total sec-
APPENDIX
ondary treatment rate of 37%. This secondary treatment rate
Administrative Codes Used to Identify Subjects
is much larger than that reported in published clinical series
With BPH, or Use of BPH Related Medication
(range to Our higher rates of secondary treatment
or Procedures
may reflect the relatively long followup in our cohort. Studies ofTURP re-treatment rates describe outcomes at less than 2
1) Any male 40 years or older with
Additionally, subsequent treatment with BPH targeted
600.9 “Prostatism” not otherwise specified (median lobe) (prior to 2000,
A strength of our study design was that we were able to
capture all resource use in our cohort during 5 years. Ex-
600.1 “Nodular prostate” excluding prostate cancer (prior to 2000, was
cluding TURP failures treated with medication only, our
600.2 Benign localized hyperplasia (eg adenoma of prostate, adenofi-
TURP failure rate is similar to that in prior reports. Our
bramatous hypertrophy of prostate) of prostate, excludes hypertrophy
failure rate for initial medical treatment is similar to that
reported in the literature. The MTOPS trial described an
If occurring with any of the procedure or BPH medication codes2) Any male 40 years or older with
approximately 8% incidence of surgical therapy at 5 years
788.20 Urine retention or stasis not elsewhere classified
for BPH in subjects initially treated with an ␣-adrenergic
blocking as were most subjects in our study.
788.29 Other “specified” retention of urine788.41 Urinary frequency
This concordance may reflect similar followup in the 2 stud-
ies. Differences in failure rates in our study cohorts may
788.43 Nocturia788.61 Intermittent or splitting urinary stream
reflect underlying clinical differences in this nonrandomized
group since patients undergoing TURP as initial BPH treat-
But not carrying diagnosis code 185 (prostate cancer) as another diagno-
ment in the current decade likely present more frequently
3) Any male undergoing 1 of the following BPH related procedure
with severe disease. Adverse risk factors, such as detrusor
fibrosis due to longstanding high pressure voiding, may be
International Classification of Disease-9 procedure codes
more prevalent in the surgical arm, clouding definitive con-
60.2 Transurethral prostatectomy60.21 Transurethral ultrasound guided laser induced prostatectomy
clusions regarding failure rates between our study cohorts.
60.29 Other transurethral prostatectomy (transurethral electrovaporiza-
Nevertheless, the failure rates in this analysis provide a
tion of prostate, excision of median bar)
portrait of existing resource use for BPH treatment.
60.4 Retropubic open prostectomy60.94 Control (postoperative) hemorrhage of prostate60.95 Balloon dilation of prostatic urethra
Limitations
60.96 Transurethral microwave thermotherapy (added 2000, was 60.29)
Our study is a retrospective analysis and it has the limita-
60.97 Other transurethral destruction of prostatic tissue (eg transure-
tions common to such studies. Our cohorts were subject to
thral needle ablation) (added 2000, was 60.29)
Common Procedural Terminology procedure codes
selection bias since subjects presenting with more severe
symptoms, including those in acute urinary retention, were
52510 Transurethral balloon dilation of prostatic urethra
most likely over represented in the cohort treated initially
52601 Transurethral electrosurgical resection of prostate52606 Transurethral fulguration of postoperative bleeding occurring af-
with surgery. Subjects who were suboptimal surgical candi-
dates were most likely over represented in the cohort ini-
52612 Transurethral resection of prostate, first stage of 2-stage resection52614 Second stage of 2-stage resection
tially treated with medication. This may have decreased
52620 Transurethral resection of residual tissue after 90 postoperative
expenditures in the medication arm by limiting the number
of subjects who subsequently underwent surgical therapy.
52630 Of regrown tissue after 1 year post op52640 Of resultant bladder neck contracture
We were unable to identify any cases in which minimally
52647 Noncontact laser coagulation of prostate
invasive surgical modalities were used, such as transure-
52648 Contact laser vaporization with or without transurethral resection
thral microwave thermotherapy. These therapies avoid the
53850 Transurethral destruction of prostate tissue by microwave ther-
surgical costs derived from use of the hospital operating
53852 By radio frequency thermotherapy (added 1998)
room, and so they may alter the costs of surgical therapy if
55801 Prostatectomy, perineal, subtotal55821 Prostatectomy, suprapubic, subtotal
used widely. However, re-treatment rates for these technol-
55831 Prostatectomy, retropubic, subtotal
ogies have yet to be clearly defined. We were unable to
4) Or any male taking 1 of the following medications
describe out of pocket costs for herbal medicines used by
Hytrin®, Proscar®, terazosin, terazosin HCl, tamsulosin, dutasteride
subjects for BPH treatment. Because our expenditure anal-ysis is from the point of view of the health care system, weonly present economic data. We do not consider the impact oftreatment on quality of life or indirect costs of care. We also
Abbreviations and Acronyms
cannot account for a critical deciding factor in BPH treat-
CONCLUSIONS
In a cohort of privately insured men with newly diagnosed
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Lesson 1 Introduction to Transformation In this lab you will perform a procedure known as genetic transformation. Rememberthat a gene is a piece of DNA which provides the instructions for making (codes for) a protein. This protein gives an organism a particular trait. Genetic transformation literallymeans “change caused by genes,” and involves the insertion of a gene into an organismin ord
aDepartment of Psychiatry, University of Washington, 1959 Pacific Street,bDepartment of Rehabilitation Medicine, University of Washington, 1959 Pacific Street,The evolution of contemporary clinical pain care dates back to the pub-lication of Melzack and Wall’s gate control theory in the journal Science in1965 . Around that time, most of the attention was given to the ‘‘gate’’ inthis