1) This study examined the long-term effects of finasteride versus placebo on clinical progression of benign prostatic hyperplasia (BPH) in men with different baseline prostate volumes. 2) In men with a baseline prostate volume ≥30ml, finasteride significantly reduced clinical progression of BPH compared to placebo. However, in men with a baseline prostate volume <30ml, finasteride did not significantly affect clinical progression compared to placebo. 3) Finasteride also significantly improved American Urological Association symptom index scores and maximum urinary flow rates compared to placebo in men with a baseline prostate volume ≥30ml, but not in men with a baseline volume <30ml.

1. Long-Term Treatment With Finasteride Improves Clinical
Progression of Benign Prostatic Hyperplasia in Men With an
Enlarged Versus a Smaller Prostate: Data From the MTOPS Trial
Steven A. Kaplan,* Jeannette Y. Lee, Alan G. Meehan†
and John W. Kusek for the MTOPS Research Group‡
From Weill Cornell Medical College, New York, New York (SAK), University of Arkansas for Medical Sciences, Little Rock,
Arkansas (JYL), Merck & Co., Inc., Rahway, New Jersey (AGM), and the National Institute of Diabetes and Digestive and
Kidney Diseases, Bethesda, Maryland (JWK)
Purpose: This post hoc analysis of the Medical Therapy of Prostatic Symptoms Abbreviations
and Acronyms
trial examined the effect of finasteride alone compared to placebo on the clinical
progression of benign prostatic hyperplasia in men with a baseline prostate AUA-SI American Urological
volume less than 30 ml, or 30 ml or greater. Association symptom index
Materials and Methods: Men were randomized to placebo (737), 4 to 8 mg 5AR 5 -reductase
doxazosin alone (756), 5 mg finasteride alone (768) or doxazosin plus finasteride BPH benign prostatic
(786) (average followup was 4.5 years). Approximately 50% of patients had a hyperplasia
baseline prostate volume of 30 ml or greater. The present analysis was based on ITT intent to treat
the finasteride alone and placebo arms only, and included patients for whom LUTS lower urinary tract
baseline and end of study data were available. We examined the effect of treat- symptoms
ment on the cumulative percentage of men who did not experience clinical MTOPS Medical Therapy of
progression of benign prostatic hyperplasia by study end. Prostatic Symptoms
Results: In men with baseline prostate volume 30 ml or greater treatment with
PV prostate volume
finasteride produced a significant (p 0.001) increase relative to placebo in the
PVR post-void residual volume
cumulative percentage of patients who did not experience clinical progression of
benign prostatic hyperplasia (finasteride 88.1% vs placebo 77.8%). There was no Qmax maximum urinary flow
significant (p 0.441) between-group difference in men with baseline prostate rate
volume less than 30 ml (91.4% vs 89.1%, respectively). TRUS transrectal ultrasound
Conclusions: Long-term treatment with finasteride led to a significant beneficial
effect compared to placebo on the clinical progression of benign prostatic hyper- Submitted for publication June 14, 2010.
plasia in patients with lower urinary tract symptoms with an enlarged prostate MTOPS was supported by the following coop-
erative agreements from the National Institute of
(baseline prostate volume 30 ml or greater). Finasteride had no significant effect Diabetes and Digestive and Kidney Diseases: U01
compared to placebo on the clinical progression of benign prostatic hyperplasia in DK49977, U01 DK46416, U01 DK41418, U01 DK46429,
patients with lower urinary tract symptoms with a smaller prostate (baseline U01 DK46431, U01 DK46437, U01 DK46437, U01
DK46468, U01 DK46472, U01 DK49880, U01 DK
prostate volume less than 30 ml). 49912, U01 DK49921, U01 DK49951, U01 DK49954,
U01 DK49960, U01 DK49961, U01 DK49963, U01
Key Words: prostatic hyperplasia, urinary tract, finasteride, DK49964, U01 DK49971, U01 DK49980, as well as by
the National Center on Minority Health and Health
organ size, prostate Disparities, National Institutes of Health. Financial sup-
port and drug products for MTOPS were also provided
by Merck and Pfizer.
THE MTOPS trial, to our knowledge, teride (34% relative risk reduction) * Correspondence and requests for reprints:
Institute of Bladder and Prostate Health, Weill
is the largest and longest placebo con- and doxazosin (39% relative risk re- Cornell Medical College, Cornell University, 1300
trolled study to assess the effect of duction) alone compared to placebo. York Ave., F9 West, Box 261, New York, New
York 10021 (telephone: 212-746-4811; FAX: 212-
medical (drug) therapy on the clinical However, the 2 drugs combined re- 746-5329; e-mail: kaplans@med.cornell.edu).
progression of BPH.1,2 In that trial sulted in a superior placebo corrected † Financial interest and/or other relationship
the risk of clinical progression of BPH risk reduction (66% relative risk re- with Merck.
‡ A list of the MTOPS study investigators has
was significantly reduced by finas- duction) compared to that for either been provided previously.1
0022-5347/11/1854-1369/0 Vol. 185, 1369-1373, April 2011
THE JOURNAL OF UROLOGY® Printed in U.S.A.
www.jurology.com 1369
© 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC. DOI:10.1016/j.juro.2010.11.060

2. 1370 PROSTATE SIZE AND SYMPTOM IMPROVEMENT WITH FINASTERIDE
drug alone.1 Finasteride is an inhibitor of type 2, change from baseline to study end in AUA-SI score, Qmax,
5AR, which is the predominant 5AR isozyme in the PVR and PV, as well as the cumulative percentage (95% CI) of
prostate that catalyzes the reduction of testosterone to patients who did not have clinical progression of BPH by study
the more potent androgen dihydrotestosterone. Treat- end, were examined in the placebo and finasteride treatment
groups in men with baseline PV less than 30 ml, and compared
ment with finasteride results in a marked decrease in
with those with a PV of 30 ml or greater. We also performed a
intraprostatic dihydrotestosterone, leading to a reduc- per protocol analysis to assess the consistency of the results of
tion in PV, improvement in urinary symptoms and a our ITT analysis for AUA-SI, Qmax, PVR and PV. The per
reduction in the risk of serious BPH related outcomes protocol analysis excluded men who had been treated with
including acute urinary retention and the need for BPH open label medical therapy for BPH or who had undergone
related surgery.3,4 The beneficial effects of finasteride are invasive therapy for BPH before the end of study TRUS mea-
generally believed to be restricted to men with an en- surement. We used a 1-way ANOVA to compare finasteride
larged prostate.4 We assessed the long-term effects of with placebo with respect to the change from baseline for
finasteride alone compared to placebo on urinary symp- AUA-SI score, Qmax and PV separately for men with baseline
toms and clinical progression of BPH in men enrolled in PV less than 30 ml and those with baseline PV 30 ml or greater.
the MTOPS trial subgrouped by baseline PV. We defined For PVR the Wilcoxon rank sum test was used to compare
treatment arms with respect to change from baseline. The log
men with a baseline prostate volume of less than 30 ml
rank test was used to compare the treatment arms with respect
as having a smaller prostate and those with a volume of to time to clinical progression of BPH.
30 ml or greater as having an enlarged prostate.
RESULTS
MATERIALS AND METHODS
Baseline and end of study PV measurements were avail-
Study Design and Patient Selection able for a total of 1,140 men from the finasteride and
The design and major outcomes of the MTOPS study have placebo treatment groups (table 1). Baseline PV ranged
been reported previously.1,2 Men at least 50 years old with from 8.8 to 181.0 ml, with 49% of men having a baseline
an AUA-SI score of 8 to 30 and a Qmax of 4 to 15 ml per
PV less than 30 ml. Within each PV subgroup (baseline
second with a voided volume of at least 125 ml were
eligible for the trial. A total of 3,047 men were randomized
PV less than 30, or 30 ml or greater) men randomized to
1:1:1:1 to placebo, doxazosin (4 to 8 mg), finasteride (5 mg) placebo or finasteride were generally similar with respect
or combination therapy with doxazosin and finasteride. to baseline demographic and clinical characteristics. Men
The present analysis was based on the finasteride alone with baseline PV 30 ml or greater were slightly older,
and placebo arms only, and included patients for whom and had higher mean PVR and prostate specific antigen
baseline and end of study data were available. The pri- compared to those with a baseline PV less than 30 ml.
mary outcome, overall clinical progression of BPH, was
defined as the first occurrence of an increase from baseline Change in AUA-SI Score
of at least 4 points in the AUA-SI score (confirmed within In the ITT analysis treatment with finasteride led to a
4 weeks), acute urinary retention, urinary incontinence, significant (p 0.045) mean decrease from baseline to
renal insufficiency or recurrent urinary tract infection. study end in AUA-SI score relative to placebo in men
Secondary outcomes included change from baseline to end with baseline PV 30 ml or greater (mean decrease of
of study in AUA-SI score, Qmax and PVR. PV was mea- 5.69 vs 4.65 in the finasteride and placebo groups,
sured by TRUS in all men at baseline and at the end of respectively), whereas there was no significant be-
year 5 or at the end of study followup, whichever came tween-group difference in the mean change from base-
first. The average duration of followup was 4.5 years. line in AUA-SI score in men with baseline PV less than
Statistical Analysis 30 ml (mean decrease of 6.01 vs 5.06 in the finas-
We first performed an ITT analysis which included all random- teride and placebo groups, respectively, table 2, part A
ized men with evaluable PV data. Mean (median for PVR) of figure). The AUA-SI score results for the per proto-
Table 1. Baseline and disease characteristics
Baseline PV Less Than 30 ml Baseline PV 30 ml or Greater
Placebo Finasteride Placebo Finasteride
No. pts 276 281 288 295
Mean SD age 60.3 7.1 60.7 7.0 64.1 6.9 63.9 7.1
Mean SD AUA-SI 16.2 5.7 17.2 5.8 16.8 6.0 17.1 5.8
Mean SD ml/sec Qmax 10.5 2.8 10.6 2.5 10.4 2.8 10.5 2.7
Median ml PVR range 38.0 (0–399) 36.0 (0–411) 52.0 (0–535) 40.0 (0–552)
Mean SD ml PV 21.8 5.1 22.3 4.9 47.2 17.4 50.4 21.1
PV range (ml) 8.8–29.9 9.3–29.9 30.0–181.0 30.0–170.3
Mean SD ng/ml prostate specific antigen 1.3 1.1 1.3 1.2 3.1 2.3 3.3 2.3

3. PROSTATE SIZE AND SYMPTOM IMPROVEMENT WITH FINASTERIDE 1371
Table 2. Effect of finasteride vs placebo on change from baseline in urinary symptoms and prostate volume at study end
Baseline PV Less Than 30 ml Baseline PV 30 ml or Greater
Placebo Finasteride Placebo Finasteride
ITT population
AUA-SI:
No. pts 276 281 288 295
Mean SD 5.06 5.78 6.01 5.78 4.65 6.17 5.69 6.40
p Value 0.054 0.045
Qmax (ml/sec):
No. pts 273 277 282 290
Mean SD 3.06 5.96 3.67 6.97 1.78 5.83 3.31 5.74
p Value 0.268 0.002
PVR (ml):
No. pts 271 280 282 289
Median (range) 3.0 ( 275, 371) 1.5 ( 221, 262) 0.50 ( 458, 641) 3.0 ( 503, 411)
p Value 0.992 0.192
PV (ml):
No. pts 276 281 288 295
Mean SD 7.19 16.80 0.28 7.98 9.38 17.00 5.79 18.35
p Value 0.001 0.001
Per protocol population
AUA-SI:
No. pts 266 276 261 287
Mean SD 4.80 5.62 5.99 5.73 4.16 5.92 5.52 6.13
p Value 0.015 0.008
Qmax (ml/sec):
No. pts 263 272 257 284
Mean SD 2.88 5.89 3.75 6.92 1.52 5.62 3.19 5.69
p Value 0.119 0.001
PVR (ml):
No. pts 261 275 256 283
Median (range) 3.0 ( 275, 371) 0 ( 221, 262) 0 ( 421, 641) 3.0 ( 503, 411)
p Value 0.888 0.055
PV (ml):
No. pts 266 276 261 287
Mean SD 7.35 16.99 0.32 8.02 11.38 15.00 5.25 17.63
p Value 0.001 0.001
col analysis were generally consistent with those for Change in PVR
the ITT analysis, with significant between-group dif- In the ITT analysis treatment with finasteride and pla-
ferences achieved for both PV cohorts (part B of fig- cebo led to median reductions from baseline to study end
ure). The largest improvement with finasteride ob- in PVR of 3.0 and 0.5 ml, respectively, in men with
served in the per protocol analysis occurred at year 2 baseline PV 30 ml or greater, and 1.5 vs 3.0 ml,
in the baseline PV 30 ml or greater cohort, with a respectively, in men with baseline PV less than 30 ml,
mean between-group difference of approximately 2 although the between-group differences were not statis-
AUA-SI score units. This improvement was generally tically significant in either of the 2 baseline PV cohorts
sustained in years 3 and 4. (table 2). The PVR results for the per protocol analysis
Change in Qmax were generally consistent with those for the ITT analysis.
In the ITT analysis treatment with finasteride led to a
significant (p 0.002) mean increase from baseline to Change in PV
study end in Qmax relative to placebo in men with base- In the ITT analysis treatment with finasteride led to
line PV 30 ml or greater (mean increase of 3.31 and 1.78 a significantly (p 0.001) greater improvement from
ml per second in the finasteride and placebo groups, baseline to study end in PV in men with baseline PV
respectively), whereas there was no significant between- 30 ml or greater (mean decrease in PV of 5.79 ml
group difference in the mean change from baseline in with finasteride compared to a mean increase of 9.38
Qmax in men with baseline PV less than 30 ml (mean ml with placebo) and in men with baseline PV less
increase of 3.67 and 3.06 ml per second in the finasteride than 30 ml (mean increase in PV of 0.28 ml with
and placebo groups, respectively, table 2). The Qmax finasteride vs a mean increase of 7.19 ml with placebo,
results for the per protocol analysis were generally con- table 2). The results from the per protocol analysis
sistent with those for the ITT analysis. were consistent with those from the ITT analysis.

4. 1372 PROSTATE SIZE AND SYMPTOM IMPROVEMENT WITH FINASTERIDE
Mean (SE) change from baseline in AUA-SI over time for ITT population (A) and per protocol population (B) (excluding patients who
had been crossed over to open label medical therapy or who had invasive therapy before end of study TRUS measurement) in MTOPS
trial. Pbo, placebo. Fin, finasteride.
Clinical Progression of BPH DISCUSSION
Treatment with finasteride led to a significant
(p 0.001) increase relative to placebo in the cumu- 5AR inhibitors are generally recommended for use
lative percentage of men who did not meet the cri- in patients with symptomatic BPH with an enlarged
teria for the clinical progression of BPH in men with prostate.4 The wide distribution of baseline PV (8.8
baseline PV 30 ml or greater (finasteride 88.1%, vs to 181.0 ml) for men enrolled in the MTOPS study
placebo 77.8%), whereas no significant between- provided the opportunity to examine the long-term (4
group difference was observed in men with baseline or more years) effects of the 5AR inhibitor finasteride
PV less than 30 ml (91.4% vs 89.1%, table 3). alone compared to placebo on urinary symptoms and
Table 3. Effect of finasteride vs placebo on cumulative percentage at study end of men without clinical progression of BPH
Baseline PV Less Than 30 ml Baseline PV 30 ml or Greater
Placebo Finasteride Placebo Finasteride
No. pts 276 280 288 295
Cumulative % (95% CI) 89.1 (84.8, 92.3) 91.4 (87.5, 94.2) 77.8 (72.5, 82.1) 88.1 (83.9, 91.3)
p Value 0.367 0.001

5. PROSTATE SIZE AND SYMPTOM IMPROVEMENT WITH FINASTERIDE 1373
the clinical progression of BPH in patients with commonly observed in the clinical setting (less than 25
smaller and larger prostates. Although we did not to 40 ml or greater).1,3–7 About half of the men enrolled
define the volume criterion for an enlarged prostate a in the MTOPS study had an enlarged prostate at base-
priori, our categorization of PV 30 ml or greater as line as defined by PV 30 ml or greater. Whether a
enlarged is consistent with currently accepted cut similar proportion of men with an enlarged prostate as
points. seen in the MTOPS study present to physicians with
We observed in an ITT analysis that treatment bothersome symptoms of LUTS associated with BPH
with finasteride led to a statistically significant re- is uncertain. Given the significantly lower rate of clin-
duction compared to placebo in the clinical progres- ical progression of BPH observed in men with PV 30
sion of BPH in patients with LUTS with an enlarged ml or greater who were treated with finasteride com-
prostate (baseline PV 30 ml or greater), whereas pared to placebo, patients with symptomatic BPH with
treatment with finasteride did not demonstrate a an enlarged prostate and their treating physicians
significant effect relative to placebo on the clinical should consider the benefits observed in this study
progression of BPH in patients with a smaller pros- from treatment with finasteride when determining
tate (baseline PV less than 30 ml). Additionally, the treatment choice.
ITT analysis showed that finasteride produced There were a number of limitations of our analy-
significant improvement compared to placebo in sis. While the data analysis plan for the MTOPS
AUA-SI score and Qmax in men with an enlarged study prespecified examination of the effect of PV on
prostate but not in those with a smaller prostate. In outcomes, the cut points for these subgroups were
those men who had not been treated with open label not prespecified. However, the use of 30 ml or
medical therapy for BPH or those who had under- greater to define an enlarged prostate is consistent
gone invasive therapy for BPH before the end of with current practice.8 In addition, we performed a
study TRUS measurement, finasteride led to an im- subgroup analysis which may be subject to bias.9
provement in AUA-SI relative to placebo by year 2 in There were several strengths to our study including
the baseline PV 30 ml or greater cohort of approxi- the large sample size, the wide distribution of base-
mately 2 units, with this improvement being generally line PV and long-term followup.
sustained through year 4 of the study (part B of fig-
ure). The larger improvement in PV seen in patients
treated with finasteride with a baseline PV of 30 ml or CONCLUSIONS
greater (5.79 ml decrease) than in those with a base- In this post hoc analysis of MTOPS trial data, long-
line PV less than 30 ml (0.28 ml increase) may have term (4 or more years) treatment with finasteride
resulted in relieving symptomatic prostatic obstruc- led to a significant beneficial effect compared to pla-
tion, which may have contributed to the added benefits cebo on the clinical progression of BPH in patients
of finasteride on urinary symptoms and the clinical with LUTS with an enlarged prostate (baseline PV
progression of BPH in these patients. 30 ml or greater). Finasteride had no significant
Finasteride is approved for the treatment of BPH effect compared to placebo on the clinical progres-
symptoms in men with an enlarged prostate based on sion of BPH in patients with LUTS with a smaller
large long-term studies of men with a wide range of PV prostate (baseline PV less than 30 ml).
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