Re: Prednisone Plus Cabazitaxel or Mitoxantrone for
Metastatic Castration-Resistant Prostate Cancer Pro-
gressing After Docetaxel Treatment: A Randomized
de Bono JS, Oudard S, Ozguroglu M, et al;
The TROPIC study is a randomized phase 3 trial comparing
efficacy and safety of cabazitaxel plus prednisone and mito-
xantrone plus prednisone in 755 patients with castration-
docetaxel-based chemotherapy. Between January 2007 and
October 2008, 377 patients were treated with 12 mg/m2
mitoxantrone and 378 patients were treated with 25 mg/m2
cabazitaxel. Regarding overall survival (OS; primary end
point), cabazitaxel was superior to mitoxantrone with 15.1
mo in the cabazitaxel group compared with 12.7 mo in the
mitoxantrone group—a 30% reduction in relative risk of death
(hazard ratio [HR]: 0.70; p < 0.0001).
progression-free survival can be determined and was twice
as long with cabazitaxel versus mitoxantrone (2.8 mo vs 1.4
mo; HR: 0.74; p < 0.0001). The prostate-specific antigen and
tumor response rates were also significantly higher in the
cabazitaxel group. The most frequent side effects were
hematologic, with 8% febrile neutropenia in the cabazitaxel
group and 1% in the mitoxantrone group.
In conclusion, cabazitaxel has proven antitumor activity
in patients with CRPC with progressive disease after
docetaxel therapy. This results ina significant improvement
in OS in these patients.
Based on the results of the TAX 327 and Southwest Oncology
Group SWOG-S9916 studies, which revealed for the first time
a survival benefit of 2 mo in patients with hormone-refractory
prostate cancer, docetaxel-based chemotherapy is the stan-
dard of care for these patients [1,2]. Patients who progress
with this therapy have the possibility of palliative treatment
Studies to date with mitoxantrone merely showed
improvement of quality of life and symptoms but failed to
prove a survival benefit . The results of this study, which
already resulted in an approval by the US Food and Drug
Administration, are very promising and offer a therapeutic
option to affected patients. Regarding the side effects of
cabazitaxel,oneshould carefullynotethat neutropeniaisthe
primary dose-limiting factor, and a relevant proportion of
patients had grade 3 diarrhea. It is necessary to have
strategies for acute and preventive treatment, particularly
for these two side effects. Furthermore, patients must be
The role of cabazitaxel cannot yet be clearly defined. In
2010, the results of two additional important studies
became available [4,5]. The Impact study is a phase 3 trial
in which 512 patients randomly received either an
autologous active cellular immunotherapy (sipuleucel-T)
or placebo. The use of sipuleucel-T resulted in a 4.1-mo
improvement in OS . Another milestone in the treatment
of patients with CRPC is abiraterone. A phase 3 study,
presented at the 2010 European Society for Medical
Oncology Congress, revealed an improvement of 4 mo in
median survival for patients treated with this substance .
Because the results are comparable regarding OS with
these three substances, the duration and timing of
hormonal therapy and chemotherapy will become more
complex. Additionally, the effects on digestibility and
quality of life are crucial criteria that will influence the
palliative management of prostate cancer.
Conflicts of interest: The authors have nothing to disclose.
 Petrylak DP, et al. N Engl J Med 2004;351:1513–20.
 Tannock IF, et al. N Engl J Med 2004;351:1502–12.
 Tannock IF, et al. J Clin Oncol 1996;14:1756–64.
 Kantoff PW, et al. N Engl J Med 2010;363:411–22.
 De Bono J, et al. Abiraterone acetat improves survival in metastatic
castration-resistant prostate cancer: Phase III results. Paper pre-
sented at: 35th European Society for Medical Oncology Congress;
8–12 October 2010; Milan, Italy.
Dieter Jocham*, Martin Sommerauer
Universita ¨tsklinikum, Schleswig-Holstein, Campus Lu ¨beck,
Ratzeburger Allee 160, D-23538 Lu ¨beck, Germany
E-mail address: Prof.Jocham.MUL@t-online.de (D. Jocham)
RE: Mortality Results From the Go ¨teborg Randomised
Population-Based Prostate-Cancer Screening Trial
Hugosson J, Carlsson S, Aus G, et al.
Lancet Oncol 2010;11:725–32
After 14 yr of median follow-up, the Go ¨teborg randomized
population-based study of screening for prostate cancer (PCa)
demonstrated a significant mortality reduction of 44% in the
screening group compared with the control group in the
intention-to-screen analysis. This translated into a relative
risk reduction of 56% for those men who were in fact screened
after adjustment for noncompliance (25% in the screening
The percentage of high-risk or advanced disease in the
control group was 32% ([126 + 87] / [718 ? 57]), which was
higher than in the screening group (13%) and lower than
nonattendees in the screening arm (52%). The number of
E UR O P E A N U R OL O GY 59 ( 2 01 1) 6 5 7 – 6 6 1
men needed to screen (NNS) was low at 293. The number of
men needed to treat (NNT) amounted to 12 and was very
low, despite the high percentage of patients who were
under active surveillance. This percentage was higher at
27.6% (314 of 1138) in the screening group compared with
21.2% (152 of 718) in the control group.
Details of outcome in relation to birth cohort may be
relevant for the development of optimal screening systems.
The authors demonstrated that the crude mortality rate of
PCa in attendees in the screening group was lowest at 0.36%
compared with 0.72% in nonattendees in the screening
group and 0.78% in the control group. Considering the
by birth cohorts, attendees between 60 and 64 yr of age at
study entry showed a higher crude mortality rate at 0.92%
than 0.25% and 0.06% in those aged 55–59 yr and 50–54 yr,
respectively. Furthermore, among 27 men who participated
in the screening group and who died due to PCa, 13 (48%)
were screened for the first time. Of those 13 cases, 12 men
(92%) were between 60 and 64 yr old at study entry. At least
some of those men might have had the possibility of being
cured by timely and appropriate treatments if they had
started screening at 50 yr of age.
The efficacy of cancer screening for individuals should be
evaluated as the probability of mortality reduction through-
out the whole life. The Swedish study contributes heavily to
determining the effectiveness of prostate-specific antigen
(PSA) screening by adding level 1 evidence to the first inten-
tion-to-screen analysis of the European Randomized Study of
Screening for Prostate Cancer (ERSPC) , in which the Swed-
ish study is a partner and which showed a significant mortali-
ty reduction for the first time after 9 yr of follow-up.
Interms of thedrawbacks ofscreening forPCa, the ERSPC
showed an increased risk of overdetection and overtreat-
ment by intensive screening exposure and invasive
treatment strategies. An NNT of 48 and an NNS of 1410
were reported, according to this interim analysis of the
study; however, the drawbacks of PSA screening might be
overestimated because of the short follow-up duration. At
the same time, we should also consider the likelihood of
underdetection of significant PCa and delay in the
appropriate treatment timing in the nonscreening cohort.
In the Swedish study, there was a 1.6-fold difference in the
number of men with PCa diagnosed in the screening cohort
and the control cohorts during 14 yr of follow-up. On the
one hand, there may be some bias between the screening
cohort and the control group in terms of increased risk of
overdetection and overtreatment in the screening cohort.
On the other hand, the outcomes of the control cohort are
likely to differ in terms of an increased risk of missing
clinically significant cancer and missing the chance of cure
by appropriate treatment strategies compared with the
Although the both cohorts had completely inverse
potential drawbacks, from my current perspective as a
clinician, it would be possible to reduce the risk of
overdetection by using already available nomogram-based
risk calculators like the Prostate Risk Indicator .
and willdecrease further inthecurrent ongoing prospective
clinical study by applying active surveillance. The negative
impact on quality of life has also decreased and will
decrease further by the continuing development of mini-
mally invasive treatment strategies. In contrast, by applying
active surveillance and focal treatments, many urologists
are afraid that they ineffectively treat more advanced life-
threatening disease by delaying early detection and
aggressive treatment, as is seen in the not-screened cohort
and in the nonattendees in the screening cohort. The NNS
and the NNT shown in the Swedish study were not high
compared with the other cancer screening program and
may be acceptable for many men who are at risk of
developing PCa. However, the NNT cannot estimate how
large the drawbacks of the cancer screening would be
because NNT is simply estimated with the assumption that
any stage of PCa is equal.
The treatment duration and quality-adjusted life-years
of metastatic PCa patients are different from those with
localized PCa. Increasing the number of patients with
advanced-stage PCa might cause a lot of socioeconomic
damage, not only to individuals but also to the community,
because of loss of quality of life, high treatment cost, loss of
activity as a result of long-term treatment, and severe
adverse effects caused by some treatments . A treatment
for metastatic PCa and a treatment for localized PCa should
not be handled as the same entity from a clinical
perspective. In fact, the number of patients with high-risk
and advanced PCa in the control group of the Swedish study
was 2.5 times higher than that in the screening group.
Before introducing screening for cancer to the community,
it should be investigated whether introducing cancer
screening in the community improves quality-adjusted
life-years compared to routine medical care without cancer
screening. From a socioeconomic point of view, it may be
important to estimate the incremental cost-effectiveness
ratio (ICER) in the screening group. The ICER is the total
social cost of introducing a long-term cancer screening
system divided by the total social benefit from improved
quality-adjusted life-years due to intervention.
Regarding PSA screening, our mission must focus on
establishing an optimal screening system that minimizes
overdetection, overtreatment, and socioeconomic damage
and maximizes screening effects in terms of mortality
reduction and avoiding development of metastatic PCa.
Conflicts of interest: The author has nothing to disclose.
 Schro ¨der FH, Hugosson J, Roobol MJ, et al. Screening and prostate-
cancer mortality in a randomized European study. N Engl J Med
 Roobol MJ, Kerkhof M, Schro ¨der FH, et al. Prostate cancer mortality
reduction by prostate-specific antigen–based screening adjusted for
nonattendance and contamination in the European Randomised
EUROPEAN UROLOGY 59 (2011) 657–661
Study of Screening for Prostate Cancer (ERSPC). Eur Urol 2009;56: Download full-text
 Naito S, Kakehi Y, Ito K, et al., the Committee for Establishment of the
Guidelines on Screening for Prostate Cancer and Japanese Urological
Association. Updated Japanese Urological Association Guidelines on
prostate-specific antigen-based screening for prostate cancer in
2010. Int J Urol 2010;17:830–8.
Gunma University Graduate School of Medicine,
Department of Urology, Maebashi, Gunma, Japan
E-mail address: firstname.lastname@example.org
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