EUROPEAN UROLOGY SUPPLEMENTS 8 (2009) 843847

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Oncoforum Urology: Prostate Cancer 2008 at a Glance

Nicolas Mottet *
Clinique Mutualiste, Departement dUrologie, 3, rue le Verrier - B.P. 210, 42013 St. Etienne, France

Article info

Abstract

Keywords:
Androgen deprivation therapy
Diagnosis
Hormone-refractory prostate
cancer
Nomogram
Prostate cancer
Radical prostatectomy
Radiotherapy

Context: Many new findings on prostate cancer (PCa) were presented at the 2008
annual meetings of the European Association of Urology (EAU), the American
Urological Association (AUA), the American Society of Clinical Oncology (ASCO),
and the American Society for Therapeutic Radiology and Oncology (ASTRO).
Objective: To summarise interesting topics on PCa from urological and oncological
congresses in 2008.
Evidence acquisition: This manuscript is based on a presentation given at a satellite
symposium on PCa held at the 2009 annual meeting of the EAU in Stockholm,
Sweden. Data were retrieved from selected abstracts on PCa presented at urological
and oncological congresses in 2008.
Evidence synthesis: The frequency of lymph node metastases seems low in patients
with low-risk PCa and the percentage of positive biopsy cores may be used to
predict lymph node involvement. Therefore, the diagnostic benet of extended
pelvic lymphadenectomy is questioned in patients with low-risk PCa undergoing
radical prostatectomy. According to two studies presented at the EAU annual
meeting, appropriately selected patients with very low-risk PCa might be safely
managed by active surveillance. Furthermore, it is still unclear whether the risk of
developing secondary malignancies increases after primary radiation of PCa.
Confounding factors such as smoking should be taken into consideration before
drawing any conclusions. With regard to locally advanced PCa, an update of the
Southwest Oncology Group (SWOG) 8794 trial conrmed that adjuvant radiotherapy
to radical prostatectomy reduces recurrence. In addition, adjuvant radiotherapy
signicantly reduced the risk of metastases and improved overall survival in men
with pT3 PCa. In patients with castration-resistant PCa, abiraterone acetate seems to
be well tolerated and effective.
Conclusions: Many interesting new data on PCa were presented at the 2008
oncological and urological congresses. Some may have an impact on clinical
practice, whereas other data raise new questions that will have to be answered
by further research.
# 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.
* Tel. +33 (4) 77121147; Fax: +33 (4) 77121216.
E-mail address: NMottet@mutualite-loire.com.

1.

Introduction

Prostate cancer (PCa) is recognised as one of the most

important health problems among men. Worldwide, PCa is
the most commonly diagnosed male cancer [1,2]. Although

there are some differences between countries, the incidence

of PCa has been increasing over the years [1,3]. This increase
has been suggested to result from the improved detection of
PCa and increased screening methods. The number of
patients with PCa is expected to increase even further over

1569-9056/$ see front matter # 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.

doi:10.1016/j.eursup.2009.09.005

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EUROPEAN UROLOGY SUPPLEMENTS 8 (2009) 843847

the years due to an increasing life expectancy. Furthermore,

PCa is responsible for approximately 10% of cancer deaths,
with only lung cancer associated with more deaths in men
[2]. However, a large number of cancers from the prostate
are often not clinically significant or aggressive. In Europe in
2006, the number of patients who died from PCa was
approximately a quarter of the number of newly diagnosed
cases [1]. These data emphasise the importance of early
detection of PCa and the ongoing necessity to optimise and
further improve the management of PCa.
Recent developments in the detection and management
of PCa were presented in 2008 at the annual meetings from
the European Association of Urology (EAU), the American
Urological Association (AUA), the American Society of
Clinical Oncology (ASCO), and the American Society for
Therapeutic Radiology and Oncology (ASTRO). The Oncoforum Urology programme has been developed to provide a
retrospective platform for physicians by means of communicating interesting abstracts from these urological and
oncological annual meetings. For the Oncoforum Urology
programme, experts in the field, called Oncoforum
reporters, select interesting abstracts based on the
following criteria: innovative data, relevance to current
or future clinical practice, studies with robust methodology
(eg, randomised controlled trial, high number of patients,
multicentre trial). This manuscript summarises some new
findings on PCa presented at urological and oncological
congresses in 2008 and selected by a panel of Oncoforum
reporters.
2.

Fig. 1 The risk of nodal disease in men with I50% or <50% of the biopsy
cores being positive for prostate cancer [4].

Fig. 2 Use of prostate-specific antigen (PSA) progression to predict

overall survival in patients with metastatic prostate cancer treated with
continuous androgen deprivation therapy (phase 3 S9346 trial) and
docetaxel or mitoxantrone plus prednisone (phase 3 S9916 trial) [5].

Evidence acquisition

This paper was based on a presentation given at a satellite

symposium on PCa that was held during the 24th annual
meeting of the EAU, 18 March 2009, in Stockholm, Sweden.
Data were retrieved from critically selected abstracts
presented at the urological and oncological congresses in
2008. Abstracts are selected based on the following criteria:
innovative data, relevance to clinical practice, studies with
robust methodology (eg, multicentre trial, randomised trial,
placebo-controlled trial, number of patients).
3.

Evidence synthesis

3.1.

Diagnosis and staging

Pelvic lymphadenectomy in patients with low-risk PCa

undergoing radical prostatectomy is a controversial topic.
During the AUA, Heidenreich et al [4] presented a study in
499 men with low-risk PCa who underwent radical
prostatectomy and extended pelvic lymphadenectomy. A
correlation between percentage of positive biopsies and the
presence of lymph node metastases was calculated. In 5.8%
of patients, lymph node metastases were identified. The
percentage of positive biopsies had a significant impact on
the presence and prediction of nodal disease. The risk of
lymph node metastases increased significantly if 50% of
the biopsy cores were involved with PCa (Fig. 1). Sensitivity
and specificity were 91.4% and 82.1%, respectively.

Prostate-specific antigen (PSA) progression is an

accepted indicator of disease progression in hormonesensitive and hormone-refractory PCa. Hussain et al [5]
evaluated different definitions of PSA progression as
predictors of overall survival, including consensus criteria
using data from two phase 3 trials with adequate PSA and
follow-up data. Patients from the S9346 trial received
continuous androgen deprivation therapy and patients
from the S9916 trial were treated with docetaxel or
mitoxantrone plus prednisone. PSA progression was
defined as an increase in PSA value of 25% over baseline
or nadir with an absolute increase of 2 or 5 ng/ml. Survival
analysis revealed PSA progression observed with both PSA
thresholds as a strong predictor of overall survival in
metastatic hormone-sensitive and hormone-refractory PCa
patients irrespective of the initial PSA (Fig. 2).
3.2.

Localised prostate cancer

Positive apical surgical margins have not traditionally been

treated as other positive surgical margins after radical
prostatectomy. Lassoff et al [6] examined the margin status
in 1663 clinically localised (cT1/cT2) PCa patients who
underwent surgery between 1988 and 2003 to determine if
there were any differences in outcomes. Patients were
subdivided into nonapical positive surgical margin (SM+),

EUROPEAN UROLOGY SUPPLEMENTS 8 (2009) 843847

Table 1 Outcomes of men with screen-detected prostate cancer

eligible for active surveillance who were managed expectantly
[8]
Mean PSA at diagnosis (ng/ml)
Death (% of patients)
Disease-specic death (% of patients)
10-yr overall survival (%)
10-yr disease-specic survival (%)

4.3
9
0
77
100

PSA = prostate-specic antigen.

apical positive surgical margin (AM+), and negative surgical

margin (SM ): 16% of patients had SM+, 11% of patients had
AM+, and 73% of patients had SM . At a median follow-up
period of 6.8 yr, patients with AM+ seem to behave similarly
to patients with SM+ with respect to overall survival,
biochemical recurrence-free survival, and clinical recurrence-free survival. Therefore, these patients may warrant a
similar treatment approach following surgery. Quality of
life after curative treatment of localised PCain particular,
satisfaction of patients with treatment choice and treatment resultsis an important end point. Between 2003 and
2004, 1083 PCa patients underwent radical prostatectomy
in a German institution [7]. Complete follow-up data were
available for 779 patients. Three questionnaires were used
to evaluate quality of life, potency, and continence. In
addition, the degree of information that patients received
on PCa and their treatment before surgery was assessed.
Overall, satisfaction with treatment was very good in 84% of
the patients and good in 14% of the patients. In uni- and
multivariate analyses, a high level of preoperative information about disease and treatment ( p < 0.001), postoperative
potency ( p < 0.001), and postoperative continence
( p < 0.001) were significantly associated with good satisfaction with treatment. Aspects of cancer control (ie, cancer
stage and surgical margin) had no significant impact on
treatment satisfaction.
Active surveillance has emerged as an alternative to
radical therapy for patients with small, localised, welldifferentiated PCa, the incidence of which is increasing due
to screening. A retrospective study presented at the EAU
annual meeting validated the currently used criteria for
eligibility for active surveillance [8]. Data from 616 men
who were diagnosed with PCa between 1994 and 2007 in
four centres of the European Randomised Study of Screening for Prostate Cancer (ERSPC) were combined. All patients
fit the Prostate Cancer Research International Active
Surveillance (PRIAS) criteria for active surveillance (PSA
10.0 ng/ml, PSA density < 0.2 ng/ml per millilitre,
category T1c/T2, Gleason score 3 + 3 = 6, and 2 positive
biopsy cores) and were managed expectantly. Median
follow-up was 3.91 yr. PSA characteristics and diseasespecific and overall survival were studied (Table 1). Another
multicentre retrospective study investigated the safety and
risk of systemic progression in 262 patients with localised
and low-risk PCa electing active surveillance between 1991
and 2007 [9]. At a median follow-up of 29.7 mo, 16.4% of
patients subsequently underwent primary therapy. The 1-,
2- and 5-yr actuarial probabilities of remaining on active
surveillance were 95%, 91%, and 75%, respectively. Twenty-

845

six patients (9.9%) underwent radical prostatectomy. One

patient (0.4%) on active surveillance had a PSA rise from 6 to
24 ng/ml over a 6-mo period and developed skeletal
metastases.
With regard to radiotherapy, a multicentre, randomised,
controlled Groupe dEtude des Tumeurs Uro-Genitales
(GETUG) 06 study was conducted in 306 patients with
intermediate-risk PCa to compare clinical outcomes after
70 Gy (n = 153) or 80 Gy (n = 153) dose radiotherapy [10].
The median follow-up was 59 mo. Using the Phoenix
relapse definition (nadir plus 2 ng/ml), biological relapses
were 31.0% and 23.5% for the 70 Gy group and 80 Gy
group, respectively. There were no statistically significant
differences between the two arms for rectal toxicity
and quality of life at 5-yr follow-up. Therefore, 80 Gy did
not seem to provide a better outcome than 70 Gy
radiotherapy in patients with intermediate risk PCa at a
short follow-up.
Conflicting results on the risk of developing secondary
malignancies following treatment for PCa have been
reported. Several studies presented at the ASTRO annual
meeting investigated a putative increased secondary cancer
risk subsequent to PCa treatment. An analysis of the
Surveillance, Epidemiology, and End Results (SEER) registry
demonstrated that the incidence of bladder cancer seems to
remain low but slightly increased after curative treatment
for PCa [11]. In multivariate analysis, increasing age,
surgery, and irradiation were highly significant predictors
of developing bladder cancer. In contrast, Tward et al [12]
reported that men from a large SEER database with primary
PCa undergoing radical prostatectomy, external beam
combined with brachytherapy or brachytherapy alone
had no statistically elevated risk of developing any overall
or particular in-field malignancy. Another retrospective
multicentre study demonstrated that external beam radiotherapy was predisposed to a 3.0-fold higher rate of
cystectomy for bladder cancer ( p = 0.04), a 1.8-fold higher
rate of lung cancer surgery ( p = 0.02), and a 1.7-fold higher
rate of rectal cancer ( p = 0.02) by multivariate analyses [13].
Overall, we do not have apparent data yet on the risk of
developing secondary malignancies after PCa treatment.
Confounding factors such as smoking, which have never
been studied, should be taken into consideration.
3.3.

Locally advanced prostate cancer

Men with pT3 PCa are considered to have a higher risk of

recurrence than those with organ-confined disease. The
randomised phase 3 Southwest Oncology Group (SWOG)
8794 trial enrolled 425 men with pT3 PCa between 1988
and 1997 and addressed the benefit of adjuvant radiotherapy to surgery [14]. At a median follow-up of 10 yr,
adjuvant radiotherapy to radical prostatectomy resulted in
an increased biochemical control and a decreased local
failure over surgery alone. Although there was a trend
towards improvement, the impact of adjuvant radiotherapy
on overall and metastatic-free survival was not statistically
significantly improved. At the ASTRO annual meeting,
updated results were presented. Adjuvant radiotherapy

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EUROPEAN UROLOGY SUPPLEMENTS 8 (2009) 843847

Table 2 Effect of abiraterone acetate on prostate-specific antigen (PSA) levels in patients with castration-resistant prostate cancer
Logothetis et al [18] (n = 17)

Ryan et al [19] (n = 30)

8
41.1

12
43.0

Treatment (wk)
PSA decline 50% (% of patients)

4.

Fig. 3 Benefit of adjuvant radiotherapy to radical prostatectomy among

men with pT3 prostate cancer enrolled in the Southwest Oncology Group
(SWOG) 8794 trial [15].

significantly improved 15-yr metastasis-free survival

(Fig. 3) [15]. According to a recent publication, overall
survival also was significantly improved with adjuvant
radiation ( p = 0.023) [16]. With regard to patients with
lymph node-positive PCa treated with radical prostatectomy and pelvic lymph node dissection, only a few studies
have assessed factors predicting long-term survival.
Briganti et al [17] developed and internally validated a
nomogram predicting cancer-specific survival in nodepositive PCa patients treated with a multimodal approach.
By multivariate analysis, number of positive nodes,
pathologic Gleason score, surgical margin status, and
adjuvant radiotherapy were significant predictors of
cancer-specific survival (all p  0.01). A nomogram based
on preoperative PSA, pathologic stage, Gleason score,
surgical margin status, number of positive nodes, and
adjuvant radiotherapy demonstrated an accuracy of 72.7%.
3.4.

Hormone-refractory prostate cancer

A proportion of castration-resistant PCa overexpresses

androgen synthetic enzymes and remains dependent on
androgens for growth. Abiraterone acetate is an inhibitor of
17 a-hydroxylase C17,20-lyase (CYP17), a dual enzyme
responsible for androgen synthesis. The mechanism of
action of abiraterone is similar to ketoconazole, which
inhibits multiple adrenal CYP enzymes, including CYP17.
Several phase 1/2 studies presented at the ASCO annual
meeting investigated the effect of abiraterone acetate on
PSA decline [1820]. In addition, the impact of prior
ketoconazole therapy on abiraterone response was examined [19]. Abiraterone acetate appears to be well tolerated
and effective in patients with castration-resistant PCa, even
in patients experiencing disease progression on ketoconazole (Table 2) [1820].

Danila et al [20] (n = 38)

12
40.0

Conclusions

At the EAU, AUA, ASCO, and ASTRO 2008 annual meetings,

several interesting new data on PCa were presented. It was
shown that the frequency of lymph node metastases is low
in low-risk PCa patients. In addition, the percentage of
positive biopsies may be used to predict lymph node
involvement. As a result, the diagnostic benefit of extended
pelvic lymphadenectomy is questioned in patients with
low-risk PCa undergoing radical prostatectomy. According
to two studies presented at the EAU annual meeting, active
surveillance seems justified for appropriately selected
patients with very low-risk PCa. Furthermore, it is still
not clear whether primary radiation of PCa is associated
with a higher risk of developing secondary malignancies.
Confounding factors, including smoking, should be taken into
consideration before drawing final conclusions. With regard
to locally advanced PCa, an update of the SWOG 8794 trial
confirmed that adjuvant radiotherapy to surgery increases
biochemical control and decreases local failure. Moreover,
adjuvant radiotherapy significantly reduced the risk of
metastases and improved overall survival in men with pT3
PCa. Lastly, abiraterone acetate seems to be well-tolerated
and effective in patients with castration-resistant PCa.
Conflicts of interest
The author has nothing to disclose.
Funding support
The publication of this review was supported by Astellas
Pharma Europe Ltd.
Acknowledgements
The author is grateful to Dr. Patrick Bastian, Dr. Alberto
Bossi, Dr. Francesco Gomez-Veiga, Professor Axel Heidenreich, Dr. Andrea Mancuso, Dr. Stephan Madersbacher, Dr.
Laurent Salomon, and Professor Michel Soulie for selecting
data on prostate cancer presented at urological and
oncological congresses in 2008 and to Ismar Healthcare
NV for assistance in writing of the manuscript.

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