E U R O P E A N U R O L O G Y 5 6 ( 2 0 0 9 ) 4 7 9 – 4 8 5

Prostate Cancer

Platelet Microparticles: A Potential Predictive Factor of Survival

in Hormone-Refractory Prostate Cancer Patients Treated with

Docetaxel-Based Chemotherapy

Dominique Helley a,b,c,*, Eugeniu Banu d, Abdelkader Bouziane a, Adela Banu d,Florian Scotte d, Anne-Marie Fischer a,b,c, Stephane Oudard b,c,d

a AP-HP (Assistance Publique–Hopitaux de Paris), Service d’Hematologie Biologique, Hopital Europeen Georges Pompidou, Paris, F-75015, Franceb Universite Paris Descartes, Faculte de Medecine, Paris, F-75014, Francec INSERM Unite 765, Paris, F-75006, Franced AP-HP (Assistance Publique–Hopitaux de Paris), Service d’Oncologie Medicale, Hopital Europeen Georges Pompidou, Paris, F-75015, France

ava i lable at www.sciencedirect .com

journal homepage: www.europeanurology.com

Article info

Article history:

Accepted June 11, 2008Published online ahead ofprint on June 20, 2008

Keywords:

Hormone-refractory prostate

cancer

Platelet microparticles

Predictive factor

Abstract

Background: Several studies suggest a causal relationship between platelet activation and

cancer metastasis. Activated platelet microparticles (PMPs) release vascular endothelial

growth factor (VEGF) and basic fibroblast growth factor (bFGF), which play a major role in

angiogenesis.

Objective: We conducted a prospective, nonrandomised, single-centre study in hormone-

refractory prostate cancer (HRPC) patients to determine the impact of PMPs on the outcome.

Design, setting, and participants: Eligible chemonaive and metastatic HRPC patients

received docetaxel-based chemotherapy and a low dose of prednisone.

Intervention: PMPs in whole blood were quantified before the start of chemotherapy through

flow cytometry using an anti-CD41a monoclonal antibody, and plasma VEGF and bFGF were

determined with an enzyme-linked immunosorbent assay.

Measurements: The primary end point was to evaluate the impact of the PMPs on overall

survival (OS). We also studied the statistical interaction between PMPs and platelets and their

relationship with OS. The median PMP value was used to sort patients into two groups.

Results and limitations: Data of 43 consecutive HRPC patients treated in a single French

centre were analysed. Significant correlations were observed between Eastern Cooperative

Oncology Group performance status (ECOG PS), platelets, and PMP level. The median OS was

significantly shorter for patients with >6867 PMPs per ml of whole blood than for those with

lower values (16.7 vs 26.4 mo, p = 0.013). A significant relationship was found between OS and

PMPs, whereas a statistical interaction term between PMPs and platelets was significantly

associated with OS ( p = 0.019). No association was found between OS and plasma VEGF and

bFGF. In the multivariate analysis, only baseline prostate-specific antigen (PSA) and ECOG PS

remained significantly predictive of risk of death.

Conclusions: In HRPC patients, PMPs and their interaction with platelets were predictive of

outcome. A biologic association between PMPs and the OS of HRPC patients, independent of

chemotherapy regimen, should be demonstrated by confirmatory prospective studies.

# 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved.

* Corresponding author. Hopital Europeen Georges Pompidou, Service d’Hematologie Biologique, 20,rue Leblanc, 75908 Paris Cedex 15, France. Tel. +33 1 56 09 39 05; Fax: +33 1 56 09 33 93.E-mail address: dominique.helley@egp.aphp.fr (D. Helley).

0302-2838/$ – see back matter # 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2008.06.038

E U R O P E A N U R O L O G Y 5 6 ( 2 0 0 9 ) 4 7 9 – 4 8 5480

1. Introduction

Prostate cancer is currently the most frequent malignancy

in men and represents the second leading cause of cancer-

related deaths [1]. About 186 320 new cases of prostate

cancer will be diagnosed in the United States in 2008 and

almost 28 660 deaths are expected [1]. More than 90% of

these new cases are expected to be diagnosed at local or

regional stages [1]. Around 306 369 cases are diagnosed

each year in Europe [2]. Androgen deprivation therapy

allows a primary response rate of 80% to 90% [3]. Those

remissions last 2 or 3 yr, but almost all metastatic prostate

cancer patients evolve towards an androgen-refractory

state resulting in death due to widespread metastases [4].

Docetaxel-based chemotherapy is the standard of care for

hormone-refractory prostate cancer (HRPC) patients [5–7].

Platelets have been reported to contribute to the

metastatic process and to tumour growth [8]. They may

participate in metastatic spread by accumulating on

embolic tumour cells, thus protecting them from the

clearance exerted by the immune system [4]. A two-way

interaction has been shown between cancer spread and

platelet activation, with a hypercoagulable state found in

most cancer patients [9]. Platelets can act as bridges

between endothelial cells and lymphocytes or monocytes,

and thrombin-based platelets activation can enhance this

function [10]. In the same way, by facilitating tumour cell

arrest and adhesion to the endothelium, platelets may

promote micrometastases [11]. Moreover, cancer procoa-

gulant and tissue factor generated by the tumour itself

induce platelet activation and thrombin generation [12].

The authors demonstrated that metastatic patients with

breast or pancreatic cancer had increased levels of

microparticles associated with tissue factor compared to

nonmetastatic patients. Formation of metastatic deposits in

target organs depends on the balance between positive and

negative growth factors (eg, vascular endothelial growth

factor [VEGF] and basic fibroblast growth factor [bFGF]),

many of which are released by platelets. Thrombin-

activated platelets may promote proliferation of tumour

cells by secreting growth factors such as VEGF. Platelets

adhering to circulating tumour cells may release VEGF at

the adhesion points to endothelium, enhancing vascular

permeability and extravasation. VEGF-induced platelet

adhesion to endothelial cells depends on tissue factor

activation [13]. Platelet activation results in the shedding of

PMPs which promote proliferation, survival, and migration

of human umbilical vein endothelial cells as well as the

ability to form vascular tubes in vitro [14]. Furthermore,

PMPs induced angiogenesis in vivo according to a model of

chronic myocardial ischemia in rats. Additionally, ischemia

induces a decrease in the number of functional capillaries,

but their amount increased after injection of PMPs into the

myocardium [15]. Thus, PMPs shed from the circulating

platelets may reach adequate concentrations and their

elevated levels could contribute to florid formation of new

blood vessels and enhance tumour growth and metastases.

Angiogenesis appears to be essential to the growth and

spread of prostate cancer cells [16]. Microvessel density, a

quantitative measure of tumour angiogenesis, is signifi-

cantly greater in tumours from men with metastatic

prostate cancer than in those with localised disease [17].

Similarly, plasma levels of VEGF increase incrementally and

significantly from healthy men to men with localised

prostate cancer and then to those with metastatic disease

[18]. Moreover, plasma VEGF level at the initial diagnosis

predicts prostate-specific antigen (PSA) biochemical relapse

and clinical progression [18], and the VEGF level at

diagnosis of HRPC correlates with survival [19].

The aim of the present study was to isolate and estimate

the absolute number of PMPs in plasma of HRPC patients

and to investigate the predictive value of baseline PMPs on

overall survival (OS).

2. Methods

2.1. Study population

Eligible patients had histologically proven prostate adenocarcinoma

with distant metastases. The hormone-refractory status was defined as a

progressive increase in PSA level (three consecutive determinations)

after hormonal treatment (surgical castration or androgen blockade).

Patients had to fail both androgen blockade and antiandrogen with-

drawal. Hormonal castration had to be confirmed biologically (serum

testosterone <0.5 ng/ml). Patients had not previously undergone

chemotherapy, and time elapsed between blood sample collection

and start of chemotherapy might not exceed 90 days. Docetaxel-based

chemotherapy (docetaxel single drug or associated with estramustine or

capecitabine) was combined with a low dose of orally administered

prednisone. Main eligibility criteria were Eastern Cooperative Oncology

Group (ECOG) performance status (PS) �2, adequate haematologic

(granulocyte count >1.5 � 109/l, platelets count >100 � 109/l, haemo-

globin>8.5 g/dl), hepatic (transaminases�2.0 the upper limit of normal

[ULN], alkaline phosphatases �4 ULN or 8 ULN in case of bone

metastases), and renal (creatinine <150 mmol/l) levels. Only HRPC

patients with >4 ng/ml of PSA at baseline were included. Whole-blood

PMPs have to be measured 2 h after sampling; thus, only those patients

consulting in the morning were eligible. Written informed consent was

obtained before inclusion.

2.2. Blood sample collection and laboratory tests

Before the start of chemotherapy, a venous blood sample was collected

into trisodium citrate 0.105M Vacutainer tubes (Becton Dickinson, San

Jose, CA, USA). The whole blood sample was centrifuged for 15 min at

2800 g, and then plasma was recentrifuged for 15 min at 2800 g. Platelet-

poor plasma was aliquoted and kept frozen at �80 8C until assay. The

VEGF and bFGF plasma levels were quantified using a commercial

enzyme-linked immunosorbent assay (ELISA) kit (Quantikine human

VEGF and Quantikine high-sensitivity human fibroblast growth factor

[FGF] basic immunoassays, R&D Systems, Minneapolis, Minnesota, USA)

according to the manufacturer’s protocol. Duplicate assays were

performed to control the internal validity.

PMPs were determined in whole blood through flow cytometry

using an anti-CD41a, PE-coupled antibody, purchased from Becton

Dickinson (BD BioScience). A 1:10 dilution of whole blood drawn on

citrate Vacutainer tubes was analysed within 2 h of blood collection.

Fifty ml of these blood dilutions were incubated during 20 min with

10 ml of platelet-specific antibody (CD41a-PE) or isotype control (BD

BioScience). Calibrated polypropylene beads in Tru-count tube (BD

BioScience) were used for quantification. The reaction was stopped by

E U R O P E A N U R O L O G Y 5 6 ( 2 0 0 9 ) 4 7 9 – 4 8 5 481

1 ml of phosphate-buffered saline solution. The sample was immedi-

ately analysed by using a FACSCalibur flow cytometer with CellQuest

software (BD BioScience).

PMP gate was defined using 1-mm diameter beads on a log forward (FS)

and log side (SS) scatter cytogram. Among events within this gate (size

<1 mm), PMPs were discriminated from microparticles of other cellular

origin and background noise, according to their positive fluorescence

intensity on a log fluorescence–log FS dot plot. Events with size of>1 mm

that were positive for CD41a were defined as platelets. Results were

expressed as total number of PMPs and platelets per ml of whole blood. This

concomitant platelets count allows an internal control of PMP quantifica-

tion. The platelet count, performed through flow cytometry, was

compared to the standard platelets numeration on the whole blood

obtained with GEN’s counter (Beckman Coulter).

2.3. Statistical analysis

We selected a homogenous cohort of patients with a long follow-up and

treated consecutively. The primary end point was OS defined as the time

from start of chemotherapy until death from any cause or last follow-up

for censored patients. Categorical and quantitative data were presented

as percentages (with 95% confidence interval [CI]) and median with

range, respectively. Observed cumulative OS probabilities were com-

puted according to the Kaplan-Meier method, and curves were

Table 1 – Baseline characteristics of patients according to platelet mic

Characteristic �6867 per ml (n = 20)

n %

Age (yr)

Median 68

Range 52–82

ECOG performance status

0 16 8

1 4 2

2 0

Gleason score

2–6 3 1

7 6 3

8–10 11 5

UK 0

Hormone-sensitivity duration (mo)

Median 38.3

Range 6.3–148.5

Serum PSA (ng/ml)

Median 80.1

Range 4–3014

Haemoglobin (g/dl)

Median 12.3

Range 8–17

PSA-DT (days)

Median 43.4

Range 5.1–358.9

Number of metastatic sites

1 12 6

2 8 4

�3 0

Sites of metastases

Bone 18 9

Lymph nodes 9 4

Visceral 0

n = number of patients; PSA-DT = prostate-specific antigen doubling time; ECOG P

compared using Breaslow-Gehan (generalized Wilcoxon test) as a

nonparametric method. The following covariates were selected for the

univariate analyses: Gleason score, PSA and PSA doubling time (PSA-DT),

platelets, haemoglobin, PMPs, VEGF, bFGF level at baseline, age, ECOG PS,

number of metastatic sites, and hormone-sensitivity duration. A

multivariate Cox proportional hazards regression analysis using

significant variables for the univariate analyses ( p < 0.05) was

performed by forward stepwise selection. Hazard ratios (HR) were

presented with 95% CI. All p values were two-sided. A relational database

containing all data was constructed using FileMaker Pro 8.5v2 (File-

Maker Inc, Santa Clara, CA, USA) software. Both SPSS 16.0 (SPSS Inc,

Chicago, IL, USA) and Epi Info 3.3.4 (Centers for Disease Control and

Prevention, Atlanta, GA, USA) were used for the statistical analysis.

3. Results

3.1. Patients characteristics

Between July 2001 and November 2006, 43 consecutive

HRPC patients were treated in a single French institution

(Georges Pompidou European Hospital, Medical Oncology

Department, Paris, France). The main characteristics of

eligible patients are described in Table 1. Patients received a

roparticle (PMP) level

>6867 per ml (n = 23)

n %

72

53–85

0 7 30

0 13 57

0 3 13

5 4 17

0 8 35

5 10 44

0 1 4

38.6

3–215.6

63.9

4.2–2416

12.5

7.8–15.7

53.6

8.1–220.1

0 15 65

0 5 22

0 3 13

0 20 87

5 9 39

0 4 17

S = Eastern Cooperative Oncology Group performance status; UK = unknown.

Fig. 1 – Kaplan-Meier analysis of overall survival: Probabilities of overall survival among 43 patients split into two groups according to the median plateletmicroparticle (PMP) level.

E U R O P E A N U R O L O G Y 5 6 ( 2 0 0 9 ) 4 7 9 – 4 8 5482

chemotherapy-based regimen combined with a low dose of

prednisone in all cases. Docetaxel was administered as

single chemotherapy in 28 patients (65%); it was combined

with estramustine phosphate or capecitabine orally in 9

(21%) and 5 (12%) patients, respectively. The median age,

haemoglobin, and PSA at baseline were 69 yr (range: 52–

85), 12.5 g/dl (range: 8.6–14.6), and 53.9 ng/ml (range:

4.24–3720), respectively. PMP data were normally dis-

tributed; the median value was 6867 per ml (range: 3319–

16 270). Only 7% of patients had a poor ECOG PS of 2, and

only one involved metastatic site was found in 63% of HRPC

patients. Bone metastases were found in more than 90% of

cases. Half of patients had an aggressive disease expressed

by an elevated Gleason score between 8 and 10. No major

imbalances were found between two groups of HRPC

patients (according to baseline PMP level), including PSA-

DT and excepting ECOG PS ( p = 0.004). Patients with poor

clinical status (ECOG PS = 2) were found to have >6867

PMPs per ml of whole blood. Highly significant positive

correlations were found among ECOG PS, platelets, and PMP

level at Spearman test (correlation coefficients of 0.46 and

0.40, respectively, p < 0.009); however, younger patients

had significantly more platelets. No significant correlations

were found among VEGF, bFGF, and PMP level.

3.2. Survival analysis

At the moment of the analysis, 32 patients (74%) had died.

Overall, the median survival time for the entire cohort was

22.1 mo (95% CI: 20.4–23.7 mo), and observed cumulative

survival probabilities at years 1, 2, and 3 were 72% (95% CI:

Table 2 – Overall survival distribution according to platelet micropart

PMP category Median OS, months (95% CI) 1-yr OS, % (9

�6867 per ml (n = 20) 26.4 (16.7–36) 85 (69–1

>6867 per ml (n = 23) 16.7 (5.6–27.8) 60 (39–8

n = number of patients; OS = overall survival; CI = confidence interval.

58–85%), 43% (95% CI: 27–59%), and 25% (95% CI: 10–39%),

respectively. At a cut-off level of 6867 per ml of PMPs

(defined according to the baseline median value), the

median OS was significantly shorter for patients with higher

PMP values than for those with lower levels: 16.7 mo (95%

CI: 5.6–27.8 mo) versus 26.4 mo (95% CI: 16.7–36 mo),

respectively (Fig. 1; p = 0.034 [Breaslow-Gehan test]).

Cumulative survival probabilities with 95% CI for both

PMP categories are shown in Table 2. The univariate Cox

regression analysis demonstrated that the absolute PMP

level as a continuous variable was significantly associated

with OS ( p = 0.013). When the categorical variable was used

(>6876 versus �6876 per ml), the associated HR was 1.97

(95% CI: 0.94–4.15, p = 0.074), and the OS impact was

considered to be borderline. Other prognostic factors

significantly related with OS were baseline PSA and ECOG

PS. Moreover, a significant impact on OS was found for

statistical interaction between PMPs and platelet level

( p = 0.019). No association was found between plasma

VEGF and bFGF with OS; however, in the multivariate

analysis, PMPs were not predictive of survival ( p = 0.19),

whereas baseline PSA ( p = 0.013) and ECOG PS ( p = 0.014)

remained significantly predictive of risk of death.

4. Discussion

Prognostic and predictive factors were described in HRPC

patients and some recently published guidelines focused on

the role of chemotherapy as an evolving tool in the

management of these patients [20–22]. Platelets and PMPs

were extensively studied in thrombotic and vascular

icle (PMP) level

5% CI) 2-yr OS, % (95% CI) 3-yr OS, % (95% CI) p value

00) 58 (35–80) 29 (8–50) 0.034

0) 28 (6–50) 21 (1–41)

E U R O P E A N U R O L O G Y 5 6 ( 2 0 0 9 ) 4 7 9 – 4 8 5 483

diseases [23] and only recently studied in cancer patients. In

haematological cancers, elevated levels of PMPs were found

in 11% to 12% of patients with chronic myeloproliferative

syndromes such as chronic myelogenous leukaemia, poly-

cythemia vera, chronic myelofibrosis, and essential throm-

bocythemia [24]. More recently, in gastric cancer, Kim et al

[25] showed that PMPs levels are better predictors of

metastasis than VEGF, IL-6, and RANTES. Platelet level was

also claimed as a prognostic factor in cancer; thrombocy-

tosis was associated with a poor outcome in patients with

localized pancreatic cancer, operated with curative intent,

as demonstrated by a recent study on 105 patients [26]. Our

findings were based on a mature analysis: more than 80% of

HRPC patients are dead at the moment of the analysis. We

found that baseline PMP level was significantly related with

survival of HRPC patients treated with docetaxel-based

chemotherapy. Other important variables such as baseline

PSA and ECOG PS were associated with the outcome of HRPC

patients, as recently shown by Bamias et al [27]. Our cohort

of patients was homogeneous, with no potential source of

bias; however, the sample size and the short follow-up

restricted the statistical power of this exploratory analysis,

which possibly explains why the multivariate model did not

highlight a significant impact of PMPs on OS. Indeed, the

analysis was underpowered for some of other prognostic

covariates that are already known to significantly affect the

outcome, such as haemoglobin level or number of meta-

static sites at baseline [28]. Some expected statistical

associations were not found in the present analysis.

The role of PMPs on AKT cascade activation was explored

by recent research [29]. Several transmembrane-span

receptors could be transferred by PMPs to the membranes

of normal cells as well as to malignant ones. Observations

showed that PMPs chemo-attracted these cells; increased

their adhesion, proliferation, and survival; and activated in

these cells various intracellular signalling cascades, includ-

ing MAPK p42/44, PI-3K-AKT, and STAT proteins [18]. This

effect could explain one of multiple pathways enhancing

proliferation, angiogenesis, and metastasis. Our results

highlighted a potential statistical interaction between

platelets and PMPs. This possibility may be the expression

of a biological and physical interaction between two major

players implicated in the metastatic cascade. PMP levels

were significantly correlated with Gleason score, platelets,

and ECOG PS, meaning that a high PMP level was highly

correlated with aggressive tumours, elevated number of

platelets, and a poor clinical status. It is a potential

biological marker of tumour burden. Today, PMPs could

be considered as an actor in the intricate metastatic process,

adding a potential new target for specific, directed therapies

such as antiplatelet agents (antibodies against glycoprotein

IIb-IIIa, direct thrombin inhibitors, protease activated

receptor-1 inhibitors, cyclo-oxygenase inhibitors) [30].

Moreover, if PMPs are also thought to reflect a proangio-

genic effect of platelet release, they could be proposed as a

sign to suggest that antiangiogenic therapy is needed.

Plasma PMPs are increased in some patients with localised

prostate cancer, and a significant correlation with tissue-

factor (TF) antigen level was demonstrated, potentially

linking positive TF tumour cells with in vivo platelet

activation [31]. Moreover, a recent study shows that PMP

membranes have specific procoagulant activity that is 50-

to 100-fold higher than that of activated platelets [32].

5. Conclusion

In spite of a limited sample size, we have demonstrated a

significant impact of PMPs on survival. Our results warrant

confirmation in larger cohorts as well as in nonmetastatic

prostate cancer patients with a rising PSA after prostatect-

omy or external radiotherapy. Such studies would also test

the correlation between PMP levels and responsiveness to

hormonal treatment. In this group of patients, the role of

PMPs could be even more important; a high level of PMPs

could be predictive of poor prognosis and of shorter,

relapse-free, or overall survivals. These results raise

questions for therapeutic strategies: Could a treatment

modality have a goal of decreasing the absolute PMP level?

Is there a place for antiplatelet agents? Is PMP level a new

goal for targeted therapies? What is the effect of conven-

tional chemotherapy on PMPs? Serial PMPs assessments

during the course of chemotherapy and follow-up period

should be the best way to isolate potential effects on the

outcome. An extended Cox regression integrating PMPs as a

time-dependent variable could be the optimal modality to

identify possible relationships.

Author contributions: Dominique Helley had full access to all the data in the

study and takes responsibility for the integrity of the data and the accuracy

of the data analysis.

Study concept and design: Oudard, Helley, Fischer.

Acquisition of data: Banu E, Banu A, Helley, Bouziane.

Analysis and interpretation of data: Banu E, Banu A, Helley, Oudard.

Drafting of the manuscript: Banu E, Helley, Oudard.

Critical revision of the manuscript for important intellectual content:

Oudard, Fischer, Banu E, Scotte.

Statistical analysis: Banu E, Banu A.

Obtaining funding: Oudard, Helley, Fischer.

Administrative, technical, or material support: Oudard, Banu A, Scotte,

Fischer.

Supervision: Banu E, Oudard, Fischer, Banu A.

Other (specify): None.

Financial disclosures: I certify that all conflicts of interest, including

specific financial interests and relationships and affiliations relevant to

the subject matter or materials discussed in the manuscript (eg,

employment/ affiliation, grants or funding, consultancies, honoraria,

stock ownership or options, expert testimony, royalties, or patents filed,

received, or pending), are the following: None.

Funding/Support and role of the sponsor: ARTIC Association supported

collection of the data, management of the data, analysis, and

preparation.

Acknowledgment statement: The authors acknowledge Isabelle Cha-

pelle-Marcillac for providing editorial assistance in the preparation of

the initial drafts of the manuscript. We thank the technicians of the

haematology laboratory of Georges Pompidou European Hospital for

performing PMPs measurements.

E U R O P E A N U R O L O G Y 5 6 ( 2 0 0 9 ) 4 7 9 – 4 8 5484

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Editorial Comment on: Platelet Microparticles:

A Potential Predictive Factor of Survival in Hormone-

Refractory Prostate Cancer Patients Treated with

Docetaxel-Based Chemotherapy

Antonio Lopez-Beltran

Faculty of Medicine, Cordoba, Spain

em1lobea@uco.es

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2003;39:184–91.

[26] Suzuki K, Aiura K, Kitagou M, et al. Platelets counts closely correlate

with the disease-free survival interval of pancreatic cancer

patients. Hepatogastroenterology 2004;51:847–53.

[27] Bamias A, Bozas G, Antoniou N, et al. Prognostic and predictive

factors in patients with androgen-independent prostate cancer

treated with docetaxel and estramustine: a single institution

experience. Eur Urol 2008;53:323–32.

[28] Oudard S, Banu E, Beuzeboc P, et al. Multicenter randomized phase

II study of two schedules of docetaxel, estramustine, and predni-

sone versus mitoxantrone plus prednisone in patients with meta-

static hormone-refractory prostate cancer. J Clin Oncol 2005;23:

3343–51.

[29] Baj-Krzyworzeka M, Majka M, Pratico D, et al. Platelet-derived

microparticles stimulate proliferation, survival, adhesion, and

chemotaxis of hematopoietic cells. Exp Hematol 2002;30:

450–9.

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offer a chance of better cancer progression control? Semin Thromb

Hemost 2007;33:712–21.

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factor antigen in localized prostate cancer: Distribution, clinical

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Thromb Haemost 2007;97:464–70.

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Rodolfo Montironi

Polytechnic University of the Marche Region,

Ancona, Italy

r.montironi@univpm.it

Platelet activation results in the production of platelet

microparticles (PMPs) and has been found to be increased

in several types of cancer. PMPs are suggested to be useful

in a number of basic and preclinical papers. The study by

Helley et al [1] found that hormone refractory prostate

cancer patients treated with docetaxel showing PMP levels

above the median had a significantly lower overall

survival. PMPs presumably reflect microthrombosis, a

finding that seems to be commonly seen in prostate

cancer. Although the topic of this report [1] is of interest to

urologists and scientists who work in the field of prostate

cancer research, there is no ‘‘major impact on treatment’’

[2–4], and the study shows a biologic association resulting

in a negative study since PMPs were not independently

associated with overall survival in multivariate analysis. In

addition, the study series is of value because it is

prospective, but limited in size because it includes only

43 cases recruited over a period of 5 years. This represents

a major limitation, and the paper should be considered as a

preliminary data report. Adding more cases to the

reported series would thus add strength to the paper in

terms of clinical value. Finally, although the authors

suggest that therapies targeting PMPs may be useful, it is

not clear whether they contribute to disease progression

or are only a marker of disease extension and ongoing

thrombosis [2–4]. In summary, this study represents a

limited advance that is consistent with previous data [2–4]

and suggests that PMPs or other markers of ongoing

thrombosis might be indicators of disease burden; none-

theless, the potential value of PMP as an independent

marker remains unclear. The data reported by Helley et al

[1] underscore the need for more studies with appropriate

sample size confirming the suggested clinical potential of

PMP formation in hormone refractory prostate cancer

patients.

References

[1] Helley D, Banu E, Bouziane A, et al. Platelet microparticles: a

potential predictive factor of survival in hormone-refractory

prostate cancer patients treated with docetaxel-based che-

motherapy. Eur Urol 2009;56:479–85.

[2] Calabro F, Sternberg CN. Current indications for chemotherapy in

prostate cancer patients. Eur Urol 2007;51: 17–26.

[3] Heidenreich A, Aus G, Bolla M, et al. EAU guidelines on prostate

cancer. Eur Urol 2008;53:68–80.

[4] Bamias A, Bozas G, Antoniou N, et al. Prognostic and predictive

factors in patients with androgen-independent prostate cancer

treated with docetaxel and estramustine: a single institution

experience. Eur Urol 2008;53:323–32.

DOI: 10.1016/j.eururo.2008.06.039

DOI of original article: 10.1016/j.eururo.2008.06.038

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