Med Clin (Barc).

2016;146(3):121127

www.elsevier.es/medicinaclinica

Review

Prostate cancer
Joan Morote a, , Xavier Maldonado b , Rafael Morales-Brrera c , on behalf of the multidisciplinary group
for the study and management of prostate cancer Vall dHebron
a
Servicio de Urologa, Hospital Universitari Vall dHebron, Universitat Autnoma de Barcelona, Barcelona, Spain
b
Servicio de Oncologa Radioterpica, Hospital Universitari Vall dHebron, Universitat Autnoma de Barcelona, Barcelona, Spain
c
Servicio de Oncologa Mdica, Hospital Universitari Vall dHebron, Universitat Autnoma de Barcelona, Barcelona, Spain

a r t i c l e i n f o a b s t r a c t

Article history: The Vall dHebron multidisciplinary prostate cancer (PC) team reviews recent advances in the manage-
Received 20 October 2014 ment of this neoplasm. Screening studies with long follow-up show a reduction in mortality, whereas
Accepted 11 December 2014 active surveillance is emerging as a therapeutic approach of non-aggressive cancers. New markers
Available online 18 May 2016
increase the specicity of PSA and also allow targeting suspected aggressive cancers. Multiparametric
magnetic resonance (mMRI) has emerged as the most effective method in the selection of patients for
Keywords: biopsy and also for local tumour staging. The paradigm of random prostatic biopsy is changing through
Prostate cancer
the fusion techniques that allow guiding ultrasonography-driven biopsy of suspicious areas detected in
Diagnosis
Treatment
mMRI. Radical prostatectomy (RP) and radiotherapy (RT) are curative treatments of localized PC and both
have experienced signicant technological improvements. RP is highly effective and the incorporation
of robotic surgery is reducing morbidity. Modern RT allows the possibility of high tumour dose with
minimal adjacent dose reducing its toxicity.
Androgen deprivation therapy with LHRH analogues remains the treatment of choice for advanced PC,
but should be limited to this indication. The loss of bone mass and adverse metabolic effects increases
the frequency of fractures and cardiovascular morbimortality. After castration resistance in metastatic
disease, new hormone-based drugs have demonstrated efcacy even after chemotherapy resistance.
S.L.U. All rights reserved.
2015 Elsevier Espana,

Cncer de prstata

r e s u m e n

Palabras clave: El equipo multidisciplinario de cncer de prstata (CP) del Hospital Universitario Vall dHebron revisa
Cncer de prstata los avances recientes en el tratamiento de esta neoplasia. Estudios de cribado y largo seguimiento ponen
Diagnstico de maniesto una reduccin de la mortalidad, mientras la vigilancia activa emerge como una actitud
Tratamiento
teraputica frente al diagnstico de cnceres no agresivos. Nuevos marcadores incrementan la especi-
cidad del PSA y, adems, permiten focalizar la sospecha de cnceres con comportamiento agresivo. La
resonancia magntica multiparamtrica (RMm) se ha posicionado como el mtodo ms ecaz en la selec-
cin de pacientes para biopsia y tambin para estadicar el tumour a nivel local. El paradigma de biopsia
aleatoria ecodirigida est cambiando, y a travs de la fusin de imgenes entre RMm y ecografa se est
convirtiendo en una biopsia guiada a zonas sospechosas. La prostatectoma radical (PR) y la radioterapia
(RT) son los tratamientos curativos del CP localizado y en ambas se han experimentado mejoras tec-
nolgicas notables. La PR es altamente ecaz y la incorporacin de la ciruga robtica est reduciendo su
morbilidad. La moderna RT permite administrar mayores dosis en el tumour y mnimas dosis adyacentes,
reducindose signicativamente su toxicidad.

Please cite this article as: Morote J, Maldonado X, Morales-Brrera R. Cncer de prstata. Med Clin (Barc). 2016;146:121127.
Corresponding author.
E-mail address: jmorote@vhebron.net (J. Morote).

The names of the components of the multidisciplinary group for the study and treatment of prostate cancer Vall d Hebron are listed in Appendix.

S.L.U. All rights reserved.

2387-0206/ 2015 Elsevier Espana,
122
Introduction
Prostate cancer (PC) is the most common male malignancy in
developed countries and its mortality is only behind lung and colo-
rectal cancer.1 In Spain the incidence is 82 cases per 100,000 men.
90% of PCs are diagnosed at localized stage, 6% at locally advanced
and 4% at dissemination.2
Diagnosis
PC screening is controversial.3 The Gteborg trial has shown a
reduction in mortality from the seventh year of follow-up, which
reached 44% at 14 years. A reduction of 41% in advanced tumours
was also observed.4 The high rate of overtreatment is the most
questionable aspect of the screening.3 In Gteborg, 60% of PCs were
localized-low risk. However, 45% of patients undergoing active
surveillance (AS), exceeding 80% survival at 10 years.5
The high number of negative biopsies is another controversial
aspect in the diagnostic process of the PC. Today we can increase
the specicity of PSA using the PCA3 test, the Prostate Health Index,
and also the multiparameter magnetic resonance imaging (mMRI).6
Further, the 4K test provides a high diagnostic efcacy for interme-
diate and high risk tumors.7 mMRI has superior efcacy to 90%.6 The
introduction of browser based MRI and ultrasound image fusion is
changing the concept of random prostate biopsy to biopsy target-
ing at suspected areas. This new biopsy method is more efcient
and reduces the number of punctures.8
Once the diagnosis of lung cancer is conrmed, the patholo-
gist reports the Gleason grade and its extension in each cylinder.
PC staging with CT scan and bone scan has been the standard in
patients with PSA above 20 ng/ml and/or Gleason score above 7.
Today, the mMRI can effectively determine the local stage.9 In addi-
tion to the TNM, the localized PC is classied according to their risk
of biochemical recurrence.10
The last pharmacological advances have contributed to a bet-
ter denition of the terminal stages of the disease (Fig. 1).
PSA level/tumour mass
Initial diagnosis and
treatment
Castration
Time
Localized
Asymptomatic
Castration sensitive Castration resistant
Hormone-sensitive Hormone-refractory
Fig. 1. Natural history of localized prostate cancer.
J. Morote et al. / Med Clin (Barc). 2016;146(3):121127
La supresin andrognica con anlogos de la LHRH sigue siendo el tratamiento de eleccin del CP
avanzado, pero debe limitarse a esta indicacin. La prdida de masa sea y los efectos metablicos adversos
incrementan la frecuencia de fracturas y morbimortalidad cardiovascular. En la fase de resistencia a la
castracin con diseminacin metastsica nuevos frmacos de base hormonal han demostrado ecacia
incluso despus de resistencia a quimioterapia.
S.L.U. Todos los derechos reservados.
2015 Elsevier Espana,
Asymptomatic PC along its natural history becomes symptomatic
with bone dissemination. The survival of a patient with localized
PC exceeds 15 years, which is reduced to less than 5 in cases of
dissemination, and only 12 months when it is castration-resistant.
Active surveillance
The incidence of insignicant PC is 18% and mortality does not
exceed 3%.11 This shows that many PCs may be overtreated.12 They
are localized tumours, well-differentiated, under 5 mm and with no
possibility of spreading.13 Therefore, these tumours do not need to
be treated, and can be subject to AS, avoiding the adverse effects of
radical treatment.
The most restrictive inclusion criteria considered tumours
with a Gleason score lower than 7, PSA less than 10 ng/dl, PSA
density exceeding 0.15, a maximum stage of cT2a, maximum
involvement of two cylinders with less than 50% involvement.
The criteria for implementing treatment are the patients non-
acceptance of AS and suspicion of progression, based on a Gleason
grade increase and/or tumour extension in monitoring biop-
sies and PSA doubling time of less than 3 years.14,15 There is
no current consensus on the lack of biopsies during follow-up
(Table 1). mMRI normality is a good method to select candidates for
AS.16,17 PCA3 levels below 20 are also associated with insignicant
tumors.18
The progression of patients undergoing AS is similar to that
observed with radical treatments.19 In a series of 453 patients sub-
ject to follow-up for 10 years, it was observed that 72% remained
on AS at 5 years, 13% were rescued with a biochemical recurrence
rate of 50%. Overall survival at 10 years was 79% and specic,
97%.20 AS is currently recommended, especially in patients over
65 years.
Radical prostatectomy
Radical prostatectomy (RP) is the surgical treatment for local-
ized PC and its indication is based on their risk of recurrence.10 It
is the treatment of choice in low and intermediate risk PC and life
Exitus
expectancy exceeds 10 years. The specic 10-year survival is above
94%.21 In high-risk PC, RP is optional, especially in younger patients
Skeletal- and in the context of a multimodal treatment. Due to the high
related events probability of surgical margins (3366%) and positive lymph nodes
(849%), between 56 and 78% of patients require adjuvant or sal-
Metastasis
vage therapy with radiotherapy or androgen suppression. Specic
survival at 5, 10 and 15 years is 95, 90 and 79%, respectively.21
There are no prospective studies that support the RP as a treat-
Castration resistance ment of choice in locally advanced PC. However, it is estimated
that 10% of patients may be over-staged.22 Patients with pT3a
(extracapsular involvement in the RP specimen) and negative mar-
gins have biochemical recurrence and survival rates similar to
Disseminated those of patients with localized PC. Retrospective studies sup-
Symptomatic port that young and healthy patients with T3b and T4N0 stages,
could benet from the RP in the context of a multidisciplinary
approach.21
There is growing evidence that RP with extensive lymphadenec-
tomy increases biochemical and specic recurrence-free survival
 J. Morote et al. / Med Clin (Barc). 2016;146(3):121127 123

Table 1
Characteristics of active surveillance programmes.

Group Inclusion criteria Monitoring Criteria for

treatment

DRE PSA Rebiopsy Imaging test

Klotz et al., 2010 No. 450; Every 3 months/ Every 3 months/ Conrmatory Optional MRI PSADT < 3 years.
Gleason 6; 2 years. Then, 2 years. Then, in 612 months. Gleason
PSA 10 ng/ml every 6 months if every 6 months if Every 34 years up progression to 4 + 3
(in patients stable PSA stable PSA to 80 years of age
> 70 years).
PSA 15 ng/ml
or Gleason 3 + 4
Soloway et al., 2010 No. 230; CS: Every 34 Every 34 Conrmatory in Gleason > 6.
T1a-T2; months/2 years. months/2 years. 912 months. Tumour/cylinder
Gleason 6; Then, every 6 Then, every 6 Subsequently, percentage
PSA < 10 ng/dl; 2 months if stable months if stable annual or earlier if increase. Increased
affected cylinders PSA PSA severe rise in PSA number affected
(<20% length of the or DRE anomalies cylinders. Patient
cylinder) decision
Venkitaraman et al., No. 119; CS: Each month/year. Repeat PB after Gleason increased
2007 T1-T2a; Every 3 months 1824 months. 67.
Gleason 3 + 4; during the second Re-immediate PB Gleason 4 + 3. 50%
PSA < 15 ng/dl; year. Subsequently, only if of cylinders
50% affected every 6 months PSADT > 2 ng/ml/ml affected. PSADT < 4
cylinders years
Berglund et al., 2008 No. 104; CS: T1c; Conrmatory MRI prior to Gleason > 6. Two
Gleason 6; in 3 months. re-conrmation PB affected cylinders.
PSA < 10 ng/dl; 3 Subsequently, >50% involvement
affected cylinders annual of any cylinder
(<50% length of the
cylinder)
Carter et al., 2007 No. 407; CS: T1c; Every 6 months Every 6 months Annual Gleason > 6. Two
Gleason 6; affected cylinders.
PSADT < 0.15 ng/ml; >50% involvement
PSA < 10 ng/dl; 2 of any cylinder
affected cylinders
(<50% length of the
cylinder)

Taken from Celma et al.14

PB: prostate biopsy; CS: clinical stage; MRI: magnetic resonance imaging; PSA: prostate-specic antigen; PSADT: prostate-specic antigen doubling time; DRE: digital rectal
examination.

in patients with limited lymph node involvement.23 Salvage RP
would be indicated after failure of radiotherapy or other treat-
ments with curative intent. Needs histological conrmation and
absence of disseminated disease. The ideal candidate would be a
patient with a life expectancy of over 10 years, localized initial
stage and PSA lower than 10 ng/ml. The biochemical recurrence-
free survival at 5 years would range between 37 and 55%, and the
specic at 10 years between 70 and 83%. This procedure has a signif-
icant rate of complications and urinary incontinence in 3681% of
cases.24
There are nomograms that estimate the risk of lymph node
involvement, recommending lymphadenectomy when it is higher
than 5%. The current standard for lymphadenectomy covers the
obturator fossa and the internal and external iliac vessels.25
Perioperative mortality of RP is less than 1%, and the transfusion
rate is lower than 2%. RP complications are: rectal injury 35%, deep
vein thrombosis in 08%, pulmonary embolism in 0.88%, lympho-
cele in 13%, urinary stula in 0.315%, mild urinary incontinence
in 450% and severe in 415%, erectile dysfunction in 29100%,
ureteral obstruction in 1% and ureterovesical junction stenosis
29%.
The conventional approach for the RP is open retropubic and,
exceptionally, the perineal approach. The laparoscopic and robotic
approaches are currently of choice due to their lower morbidity.
It is estimated that oncologic and functional outcome is com-
parable in all of them; however, laparoscopic approaches offer
lower transfusion rates and a shorter hospital stay.21,26 Recent
meta-analyses show less need for transfusion in robotic RP,27 bet-
ter rates of urinary continence and early erection recovery.26,28,29
No differences were observed in the rate of surgical mar-
gins between different approaches and the oncological results
are similar.30 Follow-up after the RP is done with serial PSA
determinations, which can be supplemented with digital rectal
examination and imaging tests when biochemical recurrence is
detected.21
Radiotherapy
External radiotherapy in PC has evolved in the last decade
from the three-dimensional conformal to intensity modulated
(IMRT), with which it is possible to modulate the radiation beam
more accurately. This allows the administration of high doses,
minimizing adverse effects.31 Image-guided radiotherapy further
increases the accuracy and therapeutic index. These techniques
allow safe dose escalation and a biochemical control ranging
between 60 and 80%.32 The optimal dose for treating low-risk PC is
76 Gy, and 81 Gy for intermediate and high risk. Moderate hypofrac-
tionation schemes with IMRT, of 2.44.0 Gy in 46 weeks, may
soon be the new standard of care, as they have demonstrated bio-
chemical and toxicity control equivalence in comparison to longer
regimens.33 Extracranial stereotactic radiotherapy is an emerging
technique that combines high accuracy with extreme hypofrac-
tionation of between 5 and 7 fractions. Some trials, with 5-year
follow-up, have shown a biochemical control in low, intermediate
124 J. Morote et al. / Med Clin (Barc). 2016;146(3):121127

and high risk of 95, 84 and 81%, respectively, and excellent toxicity
results.34
The oncological results of external radiotherapy in low-risk
localized PC at 15 years are equivalent to those of the RP, although
its toxicity prole is different.35 There are no randomized trials that
compare them, and quality of life studies show equivalent results
in overall scores, with differences in sexual, urinary and gastroin-
testinal areas.36
In intermediate risk localized PC, the combination of external
irradiation and ADT (androgen deprivation therapy), between 4 and
6 months, has demonstrated a 13% increase in overall survival at
8 years.37 In locally advanced PC, the EORTC 22961 trial showed
an improvement of 5% in the overall survival rate at 5 years in
patients undergoing ADT for 3 years compared to 6 months.38 The
association of short-term ADT is currently the standard in patients
with intermediate-risk localized PC and unfavourable factors, while
the long-term ADT, between 24 and 36 months, is the standard in
patients with high and very high risk PC.
Low dose rate brachytherapy is an appropriate treatment in
low-risk patients with glandular volume lower than 50 cm3 and
absence of urethral obstruction and bladder instability. The 10-
year biochemical control ranges between 85 and 93%.39 High dose
rate brachytherapy represents the temporary implantation of a
radioactive source in order to superimpose the dose administered
with external beam radiation. This treatment is indicated in high-
risk PC, with excellent results in biochemical control and specic
survival.40 Some authors use this technique as monotherapy in
intermediate risk patients.
Three randomized trials have shown that administration
between 60 and 66 Gy, as adjuvant to RP when there is extracap-
sular extension, seminal vesicle involvement or positive margins,
improved biochemical control by 20% (Table 2).
Androgen suppression
Castration is the palliative treatment of disseminated PC.41
Serum testosterone levels allow to assess the effectiveness of the
ADT and should be lower than 50 ng/dl. Current analytical methods
can detect levels below 20 ng/dl, and some estimate that this level
of castration would be more appropriate. A recent study showed
that 32 ng/dL was the lowest level of testosterone that predicted
Table 2
Indications for radical prostatectomy.
Treatment of choice
Patients with low-risk disease, cT1a-T2a, Gleason 6, PSA < 10 ng/ml
and life expectancy > 10 yearsa
Patients with intermediate-risk disease, cT1a-T2b, Gleason 7,
PSA < 20 ng/ml and life expectancy > 10 yearsb
Optional treatment
cT1a or Gleason 7 and life expectancy > 15 years
Selected patients with high-risk localized disease, cT3a or Gleason 810
or PSA > 20 ng/ml
Highly selected patients with very high risk, localized, locally advanced or
metastatic disease, cT3b-T4N0 or TN1, in the context of a multidisciplinary
treatment
Ilio-obturator lymphadenectomy
Low-risk patients > 50% of cylinders affected
Intermediate and high risk patients
Taken from Heidenreich et al.21
PSA: prostate-specic antigen.
a
Bilateral preservation of neurovascular bundles would be indicated in patients
with low risk of extracapsular disease, cT1c, Gleason 6 and PSA < 10 ng/ml.
b
The unilateral preservation of neurovascular bundles is an option in T2a-T3a
tumours.
a difference in castration-resistant-free survival, therefore it was
dened as the castration level with clinical impact.42
AD is achieved by suppressing testicular androgen secretion by
surgical castration or LHRH analogues. The maximum androgen
blockade (MAB) is achieved by combining castration and antian-
drogen (Table 3). Systematic reviews have shown that the MAB
provides marginal benet to 5 years versus castration43 and a
higher rate of adverse effects. So its benet is currently being ques-
tioned.
ADT does not benet patients with localized PC. However, in
high-risk patients, it signicantly reduces mortality when asso-
ciated with radiotherapy.44 Some studies have shown a clinical
benet when ADT is combined with radiotherapy during 46
months in intermediate-risk patients and for 23 years in high-risk
patients.45
Early implementation of ADT increases survival in patients
undergoing RP with lymph node involvement.46 The EORTC
30846 study showed no benet when it compared imme-
diate with delayed treatment.47 However, the EORTC 30891

Table 3
Characteristics of androgen deprivation therapy.

Mode and agents Mechanism of action Observations

Surgical castration
Estrogenic agonist: diethylstilbestrol
LHRH agonist: buserelin, goserelin,
histrelin, leuprorelin, triptorelin
LHRH antagonists: abarelix, degarelix
Steroidal antiandrogens: cyproterone
acetate, megestrol acetate,
medroxyprogesterone
Non-steroidal antiandrogens:
bicalutamide, utamide, nilutamide
Testicular androgen deprivation therapy
Suppression of LHRH. It inhibits LH and testicular
androgens secretion
Suppression of LHRH. Inhibits LH secretion and testicular
androgen production
Direct inhibition of LHRH without agonist properties
Suppression of testosterone production due to feedback
effect in the hypothalamus and pituitary gland
Competitive inhibition of androgens binding in their target
tissue
Quickest way to reduce testosterone levels (<12 h).
Irreversible, psychological impact
Thrombogenic side effects associated with increased
cardiovascular mortality
Castration levels in 24 weeks. Transient increase of LH
and FSH with elevated testosterone levels during the rst
27 days. In patients with advanced disease this situation
may involve bone pain and spinal cord compression.
Simultaneous administration of an antiandrogen during
the rst 2 weeks reduces the risk of adverse effects
Rapid decrease in LH, FSH and serum testosterone levels,
preventing testosterone are. Severe systemic reactions
by histamine release have been reported
Reduce testosterone levels with the consequent decrease
in libido/impotence and changes in bone mineral density
Testosterone levels are not reduced. They can cause
gynecomastia, liver and gastrointestinal disorders. It can
be considered as monotherapy in patients with locally
advanced prostate cancer (not inferior to LHRH agonists
or surgical castration), but not in metastatic patients

FSH: follicle stimulating hormone; LH: luteinizing hormone; LHRH: luteinizing hormone-releasing hormone.
 J. Morote et al. / Med Clin (Barc). 2016;146(3):121127 125

Table 4
New treatments for castration-resistant prostate cancer.

Drug Mechanism of action Study design Population Primary objective

Abiraterone (COU-AA-301,a Inhibits CYP17 Abiraterone + PDN; CRMPC previously treated OS: 15.6 versus 11.2 m; HR 0.74
De Bono et al.55 , 2011) placebo + PDN with DP
Abiraterone (COU-AA-302,a Inhibits CYP17 Abiraterone + PDN; CRMPC not previously treated rPFS: 16.5 versus 8.3 m; HR
Ryan et al.53 , 2013) placebo + PDN with DP 0.53. OS: 35.3 versus 30.1 m;
HR 0.79
Enzalutamide (AFFIRM,a Scher AR antagonist Enzalutamide; placebo CRMPC previously treated OS: 18.4 versus 13.6 m; HR 0.63
et al.56 , 2012) with DP
Enzalutamide (PREVAIL,a Beer AR antagonist Enzalutamide; placebo CRMPC not previously treated rPFS: NR versus 3.9 m; HR 0.19.
et al.54 , 2014) with DP OS: 32.4 versus 30.2
Cabazitaxel (TROPIC,a De Bono Microtubule inhibitor Cabazitaxel/PDN; CRMPC previously treated OS: 15.1 versus 12.7 m; HR:
et al.57 , 2010) mitoxantrone/PDN or not with DP 0.70
Radio223 (ALSYMPICA,a Parker Radioisotope emitter, Radio223 ; placebo CRMPC with symptomatic OS: 14.2 versus 11.2 m; HR 0.69
et al.58 , 2013) calcimimetic bone metastases previously
treated with ADT

CRMPC: castration-resistant metastatic prostate cancer; DP: docetaxel/prednisone; m: months; PDN: prednisone; AR: androgen receptor; OS: overall survival; rPFS: radio-
graphic progression-free survival.
a
Name of clinical trial.

study showed improved survival in patients who received
immediate treatment, although differences between specic mor-
tality and symptom-free-survival were observed.48 In patients
with biochemical recurrence after surgery or radiotherapy, ADT
does not seem to yield any benets. Although the ADT does
not increase survival in disseminated PC, early use reduces
the risk of bone fractures, kidney failure and spinal cord
compression.49
As a result of the reduction of testosterone, ADT causes loss of
libido, erectile dysfunction, bone mass loss, sarcopenia, lipid dis-
orders, insulin resistance and metabolic syndrome. These changes
increase the risk of fractures and cardiovascular morbidity. There-
fore, prevention and early treatment is recommended.
Intermittent ADT is currently accepted, since several clinical tri-
als have shown no inferiority when compared to continuous ADT,
with reduced side effects and increased quality of life. Intermit-
tent ADT should especially be offered to patients with biochemical
recurrence after local treatment.50
Castration-resistant prostate cancer
Castration resistance appears during ADT, despite low lev-
els of testosterone, and is manifested by disease progression at
radiological and/or biochemical levels.51 New agents allow to
increase survival in patients with metastatic castration-resistant
PC (CRMPC) (Table 4).
In 2004, docetaxel/prednisone was approved as rst-line treat-
ment in CRMPC. The SWOG-9916 and TAX-327 studies showed
increased survival at 2 months compared to placebo/prednisone.52
Before docetaxel, abiraterone acetate, a selective inhibitor of
CYP17--hydroxylase and C17,20-lyase, which blocks androgen
synthesis, showed an increase in progression free survival from 8.3
to 16.5 months and a reduction in the risk of death by 25% versus
placebo/prednisone53 in the COU-AA-302 trial and when associated
with prednisone.
Enzalutamide is an androgen receptor antagonist which also
inhibits its translocation to the nucleus and interaction with DNA;
in the PREVAIL trial it showed a progression-free survival increase
of 14% at 12 months and reduced the risk of death by 29% compared
to placebo.54
After docetaxel, abiraterone/prednisone showed an increase
in survival of 4.8 months compared to patients treated with
placebo/prednisone (15.8 and 11.2, respectively) in the COU-AA-
302 trial.55 Enzalutamide has also shown an increase in survival of
4.8 months compared to placebo (18.4 and 13.6, respectively).56
Cabazitaxel, a new generation taxane was tested versus mitox-
antrone, with a 2.4 month-survival increase (15.1 and 12.7,
respectively).57
Radio223 is the rst radiopharmaceutical particle emitter
with specic action on the bone due to its calcimimetic activ-
ity. The ALSYMPCA study, conducted in CRMPC patients who had
received or not treatment with docetaxel (57% of patients) showed
a survival of 14.9 months compared to 11.3 in placebo-treated
patients.58
Conclusions
PC mortality has been declining since the early nineties.
Screening and improved curative treatments has contributed
to this. Diagnostic methods have signicantly improved in the
past 10 years, and new, less invasive, curative intent treatments
have been introduced which have signicantly reduced morbid-
ity. AS has emerged as an alternative to overdiagnosis secondary
to the screening of tumours with low and very low risk to a
stronger androgen deprivation in some patients. Hormone-based
new molecules have shown their efcacy in castration resis-
tance, showing how some of these patients exhibit sensitivity to
hormones.
Conict of interests
The authors declare no conicts of interest.
Appendix
Jacques Planas, Anna Celma, Jos Placer, Cristina Suarez and Joan
Carles.
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