PROGRESS IN MANAGEMENT OF PROSTATE CANCER

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PROGRESS IN MANAGEMENT OF PROSTATE CANCER

• Presented by Dr. J. Nkusi on the October 2007,
  38th Congress of the Botswana Medical
  Association.

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INTRODUCTION

Treatment options
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Localised Disease
1.Watchful waiting No randomized study has
demonstrated the benefit of radical treatment for
early stage cancer of the prostate (T1 and T2)
4
2. Radical prostatectomy Prognosis (outcome) of
patients treated by radical operation correlates
with the stage of the disease (involvement of
lymph nodes, Gleason score and PSA). Morbidity
associated with radical treatment can be
significant!
5
3. Radiotherapy Possible improvement of PSA
levels, however improvement of prognosis not
proved.
6
4. Brachytherapy Early data in patients with
low volume and low grade cancer of the prostate
are encouraging compared to other forms of
radiotherapy. Cave possibility of urine
obstruction , seed migration and impotence.
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5. Cryotherapy At least at short term
cryotherapy can bring to negative prostate biopsy
and low or undetectable PSA. Cave impotence,
recto urethral fistula and urinary obstruction!
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6.Thermo Ablation An alternative treatment using
High Intensity Focused Ultrasound (HIFU) in
patient non eligible for a radical prostatectomy.
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Locally Advanced Disease At T3 stage the
treatment involves External beam radiotherapy
(XRT) preceded by complete androgen blockade.
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C. Metastatic Disease Androgen ablation therapy
and or orchiectomy .
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PROGRESS
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1. Diagnosis and screening
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1. PCa in men with prostate specific antigen lt4 ng/ml

The widespread use of PSA as a screening tool has
led to an increase in PCa patients number.
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PSA levels gt4ng/ml have been considered an
indication for prostate biopsy.There is
continuous debate whether the threshold for PCa
detection should be lowered to detect more Tm at
an organ confined stage.
15
Contradictory, histopathology results of operated
prostates have sometimes come out free of
malignancy even with PSA levels well over
10ng/ml. Conclusion No distinct PSA threshold
is suitable for early clinically relevant PCa.
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1.2Prostate cancer gene 3 (PCA3) A new test may
help the Prostate CancerGene3 (PCA3) assay. The
PCA3 assay uses urine to measure PCA3 and PSA
messenger RNA (mRNA) concentrations, of which the
ratio is taken to calculate the PCA3 score
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The PCA3 assay provides near complete separation
of young healthy men vs men with BPH vs men with
PCa and those after radical prostatectomy. PCA3
is highly specific for PCa versus BPH and may
therefore be used in the diagnosis of PCa.
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2.Radical therapy 2.1Surgical skills and PCa
recurrence It was established that the surgeons
skills may influence the outcomes of radical
prostatectomy in terms of morbidity and positive
margin rates. The number of cases done was not
proof of well done procedure.
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More and more classical retropubic radical
prostatectomy is being replaced by endoscopic
procedure and robot assisted prostatectomy.
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2. 2. Adaptive radiotherapy Adaptive
radiotherapy intends to improve radiation
treatment by systematically monitoring treatment
variations and incorporating them to re -
optimise the treatment early on during the course
of treatment.
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A recent study (Forsky MS, et all Int. J Radiat
Oncol Biol Phys 200666) has shown that adaptive
radiation therapy may improve biochemical
relapse-free survival and reduce the risk of late
rectal complications.
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2.3. Histopathology At the European Association
of Urology 2006 Congress a report mentioned a
marked discrepancy between the local pathologists
and the review pathologist on the histopathologic
evaluation of prostatectomy specimens concerning
extracapsular extension and margin status.
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Central review of specimens may improve the
quality of examinations and play a role in future
clinical trials.
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2.4. Salvage radiotherapy for biochemical
recurrence. In case of recurrence after radical
prostatectomy, salvage radiotherapies may be
started. The outcomes depend on the pre
radiation PSA levels.
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Salvage treatment should be started as soon as
possible when PSA failure is observed, according
to a recent presentation at the AUA 2006 annual
meeting. A predictive 5 year progression-free
probability model was developed.
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3.Hormone Therapy 3.1. Immediate versus deferred
treatment There is no consensus whether a
hormone therapy( orchidetomy or LHRH agonist) for
locally advanced, and asymptomatic metastatic PCa
at diagnosis, favorably influences survival and
quality of life compared to deferred therapy.
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However it is accepted that patients with a PSA
8-50 ng/ml and a PSA doubling within a year are
at high risk of disease progression and death,
and should be elected for immediate total
androgen blockade.
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3.2. Androgen-deprivation for biochemical
recurrence after prostatectomy Patients with a
rising PSA after RP benefit of androgen
blockade. It was found that a prolonged response
to androgen-deprivation therapy over 12.4 years
can be achieved when the immediate response is a
PSA at the nadir level of lt0.2ng/ml.
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3.3. Intermittent versus continuous androgen
blockade It is common knowledge that all
patients on hormone therapy end up advancing to
hormone independence and ultimately to
hormone-refractory state.
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A recent study showed that intermittent therapy
may be a way of delaying hormone resistance while
improving quality of life at the same time (
sexual life e.g.).
31
Survival rate at 5 years was comparable and even
better in the intermittent group (53.8 vs 51.0)
compared to the continuous group. Therefore
intermittent hormone therapy was adopted by the
EAU 2007 guidelines to be an option in regular
practice.
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3.4. Prevention of mineral loss Patients on
hormone therapy for PCa are at risk of decreased
bone mineral density and osteoporotic fractures .
33
The administration of Zoledronic acid 4mg yearly
injection has been found effective in preventing
the decrease of BMD in a recent randomised study
(Michaelson MD, Lee H, Smith MR. J Clin Oncol
200624220 Abstr no. 4515).
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4.Hormone-resistant Prostate Carcinoma Until
recently options were limited for the treatment
of hormone refractory PCa and no single or
combined chemotherapy had proven to prolong
survival. Two recent phase3 studies have
brought some hope it appears that
Docetaxel-based chemotherapy may prolong survival
in patients with hormone refractory PCa.
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Although relapse happened after a period of 12
months in 80 of the patients enrolled in the
study, who were then restarted on treatment with
some success (gt50 decrease in PSA), the results
suggested that rechallenge with low dose
intermittent docetaxel may be effective and well
tolerated in patients with hormone refractory PCa
and PSA progression after initial treatment.
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THANK YOU FOR YOUR ATTENTION