Transcript Prostate cancer -what is important and what is new

Prostate cancer
-what is important and what is new Anette Hylen Ranhoff, MD PhD
Ullevaal University Hospital
Oslo Norway
Prostate cancer – epidemiology
the old man’s cancer
•Increase of clinical and subclinical
cases with increasing age
–5/100 000 at 60 yrs
–70/100 000 at 85 yrs
–In autopsies: 80 % of men at 85+
yrs have foci of invasive PC
•Second most frequent cancer in men
(after skin cancer)
•Second leading cause of cancerdeath in men > 50 yrs (after lung
cancer)
•More PC patients dies from other
causes than from their PC
•More common among black in USA
Incidence pr. 1 000 000 men (USA)
Etiology
a hormon depended cancer
Genetic
5-10 % Dominant
Early onset
PC-gene: HPC1
Susceptibility of male
Androgen receptors
 response and  prostate cancer
 response and  prostate cancer
Life style
Diet
Exercise
Sexual activity
Fat: high risk
Antiox.: low risk
Exercise: low risk
Environmetal
Contaminated food
and drinking water
Environmental oestrogens
(DDT, PCB)
agrichemicals
Screening for prostate cancer
• Digital rectal examination
– Sensitivity: 55-69 %
– Specificity: 89-97 %
• PSA: prostate specific antigen
(prostate-spesific – not cancer
spesific)
– Sensitivity: 75-78 %
– Specificity: 40 %
•
Novel proetomic tests (protein
pattern) J Nat Cancer Inst, 2002;94:1576-8.
– 95 % of cases of PC correctly
identified
– Sensitivity 71 %
No consensus about whom to screen,
when to screen and what to do if cancer
is discovered
Gambert SR, Geriatrics Jan 2001
• Rationale: When detected
and treated early – the
disease can be cured
• Useful for families with
heriditary PC
• Not proven that
screening reduces
mortality !
• High number of false
positives
– Anxiety
– Risk of complications to
biopsy-taking
• Many men treated
unnecessary with reduced
quality of life
Algoritm for early detection of
prostate cancer
Am Urol Ass, Oncology 2000;14:267-86
Candidates for early detection testing
Men 50+ yrs
Life exp. >10 yrs
Afroamerican
40+ yrs
PSA and DRE
One or both tests abnormal
Both tests normal
Possible PC, BPH, prostatitis
Return regularly for PSA
and DRE
For diagnosis: biopsi
Biopsi negative
Diagnosis of prostate cancer
• Digital rectal examination
• PSA
– <10 is non-spesific
– good guide to disease stage
• Transrectal Ultrasond
– Normal does not exclude PC
– Guide to biopsy
• MRI
– Localization and distribution
of cancer
• Biopsi
– Negative in ¼ of men with PC
• Assessment for metastasis
– Ultrasond, X-ray, CT and MRI
– Scintigrafic bone assessment
• Confirm the
diagnosis
• Localization and
distribution:
– TNM
• Histology:
– Type of neoplasm
– Grading
Staging of prostate cancer
•TNM
–Tumor localization and
distribution
–Nodes
–Metastases
•Gleason system: Histology: glandular
architecture
–1: close to normal
–2-4: well differentiated
–5-7: moderate diff.
–8-10: poorly diff.
Treatment of potentially curable disease
– localized disease
a controversal matter – particularly in the elderly
• Watchful waiting
• Radical prostatectomi (+/- neoadjuvant therapy)
– laprascopic
– open
• Radiation therapy (+/- neoadjuvant and adjuvant therapy)
– External
– Interstitial (brachytherapy)
• Hormonal therapy
– Neoadjuvant therapy with GnRH antagonist (Zoladex) and
antiandrogens (Androcur) before surgery and as supplement to
radiation therapy (T2/3, N0/X)
– Adjuvant therapy with LHRH analog (Procren) after radiation
therapy and antiandrogens (T2 and T3, G3 tumor)
To treat or not to treat
• Risk for progressing
disease (TNM, grading)
• Age and life expectancy
• Quality of life
– Adverse effects of treatment
(incontinence, sexual
dysfunction, osteoporosis)
– Symptoms of progressing
disease
– Psychological factors
Palliative care of metastatic disease:
to slow progression and releave symptoms
First line treatment is castration:
•
•
Chemical: LHRH analog (+/antiandrogen)
Surgical: Testicular ablation
Limited metastasis or isolated
elevation of PSA:
• Antiandrogen monotherapy
Hormone-refractory cancer
• Chemotherapy is not standard
treatment, but assessment for trials
when hormonresistant metastatic
disease
• Bisfosfonates: experimental, but
experience of effect on bone pain
New perspectives
• Better knowledge about etiology of Prostate
Cancer can make prevention possible
• New and better tests for screening
• Selection for screening from genetic susceptibility
• More effective treatment with less side effects - to
improve quality of life
• Better palliative therapy:
– Bisfosfonates
– Radiation
Key points
• Hormon depended cancer and
the most important cancer in
old men
• Many undiagnosed cases with
unknown disease progression
• Genetic predisposition and
exogenous disposure
• Screening with PSA and DRE,
but no consensus when to
screen, whom to screen and
what to do if cancer is
discovered
• Palliative treatment most
important in old men (75+)
References
• Dearnaley DP, Kirby RS, Kirk D, Malone P, Simpson RJ, Williams G.
Diagnosis and management of early prostate cancer. Report of a
British Association of Urological Surgeons Working Party. BJU int
1999; 83:18-33.
• Gambert SR. When to offer screening in the primary care setting.
Geriatrics 2001;56:22-31
• Kirk D. (ed.): International handbook of prostate cancer, 2nd edition.
2002
• Kirby RS, Christmas TJ, Brawer M. Prostate cancer. Mosby, London
1996.
• Kirk D. Prostate cancer in the elderly. Eur J Surg Oncol 1998;24:37983.
• Martin GE. The paradoxes of longevity. Springer-Verlag Ed. Berlin
1999.