Download Localised Prostate Cancer - North West Urology Registrar Group

Oncology 11
Localised Prostate Cancer
Louise Olson
Paul Cleaveland
Arie Parnham
Mr Mokete
22nd December 2014
Objectives
•
•
•
•
•
Natural history Prostate Cancer
Treatments
Complications of Treatment
Brachytherapy & External Beam XRT
VIVAs
Natural History - Incidence
• Most common cancer diagnosis in UK
(2011)
• Accounts for nearly 25% of all new male
cancers
• Huge rise in CaP incidence past 20yrs
- increase in T1c tumours
- increase in PSA screen-detected tumours
• Increase in incidence not reflected in
mortality rates
Office of National Statistics 2013
UK CaP incidence statistics
In 2010, in the UK, the lifetime risk of developing prostate
cancer is 1 in 8
Cancer Research UK
CaP Incidence by Age
Cancer Research UK
Trends over Time
• Substantial increases in incidence have
been reported in recent years for many
countries
– TURP
– PSA testing
1. Hsing AW, Tsao L, Devesa SS. International Journal of Cancer (Pred.Oncol) 2000; 85:60-67.
2. Bray F, Lortet-Tieulent J, Ferlay J, et al. Eur J Cancer 2010; 46:3040-52.
3. Quinn M, Babb P. BJU Int 2002; 90:162-73.
Post-Mortem Studies
•
•
•
•
Half of men in their fifties will have histological
evidence of CaP on post-mortem
This rises to almost 80% of men in their
eighties1
BUT only 1 in 26 men die from CaP
In other words, men are more likely to die with
prostate cancer than from it – an important fact
when considering population screening of
asymptomatic men2
1. Sakr WA et al. Eur Urol. 1996; 30(2): 138-44
2. Frankel S et al. Lancet. 2003; 361(9363): 1122-8
Geographic Variation in CaP
Incidence
88.9
98.2
5.29
115.2
UK Mortality Statistics CaP
Cancer Research UK
Geographic Variation in CaP
Mortality
Prostate Cancer Mortality By Age
Mortality Trends in CaP
Age-specific mortality trends in
CaP
Prostate Cancer Risk Factors
• No modifiable RF has been identified on
which to base a prevention strategy
• Accepted RFs include:
- Age
- Family history
- Ethnicity
• Other RFs have been studied but evidence
inconclusive
Age and Prostate Cancer Risk
• Age strongest known RF for CaP
• Very low incidence in men under 50 yrs
• Incidence in men aged 85+ is five times that
of men aged 55-59
• Post-mortem studies
PSA
•
•
•
•
•
Loeb et al. UROLOGY 67: 316–320, 2006
1991-2001
13,943 men <60 years
Median PSA level was 0.7 aged 40-49 & 0.9 aged 50 to 59
Men <60, baseline PSA value between the age-specific
median and 2.5 ng/mL was a significant predictor of later
CaP and was associated with a significantly greater PSA
velocity
• A young man’s baseline PSA value was a stronger
predictor of CaP than family history, race, or suspicious
DRE findings. A greater baseline PSA level was associated
with significantly more adverse pathologic features and
biochemical progression
Family History and CaP Risk
•
A family history of prostate cancer is one of the
strongest known risk factors for this disease
•
5–9% of all CaP cases
•
Risk 2.1-2.4 for men with a father has/had CaP, risk
2.9-3.3 brother, 1.9 2nd degree relative1-3
•
Familial CaP higher in men aged under 65
1. Bruner DW, Moore D, Parlanti A, et al. Int J Cancer 2003;107:797-803.
2. Johns LE, Houlston RS. BJU Int 2003;91:789-94.
3. Kicinski M, Vangronsveld J, Nawrot TS. PLoS One 2011;6:e27130.
Family History and CaP
• 19-24% higher in men whose mother
has/had breast cancer (not associated with
risk in sister)1,2
• 5 times higher in men with BRCA2
mutation3
• May be higher in men with BRCA1 –
evidence unclear4-6
1. Hemminki K, Chen B. Prostate 2005;65:188-94.
2. Chen YC, Page JH, Chen R, et al. Prostate 2008;68:1582-91.
3. Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 1999;91:1310-6.
4. Thompson D, Easton DF. J Natl Cancer Inst 2002;94:1358-65.
5. Fachal L, Gomez-Caamano A, Celeiro-Munoz C, et al. Prostate 2011;71:1768-79.
6. Leongamornlert D, Mahmud N, Tymrakiewicz M, et al. Br J Cancer. 2012;106(10):1697-701.
Ethnicity and CaP
• In the UK, black Caribbean and black
African men have 2 - 3 x the risk of being Δ
or dying from CaP than white men1
• Asian men have a lower risk than the
national average2
1. Ben-Shlomo Y et al. Eur Urol. 2008; 53(1): 99-105
2. Jack RH et al. Int J Androl. 2007; 30(4): 215-20
Diet and CaP
The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) are the gold standard in cancer epidemiology.
Alcohol and Smoking and CaP
•
EtOH – 2 meta-analyses: The largest
showed no increased risk whilst the other
demonstrated modest risk increases1,2
•
Smoking inconclusive as a risk factor3,4
1.Bagnardi V et al. Br J Cancer. 2001; 85(11): 1700-5
2. Dennis L.K. Prostate. 2000; 42(1): 56-66
3. Gong Z et al. Cancer Causes Control. 2008; 19(1): 25-31
4. Doll R et al. Br J Cancer. 2005; 92(3): 426-9
Other Risk Factors
•
•
•
•
IGF-1 38-83% risk1-2
Vasectomy risk by 10%3 but meta-analysis
inconsistent4-5
Prostatitis 60-80% risk6,7
High BMI & metabolic syndrome (30% risk)8
1. Renehan AG, Zwahlen M, Minder C, et al. Lancet 2004;363:1346-53.
2. Roddam AW, Allen NE, Appleby P, et al. Ann Intern Med 2008;149:461-71, W83-8.
3. Siddiqui MM, Wilson KM, Epstein MM, et al. J Clin Oncol 2014.
4. Tang LF, Jiang H, Shang XJ, et al. Zhonghua Nan Ke Xue 2009;15:545-50.
5. Dennis LK, Dawson DV, Resnick MI. Prostate Cancer Prostatic Dis 2002;5:193-203.
6. Dennis LK, Lynch CF, Torner JC. Urology 2002;60:78-83.
7. Jiang J, Li J, Yunxia Z, et al. PLoS One. 2013;8(12):e85179.
8. Esposito K, Chiodini P, Capuano A, et al. J Endocrinol Invest. 2013;36(2):132-9.
Molecular Biology and Genetics
•
•
•
•
•
•
5–10% of all CaP may have a substantial inherited component
Searches for high-risk prostate cancer loci identified BRCA2 as
important susceptibility factor1
Carriers of germline mutations in BRCA2 have 5x  risk of CaP &
develop aggressive disease2
However, BRCA2 mutations account for only 2% of all earlyonset cases (<55years) indicating that further susceptibility loci
exist
Mutations in the BRCA1 gene have a smaller effect, increasing a
man’s risk of prostate cancer by less than two-fold3
Many other loci implicated - Genetic profiling likely to be
important in the future to provide prognostic information and
guide treatment
1.
2.
3.
Edwards SM et al. Am J Hum Genet. 2003; 72(1): 1-12
Mitra A et al. Br J Cancer. 2008; 98(2): 502-507
Thompson D et al. J Natl Cancer Inst. 2002; 94(18): 1358-65
Natural History of Localised CaP
• How can we distinguish between those
men who are likely to die from CaP, from
those with indolent disease?
- In the absence of RCTs, understanding the
natural history of CaP can help decisionmaking process for treatment
Natural History of Localised CaP
•
Insight into natural history inferred from
a number of sources:
–
–
Results of deferred treatment
Longitudinal studies of serum PSA
Results of Deferred Treatment
Individual series:
- Popiolek M et al 1
Meta-analyses:
- Chodak et al 2
Cohort:
- Albertsen et al 3
1. Popiolek et al. Eur Urol. 2013 Mar;63(3):428-35
2. Chodak et al. NEJM. 1994; 330:242
3. Albertsen et al. JAMA. 2005; 293:2095
Popiolek M et al 2013
• Eur Urol. 2013 Mar;63(3):428-35
• Natural history of early, localised prostate cancer: a final
report from three decades of follow-up.
•
•
•
•
30yrs F/U
223 pts
Sweden
Androgen deprivation therapy was administered when
symptomatic tumour occured
RESULTS: Popiolek M et al 2013
•
•
•
•
•
All but 1 man (1%) had died
41.4% locally progressed
18.4% distant metastatic disease
17% men died of prostate cancer
4% men with gleason 8-10 died within first 10yrs (55%
from CaP)
• Survival for men with well-differentiated, non palpable
tumours declined slowly over 20yrs & more rapidly
between 20 & 25yrs (from 75% to 25%)
• Conclusion: Localised CaP often has an indolent course,
local progression & distant metastasis can develop over
the long term, even if considered low risk at diagnosis
Chodak et al. 1994
• Pooled analysis of 828 pts with localised
CaP treated with WW
• 6 non-randomised studies
• Results measured as cause-specific survival
(CSS) and metastasis-free survival at 5 & 10
yrs of f/u
• Mean age 70yrs
Chodak et al. 1994
• Outcome of deferred treatment in localised CaP
in relation to tumour grade
Chodak et al. 1994
• Drawbacks of study:
- F/U period insufficient
- Highly selected series (60% of pts had Grade 1
disease)
- Many pts received hormonal therapy at time of
progression therefore delaying development of
mets
- Therefore probably overestimates CSS rates and
under-estimates rate of progression
Chodak et al. 1994
• Discussion:
- Prostate cancer a progressive disease
when managed conservatively
- Even though low grade tumours have
good CSS rates at 10 yrs, progression rates
are still substantial
- If life expectancy <10yrs and low/mod
grade disease, WW is acceptable
Albertsen et al. 2005
• Re-evaluated biopsy specimens using more
widely accepted Gleason score
• 767 men aged 55-74 at diagnosis between
Jan 1971 & Dec 1984
• Follow up reported at 5, 10, 15 & 20 yrs
• Median F/U 24yrs
Albertsen et al. 2005
• Drawbacks:
– Pre-PSA era, therefore it is likely that series
contains a number of men with extra-prostatic
disease
– Therefore study probably underestimates
actual survival rates
Albertsen et al. 2005
• Discussion:
– Men with high grade (Gleason 8-10) have high chance
of dying from CaP within 10 yrs
– Men with low grade disease have minimal chance of
dying from CaP within 20 yrs
– PSA testing introduces lead time bias, so PSA-screened
men with CaP should have improved CSS in
comparison to this cohort
Longitudinal Series of Serum PSA
• Retrospective evaluation of progression in men with CaP
• Baltimore Longitudinal Study of Aging
• 15 yrs before diagnosis, men with metastatic CaP had PSA
significantly higher than controls & BPH, and higher yearly
rates of change (Carter et al 1992)
• Suggests death rates in first 10 yrs from diagnosis with
screening do not measure efficacy of any form of
treatment
• Lead time in diagnosis associated with PSA screening 45yrs (Gann et al 1995)
Natural History Localised CaP
Summary
• Localised CaP is a progressive disease
- Even low grade tumours with an indolent course in
first 15 yrs eventually progress
• 15 years is the earliest time when CSS analysis has
any significance
• Lead time in diagnosis associated with PSA testing
needs to be factored in when analysing treatment
• Age at diagnosis important factor in determining CSS