Download Current Diagnosis and Management of Prostate Cancer

Updates in the Management of
Localized Prostate Cancer
Abdul Naser Shunaigat, MD. FACS
Cancer Incidence and Mortality Rates
age-adjusted, standardized over time
http://www.cancer.org/Research/CancerFactsFigures/CancerFactsFigures/cancer-facts-figures-2012
PROSTATE CANCER PREVALENCE AND
MORTALITY
• Newborn American male has 16% lifetime
risk of being diagnosed with prostate cancer
– 1 new case every 3 minutes
• 1/3 of men over age 60 and 1/2 of men over
age 70 have prostate cancer
• But lifetime risk of death from prostate
cancer is only 3%
Prostate Cancer
• Risk Factors
– Age-median age of diagnosis is 72 years.
• Incidence of prostate cancer increases with age so that
up to 70-80% of men in their 80-90’s have autopsy
evidence of prostate cancer
– Smoking
– High Fat/ Western diet
– Family History-8-9% of all cancers due to
inherited gene higher for younger men
Prostate Cancer
• Prostate Cancer Development
– Develops from the epithelium
• Possibly from the basal cell layer
– Requires androgens to develop
• Patients castrated before puberty do not develop BPH or
Prostate cancer
– Increased cell proliferation and decreased
apoptosis
– BPH is not a risk factor
Prostate Cancer
• Premalignant Lesions
• PIN-prostatic intraepithelial neoplasia
– May be a precursor lesion to prostate cancer
• Characterized by cytologically atypical cells with
architecturally benign glands
• Approximately 20% of patients with PIN will go on to
have a subsequently positive biopsy
• ASAP-atypical small acinar proliferation
– Atypical glands and cells but can’t quite call it cancer
• Up to 50% will have a future positive biopsy
Prostate Cancer
• Screening??
• Is PSA Screening for Prostate Cancer Dead?
• Is there anything better?
Prostate Cancer Screening Trials
American Trial:
• 76,693 men between 55 and 74 randomized to either
annual screening or usual care
• After 7-10 years of follow-up, death rate from prostate
cancer was very low and did not differ significantly
between the two study groups
European Trial:
• 162,243 men between 55 and 69 randomized to either
annual screening or no screening
• For first 10 years of follow-up, risk of death from prostate
cancer was the same between the two groups, but, after 10
years, there was a 20% decrease in risk of death in the
screened group
Why the recommendation against
screening for prostate cancer?
Screening and consequent treatment, as currently practiced, are
often harmful:
– Too much screening of elderly men with a short life
expectancy
– Too liberal criteria for biopsy
– Too aggressive treatment of low risk cancers
– Inadequate treatment of high risk cancers
– Treatment largely administered by low volume providers
(higher risks of side effects and lower risks of cure)
Vickers AJ, Lilja H. Time for another rethink on prostate cancer screening. Nat Rev Clin Oncol. 2011; 9:7-8.
• 5 treated tp prevent one death
Screening Smarter:
How to Increase the Benefits and Reduce the Risks
of Screening for Prostate Cancer
•
Risk-adjust screening by age and PSA (reduce false
positives)
•
Reduce false positive PSA results by repeating
(verifying) positives and by adding additional markers
(reduce indications for biopsy)
•
Active surveillance for low-risk cancers (reduce harms
of unnecessary therapy)
•
Refer patients who need treatment to high-volume
physicians or centers (reduce harm of necessary
therapy)
Vickers A, Roobol M, Lilja H. Annu. Rev. Med. 2012. 63:161–70.
Memorial Sloan-Kettering Cancer Center 2010
Guidelines
Risk-adjusted Screening for Prostate Cancer
• Begin PSA testing at age 45
• For men age 45 - 59
• PSA ≥ 3 ng/ml : consider biopsy
• PSA > 1 but < 3 ng/ml : return for PSA every 2-4 years
• PSA <1 ng/ml : return for PSA in 5 years or at age 50 or 60,
whichever comes first
•For men age 60 – 70
• PSA ≥ 3 ng/ml : consider biopsy
• PSA > 1 but < 3 ng/ml : return for PSA every two years
• PSA < 1 ng/ml : no further screening
• For men age 71 or higher
•
No further screening
Prostate Cancer
• Who should I treat?
• How to treat?
• When to treat?
Prostate Cancer
• Current guidelines from the AUA, recommend
that initial evaluation of, and treatment
discussion with a patient with PC focus on the
following two factors:
– Patient’s overall life expectancy
– The biologic characteristics of the tumor, together
with its predicted aggressiveness and behavior
Prostate Cancer
• Whether one of the several different modalities
used for treating localized prostate cancer
offers survival benefits over others remain
controversial.
• The choice of definitive therapy has been
suggested to make a significant difference in
long term survival in less than 10% of patients.
Risk Stratifications
Organizational pre-treatment Prostate Cancer risk stratification
Organization
Low Risk
Intermediate
High Risk
Harvard,AUA, EAU
T1-T2a and GS ≤6 and PSA≤10
T2b and/or GS=7 and/or
PSA˃10-20 Not low risk
≥T2c or PSA˃20 or GS 8-10
GUROC, NICE
T1-T2a and GS ≤6 and PSA≤10
T1-T2 and/or GS≤7 and/or
PSA≤20 NOT low risk
≥T3a or PSA˃20 or GS 8-10
CAPSURE
T1-T2a and GS ≤6 and PSA≤10
T2b and/or GS=7 and/or
PSA˃10-20 not low risk
T3-4 or PSA˃20 or GS 8-10
NCCN
T1-T2a and GS ≤6 and PSA≤10
Not very low risk AND very low
risk category
T1c and GS≤6 and PSA˂10 and
fewer than 3 biopsy cores positive
T2b or T2c and/or GS=7
and/or PSA˃10-20 not low risk
T3a or PSA˃20 or GS 8-10
ESMO
T1-T2a and GS ≤6 and PSA˂10
Not high and Not low risk (the
remainder)
T3-4 or PSA˃20 or GS 8-10
AUA: American Urological Association; EAU: European Association of Urology; GUROC:
GenitoUrinary Radiation Oncologists of Canada; NICE: National Institute for Health and Clinical
Excellence; CAPSURE: Cancer of the Prostate Strategic Urologic Research Endeavour; NCCN:
National Comprehensive Cancer Network; ESMO: European Society of Medical Oncology
Localized Prostate Cancer
• Standard treatments for clinically localized Pca
includes the following: (Low risk)
–
–
–
–
–
–
Active Surveillance
Watchful Waiting
Radical Prostatectomy
Radiation Therapy
Hormonal Therapy
Cryotherapy. - Proton Beam Radiation. - HIFU
Deferred treatment (active
surveillance/watchful waiting)
• Active Surveillance.
– Active surveillance aims to achieve correct timing
for curative treatment, rather than delayed
application of palliative treatment
– Patients remain under close surveillance, and
treatment is prompted by predefined thresholds
indicative of potentially life-threatening disease,
while considering individual life expectancy.
Watchful Waiting
• Watchful Waiting:
– (deferred or symptom-guided treatment). It refers to
conservative management, until the development of
local or systemic progression.
• TURP or other procedures for urinary tract obstruction,
• Hormonal therapy or radiotherapy for palliation of
metastatic lesions.
• No standardized follow-up is recommended.
Bill-Axelson; NEJM, 2005
Iverson P; Scand J Urol Nephrol Suppl, 1995
Wilt, T. J, J Urol, 1994
Active surveillance
• Increasingly being recommended for men with
low-risk disease
• Evolving option, although no randomized
studies have yet been conducted
• Current NCCN recommendations for active
surveillance include the following:
– PSA no more often than every 6 mo unless clinically indicated
– DRE no more often than every 12 mo unless clinically indicated
– Repeat prostate biopsy no more often than every 12 mo unless
clinically indicated
Klotz L et al. J Clin Onc 2010; 28:126
All-cause mortality for men with conservatively managed prostate cancer
Charlson Comorbidity index 0
J Rider et al. Long-term outcomes according to risk category of prostate cancer.
Nation-wide, population-based cohort. Eur Urol 2012.
Radical Prostatectomy
• Currently, RP is the only treatment for localized PCa
to show a benefit for OS and cancer-specific survival
(CSS), compared with conservative management, as
shown in one prospective randomized trial.*
• RALP is displacing RRP as the gold standard surgical
approach for clinically localized PCa in the USA and
is being increasingly used in Europe and other parts
of the world.
*Bill-Axelson A. N Engl J Med 2014 Mar;370(10):932-42.
Intermediate
and High Risk
Pathologic Organ Confined
Biopsy Gleason 6
1000
800
600
Low Risk
400
200
0
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
0.80
0.70
0.60
0.50
0.40
0.30
0.20
0.10
0.00
Number of new
patients
enrolled in
active
surveillance by
year
PIVOT: RP v. Observation
Overall results: all-cause and prostate cancer-specific mortality
N=731
Wilt et al. N Engl J Med 2012; 367:203
PIVOT: RP v. Observation
Patients with high risk cancers
PSA > 10
All cause mortality in patients (n=251)
with PSA > 10 ng/mL (HR 0.36, p<0.02).
AUA High risk
Prostate cancer mortality in patients (n=157)
with high-risk cancer (HR 0.40, p=0.05)
Wilt et al. N Engl J Med 2012; 367:203213
PIVOT
• The Prostate Intervention Versus Observation
Trial (PIVOT), showed no statistically
significant difference between radical
prostatectomy and watchful waiting with
respect to either:
– all-cause mortality (47% versus 49.9%,
respectively), or
– prostate cancer–specific mortality (5.8% versus
8.4%, respectively) after a median follow-up of 10
years.
RANDOMIZED TRIAL OF WATCHFUL
WAITING VERSUS RADICAL
PROSTATECTOMY
• Scandinavian randomized trial of 695 men found absolute risk
reduction of 6.1% in prostate cancer deaths at 15 years in men
undergoing radical prostatectomy vs watchful waiting
– Number needed to treat to prevent 1 prostate cancer death – 15
• Benefit more pronounced in men < 65 years of age
– Number needed to treat – 7
• Men in “low risk” group also derived benefit
– 4.2% reduction
Bill-Axelson, A, et al, Radical prostatectomy versus watchful waiting in
early prostate cancer: NEJM 364:18 (1708-1717), 2011.
Indications for nerve-sparing
surgery
• Nerve-sparing RP can be performed safely in most men with
localized PCa undergoing RP. In the past decade, a dramatic
shift towards lower-stage tumors has become evident. More
importantly, men are younger at the time of diagnosis and
more interested in preserving sexual function. Nevertheless,
clear contraindications are patients in whom there is a high
risk of extra-capsular disease, such as any cT2c or cT3 PCa,
any GS > 7 on biopsy, or more than one biopsy > 6 at the ipsilateral side.
External Beam Radiation therapy
• Offers potential for curative treatment of local
disease.
– 3-D conformal Radiation Therapy (3-D CRT)
– Intensity Modulated Radiation Therapy. (IMRT)
• QoL after 2 years: IMRT is equal to RP *
• Early salvage RT is comparable to adjuvant
RT with regard to biochem. recurrence. **
•Geinitz H; Int J Radiat Oncol Biol Phys. 2011
** Briganti A; Eur Urol. 2012
Radiation vs Surgery
• No solid evidence to determine whether any
type of RT results in fewer deaths or cancer
recurrence than RP in low risk patients.
Agency for Healthcare Research and Quality. October 2012
Treatment: definitive
radiotherapy
• Intensity-modulated radiotherapy (IMRT), with or
without image-guided radiotherapy (IGRT), is the
gold standard for EBRT. All centers that do not yet
offer IMRT should plan to introduce it as a routine
method for the definitive treatment of PCa.
Hormonal Therapy
• ADT alone, has not been considered a "standard"
treatment option for localized disease
• Increased risk of cardiovascular disease and diabetes
• In some cases only.
Neoadjuvant and adjuvant hormonal
therapy and radical prostatectomy
• Since PCa is an androgen-dependent tumor, NHT is an
appealing concept. A recent review and meta-analysis
studied the role of NHT and prostatectomy. NHT significantly
reduced positive margin rates, extra-prostatic extension, and
lymph node invasion.
• However, this was not associated with improved OS or
disease-free survival (DFS).
Locally Advanced PCa
•
•
•
•
Radiation Therapy
Hormonal Therapy
Radical Prostatectomy
Brachytherapy
Intermediate risk
•
•
•
•
•
Active surveillance
Brachytherapy
Radiotherapy
Radical prostatectomy
Cryotherapy *
* Bahn D, et al. Eur Urol. 2012
High-risk and locally advanced
prostate cancer
• At an increased risk of:
– PSA failure
– Need for secondary therapy
– Mets progression
– Death.
• Radical Prostatectomy & Extended PLND
Metastatic PCa
• Rarely curable
• Directed toward symptomatic relief
Prostate Cancer
• Categorize your patient
– Complete work up
– General health
• Complete and Comprehensive patient
counseling.