Advanced Stage Prostate Cancer
Management
Michael E. Karellas
Assistant Professor of Urologic Oncology
May 15, 2010
Outline
• Defining advanced stage/high risk disease
• Treatment considerations
• Rising PSA after primary treatment
• Systemic therapies
Clinical Staging
T1
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T2
T3
T4
T1: Microscopic disease discovered by PSA
T2: Tumor can be felt on rectal exam
T3: Tumor spreads through the capsule
T4: Spread to contiguous organs (bladder, rectum)
Advanced Stage Disease
• Generally defined by:
– High grade/Gleason sum ≥ 8
– Serum PSA level > 20ng/mL
– Clinical stage T3 disease or higher
• Patients are likely to have greater tumor volume, higher
grade, and increased likelihood of regional spread
Cancer Specific Survival After Surgery
(Data adapted from the series of Patrick C. Walsh, The Johns Hopkins Hospital,
1982-1999.)
Diagnostic Tools
• CT Scan
– Assess for enlarged
lymph nodes
suggestive of disease
spread
• Bone Scan
– Assess for tumor
spread to the bone
Trends in Diagnosis
• Fewer men are presenting with locally advanced
prostate cancer
• ~10% of men with newly diagnosed prostate cancer
have locally advanced disease (T3)
• There is an increasing use of treatment modalities other
than surgery for high-risk prostate cancers
Trends Continued
• Currently, no consensus exists regarding the
optimal management of locally advanced
prostate cancer
• Treatment is individualized
Surgical Treatment Approaches
• Patients classified with high-risk prostate cancer
by common definitions do not have a uniformly
poor prognosis after surgery
• Radical prostatectomy with pelvic lymph node
removal is usually reserved for those high-risk
men with smaller tumors that can be completely
removed
Surgical Considerations
• The most important pathologic criteria predicting
prognosis after surgery
– Gleason score
– Surgical margin status
– Non–organ-confined disease (extracapsular
extension, seminal vesicle invasion, lymph node
involvement)
Surgical Treatment Approaches
• For some high-risk patients, an integrated
approach combining local and systemic therapy
may be advantageous
• Without the use of secondary treatments after
surgery, 5-year biochemical relapse can be
higher than 60%
Secondary Treatments
Radiation Therapy
• Early adjuvant radiation therapy was administered
within 3 to 6 months of surgery with undetectable PSA
• Results showed patients had longer time until cancer
progression and lower rates of metastasis at 5 years
• Treatment effects from radiation can affect quality of
life
Secondary Treatments
Hormonal Therapy
• Early androgen deprivation (hormone therapy) may
improve survival
• Alternative methods of androgen manipulation
(antiandrogen, intermittent) remain investigational
• Treatment effects may affect quality of life
Primary Treatment with Radiation
• Radiation therapy (RT) is an alternative treatment
strategy for these men with locally advanced disease
• Overall survival after RT alone for locally advanced
cancer is below 50% at 10 years
• Hormonal therapy typically started for 2 months prior
and continued for 2 years after treatment in
advanced/high risk cancers
PSA Recurrence
• PSA relapse or biochemical recurrence (BCR)
after surgery or radiation occurs in
approximately 50,000 men per year
• Management remains controversial as the course
of their disease is highly variable
PSA Recurrence After Surgery
• PSA recurrence is defined as PSA ≥ 0.4ng/mL at
least 8 weeks post-op with continued PSA rises
• Date of failure is date of first detectable PSA
PSA Recurrence After RT
• ASTRO Definition used for BCR after RT
– Three consecutive PSA rises, optimally separated by 3 months
between measurements after radiation therapy starting at least
2 years after the start of radiation
– Time of failure defined as the midpoint between the nadir and
first confirmed rise
– “PSA Bounce” occurs in 12 to 61% of patients as long as 18
to 36 months after treatment
Nomograms
• The majority of patients will have a BCR far
earlier than will be see on imaging studies
• 14 Nomograms (models) exist that attempt to
predict clinically significant events in patients
with rising PSA after surgery or radiation therapy
nomogram.org
mskcc.org
Local vs Distant Recurrence
• Imaging studies with CT scans or Bone Scans
• Often difficult to detect early (small) metastatic sites
– Bone scan often required PSA > 20ng/mL
• PET scan and ProstScint scanning are considered
investigational
• MRI scanning can be helpful in identifying local recurrence
Where is the Recurrent Disease?
• Local recurrence
– Low PSA
–Lower grade tumors
– Low C/T stage
–Long time from treatment
– Long PSA doubling times
• Usually patients have a durable remission after
salvage radiation to the prostate bed
Local Recurrence
• Salvage radiation is delivered to the prostate bed and
pelvis
• Consider starting radiation when PSA >1.5ng/mL
• Treatment related effects
– Bowel and bladder irritation/bleeding
– Bladder neck contractures
– Erectile dysfunction
Biopsies for BCR
• Abnormal DRE in post-surgery patient often
leads to biopsies of the mass/nodule
• Most patients will not have a mass that can be
felt on exam
• Abnormalities discovered on imaging are often
biopsied
Where is the Recurrent Disease?
• Distant metastatic disease favored in
– High grade disease
– PSA recurs in less than 2 years
– PSA doubling time less than 10 months
• Systemic therapy needed
Hormone Therapy for Rising PSA
• Also called androgen deprivation therapy
• Usually given for patients with a rising PSA
from distant spread of CaP
• Can be given in combination with salvage
radiation therapy for local recurrence
Hormonal Therapy
• Testosterone and its metabolites are responsible for
growth of normal and cancerous prostate tissue
• Medications block the production of testosterone or can
block its action on cells which prevents prostate cancer
cells from growing
• Temporary solution, not intended to be curative
Hormonal Therapy
• Usual regimen is oral medication (biclutamide)
for 14 days followed by monthly or every 3
month injections of another medication
• Orchiectomy
Side Effects of Hormonal Therapy
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Risk of impotence
Gyencomastia
Depression
Weight gain
Osteoporosis
Fatigue
Anemia
Decreased mental acuity
Androgen (Testosterone)
Independence
Gasoline fuels the Hummer like Testosterone
originally fueled the prostate cancer
Systemic Therapies
• Chemotherapy should be discussed and offered to all
patients with hormone-refractory prostate cancer
• Chemotherapy Regimens
– Docetaxel
– Mitoxantrone
– Clincal trials
Docetaxel
• Docetaxel is the standard treatment for hormonerefractory prostate cancer
– prolongs progression-free and overall survival, improves pain,
and improves quality of life
• Toxicity of docetaxel includes myelosuppression,
fatigue, edema, moderate to modest neurotoxicity, and
changes in liver function
Summary
• Rates of advanced stage/high risk prostate cancer have
decreased
• Advanced stage prostate cancer treatment is
individualized and often requires multiple methods of
treatment
• Hormonal therapy is palliative and has associated side
effects
• Systemic chemotherapy is indicated when hormonal
therapy fails