Prostate Cancer
Terms
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- Define low-risk prostate cancer
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PSA <= 10ng/mL AND
Gleason score <= 6 and
T1 or T2 stage - Define intermediate-risk prostate cancer
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PSA of 10-20 ng/mL OR
Gleason score 7 AND
T1 or T2 stage - Define high-risk prostate cancer
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PSA > 20 ng/mL OR
Gleason score 8-10 AND
T1 or T2 stage - What is the typical prescription for prostate brachytherapy in the low-risk patient?
- Permanent prostate implant with total dose 145 Gy with I125
- Describe prostate cancer risk factors
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Age
-Increases at age 50 for white men
-Increases at age 40 for black men
-Increase at age 40 for those with first-degree relative with prostate cancer
Age-no peak but increases with age
Family history
-Twofold risk if first-degree relative with prostate cancer
-Ninefold risk if two first-degree relatives with prostate cancer - What increases serum PSA?
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Prostate cancer
Urinary retention
Prostatitis
BPH
Prostatic manipulation - Of those patients with a PSA > 4.0 ng/mL, what percent will have a diagnosis of cancer?
- 15-25%
- Since there is little specificity in the 4-10ng/mL range, how can you increase testing specificity?
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Use the percent-free PSA in this indeterminate zone
Biopsy men with percent-free PSA < 10%
No biopsy if > 25% - Define percent-free PSA
- free PSA / total PSA
- Where do adenocarcinomas of the prostate usually arise?
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70% peripheral zone
20% transitional zone
10% central zone - Define Gleason score
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Based on growth pattern and degree of differentiation
Equal to the sum of the two most prevalent differentiation patterns
Each is scored 1-5 - What Gleason scores correspond to low-grade (well differentiated), moderately differentiated, and high-grade (poorly differentiated) cancers?
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Low-grade=2,3, or 4
Mod=5,6, or 7
High grade=8,9, or 10 - What are the most common sites of metastatic prostate cancer?
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Direct extention to periprostatic fat
Via ejaculatory ducts into the seminal vesicles
Lymphatically to regional lymph nodes (hypogastric and obturator lymph nodes)
Hematogeneously to bone (lumbosacral spine) -
Risk of prostate cancer on biopsy by PSA level
< 4:
4-10:
>10: -
Risk of prostate cancer on biopsy by PSA level
< 4: 5-25%
4-10: 15-25%
>10: 50-67%
Rule of thumb: Risk of prostate cancer with Gleason score 7-10 is PSA x 2 -
__% of tumors involve prostate apex
__% of patients have multifocal disease -
50-80% of tumors involve prostate apex
85% of patients have multifocal disease - What histology comprises 95% of prostate cancers?
- Adenocarcinoma
- Primary prostatic lymph node drainage pattern
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Primary prostatic lymph node drainage pattern
1 Internal iliac obturator
2 External iliac
3 Presacral
But also
1 perirectal
2 Common iliac
3 Paraaortic -
Most frequently used prognostic indicators
1
2
3 -
Most frequently used prognostic indicators
1 Gleason score
2 Clinical stage
3 Pretreatment PSA - Percentage of positive cores is related to risk of recurrence. What % of positive cores behaves more aggressively?
- Percentage of positive cores is related to risk of recurrence. What % of positive cores behaves more aggressively? 50%
- What PSA velocity in the year before RP or EBRT may be associated with increased risk of death from prostate cancer? Reference?
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What PSA velocity in the year before RP or EBRT may be associated with increased risk of death from prostate cancer? <2 mg/ml
D'Amico NEJM 2004; JAMA 2005. - Workup for prostate cancer
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H&P: AUA sx score, baseline erectile function, bony pain, DRE
Labs: PSA, testosterone, CBC, LFTs
Bone scan & pelvic CT if T3-4, GS >=8, or PSA >= 20 -
RTOG Meta-Analysis Risk Groups with 10yr DSS
I:
II:
III:
IV: -
RTOG Meta-Analysis Risk Groups
I: T1-2 & GS < 7 (low: 86%)
II: T1-2 & GS 7 or T3 or N1 with GS < 7 (intermediate: 75%)
III: T1-2 & GS 8-10 or T3 or N1 with GS 7 (high: 62%)
IV: T3 or N1 with GS 8-10 (very high: 34%) -
Roach formulae
ECE:
SV involvement
LN involvement: -
Roach formulae
ECE: 3/2 PSA + 10 (GS-6)
SV involvement: PSA + 10 (GS-6)
LN involvement: 2/3 PSA + 10 (GS-6) - Kattan nomograms
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Computerized models
Predict primarily PSA recurrence
May predict pCa mortality after tx -
RTOG 94-13
- Patients
- Selection criteria
- Randomization - 1323 pts with PSA < 100 with LN risk > 15% to compare WP RT to prostate only (PO) and neoadj/concurrent HT (NCHT) to adj HT (AHT)
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RTOG 94-13
- Radiation
- Whole pelvis RT:
- Final prostate RT dose:
- Hormone therapy:
-- NCHT timing:
-- AHT timing:
-- Bias? -
RTOG 94-13
- Radiation
- Whole pelvis RT: 50.4 Gy
- Final prostate RT dose: 70.2 Gy
- Hormone therapy
-- Goserelin or leuprolide + flutamide
-- NCHT timing: 2m before 2m during RT
-- AHT timing: 4 m after RT
-- 2m bias in favor of AHT since PFS defined from time of randomization -
RTOG 94-13 Results
- WPRT vs PO RT:
- WPRT + NCHT vs other arms:
- OS: -
RTOG 94-13 Results
- WPRT vs PO RT: 4yr PFS 40 --> 56%
- WPRT + NCHT vs other arms: PFS 61% --> 45-49%
- OS: No diff in 4yr OS - EORTC Bolla Lancet 2002
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415 pts
T1-2N0 GS > 6 or T3-4N0 any grade
RT +/- gosereln for three years
RT WP to 50 Gy --> prostate boost to 70 Gy
HT improved
- 5 yr OS 62 --> 78%
- DFS 40 --> 74% -
Prostate cancer: PIN
Definition
Grades
Coincident with cancer -
Prostate cancer: PIN
Definition: Prostatic intraepithelial neoplasia
Grades: Low and high
Coincident with cancer: 35% of patients with PIN had cancer on subsequent biopsy -
Prostate cancer: Chemoprevention
1
2
3 -
Prostate cancer: Chemoprevention
1 LHRH anaalogues (goserelin, leuprolide)
- Side effects: anemia, atrophy of reproductive organs, decreased muscle mass, loss of libido, vasomotor instability
2 Nonsteroidal antiandrogens (flutamide, bicalutamide)
- SE: GI, gynecomastia, vasomotor sx
- Competitively bind to androgen receptors in target tissues
3 Competitive inhibitors of 5-alpha reductase (finasteride)
- Suppress intraprostatic dihydrotestosterone to castrate levels
- SE: No libido, potency, or muscle change -
Prostate cancer: PSAV
Definition
Formula
Exponential increase in PSA begins ___ years before dx
Cutoff -
Prostate cancer: PSAV
Definition: PSA Velocity
Formula: sPSA/time
Exponential increase in PSA begins 5 years before dx
Cutoff: Greater than or equal to 0.75 ng/mL/year=biopsy -
Prostate cancer: PSAD
Definition
Formula
Cutoff -
Prostate cancer: PSAD
Definition: PSA Density
Formula: sPSA/prostate vol (US-prolate elipsoid)
Cutoff: Greater than or equal to 0.15 ng/mL/cm3=biopsy -
Prostate cancer: free PSA
Physiology
Cutoff -
Prostate cancer: free PSA
Physiology: The proportion of PSA complexed to alpha one-antichymotrypsin > in patients with pCa, ratio freePSA/totalPSA (percent free PSA) is lower in men with cancer
Cutoff
- <15-20%=biopsy
- >25% cancer unlikely - Prostate Cancer: What are the arterial and venous vessels for the prostate?
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Prostate Cancer: What are the arterial and venous vessels for the prostate?
Arterial: Internal iliac artery
Venous: Prostatic plexus to internal iliac vein -
Prostate Cancer: What are the three main histologic types of prostatic epithelium?
Which produces PSA? -
Prostate Cancer: What are the three main histologic types of prostatic epithelium?
1 Secretory
2 Basal
3 Neuroendocrine
Which produces PSA? Secretory even though it has the lowest proliferative activity of the three. - Prostate Cancer: What is the definition of a positive resection margin in pCa?
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Prostate Cancer: What is the definition of a positive resection margin in pCa?
Tumor cells touching the inked surface of the prostate. -
Prostate Cancer: What are the primary sites of bony metastasis?
1
2
3
4
5 -
Prostate Cancer: What are the primary sites of bony metastasis?
1 Vertebral column (74%)
2 Ribs (70%)
3 Pelvis (60%)
4 Femurs (44%)
5 Shoulder girdle (41%) - Prostate Cancer: When is a bones scan indicated in pretreatment evaluation?
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Prostate Cancer: When is a bones can indicated in pretreatment evaluation?
Oesterling JAMA 1993;269:57:
Symptomatic patient
sPSA > 10 ng/mL
High-grade tumor
NCCN
T1/T2 with PSA > 20
Gleason >= 8
T3/T4
Symptomatic - Prostate Cancer: When is a ProstaScint scan indicated?
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Prostate Cancer: When is a ProstaScint scan indicated?
In postprostatectomy patients with increased sPSA to differentiate between locoregional and distant disease but NOT in routine pretreatment evaluation - Prostate Cancer: What is the physiologic variation of PSA and what does it mean?
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Prostate Cancer: What is the physiologic variation of PSA and what does it mean?
- Difference in PSA levels observed when a second sample is obtained from the same patient within a few weeks
- May be as high as 0.298; for a sPSA of 4, an increase to 5.2 (4 x 0.298) is in the range of physiologic variability - Prostate Cancer: What is the serum half-life of PSA and what does it mean?
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Prostate Cancer: What is the serum half-life of PSA and what does it mean?
- 2.2-3.2 days
- May take several weeks for PSA to return to baseline after prostatic biopsy or to reach nadir after prostatectomy - Prostate Cancer: Which of the following causes increased sPSA: digital exam, prostatic massage, TRUS, ejaculation, cystoscopy, TURP, and prostate biopsy?
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Prostate Cancer: Which of the following causes increased sPSA: digital exam, prostatic massage, TRUS, ejaculation, cystoscopy, and prostate biopsy?
TURP and biopsy