Definitive Prostate as through a Junior Residents Ojos

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Definitive Prostate as through a Junior
Residents Ojos

• Celine Bicquart, MD

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Epidemiology and RFs

• Most common cancer in men.
• Age adjusted incidence of PCA dramatically
  increased in last 2 decades.
• Age
• Hereditary Factors
• Environmental exposure

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Anatomy
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Histology

• 3 types of cells
• Secretory- produce PSA, PAP, mucin.
• Basal- stem cells that repopulate. Used for
  benign differentiation.
• Neuroendocrine- least common.

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Gleason scoring
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Presentation

• Earlier stages may be asymptomatic.
• Encroachment on urethra produces obstructive
  symptoms.
• Then bladder detrusor loses compliance and then
  getting irritative symptoms.
• Denonvilliers is barrier to rectal involvement.
• Extension to bladder trigone/periureteral
  tissues retention, electrolyte abnl.
• Invasion to NV bundles, UGD pain, impotence

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Workup

• HP
• DRE
• PSA
• CT
• MRI
• Bone scan

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Predicting Outcome

• Partin Table pic

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Quick Formulas

• risk SVI PSA (GS- 6) x 10 by Diaz, but
  underestimates.
• risk LN 2/3 PSA (GS- 6) x 10 ROACH
  FORMULA.

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Using PSA to predict outcome

• Pre-TX PSA
• PSA velocity prior to dx
• nPSA after TX

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• Risk of relapse by PSA category at 6y(actuarial)
• 4-10 34
• 10-20 51
• 20 89

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• -1095 men with early (T1c, T2) PCA.
• -Had PSAs for at least 1y prior to dx.
• -Followed for median 5.1y post-RRP.
• -Disease recurrence defined as 2 consecutive
  detectable PSAs.
• -Death from PCA documented hormone-refractory
  met. PCA with evidence of rising PSA

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A- recurrence B- Death from any cause C- Death
from PCA
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In PSA velocity 2ng/mL A- Stage B- PSA C-
Gleason score
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• 9 institutions
• 4839 patients between 1986 and 1995 s/p
  definitive RT 60Gy.
• Median f/u time 6.3y.
• nPSA- lowest PSA measured in f/u
• TnPSA- time from completion RT to nPSA

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• P

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P 25
Both p 26
nPSA

• The lower the nPSA, the higher the PSA-DFS, and
  DMFS.
• The longer the time to nPSA, the higher the
  PSA-DFS and DMFS.

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Organ confined Disease

• Does everyone need to be treated?

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• 223 pts with T1-2 PCA (1977- 1984)
• Cohort study looking at natural history of
  untreated PCA.
• Median f/u now 21y.

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• EPE dev in 36, mets in 17.
• Latest update showed increase in PC mortality
  beyond 15y.

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• Retrospective cohort analysis of clinically
  localized men
• 767 men, age 55-74. 1971- 1984.
• Median observation 24y.
• For 87 of men, f/u 20y.
• Aim Confirm Johannsons data about mortality
  after 20y.
• -51 of men with normal DRE, 60 dx on TURP.

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Percentage mortality at 15y
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• Knowing that there is a predictable increase in
  mortality without treatment, if we decide to
  treat, which is better.

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NOT!!!!
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• Cohort study following 1682 men with T1-2 PCA
  from 1990-1998.
• Randomized to RRP vs RT (median 70.2Gy)
• Median f/u 51m
• Primary endpoint bRFS

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• 1054/1682 (63) RP
• 628/1682 (37) RT
• RP BCR detectable PSA 0.2ng/mL
• RT BCR 3 rising PSAs

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5y bRFS 80 RP vs 73 RT8y bRFS 72 RP vs 70
RT p0.01
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Analysis by risk groups

• Favorable T1-T2a, GS6, iPSA10
• Unfavorable not favorable
• RP 51 favorable
• RT 34 favorable
• No difference in outcome in favorable.
• 8y bRFS 86 RP vs. 90 RT p.53
• No difference in outcome in unfavorable.
• 8y bRFS 62 RP vs. 59 RT p.21

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• But, in unfavorable group,
• When RP compared to RT of 72Gy

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5y bRFS 70 RP vs 50 RP vs 82 72Gy RT p.004
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Using alternative definition of BCR 0.058y
bRFS 72 RP, 68 RT, 34 rt
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Favorable- 8y bRFS 86, 86, 48
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Unfavorable- 8y bRFS 62, 61, 28
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• Not randomized
• RT patients were generally more unfavorable
• Subpar RT used. Better outcome with 72Gy.
• Treatment modality not as important as intrinsic
  tumor characteristics.
• What is better dose for RT?

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• Update of Initial Randomized study
• 301 men with T1-3 PCA accrued from 1993- 1998.
• Randomized to 70Gy vs. 78Gy.
• Primary endpoint FFF (BCR then was ASTRO
  definition of 3 PSA rises)
• BCR for this update used nPSA 2ng/mL
• Median fu now 8.7y vs. prior 60m.

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FFF in all patients 78 vs 59 p.004
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FFF when iPSA10 78 vs 39 p0.001
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Risk stratification

• LowT
• Intermediate not low or high
• HighT3 GS8 PSA20

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• 8y FFF benefit in low risk 88 vs 63 p0.042
• 8y FFF benefit in high risk 63 vs 26 p0.004
• Note Benefit in high risk group seen only in
  those with PSA10

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IntermediateBenefit only in PSA10
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Death from PCA Alive WD 21 vs 43 pts
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G2 Rectal complications 26 vs 13 GU toxicity
13 vs 8 but not SS
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• Randomized Phase III trial to look at value of
  adding long-term ADT in treatment of PCA with RT.
• 1987- 1995
• 415 men with T1-2 of G3 or T3-4 N0-1M0
• Age 50-81
• Presence of CV disease RT 29 vs 24 CT
• Randomized to RT alone vs. RT Goserelin
• RT 50Gy whole pelvis 20Gy boost
• Goserelin monthly x 3y

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• Primary endpoint DFS
• Secondary endpoints OS, DSS
• Median f/u time 66 months
• 5y DFS
• 40 RT
• 74 CT p.0001
• 5y DSS
• 79 RT
• 94 CT p.0001

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5y biochemical DFS
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5y overall survival
62 RT alone vs. 78 RT ADT p.00001
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10 year update

• Demonstrate maintenance of OS benefit without
  increasing long-term morbidity
• Median f/u time 9.1 years
• 10y OS
• 39.1 RT alone
• 58.1 Combined p .0004
• 10y PFS
• 22.7 RT alone
• 47.7 Combined p.0001

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• 10y PFS
• 30.2 RT
• 51.0 CT p
• 10y biochemical PFS
• 17.6 RT
• 37.9 CT p
• CV mortality 11.1 RT vs. 8.2 CT p.75
• Pathological fx 2 in CT group at 7.2y and 9.9y

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Brachytherapy

• Ideal for patients with small prostates, small
  volume disease, low Gleason grade, few
  obstructive symptoms.

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• Prospectively measured outcomes by patients and
  spouses.
• 9 institutions from 2003- 2006
• 1201 patients with T1-2 PCA 625 spouses
• s/p RP, EBRT, brachy
• EPIC-26 and SCA at 2, 6, 12, 24m after the start
  of treatment.

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What to look forward to