Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in...
Transcript of Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in...
Active Surveillance in Intermediate-Risk
Prostate Cancer: PRO
Larry Goldenberg, CM, OBC, MD, FRCSC
Professor, UBC Dept of Urologic Sciences
Director of Development and Supportive Care, Vancouver Prostate Centre
Vancouver, BC, Canada
Financial and Other Disclosures
• Off-label use of drugs, devices, or other agents: None
• Data from IRB-approved human research is presented
I have the following financial interests or
relationships to disclose: Disclosure code
No financial relationships N
Road Map
• Not all intermediate risk cancers are the same
• We all agree that “high-intermediate” require Rx
• Favourable intermediate risk cases require more
stringent followup protocol (eg MRI), but deferred
therapy is not dangerous
• Ultimately, it comes down to a particular man’s
risk threshold (comfort zone)?
What we know so far: AS
• AS is underutilized
• Patient selection and buy-in is critical
• 25-50% of patients will progress, usually in first 3 to 5 years
• Death due to CaP on AS is 1- 2.4%
• Death due to non-CaP causes is 15-20 times more likely
• Triggers for intervention are not clearly validated
Why not AS for intermediate risk cancer??
• The inability to accurately predict the biological behavior of a cancerin a given individual (Biology vs Histology)
• “CYA”: If you recommend aggressive therapy, then…..
– If the disease progresses, you have done everything possible
– If the disease does not progress, you have cured the patient
Achilles Heel of AS:
Missed High Grade Cancer
Gleason 6
Gleason 8
Today's metastasis was once
organ-confined cancer
It Should Not be a Slippery Slope to IMMEDIATE RP
Dr Klotz
What about the Bunny Rabbits?
Firstly, not all Rabbits are the same!
Risk stratification definitions have changed over time!
Definition: Original AUA/D’Amico-NCCN
• Low Risk: PSA <10, GS≤6, T1/2a
• Intermediate: PSA 10-20, GS=7, T2b
• High Risk: PSA >10, GS>7, T2c/3
• Overweights T-stage
• Does not distinguish 3+4 vs. 4+3
• Does not account for many important variables
All Intermediate risk: “The same, but not the same”?
Definition: CAPRA?
• Low Risk: 0 – 2
• Intermediate Risk: 3-5
• High Risk: 6-10
New NCCN:
• Very low risk: T1c, GG1, 3 or fewer of 12 cores, 50% or less core volume and
PSAD <0.15 ng/ml
• Low Risk: PSA <10, GG1, T1/2a
• Favourable Intermediate: Major pattern grade 3 and less than 50% positive biopsy
cores, with 1 intermediate risk factor, including T2b/c, Grade Group 2 or PSA 10-
20.
• Unfavourable Intermediate: > 1 intermediate risk factor, Grade group 3
• High Risk: PSA >10, GS>7, T2c/3
Quantitative Gleason Score (qGS)
Reese A et al. Cancer, epub 2012.
Pathologists are restratifying (Grade groups):
So we agree that not all intermediate risk cancers are the same and
indeed there is a “Klotz grey zone”
Not all Intermediate Risk are equal
• % of Gleason Pattern 4 (Stamey and McNeal, 1980’s)
• Scattered vs Clustered Grade 4 on a background of Grade 3
• Continuous vs Discontinuous tumour involvement
• Cribriform/Glomeruloid pattern vs poorly formed/fused vs a mix
• Total tumour involvement of a core
• Pathologist interobserver agreement is approximately 74% with greatest
discrepancy differentiating 3 and 4
• Gleason 3+4 without cribriform and intraductal = prognosis of 3+3
(Kweldam et al, Mod Path, 2016)
J Urol, Sept, 2017
Comparison of Outcomes of GG1 And GG2
8095 RPs: GG1 or GG2, PSA≤10, ≤T2a
Gearman et al, J Urol, 2018
GG1 GG2
OC 94% 83%
N1 0.3% 1.8%
XRT postop 3.1% 8.5%
BCR 10 yrs 89% 81%
PFS 10 yrs 99% 96%
Aghazeda et al, J Urol, 2018
N-3,686 RP patients
15%
27%
48%
n
Göteborg Trial: Stopping Active Surveillance
Godtman et al, Eur Urol, 2012
UBC VPC: 1993 – 2014
• 915 men initially Rx with AS
• 651 men met strict inclusion criteria
• Confirmatory biopsy within 18m
• Minimum 6 months f/u, intention to treat
curatively
• Outcomes : – Cessation of AS
– Cancer progression (Repeat Biopsy, PSADT)
– Radical prostatectomy outcomes
– PSA recurrence
– CSM and OM
AS Patient Characteristics at diagnosis
2014
Predictors of Progression
Minimal GP 4 on biopsy is associated
with low-risk tumour in RP specimen
Huang, Taneja et al. AJSP, 2014
Clinical outcomes following deferred RPx
2014
Intermediate risk tumour:
Significant or insignificant?
The “Holy Grail” of Treating Prostate Cancer Today
• To differentiate the biologically significant
cases from the insignificant, and to avoid the
morbidity of treatment whenever possible.
Risk Calculators
• Milan Calculator (Gandaglia et al,
https://onlinelibrary.wiley.com/doi/abs/10.1111/bju.14391)
• Canary Calculator (https://canarypass.shinyapps.io/biopsy_nomogram/)
• ERSPC (PRIAS) calculator (http://www.prostatecancer-riskcalculator.com/active-surveillance-
and-prias-study)
Biomarker Assays and Genomic Classifiers
MRI may be the best “biomarker”
• MRI is very promising*
– to ensure better sampling of prostate (current)
– to reduce number of biopsies needed (future)
* But is it the standard of care yet?
Defining Boundaries in Prostate Cancer
13 to 30% missclassification Delayed intervention Anxiety
45-70% avoid early Rx Preserve Q of L
Balance: probability of dying from untreated- or delayed Rx against chances of having to live with the complications of Rx
Do you feel lucky, Punk?
Risk Threshold - Individualize
CHOICES
Summation
• Not all intermediate risk cancers are the same
• We all agree that “high-intermediate” require Rx
• We have the tools today to better risk stratify and
followup: serum/urine biomarkers, mp-MRI,
radiopharmaceuticals and genomic classifiers
• Ultimately, what is a particular man’s risk
threshold (comfort zone)? His choice!!
Thankyou