active surveillance in intermediate-risk prostate cancer: pro · active surveillance in...
TRANSCRIPT
![Page 1: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/1.jpg)
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
![Page 2: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/2.jpg)
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
![Page 3: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/3.jpg)
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)?
![Page 4: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/4.jpg)
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
![Page 5: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/5.jpg)
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
![Page 6: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/6.jpg)
Achilles Heel of AS:
Missed High Grade Cancer
Gleason 6
Gleason 8
![Page 7: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/7.jpg)
Today's metastasis was once
organ-confined cancer
![Page 8: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/8.jpg)
![Page 9: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/9.jpg)
It Should Not be a Slippery Slope to IMMEDIATE RP
Dr Klotz
![Page 10: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/10.jpg)
What about the Bunny Rabbits?
![Page 11: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/11.jpg)
Firstly, not all Rabbits are the same!
![Page 12: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/12.jpg)
Risk stratification definitions have changed over time!
![Page 13: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/13.jpg)
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
![Page 14: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/14.jpg)
All Intermediate risk: “The same, but not the same”?
![Page 15: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/15.jpg)
Definition: CAPRA?
• Low Risk: 0 – 2
• Intermediate Risk: 3-5
• High Risk: 6-10
![Page 16: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/16.jpg)
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
![Page 17: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/17.jpg)
Quantitative Gleason Score (qGS)
Reese A et al. Cancer, epub 2012.
![Page 18: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/18.jpg)
Pathologists are restratifying (Grade groups):
![Page 19: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/19.jpg)
So we agree that not all intermediate risk cancers are the same and
indeed there is a “Klotz grey zone”
![Page 20: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/20.jpg)
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)
![Page 21: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/21.jpg)
![Page 22: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/22.jpg)
![Page 23: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/23.jpg)
![Page 24: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/24.jpg)
J Urol, Sept, 2017
![Page 25: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/25.jpg)
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%
![Page 26: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/26.jpg)
Aghazeda et al, J Urol, 2018
N-3,686 RP patients
15%
27%
48%
n
![Page 27: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/27.jpg)
Göteborg Trial: Stopping Active Surveillance
Godtman et al, Eur Urol, 2012
![Page 28: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/28.jpg)
![Page 29: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/29.jpg)
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
![Page 30: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/30.jpg)
AS Patient Characteristics at diagnosis
2014
![Page 31: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/31.jpg)
Predictors of Progression
![Page 32: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/32.jpg)
![Page 33: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/33.jpg)
![Page 34: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/34.jpg)
Minimal GP 4 on biopsy is associated
with low-risk tumour in RP specimen
Huang, Taneja et al. AJSP, 2014
![Page 35: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/35.jpg)
Clinical outcomes following deferred RPx
2014
![Page 36: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/36.jpg)
Intermediate risk tumour:
Significant or insignificant?
![Page 37: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/37.jpg)
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.
![Page 38: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/38.jpg)
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)
![Page 39: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/39.jpg)
Biomarker Assays and Genomic Classifiers
![Page 40: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/40.jpg)
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?
![Page 41: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/41.jpg)
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
![Page 42: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/42.jpg)
Do you feel lucky, Punk?
![Page 43: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/43.jpg)
Risk Threshold - Individualize
![Page 44: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/44.jpg)
CHOICES
![Page 45: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/45.jpg)
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!!
![Page 46: Active Surveillance in Intermediate-Risk Prostate Cancer: PRO · Active Surveillance in Intermediate-Risk Prostate Cancer: PRO Larry Goldenberg, CM, OBC, MD, FRCSC Professor, UBC](https://reader036.vdocument.in/reader036/viewer/2022081217/5f79318b97249f314741fb62/html5/thumbnails/46.jpg)
Thankyou