the grey zone in prostate cancer management
TRANSCRIPT
Urology-Oncology Interface The Grey Zone
in Prostate Cancer Management
Mohamed Abdulla M.D.Prof. of Clinical Oncology
Cairo University
Grand Nile Hotel & TowerWednesday, 28/12/2016
Member of Advisory Board, Consultant, and Speaker for:• Amgen, Astellas, AstraZeneca, Hoffman la Roche, Janssen Cilag,
Merck Serono, Novartis, Pfizer, Mundipharma, MSD.
Speaker Disclosures:
Basic Facts:
• 2nd most common cancer in men (27%).• 1/6 men prostate cancer.• 2nd leading cause of cancer related death in men
(10%).• World Wide: > 1000000 new case annually.• > 300000 death/year.• Closely related to age & Androgens• Wide geographic and ethnic variations.• Pre- and post-PSA era.
MJA 2008; 189: 315–318
Prostate Cancer: The Story:
Dr. Huggins(1941): Orchiectomy and DES Effective Disease Control Noble Price 1966.
Dr. Shcally et al: (1977): LHRH Analogue Effective disease Noble Price
Prostate Cancer: Best Identity:
Natural History
Androgen Biosynthesis
Androgen Receptor Activity
Aggressiveness
AndrogenicDisease
Prostate Cancer:Natural History:
Locoregional Disease
Biochemical Failure
Metastatic “Sensitive”
Metastatic “Refractory”
Deat
h
TIME
Tum
or B
urde
n
Risk Stratification
A.S.Local Therapy+/- Hormonal
Local Therapy+ Hormonal
Hormonal+/- Others
2nd HormonalOthers
Maintaining testosterone <32 ng/dL was associated with significantly longer mean survival free of CRPC compared with levels >32 ng/dL
Survival free of CRPC in 73 patients with non-metastatic prostate cancer receiving ADT.*Patients with three serum testosterone determinations <32 ng/dL; †Patients with breakthrough
increases >32 ng/dL.Serum testosterone was measured every 6 months.
ADT=androgen-deprivation therapy; CRPC=castration-resistant prostate cancer.Figure adapted from Morote J, et al. J Urol 2007;178:1290–5.
100
80
60
40
20
0
Cum
ulat
e su
rviv
al fr
ee o
f CRP
C (%
)
0 50 100 150 200 250
Follow up (months)
>32 ng/dL†
<32 ng/dL*
p=0.0258
Testosterone ≤30 ng/dL has been associated with longer overall survival versus >30 ng/dL
VariableTestosteroneContinuous variable*
Testosterone<50 ng/dL
(n=94)
Testosterone≤30 ng/dL
(n=56)
Testosterone<20 ng/dL
(n=25)Time to progressionHR (95% CI)p value
1.76 (0.62–5.01)0.29
0.84 (0.52–1.37)0.51
0.76 (0.46–1.26)0.30
0.58 (0.30–1.15)0.12
Overall survivalHR (95% CI)p value
2.47 (0.70–8.75)0.16
0.74 (0.42–1.33)0.32
0.45 (0.22–0.94)0.034
0.19 (0.04–0.76)0.020
*Testosterone was considered a continuous (values were measured on a continuous scale) not categorical variable in this analysis.
CI=confidence interval; HR=hazard ratio.Bertaglia V, et al. Clin Genitourin Cancer 2013;11:325–30.
ADT: Key points from EAU guidelines 2014:“Oncologist & Urologist are Besides & Not A Side”
ADT=androgen-deprivation therapy; EAU=European Association of Urologists; mCRPC=metastatic castration-resistant prostate cancer.Mottet N, et al. EAU Guidelines on Prostate Cancer 2014. Available at: http://www.uroweb.org. Last accessed January 2015.
Optimal castration testosterone level is defined as <20 ng/dL
In high-risk localised and locally advanced prostate cancer, the combination of radiotherapy and ADT is recommended because it improves survival
First-line ADT is the standard of care for metastatic prostate cancer
Testosterone suppression should be continued indefinitely even when the disease becomes castration resistant
Second-line therapies for mCRPC should not be started unless patient testosterone levels are <50 ng/dL
Monitoring testosterone levels should be considered as part of routine clinical practice
Metastatic Sensitive Prostate Cancer:
EUROPEAN UROLOGY 67 (2015) 1028–1038
Metastatic Sensitive Prostate Cancer:Prognostic Factors:
EUROPEAN UROLOGY 67 (2015) 1028–1038
Metastatic Sensitive Prostate Cancer:Prognostic Factors
EUROPEAN UROLOGY 67 (2015) 1028–1038
1. ADT versus CAB?
When Do We Need CAB?
Surgical Castration
Serum Testosterone >
20 ng/dL
Medical Castration
Serum Testosterone >
50 ng/dL
Anti-Androgen
Antiandrogens:
• Competitive inhibition of peripheral androgen receptors.
• No action on hypothalamic receptors.• Inferior to ADT in phase III trials. • Not suitable in hormone naive patients as a
mono-therapy.• Used prior ADT to prevent flare & to manage
non-satisfactory results after ADT only.
CAB versus ADT:
2004 BJU INTERNATIONAL | 93, 1177–1182
OAS: CAB > ADT Alone
OAS: ADT + Bicalutamide > ADT + Flutamide
CAB versus ADT:
Cancer Sci. January 2011 vol. 102 no. 1 51–56
• OAS: MAB > ADT.• Bicalutamide > Flutamide.• Bicalutamide: 80 mg/day.
CAB versus ADT:
Cancer Sci. January 2011 vol. 102 no. 1 51–56
Slide 5
Presented By Maha Hussain at Genitourinary Cancers Symposium 2016
50%35%
15% No CABYes in Minority of PatientsYes in Majority of Patients
2. Intermittent versus Continuous ADT?
Continuous (CAD) vs Intermittent Androgen Deprivation (IAD): Trials in mHNPC Patients & Survival End Point
Slide 7
3. Immediate versus Deferred ADT ?
3. Immediate versus Deferred ADT:
Lancet Oncol 2016; 17: 727–37
Lancet Oncol 2016; 17: 727–37
3. Immediate versus Deferred ADT:
4. The Use of Cytotoxic Therapy in mHSPC?
Slide 10
Slide 12
Role of Cytotoxics in HSPC:
Role of Cytotoxic Therapy in HSPC:
Effect of Adding Docetaxel on OAS in M1 Disease:
Role of Cytotoxic Therapy in HSPC:
Effect of Adding Docetaxel on FFS in M1 Disease:
Management of Oligometastatic Disease:
Take Home Message:
• Management of advanced prostate cancer represents a definite oncologic burden.
• “Stick adherent to treatment guidelines” is the gold standard of practice.
• ADT is the cornerstone in the management of metastatic disease, while Docetaxel has been moved earlier in the treatment course of mHSPC.
• Oligometastatic prostate cancer is a new terminology that should be dealt only within clinical trial in high volume centers with experienced MDT practice.
Thank You