Review of evidence for treatment options available in LMIC for prostate cancer

1. Metastatic Prostate Cancer
Dr Salman Arif
FCPS Radiation Oncology
FRCR Clinical Oncology
Fellowship in Uro-Oncology & Gynae-Oncology (UHB)
Options are Open or Limited

2. Learning Objectives
• Castrate sensitive Vs Castrate resistant prostate cancer
• Risk categories of mCSPC
• Optimal therapies for mCPSC & mCRPC
• Options for a local patient

3. Hormone Sensitive Prostate Cancer –
mCSPC vs mCRPC
The definition has changed:
• CRPC - Men with tumour progression after ADT have Castrate-Resistant Prostate
Cancer (CRPC)
• Men with CRPC are often still responsive to hormonal agents
Laboratory studies have shown that at
progression
• Prostate cancer is often still driven by
androgens
• Androgens are produced in prostatic
tissue
Treatment has changed following the
development of
• Androgen biosynthesis inhibitors
(abiraterone)
• 2nd generation anti-androgens
(enzalutamide, apalutamide,
darolutamide)

4. Metastatic Prostate Cancer Patients
Low Volume
• ≤ 3 bone metastases (± NRLN)
High Volume
• ≥ 4 bone metastases* and/or visceral
metastases
Synchronous
• De Novo metastatic disease
Metachronous
• Developed metastatic disease ~ 12 m
after local treatment +/- ADT
Low Risk
• Not High Risk
High Risk
At least 2 of the following
• Gleason score ≥ 8
• 3 or more bone mets
• Visceral mets

5. Metastatic Castrate Sensitive Prostate Cancer
Before 2015
mCSPC – ADT / Bilateral SC orchidectomy

6. mCSPC
NCCN
Guidelines
Version 4.2023

7. mCSPC – The Doublet Therapies

8. mCSPC – The Doublet Therapies
LATITUDE Trial Included high risk patients only HR 0.62
STAMPEDE Trial Benefit seen regardless of volume or risk of disease HR 0.63
ARCHES Trial 36% had low volume disease; 25% had prior local therapy HR 0.66
ENZAMET Trial 50% had low volume disease; 50% had prior local therapy HR 0.67
TITAN Trial 37% had low volume disease; 16% had prior local therapy HR 0.65

9. mCSPC – The Doublet Therapies

10. PEACE-1: A phase 3 trial with 2x2 factorial design investigating overall survival of
abiraterone acetate + docetaxel + ADT in de novo mCSPC patients
mCSPC – Triplet Therapies

11. PEACE-1: A phase 3 trial with 2x2 factorial design investigating overall survival of
abiraterone acetate + docetaxel + ADT in de novo mCSPC patients
mCSPC – Triplet Therapies
Subgroup of patients with High
Volume metastatic burden per
CHAARTED, OS and rPFS was
significantly improved

12. PEACE-1: A phase 3 trial with 2x2 factorial design investigating overall survival of
abiraterone acetate + docetaxel + ADT in de novo mCSPC patients
mCSPC – Triplet Therapies

13. mCSPC – Triplet Therapies
ARASENS

14. mCSPC – Triplet Therapies
Improved OS.
Overall mortality 32% lower in
treatment group.
Significantly longer time to the
development of CRPC, pain
progression and institution of
subsequent systemic antineoplastic
therapy.
ARASENS

15. How to decide optimal therapy for a mCSPC patient
Patient specific factors
• Disease characteristics
• Comorbidities
• Age
• Quality of life / tolerability
• Adherence to therapy
Agent specific factors
• Physician knowledge of data
• Experience of drug usage
• Safety profile of different agents
• Availability/ access to drugs
• Drug interactions
• Route of administration
• Dosing schedule

16. mCSPC Treatment Plans
Risk Group Presentation of
metastases
Metastases on CT /
WBBS
Main Plan –
TESTOSTERONE
SUPPRESSION
plus
Consider
Good Metachronous ≤ 3 bone metastases (±
NRLN)
+/- ARPI ? Adding SBRT
Intermediate Metachronous ≥ 4 bone metastases
and/or visceral metastases
+ ARPI ? Adding Docetaxel
for very select
patients
Intermediate De novo /
Synchronous
≤ 3 bone metastases (±
NRLN)
ARPI + Prostate
radiation
? Docetaxel if
extensive LAN
Poor De novo /
Synchronous
≥ 4 bone metastases
and/or visceral metastases
ARPI + Docetaxel if
Chemo-fit
More trials are
needed
Adapted from Sweeney C, presented at APCCC 2022

17. mCSPC Treatment Plans
ADT alone
• Poor PS, ECOG 3
• Co-morbidities
Intermittent Vs Continuous ADT
• IDT, if low risk metastatic disease and good response to 6 months of ADT

18. mCSPC Treatment Plans

19. • ADT alone is no longer sufficient treatment for mCSPC patients
• Treatment intensification with either doublet or triplet therapy should occur
• Patients with de novo, high-volume disease who are fit for chemotherapy should be
considered for triplet therapy with ADT + docetaxel + ARPI
• Patients who are unfit for chemotherapy or have low volume disease should be
considered for doublet therapy with ADT + ARPI
Clinical Takeaways

20. mCRPC
Metastatic Castrate Resistance Prostate Cancer
Castrate serum testosterone < 50 ng/dL or 1.7 nmol/L plus either:
Biochemical progression: Three consecutive rises in PSA at least one week
apart resulting in two 50%increases over the nadir, and a PSA > 2 ng/mL
OR
Radiological progression: The appearance of new lesions: either two or more
new bone lesions on bone scan or a soft tissue lesion using RECIST

21. mCRPC
Metastatic Castrate Resistance Prostate Cancer
Docetaxel TAX-327 (Mid 2000s) OS 18.9 Vs 16.4 m Δ 2.5m
Enzalutamide PREVAIL Trial OS 36 Vs 31 m Δ 5m
Abiraterone COU-AA-302 Trial OS 34.7 Vs 30.3 m Δ 4.4m
PARP Inhibitor PROpel Trial OS 42.1 Vs 34.7 m Δ 8.6m
Lu117 PSMA-617 PSMAfore Trial rPFS 12 Vs 5.6 m Δ 6.4m

22. mCRPC
Metastatic Castrate Resistance Prostate Cancer
• No sequencing of ARPIs
• Offer chemo after ARPIs
• Offer Cabazitaxel after PD from Docetaxel & ARPIs within 12 months
• Offer ARPIs after chemotherapy
Supportive Therapy
• Protective bone therapy with vitamin D and calcium supplements
• RT for painful mets

23. mCRPC
Metastatic Castrate Resistance Prostate Cancer
Docetaxel If prior ARPIs
Cabazitaxel If prior Docetaxel and ARPIs
Enzalutamide If prior Docetaxel
or
Abiraterone
Pembrolizumab If MMR deficient
Radium 223 If progression on 2 lines
Olaparib If DNA HRR alterations / BRCA mt
177Lu-PSMA At least one PSMA + lesion