Defining volume
Oligometastatic – low volume metastatic disease, thought to represent a state between organ confined and widespread metastatic disease, generally with less than 3 – 5 metastases.
CHAARTED:
- High volume – 4 or more bone mets, including 1 outside vertebral column or pelvis ; or visceral met
- Low volume – less than above
All prospective data in the management of metastatic prostate cancer is based on conventional imaging
Prognostic factors:
PSA after 7 months of castration (ADT only):
- < 0.2 – median survival 75 months (6 years)
- 0.2 – 4 – median survival 44 months (3-4 years)
- > 4 – median survival 13 months
Other proposed prognostic factors (unvalidated):
- Number of bone metastases
- Presence of visceral metastases
- ISUP / Gleason grade
- Performance status
- ALP
Principles and goals of management
- Identify and exclude conditions requiring urgent intervention
- Prolong overall survival
- Prevent or reduce complications of metastatic prostate cancer (local and distant)
- Reduce or avoid morbidity of treatment
Identify those needing urgent treatment
Namely spinal cord compression and bilateral ureteric obstruction
These men should be treated initially with bilateral orchidectomy or LHRH antagonist (degarelix)
Hormonal treatment and combination therapy
ADT has been standard of care for metastatic disease for decades.
Recent trials have shown that combination therapy improves survival in newly diagnosed metastatic disease.
STAMPEDE (arm G)
- ADT vs ADT and abiraterone – improved overall survival with abi (HR 0.61 for death in metastatic disease group)
LATITUDE
- ADT vs ADT and abiraterone – improved overall survival with abi (53 vs 36 mo, HR 0.66)
ENZAMET
- ADT + bicalutamide +/- docetaxel vs ADT + enzalutamide +/- docetaxel
- Improved OS, PFS with enzalutamide (HR 0.67)
TITAN
- ADT vs ADT and apalutamide – improved overall survival with apalutamide (HR 0.66)
3 trials have looked at upfront docetaxel with ADT vs ADT alone in metastatic disease – STAMPEDE, CHAARTED and GETUG – meta-analyses show improved overall survival with docetaxel.
EAU guidelines:
- ADT based combination therapy is standard of care for new diagnosed hormone sensitive prostate cancer
- No head to head for docetaxel vs novel anti-androgen; no clear evidence or recommendation can be extracted from trial sub-analyses
- All patients should be offered combination therapy
- Choice of agent likely based on patient preference, fitness for docetaxel, availability, cost and specific side effects.
Only docetaxel is currently available on the PBS for initial treatment of de novo hormone sensitive metastatic prostate cancer.
Treatment of the primary
STAMPEDE randomised ADT alone vs ADT and radiation to the prostate.
No overall survival benefit in an unselected cohort (same as HORRAD trial).
Overall survival benefit seen in low volume metastatic group – < 4 bone metastases (or none outside vertebral column/pelvis), no visceral mets
The dose used in STAMPEDE was lower than normal (55 Gy / 20#, or 36 Gy)
Absolute improvement in OS of 7 % at 3 years in low risk group.
No recommendation can be made about surgery in metastatic disease outside of a clinical trial.