The aim of all of these investigational therapies is to provide satisfactory oncological control, with a reduction in the morbidity associated with conventional treatments.
Other goals are long term efficacy on extended follow up, allowing for options for salvage curative therapy in cases of recurrence.
Cryotherapy
- Rapid freezing, followed by gradual thawing, then repetition of the freeze-thaw cycle -> disruption of organelles and cell membrane -> delayed microcirculatory occlusion causes cellular hypoxia
- Delivered by cryo-needles under TRUS guidance as well as thermo-sensors at the sphincter and rectal wall. Also a urethral warmer is placed.
- Side effects:
- ED up to 18 %
- Urinary incontinence 2 – 20 %
- Urethral sloughing up to 38 %
- Rectal pain and bleeding
- Recto-urethral fistula, up to 6 %
- No long term prospective comparative data
HIFU
- High intensity ultrasound primarily causes cell death by thermal effects (coagulative necrosis secondary to heat) but also has some mechanical effects (cavitation)
- Initially used for whole gland treatment, but now being used as focal therapy in some centres
- Side effects:
- Urinary retention 10 %
- ED up to 23 %
- Stricture up to 8 %
- Rectal pain and bleeding
- Urinary incontinence 10 %
- Recto-urethral fistula, up to 5 %
- No long term prospective comparative data.
Focal therapies
Irreversible electroporation (NanoKnife)
- Non thermal – delivery of high voltage short pulse electrical currents creating cellular membrane nanopores, leading to apoptosis
Others – laser interstitial thermotherapy; photodynamic therapy; focal SBRT (cyberknife).
All of these therapies are considered experimental and should only be offered within a clinical trial setting
Argued benefits:
- Provides another option for cancer treatment for those unwilling or unfit for radical treatment
- Less morbidity than radical treatment
- Allows retreatment
- May not preclude whole gland treatment in future
- Focal therapy is not a new concept – parallels to breast cancer etc
Arguments against / disadvantages
- No known data on long term outcomes oncologically or functionally
- Likely poorer oncological outcomes cf. surgery
- Prostate cancer often multifocal disease
- Expensive and not funded
- Makes salvage treatment more difficult and morbid
- Difficulty interpreting treatment ‘success’