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Minimally Invasive Therapies for Radiorecurrent Prostate Cancer
practised by some clinicians; however, minimally invasive options are The PSA nadir is frequently used as an early surrogate of successful
now widely available and the balance of benefit and risk is somewhat treatment. The value used varies throughout the literature; however, it
inclined against radical salvage surgery. is clear that long-term control is unlikely in those whose PSA nadir is
Salvage Prostatic Cryotherapy
Rapid freezing of tissue to a very low temperature results in a lethal
Recent studies using third-generation
injury to cells. The cell death is caused by a combination of
devices have generally shown
extracellular and intracellular ice crystal formation, cellular
dehydration, pH changes and vascular endothelial injury that leads to
improved oncological efficacy and
microthrombosis. Furthermore, freezing induces an immune response
reduced morbidity, reflecting advances
against tumour cells. During active re-warming, further cell
in technology and technique.
destruction is caused through vascular hyperpermiability and cellular
swelling due to osmotic gradients.
>1.0ng/ml. Increasingly, studies such as those above define success
The modern technique of prostate cryotherapy involves the more strictly as a nadir PSA <0.5ng/ml. In summary, while salvage
percutaneous placement of probes under transrectal ultrasound (TRUS) cryotherapy is less invasive than salvage RRP, it is probably less
guidance. Typically, six to eight probes will be placed, along with efficacious. However, improvements in technique and better patient
thermocouples that monitor the temperature at key anatomical points selection have led to good results. It is probably the most established
(external urethral sphincter, neurovascular bundles, Denonvillier’s minimally invasive treatment modality in radiorecurrent PCa and is
fascia and prostatic apex). A urethral warming device aims to prevent supported by guidance from the National Institute of Clinical
tissue sloughing. Taking advantage of the Joule–Thompson effect, two Excellence (NICE).
freeze–thaw cycles are completed by passing argon gas to cool
followed by helium to warm. Planning software and data from High-intensity Focused Ultrasound
temperature probes and TRUS images ensure the entire prostate is Initial studies have shown that high-intensity focused ultrasound (HIFU)
treated and the temperature at the external sphincter and is a well tolerated and effective treatment for localised PCa.
12–18
HIFU
Denonvillier’s fascia remains above 0°C. uses focused ultrasound waves emitted by a transrectal transducer to
cause a lethal rise in temperature in the targeted tissue. Following
Recent studies using third-generation devices have generally shown treatment, there is coagulative necrosis and, eventually, cavitation.
improved oncological efficacy and reduced morbidity, reflecting There are two HIFU devices available: the Ablatherm
®
(EDAP S.A., Lyon,
advances in technology and technique. Chin et al. treated 118 patients, France) and the Sonablate™ (Focus surgery Inc., Indiana, US) HIFU
of whom 114 had a nadir PSA <0.5ng/ml.
10
The median follow-up was device. The potential advantage of the Sonablate device is the realtime
only 18.6 months (range 3–54) and the bDFS rate was 68, 55 and 34%, ultrasound imaging of the treatment zone, which allows HIFU intensity
according to the PSA cut point used (4, 2 and 0.5ng/ml, respectively). A to be modulated according to visual cues. Patients treated with HIFU
pre-treatment PSA >10ng/ml, Gleason score >7 before radiation and can be discharged from hospital within a few hours. A urethral or
stage III or IV tumour disease appeared to predict an unfavourable supra-pubic catheter is left for five to 10 days to allow the passage of
biochemical outcome. Serious complications included four recto- sloughing tissue. Generally, the procedure is well tolerated with a low
urethral fistulas (3.3%) and severe incontinence (6.7%). incidence of serious complications.
In the only published articles on salvage HIFU, Gelet et al. used the
Ablatherm device to treat a group of 71 EBRT-failure patients.
19
At the
The modern technique of prostate
last follow-up, 80% of patients treated had negative biopsies
cryotherapy involves the percutaneous
(corresponding to a 73% 30-month actuarial negative biopsy rate) and
61% achieved a PSA nadir <0.5ng/ml within three months. Despite these
placement of probes under transrectal
results, 56% of cases required adjuvant therapy. It appears the ‘standard
ultrasound guidance.
cancer work-up’ used in this study underestimated the presence of
micrometastatic disease. They did not employ LLND to stage high-risk
patients. At 30 months there was a 38% clinical disease-free rate.
Adverse effects of HIFU included bladder neck stenosis (17%),
Recently, the experience of a UK centre has been published.
11
One incontinence (grade I 13%, grade II 15% and grade III 7%) and
hundred cases were closely studied with a mean follow-up of rectourethral fistula (6%). Four patients (6%) were treated with an
33.5 months. bDFS was defined by a PSA <0.5ng/ml. Patients were artificial sphincter. The latest Ablatherm algorithms have been modified
stratified into risk groups: high-risk (68 men), intermediate-risk since this study and fewer fistulas have been reported in the recently
(20) and low-risk.
12
Five-year actuarial biochemical relapse-free survival presented series.
20
This modification includes limiting the treatment zone
(bRFS) was 73, 45 and 11% for the low-, intermediate- and high-risk to 5mm proximal to the apex of the gland. This may lead to
groups, respectively. Complications included incontinence (13%), undertreatment in this area.
erectile dysfunction (86%), lower urinary tract symptoms (16%),
prolonged perineal pain (4%), urinary retention (2%) and rectovesical HIFU appears to be a feasible salvage treatment for EBRT-failure
fistula (1%). patients. It has been approved by NICE for use in primary and salvage
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