IRE is unique among focal ablation therapies in that it is
non-thermal and precise down to the cellular level. There was a very thorough
analysis of IRE on The New Prostate Cancer Infolink
in 2013, which interested patients are well advised to read. There is still not enough clinical data to recommend it, but there has been one
promising pilot study with published results.
Valerio et al.
reported on 34 low and intermediate risk patients treated at two institutions
(St. Vincent Cancer Centre in Sydney and Princess Grace Hospital in London)
between 2011 and 2013. All patients received multiparametric MRI-targeted
biopsies in which 20-30 cores were taken. Patients were selected who had a
focus of cancer,
Predominantly Gleason grade 4, or
Core length ≥ 4 mm
Patients had to have good performance status, as the
procedure involves full anesthesia and complete muscle paralysis.
Acute complications included blood in urine (18%), urinary
tract infection (15%), painful urination (15 %), and urinary retention (6%).
All toxicities were low grade - grade 1 (35%) or grade 2 (29%) - and were
transient. One patient developed tachycardia and had to be watched for a day
after the operation. At 6 months follow-up, all patients were continent and
potency was preserved in 95%. One of the potential dangers of focal ablation is
recto-urethral fistula, but none have so far been reported for IRE.
With up to 2 years of follow-up with mpMRI, 6 patients (18%)
had residual disease:
2 stayed on active surveillance
3 had a second ablation treatment
1 had a radical prostatectomy
As with all forms of focal ablation, residual disease was
found in some cases, and multiple treatments may be necessary. With IRE, its
sub-millimeter precision is both its greatest strength and its greatest
weakness. The strength is in its low risk of harming nearby structures like the
bladder neck, urethral sphincter, neurovascular bundles, and rectum. It is also
believed to be somewhat sparing of the connective tissue in muscle, blood
vessels and nerves. The weakness is that even with our most accurate mpMRIs, it
is impossible to discern microscopic amounts of cancer in the prostate. Even
leaving a 5 mm margin around the index lesion, it is impossible to know if it
ablated all the cancerous tissue.
Thermal ablation therapies, like HIFU, cryo or laser, are
problematic because heat (or cold) dissipates away from the intended treatment
zone. That can result in sublethal ablation of the intended target while
causing thermal injury to nearby organs at risk as well as the neurovascular
bundles. Tumors may repopulate in the sub-lethal ablation zone with enhanced
vigor. With IRE there is no sub-lethal ablation, and no thermal damage to
nearby healthy tissue.
Index tumor theory
Another issue that applies to all focal therapies is the
theory of index tumors. There is a theory that the spread of prostate cancer is from a
primary, relatively large and often higher-grade tumor called an index
tumor. According to this theory, all metastases are clones from the
original index tumor. If true, ablating the index tumor will stop the cancer. Prostate
cancer is known to be multifocal (lots of little tumors) in 80% of men, but if
the index tumor theory is correct, the multiple tumor foci will not seed any
spread -- only the index tumor can do that. Liu et al. and Mao et al. showed that
metastases arise as clones from a single parent cancer cell, but did not show
that the parent cell was in an index tumor. Several studies provide evidence to
- · A case report
from Johns Hopkins showed that
metastases arose from a small, low grade tumor rather than an index tumor.
- · Cheng et al. found that multiple tumors had
independent origins. In 15/18 tumors, he found that they arose independently within a
single gland, and in 3/18 tumors they arose through intraglandular
dissemination from an index lesion.
- · Ibeawuchi et al. showed that
there was as much genetic diversity in a unifocal tumor as there were in
Clinical evidence for the index tumor theory is based on the
fact that a single focal therapy treatment is effective much of the time, at
least in the short term. Most likely, it is true in some men but not in others,
and it may be true of some, but not all, of the cancer within a single man. The
other issue raised by the multifocal nature of prostate cancer is that the
satellite tumors, whether they arise independently or are spawned from the
index lesion, may be outside of the treatment range of the focal therapy. Hollmann et al. found that
satellite tumors were a median of 1 cm, and up to 4.4 cm, away from the index
It has not yet been established that immediate focal ablation
has any advantage over active surveillance. In low risk men, active
surveillance is certainly safer. Active surveillance is increasingly being used
by men with favorable intermediate risk prostate cancer. Arguably, there is a
window of time during which focal ablation is possible, but we really don’t
know that with any certainty. Men who have focal therapy must be closely
followed for recurrence because we don’t know whether residual tumors may
become active. Focally treated patients are effectively on lifetime active
There is obviously much to be learned from clinical trials.
There is a second small-scale
clinical trial (NEAT
that has been completed and should have results soon. NEAT included
patient-reported quality-of-life outcomes, and allows for adaptive surgical
technique to optimize treatment. They treated increasingly larger margins
unless toxicity increased. To avoid risk of recto-urethral fistulae, only
anterior zone tumors were treated.
There is an on-going full-scale clinical trial (NCT01835977
Amsterdam. They are also running a registry
to treat 2,000 patients before 2020.
In the US, there are a few practitioners who are experimenting
with IRE: Jaime Wong (Jenkins Clinic, Atlanta, GA), Gary Onik (Carnegie Mellon
(Memorial Sloan Kettering Cancer Center) have done over a dozen cases each.
There is a pilot trial of 6 cases at Duke University (NCT01972867