The information which follows is the opinion of the named author(s).
It does not necessarily constitute the opinion of The Prostate Cancer InfoLink or of
CoMed Communications, Inc.
Percutaneous Prostate Cryoablation
by Gary M. Onik, MD
Department of Minimally Invasive Therapy, Princeton Hospital,
and
University of Florida School of Medicine, Orlando, Florida
Originally Received December 14, 1995; Last Revised December 18, 1995
Introduction |
Patient selection for percutaneous prostate cryosurgery |
Technical factors in prostate cryosurgery |
Expected clinical results |
Future developments |
Conclusion |
References |
Editorial comment
Introduction
Prostate cancer presents a patient with several unique challenges.
This particular cancer has a variable biologic behavior with a clinical
presentation that can range from benign to rapidly aggressive. Unfortunately,
as yet, there is no definitive way to determine which course any individual
patient will take based on the available diagnostic and prognostic
information.
It is currently being suggested that a large percentage of patients are
being
aggressively treated who may, in fact, gain no benefit from such treatment.
A number of recent studies have suggested that "watchful waiting" may be an
appropriate alternative to aggressive treatment of organ-confined prostate
cancer
[1, 2]. Whether a patient should consider
treatment for his prostate cancer is now recognized as a complex interplay of
multiple factors, including the patient's age, tumor size, grade, stage,
associated medical problems, and psychological ability to "have" cancer and
yet not have it treated. This problem is being compounded by the recent
advances in prostate cancer testing and diagnosis, most specifically including
PSA testing, which is being used to find more and more patients with early
stages of prostate cancer.
This situation places many patients in a dilemma. They find themselves having
to choose between watchful waiting on the one hand -- an option that many
patients find plays havoc with their peace of mind -- and other treatment
options which have variable results (e.g., a 30-50% positive surgical margin
rate for radical prostatectomy [3]) and significant degrees of
morbidity. It is clear that a form of treatment which offered low morbidity
and a comparable rate of success to currently "definitive" treatment options
would present a welcome alternative for patients who find themselves faced
with this difficult dilemma.
These facts are the fuel stoking the fire of the rapid propagation of
percutaneous prostate cryosurgery. When evaluating cryosurgery as a
treatment option, physicians and patients alike can take some comfort from
prior experience with open transperineal cryosurgery. Although this older
technique was abandoned, patients treated with this earlier form of
cryosurgery had equivalent survival to patients treated by radical
prostatectomy or external beam radiation [4]. In
addition, long-term data from patients undergoing ultrasound-guided
cryosurgery of the liver (which has now been practiced for over 10 years)
show equivalent responses to patients treated by surgical resection of the
liver, in management of a form of tumor which is much aggressive and
considered much more difficult to treat [5]. It must be
appreciated, however, that the major problem in assessing the value of
percutaneous prostate cryoablation is still the preliminary nature of the
available data. Patients who feel uncomfortable with this state of
affairs should certainly consider a more time-tested procedure, e.g.,
radical prostatectomy or radiation therapy.
Percutaneous prostate cryoablation has proliferated, despite the
preliminary nature of the available data, because of what appear to be some
compelling advantages by comparison with more traditional treatments.
- Blood loss associated with percutaneous prostate cryoablation is
negligible, and in the experience of the present author there has been
no instance in which a transfusion has been needed. The rates of all
other complications (with the exception of impotence), including
incontinence, have been lower than those associated with radical
prostatectomy, and at this point cryoablation has not been associated
with any mortality. However, patients should be aware that complication
rates can vary from institution to institution based on equipment used,
preoperative patient preparation, previous treatment(s) received by the
patient (e.g., radiation therapy), and the experience of the cryosurgeon.
- Cryosurgery can be successfully followed by radiation therapy or by
surgery if, after cryosurgical treatment, there is evidence of residual
disease [6].
- Cryosurgery can be repeated. In fact, very few patient appear to
choose to have radiation therapy or a radical prostatectomy if there is
evidence of residual disease following cryosurgery. Rather they elect to
have repeat cryosurgery. Percutaneous prostate cryosurgery is the
only treatment which can be repeated when evidence indicates that a
local recurrence has occurred.
- Cryosurgery is an outpatient procedure for many patients. The
minimally traumatic nature of the procedure has markedly reduced the need
for hospital admissions. Approximately 95% of patients are discharged
from the hospital the same day or the morning after the procedure. This
can result in a significant financial saving [7].
- Cryosurgery can be used to successfully treat locally extensive
disease. Due to the technical opportunity to place a small cryoprobe
percutaneously and destroy large amounts of tissue, which are then
left in situ to be resorbed, data show that patients with locally
advanced disease (stage C or T3) can be consistently treated and that over
80% of these patients have negative biopsies after cryoablation
[8]. Since 50% of stage T3 patients have negative
lymph nodes, successful eradication of local tumor in this patient
population could (eventually) have a significant and positive effect on
patient survival. However, this possibility will require confirmation by
long-term studies.
It is of importance that a large proportion of patients who are clinically
believed to have organ-confined disease are, in fact, understaged. This
may account for the 30-50% of patients with positive surgical margins
(i.e., cancer left behind) following radical prostatectomy. Cryosurgery
may offer a very reasonable alternative to radical prostatectomy for those
patients who have a higher likelihood of having extracapsular disease
(i.e., those patients with high PSA values, high Gleason grades, and
larger or bilateral tumors).
Nomograms are now available which allow
an estimation of a patient's risk for extracapsular disease and other risk
factors based on these parameters [9]. As the
probability for extracapsular disease increases, the advantage of choosing
cryosurgery may, therefore, also increase.
- Cryosurgery can be used successfully to treat radiation failures. The
same technical advantage that allows successful treatment of locally
advanced disease allows treatment of patients who have failed radiation
therapy. While it now appears that patients who fail radiation therapy
and go on to be treated with cryoablation have a higher incidence of
incontinence than equivalent but previously untreated patients
[10], excellent preliminary results are being obtained
in this population of patients who had previously been extremely difficult
to treat.
Adverse reactions to cryosurgery
The most serious complication associated with prostate cryosurgery has to
date been urethrorectal fistula (the development of an abnormal
communication between the urethra and the rectum). This complication is
a direct consequence of freezing of rectal tissue. This complication has
been reported to occur in less than 1% of patients in several large series
carried out by experienced cryosurgeons [11]. However,
this is a serious problem, and is certainly more likely to occur if the
cryosurgeon has less experience. The repair of this complication may
require a temporary colostomy and an additional surgical procedure to
close the hole between the rectum and the urethra.
Impotence is the other major complication of cryosurgical ablation of the
prostate. However, the true rate of impotence following cryosurgery awaits
long-term data. The rate in one series has been reported at approximately
50% at one year [12]. Unfortunately, prostate cancer
spreads preferentially into the neurovascular bundles which control
erection. It is therefore critical that these areas be well treated.
The initial impotence rate after cryosurgery should be expected to be 100%
if all patients are well treated. However, with careful staging biopsies
being carried out, it seems possible that in the future we may be able to
identify a subclass of patients in whom a "nerve-sparing" cryoablation on
one or both sides could be effected. Until the results of such an approach
can be better recognized, it is prudent for the physician to discuss with
the patient the options that are available for impotence management
prior to cryosurgical treatment and to make clear to the patient
that either long-term or permanent impotence is a near certainty.
Patient selection for percutaneous prostate cryosurgery
Given the potential advantages of cryosurgery outlined above, the patients
who may be most appropriate
candidates for cryosurgery are relatively easily defined. They include
- Older individuals, over 70 years of age, or individuals who might have
medical problems that would
increase their risks of undergoing major surgery
- Patients at higher risk of extracapsular disease (who might be able to
have repeat cryosurgery or other
forms of treatment should initial cryoablation be followed by disease
recurrence)
- Patients who have failed radiation therapy and have no other
potentially curative options.
The use of cryosurgery in younger patients with small volume, low grade
cancers remains controversial and is
certainly experimental. However, it is reasonable to ask whether it is
appropriate to prohibit cryosurgery in this
patient population.
In the opinion of a number of investigators, treatment of this patient
population is permissible under appropriate
study protocols and with extensive and carefully recorded informed consent
from the patient. These investigators
make the argument (a) that long-term data from liver cryosurgery and from
open perineal prostate cryosurgery indicate
that cryosurgery is equivalent to surgical resection, and (b) that it is
precisely the young patient that has the most to
lose from an inadequate treatment by a radical prostatectomy, leaving the
patient with no curative treatment options
and sufficient life expectancy to be negatively impacted by the residual
disease. Only additional data and longer
follow-up of the currently available data will clarify the potential value
of cryosurgery in this patient population.
Technical factors in prostate cryosurgery
It has been said that, "You can't make a baby in one month by making nine
women pregnant."
For obvious reasons, in the early development of a new procedure, it is
far preferable to have 10
centers doing 100 cases each than 100 centers doing 10 cases each.
Unfortunately,
rapid distribution of the capability to carry out percutaneous prostate
cryoablation, which is
a procedure with many subtleties and which is not as simple as might first
appear,
has occurred while the procedure is in an early evolutionary phase. There
is,
as yet, no standard surgical protocol that is universally followed, nor
are there
any multi-institutional studies evaluating this procedure. Such a
situation raises
the specter that the results of the procedure may not be reproducible
from
institution to institution. Under these circumstances, how should the
patient who
wishes to consider percutaneous prostate cryosurgery choose an institution
at which he might consider having this procedure?
On the basis of animal experiments and early patient experience, the
fundamental
technical factors that need to be adhered to in order to attain the most
reproducible
results with percutaneous prostate cryosurgery are known
[13, 14].
The remainder of this section will outline the basis of the cryosurgical
procedure
and has been designed to give the potential cryosurgery patient sufficient
information to evaluate an institution's technical capabilities and its
ability to offer
percutaneous prostate cryosurgery in an safe and effective manner.
The basic procedure
Percutaneous prostate cryosurgery can be carried out under general or
spinal anesthesia.
The cryoprobes are placed transperineally using a stepwise modified
Seldinger technique.
(First a needle is placed; then a wire is inserted through the needle;
finally, over the wire
are placed the larger instruments.)
After the appropriate placement of an array of five or six cryoprobes under
transrectal ultrasound (TRUS) guidance, freezing is carried out (again under
TRUS monitoring). The freezing can be observed under TRUS as a rim of
increased echoes
as it approaches the rectal mucosa. Such monitoring minimizes the risk of
rectal freezing. The possibility of injury to the urethra is decreased
(but not entirely eliminated) by the use of a warming device which is
inserted into
the urethra.
The optimal implementation of the overall procedure is dependent upon
the appropriate degree of attention to detailed addressed below.
Preoperative staging biopsies
It may seem like an obvious point, but knowing the precise location and
extent of
the tumor is extremely important in optimizing the results and reducing
the morbidity of
any oncologic surgical procedure. Certainly this is no less the case for
percutaneous prostate cryoablation, and it may be more so.
Unfortunately, we now know that even the most sophisticated imaging studies
using magnetic resonance imaging (MRI) and TRUS cannot adequately stage
prostate
tumors when used on their own. At this time, therefore, in order to know
the full extent of the tumor, TRUS-guided staging biopsies of the tumor
should be
carried out as described by Lee et al. [14]. (It is worth
noting that such staging biopsies are also reasonable for any patient
contemplating a radical prostatectomy, since they may demonstrate the
presence
of unsuspected extracapsular disease.) Any demonstrable lesion observed on
TRUS
should be biopsied, as should both lobes of the prostate at the base,
the mid-gland,
and the apex. In addition, the neurovascular bundle (NVB) on the side of
the
lesion, which is a common
site of prostate cancer spread, should also be biopsied. Finally, a biopsy
in the midline ejaculatory duct region can indicate whether tumor has gained
access to the invaginated extraprostatic space (IES) with consequent high
likelihood of spread into the seminal vesicles.
Knowledge gained from these staging biopsies allows careful tailoring of the
cryoablation procedure to the patient's pathology. When extracapsular
spread
has been demonstrated on biopsy, for example, a probe can be placed into the region of the
neurovascular bundle or into the seminal vesicles at the site of the
extracapsular
disease. This information also decreases the need to aggressively freeze
in areas that are known not
to be involved with tumor. This approach will, over time, eventually
decrease the overall
early complication rates associated with prostate cryoablation.
Downsizing of the prostate gland with combined androgen ablation
Downstaging of the prostate gland prior to radical prostatectomy is
controversial. However downsizing of a gland prior to cryosurgery
has a very different rationale.
Larger prostate glands require more exact placement of cryoprobes, leaving
little margin for error to ensure adequate freezing and destruction of the
cancer.
Some larger glands may actually outstrip the freezing capabilities of the
currently available cryosurgical equipment.
In addition, we now have learned that the temperature reached by the
frozen tissue is a critical
determinant of complete tissue destruction. Because larger prostate
glands
imply that cryoprobes be placed farther apart than they are in "normal"
prostate glands,
the tissue in larger prostate glands tends to be exposed to higher average
temperatures throughout
the gland, making complete tissue destruction less certain.
Combined androgen deprivation prior to cryosurgery actually has two
effects. First it shrinks
the gland, thus ensuring more complete tissue destruction throughout the
gland. Second, it has the additional
effect of increasing the amount of fat in the region of Denonvilliers
fascia, thus
increasing the space between the rectum and the prostate capsule and
thereby decreasing the risk of freezing the rectum.
It is the belief of this author (although it should be made clear that this
belief is, as yet, completely unsupported by any
long-term data) that preoperative (or neoadjuvant) hormonal ablation of
3-6 months duration may eventually be shown to improve survival in those
patients with more advanced disease by decreasing the risk of distant
metastasis over time.
It also seems possible that the cancer-destructive effects of androgen
deprivation therapy,
when applied to micrometastatic prostate cancer at a relatively early
stage,
could positively effect patient survival. (A comparable effect has been
observed
in breast cancer patients treated with adjuvant therapies.)
The use of appropriate ultrasound equipment
Three basic ultrasound equipment factors influence the quality of the TRUS
image generated, and therefore the ability to
observe important details such as the layers of the rectal wall. The
quality of the TRUS image, in turn, affects
the ability of the cryosurgeon to adequately monitor the freezing process.
The patient is advised to determine whether the
center at which he is considering having cryosurgery has ultrasound
equipment adequate to carry out
cryosurgery effectively and safely by asking the following questions:
- How many channels does the ultrasound machine being used for cryosurgery have?
The number of channels on an ultrasound machine determines how much
information that that particular
machine can gain from the ultrasound transducer. A machine with 128
channels can process twice as much information
as a machine with 64 channels, thereby adding to the detail available in
the ultrasound image. State
of the art TRUS equipment now has at least 128 channels.
- What is the frequency of the linear array transducer used to monitor the cryosurgery?
The transducer frequencies generally available for the TRUS equipment used
to
monitor prostate cryosurgery are 5 and 7.5 MHz. The higher the frequency
is, the
better the ultrasound transducer can depict fine details, particularly in
the area close to the transducer.
In monitoring prostate cryosurgery this means that with higher-frequency
transducers it is
possible for the cryosurgeon to better observe the freezing zone as it
approaches the rectum.
- Is the ultrasound transducer biplanar, with a linear array
and
a sector transducer, or does it only have a sector transducer?
The ultrasound image produced by a linear array transducer appears as a
large rectangle, whereas the
image produced by a sector scanner looks like a slice of pie. Unfortunately,
the sector ultrasound
transducers, long used for guiding prostate biopsies, and which most
urologists have ready access to,
are not adequate for monitoring cryosurgery, although they are still
being used for that
purpose. A sector scan transducer is not adequate for monitoring
cryosurgery because ultrasound does not
penetrate the frozen tissue which causes shadowing behind the ice front.
When
the ultrasound image is pie-shaped, the shadow is larger and freezing is
overestimated. This can
best be likened to sitting behind a pole in an old baseball stadium: the
closer you sit to the pole, the less of the field you can see!
The linear array transducer solves this problem by using multiple parallel
crystals (e.g., several sets of
eyes instead of just one). To reiterate, adequate monitoring of
cryosurgical freezing requires a
linear array ultrasound transducer.
- Does the ultrasound machine being used have color Doppler capabilities?
There is some recent evidence to suggest that some prostate cancers that
are not well visualized by standard gray-scale ultrasound
may be detected by the use of color Doppler blood flow imaging. While the
use of this imaging technique
has yet to show definitive benefits during the cryosurgical process, if you
are
a patient in whom the physician has had difficulty finding tumor, an
ultrasound study using color Doppler equipment may help to better define
the
extent of your tumor.
The appropriate use of thermocouples to monitor temperature
It is now clear that the use of thermocouples to monitor temperature is
essential to the
proper treatment of patients by cryoablation. Thermocouples are used to
confirm that all areas of the prostate are properly frozen, particularly
those
areas of the prostate which can be difficult to evaluate due to the
shadowing
effect of the ice. The apex of the prostate gland is an area in point;
here,
if the cryoprobes are placed too far apart, inadequate freezing can occur
but ultrasound may not be able to detect this failure.
In addition, animal experimentation now suggests that prostate tissue must
reach at least -25 C to ensure
complete tissue destruction. Thermocouples may be used to ensure that
this
target temperature is reached in critical areas such as the apex of the
gland,
the neurovascular bundle on the side of the lesion, the anterior
fibromuscular
stroma, and the confluence of the seminal vesicles.
Use of a double freeze-thaw cycle
The destruction of tissue by cryosurgical means involves a complex
interplay between a number of
different mechanisms of tissue damage. It is therefore not surprising
that
during the freezing process a number of different parameters have been
found to be to be important to complete
tissue destruction. These parameters include the temperature to which the
tissue is frozen, how long the tissue is frozen, and the number of
freeze-thaw cycles that the tissue undergoes.
It has already been stated that the target temperature during cryosurgery is
-25 C. It should also be recognized that the surgeon is only able to
actually monitor
temperature with thermocouples in a small number of particularly critical
areas. It
therefore makes sense for the surgeon to attempt to optimize other potentially
critical freezing parameters. A number of investigators have now noted
markedly improved results by subjecting the tissue to a second freeze-thaw
cycle
at the same operation. While this takes more operative time than a single
freeze-thaw
cycle, it can be considered prudent to carry out a second freeze at least
in the area of known tumor on
all patients [15].
Expected clinical results
If the above-mentioned equipment and parameters are all carefully taken
into account and appropriately used, then a 1-year
negative biopsy rate of 90% can currently be expected [12].
Future developments
The major developments in prostate cryoablation are occurring in the areas
of improved monitoring and visualization
of cryosurgery.
Transurethral ultrasound for monitoring freezing adjacent to the urethra
The "blind" area for prostate cryosurgery (due again to the shadowing
caused by the freezing
when using TRUS) is the urethra. This remains one of the most problematic
issues in prostate cryoablation.
Once visualization of freezing is available to monitor the urethra,
improved results can be expected in
terms of fewer patients undergoing urethral sloughing and better treatment
of
tumors at the apex of the gland (where the peripheral zone abuts the
urethra).
A transurethral ultrasound (TRUS) system that can be incorporated into a
urethral
warmer has recently been tested. This TRUS system allows better
visualization
of the freezing zone in relation to the urethra. However, the clinical
benefit of
such a system remains to be demonstrated.
Three-dimensional ultrasound
A three-dimensional ultrasound system has now been successfully used in a
small number of patients and allows increased information to be made
available to the surgeon. For example, using such a system the physician
can obtain a corneal view of the prostate which shows the orientation of the
cryoprobes to the shape of the prostate. Such a view is not available
by use of standard ultrasound transducers. It is hoped that continued
development of
such a system will allow physicians who are inexperienced in the use of
ultrasound to practice percutaneous prostate cryoablation with the skill
of an ultrasound expert.
MRI-guided percutaneous prostate cryoablation
Work carried out by Rubinsky and his associates at the University of
California
at Berkeley has indicated that MRI may have some major advantages over
ultrasound in monitoring cryosurgical procedures. Freezing does not appear
to cause shadowing on
MRI images, and therefore "blind areas" do not occur. In addition, computer
programs have already been tested that allow noninvasive temperature
monitoring
anywhere within the frozen region under MRI. The advent of low-cost open
MRI scanners in which
surgery is possible may make such procedures cost effective in the future.
Conclusion
The procedure of percutaneous prostate cryoablation, while showing tremendous
potential, is in its infancy. Many improvements need to be made to this
procedure
before it is capable of reliable, reproducible results in the hands of all
practitioners. Improved preoperative planning and improved monitoring of
the freezing
process need to occur. In addition, elucidation of the optimal freezing
protocols is essential, and must be based upon continuing basic research
into the
thermal sensitivity of prostate cancer.
Percutaneous prostate cryoablation under transrectal ultrasound guidance
offers a significant opportunity for the treatment of prostate cancer. The
major constraint on more widespread utilization at this time would appear
to be the lack of long-term data confirming the equivalence of this new
procedure to radical prostatectomy and radiation therapy. Based on the
technique's low morbidity, and a number of other demonstrated advantages,
certain patients -- after careful consideration and fully informed consent --
may want to choose cryoablation as a treatment option despite the fact that
long term safety and effectiveness data are still required.
References
1. Adolfsson J, Steineck G, Whitmore WF. Recent results of
management of
palpable clinically localized prostate cancer. Cancer 1993; 72: 310-322.
2. Fleming C, Wasson JH, Albertsen PC, et al. A decision
analysis of
alternative treatment strategies for clinically localized prostate cancer. JAMA 1993; 269: 2650-2659.
3. Jones EC. Resection margin status in radical retropubic
prostatectomy
specimens: relationship to type of operation, tumor size, tumor grade, and
local tumor
extension. J Urol 1990; 144: 89-93.
4. Bonney WW, Fallon B, Gerber WL, et al. Cryosurgery in
prostatic cancer survival. Urology 1982; 19: 37-42.
5. Steele G. Cryoablation in hepatic surgery. Semin
Liver Dis. 1994; 14: 120-125.
6. Grampsas SA, Miller GJ, Crawford ED. Salvage radical
prostatectomy after failed transperineal cryotherapy: histologic findings
from prostate whole-mount specimens coprrelated with intraoperative
transrectal ultrasound images. Urology 1995; 45: 936-941.
7. Onik GM, Cohen JK, Reyes GD, et al. Percutaneous
radical cryosurgical ablation of the prostate under transrectal ultrasound
guidance. Cancer 1993; 72: 1291-1299.
8. Onik GM, Cohen JK, Miller R, et al. Treatment of
non-organ-confined prostate cancer with percutaneous prostate cryosurgery,
Radiology 1993; 189: 277.
9. Partin AW, Yoo J, Carter HB, et al. The use of prostate
specific antigen, clinical stage, and Gleason score to predict
pathological stage in men with localized prostate cancer. J Urol.
1993; 150: 110-114.
10. von Eschenbach AC, Pisters LL, Swanson DA, et al.
Results of a phase I/II study of cryoablation for recurrent carcinoma
of the prostate: the University of Texas, M D Anderson Cancer Center
experience [abstract]. J Urol. 1995; 153; 503A.
11. Schmidt JD, Parson CL, Casola GF, et al. Transperineal
cryoablation for prostate cancer [abstract]. J Urol. 1995; 153: 502A.
12. Bahn DK, Lee F, Solomon MH, et al. Prostate cancer:
ultrasound-guided percutaneous cryoablation. Radiobiology 1995; 194:
551-556.
13. Onik G, Rubinsky B, Zemel R, et al. Ultrasound-guided
hepatic cryosurgery in the treatment of metastatic colon carcinoma.
Preliminary results. Cancer 1991; 67: 901-907.
14. Lee F, Bahn DK, McHugh TA, et al. Ultrasound-guided
percutaneous cryoablation of prostate cancer. Radiology 1994; 192:
769-776.
15. Onik G. Transperineal prostatic cryosurgery under
transrectal ultrasound guidance. Semin Invest Radiol. 1989; 6: 90-96.
16. Shinohara K, Carroll PR: Improved results of
cryosurgical ablation of the prostate [abstract]. J Urol. 195; 153:
385A.
Editorial comment
This article offers a useful and interesting assessment of the current
state of cryosurgery by a
recognized specialist in this technique. The Prostate Cancer InfoLink
advises its readers that not all
surgeons or other physicians would necessarily agree with Dr Onik's
assessment. On the other hand, Dr Onik is careful to point out
that the "proof of the pudding" will only come when long-term survival
data
on patients receiving cryourgery can be compared to similar data for
patients undergoing other forms of therapy.
The Prostate Cancer InfoLink also continues to advise patients that
cryosurgery should be considered
an investigational or experimental technique at this time, pending the
availability of suitably
monitored disease progression and survival data on patients at least 5
years after their initial treatment.
[Reminder: This was written and posted to InfoLink in 1995. Some procedures may have changed.]
|
