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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


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.


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.


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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.]

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