The local application of extreme cold as a technique to freeze prostate cancer tissue dates back to the 1960s, but its use in combination with ultrasound imaging to assure appropriate placement of fine cooling probes in carefully selected areas of the prostate only really began in the late 1980s and early1990s. This technique is variously referred to as cryosurgery or cryotherapy or cryoablation.
The initial work in this area was conducted by Gary Onik and Jeffrey Cohen at Allegheny General Hospital, and their pilot data were published in 1993. In subsequent years there has been vast improvement in the technology available for prostate cancer cryotherapy, and a number of centers in the USA and internationally now practice cryotherapy on a regular basis. Cohen addressed the development of cryosurgery for prostate cancer into the early application of “third-generation” technology in a review article in 2004.
In 2008 the American Urological Association published a “Best Practice Policy Statement” entitled Cryosurgery for the Treatment of Localized Prostate Cancer, acknowledging that cryotherapy is an accepted form of first-line treatment for selected patients with early stage (localized) disease.
The Basics of Modern Cryotherapy
Cryotherapy for the treatment of prostate cancer is designed to eradicate prostate cancer cells by exposing them to extreme sub-zero temperatures within the prostate gland.
Modern (“third-generation”) cryotherapy is normally carried out as an outpatient procedure (sometimes under general anesthesia). Extremely fine (“ultra-thin”) needle probes are inserted into the prostate gland through the perineum (the area of skin between the scrotum and the anus). Argon gas is then circulated through the needle probes to drop the temperatures to between –150 °C and –140 °C. So-called “ice balls” form in the tissue around the needle probes.
The cryotherapist uses ultrasound or even MRI guidance to ensure accurate positioning of the needle probes within the prostate, thus being able to accurately control the size, shape, and placement of the ice balls within the prostate, and allowing him/her to monitor the freezing process. Technical data about the use of cryosurgical techniques in the management of prostate cancer — including videos of the procedure – are available on the web sites of the two companies (Galil Medical and Endocare) that dominate the cryosurgery market. The two companies have recently agreed to merge.
Under normal circumstances prostate cryotherapy takes approximately 2 hours for complete treatment of a patient with localized disease. One of the most important and unique aspects of cryosurgery in the treatment of localized prostate cancer is the role of the so-called “urethral warmer” which is used to ensure that the patient’s urethra is not frozen as part of this procedure.
Who is an Appropriate Patient for This Procedure?
The AUA’s “Best Practices Policy Statement” makes the following recommendations about patient selection for primary cryosurgery as a curative, first-line treatment option for early stage prostate cancer:
- The patient should have cancer that is clinically confined to the prostate.
- Gland volume is an important factor: “the larger the prostate, the more difficult [it is] to achieve a uniformly cold temperature throughout the gland.” (And while hormone therapy can be used to reduce the size of larger glands, there is no evidence to date that such “cytoreduction” of the size of the gland has a positive impact on the overall outcome of cryosurgery.)
- A prior transurethral resection of the prostate or TURP is normally a strong signal that cryosurgery may be associated with serious complications.
- The best results of cryosurgery for treatment of localized prostate cancer have been obtained in men with PSA levels < 10 ng/ml.
- Cryosurgery is a minimally invasive treatment option for men who do not want or are not appropriate for radical prostatectomy and may also be a reasonable option for men who are not appropriate candidates for external beam radiotherapy.
- For men who have intermediate risk, localized prostate cancer, cryosurgery is an appropriate form of minimally invasive treatment if they have
- A Gleason score of < 7 and/or
- A Gleason score of < 8 with a PSA level between 10 and 20 ng/ml and/or
- Clinical stage T2b disease
We would add that (as you will find out further down the page), total gland cryosurgery is associated with a very high incidence of erectile dysfunction, and is therefore not a good choice of therapy for a man who is determined to try to retain erectile function post-treatment. (Focal forms of cryotherapy may have more promising outcomes but such techniques are still considered to be investigational at this time.)
The Results You Can Reasonably Expect
Biochemical outcomes: The regular measurement of PSA levels following cryosurgery is normal (as it is after every other form of treatment for localized prostate cancer). However, there is no consensus to date about how to assess the “meaning” of those PSA levels over time. Most cryotherapy specialists today seem to be using the ASTRO Phoenix definition of biochemical success and failure. According to this definition, the PSA should be followed until it reaches its lowest (“nadir”) value. Ideally the PSA then stabilizes. If the PSA starts to rise again, the patient will be defined as having a biochemical recurrence if his PSA rises to a value defined by the sum of the nadir value + 2 ng/ml.
Using the data compiled by the Cryo On-Line Database (COLD) registry, and applying the Phoenix definition of biochemical recurrence to the data from men accumulated in that registry, the percentage of men who are free of biochemical progression at 5 years of follow-up can be characterized as follows:
- 91 percent of men with low-risk, localized prostate cancer
- 78 percent of men with intermediate-risk, localized prostate cancer
- 62 percent of men with high-risk, localized prostate cancer
According to the American Urological Association, long-term data on progression to metastatic disease, prostate cancer-specific survival, and overall survival are not well defined at this time. The same conclusions have been published by Jones et al. based on the same database.
Post-treatment biopsy results: It used to be customary for cryotherapy patients to receive regular post-treatment biopsies as a method to assess risk of trratment failure. Recently, however, because of the increasingly high proportion of negative post-treatment biopsies since the application of “third generation” technology, this practice has largely ceased. All we can really say about the value of post-treatment biopsies is that negative post-treatment biopsies do signal a reduced risk for treatment failure — but a negative biopsy is no guarantee that treatment has eradicated all the cancer. The same applied to radiotherapy for localized prostate cancer.
The Adverse Events of Treatment
The common, short-term side effects — There are a small number of relatively “normal” short-term consequences of cryotherapy in men with early stage, localized prostate cancer:
- Almost all men will have some degree of urinary retention for 1-2 weeks post-treatment. It is therefore normal for patients to go home with a suprapubic or a Foley catheter, just like men who have surgery for prostate cancer.
- The freezing of the prostate causes some initial swelling of the gland, and this can be painful. Aspirin or prescription anti-inflammatory agents may be needed to manage this problem.
- Penile and scrotal swelling are also common during the first 1-2 weeks after surgery, but will normally just go away after a couple of months or less.
- Penile parasthesia (an altered sensation often described as burning, tingling, or pin pricks) may be experienced, but this side effect usually resolves itself without problem within 2-4 months.
Significant, longer term problems — There are four well-known, long-term side effects of prostate cancer cryotherapy: formation of fistulas, incontinence, erectile dysfunction, and so-called “urethral sloughing.” Each of these addressed below.
In the early days of prostate cancer cryotherapy, the formation of fistulas was a common and serious problem. A fistula is an abnormal duct or passage that connects an abscess, cavity, or hollow organ to the body surface or to another hollow organ. In the case of prostate cancer cryosurgery, fistulas were common between the prostate bed and the rectum. However, improvements in technology have significantly lowered the risk of this side effect. In modern series of patients the reported incidence of this event is between 0 and 0.5 percent.
When cryosurgery is used to treat prostate cancer, even though the external sphincter is partially protected by the urethral warming device, this sphincter can be significantly affected by the “surgical freeze” — as can the urethral mucosa. The consequence can be temporary or permanent incontinence. When incontience occurs, it is usally limited to mild forms of stress incontinence that may improve over time (i.e., incontinence on trying to lift heavy weights or similar). However, permanent long-term incontinence is also possible. The incidence of physician-reported permanent incontinence ranges in literature reports from < 1 percent to as high as 8 percent of patients.
Erectile dysfunction is a very common long-term effect of total gland cryosurgery, observed in 49-93 percent of patients at 1 year of follow-up, based on published reports.
The last significant, long-term complication of cryosurgery is “urethral sloughing,” in which dead prostate tissue can be expelled into and through the urethra, with the postential to block or infect the urinary tract. The introduction of the urethral warming device has massively reduced the risk of this problem in recent years, but urthral sloughing continues to be a normal risk associated with 0 to 15 percent of patients in modern cryosurgical series for terament of prostate cancer.
The AUA’s “Best Practice Policy Statement” contains detailed information on the side effects of cryosurgery in treatment of localized prostate cancer, extracted from an original review by Mouraviev and Polascik.
As discussed above, cryotherapy, in the hands of a specialist who treats many patients a year, using the most current forms of third- or fourth-generation cryosurgical equipment, is now a sound and viable option for the treatment of men with localized, early stage prostate cancer, particularly older men who are less concerned about the potential for loss of erectile function.
We should, however, note that other uses of cryosurgery in prostate cancer are still, at best, investigational. These include the use of focal or “hemi-glandular” cryosurgery (in which only part or half of the prostate is treated for localized disease) and the use of cryosurgery as salvage therapy (alone or in combination with hormone therapy) for men who have biochemical progression following other forms of first-line treatment.
Patients should appreciate that this is not, nor is it intended to be, a complete list of every possible risk associated with cryosurgery for the treatment of localized prostate cancer. If you decide to work with a specialist who intends to use this procedure, you should be sure to review these and other risks — infertility, infection, injury to other organs, pain, recurrence — with that cryotherapist prior to your operation, and you will certainly be asked to sign a relevant consent form prior to surgery.