Prostate cancer is one of the most common forms of cancer in men and some of its traditional treatments can result in serious complications. However, cryoablation is an emerging alternative therapy for prostate cancer that shows great promise. Due to recent advances with smaller needles and computer guided programs to insert the needles, the procedure has become much more effective and offers patients an outpatient treatment with minimal side effects. What does this new treatment entail? What are its advantages and disadvantages? The following information should help answer those questions and more.
What is cryoablation?
Cryoablation for prostate cancer involves the controlled freezing of the prostate gland in order to destroy cancerous cells. Cryoablation however is not cancer specific, and the treatment will ablate all of the epithelial cells that are in the targeted area. The damage caused by freezing occurs at several levels: molecular, cellular and whole tissue structure. In particular, cryotherapy kills targeted tissue by three modes of cell death: (1) cell trauma (secondary to intracellular ice formation), (2) necrosis (immediate cell death and also delayed death secondary to vascular stasis preventing oxygen to tissues), and (3) apoptosis (programmed cell death). In addition, there may be an immunological effect when the cancerous cells are killed. Important factors influencing freezing injury are the rate of temperature reduction after the initiation of freezing, the end-temperature reached and performing two freeze-thaw cycles.
The cells are not the only structures damaged during freezing. During cryoablation of the prostate, the surrounding connective tissue (stroma) and the smallest blood vessels (capillaries) are damaged and subsequently have an inadequate blood supply that is also believed to eradicate cancer.
Who are the most suitable candidates for cryoablation of the prostate?
Suitable candidates for this procedure are patients who have organ-confined prostate cancer or those who have minimal spreading beyond the prostate (clinical stage up to T3a). This includes patients undergoing prostate cancer treatment for the first time and those with recurrent cancer following radiation treatment (external beam or brachytherapy). One benefit of cryotherapy is that it is equally effective when ablating (removing) cancers of any Gleason grade. Due to the ability to use smaller needles, it may be possible to eradicate an area of the prostate that contains the cancer rather than treating the entire prostate gland. This new form of focal cryotherapy is emerging and may change the way that prostate cancer is treated in the future.
How is the procedure performed?
Under anesthesia (either general or spinal), an ultrasound probe is guided into the rectum. The prostate is imaged and its dimensions measured. An aiming grid software program is then activated and images of the prostate are projected on a screen. Under continuous monitoring with ultrasound imaging, cryoablation probes or needles are placed at predetermined sites within the prostate. Each of the commercially available cryosurgical systems has a different type of probe and placement strategy, but all aim to freeze the prostate, tumor(s) and surrounding tissue—except the urethral area. A urethral warming catheter keeps the urethra warm throughout the procedure and is kept active for about 20 minutes after the final thaw cycle to prevent the urethra from freezing. In addition to the freezing probes, small temperature probes are also placed in and around the gland to monitor the temperature of the rectal wall as well as other sites such as the urinary sphincter. This has led to a dramatic reduction in side effects such as urinary incontinence and rectal fistula formation.
Prior to the freezing process, cystoscopy (direct visual inspection of the bladder using a small telescope) is performed to ensure that cryoprobes have not inadvertently pierced the urethra; if so the probes are simply repositioned. A commercially available urethral warming catheter is placed at this time thereby protecting the urethra from freezing. This is important, as it minimizes the risk of urethral damage, obstruction and urinary incontinence.
Freezing starts at the anterior part of the prostate by activating the anterior probes, followed by the middle and finally the posterior probes. This sequence allows continuous monitoring (by visualizing the freezing process through the (trans-rectal ultrasound) and sculpting of the ice balls. The physician knows when to stop freezing using both the ultrasound image as a guide as well as monitoring the temperature probes. Two freezing cycles are usually done. Between them, the prostate is allowed to thaw either passively or actively by using helium or argon gas. If the prostate is longer than the active portion of the cryotherapy probe, an apical pullback maneuver is usually done to freeze the apex of the prostate. Double freezing is performed again. Following the final thaw, either a urethral Foley catheter or a suprapubic catheter (a small tube that is pierced into the bladder through a small opening in the lower abdomen) is inserted and secured in place. The physician will typically remove this catheter several days after cryotherapy when the patient is able to urinate. For most cases, the procedure can be performed under 2 hours.
What can be expected after treatment?
Cryoablation of the prostate is currently an outpatient procedure. The patient is usually discharged from the recovery room with either a urethral catheter or a suprapubic tube in place for drainage.
Prostate cryoablation will cause the prostate to swell in the short term. Once the swelling has resolved, typically in the order of several days to a few weeks after the procedure, the urinary catheter may be removed. The patient has to demonstrate that he is capable of urinating on his own, lest the catheter need to reinserted again until the prostate swelling has had sufficient time to resolve. If the patient is unable to urinate, the catheter is reinserted for a few more days. Most patients are able to urinate in about 5 to 15 days but some may require longer recovery periods. Oral antibiotics and other medications that help with urination or reduce catheter irritation may be given after treatment, depending on physician preference. Other less common side effects that the patient may experience are scrotal swelling, numbness at the tip of the penis, passage of flecks of tissue, pain or burning sensation during urination and increased urinary frequency and/or urgency. Most men are pleasantly surprised that there is little to no pain after treatment, and recovery to normal health typically occurs within that first week. Of course, the most common symptoms that a man may experience are those related to having a catheter: urinary urgency and a minor amount of blood in the urine.
A PSA test is usually done at three months. Also, a prostatic biopsy may be recommended some time after the procedure to assess for prostate destruction and absence of viable cancer cells especially if PSA level continues to climb. Once the PSA level has stabilized, the PSA may be checked every 6 months or annually. Of course, if the PSA level is in a state of flux, it will likely be monitored more closely by your physician.
What type of results can be expected?
Currently there have been numerous publications on the use of cryoablation in the literature, both on the primary side as well as for salvage (those that have had prior radiation). One of the largest trials published compared the results of cryotherapy to those of conformal radiotherapy and brachytherapy. Patients with a previous history of failed radiotherapy were excluded and androgen deprivation was determined and categorized separately. Patients were classified as low risk, moderate risk or high risk according to the cancer characteristics (stage of the disease, Gleason grade and PSA level). The procedure was not consistent at all institutions. Differences included the number of probes used, number of freeze cycles per patient, length of apical pullback maneuver, real-time monitoring during freezing and the system used for freezing. A total of 975 patients were studied, of whom 238 were low risk, 321 were moderate risk and 385 were high risk; risk was not determined in 38 patients. The five-year rate for non-rising postoperative PSA levels for low and medium risk patients ranged between 60 and 76 percent and for high-risk patients it was 41 percent. Only about 18 percent of the patients were found to have a positive biopsy following the procedure. These results are encouraging and may place cryoablation therapy between radical prostatectomy and radiotherapy in effectiveness.
In addition, there are three peer-reviewed publications on the subject of focal cryotherapy. The number of patients studied is small, only 77 subjects combined. The average follow-up is also relatively short, 60 months, 70 months, and 28 months respectively. Various definitions of PSA or biochemical failure have been used to evaluate the clinical outcomes. These include the ASTRO (American Society for Therapeutic Radiology Oncology) definition that is three consecutive PSAs rising, the Phoenix definition that is the PSA nadir plus 2, and PSA nadir less than 50% of the pre-operative level. The biochemical disease free survival rates range from 84% – 95%. A biopsy was performed when biochemical failure was suspected, or as a protocol regardless of PSA levels. With every definition used, these three papers report fairly similar outcomes. A total of 71 of the 77 men had undergone post-cryotherapy biopsy with cancer identified in 4 patients (6 %). All except one of these residual cancers were seen in the untreated lobe.
Overall these are excellent results which indicate that prostate cryotherapy can result in high cure rates for men with early stage prostate cancer. This is really no surprise and somewhat expected. Since cryotherapy can cure recurrent high grade cancer that recurs after radiation, we would expect better results in the early stage, non radiated patient. The reason that this technology had not been used more frequently until fairly recently was because historically the imaging was not sophisticated enough to allow us to target or focus? On small cancers; there was no planning computer-guided software as there is today, and the cryotherapy needles that were available were just too big and bulky to perform a focal procedure with precision. As more follow-up studies are carried out and publications enter into the main stream journals, it is our strong belief that this form of therapy will continue to expand, as it should. We have seen this with breast cancer, where we are doing more lumpectomies than radical mastectomies, and we have seen this in kidney cancer, where the rise of partial kidney removals for renal cell cancer (partial nephrectomy) are becoming more common place and replacing the old total removal of the kidney. Minimally invasive treatment focusing on the cancerous lesion and sparing healthy normal tissue that is disease free has to be the way forward to reduce side effects of treatment and thus improve patient quality of life.
What are the risks associated with this procedure?
New technological advances have resulted in a significant reduction of the rate of complications. An improved FDA-approved urethral warming device has minimized urethral complications. Better spacing of the probes now contributes to the effectiveness and safety of the procedure. Improved monitoring of the freezing with real-time trans-rectal ultrasound and temperature thermistors has given the treating physician control over the size and shape of the ice balls formed. However, some risks still exist. Perhaps one of the most critical is the risk of urinary rectal fistula, which creates a channel between the urethra and the rectum and may cause diarrhea due to urine in the rectum and possibly severe infection due to bacteria in the bladder. However, this has largely been a complication using older technology and is rarely seen today. In fact, a recent study that included over 1000 patients in the COLD registry (Cryo On Line Database) revealed that the rectal fistula rate was only 0.4%. There is also a high incidence of erectile dysfunction when freezing the entire prostate. However, several physicians have developed methods to better preserve erections in those patients who are candidates for a nerve-preserving procedure. Other complications, although uncommon given technological advances, include urinary incontinence, urinary retention requiring transurethral resection of the prostate (TURP) and inflammation of the testicle. Almost all patients have a temporary need for a catheter to empty the bladder for several days after the procedure. Permanent, severe incontinence is rare (approximately 1 percent) and other rare complications include prostatic abscess and permanent penile numbness.