Data support cryoablation as primary treatment option for localized tumors.
Cryoablation as a primary treatment for localized prostate cancer has come a long way since the 1980s and now should be considered part of the therapeutic armamentarium for the malignancy, according to researchers.
Their conclusion is based on an analysis ofthe Cryo Online Database (COLD), which has information on more than 2,000 patients who received primary, salvage, and subtotal cryoablation for localized prostate tumors at various centers throughout the United States. To date, it is the largest such data set assembled.
At the annual meeting of the Society of Urologic Oncology in Bethesda, Md., lead investigator J. Stephen Jones, MD, of the Cleveland Clinic, presented findings on 1,198 men who had a mean follow-up of 24 months, with 182 patients followed for more than five years.
The study showed that patients with low-, moderate-, and high-risk disease had five-year biochemical disease-free survival (bDFS) rates of 84.7%, 73.4%, and 75.3%, respectively, based on the traditional definition for PSA relapse (three consecutive rises) developed by the American Society for Therapeutic Radiology and Oncology (ASTRO). The five-year bDFS was 91.1%, 78.5%, and 62.2% using the “new” ASTRO criteria of PSA nadir +2.0.
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Overall, bDFS rates for cryoablation appear competitive with those achieved with radical prostatectomy and radiation therapy for localized prostate tumors. Cryoablation, however, may have an advantage for patients with high-risk malignancy, based on findings showing these patients have bDFS results that appear to be better than the 33% described in Campbell’s Urology 9th Edition. Dr. Jones points out that even though this is the largest series reported, the numbers are still too small to make broad statements of superiority of one modality over the other.
With respect to complications, cryotherapy was associated with a 0.4% rate of rectal fistula, which is higher than would be expected from radical prostatectomy but far less common than most urologists would have predicted, based on experience with previous technology.
At 12 months, the urinary incontinence rate was 4.8% with only 2.9% of patients requiring pad use. Of the patients potent at the time of therapy, only 14.8%, 19.0%, and 11.7% had resumed intercourse by 12, 24, and 36 months, Dr. Jones reported.
Other than erectile dysfunction (ED), cryoablation was associated with much less morbidity than radical surgery, which is more invasive and requires longer recovery times. Except perhaps for superior reported rates of bDFS survival for high-risk patients and higher rates of ED, the data suggest comparable outcomes with cryoablation and radiotherapy, he said.
Men with a PSA level below 10 ng/mL, clinical stage T1c-T2a tumors, and a Gleason score of 6 or less were considered to have low-risk disease. Men with a PSA level of 10-20 ng/mL, clinical stage T2b tumors, or a Glea-son score of 7 were considered tohave intermediate-risk disease, and patients with a PSA level greater than 20 ng/mL, clinical stage T2c tumors, or a Gleason score of 8 or higher were considered to have high-risk disease.
In the 1980’s and early 1990’s, primary cryotherapy for localized pros-tate cancer was cumbersome and “there were lots of people advocating cryo without a lot of data to support its use,” observed Dr. Jones, vice chairman of the Cleveland Clinic’s Glickman Urological Institute.
At the time, surgeons used liquid nitrogen, whose physical properties made it difficult to freeze tissue with precision, resulting in less than optimal outcomes, Dr. Jones related. It was hard to know how long to apply liquid nitrogen to create an appropriately sized “ice ball” to destroy tissue. “The ice ball would continue to progress after you turned [the nitrogen] off.”
Today, urologists use argon gas, which gives them greater control over freezing. Ice ball formation ceases almost immediately upon stopping argon application. In addition, improvements in ultrasound imaging and the use of thermocouples to measure temperature in prostate tissue have given surgeons a greater ability to monitor ice ball formation.
This has led to a greater ability to confirm adequate treatment of what should be frozen (the neurovascular bundles and apex) and what should not be frozen (external sphincter and the Denonvilliers’ fascia of the rectal wall).
“The misfortune of cryotherapy in the past has so colored our perception of current technology, I think it’s tempting not to look carefully at what really goes on with modern cryotherapy,” said Dr. Jones, associate professor of surgery (urology) at the Cleveland Clinic Lerner College of Medicine, which is part of Case Western Reserve University. At this point, he said, he is not advocating primary cryoablation over other treatments for prostate cancer, but stated that “it’s an area that merits careful consideration, and it is clearly an increasing part of the armamentarium in many academic and community practices.” Despite his research interest in cryoablation, he still performs many more radical prostatectomies and brachytherapy procedures for localized prostate tumors, he said.
It is unlikely that randomized trials comparing cryotherapy with radical prostatectomy and radiotherapy will be conducted, so urologists will have to rely on case series for outcomes data, he said.
Duke K. Bahn, MD, of the Prostate Institute of America in Ventura, Calif., called Dr. Jones’ study a “timely and a nice summary of clinical outcomes of cryoablation as a primary treatment for localized prostate cancer based on multicenter experiences. The number of patients in this study is substantial.” The only limitation, he said, is the relatively short follow-up period.
Dr. Bahn, who has conducted re-search on focal cryoablation of prostate tumors, said that in his personal experience with more than 1,000 patients over 10 years, the overall bDFS rates are similar in all risk groups. The finding by Dr. Jones of a bDFS rate of 75.3% in the high-risk group appears to be one of the advantages of cryoablation over other treatments. “This is due to the ability to extend the ice to-wards the peri-prostatic tissue, including the seminal vesicles in cases were they are proven to be involved,” Dr. Bahn said.
One of the new applications of cryo-ablation is a focal, targeted therapy, he added. “With a trend of down-ward migration of prostate cancer, we may over-diagnose and over-treat prostate cancer. As a compromise between doing nothing (watchful waiting or active surveillance) and something radical, a focal cryoablation would be an ideal compromise. Definitely, the patient selection methods and criteria should be carefully studied and discussed within the urologic community.”
