THE UNIVERSITY OF TEXAS
To: The Honorable Charles E. Grassley, Iowa
Special Committee an Aging
United States Senate
CONGRESSIONAL HEARINGS ON PROSTATE CANCER
Testimony by Richard J. Babaian, M.D.The University of Texas M.D. Anderson Cancer Center
The Potential Role of Cryosurgery as a Treatment Alternative for
Cryosurgery, or freezing of the prostate, was first reported by Soanes and Gonder in 1964. Thereafter, several other investigators in the 1970s employed this technique to treat prostate cancer. In this era, cryoablation of the prostate was achieved by circulating liquid nitrogen through probes that were designed for placement intraurethrally or transperineally. Although the extent of tumor destruction was most impressive, the delivery system was cumbersome and did not allow the operator to control precisely the extent of the freezing process, frequently resulting in extensive damage to the surrounding tissues. This, therefore, resulted in severe complications such as urethrocutaneous and urethrorectal fistulas, as well as prolonged intraurethral tissue sloughing with urinary obstruction. Despite its promise as a method of destroying prostate tissue, the early technique of cryoablation was abandoned because of its associated morbidity. The mechanism by which cryosurgery produces tissue destruction is intracellular dehydration, toxic electrolyte concentration, crystallization with secondary membrane rupture, denaturation of proteins, thermal shock and vascular stases.
Modern Era of Cryosurgery
In 1992, there was a reemergence of interest in the application of cryoablation of the prostate because of a series of technical advances which modernized the procedures for cryoablation. In the late 1980s, transrectal ultrasonography of the prostate became wide-spread with urologists becoming adept at prostate imaging and ultrasound-guided biopsies of this organ. As a consequence of the ultrasound technology, the procedure for cryoablation could be performed with real-time visualization of the prostate and surrounding structures. The resolution of this technology allowed safe and accurate placement of cryoprobes directly into the prostate. In the early 1990s, Onik and Associates demonstrated that the extent of freezing and consequently tissue destruction could be monitored and precisely controlled employing transrectal ultrasound. This was possible because of the ice ball phenomenon which resulted in a striking acoustic image. Therefore, as a direct consequence of modem ultrasound technology, cryoablation could be performed with less risk of the severe complications which led to its abandonment in the 1960s and 1970s. In addition to the technological improvements in ultrasound, advances have also occurred in percutaneous instrumentation (needles, guide wires, dialators, and sheaths) resulting in marked improvement of transperineal insertion of the temperature probes into the prostate. As previously mentioned, the initial cryosurgery units were cumbersome and have bean replaced by more innovative systems which can circulate liquid nitrogen or argon in up to eight slender probes at individually controlled rates. Temperature monitoring has also been recently introduced to facilitate the monitoring of the freezing process.
A Summary of Recent Clinical Experience
with Cryoablation of the Prostate
Our experience at The University of Texas M.D. Anderson Cancer Center with patients undergoing salvage cryotherapy of the prostate was recently published in the March, 1997 issue of The Journal of Urology. Short-term PSA follow-up in our patient population revealed that 31 percent of patients have a persistently undetectable PSA. Patients who had a local recurrence following radiation therapy and who were treated with a double freeze-thaw cycle of cryoablation had a 93 percent negative biopsy rate six months following cryoablatlon. This was significantly better than the negative biopsy rate of 71 percent in those men who were treated with only a single freeze-thaw cycle of cryoablation. In the 150 patients we reported, there were no operative deaths and no bleeding that required transfusion. There was a 1 percent incidence of fistula formation in this pre-treated group of men with a 3 percent incidence of ostitis pubis, a 1 percent incidence of prostatic abscess formation, and a 17 percent rate of urinary obstruction requiring transurethral prostatectomy. The major complications of salvage cryotherapy reported by patients who responded to a questionnaire were urinary incontinence occurring in 73 percent, impotency in 72 percent, obstructive symptoms in 67 percent, and severe perineal pain in 8 percent.
In a smaller group of men treated at The University of California in San Diego following relapse alter radiation therapy, 86 percent of the men were found to have negative biopsies 3 and 6 months following cryoabablation. A serum PSA of less than 0.5 ng/ml was reported in 40 percent of these men. The three-month positive biopsy rate in men undergoing cryoablation for radiation therapy failure reported by Onik, Miller, and Cohen from Allegheny General Hospital was 27.3 percent.
Primary Therapy of Localized Prostate CancerUsing Cryoablation
A preliminary study reported by Shinohara and Associates from The University of California at San Francisco reveals an undetectable PSA at 6-months in 48 percent of patients and a 70 percent negative post-cryotherapy biopsy rate. Excluding impotence, they reported an overall complication rate of 51 percent. The two most common symptoms were urinary obstruction requiring transurethral resection in 23 percent and penile numbness in 10 percent. It is important to note that the incidence of incontinence in this group of men treated with primary cryotherapy was only 4 percent. A report from The University of California at San Diego with short-term follow-up for patients with localized cancer of the prostate who have received cryoablation reveals that approximately 40 percent of patients have PSAs less than 0.5 ng/ml which is exceedingly low and that the negative biopsy rate in patients undergoing cryoablation as their primary form of treatment was 86 percent. In a report on primary cryotherapy for men with localized prostate cancer using adjuvant hormonal therapy and temperature monitoring, Lee and Associates from Crittenton Hospital report a positive biopsy rate of 3.3 percent one-year following cryotherapy. They also report that one-half of the patients with negative biopsies had an undetectable PSA. Approximately 80 percent of all the patients with negative biopsies had a PSA less than or equal to 0.5 ng/m1. The complication rates reported at one year in their 347 patients included an operative mortality rate of 0 percent, a 0.33 percent urethral-rectal fistula rate, an incontinence rate of 0.33 percent, with a 3.2 Percent incidence of outlet obstruction. In an unpublished update of their results the distribution of failures by pre-operative PSA levels reveals that 8 percent of men with a PSA of less than 4 have failed. The failure rates in men with a pre-treatment PSA between 4.1 and 10 and greater than 10 were 11 percent and 23 percent respectively. In an unpublished report presented at the Endourology World Congress in September of 1997, Orihuela and Associates from The University of Texas Medical Branch at Galveston reported a comparison of the results in 167 consecutive patients with localized prostate cancer who were treated between July, 1992 and April, 1996 by cryosurgery, radical prostatectomy, and radiation therapy.
This preliminary data at 24 months of follow-up shows that the disease-free survival measured by PSA was comparable for radical prostatectomy and cryosurgery (78 percent versus 74 percent, respectively) and was superior to the group receiving radiation therapy (51 percent). These investigators reported that significant complications were more frequently seen in men undergoing radical prostatectomy.
I believe that there is indisputable evidence that freezing destroys cancer cells. The modern techniques of percutaneous instrumentation and ultrasound have been readily adapted for use in cryosurgery of the prostate. There is considerable potential that the use of temperature monitoring which has only recently become available will enhance the treatment outcomes in patients who elect to undergo cryosurgery. While the complication rate for cryosurgery following radiation therapy is formidable, it appears to be considerably lower when used as the primary treatment modality. While the preliminary results with primary cryotherapy are encouraging, clinical trials and long-term follow-up are required before the exact role of this treatment modality for localized prostate cancer can be determined.
Richard J. Babaian, M. D.
Professor of Urology -
Blanche Bender Professor in Cancer Research
The University Texas
M. D. Anderson Cancer Center
1515 Holcombe Boulevard
Urology Department, Box I 10
Houston, Texas 77030
After completing a urology residency at The University or North Carolina, he completed a 3 year fellowship in the field of Urologic Oncology. He has practiced urologic oncology exclusively for the last 17 years. Dr. Babaian has authored or co-authored over 120 scientific publications the majority of which focus on prostate cancer. He has a wide range of experience in the early detection, diagnosis, staging and management of prostate cancer. He is experienced in the technique of cryosurgery and has utilized this modality in the treatment of prostate cancer both as primary therapy and as salvage following radiation therapy. M.D. Anderson Cancer Center, where Dr. Babaian has spent the last 13 years of his career, has extensive experience with cryosurgery. In excess of 200 procedures have been accomplished at that institution; approximately 25% of which were performed personally by Dr. Babaian.