Cryosurgery Results in 102 Prostate Cancer Patients at UCSF

April 1, 1996

MARINA DEL REY, Calif--Preliminary studies show that cryosurgical ablation of the prostate can be used to treat localized prostate cancer, resulting in negative post-treatment biopsies and undetectable serum PSA levels, reported Peter R. Carroll, MD, associate professor of urology and director, Urologic Oncology Program, University of California, San Francisco (UCSF).

MARINA DEL REY, Calif--Preliminary studies show that cryosurgicalablation of the prostate can be used to treat localized prostatecancer, resulting in negative post-treatment biopsies and undetectableserum PSA levels, reported Peter R. Carroll, MD, associate professorof urology and director, Urologic Oncology Program, Universityof California, San Francisco (UCSF).

However, potential candidates for the surgery should be informedthat the treatment is moderately morbid, equivalent in cost tostandard therapy, and very operator dependent, Dr. Carroll saidat a conference jointly sponsored by the UCLA School of Medicineand Clark Urological Cancer Center.

Dr. Carroll attributes the resurgent interest in cryosurgery toimprovements and increased expertise in percutaneous techniques,transrectal ultrasound, cryotechnology, and the science of cryobiology.He also said that prospective registration studies of cryotherapyare currently being undertaken, and are clearly needed to fullyevaluate the technology.

Results at UCSF

Dr. Katsuto Shinohara and Dr. Carroll have now performed morethan 150 cryosurgeries in prostate cancer patients, and Dr. Carrollreported on the results from the first 102 of these patients.

The mean age of the men was 68 years, preoperative PSA valuesaveraged 21.8 ng/mL, and Gleason scores had a mean value of 6.5.Forty-four patients had T1 and T2 lesions, and the remaining 58had more extensive disease (stage T3 or T4).

In the UCSF study, PSA values at 6 months postcryosurgery wereassessed in the 73 patients who received no hormone therapy followingthe procedure, and who did not have any evidence of nodal or othermetastatic disease. PSA was undetectable in 35 men (48%), between0.1 and 0.5 ng/mL in 22 (30%), and 0.5 or more in the remaining17 (22%).

"It turns out that if a patient had an undetectable PSA at6 months, he was likely to maintain that level, at least for the12 months we've followed up. These results may be better thanthose for radiation therapy," Dr. Carroll noted.

These findings emphasize the importance of analyzing PSA valuesfollowing surgery, to measure the success of the procedure, headded.

Postoperative biopsies were performed on 91 of the patients, 3to 6 months after cryosurgery, and 21 patients (23%) had residualcancer seen on one or more biopsies. The remaining 70 patients(77%) showed no evidence of tumor.

Dr. Carroll stressed that when PSA values and biopsy results wereanalyzed over time, evidence of a definite learning curve forthe procedure was seen. "In our most current series of patients,the positive biopsy rate was 8%, and more than 60% had undetectablePSAs," he said.

PSA values following cryosurgery were higher in those men withmore advanced disease (stage T3 and certainly stage T4), and inthose with high PSA values before the surgery, Dr. Carroll said.In all likelihood these patients harbored micrometa-static prostatecancer, he commented.

When analyzing the pattern of failure in the UCSF patients, recurrenceswere seen in the seminal vesicles, the base, and the apex of theprostate. No positive biopsies were seen in those patients withmidgland lesions.

"We probably need to rethink who we're treating with cryosurgery.Maybe the best candidates are those with mid-gland lesions anda low risk of extrapros-tatic disease," he said.

While cryotherapy is often viewed as an effective, low morbidityprocedure, Dr. Carroll said, the UCSF group saw many complicationsarise in their patients following cryosurgery.

Of patients who were potent before the procedure, 84% became impotent,although some may regain potency over time, he noted. Some ofthe other complications included penile numbness (10%), acuteincontinence (4%), epidi-dymitis (4%), urosepsis (3%), and prolongedperineal pain (3%).

The "Achilles heel" of the procedure, however, has beenthat 23% of the patients developed output obstructions requiringtransurethral resection (TUR). In addition, in patients who underwenta TUR to clear obstructions, 50% then experienced "at leaststress incontinence, so in fact, the incontinence rate was not3% to 4%, but more likely 12% to 13%," Dr. Carroll said.

The mean length of stay for radical prostatectomy patients wasgreater than for cryosurgery patients, he said. But when the costsof the disposables and the operating room equipment were addedin, overall costs for the two procedures were comparable.

UCSF researchers also compared measurements of 50 quality of lifedimensions between a group of 21 men who had radical prostatectomiesand 23 men who had cryoablation of the prostate.

Dr. Carroll noted that this was not a randomized study--thosein the cryo-therapy group were slightly older, and the radicalprostatectomies had been performed by a single surgeon.

"We wanted to see if cryosurgery was associated with improvedquality of life 6 months after treatment, compared to radicalprostatectomy. It turned out just the opposite," he said.

The study showed that social functioning, energy, health perception,and limitation of vigorous activities all favored surgery. Inaddition, patients who underwent surgery were less afraid of thediagnosis of cancer.

"If this procedure is to become standard therapy, or be usedin lieu of radical prostatectomy for defined disease, we needto decrease its morbidity and be sure that its efficacy standsthe test of time," Dr. Carroll concluded.

Cryosurgery Procedures at UCSF

At UCSF, patients with large prostate glands (greater than 50cc), or those with large tumors that have invaded the seminalvesicles, are placed on androgen deprivation therapy for 3 monthsprior to cryosurgery, to shrink the prostate, Dr. Peter Carrollsaid at a UCLA-sponsored urology conference (see story above).

This allows for more even distribution of the cryoprobes, thusavoiding steep temperature gradients between the probes, and alsoallows for increased space around the prostate, which protectsthe surrounding structures during freezing, he said.

Five cryoprobes are inserted into the prostate and turned on sequentially,so that the iceball (area of frozen tissue around the cryoprobe)extends through the prostate and prostatic capsule to the anteriorrectal wall.

Ultrasound monitoring is crucial, Dr. Carroll stressed, because,to achieve complete cyto-destruction, the tissue must reach atemperature of -22° C.

While most of the iceball is much colder than needed to kill thetissue, the edges (outer 2 to 3 mm) are not. This must be takeninto account, and the iceball extended somewhat beyond the boundariesof the prostate.