Cryosurgery For Localized Prostate Cancer After Radiation Failure "Safe and Effective" - Columbia Urologists

New York: PSA Rising, September 9, 2001. Cryosurgery after failed radiation for prostate cancer is now covered by Medicare for services performed after June 30, 2001. Medicare coverage applies only to patients after a failure of radiation therapy who meet one of the following conditions: disease Stage T2B (palpable tumor on one side of prostate only); Gleason score below 9, PSA below 8 ng/mL.

Is it a good option? Cryosurgery is often called "minimally invasive." A man can be home within 24 hours and he undergoes no major surgery, no weeks of radiation exposure nor implantation or radioactive pellets, no chemicals in the veins, no permanent or long-term hormonal blockade with loss of libido, muscle and bone weakness and anemia....

Cryosurgery has a corps of passionate and fully satisfied advocates; but until recently many urologists and patients too viewed it, especially for "second-chance" or salvage purposes, as a desperate measure, with uncertain survival rates and high rates of bad side effects.

A track record positive enough to convince Medicare was built up at leading institutions. The latest of a series of studies from Columbia College of Physicians and Surgeons, New York City appears next month in Journal of Urology. Columbia's Dr. Aaron Katz M. D. says their report "supports cryosurgery of the prostate as safe and effective treatment in patients in whom radiation therapy fails."

Cryosurgery destroys tissue by controlled freezing -- and it has taken decades for this control to be achieved. The object is to destroy both the cancerous and the normal prostatic cells. In 1968, Gonder and Soans introduced cryoablation of the prostate and achieved tissue necrosis (destruction). In the 1970's, Bonny reported his cryosurgical experience with an open-perineal approach on a couple of hundred patients. Bonny showed that cryosurgery patients had a probability of long-term survival equal to that seen in radical prostatectomy patients in each cancer stage.

However, a high rate of complications resulting from a lack of precise monitoring of the freezing process forced the abandonment of this technique. In 1988, interest revived with monitoring of the freezing process using real-time ultrasound. In 1994, Bahn and Lee reported improved technique with advanced transrectal ultrasound and advanced freezing technology coupled with improved radiology skills.

Patients can expect to go home in under 24 hours.

Like all treatments for prostate cancer, cryosurgery has side effects; and like any "salvage" procedure, these pile on top of side effects caused by the initial, failed therapy, in this case radiotherapy. Many urologists view salvage cryo as potentially "feasible" but less than highly desirable. Some, including the Columbia physicians, are much more optimistic, focusing on how new ly refined technique and equipment are enhancing cryosurgical results. The main engineering advance is a form of cryosurgery developed by Endocare in Irvine, CA, which combines cryosurgery with ultrasound and temperature monitoring and is said to improve safety and efficiency in the procedure.

In 1995, Dr. Gerald Chodak at the University of Chicago ran a small Phase II trial that found cryosurgery to be quite abysmally ineffective -- most of the patients (19 of 22, or 86%) reverted to a PSA level equal to or greater than 0.3 ng/mL (that is, their PSA returned as high what had been taken to indicate failure of the primary radiation therapy). "Complications occurred in 100% of the patients," Chodak's study said, "with 12 of 22 (55%) requiring at least one transurethral resection of sloughed, necrotic tissue,"

In June 1999 a technology assessment by the U.S. Agency for Health Care Policy and Research decided that more research was needed to find out long-term outcomes of cryosurgery in men who undergo the procedure after failure of radiation therapy for their prostate cancer. "Our preliminary results suggest," they said, " that the current cryosurgical technique used in men failing radiation therapy has a low probability of biochemical cure and a high complication rate."

Equipment and know-how have improved since then. Even so, patients who consider this procedure are wise to seek out experienced operators -- and to question them closely about Disease Free Survival -- i.e. with this procedure, what are your chances of not being seriously bothered again by prostate cancer in your lifetime? And what are the risks that you will suffer miserable after effects?

Columbia used the argon based CRYOCare system (Endocare, Inc, Irvine, California), From October 1997 to September 2000 Aaron Katz MD and others in the Urology section at Columbia treated 38 men with a mean age of 71.9 years with salvage cryosurgery for recurrent prostate cancer after failed radiation therapy. All patients had had biochemical disease recurrence, defined as an increase in prostate specific antigen (PSA) of greater than 0.3 ng./ml. above the post-radiation PSA nadir. When their PSA's rose, the men took biopsies, which showed positive for cancer. Pre-cryosurgery scan demonstrated no evidence that the cancer had spread to the bones.

Before cryosurgery, all the patients took 3 months of neoadjuvant androgen deprivation therapy. (Of note, although shrinking of prostate and tumor with hormone ablation is considered helpful and even essential for the cryotherapy, M. D. Anderson a few years ago concluded that hormonal therapy at time of the first, radiation therapy treatment made cryo outcomes worse).

Columbia's Latest Results

PSA NADIR (low point)	Number of patients	Percent of Patients
0.1 or less	31	81.5%
1 or less	5	13.2%
greater than 1 ng./mL.	2	5.3%

Biochemical recurrence-free survival calculated from Kaplan-Meier curves was 86% at 1 year and 74% at 2 years.

Complications reported by patients and/or observed by their doctors included rectal pain in 39.5% of cases, urinary tract infection in 2.6%, incontinence in 7.9%, hematuria (blood in urine) in 7.9% and swollen scrotum (from edema) in 10.5%.

PSA NADIR (low point)	Percent of Patients
rectal pain	39%
swollen scrotum	10.5%
incontinence	7.9%
blood in urine	7.9%
urinary tract infection	2.6%

The rate of rectourethral fistula, urethral sloughing and urinary retention was 0%.

These results, the Columbia urologists say, support cryosurgery of the prostate "as safe and effective treatment in patients in whom radiation therapy fails." Using the CRYOCare machine, they say, "resulted in a marked decrease in complications."

Not for Everyone

Patient selection is paramount in successful salvage cryotherapy. If you are the prospective patient, be realistic about what this procedure might be able to do for you. Medicare is not just mean is making payment contingent on PSA below 8 or Gleason below 9. At M. D. Anderson a few years ago, Dr. Anthony von Eschenbach found that "Patients failing initial radiation therapy with a PSA more than 10 ng/mL and Gleason score of the recurrent cancer more than or equal to 9 are unlikely to be successfully salvaged." And, he said, "patients failing initial hormonal therapy and radiation therapy are less likely to be successfully salvaged than patients failing radiation therapy only."

Another M. D. Anderson study found 72% of salvage cryo patients were left with erectile dysfunction, 73% had urinary incontinence and 67% had urinary obstruction. Those patient were treated between 1992 and 1995. Temperature monitoring equipment has improved the odds, but those findings must still be relevant.

At Crittendon Hospital, Michigan, which has the status of Lourdes among some prostate cancer patients, Duke K. Bahn, M.D and Fred Lee M.D. emphasize that cryosurgery "is highly operator dependent." In a detailed report of complications after first-line (not salvage) cryoablation, Bahn and Lee state that impotency (erectile dysfunction) is an expected side effect of cryotherapy. "It is due to the intentional freezing of tissue outside of the prostate gland to kill cancer cells that may have already spread beyond the prostate capsule," they say. "Our study showed only 15 % of patients gained potency (defined as a firm erection enough for vaginal penetration) and additional 23 % men claimed partial recovery. These numbers are essentially same when compared to the radiation and radical surgery reports. (1,2)."

Cryotherapy equipment designers aim to improve temperature monitoring during the procedure "to ensure effective treatment of the entire prostate gland with minimal risk of damage to adjacent tissues."

"Targeted cryosurgery continues to emerge as an option for prostate cancer patients," according to Thayne R. Larson, MD, Associate Professor of Urology, Mayo Clinic Graduate School of Medicine. "As such, it is critical to define the best possible methods of performing the procedure. Data from our basic science study clearly showed that the ability to monitor and precisely control the temperature plays a critical role in ensuring the cancer is destroyed while sparing the sensitive tissues which surround the gland."

Often, prostate cancer is not so cooperative -- and for the salvage therapy patient, boundaries are less than well defined. The best operators do not promise to work magic. One as experienced and cautious as Dr. Lee will, to help you try save your life, aim to spare only tissue which is cancer free.

by JACQUIE STRAX

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Related abstracts & reports:

J Urol 2001 Jun;165(6 Pt 1):1937-1941 Results of salvage cryoablation of the prostate after radiation: identifying predictors of treatment failure and complications. Chin JL, Pautler SE, Mouraviev V, Touma N, Moore K, Downey DB. Division Of Urology and Department Of Diagnostic Radiology, London Health Sciences Centre, University Of Western Ontario, London, Ontario, Canada.

"Salvage" Cryosurgery for Prostate Cancer - More Research Needed on Long-Term Survival June 22, 1999.

J Clin Oncol 1999 Aug;17(8):2514-2520 Patient selection for salvage cryotherapy for locally recurrent prostate cancer after radiation therapy. Pisters LL, Perrotte P, Scott SM, Greene GF, von Eschenbach AC. Department of Urology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

Endocare Announces National Medicare Coverage for Its Prostate Cancer Treatment Procedure February 1999

Urology 1995 Nov;46(5):676-680 Short-term outcomes after cryosurgical ablation of the prostate in men with recurrent prostate carcinoma following radiation therapy. Bales GT, Williams MJ, Sinner M, Thisted RA, Chodak GW. Department of Surgery, University of Chicago, Illinois, USA.

PATIENT-REPORTED COMPLICATIONS AFTER CRYOABLATION THERAPY FOR PROSTATE CANCER Duke K. Bahn, M.D. Crittenton Hospital, Rochester, MI