Salvage Cryotherapy for Prostate Cancer Studied at M.D. Anderson

ORLANDO--Treatment of recurrent prostate cancer, whether by prostatectomyor chemotherapy, has not yielded very effective or long lastingresults. Many patients now ask about cryotherapy, in the hopesof better effectiveness and/or improved quality of life (lessincontinence and less chance of impotence). However, urologistshave been reluctant to use salvage cryosurgery for prostate cancerpatients after radiation or hormonal therapy, because the outcomeand quality of life data were simply not there, Louis L. Pisters,MD, said at the American Urological Association meeting earlierthis year.

Now, research from The University of Texas M.D. Anderson Cancer,where Dr. Pisters is assistant professor of urology, has identifieda subset of patients likely to benefit from salvage cryotherapy,although they would also likely be candidates for standard prostatectomy.

The study also provides some of the first data on complicationsafter salvage cryo-therapy from the patient's perspective, ratherthan physician-directed questioning, he said.

Dr. Pisters and his colleagues reviewed their experience withsalvage cryotherapy in 145 patients treated between 1992 and 1995,to define a group of patients most likely to show persistentlyundetectable PSA levels after the procedure.

They considered several pretreatment factors as possible predictorsof biochemical recurrence: stage/grade at initial diagnosis, typeof prior therapy, stage/grade of local recurrence, number of positivebiopsy cores at recurrence, precryother-apy PSA, prior transurethralresection of the prostate, and time interval between initial diagnosisand recurrence.

Three factors were found to be important predictors of PSA recurrence:pretreatment PSA, Gleason grade at the time of recurrence, andtime interval between initial diagnosis and recurrence. "APSA under 10 ng/mL in radiation failures and a PSA less than 5ng/mL in patients failing hormonal therapy were associated witha higher rate of PSA cure," he said.

In the group treated first with radiation, only one patient witha PSA greater than 15 ng/mL did not have a biochemical recurrenceafter salvage cryotherapy, while in those who failed hormonaltherapy, salvage cryotherapy did not achieve biochemical curein any patients with a pretreatment PSA greater than 5 ng/mL.

"Patients with a Gleason grade of 9 to 10 at recurrence hada statistically higher frequency of subsequent biochemical failure,"he added.

Patients who recurred more than 6 years after initial diagnosishad the worst biochemical failure rates after cryother-apy, independentof the pretreatment PSA or grade of the recurrence. Dr. Pistersattributes these failures to the development of new aggressivetumor or to inadequate initial treatment.

These data suggest that patients treated with primary radiationtherapy should be followed closely, he said. "If you waituntil the PSA rises above 10 ng/mL, you won't have a great shotat salvage."

Quality of Life Findings

In another study, Dr. Pisters sent a modified UCLA/RAND Qualityof Life questionnaire--an instrument he claims is a "muchmore sensitive mechanism than physician chart review"--to150 patients who underwent salvage cryother-apy between July 1992and April 1995. The study had an unusually high response rateof nearly 75%, suggesting that patients are quite interested inquality of life issues, Dr. Pisters pointed out.

Using any leakage as the stringent definition of incontinence,a criterion that patients consider important, he argued, 73% ofrespondents said they were incontinent. Use of a urethral warmingcatheter brought the incontinence rate down only to 65%, suggestingthat the device only mildly reduces incontinence.

Recently, cryosurgery has been modified to incorporate a doublefreeze-thaw cycle, a technique believed to better eradicate cancer.The downside is that this technique confers higher impotence rates,a complication confirmed in this series.

"While the double-freeze technique may improve tissue destructionat the periphery of the zone of freezing, it probably increasesdamage at the neurovas-cular bundle," Dr. Pisters explained.Even so, he added, potency is not a major concern of patientsconsidering salvage cryotherapy. Only 46 of 112 respondents saidthey were potent before undergoing salvage cryosurgery.

"The real challenge in the salvage arena is to lower therisk of complications without sacrificing cancer control,"he said. So far, Dr. Pisters, working with incontinence expertEdward McGuire, also at M.D. Anderson, has been able to minimizeincontinence in patients treated with salvage prostatectomy byoffering patients a modified continent reconstruction. However,he added, "I am not sure how we could modify cryosurgerysimilarly to reduce incontinence rates."

If salvage cryotherapy is being considered, Dr. Pisters advisessharing quality of life data with patients so that they can makean informed choice.

Even though this study found a high rate of complications withsalvage cryo-therapy, Dr. Pisters pointed out that recent publisheddata indicate that the incontinence following standard salvageprostatectomy is serious enough to require some 58% to 65% ofpatients to use urinary pads.

"These series used retrospective chart review to assess incontinence,"he said. "An even higher incontinence rate might be revealedif a similar patient-oriented quality-of-life questionnaire wereused in salvage prostatectomy patients."

At a minimum, Dr. Pisters recommends more studies with carefulpatient-directed assessment of quality of life so that competingsalvage therapies can be compared head to head.