Cryotherapy is a viable, minimally invasive option agaist aggressive tumors


Chicago--As the new horse at the track, cryotherapy is struggling to show its stride as a viable, effective treatment option for early prostate cancer.

"Cryotherapy is coming up from behind," James Lugg, MD, assistant clinical professor at the University of Colorado, Denver, told participants at the Windy City Shoot-Out, a debate-style conference held in Chicago.

Speaking on the advantages of cryotherapy, Dr. Lugg pointed out the fear that patients have of radical surgery and radiation therapy and presented cryotherapy as an opportunity to offer fearful patients a treatment that is truly minimally invasive.

"I would argue that in high-stage, high-risk patients and patients with obstructive symptoms, cryotherapy will play a unique treatment role," he said.

He based his assertion on the ability of cryotherapy to kill cells with an aggressive phenotype, which may confer a survival advantage. Unlike radiation therapy, to which aggressive tumors respond poorly, the efficacy of cryotherapy is independent of DNA ploidy, Dr. Lugg said. Another advantage of cryotherapy is its ability to improve obstructive symptoms in some patients treated for their cancer, whereas the use of seeds in the same patient may worsen these symptoms and may lead to significant morbidity.

Current cryotherapy procedures, which destroy cell membranes by freezing them to –40° C, have greatly improved from first-generation techniques, which were associated with injury to the prostate and adjoining structures.

"Problems with the early technology made practitioners apprehensive about this [cryotherapy]," said Dr. Lugg.

Evolved cryo improves results

With the evolution of technologies that allow for a rapid freeze and slow thaw, the creation of customized kits to ensure appropriate technique, and the development of expert paradigms to standardize treatment, cryotherapy is showing impressive results.

In the study that put cryotherapy on the map, Donnelly et al reported that 75% of patients with low-risk disease, 89% with moderate-risk disease, and 76% with high-risk disease achieved biochemical disease-free control at 5 years with a PSA cutoff of <1.0 ng/mL (Urology 2002; 60:645-9).

Using the American Society for Therapeutic Radiology and Oncology definition of biochemical disease-free control, Bahn and colleagues reported control rates of 92%, 89%, and 89% in low-, moderate-, and high-risk patients, respectively (Urology 2002; 60[suppl 1]:3-11).

More recent retrospective data with a longer follow-up of 9 years using a more restricted PSA definition of biochemical control of <0.5 ng/mL found a disease-free rate of 88% in low-risk disease, 74% in moderate-risk disease, and 50% in high-risk disease, Chinn and colleagues reported at the 2005 International Prostate Cancer Update in Vail, CO.

Using a more liberal definition of PSA of <2.0 ng/mL, retrospective results of another study with 10-year follow-up showed 85% biochemical disease-free survival, Derrick et al reported at this year's AUA Southeastern Section annual meeting in Charleston, SC.

How is success measured?

One problem highlighted by these studies is the need to develop criteria to measure success with cryotherapy.

For Dr. Gregory Merrick, medical director of the Schiffler Cancer Center at Wheeling (WV) Hospital, the ASTRO definition of biochemical control to measure the efficacy of cryotherapy is not a sufficient measure and is, in fact, inappropriate, in part "because it results in such widely divergent measures of success."

Citing the data from the Bahn study, Dr. Merrick pointed out that, although biochemical progression-free survival was obtained in 92% of low-risk patients using the ASTRO PSA definition, it was achieved in only 61% when a PSA cutoff of 0.5 ng/mL was used.

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