The Promise of Cryotherapy in Prostate Cancer

This is an expertly written summary of the experience with cryotherapy as primary treatment of prostate cancer and the rationale for proceeding toward more limited, organ-sparing approaches with this procedure as focal treatment for low-risk cancers. Growing evidence of overdetection and overtreatment in many men with low-risk tumors has resulted in the recognition that alternatives to conventional treatment strategies are needed. Observation, a laudable and appropriate approach, appeals to relatively few patients.

Focal therapy is conceptually an attractive option that may offer effective ablation of the detected cancer with diminished side effects, relative to radiation or surgery. A number of technologies with the potential to achieve these goals are available or under development, each with advantages for use in this setting. Thermal tissue ablative modalities include high-intensity focused ultrasound, cryotherapy, and radiofrequency ablation. Nonthermal approaches include photodynamic therapy and electroporation. While all these techniques may be effective, comparison of their side effects and limitations will prove difficult outside of well-defined clinical trials with clear criteria for patient selection and definition of endpoints.

Pretreatment Assessment

Accurate pretreatment assessment of tumor location and extent is necessary to confirm that subtotal gland treatment does not result in subtotal tumor treatment. It is not clear who should be treated with focal treatment and how they can be identified. As referenced in the current paper, retrospective studies of radical prostatectomy specimens have identified roughly 15% to 20% of men who have unilateral or unifocal tumors amenable to focal treatment.

Unfortunately, standard-template transrectal biopsy techniques, developed to diagnose cancer, perform poorly in accurately staging or localizing all sites of tumor. As confirmed by Barzell and others, 50% or more of suspected low-volume tumors will be discovered as either bilateral or with higher volume or grade when repeat prostate biopsy is performed using transperineal stereotactic mapping biopsy.[1] At present, this biopsy approach appears to represent the best means by which to evaluate each individual who might be considered for a clinical trial in an experimental treatment with focal therapy.

Appropriate Endpoints

Similarly, posttreatment endpoints remain to be defined. As focal cryoablation remains a new experimental treatment, evaluation should include repeat biopsy data in all subjects to confirm adequate tumor eradication at the site of treatment as well as the absence of progressive disease at other regions within the gland. Discrepant results will be expected, requiring means of interpreting outcomes when cancer is found outside the treatment zone.

The use of prostate-specific antigen dynamic changes such as the American Society for Therapeutic Radiology and Oncology (ASTRO) or Phoenix criteria, devised for total gland treatment using radiation, are not validated for use with focal treatment, and their application in that setting is unjustified. Repeat biopsy at 3 to 6 months following treatment would be an appropriate interval, based on prior studies of cryobiology. Urine sediment studies such as PCA3 may also prove useful but require validation. Standards with criteria for functional and quality-of-life assessment, adverse events, and cost need to be addressed along with other related details.

Conclusions

Focal therapy holds great promise for the future of prostate cancer care if it is applied appropriately. As trials are designed to assess these techniques, it is imperative that the urologic community work together to ensure that patients are appropriately selected, adequately treated, and undergo confirmatory posttreatment evaluation of outcomes. This is particularly critical in men with favorable tumor features, where an experimental therapy could adversely affect curability with more conventional therapies.

Disclosures:

Financial Disclosure:The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

References

1. Barzell WE, Melamed MR: Appropriate patient selection in the focal treatment of prostate cancer: The role of transperineal 3-dimensional pathologic mapping of the prostate-a 4-year experience. Urology 70(6 suppl):27-35, 2007.