In Treating Localized Prostate Cancer the Efficacy of Cryoablation is Independent of DNA Ploidy Type

Abstract

While the prognostic value of DNA ploidy has been well established for radical prostatectomy, external beam radiation, brachytherapy and androgen deprivation therapy its role as a survival outcome predictor for prostate cancer patients treated with cryoablation has not yet been examined. Anecdotal evidence suggesting that cryoablation may be independent of DNA ploidy type led to the implementation of the current study. Retrospective analysis of data including flow digital cytometry was performed on 447 archival specimens taken from patients who had undergone cryosurgical ablation of primary prostate cancer. Five-year biochemical disease free survivals (bDFS) (defined as PSA thresholds of 0.5 and 1.0 ng/ml) were determined with Kaplan-Meier analysis. Patients were grouped according to DNA ploidy types then stratified by Gleason grade, risk group, pre-surgical PSA level, and disease stage.Mean and median age of the cohort was 65 and 64.6 years. Mean follow-up was 65.7 months. The DNA ploidy status of the population was found to be 59% diploid, 13% tetraploid, and 28% aneuploid. Using PSA < 1.0 ng/ml criterion, the bDFS rates for diploid, tetraploid, and aneuploid were 78%, 75%, and 79% respectively. The bDFS rates using a PSA < 0.5 ng/ml criterion were 67%, 59%, and 69% for diploid, tetraploid, and aneuploid groups. No significant outcome differences were found in stratified analysis. This investigation demonstrates that the efficacy of cryoablation is independent of DNA ploidy type.

The Combination of DNA Ploidy Status and PTEN/6q15 Deletions Provides Strong and Independent Prognostic Information in Prostate Cancer

“…Markedly higher rates-ranging from 39.7% to 74.8%-were mainly found in studies enriched for advanced (7,10,14,16,17,23,32) or high grade cancers (22,33). Some of the studies resulting in particularly low frequencies of nondiploid cancers had preselected for T1a or clinically localized cancers (7,8,13,16,20,34). Non-diploid DNA status was tightly linked to unfavorable cancer features, such as high Gleason grade, advanced tumor stage, and positive nodal stage.…”

“…Studies evaluating DNA ploidy in prostate cancer have come to varying conclusions. Some studies on 45-850 (mean 139) cancers have suggested a relevant prognostic impact of ploidy (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), while other studies on 33-447 (mean 122) cancers have failed to find significant associations (7,(20)(21)(22)(23)(24). Deletions affecting various chromosomal loci are a hallmark of prostate cancer.…”

Primary cryoablation for Gleason 8, 9, or 10 localized prostate cancer: Biochemical and local control outcomes from the Cryo OnLine database registry

“…[2] This has led to the suggestion that it may be preferentially useful for patients with high-grade disease. [3]…”

Cryoablation and cryolocalization in the management of breast disease

“…It is important to note that freezing injures not only individual cells at the time of therapy (direct damage) but also impairs the tissue as a whole by damaging the microcirculation (indirect damage) [8]. Unlike radiation, the ability of cryoablation to induce uniform necrosis is not dependent upon the nuclear characteristics of individual cells but rather on the exposure of the entire tumor volume to a lethal freezing process [9]. Cell survival during cryoablation not only depends on the freezing and thawing rates but, most importantly, upon the lowest temperature reached and the hold time at subzero temperatures [10].…”