Hemigland Cryoablation of Localized Low, Intermediate and High Risk Prostate Cancer: Oncologic and Functional Outcomes at 5 Years.

PURPOSE: We evaluated 5-year oncologic and functional outcomes of hemigland cryoablation of localized prostate cancer. MATERIALS AND METHODS: We reviewed the records of 160 consecutive men who underwent hemigland cryoablation of localized prostate cancer. Recurrent and/or residual clinically significant prostate cancer was defined as Grade Group 2 or greater on followup biopsy. A prostate specific antigen nadir plus 2 ng/ml according to the Phoenix criteria was used to define biochemical failure. Radical treatment was defined as any whole gland therapy. Treatment failure was defined as any radical and/or whole gland treatment, systemic therapy initiation, metastasis or prostate cancer specific mortality. The study primary end point was treatment failure-free survival. The secondary end points were survival free of biochemical failure, clinically significant prostate cancer and radical treatment. Followup biopsy and functional outcomes were also evaluated. Statistical analysis included the Kaplan-Meier method, and univariate and multivariable Cox and logistic regression with significance considered at p <0.05. RESULTS: Median patient age was 67 years, baseline prostate specific antigen was 6.3 ng/ml and followup was 40 months. A total of 131 patients (82%) had D'Amico intermediate (66%) or high risk (16%) prostate cancer. At 5 years the treatment failure-free survival rate was 85%, the biochemical failure-free survival rate was 62% and the survival rate free of clinically significant prostate cancer was 89%. Higher baseline prostate specific antigen independently predicted treatment failure (p <0.001), biochemical failure (p=0.048), recurrence and radical treatment (p <0.01). Grade Group 3 or greater independently predicted treatment failure (p=0.04). The metastasis-free survival rate was 100% at 5 years. Pad-free continence and potency (erections sufficient for intercourse) were retained in 97% and 73% of patients, respectively. There was no rectal fistula or mortality. CONCLUSIONS: Hemigland cryoablation of localized prostate cancer provides effective midterm oncologic outcomes with good continence and potency. Patients with higher baseline prostate specific antigen are at increased risk for biochemical failure, recurrent cancer and treatment failure.

Primary androgen deprivation (AD) followed by active surveillance (AS) for newly diagnosed prostate cancer (PC): A retrospective study.

BACKGROUND: Active surveillance (AS) is only recommended for Low-Risk prostate cancer (PC) with <34% biopsies positive. Studies describing the long-term outcome of men treated with androgen deprivation (AD) followed by AS are sparse. MATERIALS AND METHODS: One hundred two men were treated with 12 months of AD in a medical oncology clinic specializing in PC between 1998 and 2007 and were followed for a median of 7.25 years. The biopsy complete response rate after AD and the incidence of disease progression while on subsequent AS was assessed. Baseline age, D'Amico risk category, PSA velocity, percentage core biopsies, and prostate volume were evaluated as potential predictors of disease progression. RESULTS: D'Amico risk category for the 102 men: Low: n = 22, Intermediate: n = 30, and High: n = 50. Medians: Age 67.3, PSA 7.8, Gleason 3 + 4, >50% core biopsies positive, stage T1c. Seventy men had a clear biopsy and 31 of these had disease progression leading to additional treatment after a median of 52 months. D'Amico risk category of the 57 men with a positive biopsy after AD or disease progression on AS was: Low: n = 4 (18%), Intermediate: n = 16 (53%), and High: n = 37 (74%). No PC deaths occurred. Three men had clinical progression. In stepwise logistic regression analysis only higher D'Amico risk category and lower prostate volume predicted disease progression. CONCLUSIONS: Despite a high prevalence of ≥50% core biopsies positive at baseline, AD induces durable remissions in most men with Low-Risk and about half with Intermediate-Risk PC.

Primary Whole-gland Cryoablation for Prostate Cancer: Biochemical Failure and Clinical Recurrence at 5.6 Years of Follow-up.

We retrospectively evaluated complications and functional and oncologic outcomes of 94 consecutive men who underwent primary whole-gland cryoablation for localized prostate cancer (PCa) from 2002 to 2012. Kaplan-Meier and multivariable Cox regression analyses were performed using a landmark starting at 6 mo of follow-up. In total, 75% patients had D'Amico intermediate- (48%) or high- (27%) risk PCa. Median follow-up was 5.6 yr. Median time to prostate-specific antigen (PSA) nadir was 3.3 mo, and 70 patients reached PSA <0.2ng/ml postcryoablation. The 90-d high-grade (Clavien Grade IIIa) complication rate was 3%, with no rectal fistulas reported. Continence and potency rates were 96% and 11%, respectively. The 5-yr biochemical failure-free survival (PSA nadir+2ng/ml) was 81% overall and 89% for low-, 78% for intermediate-, and 80% for high-risk PCa (p=0.46). The median follow-up was 5.6 and 5.1 yr for patients without biochemical failure and with biochemical failure, respectively. The 5-yr clinical recurrence-free survival was 83% overall and 94% for low-, 84% for intermediate-, and 69% for high-risk PCa (p=0.046). Failure to reach PSA nadir <0.2ng/ml within 6 mo postcryoablation was an independent predictor for biochemical failure (p=0.006) and clinical recurrence (p=0.03). The 5-yr metastases-free survival was 95%. Main limitation is retrospective evaluation. Primary whole-gland cryoablation for PCa provides acceptable medium-term oncologic outcomes and could be an alternative for radiation therapy or radical prostatectomy. PATIENT SUMMARY: Cryoablation is a safe, minimally-invasive procedure that uses cold temperatures delivered via probes through the skin to kill prostate cancer (PCa) cells. Whole-gland cryoablation may offer an alternative treatment option to surgery and radiotherapy. We found that patients had good cancer outcomes 5 yr after whole-gland cryoablation, and those with a prostate-specific antigen value ≥0.2ng/ml within 6 mo after treatment were more likely to have PCa recurrence.

Focal cryoablation of prostate: a review.

Current treatment options for men with early localized prostate cancer are either some form of radical therapy or active surveillance. Radical therapy is usually associated with significant adverse effects that might jeopardize a man's quality of life. Some observers believe that PSA screening has resulted in the over diagnosis and over treatment of prostate cancer. Many men are being diagnosed with an early stage, small volume, unifocal or unilateral prostate cancer but are reluctant to accept watchful waiting or active surveillance. Focal cryoablation is the less than complete ablation of the gland with ice. Based on review of the limited amount of material available in the current literature, focal cryoablation can provide acceptable cancer control while preserving sexual potency and urinary continence. Focal cryoablation may fill a void in the therapeutic options available to patients with unifocal or unilateral prostate cancer who have a strong desire to maintain their quality of life.

Focal prostate cryoablation: initial results show cancer control and potency preservation.

BACKGROUND: Focal prostate cryoablation is the less-than-complete ablation of the gland with ice. Known tumor is ablated aggressively, whereas contralateral prostate tissue and surrounding structures are spared. This method offers targeted local cancer control aiming at sexual potency and urinary continence preservation in patients whose prostate cancer is believed to be unilateral. PATIENTS AND METHODS: Patients who had a strong desire for preservation of sexual function and continence were informed of focal prostate cryoablation as an investigational treatment option for clinically organ-confined, unilateral tumor identified by color Doppler ultrasonography and confirmed by targeted and systematic biopsy. Only stage, not preoperative serum prostate specific antigen concentration (PSA) or tumor differentiation, was considered a potential contraindication. Thirty-one men with a mean age of 63 years underwent the procedure. Follow-up consisted of PSA measurement every 3 months for 1 year and every 6 months thereafter, with biopsies at 6 months and 1, 2, and 5 years and following any three consecutive PSA rises. Potency was determined with a patient questionnaire filled in without the physician present. RESULTS: At a mean follow-up of 70 months, biochemical disease-free status, according to the ASTRO definition, was maintained by 92.8% of patients (26/28) and a 96.0% negative-biopsy rate (24/25) was observed. The one biopsy-positive patient was subsequently treated with full-gland cryoablation and remains disease free. Potency was maintained by 48.1% of patients (13/27) and another 40.7% (11/27) were potent with oral pharmaceutical assistance, yielding a total potency-preservation rate of 88.9%. No complications were observed. CONCLUSION: Focal cryoablation can provide biochemical and local control of prostate cancer while preserving potency and continence. Further investigation is needed.

Salvage cryosurgery for recurrent prostate cancer after radiation therapy: a seven-year follow-up.

Cryosurgery of the prostate presents as an efficient therapy following failed radiation therapy. We report on a 7-year retrospective analysis evaluating the morbidity adn biochemical disease-free survival(bDFS) of this therapy. Between 1993 and 2001, 59 patients who had been previously treated with radiation therapy and had rising serum prostate-specific antigen(PSA) values underwent salvage cryoablation of the prostate for localized, histologically proven, recurrent prostate cancer. Serial serum PSA testing was performed, and biopsies were taken at 6, 12, and 24 months, and again at 5 years, and any time the PSA rose above 0.5 ng/mL. Patients were stratified along clinical parameters. The combined postsalvage bDFS rate using a PSA cutoff of 0.5 ng/mL was 59% and 69% with a 1.0 ng/mL PSA cut off. Using a PSA threshold of 0.5 ng/mL as evidence of biochemical recurrence, 61%, 62%, and 50% of patients with <4 ng/mL, 4-10 ng/mL, and > 10 ng/mL PSA, respectively, remain biochemically relapse free at 7 years. A threshold of 1.0 ng/mL yielded a disease-free status of 78%, 74%, and 46% respectively. Patients biopsies showed no evidence of residual or recurrent disease. Improved survival rates and no known latent complications indicate cryosurgery is a promising form of treatment for radiation-resistant prostate cancer. This 7-year analysis shows a promising validation of cryosurgery as an efficacious treatment modality for locally confined T1-T3 prostate cancer following primary radiation therapy failure.

In treating localized prostate cancer the efficacy of cryoablation is independent of DNA ploidy type.

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.

Targeted cryoablation of the prostate: 7-year outcomes in the primary treatment of prostate cancer.

The efficacy and safety of the long-term experience with targeted cryoablation of prostate cancer (TCAP) at a community hospital is retrospectively reviewed. A series of 590 consecutive patients who underwent TCAP as primary therapy with curative intent for localized or locally advanced prostate cancer from March 1993 to September 2001 were identified. Patients were stratified into 3 risk groups according to clinical characteristics. Biochemical disease-free survival (bDFS), post-TCAP biopsy results, and post-TCAP morbidity were calculated and presented. The mean follow-up time for all patients was 5.43 years. The percentages of patients in the low-, medium-, and high-risk groups were 15.9%, 30.3%, and 53.7%, respectively. Using a prostate-specific antigen (PSA)-based definition of biochemical failure of 0.5 ng/mL, results were as follows: (1) the 7-year actuarial bDFS for low-, medium-, and high-risk patients were 61%, 68%, and 61%, respectively; (2) the bDFS probabilities for a PSA cutoff of 1.0 ng/mL for low-, medium-, and high-risk patients were 87%, 79%, and 71%, respectively; and (3) the bDFS probabilities for low-, medium-, and high-risk patients using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical failure (3 successive increases of PSA level) were 92%, 89%, and 89%, respectively. The rate of positive biopsy was 13%. After a positive biopsy, 32 patients underwent repeat cryoablation. For those patients who underwent repeat cryoablation, 68%, 72%, and 91% remain bDFS using definitions of 0.5 ng/mL, 1.0 ng/mL, and the ASTRO criteria, respectively, after a mean follow-up time since repeat cryoablation of 63 months. The rates of morbidity were modest, and no serious complications were observed. TCAP was shown to equal or surpass the outcome data of external-beam radiation, 3-dimensional conformal radiation, and brachytherapy. These 7-year outcome data provide compelling validation of TCAP as an efficacious treatment modality for locally confined and locally advanced prostatic carcinoma.