John C. Rewcastle

Salvage Prostate Cryoablation: Initial Results From the Cryo On-Line Data Registry

PURPOSE We report contemporary outcomes of salvage cryoablation at a large number of centers which have participated in the COLD (Cryo On-Line Data) Registry. MATERIALS AND METHODS A secure online database was developed to collect data for patients undergoing prostate cryoablation. Kaplan-Meier analysis was performed with biochemical failure defined using the American Society of Therapeutic Radiology and Oncology, and the Phoenix definitions. RESULTS Data from 279 patients who had undergone salvage cryoablation were entered. Average patient age was 70.0 +/- 7.1 years. Pretreatment prostate specific antigen was 7.6 +/- 8.2 ng/ml and Gleason score was 7.5 +/- 1.1 (median 7). Patients were followed for 21.6 +/- 24.9 months and 47 were followed longer than 5 years. The 5-year actuarial biochemical disease-free rates were 58.9% +/- 5.7% (American Society of Therapeutic Radiology and Oncology) and 54.5% +/- 4.9% (Phoenix). As predicted based on the preservation of some prostatic tissue, 83% +/- 3.5% of patients had a detectable prostate specific antigen 0.2 ng/ml or greater at 5 years. Positive biopsies were observed in 15 of the 46 patients (32.6%) who underwent prostate biopsy after salvage cryotherapy. The incontinence rate (requiring pad use) was 4.4%. The rectal fistula rate was 1.2% and 3.2% of patients underwent transurethral prostate resection to remove sloughed tissue. CONCLUSIONS Biochemical and local control rates support the use of salvage cryoablation for localized recurrence following failed radiation therapy. Efforts to continue to minimize these complications and to improve disease control in patients with persistent cancer following definitive radiotherapy should continue.

Prospective trial of cryosurgical ablation of the prostate: five-year results

OBJECTIVES To determine in a prospective pilot study the safety and efficacy of cryosurgical ablation for localized prostate carcinoma. METHODS A total of 87 cryosurgical procedures were performed on 76 consecutive patients between December 1994 and February 1998. All patients had histologically proved adenocarcinoma of the prostate, with prostate-specific antigen (PSA) readings of less than 30 ng/mL. Clinical evaluations, PSA determinations, and patient self-reported quality-of-life questionnaires (functional assessment of cancer treatment-prostate; FACT-P) were used to determine biochemical and clinical disease-free status and complications. Patients had a mean follow-up of 50 months (minimum 36). RESULTS Follow-up biopsies were performed in 73 patients, and 72 were negative for malignancy after one or more treatments. Ten patients required two treatments and 1 patient required three treatments. The 5-year overall and cancer-specific survival rate was 89% (95% confidence interval, 83% to 97%) and 98.6% (95% confidence interval, 96% to 100%), respectively. The undetectable PSA rate (less than 0.3 ng/mL) for low-risk patients (n = 13) was 60% at 5 years; for moderate-risk patients (n = 23), it was 77%, and for high-risk patients (n = 40), 48%. The corresponding percentage of patients with a PSA level less than 1.0 ng/mL at 5 years was 75%, 89%, and 76%. Sloughing occurred in 3 patients (3.9%), incontinence in 1 (1.3%), and testicular abscess in 1 (1.3%). At 3 years, 18 (47%) of 38 patients capable of unassisted intercourse at the time of cryosurgery had resumed sexual intercourse, 5 spontaneously and 13 with sildenafil or prostaglandin. CONCLUSIONS The results of this prospective evaluation show cryosurgery to be both a safe and an effective option in the treatment of localized prostate cancer.

Focal Cryosurgery Followed by Penile Rehabilitation as Primary Treatment for Localized Prostate Cancer: Initial Results

The study reported here was undertaken to assess medium short-term efficacy of focal cryoablation as primary therapy for localized prostate cancer and to determine the rate of morbidity in patients who undergo this treatment. Patients were treated with focal cryoablation with argon cryoprobes under ultrasonographic visualization with temperature monitoring. Men who were potent at the time of intervention were encouraged to use a vacuum erectile dysfunction device on a regular basis after treatment. Incontinence was defined as any urine leakage regardless of the number of pads worn (if any). Potency was defined as the ability to achieve an erection sufficient to complete intercourse with or without oral pharmaceuticals. Biochemical failure was defined as 3 successive rises in serum prostate-specific antigen (PSA) concentration. A total of 60 consecutive patients were treated. Mean patient age was 69.0 years; mean PSA was 7.2 ng/mL, median Gleason score was 6, and median stage was T1c. Before treatment was initiated, all patients were continent and 72.7% were potent. Mean follow-up for the entire population was 15.2+/-7.4 months. Of those patients who were continent before receiving treatment, 3.6% were incontinent at 6 months, but none used any absorbent pads. At last follow-up, 80.4% of patients were biochemically disease free; mean time to failure was 3.5 months among those for whom treatment failed. The positive biopsy rate after first treatment was 23.3%, and mean time to failure was 12.0 months. Of those who underwent a second focal cryoablation procedure after positive biopsy, 66% were subsequently cancer free. All patients who were potent after the first cryoablation procedure regained their potency after the second cryoablation procedure. Focal cryoablation combined with penile rehabilitation as primary treatment for localized prostate cancer is a minimally morbid procedure with acceptable morbidity and the potential for retreatment of a patient if cancer is subsequently detected. Further study is warranted.

Whole Gland Primary Prostate Cryoablation: Initial Results From the Cryo On-Line Data Registry

PURPOSE We report the largest data set to date to our knowledge regarding outcomes for primary whole gland prostate cryoablation. MATERIALS AND METHODS The COLD (Cryo On-Line Data) Registry consists of case report forms obtaining pretreatment and posttreatment information for patients undergoing whole gland prostate cryoablation. A total of 1,198 patients were stratified into low, intermediate and high risk groups. Biochemical success was defined according to the traditional American Society for Therapeutic Radiology and Oncology definition (3 increases) and the newer (Phoenix) definition (nadir +2). Biopsy was performed at physician discretion but most commonly for cause if a patient had an increasing or suspicious prostate specific antigen. RESULTS Average patient age was 69.8 +/- 7.5 years. Pretreatment prostate specific antigen was 9.6 +/- 8.6 ng/ml and median Gleason sum was 7 (range 4 to 10). Patients were followed for 24.4 +/- 25.9 months with 136 having minimum 5-year data. The 5-year biochemical disease-free status for the entire population was 77.1% +/- 2.1% (American Society for Therapeutic Radiology and Oncology) and 72.9% +/- 2.1% (Phoenix). Five-year American Society for Therapeutic Radiology and Oncology biochemical disease-free status was 84.7% +/- 4.5%, 73.4% +/- 4.3% and 75.3% +/- 3.7% for the low, moderate and high risk groups, respectively. Using the Phoenix definition the biochemical disease-free status was 91.1% +/- 2.9%, 78.5% +/- 3.6% and 62.2% +/- 4.9%, respectively. As predicted based on intentional preservation of some prostatic tissue, 72.5 +/- 1.8% had a detectable prostate specific antigen 0.2 ng/ml or greater at 5 years. Biopsy after cryotherapy was positive during empiric without cause biopsy in 30 of 207 patients (14.5%), and the highly selected group biopsied based on suspicion of treatment failure due to abnormal or increasing prostate specific antigen had positive results in 38.0% (49 of 129). The rectal fistula rate was 0.4% and incontinence was 4.8% with 2.9% of patients using pads. Intercourse was reported by 25.2% but only 8.8% without pharmaceutical or device assistance. CONCLUSIONS Whole gland cryoablation, practiced in a spectrum of academic and community users, maintains efficacy and morbidity similar to that of single center reports.

High-intensity focused ultrasound for prostate cancer: comparative definitions of biochemical failure.

To compare the specificity and sensitivity of different definitions of biochemical failure in patients treated with high‐intensity focused ultrasound (HIFU) for prostate cancer, to identify the most accurate predictor of clinical failure after HIFU.

A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer

Localized prostate cancer can be treated several different ways, but head‐to‐head comparisons of treatments are infrequent. The authors of this report conducted a randomized, unblinded, noninferiority trial to compare cryoablation with external beam radiotherapy in these patients.

Magnetic Resonance Imaging–Transectal Ultrasound Image-fusion Biopsies Accurately Characterize the Index Tumor: Correlation with Step-sectioned Radical Prostatectomy Specimens in 135 Patients

BACKGROUND Prostate biopsies targeted by elastic fusion of magnetic resonance (MR) and three-dimensional (3D) transrectal ultrasound (TRUS) images may allow accurate identification of the index tumor (IT), defined as the lesion with the highest Gleason score or the largest volume or extraprostatic extension. OBJECTIVE To determine the accuracy of MR-TRUS image-fusion biopsy in characterizing ITs, as confirmed by correlation with step-sectioned radical prostatectomy (RP) specimens. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of 135 consecutive patients who sequentially underwent pre-biopsy MR, MR-TRUS image-fusion biopsy, and robotic RP at two centers between January 2010 and September 2013. INTERVENTION Image-guided biopsies of MR-suspected IT lesions were performed with tracking via real-time 3D TRUS. The largest geographically distinct cancer focus (IT lesion) was independently registered on step-sectioned RP specimens. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS A validated schema comprising 27 regions of interest was used to identify the IT center location on MR images and in RP specimens, as well as the location of the midpoint of the biopsy trajectory, and variables were correlated. RESULTS AND LIMITATIONS The concordance between IT location on biopsy and RP specimens was 95% (128/135). The coefficient for correlation between IT volume on MRI and histology was r=0.663 (p<0.001). The maximum cancer core length on biopsy was weakly correlated with RP tumor volume (r=0.466, p<0.001). The concordance of primary Gleason pattern between targeted biopsy and RP specimens was 90% (115/128; κ=0.76). The study limitations include retrospective evaluation of a selected patient population, which limits the generalizability of the results. CONCLUSION Use of MR-TRUS image fusion to guide prostate biopsies reliably identified the location and primary Gleason pattern of the IT lesion in >90% of patients, but showed limited ability to predict cancer volume, as confirmed by step-sectioned RP specimens. PATIENT SUMMARY Biopsies targeted using magnetic resonance images combined with real-time three-dimensional transrectal ultrasound allowed us to reliably identify the spatial location of the most important tumor in prostate cancer and characterize its aggressiveness.

A model for the time dependent three-dimensional thermal distribution within iceballs surrounding multiple cryoprobes

A time dependent three-dimensional finite difference model of iceball formation about multiple cryoprobes has been developed and compared to experimental data. Realistic three-dimensional probe geometry is specified and the number of cryoprobes, the cryoprobe cooling rates, and the locations of the probes are arbitrary inputs by the user. The simulation accounts for observed longitudinal thermal gradients along the cryoprobe tips. Thermal histories for several points around commercially available cryoprobes have been predicted within experimental error for one, three, and five probe configurations. The simulation can be used to generate isotherms within the iceball at arbitrary times. Volumes enclosed by the iceball and any isotherms may also be computed to give the ablative ratio, a measure of the iceballs killing efficiency. This ratio was calculated as the volume enclosed by a critical isotherm divided by the total volume of the iceball for assumed critical temperatures of -20 and -40 degrees C. The ablative ratio for a single probe is a continuously decreasing function of time but when multiple probe configurations are used the ablative ratio increases to a maximum and then essentially plateaus. Maximum values of 0.44 and 0.55 were observed for three and five probe configurations, respectively, with an assumed critical temperature of -20 degrees C. Assuming a critical temperature of -40 degrees C, maximum ablative ratios of 0.21 and 0.3 for three and five probe configurations, respectively, were observed.

The evolution and state of modern technology for prostate cryosurgery

Cryosurgery is the in situ ablation of a target tissue by application of extreme cold temperature. The ability of cryosurgery to ablate tissue is unquestioned. It is the controlled application of a cryoinjury in a manner to minimize morbidity that is problematic. Prostate cryosurgery is complicated by the proximity of the prostate to adjacent structures that are sensitive to a freeze injury, namely the urethra, rectal wall, and neurovascular bundles. Several recent technological advances have led to the development of an effective treatment protocol with acceptable morbidity. These include the advent of real-time transrectal ultrasound, cryomachines with almost instant freeze-thaw control through the use of the Joule-Thompson effect, and warming catheters to effectively preserve the integrity of the urethra and external sphincter. Further, temperature monitoring at the posterior margin of the prostate sometimes combined with an injection of saline solution into Denonvilliers fascia has reduced the occurrence of urethrorectal fistula formation to 0% to 0.5% in modern series. We review the key innovations of prostate cryosurgery that differentiate this state-of-the-art procedure from that used by early investigators to even that of the early 1990s. Potential future innovations, specifically related to image guidance of the procedure, are also addressed.

Quality of life and sexuality of men with prostate cancer 3 years after cryosurgery

The current study was designed to describe the long-term life quality and sexuality of men enrolled in a phase 2 clinical trial of cryosurgery for the treatment of localized prostate cancer. A total of 75 men were administered the Functional Assessment of Cancer Treatment-Prostate (FACT-P) before treatment and after treatment at 6 weeks, and at 3, 6, 12, 24, and 36 months. Additionally, these men completed a Sexuality Follow-Up Questionnaire (SFQ) 3 years after cryosurgery. By 12 months after cryosurgery, most FACT-P subscales had returned to pretreatment levels. Quality of life remained stable over the subsequent 2 years. The only exception to this general trend was persistent impairment in measures of social/family well-being. At 36 months, 13% (5 of 38) of patients had regained erectile functioning, and an additional 34% (13 of 38) of patients were sexually active with the help of aids. The 3-year quality-of-life outcomes support the renewed interest in cryosurgery. No late complications were observed. Whereas improvements in erectile function were observed between years 1 and 3 for some patients, most continue to experience erectile dysfunction. For these patients, aids are an important adjunct to the treatment of their erectile dysfunction.