Development of a Nationally Representative Coordinated Registry Network for Prostate Ablation Technologies.

PURPOSE: The accumulation of data through a prospective, multicenter coordinated registry network is a practical way to gather real world evidence on the performance of novel prostate ablation technologies. Urological oncologists, targeted biopsy experts, industry representatives and representatives of the FDA (Food and Drug Administration) convened to discuss the role, feasibility and important data elements of a coordinated registry network to assess new and existing prostate ablation technologies. MATERIALS AND METHODS: A multiround Delphi consensus approach was performed which included the opinion of 15 expert urologists, representatives of the FDA and leadership from high intensity focused ultrasound device manufacturers. Stakeholders provided input in 3 consecutive rounds with conference calls following each round to obtain consensus on remaining items. Participants agreed that these elements initially developed for high intensity focused ultrasound are compatible with other prostate ablation technologies. Coordinated registry network elements were reviewed and supplemented with data elements from the FDA common study metrics. RESULTS: The working group reached consensus on capturing specific patient demographics, treatment details, oncologic outcomes, functional outcomes and complications. Validated health related quality of life questionnaires were selected to capture patient reported outcomes, including the IIEF-5 (International Index of Erectile Function-5), the I-PSS (International Prostate Symptom Score), the EPIC-26 (Expanded Prostate Cancer Index Composite-26) and the MSHQ-EjD (Male Sexual Health Questionnaire for Ejaculatory Dysfunction). Group consensus was to obtain followup multiparametric magnetic resonance imaging and prostate biopsy approximately 12 months after ablation with additional imaging or biopsy performed as clinically indicated. CONCLUSIONS: A national prostate ablation coordinated registry network brings forth vital practice pattern and outcomes data for this emerging treatment paradigm in the United States. Our multiple stakeholder consensus identifies critical elements to evaluate new and existing energy modalities and devices.

A model for managing erectile dysfunction following prostate cancer treatment.

PURPOSE OF REVIEW: Radical prostatectomy, regardless of the technology used intraoperatively, induces erectile dysfunction for most men who undergo the procedure. For many men, this proves to be transient. Penile rehabilitation strategies have been developed with the goal of increasing the probability and speed of return of sexual function. The purpose of this work is to review the fundamentals of erectile dysfunction relevant to the postprostatectomy patient as well as the components that are often included in penile rehabilitation strategies. RECENT FINDINGS: Preservation of smooth muscle tissue is the key to preserving erectile function. This can be accomplished by providing the penis with regular exposure to oxygenated blood through intracaversonal injection therapy or vacuum erection device therapy. Dietary supplementation aimed to increase the nitric oxide production can also be beneficial. As well, chronic administration of PDE5 inhibitors may also help maintain the smooth muscle/collagen ratio in the corporal tissue. SUMMARY: These findings have led to the development of our management model that includes daily vacuum erection device therapy, dietary supplementation and PDE5 inhibitors which is described in detail. The success of any rehabilitation strategy is dependent on the patient compliance which needs to be facilitated by care-giver encouragement and the setting of realistic expectations.

Focal therapy for the treatment of localized prostate cancer: a potential therapeutic paradigm shift awaiting better imaging.

PURPOSE OF REVIEW: Prostate cancer is a complex disease entity that covers a wide prognosis spectrum. Prostate cancer treatment options do not match this spectrum well. Focal therapy is an active area of research that may allow us to better match treatment to prognosis across the prostate cancer spectrum. RECENT FINDINGS: Modern technology now allows us to perform focal ablation of prostate cancer. However, important issues remain: uncertain patient selection criteria (anatomically solitary versus biologically solitary cancer lesion), evolving management protocols (inadequate intraprostatic imaging, imprecise targeting/delivery of destructive energy), and nonstandardized follow-up metrics and failure definitions. Nevertheless, patients are already being treated at academic and private practices, sometimes as part of Institutional Review Board-approved research, more often not. SUMMARY: The potential of focal therapy in treatment of prostate cancer is undeniable. As better staging becomes possible, focal therapy will likely be offered to a considerable proportion of prostate cancer patients. Meticulous patient selection and follow-up, in the setting of well designed clinical studies and registries, will be necessary.

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

OBJECTIVES: 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. PATIENTS AND METHODS: Consecutively treated patients who underwent HIFU between October 1997 and July 2006 at two centres (Lyon, France; and Regensburg, Germany) were prospectively maintained within a central database and retrospectively reviewed for this study. Clinical failure was defined as a positive prostate biopsy after treatment, radiographic evidence of lymphatic or bony metastatic disease, or salvage treatment for prostate cancer (surgery, radiation, hormonal therapy or second HIFU). The serum prostate-specific antigen (PSA) values after HIFU were assessed as a biochemical surrogate of a therapeutic success or failure. PSA threshold values, 'PSA nadir plus', PSA velocity, PSA doubling time and the American Society or Therapeutic Radiotherapy and Oncology and Phoenix definition of biochemical failure were all considered. The sensitivity, specificity, positive predictive value and negative predictive value of each biochemical definition for predicting clinical failure were determined. RESULTS: The data from 285 patients (stage

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.

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.

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

INTRODUCTION AND OBJECTIVE: The increased use of cryoablation as an initial treatment for localized high-grade prostate cancer has been due to many factors including reports that cell kill from exposure to cryogenic temperatures is independent of cellular dedifferentiation and Gleason score. The objective of this study is to report the outcomes of primary cryoablation when used to treat Gleason 8, 9, or 10 localized prostate cancer at a large number of centers. MATERIALS AND METHODS: Data from 1608 patients who underwent primary cryoablation at 27 centers were collected using the Cryo OnLine Database (COLD) registry. This analysis considers only the 77 patients who had a Gleason score of at least 8 and a minimum of 24 months of follow-up. Biochemical failure was defined according to both the original ASTRO definition (three rises) and the 2006 updated ASTRO (Phoenix) definition of nadir + 2. Biopsy was performed at the physician's discretion, but most commonly if a patient had a rising or suspicious prostate specific antigen (PSA). RESULTS: The average age at treatment was 69.6 +/- 8.2 years. Pretreatment PSA was 16.2 +/- 17.9 ng/ml and the average Gleason was 8.5 +/- 0.6. Patients were followed for 39.0 +/- 18.8 months (range: 24-120 months) and 5-year follow-up was available for 12 patients. Eight-seven percent of the patients achieved a PSA nadir < 0.4 ng/ml. Five-year actuarial biochemical survivals was 64.4 +/- 6.0% and 44.6 +/- 8.0% for the ASTRO and Phoenix definitions, respectively. A total of 47 underwent posttreatment biopsy. Of these, 12 showed evidence of disease resulting in a positive biopsy rate for those who underwent biopsy of 25.5%. This yields a positive biopsy rate of the entire population of 15.6% (12/77). CONCLUSIONS: Cryoablation, as a primary treatment for high-grade Gleason prostate cancer practiced over a wide spectrum of users provides definable biochemical and local control for a hard to manage patient population with aggressive disease.

High intensity focused ultrasound for prostate cancer: a review of the scientific foundation, technology and clinical outcomes.

High Intensity Focused Ultrasound (HIFU) is a definitive treatment for localized prostate cancer that is currently utilized most in Europe and Japan but it not yet approved by the FDA for this indication. Within the armamentarium of definitive prostate cancer therapies it is unique as it is truly non-invasive and does not involve incision or excision. The purpose of this paper is to review the scientific foundation of the technology as well as the clinical outcomes of commercially available devices. The scientific foundation of HIFU is reviewed in terms of how it has resulted in the development of commercially available equipment. MEDLINE was used to search the medical literature for publications pertaining to HIFU for prostate cancer as a primary therapy in terms of clinical outcomes. Biochemical disease free rates as well as negative biopsy rates are reviewed. Different engineering optimization strategies in the face of technicalities inherent to HIFU for prostate cancer have led to the development of two distinct commercially available devices. Each has their own merits and limitations. HIFU provides excellent biochemical and local control and results appear to be durable. Clinical outcomes are similar for the two technologies developed but are difficult to compare due to different lengths of follow-up and varying patient populations. HIFU is a technically advanced definitive local therapy for prostate cancer. Short and medium term results are encouraging and its role as a primary therapy for prostate cancer continues to be defined as more results become available.

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.

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.

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.

Cryosurgery for breast cancer.

As the majority of breast cancers present as small non-palpable lesions, alternatives for surgical lumpectomy come into consideration. Breast tumor ablation without surgical excision may be a less morbid procedure without sacrificing cancer control. Cryosurgery is one of several ablative options for the treatment of small unifocal breast cancer. The potential advantages include avoidance of a surgical procedure, less overall discomfort, improved cosmesis, quicker recovery and the prospect of overall cost benefits. Clinical experience in 29 patients is reviewed demonstrating effectiveness in properly chosen patients. A comparison of ablation methods is discussed. Finally, future research of the role of cryosurgery in the management of breast cancer is described.

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.

A finite element model for ice ball evolution in a multi-probe cryosurgery.

The ice formation in a water body is examined for the computation of temperature field, phase change and a moving ice-water interface whose location is not known á priori. This is classically referred to as the Stefan problem [Rubinstein, L.I. (1971) The Stefan Problem (American Mathematical Society, Providence, Rhode Island 02904]. Based on the Duvaut [Duvaut, G. (1973) "Résolution d'un probléme Stefan" C.R. Acad Sci. Paris 276, 1461-1463] transformation, the governing equations for heat conduction are formulated within a variational principle that is readily amenable to a standard finite element solution without remeshing. Numerical simulation results pertaining to the freezing of tumour tissue in a multi-cryoprobe cryosurgery are presented. These results lend both quantitative and graphical support to the current empirical standards of "effective therapy" in view of refining clinical applications.

Cryotherapy simulator for localized prostate cancer.

Cryotherapy is a treatment modality that uses a technique to selectively freeze tissue and thereby cause controlled tissue destruction. The procedure involves placement of multiple small diameter probes through the perineum into the prostate tissue at selected spatial intervals. Transrectal ultrasound is used to properly position the cylindrical probes before activation of the liquid Argon cooling element, which lowers the tissue temperature below -40 degrees Centigrade. Tissue effect is monitored by transrectal ultrasound changes as well as thermocouples placed in the tissue. The computer-based cryotherapy simulation system mimics the major surgical steps involved in the procedure. The simulated real-time ultrasound display is generated from 3-D ultrasound datasets where the interaction of the ultrasound with the instruments as well as the frozen tissue is simulated by image processing. The thermal and mechanical simulations of the tissue are done using a modified finite-difference/finite-element method optimized for real-time performance. The simulator developed is a part of a comprehensive training program, including a computer-based learning system and hands-on training program with a proctor, designed to familiarize the physician with the technique and equipment involved.

Effect of targeted biopsy guided by elastic image fusion of MRI with 3D-TRUS on diagnosis of anterior prostate cancer.

PURPOSE: To evaluate the effect of targeted biopsy (TB) with elastic fused magnetic resonance imaging (MRI) and 3-dimensional transrectal ultrasound (3D-TRUS) guidance in the diagnosis of anterior prostate cancer (APCa). MATERIAL AND METHOD: A retrospective study was performed on patients who underwent TB with elastic fused MRI/3D-TRUS guidance using a 1.5-T MRI with T2- and diffusion-weighted images. APCa was defined as TB-proven cancer whose MR-imaged center was located anteriorly according to standardized MRI reporting schema. Prostate Imaging Reporting and Data System was used to quantify MRI suspicion. Maximum cancer core length (MCCL), cancer core involvement, primary Gleason grade pattern, and Gleason score (GS) on TB were assessed. A clinically significant cancer on TB was MCCL ≥ 5mm of GS 6 or any cancer with GS ≥ 7. Agreement between TB and radical prostatectomy step sections was assessed for all subjects when possible. RESULTS: A total of 211 consecutive subjects were included. APCa was found in 81% (170/211). Median (range) of TB per patient, MCCL, and cancer core involvement were 2 (1-5), 10mm (4-23), and 57% (10%-100%), respectively. According to the level of MRI suspicion, positive rate for any cancer vs. clinically significant cancer was 96% (114/119) vs. 86% (102/119) for highly suspicious, 80% (46/57) vs. 68% (39/57) for likely, and 29% (10/35) vs. 20% (7/35) for equivocal, respectively (P = 0.016 and<0.001). Step-section analysis was possible for 70 patients. Concordance of primary Gleason grade pattern and GS between TB and radical prostatectomy was 90% (κ = 0.7) and 77% (κ = 0.64), respectively. CONCLUSION: TB with elastic fused MRI/3D-TRUS guidance significantly enhanced accuracy in diagnosing clinically significant APCa.

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

BACKGROUND: 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. METHODS: From December 1997 through February 2003, 244 men with newly diagnosed localized prostate cancer were assigned randomly to receive either cryoablation or radiotherapy (122 men in each arm). All received neoadjuvant antiandrogen therapy. The primary endpoint was disease progression at 36 months based on a trifecta definition: 1) radiologic evidence of metastatic disease, or 2) initiation of further antineoplastic therapy, or 3) biochemical failure. Two definitions of biochemical failure were used: 1) 2 consecutive rises in prostate-specific antigen (PSA) with a final value >1.0 ng/mL, and 2) a rise above PSA nadir + 2 ng/mL. Secondary endpoints included overall survival, disease-specific survival, and prostate biopsy at 36 months. RESULTS: The median follow-up was 100 months. Disease progression at 36 months was observed in 23.9% (PSA nadir + 2 ng/mL, 17.1%) of men in the cryoablation arm and in 23.7% (PSA nadir + 2 ng/mL, 13.2%) of men in the radiotherapy arm. No difference in overall or disease-specific survival were observed. At 36 months, more patients in the radiotherapy arm had a cancer-positive biopsy (28.9%) compared with patients in the cryoablation arm (7.7%). CONCLUSIONS: The observed difference in disease progression at 36 months was small, 0.2%; however, because of the wide confidence interval, from -10.8% to 11.2%, it was not possible to rule out inferiority (defined a priori as a 10% difference). With longer term follow-up, the trend favors cryoablation. Significantly fewer positive biopsies were documented after cryoablation than after radiotherapy.

A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer: quality of life outcomes.

BACKGROUND: A recent randomized trial to compare external beam radiation therapy (EBRT) to cryoablation for localized disease showed cryoablation to be noninferior to external beam EBRT in disease progression and overall and disease-specific survival. We report on the quality of life (QOL) outcomes for this trial. METHODS: From December 1997 through February 2003, 244 men with newly diagnosed localized prostate cancer were randomly assigned to cryoablation or EBRT (median dose 68 Gy). All patients received neoadjuvant antiandrogen therapy. Patients completed the EORTC QLQ C30 and the Prostate Cancer Index (PCI) before treatment and at 1.5, 3, 6, 12, 18, 24, and 36 months post-treatment. RESULTS: Regardless of treatment arm, participants reported high levels of QOL with few exceptions. cryoablation was associated with more acute urinary dysfunction (mean PCI urinary function cryoablation=69.4; mean EBRT=90.7; P<.001), which resolved over time. No late arising QOL issues were observed. Both EBRT and cryoablation participants reported decreases in sexual function at 3 months with the cryoablation patients reporting poorer functioning (mean cryoablation=7.2: mean EBRT=32.9; P<.001). Mean sexual function score was 15 points lower at 3 years for the cryoablation group and 13% more of the cryoablation men said that sexuality was a moderate or big problem. CONCLUSIONS: In this randomized trial, no long-term QOL advantage for either treatment was apparent with the exception of poorer sexual function reported by those treated with cryoablation. Men who wish to increase their odds of retaining sexual function might be counseled to choose EBRT over cryoablation.

Preoperative prediction of unifocal, unilateral, margin-negative, and small volume prostate cancer.

OBJECTIVES: Contemporary prostate carcinoma is frequently of small volume and early stage. Subtotal gland ablation by minimally invasive therapies such as cryotherapy demands preoperative prediction of unifocal, unilateral, margin-negative, and small volume (less than 0.5 mL) cancer. METHODS: We examined matched biopsy and prostatectomy and clinical data from 393 patients at two institutions who underwent surgery in 2000 through 2003. Radical prostatectomy specimens were uniformly sectioned at 5-mm intervals and completely embedded. Numerous clinical and biopsy variables were correlated by regression analysis with unifocal, unilateral, margin-negative, and 0.5 mL or less volume cancer in the prostatectomy specimen. Odds ratios (OR) were determined. RESULTS: At prostatectomy, 92 (23%) had unifocal cancer, 90 (23%) had unilateral cancer, 348 (89%) had organ-confined cancer, and 106 (31%) had small volume cancer. Unilateral cancer occurred in 71% to 76% of cases of unilateral cancer in the biopsy (OR, 4.30; if 9 or more cores were sampled, OR rose to 6.83), and was predicted by unifocality in the biopsy (OR, 2.63). Unifocal cancer was predicted by unilateral (OR, 2.66) but not unifocal, cancer present in the biopsy. Negative surgical margins were predicted by unilateral (OR, 2.53; positive predictive value, 82%) cancer in the biopsy and by serum prostate specific antigen (OR, 5.33). Small volume cancer was predicted by unilateral (OR, 5.50) and unifocal (OR, 7.98) cancer in the biopsy; Gleason score greater than 7 predicted a non-small volume cancer (OR, 7.52). CONCLUSIONS: Unilateral or unifocal cancer on biopsy are among the strongest predictors of unilateral, unifocal, and small volume prostate cancer in contemporary practice.

Single center comparison of laparoscopic cryoablation and CT-guided percutaneous cryoablation for renal tumors.

BACKGROUND AND PURPOSE: Cryoablation has demonstrated therapeutic effectiveness for selected renal tumors. We compared our perioperative and short-term outcomes of laparoscopic (LAP) v percutaneous (PERC) renal cryoablation. PATIENTS AND METHODS: Thirty-four patients (18 men/16 women) underwent a LAP and 26 patients (19 men/7 women) underwent a PERC procedure between September1998 and January 2007. LAP cryoablation was performed transperitoneally with ultrasonographic monitoring. PERC cryoablation was performed with CT guidance. Follow-up imaging was obtained at regular intervals. RESULTS: Mean follow-up was 25 months. Average age (years) was 67.0 for the LAP and 69.7 for the PERC procedure (P = 0.307). Mean body mass index (kg/m(2)) was 29.8 for those undergoing LAP and 28.7 for those undergoing PERC procedures (P = 0.543). Mean tumor size (cm) was 2.9 for LAP patients and 3.1 for PERC patients (P = 0.432). Anterior tumors comprised 61.7% of LAP and 15.4% of PERC procedures (P < 0.001). Posterior tumors comprised 32.4% of LAP and 65.4% of PERC procedures (P = 0.01). Mean procedure time (minutes) was 165.7 for LAP and 106.6 for PERC procedures (P < 0.001). Hospital stay (days) was 2.6 for those undergoing LAP and 1.8 for those undergoing PERC procedures (P < 0.001). Both LAP patients (82.4%) and PERC patients (19.2%) needed postoperative narcotics (P < 0.001). Atelectasis developed in 70.6% of LAP patients and 34.6% of PERC patients (P = 0.005). Residual enhancement was seen in 11.5% of PERC patients and 2.9% of LAP patients (P = 0.192). Complications developed in 14.7% of LAP patients and 26.9% of PERC patients (P = 0.248). 1-year, 2-year, and 3-year disease-specific survival for the two groups was 100%. Tumor size > 4 cm and endophytic location were significantly associated with residual enhancement. CONCLUSIONS: LAP and PERC renal cryoablation have similar short-term outcomes. Significantly more anterior tumors were approached laparoscopically and significantly more posterior tumors were approached percutaneously. The PERC approach may offer advantages regarding hospital stay, narcotic need, and development of atelectasis. Longer-term data are needed to establish success of this approach.