Cryoablation For Prostate Cancer Research Articles

AI-Based Isotherm Prediction for Focal Cryoablation of Prostate Cancer

Focal therapies have emerged as minimally invasive alternatives for patients with localized low-risk prostate cancer (PCa) and those with postradiation recurrence. Among the available focal treatment methods for PCa, cryoablation offers several technical advantages, including the visibility of the boundaries of frozen tissue on the intraprocedural images, access to anterior lesions, and the proven ability to treat postradiation recurrence. However, predicting the final volume of the frozen tissue is challenging as it depends on several patient-specific factors, such as proximity to heat sources and thermal properties of the prostatic tissue. This paper presents a convolutional neural network model based on 3D-Unet to predict the frozen isotherm boundaries (iceball) resultant from a given a cryo-needle placement. Intraprocedural magnetic resonance images acquired during 38 cases of focal cryoablation of PCa were retrospectively used to train and validate the model. The model accuracy was assessed and compared against a vendor-provided geometrical model, which is used as a guideline in routine procedures. The mean Dice Similarity Coefficient using the proposed model was 0.79±0.08 (mean+SD) vs 0.72±0.06 using the geometrical model (P<.001). The model provided an accurate iceball boundary prediction in less than 0.4second and has proven its feasibility to be implemented in an intraprocedural planning algorithm.

Motorized template for MRI-guided focal cryoablation of prostate cancer.

MR-guided focal cryoablation of prostate cancer has often been selected as a minimally-invasive treatment option. Placing multiple cryo-needles accurately to form an ablation volume that adequately covers the target volume is crucial for better oncological/functional outcomes. This paper presents an MRI-compatible system combining a motorized tilting grid template with insertion depth sensing capabilities, enabling the physician to precisely place the cryo-needles into the desired location. In vivo animal study in a swine model (3 animals) was performed to test the device performance including targeting accuracy and the procedure workflow. The study showed that the insertion depth feedback improved the 3D targeting accuracy when compared to the conventional insertion technique (7.4 mm vs. 11.2 mm, p=0.04). All three cases achieved full iceball coverage without repositioning the cryo-needles. The results demonstrate the advantages of the motorized tilting mechanism and real-time insertion depth feedback, as well as the feasibility of the proposed workflow for MRI-guided focal cryoablation of prostate cancer.

Clinical value of normal saline injection for expansion of the anterior perirectal space during prostate cryoablation.

The objective of this study is to describe the technique and evaluate the clinical value of normal saline (NS) injection for expanding the anterior perirectal space during prostate cryoablation for prostate cancer (PCa) patients. PCa patients who received cryoablation between August 2014 and December 2019 were enrolled, and the technique of NS injection was adopted. The complications were evaluated. The prostate-specific antigen (PSA) nadir and biochemical progression-free survival (bPFS) were measured in localized PCa patients who received cryoablation as the primary treatment. A total of 159 PCa patients were included. Among 147 patients with the data of anterior perirectal space, the median (interquartile range [IQR]) distance of estimated iceball edge beyond the prostatic capsule was 8.3 (7.0-10.0) mm. No cases of urethrorectal fistula were reported; 29 patients developed urinary retention and 25 patients presented scrotal edema. All complications below Clavien-Dindo grade IIIb disappeared within 7 weeks after surgery. Urinary incontinence was reported in 6 patients. Among localized PCa patients, the median (IQR) follow-up time was 56.5 (36.0-73.5) months. The estimated 5-year bPFS was 82.3% overall, 82.8% for low-to intermediate-risk PCa patients, and 82.1% for high-risk PCa patients. For 52 patients received cryoablation alone, the median (IQR) PSA nadir was 0.147 (0.027-0.381) ng/mL. The technique of NS injection for expanding the anterior perirectal space during cryoablation surgery could avoid urethrorectal fistula and might benefit localized PCa patients with lower PSA nadir and longer bPFS.

Partial gland cryoablation for prostate cancer - where are we?

Partial gland cryoablation for prostate cancer - where are we?

Medium Term Outcomes of Focal Cryoablation for Intermediate and High Risk Prostate Cancer: MRI and PSA are Not Predictive of Residual or Recurrent Disease

To understand oncologic outcomes of focal cryoablation for prostate cancer and efficacy MRI and PSA to predict residual disease and recurrence. We retrospectively analyzed patients who underwent focal cryotherapy at a single institution. Inclusion criteria included clinically localized biopsy-proven cancer that was clearly visible on MRI or ultrasound. The primary outcomes were failure-free survival (FFS) defined as no transition to radical, whole-gland or systemic therapy and biochemical recurrence (Phoenix PSA nadir +2 increases), and secondary outcomes included changes in the Gleason grade group (GG) and MRI findings. 75 patients completed post cryotherapy biopsy with a median follow-up of 1.89 [IQR 1.19-2.77] years. Failure free survival was met by 96.2% of patients at 2 year follow up and of those who did not meet this outcome, 3 had metastasis, 1 had a salvage prostatectomy and 5 underwent radiation. On the treated side of the prostate, 7 (9.5%) of patients had residual ≥GG2 disease compared to 7 (9.5%) patients on the untreated side. Out of the 12 patients who had residual ≥GG2 disease at follow up biopsy (either on treated or untreated side of the prostate), 11 (91.7%) had PI-RADS 1-3 on follow up MRI. Using a multivariate cox proportional hazards model, Phoenix criteria for recurrence (PSA nadir +2) was not predictive for FFS. Focal cryotherapy is effective for treating focal lesions of prostate cancer, but patients require continued surveillance. MRI and PSA are not reflective of residual disease on follow up biopsy.

First experiences and results after cryoablation of prostate cancer with histopathological evaluation and imaging-based follow-up.

Aim: To share our experience after 28 cryoablation treatments for prostate cancer (PCa) with histopathology, clinical data and MRI as the follow-up methods. Methods: Clinical follow-up comprised prostate-specific antigen (PSA)-measurements, PSA-density and quality of life-parameters. multi-parametric (mp)MRI pre- and post-cryoablation were retrospectively re-analyzed in 23 cases using Likert scores. Follow-up-histopathology was performed via MRI/ultrasound fusion-guided and/or systematic biopsy. Receiver operating characteristic curve analysis was performed. Results: 17 PCa (61%) were diagnosed within 12-month post-cryotherapy (infield and out-of-field disease). PSAlevels and PSAdensity were not significantly different between patients with or without PCarecurrence. mpMRI can characterize thedecrease in prostate volume and necrosis. Area under the curvefor the detection of PCa was 81%(global Likertscores), 74-87%(T2), 78%(diffusion weighted imaging) and 57-78%(dynamic contrast enhanced imaging; Youden-selected cutoff ≥3). Conclusion: Besides histopathological evaluationandcontrol biopsy, MRI might have the potential to accurately detect PCa after cryotherapy. Clinical data and interdisciplinary communication arerequired for efficient monitoring after cryoablation treatments forPCa.

Focal Cryoablation of Image-Localized Prostate Cancer.

Focal cryoablation of localized prostate cancer can offer patients superior genitourinary functional outcomes in terms of preservation of urinary continence and potency compared with radical whole-gland therapy, while maintaining intermediate-term oncologic control. We present a step-by-step guide to focal cryoablation of localized prostate cancer. A patient with elevated prostate specific antigen (PSA) underwent multiparametric MRI (mpMRI) of the prostate that revealed a prostate imaging-reporting and data system (PI-RADS) four lesion. The patient subsequently had a transrectal ultrasound (TRUS)-guided MRI fusion biopsy of the target lesion as well as a systematic biopsy and was only found to have Gleason 3 + 4 prostate cancer in the 0.5 cc mpMRI target. The lesion plus a treatment margin was ablated with cryotherapy utilizing a traditional transperineal approach. Patient position, ultrasound and mpMRI image fusion, insertion of cryoablation needles, ablation of the prostate cancer lesion, and postoperative care were reviewed. Equipment used during the operation was itemized and described. This guide explores the necessary equipment, procedural steps, and tips for success when performing focal cryoablation of the prostate. The technique described represents the culmination of knowledge gathered with 30 years of experience performing cryoablation of prostate cancer. The accompanying video highlights the utilization of mpMRI and TRUS image fusion, triangulation of lethal ice around the prostate cancer lesion, and the importance of monitoring real-time ice formation with TRUS imaging. Cryoablation of prostate cancer can be applied to several clinical scenarios: partial-gland ablation, quadrant, hemiablation, focal-targeted, or whole gland in the primary or salvage settings. We present the surgical steps that are essential for effective focal ablation of image-localized prostate cancer.

Does prior surgical interventional therapy for BPH affect the oncological or functional outcomes after primary whole-gland prostate cryoablation for localized prostate cancer?

To assess whether prior interventional treatment for benign prostatic hyperplasia (BPH) influences oncologic or functional outcomes following primary whole-gland prostate cryoablation. Among 3831 men with prostate cancer who underwent primary whole-gland prostate cryoablation, we identified 160 with a history of prior BPH interventional therapy including transurethral needle ablation (n = 6), transurethral microwave thermotherapy (n = 9), or transurethral resection of the prostate (n = 145). Patients with a history of medically treated or unspecified BPH therapy were excluded from the study. Oncological and functional outcomes were compared between men with and without prior BPH interventional therapy. In unadjusted analyses, prior interventional BPH therapy was associated with higher risks of postoperative urinary retention (17.5% vs. 9.6%, p = 0.001) and new-onset urinary incontinence (39.9% vs. 19.4%, p > 0.001) compared with no prior therapy. Interventional BPH therapy was not correlated with the risk of developing a rectourethral fistula (p = 0.84) or new-onset erectile dysfunction (ED) at 12 months (p = 0.08) following surgery. On multivariable regression, prior interventional BPH therapy was associated with increased risk of urinary retention (OR 1.9, 95%, p = 0.015) and new-onset urinary incontinence (OR 2.13, p < 0.001). The estimated 5 years Kaplan-Meier survival analysis showed no statistically significant difference (p = 0.3) in biochemical progression free survival between those who underwent interventional BPH therapy compared with those who did not. Local disease recurrence assessed by post cryoablation positive for-cause prostate biopsy showed no significant difference between the two groups (25.4% vs. 28.7%, p = 0.59). Prior interventional BPH therapy did not affect the oncologic outcomes nor did it increase the risk of rectourethral fistula or ED in sexually performing patients prior to cryosurgery. Prior interventional BPH therapy was associated with increased risk of urinary retention and incontinence after primary whole-gland prostate cryoablation for prostate cancer.

Feasibility of in-office MRI-targeted partial gland cryoablation for prostate cancer: an IDEAL stage 2A study

ObjectivesCryoablation for prostate cancer is typically performed under general anaesthesia. We explore the safety, feasibility and costs of in-office MRI-targeted prostate partial gland cryoablation (PGC) under local anaesthesia. We hypothesise...

The Impact of Placement Errors on the Tumor Coverage in MRI-Guided Focal Cryoablation of Prostate Cancer

There have been multiple investigations defining and reporting the effectiveness of focal cryoablation as a treatment option for organ-confined prostate cancer. However, the impact of cryo-needle/probe placement accuracy within the tumor and gland has not been extensively studied. We analyzed how variations in the placement of the cryo-needles, specifically errors leading to incomplete ablation, may affect prostate cancer's resulting cryoablation. We performed a study based on isothermal models using Monte Carlo simulations to analyze the impact of needle placement errors on tumor coverage and the probability of positive ablation margin. We modeled the placement error as a Gaussian noise on the cryo-needle position. The analysis used retrospective MRI data of 15 patients with biopsy-proven, unifocal, and MRI visible prostate cancer to calculate the impact of placement error on the volume of the tumor encompassed by the -40°C and -20°C isotherms using one to four cryo-needles. When the standard deviation of the placement error reached 3 mm, the tumor coverage was still above 97% with the -20°C isotherm, and above 81% with the -40°C isotherm using two cryo-needles or more. The probability of positive margin was significantly lower considering the -20°C isotherm (0.04 for three needles) than using the -40°C isotherm (0.66 for three needles). The results indicated that accurate cryo-needle placement is essential for the success of focal cryoablation of prostate cancer. The analysis shows that an admissible targeting error depends on the lethal temperature considered and the number of cryo-needles used.

Cryothérapie totale de la prostate sous IRM par voie périnéale : résultats carcinologiques et facteurs prédictifs

To determine the pejorative predictive factors on oncologic outcomes of percutaneous MR-guided whole gland prostate cancer cryoablation (CA). Medical records of patients treated from 2009to 2012, to assess medium-term oncologic outcomes, were reviewed. Prostate biopsies were performed in local recurrence suspicion (biochemical failure, MR follow-up failure). Among 18patients, mean age of 72.6 (61-78), 2 (11%) and 7 (38.9%) biological and reported biopsy-proven local recurrence respectively with our initial technic of CA. Mean follow-up and recurrence were 56.3 (±21.7) and 20.7 (±13.9) months respectively. A previous treatment of prostate cancer (P=0.5), pre-treatment PSA (P=0.2), pre-treatment Gleason/ISUP score (P=0.4), nadir PSA post-CA (P=0.22) were not associated with recurrence. Bilateral positive cores appears as a pejorative predictive factor (P=0.04). However mean pre-treatment positive cores percentage, 25 (±16.5) in responding patients versus 40.7 (±25.2) in case of recurrence, and maximum percentage of cancer extent in each positive core, 10.6 (±9.3) in responding patients versus 18.7 (±16.5) in case of recurrence, seemed associated with local recurrence after prostate CA but our analysis wasn't able to find a difference (P=0.09and P=0.3respectively) due to a lack of power. Bilateral positive cores appears as a pejorative predictive factor. In our experience, important tumor volume seem to be a pejorative predictive factor for oncologic outcomes after PCA whereas treatment, PSA, Gleason/ISUP score, nadir PSA are not. 4.

Rectal wall saline displacement for improved margin during MRI-guided cryoablation of primary and recurrent prostate cancer.

To describe safety, efficacy, and added oncologic margin of saline displacement of the rectal wall during MRI-guided cryoablation of primary and recurrent prostate cancer. A retrospective review was conducted for patients who underwent MRI-guided cryoablation with saline displacement of the rectal wall for treatment of primary and recurrent prostate cancer over a 2-year period. Saline displacement was used when the distance from the edge of the ablation area to the rectal wall was insufficient to provide at least a 5-mm treatment margin. Pre- and post-ablation rectal wall displacement distances as well as ablative zone margins were assessed with MRI. Saline displacement distance was measured from the rectal wall to the edge of the lesion for focal lesion ablation and from the edge of the prostate for hemi-gland ablation. Immediate and intermediate-term complications were assessed. Saline displacement was used in 25 patients undergoing MRI-guided cryoablation. Twenty-one patients underwent salvage cryoablation, while four patients had it as primary treatment for prostate cancer. Median pre- and post- saline displacement rectal wall displacement distances were 6.0 and 11.2mm, respectively (P < 0.0001). Median-added oncologic margin achieved by saline displacement was 4.6mm (range 0.6-26.5). Median follow-up was 14months (range 5-29). There were no intra-procedural complications and 3 patients experienced minor (Clavien-Dindo grade I) complications. One rectal complication occurred in a patient undergoing salvage cryotherapy with a history of extensive pelvic surgery and radiation. Saline infusion at the time of MRI- guided cryoablation for prostate cancer resulted in increased distances between the target lesion and rectum. This is a useful technique in providing an added oncologic margin when treating lesions close to the rectal wall.

T cells CD4+/CD8+ local immune modulation by prostate cancer hemi-cryoablation.

Tumors escape from the immune system by decreasing CD8+ and increasing CD4+ T cells' activity, druggable targets. Thermal ablation might activate tumor-specific T cells by raising the presentation of tumor-specific antigens and hindering tumor negative immune regulation. Our aim was to assess T cell infiltrate pre- and post-cryoablation in a prospective observational study. A total of 240 sextant prostate biopsies cores (12 cores/patient) were collected from 10 unilateral prostate cancer patients (T1c, PSA density < 0.15ng/dL, Gleason grade group 1, ≤ 2 cancer biopsy cores, and < 50% cancer core involvement) at diagnosis and 12months after hemi-cryoablation. Cancer-positive (Diag+) and cancer-negative (Diag-) lobes at diagnosis and the same areas 12months after hemi-cryoablation (Cryo+ and Cryo-, respectively) were explored by immunohistochemistry for infiltrating CD4+ and CD8+ T cells (in 45 random fields per prostate lobe, 400× magnification). The quantitative analysis of cells/mm2 and CD4+/CD8+ ratio were performed and compared among Diag+, Diag-, Cryo+, and Cryo- using ImageJ software. There was a significant increase in tumor-infiltrating CD8+ T cells/mm2 in the Cryo+ tissue (mean, SD 0.31, 0.30) compared to Diag+ (0.18, 0.15), p = 0.015; confirmed in prostate acini (hot spots), p = 0.029, in which infiltrating CD4+/CD8+ T cells' ratio decreased after hemi-cryoablation, p = 0.006. Infiltrating CD4+ T cells/mm2 presented a trend to decrease in Cryo+ (0.26, 0.27) compared to Diag+ (0.38, 0.32). This is the first study to show local immune modulation after prostate cancer cryoablation, characterized by decreasing CD4+/CD8+ T cells' ratio, potential for clinical impact by unleashing the T-cell response to cancer. Future studies are necessary to explore different energies and longer follow-up clinical endpoints.

Percutaneous MR-guided prostate cancer cryoablation technical updates and literature review.

Prostate cancer (PCa) is the most common malignant tumor in males. The benefits in terms of overall reduction in specific mortality due to the widespread use of Prostate Specific Antigen (PSA) screening and the advancements in the curative treatments (radical prostatectomy or radiotherapy) appear to have reached a plateau. There remains, however, the questions of overdiagnosis and overtreatment of such patients. Currently, the main challenge in the treatment of patients with clinically organ-confined PCa is to offer an oncologically efficient treatment with as little morbidity as possible.Amongst the arising novel curative techniques for PCa, cryoablation (CA) is the most established one, which is also included in the NICE and AUA guidelines. CA is commonly performed under ultrasound guidance with the inherent limitations associated with this technique. The recent advancements in MRI have significantly improved the accuracy of detecting and characterizing a clinically significant PCa. This, alongside the development of wide bore interventional MR scanners, has opened the pathway for in bore PCa treatment. Under MRI guidance, PCa CA can be used either as a standard whole gland treatment or as a tumor targeted one. With MR-fluoroscopy, needle guidance capability, multiplanar and real-time visualization of the iceball, MRI eliminates the inherent limitations of ultrasound guidance and can potentially lead to a lower rate of local complications.The aim of this review article is to provide an overview about PCa CA with a more specific insight on MR guided PCa CA; the limitations, challenges and applications of this novel technique will be discussed.

Percutaneous MR-guided whole-gland prostate cancer cryoablation: safety considerations and oncologic results in 30 consecutive patients.

To assess the safety and oncological efficacy of percutaneous MR-guided whole-gland prostate cancer (PCa) cryoablation (CA). Between July 2009 and January 2018, 30 patients (mean age 72.9 ± 5.13 years) with histologically proven, organ-confined (≤ T2cN0M0), predominantly low/intermediate-risk PCa (median Gleason score 7; mean prostate specific antigen 6.05 ± 3.74 ng ml-1 ) underwent MR-guided whole-gland CA. Patients were selected on the basis of prior pelvic radiotherapy (n = 16; 12 for previous PCa), or contra indication/refusal of surgery or radiotherapy. Complications, local progression-free survival (LPFS) and overall survival (OS) were retrospectively investigated. Eighteen [60%] patients reported procedure-related complications: 5/18 [28%] needed surgical/interventional treatments and 13 [72%] conservative or pharmacological treatment. Eleven [73%] complications were noted in the first 15 patients and 7 [47%] in the last 15 patients (p = 0.26). Mean nadir prostate specific antigen was 0.24 ± 1.5 ng ml-1 (mean follow-up 3.8 years; range: 2 - 2915 days). Seven [23%] patients developed histologically proven local progression (mean time to recurrence 775 days, range: 172 - 2014). Mean clinical follow-up was 3.8 years (range 1-2915 days). LPFS was 92.0, 75.7 and 69.4 % at 1-, 3- and 5 year follow-up, respectively. For patients in salvage treatment, LPFS was 100%, 75%, and 75% at 1-, 3- and 5 year follow-up. OS was 100%, 94.4 and 88.5 % at 1-, 3- and 5 year follow-up respectively, with no patients dying from PCa. Whole-gland PCa CA offers good oncological efficacy, particularly in post-radiotherapy cases. Although the complication rate is significant, the majority is minor and is managed with conservative or pharmacologic management. MRI-guided whole-gland prostate cancer cryoablation offers good oncological efficacy, particularly in post-radiotherapy cases with a contained complication rate.

Use of MRI-Guided Biopsy for Selection and Follow-up of Men Undergoing Hemi-gland Cryoablation of Prostate Cancer

To investigate safety, efficacy, and quality of life impact of hemi-gland cryotherapy for clinically-significant prostate cancer (CaP), when patient selection and follow-up includes MRI-guided biopsy. Twenty-nine men with unilateral CaP (all clinically significant with prostate volume <60 cc) were enrolled in a prospective observational trial of hemi-gland cryotherapy. Mean patient age was 68.7 years. Median prostate-specific antigen (PSA) was 6.6 ng/mL. MRI-guided biopsy (3T-MRI, Artemis US fusion) was used for diagnosis and repeated at 6-month follow-up in all men. Treatment was under general anesthesia using the BTG/Galil system. Validated questionnaires were used to determine effects of treatment on urinary and sexual function and quality of life. Cryotherapy was completed satisfactorily in all 29 cases in <60 minutes with no intraoperative complications. Significant decreases in PSA (median decrease 5.6 ng/mL) and PSA density (median decrease 0.14 ng/mL/cc) were observed (P < .01). At 6 months, 23 patients (79%) demonstrated no residual cancer on follow-up MRI-guided biopsy of the treated side. Three patients (10%) revealed micro-residual disease. Three patients (10%) had residual cancer and underwent further treatment. Ipsilateral MRI lesions were present before treatment in 26 patients and after treatment in only 2, reflecting the gross ablative effect; however, MRI showed disappearance of lesions in 4 patients with residual tumor on biopsy. The single complication was 1 case of transient urinary retention; 85% of men who were sexually active continued without change after treatment. Voiding function was unchanged. Hemi-gland cryoablation for clinically-significant CaP is well-tolerated, and when patients are selected and followed by MRI/US fusion biopsy, cancer control appears promising at 6 months.

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 summaryCryoablation 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.

Predictors of Rectourethral Fistula Formation After Primary Whole-Gland Cryoablation for Prostate Cancer: Results from the Cryo On-Line Database Registry.

To define the incidence and risk factors associated with rectourethral fistula (RUF) formation following primary whole-gland cryosurgery using a multicenter centralized registry. The Cryo On-Line Data (COLD) registry was queried for men undergoing primary whole-gland cryotherapy between 1990 and 2014 who developed a RUF. Patient factors and disease parameters were correlated with RUF using chi-square and the t-test. Variables with p < 0.25 were entered into a binary logistic regression with stepwise backward elimination to determine the factors associated with RUF formation. A total of 4102 men underwent primary whole-gland cryotherapy in the COLD registry at the time of analysis. Postoperative RUF was documented in 50 out of 4102 cases (1.2%). Patients with RUF had similar demographic data, prostate volume, preoperative prostate-specific antigen level, and clinical stage in comparison to those without fistula. On both univariate and multivariate analyses, postoperative urinary retention (odds ratio [OR]: 6.30; confidence interval [95% CI] 3.43-11.58, p < 0.001), preoperative Gleason score of ≥7 (OR: 1.92; 95% CI 1.08-3.43, p = 0.027), and preoperative incontinence (OR: 2.95; 95% CI 1.12-7.76, p = 0.028) were the most significant risk factors associated with RUF formation. Primary whole-gland cryotherapy for prostate cancer is associated with a historically low rate (1.2%) of postoperative RUF formation. The rate decreased further to 0.55% over the last several years, suggesting better patient selection and technical improvement. Postoperative urinary retention, Gleason score ≥7, and preoperative urinary incontinence were the key demographic, clinical, and pathologic features associated with RUF formation in this study.

Dose Escalation of Vitamin D3 Yields Similar Cryosurgical Outcome to Single Dose Exposure in a Prostate Cancer Model.

Vitamin D3 (VD3) is an effective adjunctive agent, enhancing the destructive effects of freezing in prostate cancer cryoablation studies. We investigated whether dose escalation of VD3 over several weeks, to model the increase in physiological VD3 levels if an oral supplement were prescribed, would be as or more effective than a single treatment 1 to 2 days prior to freezing. PC-3 cells in log phase growth to model aggressive, highly metabolically active prostate cancer were exposed to a gradually increasing dose of VD3 to a final dose of 80 nM over a 4-week period, maintained for 2 weeks at 80 nM, and then exposed to mild sublethal freezing temperatures. Results demonstrate that both acute 24-hour exposure to 80 nM VD3 and dose escalation resulted in enhanced cell death following freezing at −15°C or colder, with no significant differences between the 2 exposure regimes. Apoptotic analysis within the initial 24-hour period postfreeze revealed that VD3 treatment induced both caspase 8- and 9-mediated cell death, most notably in caspase 8 at 8-hour postfreeze. These results indicate that both the intrinsic and extrinsic apoptotic pathways are involved in VD3 sensitization prior to freezing. Additionally, both acute and gradual dose escalation regimes of VD3 exposure increase prostate cancer cell sensitivity to mild freezing. Importantly, this study expands upon previous reports and suggests that the combination of VD3 and freezing may offer an effective treatment for both slow growth and highly aggressive prostate cancers.

Whole-Gland Prostate Cancer Cryoablation with Magnetic Resonance Imaging Guidance: One-Year Follow-Up

Patients who develop prostate cancer after prior abdominal perineal resection are poor surgical candidates, and have limited treatment options. Therefore, our goal is to present results from a single institutional experience of four patients who underwent whole gland MRI-guided cryoablation with a history complicated by prior abdominoperineal resection. Four MRI-guided cryoablative treatments (mean age 64, range 59-69 years) for primary and locally recurrent prostate adenocarcinoma were retrospectively reviewed in patients with prior abdominal perineal resection for colorectal cancer (3) and juvenile polyposis (1). Average prostate volume prior to ablation was 23 cc, with an average PSA of 5.6 ng/mL. For each gland, 7-10 cryoprobes were placed approximately 0.5 cm apart in the prostate gland under MRI guidance by a transperineal approach with 3-4 freeze-thaw cycles performed. Each patient had follow up imaging and PSA measurements out to 12 months post ablation. All four patient's PSA dropped below 0.1 ng/mL at 3-6 month post-ablation and remained at these levels at 12 months. Three of the 4 patients had PSA measurements to 33 months post-ablation, with no evidence of recurrence. No patient developed urinary incontinence due to the whole gland cryoablation. With all four patients in our study having undetectable PSAs 12 months post ablation, and with no patient developing urinary incontinence due to the cryoablation, MRI-guided cryoablation appears to be a promising treatment option in patients who are poor surgical candidates due to prior pelvic surgery and/or radiation.