Partial gland ablation with high intensity focal ultrasound impact on genito-urinary function and quality of life: our initial experience.

INTRODUCTION:   Partial gland ablation (PGA) using high intensity focal ultrasound (HIFU) is an alternative to active surveillance for low to intermediate risk localized prostate cancer.  This pilot study assessed quality of life (QoL) outcomes during the implementation of PGA-HIFU at our institution. MATERIALS AND METHODS:   We prospectively enrolled 25 men with a diagnosis of localized low/intermediate risk prostate cancer who elected to undergo PGA-HIFU in a pilot study at our institution between 2013 and 2016.  Patients underwent pre-treatment mpMRI and transrectal ultrasound-guided biopsies.  The primary endpoints were impact on patient-reported functional outcomes (erectile, urinary function, QoL) assessed at 1, 3, 6- and 12-months. RESULTS:   The median age was 64 years old (IQR 59.5-67).  Baseline median International Index of Erectile Function-15 score was 50, which decreased to 18 at 1 month (p < 0.0005), returned to baseline by 3 months and thereafter. International Prostate Symptom Score median at baseline was 8, which worsened to 12 at 1 month (p = 0.0088), and subsequently improved to baseline thereafter.  On the UCLA-Expanded Prostate Cancer Index Composite urinary function, there was a decrease in median score from 92.7 at baseline to 76.0 at 1 month (p < 0.0001), which improved to or above baseline afterwards.  QoL remained similar to baseline at each follow up period as assessed by EQ-5D and the Functional Cancer Therapy-Prostate score. CONCLUSIONS:   In this initial cohort of PGA-HIFU men at our institution, patients demonstrated a slight, but transient, deterioration in urinary and erectile function at 1 month prior to normalization.  All QoL metrics showed no impact upon 1 year of follow up post-treatment.

The diagnostic accuracy of micro-ultrasound for prostate cancer diagnosis: a review.

PURPOSE: Micro-UltraSound (microUS) is a new imaging modality capable of identifying and targeting suspicious areas, which might further increase the diagnostic yield of prostate biopsy (PBx). Aim of this review is to provide insights into the usefulness of microUS for the sub-stratification of prostate cancer (PCa), clinically significant PCa (i.e., any Gleason score ≥ 7 PCa; csPCa) along with non-organ-confined disease in patients undergoing PBx. METHODS: A PubMed literature search was performed using keywords: prostate cancer diagnosis, prostate cancer diagnosis surveillance, systematic biopsy, target biopsy, micro-ultrasound, and prostate risk identification using micro-ultrasound. RESULTS: MicroUS could significantly improve multiparametric magnetic resonance imaging (mpMRI) findings by adding valuable anatomical and pathological information provided by real-time examination. Furthermore, microUS target biopsy could replace systematic biopsy in clinical practice by reducing the detection of clinically insignificant (ciPCa) and increasing that of csPCa. Finally, microUS may be useful in predicting the presence of non-organ confined PCa before radical prostatectomy and it could also be an effective add-on tool for patient monitoring within the active surveillance program. CONCLUSION: MicroUS may represent an attractive step forward for the management of csPCa as a complementary or alternative tool to mpMRI. Nevertheless, further longitudinal studies are warranted, and the strength of the evidence is still suboptimal to provide clear recommendations for daily clinical practice.

The Triple-Tracer strategy against Metastatic PrOstate cancer (3TMPO) study protocol.

OBJECTIVE: To determine the prevalence of intra-patient inter-metastatic heterogeneity based on positron emission tomography (PET)/computed tomography (CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) and to determine the prevalence of neuroendocrine disease in these patients and their eligibility for radioligand therapies (RLTs). PATIENTS AND METHODS: This multicentre observational prospective clinical study will include 100 patients with mCRPC from five Canadian academic centres. Patients with radiological or biochemical progression and harbouring at least three metastases by conventional imaging will be accrued. Intra-patient inter-metastatic heterogeneity will be determined with triple-tracer imaging using fluorine-18 fluorodeoxyglucose (18 F-FDG), gallium-68-(68 Ga)-prostate-specific membrane antigen (PSMA)-617 and 68 Ga-DOTATATE, which are a glucose analogue, a PSMA receptor ligand and a somatostatin receptor ligand, respectively. The 68 Ga-PSMA-617 and 18 F-FDG PET/CT scans will be performed first. If at least one PSMA-negative/FDG-positive lesion is observed, an additional PET/CT scan with 68 Ga-DOTATATE will be performed. The tracer uptake of individual lesions will be assessed for each PET tracer and patients with lesions presenting discordant uptake profiles will be considered as having inter-metastatic heterogeneous disease and may be offered a biopsy. EXPECTED RESULTS: The proposed triple-tracer approach will allow whole-body mCRPC characterisation, investigating the inter-metastatic heterogeneity in order to better understand the phenotypic plasticity of prostate cancer, including the neuroendocrine transdifferentiation that occurs during mCRPC progression. Based on 68 Ga-PSMA-617 or 68 Ga-DOTATATE PET positivity, the potential eligibility of patients for PSMA and DOTATATE-based RLT will be assessed. Non-invasive whole-body determination of mCRPC heterogeneity and transdifferentiation is highly innovative and might establish the basis for new therapeutic strategies. Comparison of molecular imaging findings with biopsies will also link metastasis biology to radiomic features. CONCLUSION: This study will add novel, biologically relevant dimensions to molecular imaging: the non-invasive detection of inter-metastatic heterogeneity and transdifferentiation to neuroendocrine prostate cancer by using a multi-tracer PET/CT strategy to further personalise the care of patients with mCRPC.

Role of Systematic Control Biopsies following Partial Gland Ablation with High-Intensity Focused Ultrasound for Clinically Significant Prostate Cancer.

PURPOSE: Partial gland ablation (PGA) using high-intensity focused ultrasound (HIFU) is currently under investigation for clinically significant prostate cancer (Cs-PCa). Our primary objective was to assess the role of systematic control biopsies following HIFU-PGA in a cohort of Cs-PCa patients. MATERIALS AND METHODS: We studied a single-center retrospective cohort of 77 men treated with HIFU-PGA between October 2015 and December 2019. Patients with unilateral Cs-PCa, defined as Gleason grade group (GGG) ≥2, with visible lesion on multiparametric magnetic resonance imaging (mpMRI) and prostate specific antigen (PSA) ≤15 ng/ml were included. All patients underwent mpMRI with systematic and targeted biopsies before and after HIFU-PGA. The primary outcome was the rate of Cs-PCa at control biopsy within 1 year of treatment. Logistic regression was performed to identify predictive factors of our primary outcome. RESULTS: Median age was 67 years (IQR 61-71), median PSA was 7 ng/ml (IQR 5.5-8.9). Pre-treatment biopsies revealed 48 (62.3%) GGG2 lesions, 24 (31.2%) GGG3 and 5 (6.5%) GGG4 lesions. Cs-PCa was found in 24 (31.2%) patients at systematic control biopsy post-HIFU; Cs-PCa was in the treated lobe for 18 (27%) patients. No variables were identified as significant predictors of Cs-PCa at control biopsy, including PSA kinetics and control mpMRI. Median followup time was 17 months (95% CI 15-21). Median time to any retreatment was 32 months (95% CI 23-42). CONCLUSIONS: Systematic control biopsy within a year after PGA for Cs-PCa can identify the presence of residual Cs-PCa in up to a third of patients. From our early experience, control biopsy should be systematically offered patients regardless of PSA kinetics or control mpMRI results.

Is there a place for virtual reality simulators in assessment of competency in percutaneous renal access?

OBJECTIVE: To assess competency of urology post-graduate trainees (PGTs) in percutaneous renal access (PCA). METHODS: Upon obtaining ethics approval and informed consents, PGTs between post-graduate years (PGY-3 to PGY-5) from all four urology programs in Québec were recruited. PCA competency of each participant was assessed objectively by performing task 4 on the PERC Mentor™ simulator, where they had to correctly access and pop 7 balloons in 7 different renal calyces and subjectively by the validated Percutaneous Nephrolithotomy-Global Rating Scale (PCNL-GRS). RESULTS: A total of 26 PGTs with a mean age of 29.2 ± 0.7 years participated in this study. When compared with the 21 PGTs without practice, all 5 PGTs who had practiced on the simulator were competent (p = 0.03), performed the task with significantly shorter operative time (13.9 ± 0.7 vs. 4.4 ± 0.4 min; p < 0.001) and fluoroscopy time (9.3 ± 0.6 vs. 3.4 ± 0.4 min; p < 0.001), and had significantly higher PCNL-GRS scores (13 ± 0.6 vs. 20.6 ± 1; p < 0.001) and successful attempts to access renal calyces (23 ± 5 vs. 68.7 ± 11; p = 0.001). According to a pass score of 13/25, thirteen PGTs were competent. Competent PGTs performed the task with significantly shorter fluoroscopy time (9.8 vs. 6.5 min; p = 0.01) and higher percentage of successful attempts to access renal calyces (p < 0.001), higher PCNL-GRS scores (p < 0.001), and lower complications (p = 0.01). CONCLUSION: The PCNL-GRS in combination with the PERC Mentor™ simulator was able to differentiate between competent and non-competent PGTs.

Accuracy of cognitive MRI-targeted biopsy in hitting prostate cancer-positive regions of interest.

PURPOSE: Prostate cancer (PCa) diagnosis relies on clinical suspicion leading to systematic transrectal ultrasound-guided biopsy (TRUSGB). Multiparametric magnetic resonance imaging (mpMRI) allows for targeted biopsy of suspicious areas of the prostate instead of random 12-core biopsy. This method has been shown to be more accurate in detecting significant PCa. However, the precise spatial accuracy of cognitive targeting is unknown. METHODS: Consecutive patients undergoing mpMRI-targeted TRUSGB with cognitive registration (MRTB-COG) followed by robot-assisted radical prostatectomy were included in the present analysis. The regions of interest (ROIs) involved by the index lesion reported on mpMRI were subsequently targeted by two experienced urologists using the cognitive approach. The 27 ROIs were used as spatial reference. Mapping on radical prostatectomy specimen was used as reference to determine true-positive mpMRI findings. Per core correlation analysis was performed. RESULTS: Forty patients were included. Overall, 40 index lesions involving 137 ROIs (mean ROIs per index lesion 3.43) were identified on MRI. After correlating these findings with final pathology, 117 ROIs (85 %) were considered as true-positive lesions. A total of 102 biopsy cores directed toward such true-positive ROIs were available for final analysis. Cognitive targeted biopsy hit the target in 82 % of the cases (84/102). The only identified risk factor for missing the target was an anterior situated ROI (p = 0.01). CONCLUSION: In experienced hands, cognitive MRTB-COG allows for an accuracy of 82 % in hitting the correct target, given that it is a true-positive lesion. Anterior tumors are less likely to be successfully targeted.

A combination of hemostatic agents may safely replace deep medullary suture during laparoscopic partial nephrectomy in a pig model.

PURPOSE: We assessed whether a combination of the fibrin tissue adhesive Tisseel® (human fibrinogen and thrombin) plus the hemostatic matrix FloSeal® (bovine derived gelatin matrix/human thrombin) could safely replace the conventional deep medullary suture without compromising outcomes. MATERIALS AND METHODS: Laparoscopic mid pole and one-third partial nephrectomy was performed on the right kidney of 12 female pigs. The only difference between the 2 groups of 6 pigs each was the use of a fibrin tissue adhesive plus hemostatic matrix combination in group 2 instead of the deep medullary running suture in control group 1. Renal scans and angiograms were performed at baseline and before sacrifice at 5-week followup. Retrograde in vivo pyelogram was also done. RESULTS: No significant difference was seen in operative parameters or postoperative course between the groups. Renal scans revealed a statistically insignificant trend toward greater uptake loss in group 1 and angiograms showed 3 major vessel occlusions in that group. No active bleeding was detected. Those 3 kidneys had significantly poorer postoperative uptake on renal scan than that of other kidneys (18.6% vs 39.4%, p = 0.013). Only 1 small asymptomatic pseudoaneurysm was noted in group 1. No urine leakage was found in either group. No major vessel occlusion, pseudoaneurysm or urinary complications developed in group 2. CONCLUSIONS: Even after deep one-third partial nephrectomy FloSeal with concurrent Tisseel appeared sufficient to control major medullary vascular injuries and replace the deep medullary conventional suture without compromising operative outcomes. The potential advantages seen during functional and vascular examinations by decreasing the risk of unnecessary segmental vessel occlusion need further clinical evaluation.

Impact of the type of ultrasound probe on prostate cancer detection rate and characterization in patients undergoing MRI-targeted prostate biopsies using cognitive fusion.

PURPOSE: To assess the impact of ultrasound probe (end fire vs. side fire) during MRI-targeted prostate biopsy using cognitive fusion. METHODS: Inclusion criteria were as follows: consecutive patients undergoing prostate biopsies after multiparametric MRI; no PSA above 10 ng/ml; no clinical bulking disease; MRI areas suspicious for malignancy. From January 2011 to December 2012, 91 patients were included. A standard 10 TRUS-guided biopsy protocol plus 2 targeted biopsies at any MRI lesion was used. Patient's characteristics, MRI findings, and pathology evaluations were compared between the two groups. RESULTS: Mean patient age and PSA were 63 years and 5.95 ng/ml, respectively. The median number of MRI lesions was 2, and the mean volume of the index lesion was 0.64 cc. The overall PCa detection rate was 58.2 %. The MRI scoring system was significantly predictive for PCa detection and aggressiveness (p < 0.001). There was a not statistically significant trend toward greater PCa detection rate (+23 %) in the end-fire cohort (p = 0.235). The PCa detection rate is significantly improved by 1.7-fold in case of MRI score 4-5 lesion as compared to MRI score 3 lesion (p = 0.031) when using the end-fire probe. Conversely, the MRI score does not significantly influence the detection rate in the side-fire group (p = 0.250). The improvement in the PCa detection rate by the end-fire probe was predominantly reported in anterior and of apical peripheral MRI lesions. CONCLUSION: In case of high MRI score lesions, the PCa detection rate is significantly improved when using end-firing, particularly in case of anterior and apical peripheral lesions.

Prostate cancer detection rate with MRI-targeted biopsy alone using outpatient transperineal prostate biopsy.

INTRODUCTION: We aimed to compare the detection rate of prostate cancer (PCa) and clinically significant (cs)PCa by magnetic resonance imaging-guided targeted biopsy (MTBx) alone and MTBx plus systematic biopsy (SBx) using an outpatient transperineal (TP) approach under local anesthesia. METHODS: A retrospective study of patients who underwent outpatient TP prostate biopsy under local anesthesia at our tertiary institution between 2019 and 2022 was performed. To compare the proportions of PCa and csPCa in both pathways, McNemar's tests were used. Multivariable logistic regression model was fitted to determine the predictors of csPCa. RESULTS: Of 255 men included, 177 (69%) underwent MTBx alone. MTBx had similar detection rate for PCa (56%) and csPCa (47%) compared to the combination of MTBx and SBx (PCa, 61%; csPCa, 49%; p=0.1 and p=0.3, respectively). MTBx had lower median number of biopsy cores compared to the combination of MTBx and SBx (6 vs. 11, p<0.001). At multivariable logistic regression analysis, age (odds ratio [OR] 1.08 [1.04-1.13], p<0.001), prior negative biopsy (OR 0.19 [0.09-0.44], p<0.001), prostate-specific antigen density cutoff ≥ 0.15 (OR 3.17 [1.67-6.01], p<0.001), and prostate imaging reporting and data system ≥4 (OR 12.2 [4.21-35.6], p<0.001) were independent predictors of csPCa. CONCLUSIONS: MTBx showed similar diagnostic performance to the combination of MTBx and SBx in patients undergoing outpatient TP prostate biopsy. Future studies are needed to evaluate the role of MTBx in avoiding unnecessary biopsies.

Endoscopic vascular targeted photodynamic therapy with the photosensitizer WST11 for benign prostatic hyperplasia in the preclinical dog model.

PURPOSE: Vascular targeted photodynamic therapy with WST11 (TOOKAD® Soluble) is in phase III clinical trials of an interstitial transperineal approach for focal therapy of prostate cancer. We investigated the safety and efficacy of the endourethral route in the context of benign prostatic hyperplasia in the dog model. MATERIALS AND METHODS: An optical laser fiber was positioned in the prostatic urethra of 34 dogs, including 4 controls. It was connected to a 753 nm diode laser at 200 mW/cm fluence, delivering 200 to 300 J. WST11 (5 to 15 mg/kg) was infused intravenously in 2 modes, including continuous, starting 5 to 15 minutes before and during illumination, or a bolus 5 to 10 minutes before illumination. Prostate ultrasound, cystourethrogram, urodynamics and histopathology were performed. Followup was 1 week to 1 year. RESULTS: Endourethral WST11 vascular targeted photodynamic therapy was uneventful in all except 1 dog, which experienced urinary retention but reached the 1-week end point. All prostates except those in controls showed hemorrhagic lesions. They consisted of 2 levels of concentric alterations, including periurethral necrosis with endothelial layer destruction and adjacent inflammation/atrophy with normal blood vessels. Prostatic urethral width increased as early as 6 weeks after treatment, while prostatic volume decreased, reaching 25% by 18 to 26 weeks. A parallel decrease in urethral pressure at 6 weeks lasted up to 1 year. CONCLUSIONS: We confirmed the vascular effect of endourethral WST11 vascular targeted photodynamic therapy. To our knowledge we report for the first time that the resulting periurethral necrosis led to significant, sustained widening of the prostatic urethra, accompanied by long-term improvement in urodynamic parameters. These findings support future clinical applications of this minimally invasive approach to benign prostatic hyperplasia.

'A pain in the buttock': A case report of gluteal compartment syndrome after robotic partial nephrectomy.

Acute compartment syndrome is a surgical emergency that, if unrecognised, leads to tissue and muscle ischaemia, necrosis, multi-organ failure and even death. Gluteal compartment syndrome is a rare type of compartment syndrome that typically occurs as a sequela of trauma, and its presentation may be difficult to recognise. We describe a case of a patient who developed gluteal compartment syndrome following a prolonged renal surgery in lateral decubitus position. Our case report aims to raise clinicians' awareness to consideration of this rare syndrome in patients presenting with lower extremity or back pain after prolonged surgery.

Advances in PARP Inhibitors for Prostate Cancer.

Poly-adenosine diphosphate-ribose polymerase plays an essential role in cell function by regulating apoptosis, genomic stability and DNA repair. PARPi is a promising drug class that has gained significant traction in the last decade with good outcomes in different cancers. Several trials have sought to test its effectiveness in metastatic castration resistant prostate cancer (mCRPC). We conducted a comprehensive literature review to evaluate the current role of PARPi in this setting. To this effect, we conducted queries in the PubMed, Embase and Cochrane databases. We reviewed and compared all major contemporary publications on the topic. In particular, recent phase II and III studies have also demonstrated the benefits of olaparib, rucaparib, niraparib, talazoparib in CRPC. Drug effectiveness has been assessed through radiological progression or overall response. Given the notion of synthetic lethality and potential synergy with other oncological therapies, several trials are looking to integrate PARPi in combined therapies. There remains ongoing controversy on the need for genetic screening prior to treatment initiation as well as the optimal patient population, which would benefit most from PARPi. PARPi is an important asset in the oncological arsenal for mCRPC. New combinations with PARPi may improve outcomes in earlier phases of prostate cancer.

Performance of clear cell likelihood scores in characterizing solid renal masses at multiparametric MRI: an external validation study.

PURPOSE: The purpose of this study is to evaluate the accuracy and interobserver agreement of ccLS in diagnosing clear cell renal cell carcinoma (ccRCC). METHODS: This retrospective single-center study evaluated consecutive patients with solid renal masses who underwent mpMRI followed by percutaneous biopsy and/or surgical excision between January 2010 and December 2020. Predominantly (> 75%) cystic masses, masses with macroscopic fat and infiltrative masses were excluded. Two abdominal radiologists independently scored each renal mass according to the proposed ccLS algorithm. The diagnostic performance of ccLS categories for ccRCC was calculated using logistic regression modeling. Diagnostic accuracy for predicting ccRCC was calculated using 2 × 2 contingency tables. Interobserver agreement for ccLS was evaluated with Cohen's k statistic. RESULTS: A total of 79 patients (mean age, 63 years ± 12 [SD], 50 men) with 81 renal masses were evaluated. The mean size was 36 mm ± 28 (range 10-160). Of the renal masses included, 44% (36/81) were ccRCC. The area under the receiver operating characteristic curve was 0.87 (95% CI 0.79-0.95). Using ccLS ≥ 4 to diagnose ccRCC, the sensitivity, specificity, and positive predictive value were 93% (95% CI 79, 99), 63% (95% CI 48, 77), and 67% (95% CI 58, 75), respectively. The negative predictive value of ccLS ≤ 2 was 93% (95% CI 64, 99). The proportion of ccRCC by ccLS category 1 to 5 were 10%, 0%, 10%, 57%, and 84%, respectively. Interobserver agreement was moderate (k = 0.47). CONCLUSION: In this study, clear cell likelihood score had moderate interobserver agreement and resulted in 96% negative predictive value in excluding ccRCC.

Neoadjuvant versus Concurrent Androgen Deprivation Therapy in Localized Prostate Cancer Treated with Radiotherapy: A Systematic Review of the Literature.

BACKGROUND: There is an ongoing debate on the optimal sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) in patients with localized prostate cancer (PCa). Recent data favors concurrent ADT and RT over the neoadjuvant approach. METHODS: We conducted a systematic review in PubMed, EMBASE, and Cochrane Databases assessing the combination and optimal sequencing of ADT and RT for Intermediate-Risk (IR) and High-Risk (HR) PCa. FINDINGS: Twenty randomized control trials, one abstract, one individual patient data meta-analysis, and two retrospective studies were selected. HR PCa patients had improved survival outcomes with RT and ADT, particularly when a long-course Neoadjuvant-Concurrent-Adjuvant ADT was used. This benefit was seen in IR PCa when adding short-course ADT, although less consistently. The best available evidence indicates that concurrent over neoadjuvant sequencing is associated with better metastases-free survival at 15 years. Although most patients had IR PCa, HR participants may have been undertreated with short-course ADT and the absence of pelvic RT. Conversely, retrospective data suggests a survival benefit when using the neoadjuvant approach in HR PCa patients. INTERPRETATION: The available literature supports concurrent ADT and RT initiation for IR PCa. Neoadjuvant-concurrent-adjuvant sequencing should remain the standard approach for HR PCa and is an option for IR PCa.

Prophylactic A-Blockers for Radiotherapy-Induced Lower Urinary Tract Symptoms in Men with Prostate Cancer: A Phase III Randomized Trial.

PURPOSE: The present phase III randomized trial assessed the efficacy of prophylactic versus therapeutic α-blockers at improving RI-LUTSs in prostate cancer patients receiving external beam radiotherapy (EBRT). METHODS: A total of 148 prostate cancer patients were randomized 1:1 to receive either prophylactic silodosin on day one of EBRT or the occurrence of RI-LUTSs. LUTSs were quantified using the international prostate symptom score (IPSS) at regular intervals during the study. The primary endpoint was the change in the IPSS from baseline to the last day of radiotherapy (RT). Secondary endpoints included changes in IPSS from baseline to 4 weeks and 12 weeks after the start of RT. RESULTS: Patient demographics, baseline IPSS, and prescribed radiation doses were balanced between arms. On the last day of RT, the mean IPSS was 14.8 (SD 7.6) in the experimental arm and 15.7 (SD 8.5) in the control arm (p = 0.40). There were no significant differences in IPSSs between the study arms in the intention-to-treat (ITT) analysis at baseline, the last day of RT, and 4 and 12 weeks post-RT. CONCLUSION: Prophylactic α-blockers were not effective at significantly reducing RI-LUTSs in prostate cancer patients treated with EBRT. Treating patients with α-blockers at the onset of RI-LUTSs will avoid unnecessary drug exposure and toxicity.

Magnetic Resonance Imaging-Targeted Versus Systematic Prostate Biopsies: 2-year Follow-up of a Prospective Randomized Trial (PRECISE).

BACKGROUND: The prospective randomized PRECISE trial demonstrated that magnetic resonance imaging (MRI) with only targeted biopsy (TBx) was noninferior to systematic transrectal ultrasound biopsy (SBx) in the detection of International Society of Urological Pathology grade group (GG) ≥2 prostate cancer (PC). An unanswered question is the outcome for patients who avoided a biopsy because of negative MRI findings. OBJECTIVE: To explore the rate of PC diagnosis based on 2-yr MRI for PRECISE participants who had no biopsy and for patients who had a negative result or GG 1 on TBx in comparison to those with a negative result or GG 1 on SBx. DESIGN, SETTING, AND PARTICIPANTS: The PRECISE prospective trial was conducted at five Canadian academic centers. The present analysis was for trial participants who were not diagnosed with clinically significant PC (csPC) at baseline. Of 453 randomized patients, 146 were diagnosed with GG ≥2 at baseline and were excluded. Eligible patients for this study included 83 men from the MRI arm who had negative MRI findings and no biopsy, 120 from the overall cohort who had a negative SBx or TBx, and 72 from the overall cohort who were diagnosed with GG 1 disease. INTERVENTION: MRI at 2 yr in all men in the MRI and SBx arms and TBx for lesions with a Prostate Imaging-Reporting and Data System score of ≥3 or on the basis of clinical suspicion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the proportion of men diagnosed with GG ≥2 cancer. Secondary outcomes included the MRI outcome and the proportion of men diagnosed with GG 1 PC. RESULTS AND LIMITATIONS: Evaluable 2-yr MRI scans were available for 75 (56%) eligible patients in the MRI arm and 69 (49%) in the SBx arm. Of these patients, 55 (73%) in the MRI arm and 51 (67%) SBx arm had negative 2-yr MRI. Of the 76 patients in the SBx arm with 2-yr MRI, 16 (21%) had a biopsy, for which the result was negative in eight (10%), GG1 in two (2.6%), and GG ≥2 in six (7.9%) cases. Of the 75 men in the MRI arm with 2-yr MRI, eight (11%) were biopsied, for which the result was negative in four cases (5%) and GG ≥2 in the other four (5%). At 2 yr, including baseline biopsy results, 116/221 (52.5%) in the MRI arm and 113/204 (55%) in the SBx arm were free of GG ≥2 disease, treatment, death from any cause, or progression (OR 1.08; p = 0.66). CONCLUSIONS: After 2-yr follow-up including MRI for patients in both arms of PRECISE, there was no difference in the rate of csPC diagnosis between the MRI and SBx groups, even though 38% of men in the MRI group avoided an initial biopsy. PATIENT SUMMARY: The PRECISE trial compared systematic biopsy of the prostate to a strategy of magnetic resonance imaging (MRI) with targeted biopsy of any lesions suspicious for cancer on the scan. After 2 years of follow-up that included 2-year MRI with or without biopsy in both groups, there was no difference in the rate of diagnosis of significant cancer, even though 38% of men in the initial MRI arm avoided an initial biopsy, and 30% avoided biopsy altogether. The PRECISE trial is registered on ClinicalTrials.gov as NCT02936258.

Refining the orthotopic dog prostate cancer (DPC)-1 model to better bridge the gap between rodents and men.

BACKGROUND: Rodent models are often suboptimal for translational research on human prostate cancer (PCa). To better fill the gap with human, we refined the previously described orthotopic dog prostate cancer (DPC)-1 model. METHODS: Cyclosporine (Cy) A was used for immune suppression at varying doses and time-periods prior and after orthotopic DPC-1 cell implantation in the dog prostate (n = 12). Follow up included digital rectal examination, ultrasound prostate imaging and biopsies of hypoechoic areas. At necropsy, the prostate, iliosacral lymph nodes (LN), lung nodules, and suspicious bone segments were collected for histopathology. RESULTS: 15 mg CyA/kg daily for 10 days was optimal for tumor take. Maintaining these conditions post-implantation resulted in a rapid tumor development within and beyond the prostate and in iliosacral LNs. To minimize tumor burden, 10 times less DPC-1 cells were implanted. A series of dogs was next followed for 3-4 months, under continuous immune suppression (n = 3) or with CyA interruption at 8.5 weeks (n = 2). In all instances, multifocal tumors were found within the prostate. Predominant patterns were micropapillary and cribriform. Metastases were present in iliosacral LNs and lungs. Moreover, pelvic bone metastases producing a mixed osteoblastic/osteolytic reaction were confirmed in two dogs, one per group. Lastly, the release of CyA 1-2 weeks post-implantation (n = 3) did not prevent tumor growth and spreading to LNs. CONCLUSIONS: The continuing growth of DPC-1 tumors despite the release of CyA and, for the first time, spreading to bones renders this refined model closer to the spontaneous canine and hormone-refractory phase of human PCa.

Salvage external beam radiotherapy after HIFU failure in localized prostate cancer: A single institution experience.

Purpose/objectives: High-intensity focused ultrasound (HIFU) remains investigational as primary treatment for localized prostate cancer but is sometimes offered to select patients. At HIFU failure, data guiding salvage treatment is limited to small retrospective series with short follow-up. We evaluated our institutional experience using salvage radiation therapy (SRT) after HIFU failure. Materials/methods: We conducted a retrospective analysis of patients with local failure post-HIFU who received salvage image-guided external beam radiation therapy (EBRT) delivered via intensity-modulated radiotherapy (IMRT). Our primary endpoint was biochemical failure-free survival (bFFS) defined as prostate-specific antigen (PSA) nadir + 2 ng/mL. Secondary endpoints included metastasis-free survival (MFS) and overall survival (OS). Endpoints were evaluated using Kaplan-Meier analysis. Results: From 2013 to 2018, 12 out of 96 patients treated with primary HIFU received SRT via conventional or moderate hypofractionation. Median time from HIFU to SRT was 13.5 months. Seven patients had stage migration to high-risk disease at the time of SRT. Mean PSA prior to SRT was 8.2ug/L and mean nadir post-SRT was 1.2ug/L. Acute International Prostate Symptom Score (IPSS) as well as International Index of Erectile Dysfunction (IIEF) scores were similar to baseline (p = 0.5 and 0.1, respectively). Late toxicities were comparable to those reported after primary EBRT for localized prostate cancer. At a median follow-up of 46 months, the OS was 100%. The 5-year bFFS and MFS were both 83.3%. Conclusions: To our knowledge, we report one of the largest series on contemporary SRT post HIFU failure. We show that SRT is feasible, effective and carries no additional acute or delayed toxicity.

Preclinical study of the novel vascular occluding agent, WST11, for photodynamic therapy of the canine prostate.

PURPOSE: Vascular targeted photodynamic therapy with WST09 shows promise for recurrent prostate cancer after radiation but hydrophobicity in aqueous solutions limited application. We tested the safety and efficacy of WST11, a novel water soluble vascular occluding agent, for vascular targeted photodynamic therapy of the dog prostate and compared it to WST09 vascular targeted photodynamic therapy. MATERIALS AND METHODS: Optical fibers were inserted in the prostate and connected to diode lasers. WST11 (Steba Biotech, Cedex, France) at varying doses, including a drug control with no light in 34 dogs, and WST09 (Steba Biotech) (2 mg/kg) in 3 dogs were infused during 10 minutes. Illumination was initiated at 5 or 10 minutes, and lasted up to 33.2 minutes based on laser fluence and delivered energy. Blood was collected for analysis and pharmacokinetics. The end point was at 1 week. RESULTS: No vascular targeted photodynamic therapy associated change was observed in blood pressure or blood test values. Circulating WST11 increased with drug infusion and decreased rapidly during 1 hour to reach undetectable levels by 24 hours. All except 1 dog with bowel intussusception did well after vascular targeted photodynamic therapy with only mild urinary symptoms that resolved within 24 to 48 hours. Lung and liver were normal. Hemorrhage was present in all prostates except controls. This translated into necrosis at a WST11 threshold and within a window of doses at fixed illumination. Necrosis was associated with loss of the vessel endothelial layer. Fluence highly impacted necrosis. WST11 vascular targeted photodynamic therapy was advantageously comparable to WST09 vascular targeted photodynamic therapy, and optimally ablated about 5.0 cm(3) of tissue per lobe and about 10 cm(3) of the whole prostate. CONCLUSIONS: The safety and efficacy of WST11 vascular targeted photodynamic therapy in the dog prostate support clinical applications for prostate cancer and benign prostatic hyperplasia.