A Description and Safety Overview of Irreversible Electroporation for Prostate Tissue Ablation in Intermediate-Risk Prostate Cancer Patients: Preliminary Results from the PRESERVE Trial.

The PRESERVE study (NCT04972097) aims to evaluate the safety and effectiveness of the NanoKnife System to ablate prostate tissue in patients with intermediate-risk prostate cancer (PCa). The NanoKnife uses irreversible electroporation (IRE) to deliver high-voltage electrical pulses to change the permeability of cell membranes, leading to cell death. A total of 121 subjects with organ-confined PCa ≤ T2c, prostate-specific antigens (PSAs) ≤ 15 ng/mL, and a Gleason score of 3 + 4 or 4 + 3 underwent focal ablation of the index lesion. The primary endpoints included negative in-field biopsy and adverse event incidence, type, and severity through 12 months. At the time of analysis, the trial had completed accrual with preliminary follow-up available. Demographics, disease characteristics, procedural details, PSA responses, and adverse events (AEs) are presented. The median (IQR) age at screening was 67.0 (61.0-72.0) years and Gleason distribution 3 + 4 (80.2%) and 4 + 3 (19.8%). At 6 months, all patients with available data (n = 74) experienced a median (IQR) percent reduction in PSA of 67.6% (52.3-82.2%). Only ten subjects (8.3%) experienced a Grade 3 adverse event; five were procedure-related. No Grade ≥ 4 AEs were reported. This study supports prior findings that IRE prostate ablation with the NanoKnife System can be performed safely. Final results are required to fully assess oncological, functional, and safety outcomes.

The Transatlantic Recommendations for Prostate Gland Evaluation with Magnetic Resonance Imaging After Focal Therapy (TARGET): A Systematic Review and International Consensus Recommendations.

BACKGROUND AND OBJECTIVE: Magnetic resonance imaging (MRI) can detect recurrences after focal therapy for prostate cancer but there is no robust guidance regarding its use. Our objective was to produce consensus recommendations on MRI acquisition, interpretation, and reporting after focal therapy. METHODS: A systematic review was performed in July 2022 to develop consensus statements. A two-round consensus exercise was then performed, with a consensus meeting in January 2023, during which 329 statements were scored by 23 panellists from Europe and North America spanning urology, radiology, and pathology with experience across eight focal therapy modalities. Using RAND Corporation/University of California-Los Angeles methodology, the Transatlantic Recommendations for Prostate Gland Evaluation with MRI after Focal Therapy (TARGET) were based on consensus for statements scored with agreement or disagreement. KEY FINDINGS AND LIMITATIONS: In total, 73 studies were included in the review. All 20 studies (100%) reporting suspicious imaging features cited focal contrast enhancement as suspicious for cancer recurrence. Of 31 studies reporting MRI assessment criteria, the Prostate Imaging-Reporting and Data System (PI-RADS) score was the scheme used most often (20 studies; 65%), followed by a 5-point Likert score (six studies; 19%). For the consensus exercise, consensus for statements scored with agreement or disagreement increased from 227 of 295 statements (76.9%) in round one to 270 of 329 statements (82.1%) in round two. Key recommendations include performing routine MRI at 12 mo using a multiparametric protocol compliant with PI-RADS version 2.1 standards. PI-RADS category scores for assessing recurrence within the ablation zone should be avoided. An alternative 5-point scoring system is presented that includes a major dynamic contrast enhancement (DCE) sequence and joint minor diffusion-weighted imaging and T2-weighted sequences. For the DCE sequence, focal nodular strong early enhancement was the most suspicious imaging finding. A structured minimum reporting data set and minimum reporting standards for studies detailing MRI data after focal therapy are presented. CONCLUSIONS AND CLINICAL IMPLICATIONS: The TARGET consensus recommendations may improve MRI acquisition, interpretation, and reporting after focal therapy for prostate cancer and provide minimum standards for study reporting. PATIENT SUMMARY: Magnetic resonance imaging (MRI) scans can detect recurrent of prostate cancer after focal treatments, but there is a lack of guidance on MRI use for this purpose. We report new expert recommendations that may improve practice.

Novel radiomic analysis on bi-parametric MRI for characterizing differences between MR non-visible and visible clinically significant prostate cancer.

Background: around one third of clinically significant prostate cancer (CsPCa) foci are reported to be MRI non-visible (MRI─). Objective: To quantify the differences between MR visible (MRI+) and MRI─ CsPCa using intra- and peri-lesional radiomic features on bi-parametric MRI (bpMRI). Methods: This retrospective and multi-institutional study comprised 164 patients with pre-biopsy 3T prostate multi-parametric MRI from 2014 to 2017. The MRI─ CsPCa referred to lesions with PI-RADS v2 score < 3 but ISUP grade group > 1. Three experienced radiologists were involved in annotating lesions and PI-RADS assignment. The validation set (Dv) comprised 52 patients from a single institution, the remaining 112 patients were used for training (Dt). 200 radiomic features were extracted from intra-lesional and peri-lesional regions on bpMRI.Logistic regression with least absolute shrinkage and selection operator (LASSO) and 10-fold cross-validation was applied on Dt to identify radiomic features associated with MRI─ and MRI+ CsPCa to generate corresponding risk scores RMRI─ and RMRI+. RbpMRI was further generated by integrating RMRI─ and RMRI+. Statistical significance was determined using the Wilcoxon signed-rank test. Results: Both intra-lesional and peri-lesional bpMRI Haralick and CoLlAGe radiomic features were significantly associated with MRI─ CsPCa (p < 0.05). Intra-lesional ADC Haralick and CoLlAGe radiomic features were significantly different among MRI─ and MRI+ CsPCa (p < 0.05). RbpMRI yielded the highest AUC of 0.82 (95 % CI 0.72-0.91) compared to AUCs of RMRI+ 0.76 (95 % CI 0.63-0.89), and PI-RADS 0.58 (95 % CI 0.50-0.72) on Dv. RbpMRI correctly reclassified 10 out of 14 MRI─ CsPCa on Dv. Conclusion: Our preliminary results demonstrated that both intra-lesional and peri-lesional bpMRI radiomic features were significantly associated with MRI─ CsPCa. These features could assist in CsPCa identification on bpMRI.

Primary Whole-gland Ablation for the Treatment of Clinically Localized Prostate Cancer: A Focal Therapy Society Best Practice Statement.

CONTEXT: Whole-gland ablation is a feasible and effective minimally invasive treatment for localized prostate cancer (PCa). Previous systematic reviews supported evidence for favorable functional outcomes, but oncological outcomes were inconclusive owing to limited follow-up. OBJECTIVE: To evaluate the real-world data on the mid- to long-term oncological and functional outcomes of whole-gland cryoablation and high-intensity focused ultrasound (HIFU) in patients with clinically localized PCa, and to provide expert recommendations and commentary on these findings. EVIDENCE ACQUISITION: We performed a systematic review of PubMed, Embase, and Cochrane Library publications through February 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. As endpoints, baseline clinical characteristics, and oncological and functional outcomes were assessed. To estimate the pooled prevalence of oncological, functional, and toxicity outcomes, and to quantify and explain the heterogeneity, random-effect meta-analyses and meta-regression analyses were performed. EVIDENCE SYNTHESIS: Twenty-nine studies were identified, including 14 on cryoablation and 15 on HIFU with a median follow-up of 72 mo. Most of the studies were retrospective (n = 23), with IDEAL (idea, development, exploration, assessment, and long-term study) stage 2b (n = 20) being most common. Biochemical recurrence-free survival, cancer-specific survival, overall survival, recurrence-free survival, and metastasis-free survival rates at 10 yr were 58%, 96%, 63%, 71-79%, and 84%, respectively. Erectile function was preserved in 37% of cases, and overall pad-free continence was achieved in 96% of cases, with a 1-yr rate of 97.4-98.8%. The rates of stricture, urinary retention, urinary tract infection, rectourethral fistula, and sepsis were observed to be 11%, 9.5%, 8%, 0.7%, and 0.8%, respectively. CONCLUSIONS: The mid- to long-term real-world data, and the safety profiles of cryoablation and HIFU are sound to support and be offered as primary treatment for appropriate patients with localized PCa. When compared with other existing treatment modalities for PCa, these ablative therapies provide nearly equivalent intermediate- to long-term oncological and toxicity outcomes, as well as excellent pad-free continence rates in the primary setting. This real-world clinical evidence provides long-term oncological and functional outcomes that enhance shared decision-making when balancing risks and expected outcomes that reflect patient preferences and values. PATIENT SUMMARY: Cryoablation and high-intensity focused ultrasound are minimally invasive treatments available to selectively treat localized prostate cancer, considering their nearly comparable intermediate- to long term cancer control and preservation of urinary continence to other radical treatments in the primary setting. However, a well-informed decision should be made based on one's values and preferences.

Cost-effectiveness of an urinary biomarker panel in combination with MRI for prostate cancer diagnosis.

PURPOSE: The health impact and cost-effectiveness of the biomarker test SelectMDx were evaluated when used in combination with MRI, in two US populations: biopsy naïve men and men with a previous negative biopsy. METHODS: Using a decision model, the current MRI strategy was compared with two SelectMDx strategies: SelectMDx used before MRI to select men for MRI and SelectMDx used after a negative MRI to select men for biopsy. Parameters were informed by the literature most relevant for both populations. Differences in quality-adjusted life years (QALYs) and costs between the current strategy and the SelectMDx strategies were calculated using two different assumptions regarding PCa-specific mortality (SPCG-4 and PIVOT). RESULTS: In biopsy naïve men, the use of SelectMDx before MRI results in a gain of 0.004 QALY per patient under the SPCG-4 scenario, and a gain of 0.030 QALY under the PIVOT scenario. The cost savings are $1650 per patient. When used after MRI, SelectMDx results in a QALY gain per patient of 0.004 (SPCG-4), and 0.006 (PIVOT) with $262 in cost savings. In the previous negative population, SelectMDx before MRI results in a QALY gain of 0.006 (SPCG-4) and 0.022 (PIVOT), with $1281 in cost savings per patient. SelectMDx after MRI results in a QALY gain of 0.003 (SPCG-4) and 0.004 (PIVOT) with $193 in cost savings. CONCLUSION: Application of SelectMDx results in better health outcomes and cost savings. The value of SelectMDx was highest when used before MRI to select patients for MRI and subsequent biopsy.

Narrative review-focal therapy: are we ready to change the prostate cancer treatment paradigm?

Background and Objective: Prostate cancer (PCa) has seen improved detection methods with a subsequent rise in disease prevalence, making novel prostate cancer treatment options an exciting yet controversial topic. Current treatment modalities encompass traditional approaches, namely surgery (radical prostatectomy) and radiation therapy. While heralded as a standard of care, these modalities may come with significant risk profiles, primarily sexual (erectile dysfunction) and urinary incontinence. Advances in technology and imaging, specifically multi-parametric MRI, have afforded great leaps in targeted focal therapy as a primary treatment option for localized PCa. This review identifies and highlights published data for novel and emerging PCa focal therapy (FT) modalities. Methods: Our study identified and reviewed the current literature for relevant investigations related to primary FT modalities as they apply to the treatment of prostate cancer. After an internal review, relevant studies (published in English, between 2000-April 2022) were included for analysis and summarization. Key Content and Findings: We provide a concise review of several novel focal therapy modalities that offer realistic potential for primary treatment of localized prostate cancer. Our narrative includes studies that primarily include their respective results, specifically focusing on those that reported both oncologic and quality-of-life outcomes after focal therapy. While still in its cumulative infancy, we discuss the current limitations, future directions, and advancements that hopefully push focal therapy into the limelight. Conclusions: While many of the mentioned focal therapies for PCa have shown promising pathologic and quality of life outcomes, further clinical evidence is required to change overall management guidelines and recommendations. The advantages of FT in avoiding sexual and urinary side-effects of radical surgery or radiation are apparent; however, it is necessary to recognize the need for further long-term evidence that is durable over time and comparable to current gold-standard treatment options.

Alternatives to whole gland treatment for localized prostate cancer: a review of novel focal therapies.

PURPOSE OF REVIEW: The mainstays of the management of clinically localized prostate cancer have historically rested upon active surveillance, radiation therapy, or radical prostatectomy. Although both radiation and surgical treatment of localized prostate cancer can achieve excellent oncologic outcomes, the subsequent potential adverse effects of urinary stress incontinence and erectile dysfunction are unappealing to patients. This has led to investigational studies centered upon focal treatment of the cancerous lesion, with the aim to improve quality-of-life outcomes. In this review, we describe numerous novel modalities, including nanoparticle ablation and irreversible electroporation, which are being utilized for the focal treatment of clinically localized prostate cancer. RECENT FINDINGS: Although many of these novel therapies are in their investigational infancy, several have revealed very promising results both in their post-treatment pathologic outcomes as well as objective quality-of-life measures. SUMMARY: Initial data regarding novel focal therapy for prostate cancer treatment show promising short-term outcomes in regards to oncologic and quality-of-life assessments. Further investigational studies are needed to determine inclusion criteria for the selection of optimal candidates.

Available evidence on HIFU for focal treatment of prostate cancer: a systematic review

ABSTRACT Purpose: Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa. Material and methods: We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included. Results: Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade. Conclusions: This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.

Prostate MRI using a rigid two-channel phased-array endorectal coil: comparison with phased array coil acquisition at 3 T.

BACKGROUND: To compare image quality, lesion detection and patient comfort of 3T prostate MRI using a combined rigid two-channel phased-array endorectal coil and an external phased-array coil (ERC-PAC) compared to external PAC acquisition in the same patients. METHODS: Thirty three men (mean age 65.3y) with suspected (n = 15) or biopsy-proven prostate cancer (PCa, n = 18) were prospectively enrolled in this exploratory study. 3T prostate MRI including T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) was performed using an ERC-PAC versus PAC alone, in random order. Image quality, lesion detection and characterization (biparametric PI-RADSv2.1) were evaluated by 2 independent observers. Estimated signal-to-noise ratio (eSNR) was measured in identified lesions and the peripheral zone (PZ). Patient comfort was assessed using a questionnaire. Data were compared between sequences and acquisitions. Inter/intra-observer agreement for PI-RADS scores was evaluated. RESULTS: Twenty four prostate lesions (22 PCa) were identified in 20/33 men. Superior image quality was found for ERC-PAC compared to PAC for T2WI for one observer (Obs.1, p < 0.03) and high b-value DWI for both observers (p < 0.05). The sensitivity of PI-RADS for lesion detection for ERC-PAC and PAC acquisitions was 79.2 and 75% for Obs.1, and 79.1 and 66.7%, for Obs.2, without significant difference for each observer (McNemar p-values ≥0.08). Inter-/intra-observer agreement for PI-RADS scores was moderate-to-substantial (kappa = 0.52-0.84). Higher eSNR was observed for lesions and PZ for T2WI and PZ for DWI using ERC-PAC (p < 0.013). Most patients (21/33) reported discomfort at ERC insertion. CONCLUSION: Despite improved image quality and eSNR using the rigid ERC-PAC combination, no significant improvement in lesion detection was observed, therefore not supporting the routine use of ERC for prostate MRI.

Molecular biomarkers in the context of focal therapy for prostate cancer: recommendations of a Delphi Consensus from the Focal Therapy Society.

BACKGROUND: Focal therapy (FT) for prostate cancer (PCa) is promising. However, long-term oncological results are awaited and there is no consensus on follow-up strategies. Molecular biomarkers (MB) may be useful in selecting, treating and following up men undergoing FT, though there is limited evidence in this field to guide practice. We aimed to conduct a consensus meeting, endorsed by the Focal Therapy Society, amongst a large group of experts, to understand the potential utility of MB in FT for localized PCa. METHODS: A 38-item questionnaire was built following a literature search. The authors then performed three rounds of a Delphi Consensus using DelphiManager, using the GRADE grid scoring system, followed by a face-to-face expert meeting. Three areas of interest were identified and covered concerning MB for FT, 1) the current/present role; 2) the potential/future role; 3) the recommended features for future studies. Consensus was defined using a 70% agreement threshold. RESULTS: Of 95 invited experts, 42 (44.2%) completed the three Delphi rounds. Twenty-four items reached a consensus and they were then approved at the meeting involving (N.=15) experts. Fourteen items reached a consensus on uncertainty, or they did not reach a consensus. They were re-discussed, resulting in a consensus (N.=3), a consensus on a partial agreement (N.=1), and a consensus on uncertainty (N.=10). A final list of statements were derived from the approved and discussed items, with the addition of three generated statements, to provide guidance regarding MB in the context of FT for localized PCa. Research efforts in this field should be considered a priority. CONCLUSIONS: The present study detailed an initial consensus on the use of MB in FT for PCa. This is until evidence becomes available on the subject.

Available evidence on HIFU for focal treatment of prostate cancer: a systematic review.

PURPOSE: Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa. MATERIAL AND METHODS: We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included. RESULTS: Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade. CONCLUSIONS: This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.

Novel Automated Three-Dimensional Surgical Planning Tool and Magnetic Resonance Imaging/Ultrasound Fusion Technology to Perform Nanoparticle Ablation and Cryoablation of the Prostate for Focal Therapy.

Purpose: Although MRI/ultrasound fusion has been primarily used to assist in the diagnosis of prostate cancer, this technology can also be used to focally treat localized prostate cancer. We present one case of nanoparticle-directed ablation and two cases of cryoablation to focally treat prostate tumors. Patients and Methods: Three patients underwent MRI/ultrasound fusion transperineal prostate biopsies to confirm low- to intermediate-risk prostate cancer. The MRI lesions correlated with the biopsy-proven disease. Pelvic MRI segmentation was performed with DynaCAD 5.0 workstation. The MRI lesion including a 6 to 10 mm margin, prostate, bladder, urethra, urethral sphincter, rectum, and pubic bone were segmented. MRI/ultrasound fusion was performed with the novel Philips UroNav 4.0 system. Lesions were treated with focal nanoparticle ablation or focal cryoablation. Results: A 69-year-old man with a right posterior medial peripheral zone lesion positive for Gleason grade group (GG)3 cancer was treated with focal nanoparticle ablation. The UroNav 4.0 system reported 100% ablation of the segmented tumor and 94% of the 6 to 10 mm margin at the end of the case. A 68-year-old man with a left anterior fibromuscular stroma lesion positive for Gleason GG2 cancer and a 71-year-old man with a right peripheral zone posterior lateral lesion positive for Gleason GG1 cancer were treated with focal cryoablation. The UroNav 4.0 system reported 100% ablation of the segmented tumor and 82% of the 6 to 10 mm margin at the end of the case. Conclusion: Observation of the prostate tumor(s), surrounding critical structures, and pelvis in three dimensions (3D), along with the anticipated ablation zone, is one of the challenges of pelvic surgery and percutaneous ablation. The DynaCAD 5.0 Urology system can create an auto-segmented 3D rendering of critical structures and the tumor(s), as well as observation and quantification of the anticipated ablation coverage, to facilitate preoperative planning of needle placement. ClinicalTrials.gov nos.: NCT02680535 and NCT04656678.

MRI Fusion Transperineal Prostate Biopsy Instructions and Troubleshooting.

MRI fusion transperineal prostate biopsy is becoming more utilized because of its increased detection of clinically significant prostate cancer and decreased risk of sepsis. We present a video guide to properly perform this prostate biopsy technique using the Philips UroNav MRI fusion software. The MRI fusion transperineal prostate biopsy requires an ultrasound machine and transrectal ultrasound probe, MRI fusion machine, and a complete compliment of operating room supplies and staff. Local anesthesia is injected in the perineal subcutaneous tissue, prostate capsule apex, and prostate base near the seminal vesicles. Biopsy is performed through the grid plate and specimens are directly placed in formalin jars. The multitude of equipment and interfaces required by this procedure results in common problems in the setup, segmentation, and biopsy technique, which are addressed in the troubleshooting section.

Adjunctive Coil Embolization of the Prostatic Arteries After Particle Embolization for Prostatic Artery Embolization.

PURPOSE: To describe the feasibility, safety and short-term results of prostatic artery embolization (PAE) performed with adjunctive coil embolization of the main prostatic arteries (PA) following particle embolization. MATERIALS AND METHODS: A total of 95 patients who underwent PAE with adjunctive bilateral coil embolization of the PAs following particle embolization between September 2018 and May 2021 were included. The patients had a mean prostate size of 115 ± 64 ml, 18/95 with hematuria symptoms, and 16/95 with indwelling urinary catheters. Coil embolization was performed in the main PAs prior to the bifurcation into the anteromedial and posterolateral branches using detachable microcoils. International Prostate Symptoms Score (IPSS), quality of life (QOL), maximum flow rate (Qmax) and adverse events were recorded. RESULTS: IPSS were improved by - 11.2 ± 7.9 (n = 49, P < 0.001) and QOL by - 2.4 ± 1.8 (n = 49, P < 0.001) over a mean follow-up of 10.7 ± 7.9 weeks. Qmax did not demonstrate statistical significance. Twelve patients with hematuria (67%) showed improvement or resolution and twelve patients with indwelling or intermittent catheters (75%) were no longer catheter dependent. Two patients underwent a repeat PAE. There were no adverse events which were attributable to coil embolization. CONCLUSION: Adjunctive coil embolization of the main PAs following particle embolization is a technically feasible technique with similar short-term clinical outcomes compared to prior studies. This novel technique warrants further prospective investigation with controls.

Intraoperative Digital Analysis of Ablation Margins (DAAM) by Fluorescent Confocal Microscopy to Improve Partial Prostate Gland Cryoablation Outcomes.

Partial gland cryoablation (PGC) aims at destroying prostate cancer (PCa) foci while sparing the unaffected prostate tissue and the functionally relevant structures around the prostate. Magnetic Resonance Imaging (MRI) has boosted PGC, but available evidence suggests that ablation margins may be positive due to MRI-invisible lesions. This study aimed at determining the potential role of intraoperative digital analysis of ablation margins (DAAM) by fluoresce confocal microscopy (FCM) of biopsy cores taken during prostate PGC. Ten patients with low to intermediate risk PCa scheduled for PGC were enrolled. After cryo-needles placement, 76 biopsy cores were taken from the ablation margins and stained by the urologist for FCM analysis. Digital images were sent for "real-time" pathology review. DAAM, always completed within the frame of PGC treatment (median time 25 min), pointed out PCa in 1/10 cores taken from 1 patient, thus prompting placement of another cryo-needle to treat this area. Standard HE evaluation confirmed 75 cores to be cancer-free while displayed a GG 4 PCa in 7% of the core positive at FCM. Our data point out that IDAAM is feasible and reliable, thus representing a potentially useful tool to reduce the risk of missing areas of PCa during PGC.

An integrated nomogram combining deep learning, Prostate Imaging-Reporting and Data System (PI-RADS) scoring, and clinical variables for identification of clinically significant prostate cancer on biparametric MRI: a retrospective multicentre study.

BACKGROUND: Biparametric MRI (comprising T2-weighted MRI and apparent diffusion coefficient maps) is increasingly being used to characterise prostate cancer. Although previous studies have combined Prostate Imaging-Reporting & Data System (PI-RADS)-based MRI findings with routinely available clinical variables and with deep learning-based imaging predictors, respectively, for prostate cancer risk stratification, none have combined all three. We aimed to construct an integrated nomogram (referred to as ClaD) combining deep learning-based imaging predictions, PI-RADS scoring, and clinical variables to identify clinically significant prostate cancer on biparametric MRI. METHODS: In this retrospective multicentre study, we included patients with prostate cancer, with histopathology or biopsy reports and a screening or diagnostic MRI scan in the axial view, from four cohorts in the USA (from University Hospitals Cleveland Medical Center, Icahn School of Medicine at Mount Sinai, Cleveland Clinic, and Long Island Jewish Medical Center) and from the PROSTATEx Challenge dataset in the Netherlands. We constructed an integrated nomogram combining deep learning, PI-RADS score, and clinical variables (prostate-specific antigen, prostate volume, and lesion volume) using multivariable logistic regression to identify clinically significant prostate cancer on biparametric MRI. We used data from the first three cohorts to train the nomogram and data from the remaining two cohorts for independent validation. We compared the performance of our ClaD integrated nomogram with that of integrated nomograms combining clinical variables with either the deep learning-based imaging predictor (referred to as DIN) or PI-RADS score (referred to as PIN) using area under the receiver operating characteristic curves (AUCs). We also compared the ability of the nomograms to predict biochemical recurrence on a subset of patients who had undergone radical prostatectomy. We report cross-validation AUCs as means for the training set and used AUCs with 95% CIs to assess the performance on the test set. The difference in AUCs between the models were tested for statistical significance using DeLong's test. We used log-rank tests and Kaplan-Meier curves to analyse survival. FINDINGS: We investigated 592 patients (823 lesions) with prostate cancer who underwent 3T multiparametric MRI at five hospitals in the USA between Jan 8, 2009, and June 3, 2017. The training data set consisted of 368 patients from three sites (the PROSTATEx Challenge cohort [n=204], University Hospitals Cleveland Medical Center [n=126], and Icahn School of Medicine at Mount Sinai [n=38]), and the independent validation data set consisted of 224 patients from two sites (Cleveland Clinic [n=151] and Long Island Jewish Medical Center [n=73]). The ClaD clinical nomogram yielded an AUC of 0·81 (95% CI 0·76-0·85) for identification of clinically significant prostate cancer in the validation data set, significantly improving performance over the DIN (0·74 [95% CI 0·69-0·80], p=0·0005) and PIN (0·76 [0·71-0·81], p<0·0001) nomograms. In the subset of patients who had undergone radical prostatectomy (n=81), the ClaD clinical nomogram resulted in a significant separation in Kaplan-Meier survival curves between patients with and without biochemical recurrence (HR 5·92 [2·34-15·00], p=0·044), whereas the DIN (1·22 [0·54-2·79], p=0·65) and PIN nomograms did not (1·30 [0·62-2·71], p=0·51). INTERPRETATION: Risk stratification of patients with prostate cancer using the integrated ClaD nomogram could help to identify patients with prostate cancer who are at low risk, very low risk, and favourable intermediate risk, who might be candidates for active surveillance, and could also help to identify patients with lethal prostate cancer who might benefit from adjuvant therapy. FUNDING: National Cancer Institute of the US National Institutes of Health, National Institute for Biomedical Imaging and Bioengineering, National Center for Research Resources, US Department of Veterans Affairs Biomedical Laboratory Research and Development Service, US Department of Defense, US National Institute of Diabetes and Digestive and Kidney Diseases, The Ohio Third Frontier Technology Validation Fund, Case Western Reserve University, Dana Foundation, and Clinical and Translational Science Collaborative.

MRI-guided focal laser ablation of prostate cancer: a prospective single-arm, single-center trial with 3 years of follow-up.

PURPOSE: We aimed to assess post-interventional and 36-month follow-up results of a single-center, single-arm, in-bore phase I trial of focal laser ablation (FLA) guided by multiparametric magnetic resonance imaging (mpMRI). METHODS: FLA procedures were done in-bore MRI using a transperineal approach. Primary endpoints were feasibility and safety expressed as lack of grade 3 complications. Secondary endpoints were changes in international prostate symptom score (IPSS), sexual health inventory for men (SHIM), quality of life (QoL) scores, and serum prostate specific antigen (PSA) levels. Treatment outcomes were assessed by combined mpMRI-ultrasound fusion-guided and extended sextant systematic biopsy after 12, 24, and optionally after 36 months. RESULTS: Fifteen participants were included. Seven patients (46.67%) had Gleason 3+3 and 8 patients (53.33%) had Gleason 3+4 cancer. All patients tolerated the procedure well, and no grade 3/4 complications occurred. All grade 1 and 2 complications were transient and resolved completely. There was no significant change in mean IPSS from baseline (-1, p = 0.460) and QoL (0, p = 0.441) scores following FLA but there was a significant drop in mean SHIM scores (-2, p = 0.010) compared to pretreatment baselines. Mean PSA significantly decreased after FLA (-2.5, p < 0.001). Seven out of 15 patients (46.67%) had residual cancer in, adjacent, or in close proximity to the treatment area (1 × 4+3=7, 1 × 3+4=7, and 5 × 3+3=6). Four out of 15 patients (26.67%) underwent salvage therapy (2 repeat FLA, 2 radical prostatectomy). CONCLUSION: After 3 years of follow-up we conclude focal laser ablation is safe and feasible without significant complications.