Alessandro Marquis

Objectives: To assess the oncological and functional outcomes of magnetic resonance imaging‐ultrasonography (MRI‐US) fusion‐guided focal cryoablation (FC) using a novel three‐dimensional Advanced Annotation Platform (AAP) in patients with localised prostate cancer (PCa) and compare results between expert and beginner surgeons to evaluate the impact of prior focal therapy (FT) experience on FT outcomes. Patients and Methods: A prospective single‐arm trial enrolled 50 men with low‐ to intermediate‐risk PCa who underwent FC between December 2020 and September 2023. MRI‐US fusion‐guided FC was performed using the UroNav AAP by two surgeons with different FT experience (>200 vs 0), with 19 cases carried out by an expert and 31 by a beginner surgeon. Follow‐up included prostate‐specific antigen, multiparametric MRI, and protocol biopsy at 1 year. The primary outcome was failure‐free survival (FFS), defined as the transition to radical salvage treatment or to systemic therapy, development of PCa metastases, or PCa‐specific death. Secondary outcomes included oncological control and functional outcomes. Post hoc analyses were performed to assess learning curves and compare outcomes between surgeons with different experience levels. Results: The 2‐year FFS was 96% (95% confidence interval [CI] 90.7–100%). The 1‐year protocol biopsy showed a 6% in‐field (IFR) and 12% out‐of‐field recurrence (OFR) rates. Urinary function fully recovered at 3 months. Among men with baseline Sexual Health Inventory for Men score ≥17, 85% recovered erectile function at 1 year, with baseline function as the main predictor of recovery at 1 year. All complications (26%) were Common Terminology Criteria for Adverse Events Grade 1–2. There was no significant difference in FC outcomes between surgeons. Learning curves were demonstrated primarily for ablation time with a decrease of 1.44 min per case (95% CI −1.98 to −0.90), with small effects for number of cryoprobes (0.041 decrease per case, 95% CI −0.067 to −0.014) and OFR rate (0.014 decrease per case, 95% CI −0.028 to −0.0003), but not for the IFR rate and complications. No differences in learning patterns were observed between surgeons. Conclusion: Fusion‐guided FC using the UroNav AAP demonstrated good oncological control and safety profile. The device allowed precise MRI‐US fusion‐guided treatment while minimising the learning curve difference between expert and beginner surgeons.

Background: prostate fusion biopsies are key in the diagnosis of prostate cancer (PCa); however, the fusion imaging system is not always user-friendly or reliable. The aim of this study was to assess the feasibility, accuracy, and effectiveness of transperineal fusion biopsies performed with a novel fusion imaging device equipped with AI-driven auto-contouring. Methods: data from 148 patients who underwent MRI-targeted and systematic prostate fusion biopsy with UroFusion (Esaote) were prospectively collected. All biopsies were performed in-office, under local anaesthesia. Results: cancer detection rate was 64% overall and 56% for clinically significant PCa (csPCa, ISUP ≥ 2). PCa was detected in 35%, 65% and 84% of lesions scored as PI-RADS 3, 4 and 5, respectively. Outfield positive systematic cores were found in the contralateral lobe in one third of cases. Median device-time to obtain fusion imaging was 5 min and median biopsy duration was 15 min. Median difference in volume estimation between ultrasound and MRI auto-contouring was only 1 cc. Detection rate did not differ between experienced and novice, supervised users. Conclusions: in this initial prospective experience, fusion biopsies performed with UroFusion AI-driven auto-contouring system appeared time-efficient, accurate, well tolerated, and user-friendly, with comparable outcomes between experienced and novice users. Systematic biopsies remain highly recommended given the non-negligible rates of positive outfield cores.

Background/Objectives: Focal therapy (FT) for prostate cancer (PCa) is an alternative to radical treatments that aims to balance cancer control and quality of life preservation in well-selected patients. Understanding its general principles and outcomes is key for its widespread adoption and proper implementation. Methods: The International Consultation on Urological Diseases nominated a committee to review the literature on FT for PCa. A comprehensive PubMed search was conducted to identify articles focused on the different aspects of FT, including patient selection, imaging techniques, treatment modalities, cancer control and safety outcomes, integration with other approaches and future perspectives. Results: FT for PCa was introduced in the 1990s with cryotherapy and high-intensity focused ultrasound (HIFU) as pioneering modalities. Though initially guided by transrectal ultrasound (TRUS) and large biopsy templates, FT implementation expanded significantly with the advent of multiparametric magnetic resonance imaging (MRI) and the validation of the index lesion concept. Appropriate patient selection is key for FT and relies on prostate-specific antigen (PSA) metrics, MRI findings and targeted biopsy information. Multiple energy sources are now available, each with specific technical characteristics. Cancer control rates vary by energy modality, tumor characteristics, and institutional experience, demonstrating comparable outcomes to radical treatments in well-selected patients. The safety profile is excellent, with high rates of urinary continence and sexual function preservation. Post-treatment surveillance integrates PSA measurements, imaging, and histological assessment. Future directions for further FT adoption include the availability of long-term data, protocol standardization and technological improvements to enhance patient selection and treatment planning and delivery. Conclusions: FT is a valuable therapeutic option for selected patients with localized PCa, demonstrating promising oncological outcomes and better functional preservation compared to radical treatments. Understanding its principles and technical aspects is essential for offering comprehensive PCa care.

Background: Multiparametric magnetic resonance imaging (mpMRI) is pivotal in prostate cancer (PCa) diagnosis, but some clinically significant (cs) PCa remain undetected. This study aims to understand the pathological and molecular basis for csPCa visibility at mpMRI.Methods: We performed a retrospective matched‐pair cohort study, including patients undergoing radical prostatectomy (RP) for csPCa (i.e., ISUP grade group ≥ 2) from 2015 to 2020, in our tertiary‐referral center. We screened for inclusion in the “mpMRI‐invisible” cohort all consecutive men (N = 45) having a negative preoperative mpMRI. The “mpMRI‐visible” cohort was matched based on age, PSA, prostate volume, ISUP grade group. Included patients underwent radiological and pathological open‐label revisions and characterization of the tumor mRNA expression profile (analyzing 780 gene transcripts, signaling pathways, and cell‐type profiling). We compared the clinical‐pathological variables and the gene expression profile between matched pairs. The analysis was stratified according to histological characteristics and lesion diameter.Results: We included 34 patients (17 per cohort); mean age at RP and PSA were 70.5 years (standard deviation [SD] = 7.7), 7.1 ng/mL (SD = 3.3), respectively; 65% of men were ISUP 2. Overall, no significant differences in histopathological features, tumor diameter and location, mRNA profile, pathways, and cell‐type scores emerged between cohorts. In the stratified analysis, an upregulation of cell adhesion and motility, of extracellular matrix remodeling and of metastatic process pathways was present in specific subgroups of mpMRI‐invisible cancers.Conclusions: No PCa pathological or gene‐expression hallmarks explaining mp‐MRI invisibility were identified. Aggressive features can be present both in mpMRI‐invisible and ‐visible tumors.

Purpose To investigate the detection and predictors of prostate cancer (PCA) and clinically significant prostate cancer (csPCA) in patients with positive multiparametric MRI (mpMRI) followed by a negative MRI – guided target biopsy (TB) and systematic biopsy (SB). Materials and methods This retrospective multicenter study included 694 patients from 10 tertiary referral centers with an initial positive mpMRI (PI-RADS ≥ 3) and negative results on both MRI-TB and SB. Patients were classified into three groups based on follow-up: Group 1 (prostate re-biopsy without new mpMRI), Group 2 (standardized second prostate mpMRI and subsequent re-biopsy), and Group 3 (follow-up with mpMRIs and biopsy based on clinical and radiological triggers). The primary outcomes were the detection of any PCA and csPCA during follow up. Study groups were compared according to their probability of PCA and csPCA assessed with the ERSPC-MRI risk calculator. Statistical analysis included Kaplan – Meier analysis, Cox regression, and multivariable analysis for the detection of (cs)PCa. Results The overall detection of PCA and csPCA was 26.8% and 19.3%, respectively, with varying rates in different PI-RADS groups. Group 3 had the highest 2-year and 5-year PCA–free survival (94 and 84%) and csPCA – free survival (96 and 86%). Multivariable analysis revealed a significantly higher risk of PCA and csPCA in Group 1 and 2 compared to Group 3 (p < 0.01). Clinical and radiological predictors for PCA and csPCA included higher age, prostate volume, PI-RADS score, the presence of atypical small acinar proliferation (ASAP), and a smaller number of TB and SB performed during the initial biopsy. Study limitations, include the retrospective design and reliance on clinical and radiological triggers for follow–up decisions. Conclusions Patients with positive mpMRI but negative TB and SB results exhibit varying rates of PCA and csPCA depending on the follow up scheme. Tailored follow-up strategies are essential for optimal management in this clinical scenario.

Background to date, no standardized, evidence-based follow-up schemes exist for the monitoring of patients who underwent focal therapy (FT) and expert centers rely mainly on their own experience and/or institutional protocols. We aimed to perform a comprehensive review of the most advantageous follow-up strategies and their rationale after FT for prostate cancer (PCa). Methods a narrative review of the literature was conducted to investigate different follow-up protocols of FT for PCa. Outcomes of interest were post-ablation oncological and functional outcomes and complications. Results Oncological success after FT was generally defined as the biopsy-confirmed absence of clinically significant PCa in the treated zone. De novo PCa in the untreated area usually reflects an inaccurate patient selection and should be treated as primary PCa. During follow-up, oncological outcomes should be evaluated with periodic PSA, multiparametric MRI and prostate biopsy. The use of PSA derivatives and new biomarkers is still controversial and therefore not recommended. The first MRI after FT should be performed between 6-12 months to avoid ablation-related artifacts and diagnostic delay in case of FT failure. Other imaging modalities, such as PSMA PET/CT scan, are promising but still need to be validated in the post-FT setting. A 12-month “for-protocol” prostate biopsy, including targeted and systematic biopsy, was generally considered the preferred biopsy method to rule out tumor persistence/recurrence. Subsequent mpMRIs and biopsies should follow a risk-adapted approach depending on the clinical scenario. Functional outcomes should be periodically assessed using validated questionnaires within the first year, when typically recover to a new baseline. Complications, despite uncommon, should be strictly monitored mainly in the first month. Conclusions FT follow-up is a multifaceted process involving clinical, radiological, and histological assessment. Studies evaluating the impact of different follow-up strategies and ideal timings are needed to produce standardized protocols following FT.

The Bosniak classification of renal cysts aims to provide a probabilistic risk assessment indicating the likelihood of malignancy from imaging findings. Originally designed to classify adult renal cysts based on computed tomography findings, the Bosniak classification has been extended to pediatric patients, with some adjustments made with the aim of accommodating magnetic resonance imaging (MRI) and ultrasonography (US). Bosniak IV lesions are rare in adolescents, indicating localized renal cell carcinoma and requiring surgical intervention. In contrast, Bosniak III lesions can be treated conservatively, although there is a lack of specific guidelines on their management. We present a case of a 14-year-old boy with a Bosniak III lesion, which was incidentally detected during the US evaluation of a left varicocele. After a 12-month follow-up, MRI revealed progression to a Bosniak IV cyst. Robot-assisted tumor enucleation was performed with selective artery clamping when the patient was 15. Histopathology showed tubulocystic renal cell carcinoma without adverse features. Immunocytochemistry supported a favorable prognosis of this rare tumor (<1% of renal tumor), thus obviating the need for adjuvant treatment. At the 18-month follow-up, no recurrence or distant metastasis were observed. This case highlights the importance of an aggressive treatment in persistent Bosniak III and Bosniak IV renal cysts in children and adolescents and the necessity to offer a nephron-sparing surgery.