Three-dimensional automatic artificial intelligence driven augmented-reality selective biopsy during nerve-sparing robot-assisted radical prostatectomy: A feasibility and accuracy study.

Objective: To evaluate the accuracy of our new three-dimensional (3D) automatic augmented reality (AAR) system guided by artificial intelligence in the identification of tumour's location at the level of the preserved neurovascular bundle (NVB) at the end of the extirpative phase of nerve-sparing robot-assisted radical prostatectomy. Methods: In this prospective study, we enrolled patients with prostate cancer (clinical stages cT1c-3, cN0, and cM0) with a positive index lesion at target biopsy, suspicious for capsular contact or extracapsular extension at preoperative multiparametric magnetic resonance imaging. Patients underwent robot-assisted radical prostatectomy at San Luigi Gonzaga Hospital (Orbassano, Turin, Italy), from December 2020 to December 2021. At the end of extirpative phase, thanks to our new AAR artificial intelligence driven system, the virtual prostate 3D model allowed to identify the tumour's location at the level of the preserved NVB and to perform a selective excisional biopsy, sparing the remaining portion of the bundle. Perioperative and postoperative data were evaluated, especially focusing on the positive surgical margin (PSM) rates, potency, continence recovery, and biochemical recurrence. Results: Thirty-four patients were enrolled. In 15 (44.1%) cases, the target lesion was in contact with the prostatic capsule at multiparametric magnetic resonance imaging (Wheeler grade L2) while in 19 (55.9%) cases extracapsular extension was detected (Wheeler grade L3). 3D AAR guided biopsies were negative in all pathological tumour stage 2 (pT2) patients while they revealed the presence of cancer in 14 cases in the pT3 cohort (14/16; 87.5%). PSM rates were 0% and 7.1% in the pathological stages pT2 and pT3 (<3 mm, Gleason score 3), respectively. Conclusion: With the proposed 3D AAR system, it is possible to correctly identify the lesion's location on the NVB in 87.5% of pT3 patients and perform a 3D-guided tailored nerve-sparing even in locally advanced diseases, without compromising the oncological safety in terms of PSM rates.

Patient and Context Factors in the Adoption of Active Surveillance for Low-Risk Prostate Cancer.

Importance: Although active surveillance for patients with low-risk prostate cancer (LRPC) has been recommended for years, its adoption at the population level is often limited. Objective: To make active surveillance available for patients with LRPC using a research framework and to compare patient characteristics and clinical outcomes between those who receive active surveillance vs radical treatments at diagnosis. Design, Setting, and Participants: This population-based, prospective cohort study was designed by a large multidisciplinary group of specialists and patients' representatives. The study was conducted within all 18 urology centers and 7 radiation oncology centers in the Piemonte and Valle d'Aosta Regional Oncology Network in Northwest Italy (approximate population, 4.5 million). Participants included patients with a new diagnosis of LRPC from June 2015 to December 2021. Data were analyzed from January to May 2023. Exposure: At diagnosis, all patients were informed of the available treatment options by the urologist and received an information leaflet describing the benefits and risks of active surveillance compared with active treatments, either radical prostatectomy (RP) or radiation treatment (RT). Patients choosing active surveillance were actively monitored with regular prostate-specific antigen testing, clinical examinations, and a rebiopsy at 12 months. Main Outcomes and Measures: Outcomes of interest were proportion of patients choosing active surveillance or radical treatments, overall survival, and, for patients in active surveillance, treatment-free survival. Comparisons were analyzed with multivariable logistic or Cox models, considering centers as clusters. Results: A total of 852 male patients (median [IQR] age, 70 [64-74] years) were included, and 706 patients (82.9%) chose active surveillance, with an increasing trend over time; 109 patients (12.8%) chose RP, and 37 patients (4.3%) chose RT. Median (IQR) follow-up was 57 (41-76) months. Worse prostate cancer prognostic factors were negatively associated with choosing active surveillance (eg, stage T2a vs T1c: odds ratio [OR], 0.51; 95% CI, 0.28-0.93), while patients who were older (eg, age ≥75 vs <65 years: OR, 4.27; 95% CI, 1.98-9.22), had higher comorbidity (Charlson Comorbidity Index ≥2 vs 0: OR, 1.98; 95% CI, 1.02-3.85), underwent an independent revision of the first prostate biopsy (OR, 2.35; 95% CI, 1.26-4.38) or underwent a multidisciplinary assessment (OR, 2.65; 95% CI, 1.38-5.11) were more likely to choose active surveillance vs active treatment. After adjustment, center at which a patient was treated continued to be an important factor in the choice of treatment (intraclass correlation coefficient, 18.6%). No differences were detected in overall survival between active treatment and active surveillance. Treatment-free survival in the active surveillance cohort was 59.0% (95% CI, 54.8%-62.9%) at 24 months, 54.5% (95% CI, 50.2%-58.6%) at 36 months, and 47.0% (95% CI, 42.2%-51.7%) at 48 months. Conclusions and Relevance: In this population-based cohort study of patients with LRPC, a research framework at system level as well as favorable prognostic factors, a multidisciplinary approach, and an independent review of the first prostate biopsy at patient-level were positively associated with high uptake of active surveillance, a practice largely underused before this study.

A prospective randomized controlled trial comparing target prostate biopsy alone approach vs. target plus standard in naïve patients with positive mpMRI.

BACKGROUND: In the era of mpMRI guided target fusion biopsy (FB), the role of concomitant standard biopsy (SB) in naïve patients still remains under scrutiny. The aim of this study was to compare the detection rate (DR) of clinically significant prostate cancer (csPCa) in biopsy naïve patients with positive mpMRI who underwent FB alone (Arm A) vs FB+SB (Arm B). Secondary objectives were to compare the incidence of complications, the overall PCa DR and the biopsy results with final pathological findings after robotic prostatectomy (RARP). METHODS: This is a single center prospective non-inferiority parallel two arms (1:1) randomized control trial (ISRCTN registry number ISRCTN60263108) which took place at San Luigi Gonzaga University Hospital, Orbassano (Turin, Italy) from 4/2019 to 10/2021. Eligible participants were all adults aged<75 years old, biopsy naïve, with serum PSA<15 ng/mL and positive mpMRI (Pi-Rads V.2>3). FB was performed under ultrasound guidance using the BioJet fusion system; four to six target samples were obtained for each index lesion. SB was performed in accordance with the protocol by Rodríguez-Covarrubias. RARP with total anatomical reconstruction was carried out when indicated. DR of PCa and csPCA (Gleason Score >7) were evaluated. Post-biopsy complications according to Clavien-Dindo were recorded. Concordance between biopsy and RARP pathological findings was evaluated. Fisher's Exact test and Mann-Whitney test were applied; furthermore, Logistic Principal Component Analysis (LogPCA) and Pearson's correlation method, in terms of correlation funnel plots, were performed to explore data in a multivariate way. RESULTS: 201 and 193 patients were enrolled in Arm A and B, respectively. csPCa DR was 60.2% vs. 60.6% in Arm A and B respectively (Δ 0.4%; P=0.93); whilst overall PCa DR was 63.7% vs. 71.0% (Δ 7.3%; P=0.12). However, in a target only setting, the addition of SB homolaterally to the index lesion reaching a non-inferior performance compared to the combined sampling (Δ PCa DR 3%). Although the differences of 7.3% in PCa DR, during RARP were registered similar nerve sparing rate (P=0.89), positive surgical margins (P=0.67) and rate of significant upgrading (P=0.12). LogPCA model showed no distinction between the two cohorts; and Pearson's correlation values turned to be between -0.5 and +0.5. In Arm B, the lesion diameter <10 mm is the only predictive variable of positive SB only for PCa (P=0.04), with an additional value +3% for PCa DR. CONCLUSIONS: In biopsy naïve patients, FB alone is not inferior to FB+SB in detecting csPCa (Δ csPCa DR 0.4%). Δ 7.3% in overall PCa DR was registered between the two Arms, however the addition of further standard samples homolaterally to mp-MRI index lesion improved the overall PCa DR of FB only sampling (Δ PCa DR 3%). The omission of SB did not influence the post-surgical outcomes in terms of NS approach, PSMr and upgrading/downgrading.

Are tyrosine kinase inhibitors an effective treatment in testicular metastases from kidney cancer? Case report.

Testicular metastases from renal cell carcinoma (RCC) are extremely rare. Tyrosine kinase inhibitors (TKI) are the cornerstone of systemic therapy for metastatic RCC. We report a case of testicular metastasis in a 72-year-old patient with RCC that developed 17 years after nephrectomy and response to TKI treatment, a retrospective literature search on testicular metastases from RCC, and the indirect evidence described in the literature on the efficacy of chemotherapy and target therapy on testicular lesions.

Molecular Characterization of Prostate Cancers in the Precision Medicine Era.

Prostate cancer (PCa) therapy has been recently revolutionized by the approval of new therapeutic agents in the metastatic setting. However, the optimal therapeutic strategy in such patients should be individualized in the light of prognostic and predictive molecular factors, which have been recently studied: androgen receptor (AR) alterations, PTEN-PI3K-AKT pathway deregulation, homologous recombination deficiency (HRD), mismatch repair deficiency (MMRd), and tumor microenvironment (TME) modifications. In this review, we highlighted the clinical impact of prognostic and predictive molecular factors in PCa patients' outcomes, identifying biologically distinct subtypes. We further analyzed the relevant methods to detect these factors, both on tissue, i.e., immunohistochemistry (IHC) and molecular tests, and blood, i.e., analysis of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Moreover, we discussed the main pros and cons of such techniques, depicting their present and future roles in PCa management, throughout the precision medicine era.

A Fully Automatic Artificial Intelligence System Able to Detect and Characterize Prostate Cancer Using Multiparametric MRI: Multicenter and Multi-Scanner Validation.

In the last years, the widespread use of the prostate-specific antigen (PSA) blood examination to triage patients who will enter the diagnostic/therapeutic path for prostate cancer (PCa) has almost halved PCa-specific mortality. As a counterpart, millions of men with clinically insignificant cancer not destined to cause death are treated, with no beneficial impact on overall survival. Therefore, there is a compelling need to develop tools that can help in stratifying patients according to their risk, to support physicians in the selection of the most appropriate treatment option for each individual patient. The aim of this study was to develop and validate on multivendor data a fully automated computer-aided diagnosis (CAD) system to detect and characterize PCas according to their aggressiveness. We propose a CAD system based on artificial intelligence algorithms that a) registers all images coming from different MRI sequences, b) provides candidates suspicious to be tumor, and c) provides an aggressiveness score of each candidate based on the results of a support vector machine classifier fed with radiomics features. The dataset was composed of 131 patients (149 tumors) from two different institutions that were divided in a training set, a narrow validation set, and an external validation set. The algorithm reached an area under the receiver operating characteristic (ROC) curve in distinguishing between low and high aggressive tumors of 0.96 and 0.81 on the training and validation sets, respectively. Moreover, when the output of the classifier was divided into three classes of risk, i.e., indolent, indeterminate, and aggressive, our method did not classify any aggressive tumor as indolent, meaning that, according to our score, all aggressive tumors would undergo treatment or further investigations. Our CAD performance is superior to that of previous studies and overcomes some of their limitations, such as the need to perform manual segmentation of the tumor or the fact that analysis is limited to single-center datasets. The results of this study are promising and could pave the way to a prediction tool for personalized decision making in patients harboring PCa.

Adrenal Rests in the Uro-genital Tract of an Adult Population.

Ectopic adrenal rests are a rare condition which can be found in various sites, generally in the retroperitoneum or pelvis along the path of gonadal descent. Their real prevalence is unknown. Males are more commonly affected, at least in the pediatric age. Adrenal rests are usually clinically silent and incidentally found in surgical samples, mostly in the pediatric population, and rarely in adults. With the aim of increasing knowledge and estimating the prevalence of ectopic adrenocortical tissue in the adult population, 44 adrenal rests in the urogenital tract of 40 adults are described. These represent approximately 0.07% of the total number of urogenital and gynecological surgeries performed in the 22 considered years. Adrenal rests were identified in the spermatic cord (10 males) and in paraovarian, parasalpingeal, or infundibulopelvic ligament locations (30 females). All but one was incidental findings. One case regarded an adrenocortical carcinoma arisen in adrenal rests. A literature review of adrenal ectopia in the urogenital tract of adults identified 57 reported cases from 53 patients, with similar clinicopathological features as those of our series, with the exception of a lower incidence of parasalpingeal locations. Despite their limited clinical implications, awareness of ectopic adrenal rests is essential also in adults for at least two reasons: (a) to correctly identify sources of adrenocortical hormone production in case of adrenal insufficiency or hormonal imbalance and (b) to avoid misinterpretations in the diagnostic workup of renal cell carcinoma, adrenocortical tumors, and rare gonadal neoplasms, including Sertoli/Leydig cell tumors.

Diagnostic Accuracy of Single-plane Biparametric and Multiparametric Magnetic Resonance Imaging in Prostate Cancer: A Randomized Noninferiority Trial in Biopsy-naïve Men.

BACKGROUND: Urological guidelines recommend multiparametric magnetic resonance imaging (mpMRI) in men with a suspicion of prostate cancer (PCa). The resulting increase in MRI demand might place health care systems under substantial stress. OBJECTIVE: To determine whether single-plane biparametric MRI (fast MRI) workup could represent an alternative to mpMRI in the detection of clinically significant (cs) PCa. DESIGN, SETTING, AND PARTICIPANTS: Between April 2018 and February 2020, 311 biopsy-naïve men aged ≤75 yr with PSA ≤15 ng/ml and negative digital rectal examination were randomly assigned to 1.5-T fast MRI (n = 213) or mpMRI (n = 98). INTERVENTION: All MRI examinations were classified according to Prostate Imaging-Reporting and Data System (PI-RADS) version 2. Men scored PI-RADS 1-2 underwent 12-core standard biopsy (SBx) and those with PI-RADS 4-5 on fast MRI or PI-RADS 3-5 on mpMRI underwent targeted biopsy in combination with SBx. Equivocal cases on fast MRI (PI-RADS 3) underwent mpMRI and then biopsy according to the findings. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was to compare the detection rate of csPCa in both study arms, setting a 10% difference for noninferiority. The secondary outcome was to assess the role of prostate-specific antigen density (PSAD) in ruling out men who could avoid biopsy among those with equivocal findings on fast MRI. RESULTS AND LIMITATIONS: The overall MRI detection rate for csPCa was 23.5% (50/213; 95% confidence interval [CI] 18.0-29.8%) with fast MRI and 32.7% (32/98; 95% CI 23.6-42.9%) with mpMRI (difference 9.2%; p = 0.09). The reproducibility of the study could have been affected by its single-center nature. CONCLUSIONS: Fast MRI followed by mpMRI in equivocal cases is not inferior to mpMRI in the detection of csPCa among biopsy-naïve men aged ≤75 yr with PSA ≤15 ng/ml and negative digital rectal examination. These findings could pave the way to broader use of MRI for PCa diagnosis. PATIENT SUMMARY: A faster MRI (magnetic resonance imaging) protocol with no contrast agent and fewer scan sequences for examination of the prostate is not inferior to the typical MRI approach in the detection of clinically significant prostate cancer. If our findings are confirmed in other studies, fast MRI could represent a time-saving and less invasive examination for men with suspicion of prostate cancer. This trial is registered at ClinicalTrials.gov as NCT03693703.

Low-dose radiotherapy for extranodal marginal zone B lymphoma of the lip: Case report and literature review.

Non-Hodgkin lymphoma (NHL) of the lip is extremely rare. It is usually indolent and in early stages a local approach is often indicated. We present a case report of a patient with extranodal NHL of the lip treated with chemotherapy and low-dose radiation treatment (RT). The patient was affected by B-cell NHL of the marginal zone, Stage IAE. After a few months of observation with progressive disease, the patient was submitted to two cycles of chemotherapy with no response. Therefore, he was treated with very low-dose RT consisting of two fractions of 2 Gy. Complete response was observed and after 1-year follow-up, persistent complete response was recorded. In cases of localized disease, especially in patients with comorbidities of poor performance status (PS), low-dose RT can be an appropriate approach with excellent outcomes in terms of effectiveness and low risk of toxicity.

Comprehensive analysis of 34 MiT family translocation renal cell carcinomas and review of the literature: investigating prognostic markers and therapy targets.

Recently cabozantinib, a tyrosine kinase inhibitor with activity against VEGF, MET, AXL, and downregulating cathepsin K in vitro, has been proposed for the treatment of advanced clear and non-clear renal cell carcinomas. Since it is well known that cathepsin K is expressed in the majority of MiT family translocation renal cell carcinomas, we investigated cathepsin K, MET, AXL, and VEGF in a large series of those tumours, looking for possible predictive markers. We collected the clinicopathological features of 34 genetically confirmed MiT family translocation renal cell carcinomas [26 Xp11 and 8 t(6;11) renal cell carcinomas] and studied them using an immunohistochemical panel including PAX8, cathepsin K, HMB45, Melan-A, CD68 (PG-M1), CK7, CA9, MET, AXL and by FISH for VEGFA and MET. Cathepsin K was expressed in 14 of 26, HMB45 in 8 of 25, and Melan-A in 4 of 23 Xp11 renal cell carcinomas, whereas labelling for CK7 and CA9 was minimal. In t(6;11) renal cell carcinoma, cathepsin K and melanogenesis markers were constantly positive, whereas CK7 and CA9 were negative. None of the 34 carcinomas showed CD68 (PG-M1) and AXL expression. One aggressive Xp11 renal cell carcinoma showed increased VEGFA gene copy number (4-5 copies) with concurrent gains of TFE3 and TFEB. None of the 34 carcinomas showed MET gene amplification, whereas staining for MET was found in 7 of 8 t(6;11) and in 16 of 24 Xp11 renal cell carcinomas, and in the latter cases, when the expression was >50%, correlated with aggressiveness (p=0.0049). In Xp11 renal cell carcinomas, the aggressiveness was also correlated with larger tumour size (p=0.0008) and the presence of necrosis (p=0.027) but not nucleolar grading (p=1). Interestingly, in patients with tumours exhibiting two of three parameters (necrosis, larger tumour size and MET immunolabelling >50%) an aggressive clinical behaviour was observed in 88% of cases. In conclusion, cathepsin K, CD68 (PG-M1), CK7, CA9, and PAX8 is a useful panel for the diagnosis. Larger tumour size, the presence of necrosis and MET immunohistochemical expression correlate with aggressive behaviour in Xp11 renal cell carcinomas, especially in combination. VEGF, MET, cathepsin K but not AXL may be potential predictive markers for targeted therapy in MiT family translocation renal cell carcinomas.

Risk of Gleason Score 3+4=7 prostate cancer upgrading at radical prostatectomy is significantly reduced by targeted versus standard biopsy.

BACKGROUND: The aim of this study is to evaluate if multiparametric magnetic resonance (mpMRI)-transrectal ultrasound (TRUS) fusion targeted biopsy (TBx) versus untargeted standard biopsy (SBx) may decrease the rate of pathological upgrading of Gleason Score (GS) 3+4 prostate cancer (PCa) at radical prostatectomy (RP). We also evaluated the impact of percent pattern 4 and cribriform glands at biopsy in the risk of GS 3+4=7 upgrading. METHODS: A total of 301 patients with GS 3+4 PCa on biopsy (159 SBx and 142 TBx) who underwent laparoscopic robot-assisted RP were sequentially enrolled. Histological data from RP sections were used as reference standard. The concordance of biopsy with pathological GS, as well as the GS 3+4 upgrading at RP were evaluated in different univariate and multivariate binary logistic regression models, testing age, PSA, fPSA%, tumor volume, PI-RADS, clinical stage, percentage of Gleason pattern 4 (GP) and/or presence of cribriform sub-type at biopsy. RESULTS: Of the 301 biopsies, the median of GP 4 was 16% of the tissue. Minimal GP 4 (≤16%) cancers had a significant lower median volume (1.7 mL) than those with GP4 >16% (2.9 mL), (P<0.001). Pathological GS 3+4 was confirmed for 58.8% and 82.2% for SBx and TBx patients, respectively. The rate of upgraded and downgraded GS on SBx versus TBx was 38.8% vis. 16.7% and 1.8% and 2.1%, respectively. The rate of upgrading was significantly associated with the presence of GP4 >16% versus ≤16% (OR 4.4, 95% CI 1.4-12.0; P=0.021) and with the presence of cribriform sub-type at biopsy specimens (OR 6.2, 95% CI 2.2-18.7; P<0.001). CONCLUSIONS: We demonstrated that TBx technique significantly reduced the risk of GS 3+4 upgrading at RP, compared to SBx one. The rate of upgrading was significantly associated with GP4>16%, mostly when cribriform sub-type was present at biopsy specimens.

Prostate cancer management at an Italian tertiary referral center: does multidisciplinary team meeting influence diagnostic and therapeutic decision-making process? A snapshot of the everyday clinical practice.

BACKGROUND: Multidisciplinary team (MDT) management decision-making process appears as an interesting tool to answer most aspects of prostate cancer (PCa) diagnosis and treatment, allowing a fairer choice of therapies. The aim of this study to prospectively investigate the impact on prostate cancer clinical management of the uro-oncology MDT meeting at an Italian tertiary referral center. METHODS: All cases discussed over an 18-months period at San Luigi Hospital uro-oncology MDT were prospectively evaluated for the impact of the MDT discussion on PCa clinical decision-making. Dilemma and management plan in the monodisciplinary visit before and/or after primary treatment were recorded. Subsequently, the MDT discussed the case and reached a consensus decision, which was also recorded. Changes in diagnostic assessment and patient management from pre- to post-MDT meeting were evaluated by a consultant urologist. RESULTS: Overall, 201 patients, of which 99, 81 and 21 with local, advanced and metastatic disease respectively, were selected for MDT evaluation. The most frequent reasons for MDT approach after either PCa diagnosis or primary treatment were metastatic disease or locally advanced disease/positive surgical margins/biochemical recurrence, respectively. Patients with local, advanced and metastatic disease had a significative change of diagnostic/therapeutic management in 23.2%, 46.9% and 33.4%, respectively (P<0.001). Multimodal treatment was recommended in 25.3%. CONCLUSIONS: The uro-oncology MDT meeting alters management plans in at least one-quarter of patients reaching almost 50% of cases in locally advanced disease.

Three-dimensional Elastic Augmented-reality Robot-assisted Radical Prostatectomy Using Hyperaccuracy Three-dimensional Reconstruction Technology: A Step Further in the Identification of Capsular Involvement.

BACKGROUND: In prostate cancer (PCa) surgical procedures, in order to maximize potency recovery, a nerve-sparing (NS) procedure is preferred. However, cancer abutting or focally extending beyond the prostate capsule increases the risk of a positive surgical margin. OBJECTIVE: To evaluate the accuracy of our new three-dimensional (3D) elastic augmented-reality (AR) system in identifying capsular involvement (CI) location of PCa during the NS phase of robot-assisted radical prostatectomy (RARP). Secondarily, the accuracy of this technology was compared with two-dimensional (2D)-based cognitive procedures. DESIGN, SETTING, AND PARTICIPANTS: A prospective study, enrolling 40 patients with PCa undergoing RARP at our center, from May to October 2018. SURGICAL PROCEDURE: Patients underwent 3D AR RARP or, in case of unavailability of this technology, 2D cognitive RARP. In all patients, total anatomical reconstruction was used. MEASUREMENTS: Clinical data were collected. In order to compare the two groups, nonparametric Mann-Whitney and chi-square tests were performed. A metallic clip was placed at the level of suspicious CI on the basis of images given by the 3D AR or magnetic resonance imaging (MRI) report. The pathological analysis evaluated the presence of tumor at the level of the clip. RESULTS AND LIMITATIONS: Twenty patients were enrolled in each group. Focusing on the 3D AR group at macroscopic evaluation, the metallic clip was placed at the tumor and capsular bulging in all cases. At microscopic assessment, cancer presence was confirmed in the suspicious area in 95.4% of the cases. Moreover, CI was correctly identified in 100.0% of the cases, thanks to the 3D image overlap. These results were compared with the 2D MRI cognitive group, showing, at microscopic analysis, statistically significant superiority of the 3D AR group in CI detection during the NS phase (100% vs 47.0%; p<0.05). The main limitation of this technique is that the segmentation and overlapping of the images are performed manually. CONCLUSIONS: Our findings suggest that, with the introduction of the elastic 3D virtual models, prostate deformation is correctly simulated during surgery and lesion location is correctly identified, even in dynamic reality with a subsequent potential reduction of positive surgical margin rate and, in the meantime, maximization of functional outcomes. PATIENT SUMMARY: On the basis of our findings, the three-dimensional elastic augmented-reality technology seems to help the surgeon in lesion location identification even in a dynamic phase of the intervention, optimizing the oncological outcomes.

Radiological Wheeler staging system: a retrospective cohort analysis to improve the local staging of prostate cancer with multiparametric MRI.

BACKGROUND: The knowledge of tumor location and extension can allow a modulated radical prostatectomy in order to minimize positive surgical margins and reduce functional morbidity after surgery in patients with prostate cancer (PCa). Multiparametric (mp) magnetic resonance imaging (MRI) could allow the assessment of tumor extension and of its relationship with external structures. Aim of this study is to propose a new radiological Wheeler (rW) staging system applied to mp-MRI, based on the pathologic staging system (pW) for the local assessment of PCa. METHODS: This retrospective single-center multi-reader study included consecutive patients with PCa and preoperative mp-MRI, who underwent non-nerve sparing radical prostatectomy. Three radiologists reported on all examinations and classified each selected lesion according to imaging criteria following rW. Whole-mount histological sections were used as the reference standard. An experienced pathologist classified the extent of prostatic capsular invasion of each PCa according to the pW. Each histological section was scanned for comparison with mp-MRI findings. The rate of PCa correctly classified by radiologists using the pW was assessed. To evaluate the accuracy of mp-MRI in the discrimination between T2 and T3 PCa, the AUC was computed. RESULTS: One-hundred and five patients with a total of 195 PCa foci were included in the study. 130/195 tumors with a clear overlap between mp-MRI and surgical specimens were selected. The sensitivity of the most experienced reader was lower than that of the other two readers (48.6% vs. 68.6% and 62.9%, P>0.09) while specificity and PPV were higher (95.8% vs. 79.0% and 57.9%, P<0.001; 81.0% vs. 54.6% and 35.5%, P<0.041; respectively). The AUC values for the most and the intermediate experienced readers in the detection of extracapsular extension were in the range 0.72-0.74. CONCLUSIONS: The rW staging system has low accuracy in predicting each single pW class, while accuracy was over 80% for experienced readers in the identification of organ-confined (T2 stage class) tumors and non-organ confined cases (T3 stage class).

Augmented-reality robot-assisted radical prostatectomy using hyper-accuracy three-dimensional reconstruction (HA3D™) technology: a radiological and pathological study.

OBJECTIVES: To assess the use of hyper-accuracy three-dimensional (HA3D™; MEDICS, Moncalieri, Turin, Italy) reconstruction based on multiparametric magnetic resonance imaging (mpMRI) and superimposed imaging during augmented-reality robot-assisted radical prostatectomy (AR-RARP). PATIENTS AND METHODS: Patients with prostate cancer (clinical stages cT1-3, cN0, cM0) undergoing RARP at our Centre, from June 2017 to April 2018, were enrolled. In all cases, cancer was diagnosed with targeted biopsy at the level of index lesion based on high-resolution (1-mm slices) mpMRI. HA3D reconstruction was created by dedicated software to obtain the 3D virtual model of the prostate and surrounding structures. A specific system was used to overlay virtual data on the endoscopic video displayed by the remote da Vinci® surgical console (Intuitive Surgical Inc., Sunnyvale, CA, USA), and the virtual images were superimposed by the surgeon by the means of the TilePro™ multi-input display technology (Intuitive Surgical Inc.). The AR technology was used in four standardised key steps during RARP. The procedures were modulated differently in cases of prostate cancer without extracapsular extension (ECE) at mpMRI (Group A) or in cases of prostate cancer with ECE (Group B) at mpMRI. In Group A, the virtual image of the prostate was overlaid on the endoscopic view and the intraprostatic lesion was marked on the prostate surface by a metallic clip at the level of the suspicious lesion as identified by the 3D virtual AR image. In Group B, the same step was performed; moreover, a metallic clip was placed at the level of the suspicious ECE on the neurovascular bundles (NVBs) according to the virtual images. Finally, selective biopsies were taken from the NVBs at this level, and then, the entire NVBs were removed for final pathological examination, according to standard clinical indications. For Group A, the pathologist performed a targeted needle biopsy at the level of the metallic clip on the surface of prostate before the sample reduction. For Group B, the presence of tumour was evaluated during the reduction phase, at the level of metallic clip on the prostate surface and at the level of NVBs, sent separately. Finally, an image 3D scanner (Kinect, Microsoft) was used to perform a dimensional comparison between the mpMRI-based 3D virtual reconstruction and the whole-mount specimen. RESULTS: In all, 30 patients were enrolled in the present study, 11 (36.6%) included in Group A and 19 (63.4%) in Group B. In all cases (30/30), final pathology confirmed the location of the index lesion, as cancer was found at the level of the metallic clip. The suspected ECE was confirmed on final pathology in 15/19 cases (79%). The AR-guided selective biopsies at the level of the NVBs confirmed the ECE location, with 11/15 (73.3%) biopsies at the level of NVBs positive for cancer. The mismatch between the 3D virtual reconstruction and the prostate 3D scanning based on the whole-mount specimen was <3 mm in >85% of the gland. CONCLUSION: Our results suggest that a HA3D virtual reconstruction of the prostate based on mpMRI data and real-time superimposed imaging allow performance of an effective AR-RARP. Potentially, this approach translates into better outcomes, as the surgeon can tailor the procedure for each patient.

The role of side-specific biopsy and dominant tumor location at radical prostatectomy in predicting the side of nodal metastases in organ confined prostate cancer: is lymphatic spread really unpredictable?

BACKGROUND: The aim of this study was to evaluate the correlation between the location of prostate cancer (PCa) either at biopsy or at radical prostatectomy (RP) specimens and the side of positive lymph nodes (LNs). Furthermore, we assessed the risk of contralateral LN metastasis (LNMs) in patients with unilateral positive biopsy and/or dominant lesion at RP. METHODS: We reviewed retrospectively our prospectively maintained database of patients with LNM treated with robot-assisted RP and bilateral robot-assisted extended pelvic lymph node dissection (EPLND) for PCa from January 2014 to May 2018 at a surgical high-volume center. All men with a suspicion for PCa underwent a 12-cores prostate biopsy. In case of a first negative biopsy but the persistence of suspicion, all the patients underwent prostate multiparametric magnetic resonance imaging (mpMRI) and subsequently either fusion targeted biopsy (TBx) or systematic standard biopsy (SBx), in case of positive or negative mpMRI, respectively. All patients underwent a robot-assisted RP. Whole-mount histological sections resected from the RP specimens were used as reference standards. RESULTS: Eighty-seven patients were enrolled for the study. Median number of LNs retrieved per patient was 26, specifically 13 and 12, on the left and right side, respectively. Seven of 24 (29.1%) right lobe positive biopsy showed positive LNs on the left side (one exclusively left, 6 bilateral LNMs). Again, 12 of 26 (46.1%) left lobe positive biopsy showed positive LNs on the right side (one exclusively right, 11 bilateral LNMs). No significant differences of performance to predict the side of LNMs were recorded in the SBx and TBx groups. Concerning RP specimens, only five of 22 (22.7%) right lobe dominant cases showed positive LNs on the left side (two exclusively left, 3 bilateral LN metastases). Again, none of 16 left lobe dominant cases showed positive LNs on the contralateral side (15 exclusively right, 1 bilateral LNMs). CONCLUSIONS: Our results suggest confirmed that a unilateral LN dissection limited to the tumor-bearing side of the gland evaluated by biopsy specimens should not be recommended due to the substantial risk of missing contralateral LNMs.

Tissue-based multigene expression tests for pretreatment prostate cancer risk assessment: current status and future perspectives.

Prostate cancer is a highly prevalent disease with ample spectrum of aggressiveness and treatment options. Low-risk disease can be safely managed by nonintervention strategies, such as active surveillance; however, accurate risk assessment is warranted. Molecular tests have been developed and validated to complement standard clinicopathological parameters and help to improve risk stratification in prostate cancer. Herein, we review selected tissue-based assays, including genomic prostate score, cell cycle progression score and genomic classifier, with particular emphasis on their role in patient risk assessment in a pretreatment setting, in view of their current or potential utilization in active surveillance.

Human renal angiomyolipoma cells of male and female origin can migrate and are influenced by microenvironmental factors.

BACKGROUND: Improving the knowledge of angiomyolipoma physiopathology might help in refining its pharmacological treatment. We investigated if angiomyolipoma cells have migratory properties, how their growth and motility can be influenced by the hormonal milieu, and if this can be related to a specific gender. METHODS: Primary cells were isolated from angiomyolipomas surgically resected for therapeutical reasons in a female and in a male patient. The genetic control demonstrated no TSC2 deletion. Bi- (wound healing) and three-dimensional (transwell assay) migration were analyzed in vitro in basal conditions and under the influence of 17- ß-estradiol and SDF-1α. RESULTS: Treatment up to 72 hours with 17-ß-estradiol (0.1-100 nM), tamoxifen (0.2-20 µM) or with both, does not modify angiomyolipoma cells proliferation. On the other hand, SDF-1α and 17-ß-estradiol treatment induce a significant motility increase (both bi- and three-dimensional) which becomes evident already after 2 hours of incubation. Angiomyolipoma cells express mRNA coding for SDF-1α and 17-ß-estradiol receptors and secrete both the metalloproteases principally involved in malignant phenotype acquisition, i.e. MMP-2 and MMP-9. CONCLUSION: Angiomyolipoma cells behave similarly, despite their different source. Primary angiomyolipoma cells migrate in response to hormonal milieu and soluble factors, and produce active metalloproteases, both aspects being consistent with the theory claiming they can migrate to the lungs (and/or other organs) and colonizing them. No main feature, among the aspects we analyzed, seems to be referable to the gender of origin.