Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing plasma cells in renal cell cancer.

The presence of intratumoral tertiary lymphoid structures (TLS) is associated with positive clinical outcomes and responses to immunotherapy in cancer. Here, we used spatial transcriptomics to examine the nature of B cell responses within TLS in renal cell carcinoma (RCC). B cells were enriched in TLS, and therein, we could identify all B cell maturation stages toward plasma cell (PC) formation. B cell repertoire analysis revealed clonal diversification, selection, expansion in TLS, and the presence of fully mature clonotypes at distance. In TLS+ tumors, IgG- and IgA-producing PCs disseminated into the tumor beds along fibroblastic tracks. TLS+ tumors exhibited high frequencies of IgG-producing PCs and IgG-stained and apoptotic malignant cells, suggestive of anti-tumor effector activity. Therapeutic responses and progression-free survival correlated with IgG-stained tumor cells in RCC patients treated with immune checkpoint inhibitors. Thus, intratumoral TLS sustains B cell maturation and antibody production that is associated with response to immunotherapy, potentially via direct anti-tumor effects.

Assessing the efficacy of pelvic floor muscle training and duloxetine on urinary continence recovery following radical prostatectomy: A randomized clinical trial.

BACKGROUND: Urinary incontinence (UI) can negatively impact quality of life (QoL) after robot-assisted radical prostatectomy (RARP). Pelvic floor muscle training (PFMT) and duloxetine are used to manage post-RARP UI, but their efficacy remains uncertain. We aimed to investigate the efficacy of PFMT and duloxetine in promoting urinary continence recovery (UCR) after RARP. METHODS: A randomized controlled trial involving patients with urine leakage after RARP from May 2015 to February 2018. Patients were randomized into 1 of 4 arms: (1) PFMT-biofeedback, (2) duloxetine, (3) combined PFMT-biofeedback and duloxetine, (4) control arm. PFMT consisted of pelvic muscle exercises conducted with electromyographic feedback weekly, for 3 months. Oral duloxetine was administered at bedtime for 3 months. The primary outcome was prevalence of continence at 6 months, defined as using ≤1 security pad. Urinary symptoms and QoL were assessed by using a visual analogue scale, and validated questionnaires. RESULTS: From the 240 patients included in the trial, 89% of patients completed 1 year of follow-up. Treatment compliance was observed in 88% (92/105) of patients receiving duloxetine, and in 97% (104/107) of patients scheduled to PFMT-biofeedback sessions. In the control group 96% of patients had achieved continence at 6 months, compared with 90% (p = 0.3) in the PMFT-biofeedback, 73% (p = 0.008) in the duloxetine, and 69% (p = 0.003) in the combined treatment arm. At 6 months, QoL was classified as uncomfortable or worse in 17% of patients in the control group, compared with 44% (p = 0.01), 45% (p = 0.008), and 34% (p = 0.07), respectively. Complete preservation of neurovascular bundles (NVB) (OR: 2.95; p = 0.048) was the only perioperative intervention found to improve early UCR. CONCLUSIONS: PFMT-biofeedback and duloxetine demonstrated limited impact in improving UCR after RP. Diligent NVB preservation, along with preoperative patient and disease characteristics, are the primary determinants for early UCR.

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.

Outcomes of ablative therapy and radical treatment for prostate cancer: a systematic review and meta-analysis.

PURPOSE: To compare biochemical recurrence, sexual potency and urinary continence outcomes of ablative therapy and radical treatment (radical prostatectomy or radiotherapy with androgen deprivation therapy). MATERIAL AND METHODS: A systematic review and meta-analysis followed the PRISMA guidelines were performed. We searched MEDLINE/PubMed. Biochemical recurrence at three and five years; incontinence rate (patients who used one pad or more) and erectile dysfunction rate at 12 and 36 months (patients who did not have sufficient erection to achieve sexual intercourse) were evaluated. The Mantel-Haenszel method was applied to estimate the pooled risk difference (RD) in the individual studies for categorical variables. All results were presented as 95% confidence intervals (95%CI). Random effects models were used regardless of the level of heterogeneity (I²). (PROSPERO CRD42022296998). RESULTS: Eight studies comprising 2,677 men with prostate cancer were included. There was no difference in biochemical recurrence between ablative and radical treatments. We observed the same biochemical recurrence between ablative therapy and radical treatment within five years (19.3% vs. 16.8%, respectively; RD 0.07; 95%CI=-0.05, 0.19; I2=68.2%; P=0.08) and continence rate at 12 months (9.2% vs. 31.8%, respectively; RD -0.13; 95%CI, -0.27, 0.01; I2=89%; P=0.32). When focal treatment was analyzed alone, two studies with 582 patients found higher erectile function at 12 months in the ablative therapy group than in the radical treatment (88.9% vs. 30.8%, respectively; RD -0.45; 95%CI -0.84, -0.05; I2=93%; P=0.03). CONCLUSION: Biochemical recurrence and urinary continence outcomes of ablative therapy and radical treatment were similar. Ablative therapy appears to have a high rate of sexual potency.

A Multicenter, Randomized, Single-blind, 2-Arm Intervention Study Evaluating the Adverse Events and Quality of Life After Irreversible Electroporation for the Ablation of Localized Low-intermediate Risk Prostate Cancer.

PURPOSE: Our goal was to evaluate the effect of focal vs extended irreversible electroporation on side effects, patient-reported quality of life, and early oncologic control for localized low-intermediate risk prostate cancer patients. MATERIALS AND METHODS: Men with localized low-intermediate risk prostate cancer were randomized to receive focal or extended irreversible electroporation ablation. Quality of life was measured by International Index of Erectile Function, Expanded Prostate Cancer Index Composite questionnaire, and International Prostate Symptom Score. RESULTS: A total of 51 and 55 patients underwent focal and extended irreversible electroporation, respectively. The median follow-up time was 30 months. Rates of erectile dysfunction and rates of adverse events were similar between the 2 groups at 3 months. The focal ablation group seemed to have better International Index of Erectile Function scores at 3 months; it also had a better Expanded Prostate Cancer Index Composite-sexual function score than the extended ablation group across time that was close to statistical significance (mean difference 1.4; 95% CI -0.13 to 2.9, P = .073). There were no significant differences between the 2 groups in other quality-of-life measures. Upon prostate biopsy at 6 months, the rate of residual clinically significant prostate cancer (Gleason ≥3 + 4) was 18.8% and 13.2% in the focal and extended irreversible electroporation groups, respectively, without significant differences. CONCLUSIONS: Focal and extended irreversible electroporation ablation had similar safety profile, urinary function, and oncologic outcomes in men with localized low-intermediate risk prostate cancer. In addition, focal ablation demonstrated superior erectile function outcome over extended irreversible electroporation in the first 3-6 months.

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.

Diagnostic accuracy of multiparametric MRI- and microultrasound-targeted biopsy in biopsy-naïve patients with a PI-RADS 5 lesion: a single-institutional study.

PURPOSE: To evaluate the diagnostic accuracy of multiparametric magnetic resonance imaging (MRI)- and microultrasound (microUS)-guided targeted biopsy (TBx) in detecting prostate cancer (PCa) and clinically significant (cs) PCa among men with Prostate Imaging Reporting and Data System (PI-RADS 5) lesions and to compare this combined TBx (CTBx) strategy with CTBx plus systemic biopsy (SBx). METHODS: One hundred and thirty-six biopsy-naïve patients with PI-RADS 5 lesion at multiparametric MRI undergoing CTBx plus SBx were retrospectively evaluated. Analysis of diagnostic performance of microUS-TBx, MRI-TBx, CTBx, SBx and combined CTBx plus SBx was performed. Cost (downgrade, upgrade and biopsy core) to effectiveness (detection rate) was compared. RESULTS: CTBx achieved a comparable detection rate to CTBx plus SBx in diagnosis of PCa and csPCa (PCa: 78.7% [107/136] vs 79.4% [108/136]; csPCa: 67.6% [92/136] vs 67.6% [92/136]; p > 0.05) and outperformed SBx (PCa: 58.8% [80/136]; csPCa: 47.8% [65/136]; p < 0.001). Using CTB would have avoided 41.1% (56/136) unnecessary SBx, without missing any csPCa. The rate of any upgrading or csPCa upgrading was significantly higher by SBx than by CTBx [33/65 (50.8%) vs 17/65 (26.1%) and 20/65 (30.8%) vs 4/65 (6.15%), respectively, p < 0.05]. Considering csPCa detection rate, microUS showed high sensitivity and positive predictive value (94.6%, 87.9%, respectively), with lower specificity and negative predictive value (25.0% and 44.4%, respectively). At multivariable logistic regression models, positive microUS was identified as an independent predictor of csPCa (p = 0.024). CONCLUSIONS: A combined microUS/MRI-TBx approach could be the ideal imaging tool for characterizing primary disease in PI-RADS five patients, allowing SBx to be avoided.

Neoadjuvant chemotherapy does not increase peri-operative morbidity following radical cystectomy.

OBJECTIVE: To determine whether use of neoadjuvant chemotherapy (NAC) is associated with a higher risk of post-operative complications following radical cystectomy (RC) for bladder cancer (BCa). MATERIALS AND METHODS: We retrospectively reviewed records of patients undergoing RC for non-metastatic urothelial BCa at 13 tertiary care centres from 2007-2019. Patients who received NAC ('NAC + RC' group) were compared with those who underwent upfront RC ('RC alone' group) for intra-operative variables, incidence of post-operative complications as per the Clavien-Dindo classification (CDC) and rates of re-admission and re-intervention. Multivariable logistic regression analysis was performed to determine predictors of CDC overall and CDC major (grade III-V) complications. We also analysed the trend of NAC utilization over the study period. RESULTS: Of the 3113 patients included, 968 (31.1%) received NAC while the remaining 2145 (68.9%) underwent upfront RC for BCa. There was no significant difference between the NAC + RC and RC alone groups with regards to 30-day CDC overall (53.2% vs 54.6%, p = 0.4) and CDC major (15.5% vs 16.5%, p = 0.6) complications. The two groups were comparable for the rate of surgical re-intervention (14.6% in each group) and re-hospitalization (19.6% in NAC + RC vs 17.9% in RC alone, p = 0.2%) at 90 days. On multivariable regression analysis, NAC use was not found to be a significant predictor of 90-day CDC overall (OR 1.02, CI 0.87-1.19, p = 0.7) and CDC major (OR 1.05, CI 0.87-1.26, p = 0.6) complications. We also observed that the rate of NAC utilization increased significantly (p < 0.001) from 11.1% in 2007 to 41.2% in 2019, reaching a maximum of 48.3% in 2018. CONCLUSION: This large multicentre analysis with a substantial rate of NAC utilization showed that NAC use does not lead to an increased risk of post-operative complications following RC for BCa. This calls for increasing NAC use to allow patients to avail of its proven oncologic benefit.

The current role of local treatment in metastatic prostate cancer: systematic review and meta-analysis.

BACKGROUND: The aim of this study was to evaluate the current role of local treatment in prostate cancer with a low metastatic burden (or oligometastatic) in relation to survival and safety. METHODS: We performed a meta-analysis of studies published in the MEDLINE, EMBASE, and Cochrane databases until December 2021. Studies comparing local and nonlocal treatment in patients with metastatic prostate cancer were included. The risk of bias within studies was assessed using the Newcastle-Ottawa and Cochrane risk of bias tool. Oligo-metastasis was defined as low-volume metastasis with up to five lesions. The local treatment used was radical prostatectomy or external beam radiation therapy associated with systemic therapy (i.e., androgen deprivation therapy ± abiraterone, docetaxel, enzalutamide, or apalutamide). The endpoints evaluated were overall survival, cancer-specific survival, failure-free survival, and complication rates. RESULTS: Thirteen studies including 46,541 patients were included. The 5-year overall survival (16.0% vs. 6.5%, respectively; odds ratio (OR) 2.74; 95% confidence interval (CI), 2.18, 3.44; I2 = 0%; p < .00001) and 3-year cancer-specific survival (48.2% vs. 26.3%, respectively; OR 1.87; 95% CI: 1.44, 2.44; I2 = 0%; p < .00001) were higher in the local treatment group than that of the nonlocal treatment group. In addition, failure-free survival at 3 years was higher in the local treatment group than that of the nonlocal treatment group (40.5% vs. 28.4%, respectively; OR 1.72; 95% CI, 1.38, 2.14; I2 = 0%; p < .00001). The low complication rate of Clavien-Dindo grade ≥3 indicated that local treatment is feasible and safe in this setting. CONCLUSION: Recent data have shown that local treatment combined with systematic therapy, might improve the overall, cancer-specific, and failure-free survivals of patients diagnosed with metastatic prostate cancer. Furthermore, local treatment is both feasible and safe. Further studies evaluating the quality of life of these patients are needed.

Pelvic lymph node dissection in high-risk prostate cancer.

INTRODUCTION: The therapeutic role of pelvic lymph node dissection (PLND) in prostate cancer (PCa) is unknown due to absence of randomized trials. OBJECTIVE: to present a critical review on the therapeutic benefits of PLND in high risk localized PCa patients. MATERIALS AND METHODS: A search of the literature on PLND was performed using PubMed, Cochrane, and Medline database. Articles obtained regarding diagnostic imaging and sentinel lymph node dissection, PLND extension, impact of PLND on survival, PLND in node positive "only" disease and PLND surgical risks were critically reviewed. RESULTS: High-risk PCa commonly develops metastases. In these patients, the possibility of presenting lymph node disease is high. Thus, extended PLND during radical prostatectomy may be recommended in selected patients with localized high-risk PCa for both accurate staging and therapeutic intent. Although recent advances in detecting patients with lymph node involvement (LNI) with novel imaging and sentinel node dissection, extended PLND continues to be the most accurate method to stage lymph node disease, which may be related to the number of nodes removed. However, extended PLND increases surgical time, with potential impact on perioperative complications, hospital length of stay, rehospitalization and healthcare costs. Controversy persists on its therapeutic benefit, particularly in patients with high node burden. CONCLUSION: The impact of PLND on biochemical recurrence and PCa survival is unclear yet. Selection of patients may benefit from extended PLND but the challenge remains to identify them accurately. Only prospective randomized study would answer the precise role of PLND in high-risk pelvis confined PCa patients.

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.

Impact of Focal Versus Whole Gland Ablation for Prostate Cancer on Sexual Function and Urinary Continence.

PURPOSE: Focal instead of whole gland ablation for prostate cancer has been proposed to decrease treatment morbidity. We sought to determine differences in erectile function and urinary continence after focal and whole gland ablation for prostate cancer. MATERIALS AND METHODS: From 2009 to 2018, 346 patients underwent high intensity focused ultrasound or cryotherapy for prostate cancer. Urinary continence was defined as use of no pads and sexual potency as enough erection for sexual penetration. Logistic regressions to treatment groups and covariates age, prostate specific antigen, International Society of Urological Pathology grading, prostate volume and energy modality were performed to access the effect of focal therapy in sexual potency and urinary continence after 3 and 12 months. IIEF-5 (International Index of Erectile Function) and I-PSS (International Prostate Symptom Score) questionnaires were evaluated. Propensity score matching was performed to adjust for potential baseline differences between groups. RESULTS: After exclusion, 195 post-focal therapy and 105 post-whole gland therapy patients were included in analysis. No significant difference was seen in baseline I-PSS and IIEF-5 scores. In multivariate models focal therapy was the most important factor related to sexual potency at 3 (OR 7.7) and 12 months (OR 3.9). Median IIEF-5 score at 3 months was 12 and 5 (p <0.001), and at 12 months was 13 and 9 (p=0.04) in focal therapy and whole gland therapy groups, respectively. Focal therapy was the only factor related to continence (OR 0.7, p <0.001). Results remained significant after propensity score matching. CONCLUSIONS: Focal ablation instead of whole gland therapy is the most important factor related to better sexual and urinary continence recovery after high intensity focused ultrasound and cryotherapy for prostate cancer.

Association between Lesion Location and Oncologic Outcomes after Focal Therapy for Localized Prostate Cancer Using Either High Intensity Focused Ultrasound or Cryotherapy.

PURPOSE: We assessed whether prostate cancer (PCa) location might affect oncologic outcomes after focal therapy (FT) for PCa. MATERIALS AND METHODS: We identified 274 men receiving FT for PCa using either high intensity focused ultrasound (HIFU) or cryotherapy at a high volume center between 2009 and 2018. Survival analyses using Kaplan-Meier method were used to assess any additional treatment and radical treatment rates according to PCa location. Propensity-score match analysis was used to compare oncologic outcomes of HIFU vs cryotherapy according to PCa location. Covariates were prostate specific antigen, clinical stage, prostate volume, Gleason score, maximum cancer core length, percentage of positive cores and treatment modality. RESULTS: A total of 166 and 108 men received FT with HIFU and cryotherapy, respectively. Overall, 39% (106) and 31% (85) received at least an additional treatment and a radical treatment after FT, respectively, with a median followup of 51 months. At 36 months' followup, the rates of any additional treatment-free survival were 71%, 75%, and 69% for patients with basal, mid-prostate and apical disease, respectively (p=0.7). At multivariable logistic regression analysis, PCa location was not significantly associated with higher risk of either any additional treatment or radical treatment (all p >0.4). After matching, there was no difference between HIFU vs cryotherapy in terms of any additional treatment rates according to PCa location. CONCLUSIONS: The PCa location does not significantly affect the rate of failure after FT. The presence of an apical lesion should not be considered an exclusion criteria for FT. Both HIFU and cryotherapy likely achieve similar medium-term oncologic results regardless of PCa location.

Is the Toxicity of Salvage Prostatectomy Related to the Primary Prostate Cancer Therapy Received?

PURPOSE: To compare the toxicity profile and oncological outcome of salvage radical prostatectomy following focal therapy versus salvage radical prostatectomy after radiation therapies (external beam radiation therapy or brachytherapy). MATERIALS AND METHODS: Data concerning all men undergoing salvage radical prostatectomy for recurrent prostate cancer after either focal therapy, external beam radiation therapy or brachytherapy were retrospectively collected from 4 high volume surgical centers. The primary outcome measure of the study was toxicity of salvage radical prostatectomy characterized by any 30-day postoperative Clavien-Dindo complication rate, 12-month continence rate and 12-month potency rate. The secondary outcome was oncological outcome after salvage radical prostatectomy including positive margin rate and 12-month biochemical recurrence rate. Biochemical recurrence was estimated using Kaplan-Meier methods and significant differences were calculated using a log rank test. Median followup was 29.5 months. RESULTS: Between April 2007 and September 2018, 185 patients underwent salvage radical prostatectomy of whom 95 had salvage radical prostatectomy after focal therapy and 90 had salvage radical prostatectomy after radiation therapy (external beam radiation therapy or brachytherapy). Salvage radical prostatectomy after radiation therapy was associated with a significantly higher 30-day Clavien-Dindo I-IV complication rate (34% vs 5%, p <0.001). At 12 months following surgery, patients undergoing salvage radical prostatectomy after focal therapy had significantly better continence (83% pad-free vs 49%) while potency outcomes were similar (14% vs 11%). Men undergoing salvage radical prostatectomy after radiation therapy had a significantly higher stage and grade of disease together with a higher positive surgical margin rate (37% vs 13%, p=0.001). The 3-year biochemical recurrence after focal therapy was 35% compared to 32% after radiation therapy (p=0.76). In multivariable analysis, men undergoing salvage radical prostatectomy after focal therapy experienced a higher risk of biochemical recurrence (HR 0.36, 95% CI 0.16-0.82, p=0.02). CONCLUSIONS: This multicenter study demonstrates the toxicity of salvage radical prostatectomy in terms of perioperative complications and long-term urinary continence recovery is dependent on initial primary prostate cancer therapy received with men undergoing salvage radical prostatectomy after focal therapy experiencing lower postoperative complication rates and better urinary continence outcomes.

Indications for and complications of pelvic lymph node dissection in prostate cancer: accuracy of available nomograms for the prediction of lymph node invasion.

OBJECTIVES: To externally validate the currently available nomograms for predicting lymph node invasion (LNI) in patients with prostate cancer (PCa) and to assess the potential risk of complications of extended pelvic lymph node dissection (ePLND) when using the recommended threshold. METHODS: A total of 14 921 patients, who underwent radical prostatectomy with ePLND at eight European tertiary referral centres, were retrospectively identified. After exclusion of patients with incomplete biopsy or pathological data, 12 009 were included. Of these, 609 had undergone multiparametic magnetic resonance imaging-targeted biopsies. Among ePLND-related complications we included lymphocele, lymphoedema, haemorrhage, infection and sepsis. The performances of the Memorial Sloan Kettering Cancer Centre (MSKCC), Briganti 2012, Briganti 2017, Briganti 2019, Partin 2016 and Yale models were evaluated using receiver-operating characteristic curve analysis (area under the curve [AUC]), calibration plots, and decision-curve analysis. RESULTS: Overall, 1158 patients (9.6%) had LNI, with a mean of 17.7 and 3.2 resected and positive nodes, respectively. No significant differences in AUCs were observed between the MSKCC (0.79), Briganti 2012 (0.79), Partin 2016 (0.78), Yale (0.80), Briganti 2017 (0.81) and Briganti 2019 (0.76) models. A direct comparison of older models showed that better discrimination was achieved with the MSKCC and Briganti 2012 nomograms. A tendency for underestimation was seen for all the older models, whereas the Briganti 2017 and 2019 nomograms tended to overestimate LNI risk. Decision-curve analysis showed a net benefit for all models, with a lower net benefit for the Partin 2016 and Briganti 2019 models. ePLND-related complications were experienced by 1027 patients (8.9%), and 12.6% of patients with pN1 disease. CONCLUSIONS: The currently available nomograms have similar performances and limitations in the prediction of LNI. Miscalibration was present, however, for all nomograms showing a net benefit. In patients with only systematic biopsy, the MSKCC and Briganti 2012 nomograms were superior in the prediction of LNI.

Making a case "for" focal therapy of the prostate in intermediate risk prostate cancer: current perspective and ongoing trials.

Focal therapy is growing as an alternative management options for men with clinically localized prostate cancer. Parallel to the increasing popularity of active surveillance (AS) as a treatment for low-risk disease, there has been an increased interest towards providing focal therapy for patients with intermediate-risk disease. Focal therapy can act as a logical "middle ground" in patients who seek treatment while minimizing potential side effects of definitive whole-gland treatment. The aim of the current review is to define the rationale of focal therapy in patients with intermediate-risk prostate cancer and highlight the importance of patient selection in focal therapy candidacy.

Impact of COVID-19 on medical education: introducing homo digitalis.

PURPOSE: To determine how members of the Société Internationale d'Urologie (SIU) are continuing their education in the time of COVID-19. METHODS: A survey was disseminated amongst SIU members worldwide by email. Results were analyzed to examine the influence of age, practice region and settings on continuing medical education (CME) of the respondents. RESULTS: In total, 2494 respondents completed the survey. Internet searching was the most common method of CME (76%; all ps < 0.001), followed by searching journals and textbook including the online versions (62%; all ps < 0.001). Overall, 6% of the respondents reported no time/interest for CME during the pandemic. Although most urologists report using only one platform for their CME (26.6%), the majority reported using ≥ 2 platforms, with approximately 10% of the respondents using up to 5 different platforms. Urologists < 40 years old were more likely to use online literature (69%), podcasts/AV media (38%), online CME courses/webinars (40%), and social media (39%). There were regional variations in the CME modality used but no significant difference in the number of methods by region. There was no significant difference in responses between urologists in academic/public hospitals or private practice. CONCLUSION: During COVID-19, urologists have used web-based learning for their CME. Internet learning and literature were the top frequently cited learning methods. Younger urologists are more likely to use all forms of digital learning methods, while older urologists prefer fewer methods.

Optimal Surgical Outcome of Minimally Invasive Partial Nephrectomy (MIPN) Based on an Early Postoperative Estimated Glomerular Filtration Rate (eGFR).

PURPOSE OF REVIEW: To compare laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN) performed in two European tertiary centers using the classic optimal surgical definition - "MIC" - and a new optimal surgical definition: the "Novel TRIFECTA" (NT) concept. We sought to strengthen the PN evidence and to test the NT's performance. RECENT FINDINGS: The study population comprehended 505 cases of localized kidney cancer from two tertiary centers between 2012 and 2019. The NT achievement was higher in the RAPN group when compared to LPN (70.5 vs. 87.4%; p = 0.004), while no differences were found when considering the MIC criteria. Also, a similar high-grade complications rate (Clavien-Dindo > III) and operative time (105 min vs. 100 min; p = NS) were found. In the multivariable regression, the RAPN approach was a predictor of NT achievement (OR 2.45; p = 0.008). NT achievement was higher in the RAPN group, while similar results were found when evaluating the MIC criteria. The NT definition could be more sensitive to the individual-specific responses related to the PN.

Focal Therapy for Localized Prostate Cancer with Either High Intensity Focused Ultrasound or Cryoablation: A Single Institution Experience.

PURPOSE: We report oncologic outcomes in patients treated with focal therapy for prostate cancer. MATERIALS AND METHODS: We retrospectively analyzed a single institution cohort of men with localized prostate cancer who received focal therapy using high intensity focused ultrasound or cryotherapy from 2009 to 2018. Focal therapy was offered for low or intermediate risk disease (prostate specific antigen less than 20 ng/ml, Gleason score 7 or less and clinical stage T2b or less). Patients with previous prostate cancer treatment or less than 6 months of followup were excluded from study. Failure was defined as local or systemic salvage treatment, a positive biopsy Gleason score of 7 or greater in-field or out-of-field in nontreated patients, prostate cancer metastasis or prostate cancer specific death. Cox regression analysis was done to identify independent predictors of failure after focal therapy. RESULTS: Of the 309 patients included in study 190 and 119 were treated with high intensity focused ultrasound and cryotherapy, respectively. Median followup was 45 months. At 1, 3 and 5 years the failure-free survival rate was 95%, 67% and 54%, and the radical treatment-free survival rate was 99%, 79% and 67%, respectively. The 5-year metastasis-free survival rate was 98% and no prostate cancer specific death was registered in this cohort. Before focal therapy a biopsy Gleason score of 7 (3 + 4) or greater (HR 2.4, p <0.001) and nadir prostate specific antigen (HR 2.2, p <0.001) were independently associated with failed focal therapy. In the salvage focal therapy setting in-field recurrence after primary focal therapy was associated with poorer failure-free survival (p=0.02). CONCLUSIONS: Almost half of the men were free of focal therapy failure 5 years after treatment. Still, a significant proportion experienced recurrence at the midterm followup. The preoperative biopsy Gleason score and nadir prostate specific antigen were significantly associated with treatment failure.

Comparison of Initial Experience with Transrectal Magnetic Resonance Imaging Cognitive Guided Micro-Ultrasound Biopsies versus Established Transperineal Robotic Ultrasound Magnetic Resonance Imaging Fusion Biopsies for Prostate Cancer.

PURPOSE: We compared cancer detection rates in patients who underwent magnetic resonance imaging cognitive guided micro-ultrasound biopsy vs robotic ultrasound magnetic resonance imaging fusion biopsy for prostate cancer. MATERIALS AND METHODS: Among 269 targeted biopsy procedures 222 men underwent robotic ultrasound magnetic resonance imaging fusion biopsy and 47 micro-ultrasound biopsy. Robotic ultrasound magnetic resonance imaging fusion biopsy was performed using the transperineal Artemis™ device while micro-ultrasound biopsy was performed transrectally with the high resolution ExactVu™ system. Random biopsies were performed in addition to targeted biopsy in both modalities. Prostate cancer detection rates and concordance between random and target biopsies were also assessed. RESULTS: Groups were comparable in terms of age, prostate specific antigen, prostate volume and magnetic resonance PI-RADS (Prostate Imaging Reporting and Data System) version 2 score. The micro-ultrasound biopsy group presented fewer biopsied cores in random and target approaches. In targeted biopsies micro-ultrasound biopsy cases presented higher detection of clinically significant disease (Gleason score greater than 6) than the robotic ultrasound magnetic resonance imaging fusion biopsy group (38% vs 23%, p=0.02). When considering prostate cancer detection regardless of Gleason score or prostate cancer detection by random+target biopsies, no difference was found between the groups. However, on a per core basis overall prostate cancer detection rates favored micro-ultrasound biopsy in random and targeted scenarios. In addition, the PRI-MUS (Prostate Risk Identification Using Micro-Ultrasound) score yielded by micro-ultrasound visualization was independently associated with improved cancer detection rates of clinically significant prostate cancer. CONCLUSIONS: In our initial experience micro-ultrasound biopsy featured a higher clinically significant prostate cancer detection rate in target cores than robotic ultrasound magnetic resonance imaging fusion biopsy, which was associated with target features in micro-ultrasound (PRI-MUS score). These findings reinforce the role of micro-ultrasound technology in targeted biopsies.