Tumour microenvironment and focal therapy for prostate cancer.

PURPOSE OF REVIEW: Although most studies focus on the tumour component of prostate cancer (PCa), increasing attention is being paid to the prostatic tumour microenvironment (TME) and its role in diagnosis, prognosis, and therapy development. Herein, we review the prognostic capability of tumour and nontumour derived biomarkers, the immunomodulatory effects of focal therapy (FT) on TME, and its potential as part of a multidisciplinary approach to PCa treatment. RECENT FINDINGS: Tumour cells have always been the natural candidates to explore new biomarkers, but recent evidence highlights the prognostic contribution of TME cell markers. TME plays a critical role in PCa progression and tumours may escape from the immune system by establishing a microenvironment that suppresses effective antitumour immunity. It has been demonstrated that FT has an immunomodulatory effect and may elicit an immune response that can either favour or inhibit tumorigenesis. TME shows to be an additional target to enhance oncological control. SUMMARY: A better understanding of TME has the potential to reliably elucidate PCa heterogeneity and assign a prognostic profile in accordance with prostate tumour foci. The joint contribution of biomarkers derived from both tumour and TME compartments may improve patient selection for FT by accurately stratifying disease aggressivity according to the characteristics of tumour foci. Preclinical studies have suggested that FT may act as a TME modulator, highlighting its promising role in multimodal therapeutic management.

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.

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.

HRQOL related to urinary diversion in Radical Cystectomy: a systematic review of recent literature.

INTRODUCTION: The health-related QoL is a patient-centered evaluation covering several aspects. This evaluation seems to be particularly important in patients submitted to radical cystectomy (RC) and urinary diversion with ileal conduit (IC) or a neobladder (NB). OBJECTIVE: Review all recent data comparing QoL outcomes after radical cystectomy with NB and IC diversions. EVIDENCE ACQUISITION: A systematic search in PubMed/Medline, Embase, and Cochrane databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement in December 2018. All articles published from January 01, 2012 to December 31, 2018, were included. A study was considered relevant if it compared QoL outcomes using validated questionnaires (EORTC QLQ C30, FACT-G, FACT-BL, FACT-VCI, and BCI). EVIDENCE SYNTHESIS: In 11 included studies, a total of 1389 participants were accounted (730 NB and 659 IC cases). The studies were conducted in 8 different countries, two were prospective, and none was randomized. There were two studies favoring results with a neobladder, 3 with incontinent diversion and 6 with no differences. The EORTC-QLQ-C30 was the most used instrument (5 studies) followed by FACT VCI and BCI (3 studies each). Given the heterogeneity of data and lack of prospective studies, a meta-analysis was not performed. CONCLUSION: No superiority of one urinary diversion was characterized. It seems that the choice must be individualized with an extensive preoperative orientation of the patient and their relatives. That will probably infl uence how the patient accepts the new condition.

Prostate cancer in Brazil and Latin America: epidemiology and screening.

INTRODUCTION: Prostate cancer is one of the tumors with higher incidence and mortality among men in the World. Epidemiological data are influenced by life expectancy of population, available diagnostic methods, correct collection of data and quality of health services. Screening of the disease is not standardized around the World. Up till now there is no consensus about the risks versus benefits of early detection. There are still missing data about this pathology in Latin America. OBJECTIVE: to revise current epidemiologic situation and early diagnosis policies of prostate cancer in Brazil and Latin America. MATERIALS AND METHODS: Medline, Cochrane Library and SciELO databases were reviewed on the subject of epidemiology and screening of prostate cancer. Screening research was performed in websites on national public health organizations and Latin America. Screening recommendations were obtained from those governmental organizations and from Latin American urological societies and compared to the most prominent regulatory agencies and societies of specialists and generalists from around the World. RESULTS: Brazil and Latin America have a special position in relation to incidence and mortality of prostate cancer. In Brazil, it occupies the first position regarding incidence of cancer in men and the second cause of mortality. Central America has the highest rate of mortality of the continent with lower incidence/mortality ratios. Screening recommendations are very distinct, mainly among regulatory organs and urological societies. CONCLUSION: prostate cancer epidemiology is an important health public topic. Data collection related to incidence and mortality is still precarious, especially in less developed countries. It is necessary to follow-up long term screening studies results in order to conclude its benefits.

Salvage local treatment for recurrent prostate cancer after focal therapy: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the role of salvage local treatment in managing recurrent PCa following FT, focusing on oncological and functional outcomes. METHODS: A systematic review and meta-analysis were performed following the PRISMA framework. A comprehensive literature search using the PubMed/MEDLINE and EMBASE databases was performed until July 2023. Eligible studies included patients with clinically localised PCa initially treated with FT, who experienced relapse during surveillance and subsequently underwent salvage radical prostatectomy (sRP), salvage external beam radiation therapy (sEBRT) or salvage focal therapy (sFT). The primary endpoint was the biochemical recurrence rate post-salvage treatment. The secondary endpoints were functional outcomes, including urinary incontinence and erectile dysfunction rates. RESULTS: In 26 retrospective studies including 990 patients, the overall pooled biochemical recurrence rate postsalvage treatment was 26%. The subgroup analysis revealed a biochemical recurrence rate of 20%, 22%, and 42% after sRP, sEBRT, and sFT, respectively. The overall pooled rate of urinary incontinence was 20%. Salvage FT had the lowest prevalence of urinary incontinence, followed by sRP and sEBRT. The overall pooled rate of erectile dysfunction was 43%. Salvage RP had the highest prevalence of erectile dysfunction, followed by sFT and sEBRT. Substantial heterogeneity was observed among the studies, primarily due to different sample sizes. Meta-regression analysis revealed no to low contributions of salvage treatment modalities, extent of ablation, age, prostatic specific antigen level before salvage treatment, proportion of patients with Gleason score ≥7 at recurrence, and time between the primary and salvage therapies to heterogeneity. CONCLUSION: Salvage local treatment for recurrent PCa after FT is feasible, and it provides acceptable oncological and functional outcomes. Among all treatment modalities, sRP and sEBRT appeared to have the lowest biochemical recurrence rates, whereas sFT was associated with improved functional outcomes.

Development of the European Laparoscopic Intermediate Urological Skills LUSs2 Curriculum: A Delphi Consensus from the European School of Urology.

Background and objective: While programmes such as the European Basic Laparoscopic Urological Skills have made strides in foundational training, a significant gap exists for intermediate and advanced laparoscopy education. Our objective is to develop and validate the European laparoscopic intermediate urological skills (LUSs2) curriculum, which will establish uniformity in the training of urological laparoscopic procedures and facilitate proficiency among practitioners. Methods: The study combines a literature review, cognitive task analysis development by a steering group, and a two-round Delphi survey involving international experts in urological laparoscopy. Consensus was defined as agreement of ≥70% among experts. The survey included statements on various laparoscopic procedures, assessed on a Likert scale from 1 (strongly disagree) to 9 (strongly agree). Key findings and limitations: The Delphi process achieved consensus on 85% (235/275) of statements, indicating a strong agreement on the curriculum's content. Areas covered include renal hilum dissection, major vessel injury management, enucleation and renorrhaphy, vesicourethral anastomosis, and pyeloplasty. Limitations include the nonsystematic nature of the literature review and potential biases inherent in expert-based consensus methods. Conclusions and clinical implications: The LUSs2 curriculum significantly advances the standardised training of laparoscopic urological skills. It offers a detailed, consensus-validated framework that addresses the need for uniformity in surgical education and aims to enhance surgical proficiency and patient care. Patient summary: This study presents the development of a new standardised training curriculum for urological laparoscopic surgery. We intend this curriculum to improve the quality of surgical training and ensure high-quality patient care.

HIFU focal therapy for prostate cancer using intraoperatory contrast enhanced ultrasound.

OBJECTIVE: High-intensity focused ultrasound (HIFU) Focal therapy appears to have encouraging oncologic outcomes and urinary and erectile function. The control of the treated area can be done using contrast enhanced ultrasound with sulfur hexafluoride (Sonovue®) at the end of the procedure. We report oncological and functional outcomes in HIFU focal therapy (FT) for prostate cancer (PCa) management using sonovue. METHODS: A total of 274 HIFU procedures were found in our registry in the period between June 2014 and July 2018. Prospective data of 59 consecutive patients after focal high-intensity focused ultrasound (HIFU) using Sonovue were collected. FT failure was defined as positive biopsy Gleason score (GS) ≥ 7 in- or out-field, local or systemic salvage treatment, PCa-metastasis or PCa-specific death. RESULTS: A total of 59 patients submitted to HIFU with median follow-up of 18 months were included in the analysis. Median age was 66.7 yr (IQR 59.1-74.3). Median preoperative prostate-specific antigen (PSA) was 7.6 ng/ml (IQR 5-10.2) and preoperative biopsies GS 6, 7(3+4), 7(4+3) were found in 26 (44%), 30 (50.8%) and 3 (5%), respectively. Failure was found in 16 (27.1%) patients. Failure-free survival (FFS) in 2 and 4yr was 83% and 74% respectively (Figure 1). No PCa-specific death was registered in the period of study. Median nadir PSA after FT was 2.67 ng/ml. Sexual potency was achieved in 75% of previous potent patients and urinary continence in 93.4% of patients at 3 months. Fourteen (23%) patients presented with complications. Four (6.7%) patients have presented complications grade 1 and 10 (16.9%) patients have presented complications grade 2. Six (10.1%) patients have presented acute urinary retention. CONCLUSIONS: Our study shows that the use of Sonovue after HIFU FT was safe. Patients present a significant proportion of failure after HIFU FT but with good functional outcomes and without incidence of severe complications.

OBJETIVOS: La terapia focal con HIFU (High-intensity focused ultrasound) parece tener unos resultados oncológicos y de función urinaria y eréctil prometedores. El control del área tratada puede realizarse al final de la intervención utilizando Sonovue®, el contraste de ecografía con hexafluoruro de azufre. Presentamos los resultados oncológicos y funcionales de la terapia focal con HIFU en el tratamiento cáncer de próstata utilizando Sonovue.MÉTODOS: Se encontraron en nuestro registro un total de 274 intervenciones con HIFU entre Junio 2014 y Julio 2018. Se recogieron los datos prospectivamente en 59 pacientes consecutivos después de HIFU utilizando Sonovue. Se define fracaso de la terapia focal como biopsia positiva con puntuación de Gleason (GS) >7 dentro o fuera del campo, tratamiento de salvamento local o sistémico, metástasis del CaP o muerte cáncer específica por CaP. RESULTADOS: Se incluyeron en el análisis un total de 59 pacientes sometidos a HIFU con una mediana de seguimiento de 18 meses. La mediana de edad fue 66,7 años (Rango intercuartílico (RIC) 59,1-74,3). La mediana de PSA preoperatorio fue 7,6 ng/mL (RIC 5-10,2) y las biopsias fueron GS 6, 7 (3+4) y 7 (4+3) en 26 (44%), 30 (50,8%) y 3 (5%) casos, respectivamente. En 16 pacientes (27,1%) fracasó el tratamiento. La supervivencia libre de fracaso del tratamiento a 2 y 4 años fue 83% y 74% respectivamente (Figura 1). No se ha registrado ninguna muerte cáncer específica por el CaP en el periodo de estudio. La mediana del nadir de PSA después de la terapia focal fue 2,67 ng/ml. El 75% de los pacientes previamente potentes consiguieron mantener su potencia sexual y el 93,4% eran continentes a los 3 meses. Catorce pacientes (23%) presentaron complicaciones. Cuatro (6,7%) presentaron complicaciones grado 1 y 10 (16,9%) grado 2. Seis pacientes (10,1%) presentaron retención aguda de orina. CONCLUSIONES: Nuestro estudio muestra que el uso de Sonovue después de terapia focal con HIFU es seguro. Los pacientes presentan una proporción significativa de fracasos después de terapia focal con HIFU aunque tiene buenos resultados funcionales y sin incidencia de complicaciones graves.

Complications in robotic urological surgeries and how to avoid them: A systematic review.

OBJECTIVES: To review the main complications related to the robot-assisted laparoscopic (RAL) approach in urology and to suggest measures to avoid such issues. METHODS: A systematic search for articles of the contemporary literature was performed in PubMed database for complications in RAL urological procedures focused on positioning, access, and operative technique considerations. Each complication topic is followed by recommendations about how to avoid it. RESULTS: In all, 40 of 253 articles were included in this analysis. Several complications in RAL procedures can be avoided if the surgical team follows some key steps. Adequate patient positioning must avoid skin, peripheral nerve, and muscles injuries, and ocular and cognitive complications mainly related to steep Trendelenburg positioning in pelvic procedures. Port-site access and closure should not be neglected during minimally invasive procedures as these complications although rare can be troublesome. Technique-related complications depend on surgeon experience and the early learning curve should be monitored. CONCLUSIONS: Adequate patient selection, surgical positioning, mentorship training, and avoiding long-lasting procedures are essential to prevent RAL-related complications. The robotic surgical team must be careful and work together to avoid possible complications. This review offers several steps in surgical planning to reach this goal.

HRQOL related to urinary diversion in Radical Cystectomy: a systematic review of recent literature

ABSTRACT Introduction: The health-related QoL is a patient-centered evaluation covering several aspects. This evaluation seems to be particularly important in patients submitted to radical cystectomy (RC) and urinary diversion with ileal conduit (IC) or a neobladder (NB). Objective: Review all recent data comparing QoL outcomes after radical cystectomy with NB and IC diversions. Evidence Acquisition: A systematic search in PubMed/Medline, Embase, and Cochrane databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement in December 2018. All articles published from January 01, 2012 to December 31, 2018, were included. A study was considered relevant if it compared QoL outcomes using validated questionnaires (EORTC QLQ C30, FACT-G, FACT-BL, FACT-VCI, and BCI). Evidence Synthesis: In 11 included studies, a total of 1389 participants were accounted (730 NB and 659 IC cases). The studies were conducted in 8 different countries, two were prospective, and none was randomized. There were two studies favoring results with a neobladder, 3 with incontinent diversion and 6 with no differences. The EORTC-QLQ-C30 was the most used instrument (5 studies) followed by FACT VCI and BCI (3 studies each). Given the heterogeneity of data and lack of prospective studies, a meta-analysis was not performed. Conclusion: No superiority of one urinary diversion was characterized. It seems that the choice must be individualized with an extensive preoperative orientation of the patient and their relatives. That will probably influence how the patient accepts the new condition.

Prostate cancer in Brazil and Latin America: epidemiology and screening

ABSTRACT Introduction: Prostate cancer is one of the tumors with higher incidence and mortality among men in the World. Epidemiological data are influenced by life expectancy of population, available diagnostic methods, correct collection of data and quality of health services. Screening of the disease is not standardized around the World. Up till now there is no consensus about the risks versus benefits of early detection. There are still missing data about this pathology in Latin America. Objective: to revise current epidemiologic situation and early diagnosis policies of prostate cancer in Brazil and Latin America. Materials and Methods: Medline, Cochrane Library and SciELO databases were reviewed on the subject of epidemiology and screening of prostate cancer. Screening research was performed in websites on national public health organizations and Latin America. Screening recommendations were obtained from those governmental organizations and from Latin American urological societies and compared to the most prominent regulatory agencies and societies of specialists and generalists from around the World. Results: Brazil and Latin America have a special position in relation to incidence and mortality of prostate cancer. In Brazil, it occupies the first position regarding incidence of cancer in men and the second cause of mortality. Central America has the highest rate of mortality of the continent with lower incidence/mortality ratios. Screening recommendations are very distinct, mainly among regulatory organs and urological societies. Conclusion: prostate cancer epidemiology is an important health public topic. Data collection related to incidence and mortality is still precarious, especially in less developed countries. It is necessary to follow-up long term screening studies results in order to conclude its benefits.