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PurposeThe sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT).Materials and methodsIndividual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer-specific mortality.ResultsOverall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer-specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT.ConclusionADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT.

BackgroundThe importance of local failure (LF) after treatment of high-grade prostate cancer (PCa) with definitive radiotherapy (RT) remains unknown.ObjectiveTo evaluate the clinical implications of LF after definitive RT.Design, setting, and participantsIndividual patient data meta-analysis of 992 patients (593 Gleason grade group [GG] 4 and 399 GG 5) enrolled in six randomized clinical trials.Outcome measurements and statistical analysisMultivariable Cox proportional hazard models were developed to evaluate the relationship between overall survival (OS), PCa-specific survival (PCSS), and distant metastasis (DM)-free survival (DMFS) and LF as a time-dependent covariate. Markov proportional hazard models were developed to evaluate the impact of specific transitions between disease states on these endpoints.Results and limitationsMedian follow-up was 6.4 yr overall and 7.2 yr for surviving patients. LF was significantly associated with OS (hazard ratio [HR] 1.70 [95% confidence interval {CI} 1.37-2.10]), PCSS (3.10 [95% CI 2.33-4.12]), and DMFS (HR 1.92 [95% CI 1.54-2.39]), p

Introduction: This study focuses on the quantification of and current guidelines on the hazards related to needle positioning in prostate cancer treatment: (1) access restrictions to the prostate gland by the pubic arch, so-called Pubic Arch Interference (PAI) and (2) needle positioning errors. Next, we propose solution strategies to mitigate these hazards. Methods: The literature search was executed in the Embase, Medline ALL, Web of Science Core Collection*, and Cochrane Central Register of Controlled Trials databases. Results: The literature search resulted in 50 included articles. PAI was reported in patients with various prostate volumes. The level of reported PAI varied between 0 and 22.3 mm, depending on the patient's position and the measuring method. Low-Dose-Rate Brachytherapy induced the largest reported misplacement errors, especially in the cranio-caudal direction (up to 10 mm) and the largest displacement errors were reported for High-Dose-Rate Brachytherapy in the cranio-caudal direction (up to 47 mm), generally increasing over time. Conclusions: Current clinical guidelines related to prostate volume, needle positioning accuracy, and maximum allowable PAI are ambiguous, and compliance in the clinical setting differs between institutions. Solutions, such as steerable needles, assist in mitigating the hazards and potentially allow the physician to proceed with the procedure. This systematic review was performed in accordance with the PRISMA guidelines. The review was registered at Protocols.io (DOI: dx.doi.org/10.17504/protocols.io.6qpvr89eplmk/v1). [ABSTRACT FROM AUTHOR]

The article discusses the FocAL therapy CONsensus (FALCON), which aimed to establish a comprehensive statement on focal therapy (FT) for localized prostate cancer (PCa). FT is a middle-ground option between active surveillance and radical treatments for PCa. The consensus was developed through an online survey and Delphi consensus method, involving a diverse group of professionals experienced in PCa management. The consensus covered various aspects of FT, including patient selection, energy selection, treatment approach, treatment evaluation and follow-up, treatment cost and accessibility, and future perspectives. The FALCON project provides a comprehensive guide for FT and highlights areas of knowledge deficiency that will guide future research. [Extracted from the article]

This document is a list of references and sources related to the topic of focal therapy for prostate cancer. It includes studies, clinical trials, and research papers that explore various treatment options and techniques, such as high-intensity focused ultrasound (HIFU), irreversible electroporation (IRE), and photodynamic therapy. The document also mentions the importance of accurate imaging techniques, such as magnetic resonance imaging (MRI) and prostate-specific membrane antigen (PSMA) PET-CT, in guiding and assessing the effectiveness of focal therapy. The references provide a comprehensive overview of the current research and ongoing studies in the field of focal therapy for prostate cancer. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate: (i) safety, (ii) feasibility, and medium‐term (iii) oncological and (iv) functional outcomes of salvage radical prostatectomy (sRP) for recurrent localised prostate cancer (PCa) following initial focal therapy using irreversible electroporation (IRE). Patients and Methods: An international, multicentre and retrospective analysis of prospectively collected data of patients that underwent sRP for recurrent localised PCa after initial primary IRE treatment. Data were reported on (i) surgical complications, (ii) feasibility of sRP reported by surgeons, (iii) time interval between IRE and sRP and pathology results, and (iv) urinary continence, erectile function, and quality of life. Results: In four participating centres, a total of 39 patients with a median (interquartile range [IQR]) age 64 (60–67) years were identified. No serious adverse events occurred during or following sRP and surgery was deemed feasible without difficulties. The median (IQR) time to recurrence following IRE was 14.3 (9.1–38.8) months. Pathology results showed localised disease in 21 patients (53.8%) and locally‐advanced disease in 18 (46.2%). Positive surgical margins (PSMs) were observed in 10 patients (25.6%), of which six (15.4%) had significant PSMs. A persistent detectable prostate‐specific antigen level was found in one case after sRP, caused by metastatic disease. One patient had a biochemical recurrence 6 months after sRP. These two cases, together with a PSM case, required additional therapy after sRP. After a median (IQR) follow‐up of 17.7 (11.8–26.4) months, urinary continence and erectile function were preserved in 34 (94.4%) and 18 patients (52.9%), respectively, while quality of life remained stable. Conclusions: Salvage RP is safe and feasible for patients with recurrent localised PCa following initial IRE treatment. The medium‐term oncological and functional outcomes are similar to primary RP. Strict patient selection for focal therapy and standardised follow‐up is needed as some patients developed high‐grade disease. [ABSTRACT FROM AUTHOR]

Purpose: The introduction of magnetic resonance imaging (MRI)-targeted biopsy (TBx) besides systematic prostate biopsies has resulted in a discussion on what the optimal prostate biopsy strategy is. The ideal template has high sensitivity for clinically significant prostate cancer (csPCa), while reducing the detection rate of clinically insignificant prostate cancer (iPCa). This study evaluates different biopsy strategies in patients with a unilateral prostate MRI lesion. Methods: Retrospective subgroup analysis of a prospectively managed database consisting of patients undergoing prostate biopsy in two academic centres. Patients with a unilateral lesion (PI-RADS ⩾ 3) on MRI were included for analysis. The primary objective was to evaluate the diagnostic performance for different biopsy approaches compared with bilateral systematic prostate biopsy (SBx) and TBx. Detection rates for csPCa (ISUP ⩾ 2), adjusted csPCa (ISUP ⩾ 3) and iPCa (ISUP = 1) were determined for SBx alone, TBx alone, contralateral SBx combined with TBx and ipsilateral SBx combined with TBx. A subgroup analysis was performed for biopsy-naive patients. Results: A total of 228 patients were included from October 2015 to September 2021. Prostate cancer (PCa) detection rate of combined SBx and TBx was 63.5% for csPCa, 35.5% for adjusted csPCa, and 14% for iPCa. The best performing alternative biopsy strategy was TBx and ipsilateral SBx, which reached a sensitivity of 98.6% (95% CI: 95.1–99.6) for csPCa and 98.8% (95% CI: 96.3–99.9) for adjusted csPCa, missing only 1.4% of csPCa, while reducing iPCa detection by 15.6% compared with SBx and TBx. TBx or SBx alone missed a significant amount of csPCa, with sensitivities of 90.3% (95% CI: 84.4–94.2) and 86.8% (95% CI: 80.4–91.4) for csPCa. Subgroup analysis on biopsy-naive patients showed similar results as the overall group. Conclusion: This study shows that performing TBx with ipsilateral SBx and omitting contralateral SBx is the optimal biopsy strategy in patients with a unilateral MRI lesion. With this strategy, a very limited amount of csPCa is missed and iPCa detection is reduced. [ABSTRACT FROM AUTHOR]

Objectives: To compare and evaluate a multiparametric magnetic resonance imaging (mpMRI)‐targeted biopsy (TBx) strategy, contrast‐ultrasound‐dispersion imaging (CUDI)‐TBx strategy and systematic biopsy (SBx) strategy for the detection of clinically significant prostate cancer (csPCa) in biopsy‐naïve men. Patients and Methods: A prospective, single‐centre paired diagnostic study included 150 biopsy‐naïve men, from November 2015 to November 2018. All men underwent pre‐biopsy mpMRI and CUDI followed by a 12‐core SBx taken by an operator blinded from the imaging results. Men with suspicious lesions on mpMRI and/or CUDI also underwent MRI‐TRUS fusion‐TBx and/or cognitive CUDI‐TBx after SBx by a second operator. A non‐inferiority analysis of the mpMRI‐ and CUDI‐TBx strategies in comparison with SBx for International Society of Urological Pathology Grade Group [GG] ≥2 PCa in any core with a non‐inferiority margin of 1 percentage point was performed. Additional analyses for GG ≥2 PCa with cribriform growth pattern and/or intraductal carcinoma (CR/IDC), and GG ≥3 PCa were performed. Differences in detection rates were tested using McNemar's test with adjusted Wald confidence intervals. Results: After enrolment of 150 men, an interim analysis was performed. Both the mpMRI‐ and CUDI‐TBx strategies were inferior to SBx for GG ≥2 PCa detection and the study was stopped. SBx found significantly more GG ≥2 PCa: 39% (56/142), as compared with 29% (41/142) and 28% (40/142) for mpMRI‐TBx and CUDI‐TBx, respectively (P < 0.05). SBx found significantly more GG = 1 PCa: 14% (20/142) compared to 1% (two of 142) and 3% (four of 142) with mpMRI‐TBx and CUDI‐TBx, respectively (P < 0.05). Detection of GG ≥2 PCa with CR/IDC and GG ≥3 PCa did not differ significantly between the strategies. The mpMRI‐ and CUDI‐TBx strategies were comparable in detection but the mpMRI‐TBx strategy had less false‐positive findings (18% vs 53%). Conclusions: In our study in biopsy‐naïve men, the mpMRI‐ and CUDI‐TBx strategies had comparable PCa detection rates, but the mpMRI‐TBX strategy had the least false‐positive findings. Both strategies were inferior to SBx for the detection of GG ≥2 PCa, despite reduced detection of insignificant GG = 1 PCa. Both strategies did not significantly differ from SBx for the detection of GG ≥2 PCa with CR/IDC and GG ≥3 PCa. [ABSTRACT FROM AUTHOR]

Background: At present, it is not possible to predict the ablation zone volume following irreversible electroporation (IRE) for prostate cancer (PCa). This study aimed to determine the necessary electrical field threshold to ablate human prostate tissue in vivo with IRE. Methods: In this prospective multicenter trial, patients with localized PCa were treated with IRE 4 weeks before their scheduled radical prostatectomy. In 13 patients, numerical models of the electrical field were generated and compared with the ablation zone volume on wholemount pathology and T2-weighted magnetic resonance imaging (MRI) sequences. Volumegenerating software was used to calculate the ablation zone volumes on histology and MRI. The electric field threshold to ablate prostate tissue was determined for each patient. Results: A total of 13 patients were included for histological and simulation analysis. The median electrical field threshold was 550 V/cm (interquartile range 383-750 V/cm) for the software-generated histology volumes. The median electrical field threshold was 500 V/cm (interquartile range 386-580 V/cm) when the ablation zone volumes were used from the follow-up MRI. Conclusions: The electrical field threshold to ablate human prostate tissue in vivo was determined using whole-mount pathology and MRI. These thresholds may be used to develop treatment planning or monitoring software for IRE prostate ablation; however, further optimization of simulation methods are required to decrease the variance that was observed between patients. [ABSTRACT FROM AUTHOR]

Decisions regarding the primary treatment of prostate cancer depend on several patient‐ and disease‐specific factors. Several international guidelines regarding the primary treatment of prostate cancer exist; however, they have not been formally compared. As guidelines often contradict each other, we aimed to systematically compare recommendations regarding the different primary treatment modalities of prostate cancer between guidelines. We searched Medline, the National Guidelines Clearinghouse, the library of the Guidelines International Network, and the websites of major urological associations for prostate cancer treatment guidelines. In total, 14 guidelines from 12 organisations were included in the present article. One of the main discrepancies concerned the definition of ‘localised’ prostate cancer. Localised prostate cancer was defined as cT1–cT3 in most guidelines; however, this disease stage was defined in other guidelines as cT1–cT2, or as any T‐stage as long as there is no lymph node involvement (N0) or metastases (M0). In addition, the risk stratification of localised cancer differed considerably between guidelines. Recommendations regarding radical prostatectomy and hormonal therapy were largely consistent between the guidelines. However, recommendations regarding active surveillance, brachytherapy, and external beam radiotherapy varied, mainly as a result of the inconsistencies in the risk stratification. The differences in year of publication and the methodology (i.e. consensus‐based or evidence‐based) for developing the guidelines might partly explain the differences in recommendations. It can be assumed that the observed variation in international clinical practice regarding the primary treatment of prostate cancer might be partly due to the inconsistent recommendations in different guidelines. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to evaluate the genitourinary function and quality of life (QoL) following the ablation of different prostate segments with irreversible electroporation (IRE) for localized prostate cancer (PCa).Methods: Sixty patients who received primary focal IRE for organ-confined PCa were recruited for this study. Patients were evaluated for genitourinary function and QoL per prostate segment treated (anterior vs. posterior, apex vs. base vs. apex-to-base, unilateral vs. bilateral). IRE system settings and patient characteristics were compared between patients with preserved vs. those with impaired erectile function and urinary continence. Data were prospectively collected at baseline, 3, 6, and 12 months using the expanded prostate cancer index composite, American Urological Association symptom score, SF-12 physical and mental component summary surveys. Difference over time within segments per questionnaire was evaluated using the Wilcoxon's signed rank test. Outcome differences between segments were assessed using covariance models. Baseline measurements included questionnaire scores, age, and prostate volume.Results: There were no statistically significant changes over time for overall urinary (P = 0.07-0.89), bowel (P = 0.06-0.79), physical (P = 0.18-0.71) and mental (P = 0.45-0.94) QoL scores within each segment. Deterioration of sexual function scores was observed at 6 months within each segment (P = 0.001-0.16). There were no statistically significant differences in QoL scores between prostate segments (P = 0.08-0.97). Older patients or those with poor baseline sexual function at time of treatment were associated with a greater risk of developing erectile dysfunction.Conclusion: IRE is a feasible modality for all prostate segments without any significantly different effect on the QoL outcomes. Older patients and those with poor sexual function need to be counseled regarding the risk of erectile dysfunction. [ABSTRACT FROM AUTHOR]

Background: Current surgical and ablative treatment options for prostate cancer (PCa) may result in a high incidence of (temporary) incontinence, erectile dysfunction and/or bowel damage. These side effects are due to procedure related effects on adjacent structures including blood vessels, bowel, urethra and/or neurovascular bundle. Ablation with irreversible electroporation (IRE) has shown to be effective and safe in destroying PCa cells and also has the potential advantage of sparing surrounding tissue and vital structures, resulting in less impaired functional outcomes and maintaining men's quality of life.Methods/design: In this randomized controlled trial (RCT) on IRE in localized PCa, 200 patients with organ-confined, unilateral (T1c-T2b) low- to intermediate-risk PCa (Gleason sum score 6 and 7) on transperineal template-mapping biopsies (TTMB) will be included. Patients will be randomized into focal or extended ablation of cancer foci with IRE. Oncological efficacy will be determined by multiparametric Magnetic Resonance Imaging, Contrast-Enhanced Ultrasound imaging if available, TTMP and Prostate Specific Antigen (PSA) follow-up. Patients will be evaluated up to 5 years on functional outcomes and quality of life with the use of standardized questionnaires.Discussion: There is critical need of larger, standardized RCTs evaluating long-term oncological and functional outcomes before introducing IRE and other focal therapy modalities as an accepted and safe therapeutic option for PCa. This RCT will provide important short- and long-term data and elucidates the differences between focal or extended ablation of localized, unilateral low- to intermediate-risk PCa with IRE.Trial Registration: Clinicaltrials.gov database registration number NCT01835977. The Dutch Central Committee on Research Involving Human Subjects registration number NL50791.018.14. [ABSTRACT FROM AUTHOR]

Objective To investigate the value of dynamic contrast-enhanced ( DCE)-ultrasonography ( US) and software-generated parametric maps in predicting biopsy outcome and their potential to reduce the amount of negative biopsy cores. Materials and Methods For 651 prostate biopsy locations (82 consecutive patients) we correlated the interpretation of DCE- US recordings with and without parametric maps with biopsy results. The parametric maps were generated by software which extracts perfusion parameters that differentiate benign from malignant tissue from DCE- US recordings. We performed a stringent analysis (all tumours) and a clinical analysis (clinically significant tumours). We calculated the potential reduction in biopsies (benign on imaging) and the resultant missed positive biopsies (false-negatives). Additionally, we evaluated the performance in terms of sensitivity, specificity negative predictive value ( NPV) and positive predictive value ( PPV) on a per-prostate level. Results Based on DCE- US, 470/651 (72.2%) of biopsy locations appeared benign, resulting in 40 false-negatives (8.5%), considering clinically significant tumours only. Including parametric maps, 411/651 (63.1%) of the biopsy locations appeared benign, resulting in 23 false-negatives (5.6%). In the per-prostate clinical analysis, DCE- US classified 38/82 prostates as benign, missing eight diagnoses. Including parametric maps, 31/82 prostates appeared benign, missing three diagnoses. Sensitivity, specificity, PPV and NPV were 73, 58, 50 and 79%, respectively, for DCE- US alone and 91, 56, 57 and 90%, respectively, with parametric maps. Conclusion The interpretation of DCE- US with parametric maps allows good prediction of biopsy outcome. A two-thirds reduction in biopsy cores seems feasible with only a modest decrease in cancer diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: Urinary biomarker tests for diagnosing prostate cancer have gained considerable interest. Urine is a complex mixture that can be subfractionated. We evaluated 2 urinary fractions that contain nucleic acids, ie cell pellets and exosomes. The influence of digital rectal examination before urine collection was also studied and the prostate cancer specific biomarkers PCA3 and TMPRSS2-ERG were assayed. Materials and Methods: Urine samples were prospectively obtained before and after digital rectal examination from 30 men scheduled for prostate biopsy. Cell pellet and exosomes were isolated and used for biomarker analysis. Analytical and diagnostic performance was tested using the Student t-test and ROC curves. Results: Unlike the exosome fraction, urinary sediment gene expression analysis was compromised by amorphous precipitation in 10% of all specimens. Digital rectal examination resulted in increased mRNA levels in each fraction. This was particularly relevant for the exosomal fraction since after digital rectal examination the number of samples decreased in which cancer specific markers were below the analytical detection limit. Biomarker diagnostic performance was comparable to that in large clinical studies. In exosomes the biomarkers had to be normalized for prostate specific antigen mRNA while cell pellet absolute PCA3 levels had diagnostic value. Conclusions: Exosomes have characteristics that enable them to serve as a stable substrate for biomarker analysis. Thus, digital rectal examination enhances the analytical performance of biomarker analysis in exosomes and cell pellets. The diagnostic performance of biomarkers in exosomes differs from that of cell pellets. Clinical usefulness must be prospectively assessed in larger clinical cohorts. [Copyright &y& Elsevier]

What's known on the subject? and What does the study add? Focal therapy techniques are emerging in prostate cancer treatment. However, several key questions about patient selection, treatment and monitoring still have to be addressed. The concept of focal therapy is barely discussed in current urological guidelines. In the present manuscript, we report the results of a consensus meeting focused on ultrasonography, the most common used urological imaging method, in relation to focal therapy of prostate cancer. To establish a consensus on the utility of ultrasonography (US) to select patients for focal therapy. Topics were the current status of US to determine focality of prostate cancer, to monitor and assess outcome of focal therapy and the diagnostic advantages of new US methods. In addition, the biopsy techniques required to identify focal lesions were discussed., Urological surgeons, radiation oncologists, radiologists, and basic researchers from Europe and North America participated in a consensus meeting on the use of transrectal US (TRUS) in focal therapy of prostate cancer. The consensus process was face-to-face and specific clinical issues were raised and discussed with agreement sought when possible., TRUS is commonly used and essential for diagnosing men with prostate cancer. It is particularly useful for targeting specific anatomical regions or visible lesions. However, it has several limitations and there is a need for improvement. Newer visualisation techniques, e.g. colour Doppler US, contrast-enhanced US and elastography, are being developed but currently there is no US technique that can accurately characterise a cancer suitable for focal therapy. Systematic biopsy is the only known procedure that allows the identification of prostate cancers suitable for focal therapy. Scarce data exist about the role of US for monitoring patients during or after ablative therapy., Consensus was reached on all key aspects of the meeting., US cannot reliably identify focal prostate cancer. New US methods show promising results in identifying prostate cancer focality., Currently selecting appropriate candidates for focal therapy should be performed using dedicated protocols and biopsy schemes. [ABSTRACT FROM AUTHOR]

Although the worldwide urological community generally accepts the existing protocol of TRUS-guided (transrectal ultrasound-guided) random prostate biopsy, there is strong evidence that sextant, extended, and saturation protocols are not sufficiently accurate (with ranges from 28-78%). Moreover, the number of repeated biopsies remains extremely high (33%) as a consequence of using an imperfect diagnostic tool. An overview of current literature concerning common practice in prostatic biopsies has revealed discrepancies in indications, technique, number of cores collected, and pathological examination standards. This fact has prompted many authors to search for methods of improving the existing standard. The latest developments in the field are primarily related to MRI-guided (magnetic resonance-guided) targeted prostate biopsy, which is currently a promising tool in diagnosing prostate cancer. However, genetically supported molecular biopsy seems to be a highly promising avenue for developing the future biopsy standard. [ABSTRACT FROM AUTHOR]

The Prostate CAncer gene 3 (PCA3) assay is a novel tool that might aid in the diagnosis of prostate cancer and that might indicate the significance of the disease. In this review we discuss five clinical cases in which the PCA3 assay can be considered, based on scientific evidence and key patient cases from real-life clinical practice. The PCA3 assay might be used to guide biopsy decisions in: (i) Men with an elevated serum total prostate specific antigen (tPSA) level and one or more previous negative biopsies; (ii) men with a normal tPSA level and a family history of prostate cancer; (iii) men with an elevated tPSA level (2.5–10 ng/mL) and no previous biopsy; (iv) men with an elevated tPSA level and a concomitant urinary condition. In addition, in men diagnosed with prostate cancer, the PCA3 assay could aid in the decision of whether active therapy is needed or active surveillance is appropriate. [ABSTRACT FROM AUTHOR]

The article offers information on a study which developed in vitro propagation of human spermatogonial stem cells from small testicular biopsies to derive an adequate number of cells for successful transplantation. Testis material donated by six adult men who undergone orchidectomy as part of prostate cancer treatment was utilized during the duration of the study from April 2007 to July 2009. To determine the presence of spermatogonia and spermatogonial markers, reverse transcriptase polymerase chain reaction and immunofluorescence were applied, respectively. Main outcome measure was the propagation of spermatogonial stem cells. Also presented in details are the research findings.

Purpose: We compared prostate cancer detection rates achieved using an 8 and 12-core biopsy protocol in a clinical population to determine the significance of additional transition zone sampling on repeat biopsy. Materials and Methods: Between September 2004 and September 2007, 269 eligible patients with a clinical suspicion of prostate cancer referred to our department were randomized to an 8-core lateral (group 1) or a 12-core lateral and parasagittal (group 2) transrectal ultrasound guided prostate biopsy protocol. Study inclusion criteria were age dependent increased serum prostate specific antigen (1.25 ng/ml or greater at ages less than 50 years, 1.75 or greater at ages 50 to less than 60 years, 2.25 or greater at ages 60 to less than 70 years and 3.25 or greater at ages 70 years or greater), positive digital rectal examination and/or suspicious transrectal ultrasound. After negative first round biopsy patients underwent 12-core biopsy, including 4 transition zone cores. Results: Nine patients were excluded from analysis because of protocol violation or they did not complete the whole biopsy procedure due to discomfort. The cancer detection rate in groups 1 and 2 did not differ significantly (34.1% or 45 of 132 patients and 38.3% or 49 of 128, respectively, p = 0.48). Detected cancer median Gleason scores were similar in the groups. Of 109 patients who underwent repeat biopsy prostate cancer was detected in 20 (14.4%), of whom 9 had positive cores from the transition zone and 6 had positive biopsies only from the transition zone. Conclusions: There are no statistically significant differences in the prostate cancer detection rate between 8 and 12-core prostate biopsy protocols. Transition zone biopsies contribute to prostate cancer detection in a repeat biopsy protocol. [Copyright &y& Elsevier]

Abstract: Objectives: The author attempts to better define the treatment of patients with locally advanced prostate cancer following radical prostatectomy. Methods: The data of the most recent series in the international literature have been analysed. Results: The risk of biochemical or clinical relapse in the literature is not clear. Recently, two randomised phase 3 trials have been published showing a statistical significant benefit of adjuvant irradiation with respect to biochemical and clinical progression-free survival. Toxicity of adjuvant radiotherapy was moderate in these studies. However, the range of patients with pT3 disease is large (extracapsular extension with/without positive margins, positive margins only, and seminal vesicle invasion), and the challenging question now is whether we can find a subgroup of patients with pT3 disease who will benefit most from adjuvant irradiation to prevent overtreatment for a considerable number of patients, and to reduce toxicity and costs. Conclusions: Instead of offering all patients immediate adjuvant treatment, patients with minor risk of relapse could be monitored carefully and offered salvage radiotherapy once biochemical relapse is observed. [Copyright &y& Elsevier]

Objectives: This multicentric clinical study was initiated to check whether percent free PSA, PSA density (PSAD) and PSA density of the transition zone (TZ-PSAD) could enhance the specificity of total PSA alone without reducing its sensitivity in the diagnosis of clinical Tlc prostate cancer by ultrasonically guided transrectal sextant biopsies in patients with a total PSA between 3 and 15 ng/ml. Patients and methods: A total of 306 patients were evaluated in seven different centres in the Netherlands and Belgium over a 2-year period. Patients with intermediate PSA levels (3.0-15 ng/ml) underwent measurement of prostate volume by transrectal ultrasound (TRUS) and sextant biopsy under TRUS guidance. The PSAD. TZ-PSAD and percent free PSA were determined for each patient, and their relationship to prostate cancer detection was examined. Results: Identical receiver operating characteristic (ROC) curves for PSAD and TZ-PSAD could be constructed. ROC analysis showed that percent free PSA was inferior to total PSA. PSAD and TZ-PSAD in the detection of prostate cancer. Conclusion: PSAD. TZ-PSAD and percent free PSA do not enhance the specificity of total PSA for cancer detection in men with PSA values between 3 and 15 ng/ml. Each centre has to use his preferential PSA-modification. [ABSTRACT FROM AUTHOR]

Purpose: We study the value of PSA response and PSA progression as prognostic factors for survival in good prognosis metastatic prostate cancer.Methods: Data from 257 patients treated with Flutamide or Cyproterone acetate within the EORTC GU Group protocol 30892 have been used and analysis by Cox models.Results: A PSA response defined as a decrease to ≤1 ng/ml and to between 1 and 10 ng/ml was associated with a hazard ratio of 0.30 and 0.61 for overall survival, respectively, as compared to the non-responders (PSA>10 ng/ml). Five definitions of PSA progression were considered: (1) a confirmed or (2) a repeated doubling of the PSA over nadir and unconfirmed (3) 100%, (4) 50% and (5) 20% increase of the PSA over nadir, each to a value >4 ng/ml. Definition (5) was the most sensitive with sensitivity 76.20% and specificity 32.08%. With this definition, 70.0% of the patients had a PSA progression, which occurred in median 1.98 years before death.Conclusions: For good prognosis metastatic prostate cancer patients under anti-androgen treatment, PSA response at 6 months with cut-off levels of ≤1 ng/ml and ≤10 ng/ml is prognostic for survival. A 20% increase over nadir to a value >4 ng/ml is prognostic for a poor survival with a 76.20% sensitivity. In this study, confirmation of the increase by a second observation did not seem necessary. Genuine surrogacy is not established in this study. [Copyright &y& Elsevier]

Purpose: Different outcome results have been published in trials comparing maximal androgen blockade (MAB) with chemical or surgical castration alone. The conflicting results could be explained by the fact that patients were included with different prognostic factors. In this new analysis of the Anandron European Study, independent prognostic factors have been evaluated in order to identify those which could influence the study outcome and the impact of the treatment.Material and Methods: 399 out of 457 patients recruited in this study were divided in a good or poor prognostic group depending on the presence of two or more poor prognostic factors, these were pain requiring treatment, >5 bone metastases, hydronephrosis, and alkaline phosphatase >2 ULN.Results: When expressed as a percentage, the improvement in time to progression, overall and cancer specific survival in the Anandron® treated patients was identical in both groups. In absolute terms this improvement, however, was greater in the good prognostic group.Conclusion: In comparison with surgical castration MAB using Anandron®, in patients with metastatic prostate cancer improves the time to objective progression, overall and cancer specific survival, irrespective of certain poor prognostic factors. [ABSTRACT FROM AUTHOR]

The aims of the European Organization for Research and Treatment of Cancer-GU (EORTC-GU) Group are to improve the treatment of cancer related problems by carrying out multicenter, multinational and intercontinental Phases II and III trials and the dissemination of their results via workshops, congresses and symposia. The first studies in prostate cancer dealt with the use of chemotherapeutic agents in advanced tumours. Mitomycin C was the most active agent identified. We have learnt that the primary tumour should not be used for response assessment in advanced disease but that Quality of life (QoL) assessment consistently applied may be. In later studies QoL and PSA response were considered as the most important endpoints for Phase II trials in this disease. In patients with locally advanced or metastatic disease maximal androgen blockade (MAB), in different forms, has been studied. Conflicting outcomes have been observed, which could be explained by the inclusion of patients with different prognostic factors at entry in the studies. The anti-androgen monotherapy approach in patients with M+ disease with good prognostic factors has been shown to be feasible, side effects using a steroidal agent were higher compared with non-steroidal agents. The hormono-chemotherapy approach in patients with M+ disease and poor prognostic factors at entry showed not to be of any benefit in terms of survival and also QoL was worse in these patients. Patients with locally advanced disease treated with external beam radiation therapy had a significant better survival if this treatment was combined with 3 years of hormonal therapy. The ongoing Phase III study in metastatic prostate cancer is comparing intermittent hormonal therapy and continuous treatment and in locally advanced prostate cancer a Phase III trial is testing the so-called step-up and step-down regimen. [Copyright &y& Elsevier]

After skin cancer, prostate cancer (PC) is the most common cancer among men. The gold standard for PC diagnosis is based on the PSA (prostate-specific antigen) test. Based on this preliminary screening, the physician decides whether to proceed with further tests, typically prostate biopsy, to confirm cancer and evaluate its aggressiveness. Nevertheless, the specificity of the PSA test is suboptimal and, as a result, about 75% of men who undergo a prostate biopsy do not have cancer even if they have elevated PSA levels. Overdiagnosis leads to unnecessary overtreatment of prostate cancer with undesirable side effects, such as incontinence, erectile dysfunction, infections, and pain. Here, we used artificial neuronal networks to develop models that can diagnose PC efficiently. The model receives as an input a panel of 4 clinical variables (total PSA, free PSA, p2PSA, and PSA density) plus age. The output of the model is an estimate of the Gleason score of the patient. After training on a dataset of 190 samples and optimization of the variables, the model achieved values of sensitivity as high as 86% and 89% specificity. The efficiency of the method can be improved even further by training the model on larger datasets. [ABSTRACT FROM AUTHOR]

We provide the strongest evidence to date that local failure is an independent prognosticator of outcomes in high- and intermediate-risk prostate cancer patients treated with definitive radiation therapy. Distant metastasis predominantly develops from a clinical relapse-free state; however, a second wave of distant metastasis occurs subsequent to local failure, albeit less commonly. The prognostic importance of local failure after definitive radiotherapy (RT) in National Comprehensive Cancer Network intermediate- and high-risk prostate cancer (PCa) patients remains unclear. To evaluate the prognostic impact of local failure and the kinetics of distant metastasis following RT. A pooled analysis was performed on individual patient data of 12 533 PCa (6288 high-risk and 6245 intermediate-risk) patients enrolled in 18 randomized trials (conducted between 1985 and 2015) within the Meta-analysis of Randomized Trials in Cancer of the Prostate Consortium. Multivariable Cox proportional hazard (PH) models were developed to evaluate the relationship between overall survival (OS), PCa-specific survival (PCSS), distant metastasis-free survival (DMFS), and local failure as a time-dependent covariate. Markov PH models were developed to evaluate the impact of specific transition states. The median follow-up was 11 yr. There were 795 (13%) local failure events and 1288 (21%) distant metastases for high-risk patients and 449 (7.2%) and 451 (7.2%) for intermediate-risk patients, respectively. For both groups, 81% of distant metastases developed from a clinically relapse-free state (cRF state). Local failure was significantly associated with OS (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.06–1.30), PCSS (HR 2.02, 95% CI 1.75–2.33), and DMFS (HR 1.94, 95% CI 1.75–2.15, p < 0.01 for all) in high-risk patients. Local failure was also significantly associated with DMFS (HR 1.57, 95% CI 1.36–1.81) but not with OS in intermediate-risk patients. Patients without local failure had a significantly lower HR of transitioning to a PCa-specific death state than those who had local failure (HR 0.32, 95% CI 0.21–0.50, p < 0.001). At later time points, more distant metastases emerged after a local failure event for both groups. Local failure is an independent prognosticator of OS, PCSS, and DMFS in high-risk and of DMFS in intermediate-risk PCa. Distant metastasis predominantly developed from the cRF state, underscoring the importance of addressing occult microscopic disease. However a "second wave" of distant metastases occurs subsequent to local failure events, and optimization of local control may reduce the risk of distant metastasis. Among men receiving definitive radiation therapy for high- and intermediate-risk prostate cancer, about 10% experience local recurrence, and they are at significantly increased risks of further disease progression. About 80% of patients who develop distant metastasis do not have a detectable local recurrence preceding it. [ABSTRACT FROM AUTHOR]

This surgery-in-motion contribution shows that transperineal magnetic resonance–ultrasound fusion guided biopsy in men with suspected prostate cancer is well tolerated using local anesthesia in an ambulatory setting. The detection rates of clinically significant cancer are high, and even without prophylactic antibiotics, the risk of infectious complication is low. Transperineal magnetic resonance imaging–transrectal ultrasound fusion guided biopsy (MFGB) is an increasingly popular technique due to increasing rates of biopsy-related infections. However, its widespread implementation has been hampered by the supposed necessity of epidural or general anesthesia. To demonstrate the technique, feasibility, and results of transperineal MFGB under local anesthesia, in an ambulatory setting without the administration of prophylactic antibiotics. This single-center study enrolled consecutive biopsy-naïve men with a clinical suspicion of prostate cancer into a prospective database between November 2015 and November 2020. Men with Prostate Imaging Reporting and Data System (PI-RADS) version 2 scores 3–5 underwent transperineal MFGB. Transperineal MFGB was performed in an ambulatory setting under local anesthesia by a single operator. Procedure-associated adverse events were recorded. Patient discomfort during both the local anesthesia and the biopsy procedure was determined using a visual analogic scale (0–10). Detection rates of grade group (GG) ≥2 prostate cancer and the proportion of men with GG 1 cancer were assessed. A total of 1097 eligible men underwent transperineal MFGB. The complication rate was 0.73% (8/1097); complications comprised five (0.46%) urinary tract infections including one hospitalization and three (0.27%) urinary retentions. In 735 men, the median pain scores were 2 (interquartile range [IQR] 2–3) for the local anesthesia procedure and 1 (IQR 0-2) for the biopsy. Prostate cancer was detected in 84% (926/1097) of men; 66% (723/1097) had GG ≥2 and 19% (203/1097) GG 1. Transperineal MFGB can safely be performed as an outpatient procedure under local anesthesia in an ambulatory setting. The detection rate of clinically significant prostate cancer is high, and biopsy is well tolerated. Although no antibiotic prophylaxis was used, the rate of infectious complications is practicably negligible. This article shows how tissue samples (biopsies) can accurately be obtained from suspicious regions seen on prostate magnetic resonance imaging via needles inserted in the perineum (skin between the scrotum and the anus) in men with suspected prostate cancer. This technique appears to be very well tolerated under local anesthesia and has a lower risk of infection without antibiotic prophylaxis than the more common biopsy route through the rectum, with antibiotics. [ABSTRACT FROM AUTHOR]

Objectives: This trial was designed to compare the efficacy of Flutamide (FLU) versus Cyproterone acetate (CPA) in men with metastatic prostate cancer and favourable prognostic factors. The primary endpoint of the trial was overall survival, disease specific survival, time to progression and side effects were secondary endpoints. The results pertaining to sexual function were already reported [Br J Cancer 82(2) (2000) 283].Material and Methods: The trial was designed to detect a 50% improvement in median overall survival with 80% power. At the time of the present report, the trial provides 88% power to detect the planned difference of 50% with a 2-sided Logrank test and 80% power to detect a difference of 43% in median survival.Results: 310 patients were randomized to treatment by FLU (250 mg t.i.d. p.o.) or CPA (100 mg t.i.d. p.o.). Of the 310 patients, 12 (3.9%) were ineligible. The baseline characteristcs of the two groups were similar except for age which was significantly younger in the CPA group and for the presence of soft tissue metastases which were absent in the FLU group and present in 6 patients in the CPA group. The median follow-up was 8.6 years, 245 patients died, 158 (64.5%) of prostate cancer. There was no significant difference between the treatment arms with respect to overall survival, specific survival nor time to progression. Side effect profiles were studied and found to be more favourable for CPA overall and in particular with respect to gynecomastia, diarrhea and nausea.Conclusions: The trial shows no significant differences in efficacy between Flutamide and CPA monotherapy. The number of patients who died of prostate cancer up to this time is insufficient for a definitive analysis of specific survival. Erectile function and sexual activity are not preserved with FLU but decay slowly with both antiandrogens, toxicity is more pronounced with FLU. [Copyright &y& Elsevier]

Urological malignancies, including prostate cancer, bladder cancer and kidney cancer, are major causes of morbidity and mortality worldwide. Because of the high incidence, diversity in biology, and especially direct interaction with urine, urological cancers are an important resource for both scientists and clinicians for novel diagnostic and therapeutic discovery. Extracellular vesicles (EVs) are lipid bilayer encapsulated particles released by cells into the extracellular space. Since EVs work as a safe way to transport important biological information through the whole body, they are now recognized as an important mechanism of cell–cell communication and have opened a new window for us to gain a better understanding of cancer biology, novel diagnostics, and therapeutic options. In recent years, numerous evolutions in EV technologies and novel biological and clinical findings continue to be reported in the research field of urological cancers. This comprehensive review aims to give an update of recent advances in EV technologies and summarize the state-of-the-art knowledge of EVs related to prostate cancer, bladder cancer and kidney cancer, particularly focusing on the potential of EV as biomarkers and their biological roles in promoting cancer and metastasis. [ABSTRACT FROM AUTHOR]

The concentration of prostate-specific antigen (PSA) in serum is used as an early detection method of prostate cancer (PCa); however, it shows low sensitivity, specificity, and a poor predictive value. Initial studies suggested the glycosylation of PSA to be a promising marker for a more specific yet noninvasive PCa diagnosis. Recent studies on the molecular features of PSA glycosylation (such as antenna modification and core fucosylation) were not successful in demonstrating its potential for an improved PCa diagnosis, probably due to the lack of analytical sensitivity and specificity of the applied assays. In this study, we established for the first time a high-performance PSA Glycomics Assay (PGA), allowing differentiation of α2,6- and α2,3-sialylated isomers, the latter one being suggested to be a hallmark of aggressive types of cancer. After affinity purification from urine and tryptic digestion, PSA samples were analyzed by CE-ESI-MS (capillary electrophoresis-electrospray ionization coupled to mass spectrometry). Based on positive controls, an average interday relative standard deviation of 14% for 41 N-glycopeptides was found. The assay was further verified by analyzing PSA captured from patients' urine samples. A total of 67 N-glycopeptides were identified from the PSA pooled from the patients. In summary, the first PGA successfully established in this study allows an indepth relative quantitation of PSA glycoforms from urine. The PGA is a promising tool for the determination of potential glycomic biomarkers for the differentiation between aggressive PCa, indolent PCa, and benign prostate hyperplasia in larger cohort studies. [ABSTRACT FROM AUTHOR]

Background To reduce overdiagnosis and overtreatment, a test is urgently needed to detect clinically significant prostate cancer (PCa). Objective To develop a multimodal model, incorporating previously identified messenger RNA (mRNA) biomarkers and traditional risk factors that could be used to identify patients with high-grade PCa (Gleason score ≥7) on prostate biopsy. Design, setting, and participants In two prospective multicenter studies, urine was collected for mRNA profiling after digital rectal examination (DRE) and prior to prostate biopsy. The multimodal risk score was developed on a first cohort ( n = 519) and subsequently validated clinically in an independent cohort ( n = 386). Outcome measurements and statistical analysis The mRNA levels were measured using reverse transcription quantitative polymerase chain reaction. Logistic regression was used to model patient risk and combine risk factors. Models were compared using the area under the curve (AUC) of the receiver operating characteristic, and clinical utility was evaluated with a decision curve analysis (DCA). Results and limitations HOXC6 and DLX1 mRNA levels were shown to be good predictors for the detection of high-grade PCa. The multimodal approach reached an overall AUC of 0.90 (95% confidence interval [CI], 0.85–0.95) in the validation cohort (AUC 0.86 in the training cohort), with the mRNA signature, prostate-specific antigen (PSA) density, and previous cancer-negative prostate biopsies as the strongest, most significant components, in addition to nonsignificant model contributions of PSA, age, and family history. For another model, which included DRE as an additional risk factor, an AUC of 0.86 (95% CI, 0.80–0.92) was obtained (AUC 0.90 in the training cohort). Both models were successfully validated, with no significant change in AUC in the validation cohort, and DCA indicated a strong net benefit and the best reduction in unnecessary biopsies compared with other clinical decision-making tools, such as the Prostate Cancer Prevention Trial risk calculator and the PCA3 assay. Conclusions The risk score based on the mRNA liquid biopsy assay combined with traditional clinical risk factors identified men at risk of harboring high-grade PCa and resulted in a better patient risk stratification compared with current methods in clinical practice. Therefore, the risk score could reduce the number of unnecessary prostate biopsies. Patient summary This study evaluated a novel urine-based assay that could be used as a noninvasive diagnostic aid for high-grade prostate cancer (PCa). When results of this assay are combined with traditional clinical risk factors, risk stratification for high-grade PCa and biopsy decision making are improved. [ABSTRACT FROM AUTHOR]

Background There are no universally monitored outcomes relevant to men with advanced prostate cancer, making it challenging to compare health outcomes between populations. Objective We sought to develop a standard set of outcomes relevant to men with advanced prostate cancer to follow during routine clinical care. Design, setting, and participants The International Consortium for Health Outcomes Measurement assembled a multidisciplinary working group to develop the set. Outcome measurements and statistical analysis We used a modified Delphi method to achieve consensus regarding the outcomes, measures, and case mix factors included. Results and limitations The 25 members of the multidisciplinary international working group represented academic and nonacademic centers, registries, and patients. Recognizing the heterogeneity of men with advanced prostate cancer, the group defined the scope as men with all stages of incurable prostate cancer (metastatic and biochemical recurrence ineligible for further curative therapy). We defined outcomes important to all men, such as overall survival, and measures specific to subgroups, such as time to metastasis. Measures gathered from clinical data include measures of disease control. We also identified patient-reported outcome measures (PROMs), such as degree of urinary, bowel, and erectile dysfunction, mood symptoms, and pain control. Conclusions The international multidisciplinary group identified clinical data and PROMs that serve as a basis for international health outcome comparisons and quality-of-care assessments. The set will be revised annually. Patient summary Our international group has recommended a standardized set of patient-centered outcomes to be followed during routine care for all men with advanced prostate cancer. [ABSTRACT FROM AUTHOR]