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Due to the proliferation-induced high demand of cancer cells for folic acid (FA), significant overexpression of folate receptors 1 (FR1) is detected in most cancers. To our knowledge, a detailed characterization of FR1 expression and regulation regarding therapeutic and diagnostic feasibilities in prostate cancer (PCa) has not been described. In the present study, cell cultures, as well as tissue sections, were analyzed using Western blot, qRT-PCR and immunofluorescence. In addition, we utilized FA-functionalized lipoplexes to characterize the potential of FR1-targeted delivery into PCa cells. Interestingly, we detected a high level of FR1-mRNA in healthy prostate epithelial cells and healthy prostate tissue. However, we were able to show that PCa cells in vitro and PCa tissue showed a massively enhanced FR1 membrane localization where the receptor can finally gain its function. We were able to link these changes to the overexpression of GPI-transamidase (GPI-T) by image analysis. PCa cells in vitro and PCa tissue show the strongest overexpression of GPI-T and thereby induce FR1 membrane localization. Finally, we utilized FA-functionalized lipoplexes to selectively transfer pDNA into PCa cells and demonstrate the therapeutic potential of FR1. Thus, FR1 represents a very promising candidate for targeted therapeutic transfer pathways in PCa and in combination with GPI-T, may provide predictive imaging in addition to established diagnostics.
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In men aged 40-83 years, the overall incidence of urinary retention is 4.5-6.8 cases per 1000 men per year. The incidence increases significantly with age, so that a man in his 70 s has a 10% chance and a man in his 80 s has a more than 30% chance of experiencing an episode of acute urinary retention [1]. The goal of diagnosis is to quickly reach a finding through clinical examination and ultrasound to be able to relieve the bladder. The first maneuver is catheterization, followed by, if necessary, initiation of pharmacological therapy that targets the underlying cause. Despite the high association of urinary retention with benign prostatic hyperplasia (BPH), a comprehensive history and diagnosis are crucial to identify possible rare and complex causes and to enable targeted treatment. The challenge lies in finding the balance between rapid symptomatic treatment and thorough investigation of atypical and rare pathologies to develop individually adapted and effective therapy strategies.
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Retenção Urinária , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Injúria Renal Aguda/diagnóstico , Hiperplasia Prostática/complicações , Cateterismo Urinário/efeitos adversos , Retenção Urinária/etiologia , Retenção Urinária/terapiaRESUMO
Background and objective: Hydronephrosis is essential in the diagnosis of renal colic. We automated the detection of hydronephrosis from ultrasound images to standardize the therapy and reduce the misdiagnosis of renal colic. Methods: Anonymously collected ultrasound images of human kidneys, both normal and hydronephrotic, were preprocessed for neural networks. Six "state of the art" models were trained and cross-validated for the detection of hydronephrosis, and two convolutional networks were used for kidney segmentation. In the testing phase, performance metrics included true positives, true negatives, false positives, false negatives, accuracy, and F1 score, while the evaluation of the segmentation task involved accuracy, precision, dice, jaccard, recall, and ASSD. Key findings and limitations: A total of 523 sonographic kidney images (423 nonhydronephrotic and 100 hydronephrotic) were collected from three different ultrasound devices. After training on this dataset, all models were used to evaluate 200 new ultrasound kidney images (142 nonhydronephrotic and 58 hydronephrotic kidneys). The highest validation accuracy (98.5%) was achieved by the AlexNet model (GoogLeNet 97%, AlexNet_v2 96%, ResNet50 96%, ResNet101 97.5%, and ResNet152 95%). The deeplabv3_resnet50 and deeplabv3_resnet101 reached a dice coefficient of 94.74% and 94.48%, respectively, on the task of automated kidney segmentation. The study is limited by analyzing only hydronephrosis, but this specific focus enabled high detection accuracy. Conclusions and clinical implications: We show that our automated ultrasound deep learning model can be trained and used to interpret and segmentate ultrasound images from different sources with high accuracy. This method will serve as an automated tool in the diagnostic algorithm of acute renal failure in the future. Patient summary: Hydronephrosis is crucial in the diagnosis of renal colic. Recent advances in artificial intelligence allow automated detection of hydronephrosis in ultrasound images with high accuracy. These methods will help standardize the diagnosis and treatment renal colic.
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Prostate cancer is one of the most common malignancies worldwide, showing a wide range of clinical behaviors. Therefore, several treatment options arise out of the diagnosis "prostate cancer". For this reason, it is desirable to find novel prognostic and predictive markers. In former studies, we showed that THSD7A expression is associated with unfavorable prognostic parameters in prostate cancer and is linked to a high expression of focal adhesion kinase (FAK). Recently, scavenger receptor class A member 5 (SCARA5) was reported to be the downstream gene of THSD7A in esophageal squamous cell carcinoma. SCARA5 is believed to play an important role in the development and progression of several different tumor types. Most studies describe SCARA5 as a tumor suppressor. There is also evidence that SCARA 5 interacts with FAK. To examine the role of SCARA5 as a potential biomarker in prostate cancer, a total of 461 prostate cancers were analyzed via immunohistochemistry using tissue microarrays. Furthermore, we compared the expression level of SCARA5 with our previously collected data on THSD7A and FAK. High SCARA5 expression was associated with advanced tumor stage (p < 0.001), positive nodal status (p < 0.001) and high Gleason-score (p < 0.001). At least, strongly SCARA5-positive cancers were associated with THSD7A-positivity. There was no significant association between SCARA5 expression level and FAK expression level. To our knowledge, we are the first to investigate the role of SCARA5 in prostate cancer and we demonstrated that SCARA5 might be a potential biomarker in prostate cancer.
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Antibiotic prophylaxis contributes substantially to the increase in antibiotic resistance rates worldwide. This investigation aims to assess the current standard of practice in using antibiotic prophylaxis for urodynamics (UDS) and identify barriers to guideline adherence. An online survey using a 22-item questionnaire designed according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) was circulated among urologists and gynecologists in Austria, Germany, and Switzerland between September 2021 and March 2022. A total of 105 questionnaires were eligible for analysis. Out of 105 completed surveys, most responders (n = 99, 94%) regularly perform dipstick urine analysis prior to urodynamics, but do not perform a urine culture (n = 68, 65%). Ninety-eight (93%) participants refrain from using antibiotic prophylaxis, and sixty-eight (65%) use prophylaxis if complicating factors exist. If asymptomatic bacteriuria is present, approximately 54 (52%) participants omit UDS and reschedule the procedure until antimicrobial susceptibility testing is available. Seventy-eight (78%) participants do not have a standard procedure for antibiotic prophylaxis in their department. Part of the strategy against the development of bacterial resistance is the optimized use of antibiotics, including antibiotic prophylaxis in urodynamics. Establishing a standard procedure is necessary and purposeful to harmonize both aspects in the field of urological diagnostics.
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PURPOSE: Digital health information gains growing importance in the medical landscape. Despite its opportunities, there is a risk of patient misinformation which may adversely influence the patient-physician relationship. This investigation aimed to identify and compare differences in the content and quality of online health information on overactive bladder (OAB) between different digital platforms. METHODS: The platforms Google search, Facebook, Instagram, LinkedIn, and YouTube were searched for the keyword OAB. The search result links were classified as useful or misleading, advertisement and personal experience. Information regarding the organization of the source and available content on treatment modalities was collected. Descriptive analysis was applied. Univariate and multivariate analyses were performed to evaluate heterogeneity regarding the distribution of information depending on the source. A p value < 0.05 was considered statistically significant. RESULTS: The source with the highest quantity of useful content was YouTube (100%) and Google (100%), whereas LinkedIn included mostly misleading content (73%). YouTube and Google provided the greatest variety of health information and were dominated by professional associations. Surgical procedures for treating OAB were only described in 32% and 48% of Google and YouTube results, respectively. On Google, sacral neuromodulation and OnabotulinumtoxinA were described in 26% and bladder augmentation in only 16% of the search results. In contrast, alternative medicine was present in 76%. CONCLUSIONS: A large gap in the information on surgical treatments of OAB could be identified independently from the utilized source. In contrast, conservative treatments and alternative medicine dominate the current informational sources.
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Mídias Sociais , Bexiga Urinária Hiperativa , Humanos , Bexiga Urinária Hiperativa/cirurgia , PacientesRESUMO
Urothelial carcinoma of the upper urinary tract (upper tract urothelial carcinoma, UTUC) is less common than bladder carcinoma with nearly identical risk factors and has a poorer prognosis. The standard diagnostic procedure is imaging of the upper urinary tract by computed tomography urography. In cases of diagnostic uncertainty, a diagnostic ureterorenoscopy with biopsy sampling can be performed in addition to urine cytology. Treatment depends primarily on the stage and grading of the tumor. Depending on the extent and localization, organ-preserving treatment or radical nephroureterectomy is indicated. Perioperative systemic treatment in high-risk UTUC can be performed in both neoadjuvant and adjuvant settings, although the current data on neoadjuvant chemo- and immunotherapy do not yet allow standard application. For metastatic disease, a multimodal treatment approach consisting of cisplatin-based or carboplatin-based chemotherapy, immunotherapy, and treatment with enfortumab vedotin can be considered. Salvage surgery, radiotherapy and metastasectomy are available for rare individual cases.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Sistema Urinário , Humanos , Neoplasias da Bexiga Urinária/cirurgia , Carcinoma de Células de Transição/diagnóstico , Nefroureterectomia , Sistema Urinário/patologia , Terapia CombinadaRESUMO
The use of artificial intelligence (AI) in urology can contribute to a significant improvement with regard to individualization of diagnostics and therapy as well as healthcare cost reduction. The potential applications and advantages of AI in medicine are often underestimated or incompletely understood. This makes it difficult to conceptually solve relevant medical problems using AI. With current advances in computer science, multiple, highly complex nonmedical processes have already been studied and optimized in an automated fashion. The development of AI models, if applied correctly, can lead to more effective processing and analysis of patient-related data and correspondingly optimized diagnosis and therapy of urological patients. In this review, the current status on the application of AI in medicine and its opportunities and possibilities in urology are presented from a conceptual perspective using practical examples.
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Inteligência Artificial , Urologia , HumanosRESUMO
Prostate cancer is one of the most common malignancies, and there are a wide range of treatment options after diagnosis. Most prostate cancers behave in an indolent manner. However, a given sub-group has been shown to exhibit aggressive behavior; therefore, it is desirable to find novel prognostic and predictive (molecular) markers. THSD7A expression is significantly associated with unfavorable prognostic parameters in prostate cancer. FAK is overexpressed in several tumor types and is believed to play a role in tumor progression and metastasis. Furthermore, there is evidence that THSD7A might affect FAK-dependent signaling pathways. To examine whether THSD7A expression has an impact on the expression level of FAK in its unphosphorylated form, a total of 461 prostate cancers were analyzed by immunohistochemistry using tissue microarrays. THSD7A positivity and low FAK expression were associated with adverse pathological features. THSD7A positivity was significantly associated with high FAK expression. To our knowledge we are the first to show that THSD7A positivity is associated with high FAK expression in prostate cancer. This might be proof of the actual involvement of THSD7A in FAK-dependent signaling pathways. This is of special importance because THSD7A might also serve as a putative therapeutic target in cancer therapy.
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INTRODUCTION: Prostate-specific membrane antigen (PSMA)-based imaging and theranostics have played an important role in the diagnosis, staging, and treatment of prostate cancer (PCa). We aimed to evaluate the acceptance and use of PSMA theranostics among German urologists. METHODS: An anonymous online questionnaire was sent via survio.com to the members of the German Society of Urology (DGU). RESULTS: Seventy-two percent of participants performed PSMA positron emission tomography (PET) imaging regularly in biochemically recurrent PCa. Overall, 61% of participants considered PSMA-radioligand therapy to be very useful or extremely useful. PSMA PET imaging in high-risk PCa is more often considered by urologists working in a university setting than in nonuniversity settings or medical practices (51% vs. 25%, p < 0.001). Most perform PSMA-radioligand therapy as an option after all approved systemic treatments for metastatic castration-resistant PCa (56%) or after cabazitaxel (14%). A total of 93.9% and 70.3% of respondents consider the lack of reimbursement by health insurance to be the main obstacle to using PSMA PET imaging or radioligand therapy, respectively. DISCUSSION/CONCLUSION: PSMA-based imaging/theranostics are already widely applied but would find even more widespread use if reimbursement is clearly regulated by health insurance in Germany.
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Medicina de Precisão , Neoplasias da Próstata , Masculino , Humanos , Compostos Radiofarmacêuticos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/terapia , Tomografia por Emissão de Pósitrons , Inquéritos e Questionários , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodosRESUMO
Prostate and breast carcinomas are amongst the most common new diseases in men and women, with steadily rising incidences. In addition to the significant health consequences, both diseases also lead to a significantly reduced quality of life due to their influence on sexual function. The aim of this work is to identify scientific approaches and research priorities that in the future might lead to synergies in both disciplines by specifically considering the similarities and differences between the two diseases. For this purpose, clinically relevant aspects such as risk factors, treatment options, as well as scientific similarities and differences that offer direct joint research approaches in the areas of cultivation and modeling of both tumor entities were analyzed. Through this approach, we were able to demonstrate that due to the comparable biology of the two diseases and the underlying mechanisms, scientific synergies may certainly lead to targeted research. Clinical similarities also indicate that close collaboration between the two disciplines could lead to improved treatment of our patients. Evidence deficiencies in both diseases (e.g. the metastasis mechanisms of both tumor entities) and controversially discussed aspects such as risk factors clearly show that further scientific projects for a more detailed understanding of both diseases are necessary to ensure future success in the treatment of our patients.
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Neoplasias da Mama , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Incidência , Masculino , Próstata/patologia , Qualidade de VidaRESUMO
PURPOSE: To identify differences in the content and quality of online health information for pelvic organ prolapse (POP) presented in social media and digital search engines to sustainably enhance patient guidance for adequate platforms for seeking online health information on POP. METHODS: The platforms Google search, Facebook, Instagram, LinkedIn, and YouTube were searched for the keyword "pelvic organ prolapse". Results were categorized as useful, misleading, advertising, and personal experience. Data were categorized into healthcare professionals, professional organisations, industry, patients, and individuals. The readability score and Health On the Net (HON) code seal were analyzed for Google. Descriptive and univariate analysis was performed. RESULTS: The source with the highest quantity of useful content was YouTube whereas LinkedIn included mostly advertisement and misleading content. YouTube and Google provided the greatest variety of health information. Social media platforms identified emotional distress and sleep disturbances as a common side effect of POP which is limited considered in clinical practice and provide novel insights of bothersome symptoms related to the disease. The spectrum of different surgical techniques was limited in all platforms. Only 12 (40.0%) were HON-qualified websites with a mean readability score of 10.4 which is considered fairly difficult to read. CONCLUSION: Besides Google search, YouTube was identified as a valuable online source for POP information. However, encompassing information of surgical techniques was limited in all platforms. Urogynecological association may contribute to improve patient information by providing online health information which is complete and easy to understand.
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Informação de Saúde ao Consumidor , Prolapso de Órgão Pélvico , Mídias Sociais , Compreensão , Humanos , Internet , Prolapso de Órgão Pélvico/cirurgia , Ferramenta de BuscaRESUMO
BACKGROUND: Stromal components surrounding epithelial cancer cells seem to play a pivotal role during epithelial-to-mesenchymal transition (EMT), tumor invasion, and metastases. To identify the molecular mechanisms underlying tumor-stroma interactions may yield novel therapeutic targets for prostate cancer. METHODS: Gene expression profile of prostate-cancer associated fibroblast (PCAF) and prostate non-cancer associated fibroblast (PNAF) cells isolated from radical prostatectomy was performed by Illumina, analyzed, and further processed by Ingenuity®: IPA® software. qRT-PCR was performed on an independent set of 17 PCAF, 12 PNAF, and 12 fibroblast cell lines derived from patients with benign prostatic hyperplasia (BPHF). RESULTS: Using microarray analysis, we found six upregulated genes and two downregulated genes in PCAFs compared to PNAFs. To validate microarray results, we performed qRT-PCR for the most significantly regulated genes involved in the modulation of proliferation and androgen resistance on an independent set of PNAF, PCAF, and BHPF samples. We confirmed the increased expression of SCARB1, MAPK3K1, and TGF-ß as well as the decreased expression of S100A10 in PCAFs compared to PNAFs and BPHFs. CONCLUSIONS: These results provide strong evidence that the observed changes in the gene expression profile of PCAFs can contribute to functional alteration of adjacent prostate cancer cells.
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Urinary tract infections (UTIs) are characterized by a broad clinical presentation ranging from uncomplicated cystitis to septic shock. 9-31% of all septicemias have a urogenital focus and are referred to as urosepsis. Urosepsis often occurs in the context of health system-associated infections. Obstructive uropathy (e.g., urolithiasis, tumors, strictures) is a major risk factor. The severity and course of urosepsis depend not only on the pathogenicity of the pathogen but also on the type and extent of the individual immune response. Therapy is divided into causal (antimicrobial therapy and focal sanitation), supportive (hemodynamic and pulmonal stabilization), and adjunctive (glucocorticoid and insulin therapy) therapy and should be initiated without delay. Due to demographic change, a further increase in urosepsis is expected in the future, so every urologist should be familiar with targeted diagnostics and effective therapy.
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Cistite , Sepse , Choque Séptico , Infecções Urinárias , Antibacterianos/uso terapêutico , Cistite/complicações , Humanos , Sepse/diagnóstico , Choque Séptico/complicações , Infecções Urinárias/diagnósticoRESUMO
BACKGROUND: In metastatic prostate cancer, a trend towards longer survival has been observed over the last 15 years. Beyond progress due to new drugs, retrospective data also suggest a positive influence of a prior treatment of the primary tumor. OBJECTIVES: Can treatment of the primary tumor improve the prognosis of patients later developing metastases, and if yes, what are the underlying mechanisms. MATERIALS AND METHODS: In addition to a critical review and discussion of the literature, we analyzed the long-term outcomes of 115 patients with T4 prostate cancer, who had undergone radical prostatectomy after inductive hormonal therapy at our institution. RESULTS: Of the 115 patients, 84 developed prostate-specific antigen (PSA) recurrence during the further course of disease and must therefore be regarded as uncured. Tumor-specific and overall survival of these 84 patients after 150 months were 61 and 44%, respectively. A total of 47 patients were alive after a median follow-up time of 95 months, of whom 31 were still receiving standard hormonal therapy. Only 13 had developed resistance towards their primary hormonal therapy and, hence, received tertiary hormonal therapy. Again, long-term responses were found in some of these patients. CONCLUSIONS: Primary tumor resection, at least under the circumstances described here, seems to delay the development of castration resistance in metastatic prostate cancer or to completely prevent it in individual cases.
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Antígeno Prostático Específico , Neoplasias da Próstata , Biologia , Seguimentos , Hormônios/uso terapêutico , Humanos , Masculino , Prostatectomia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Estudos RetrospectivosRESUMO
Radical prostatectomy in oligometastatic prostate cancer is a matter of intense debate. Besides avoiding local complications, it is hypothesized that primary tumor resection may result in better oncological outcomes. The aim of our study was to analyze the effect of primary tumor resection on disease progression in an orthotopic prostate cancer mouse model. First, the optimal time point for primary tumor resection, when metastases have already occurred, but the primary tumor is still resectable, was determined as 8 weeks after inoculation of 5 × 105 LuCaP136 cells. In a second in vivo experiment, 64 mice with metastatic prostate cancer were randomized into two groups, primary tumor resection or sham operation, and disease progression was followed up for 10 weeks. The technique of orthotopic primary tumor resection was successfully established. Compared with the sham operation group, mice with primary tumor resection showed a significantly longer survival (p < 0.001), a significantly slower PSA increase (p < 0.01), and a lower number of lung metastases (p = 0.073). In conclusion, primary tumor resection resulted in slower disease progression and longer survival in an orthotopic mouse model of metastatic prostate cancer. In future studies, this model will be used to unravel the molecular mechanisms of primary tumor/metastasis interaction in prostate cancer.
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BACKGROUND: Even though robot-assisted operations have evolved to a standard procedure in surgery, they are underrepresented in the curriculum of current medical students. OBJECTIVES: We present our experience and findings in Germany's first elective "Robot-assisted surgery" at a urological department for undergraduate medical students. MATERIALS AND METHODS: Ten undergraduates in their final years were taught the theoretical basics and practical skills in robot-assisted surgery within six lessons each lasting 2â¯h, including the opportunity to observe a live robot-assisted surgery. The increase of knowledge (ten multiple-choice questions) and skills (exercises Camera 0, Clutch, and Sea Spikes 1) on a robotic simulation device were quantified including an evaluation of the student's perspective. RESULTS: The 10 participants had a significant increase in knowledge and gave at a median of 3.5 additional correct answers in the final assessment (pâ¯= 0.011). For two out of three practical exercises, the overall score significantly increased (Camera 0 and Sea Spikes 1, for both pâ¯< 0.05), but for the exercise "Clutch", only economy of motion significantly improved (pâ¯= 0.028). The elective was evaluated (very) good and the willingness of the participants to become urologists significantly increased (pâ¯= 0.007). CONCLUSION: There is a great interest of many undergraduate medical students in robot-assisted surgery. Offering an elective appears to be an excellent format to teach the theoretical background and practical skills in robotic (urologic) surgery. Moreover, such an elective could raise more attention to the field of urology and might attract future colleagues.
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Procedimentos Cirúrgicos Robóticos , Robótica , Urologia , Competência Clínica , Currículo , Humanos , Urologia/educaçãoRESUMO
BACKGROUND: Follow-up during Active Surveillance (AS) may result in psychological burden and discomfort due to the constant clinical monitoring. Therefore, successful implementation of AS is to some extent a challenge for the patient and the caregiver. MATERIALS AND METHODS: In this monocentric study, we analyzed the reasons for termination of AS and the rate of the postoperative adverse pathology (AP) in patients who underwent deferred radical prostatectomy (RP) after AS. These results were compared with AS candidates who underwent immediate RP. P-values were calculated with the Χ2 test. RESULTS: After 21 months of follow-up during AS, a deferred RP was performed in 74 patients. On the other hand, 214 patients underwent immediate RP. AP (Gleason score ≥7b, ≥pT3a, R1 and N+) was common in the AS group and this was statistically significant (45% vs. 29%, P-value <0.001). CONCLUSION: These findings reflect many deficits in the current AS protocols. Using the available tools to apply AS in the routine clinical practice setting may be not adequate to afford oncological safety. This requires the development of new diagnostic tools like new imaging techniques and innovative biomarkers that provide the clinician with more accurate data about disease progression and subsequent help to achieve better outcomes in active surveillance candidates.