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BACKGROUND: In addition to erectile dysfunction, urinary incontinence is the most common functional limitation after radical prostatectomy (RPE) for prostate cancer (PCa). The German S3 guideline recommends informing patients about possible effects of the therapy options, including incontinence. However, only little data on continence from routine care in German-speaking countries after RPE are currently available, which makes it difficult to inform patients. OBJECTIVE: The aim of this work is to present data on the frequency and severity of urinary incontinence after RPE from routine care. MATERIALS AND METHODS: Information from the PCO (Prostate Cancer Outcomes) study is used, which was collected between 2016 and 2022 in 125 German Cancer Society (DKG)-certified prostate cancer centers in 17,149 patients using the Expanded Prostate Cancer Index Composite Short Form (EPIC-26). Changes in the "incontinence" score before (T0) and 12 months after RPE (T1) and the proportion of patients who used pads, stratified by age and risk group, are reported. RESULTS: The average score for urinary incontinence (value range: 0-worst possible to 100-best possible) was 93 points at T0 and 73 points 12 months later. At T0, 97% of the patients did not use a pad, compared to 56% at T1. 43% of the patients who did not use a pad before surgery used at least one pad a day 12 months later, while 13% use two or more. The proportion of patients using pads differs by age and risk classification. CONCLUSION: The results provide a comprehensive insight into functional outcome 12 months after RPE and can be taken into account when informing patients.
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Disfunción Eréctil , Neoplasias de la Próstata , Incontinencia Urinaria , Masculino , Humanos , Incontinencia Urinaria/epidemiología , Disfunción Eréctil/epidemiología , Neoplasias de la Próstata/cirugía , Prostatectomía/efectos adversosRESUMEN
BACKGROUND: Circular urethral compression with an artificial sphincter allows control of voiding, even in patients with severe stress urinary incontinence, but it heightens the risk of urethral atrophy and erosion. This study of one of the largest populations of patients treated with radiotherapy investigates the additive effect of the post-radiogenic stricture of the membranous urethra/bladder neck on AMS 800 artificial urinary sphincter outcomes. METHODS: In a retrospective multicenter cohort study, we analyzed patients fitted with an AMS 800, comparing those who had received radiotherapy with patients presenting a devastated bladder outlet (stricture of the membranous urethra/bladder neck). We determined the correlation between these groups of patients using both univariate and stepwise adjusted multivariate regression. The revision-free interval was estimated by a Kaplan-Meier plot and compared by applying the log-rank test. A p value below 0.05 was considered statistically significant. RESULTS: Of the 123 irradiated patients we identified, 62 (50.4%) had undergone at least one prior desobstruction for bladder-neck/urethra stenosis. After a mean follow-up of 21 months, the latter tended to achieve social continence less frequently (25.7% vs. 35%; p = 0.08). Revision was required significantly more often for this group (43.1% vs. 26.3%; p = 0.05) due to urethral erosion in 18 of 25 cases. A stenosis recurred in five cases; desobstruction was performed in two cases, leading to erosion in both. Multivariate analysis revealed a significantly higher risk of revision when recurrent stenosis necessitated at least two prior desobstructions (HR 2.8; p = 0.003). CONCLUSIONS: A devastated bladder outlet is associated with a lower proportion of men with social continence and a significantly higher need for revision compared with irradiated patients without a history of urethral stenosis. Alternative surgical procedures should be discussed beforehand, especially in cases of recurrent urethral stenosis.
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BACKGROUND: Preexistent LUTD are considered a hostile environment, which might negatively impact KTx survival. In such cases, surgical reconstruction of the bladder is required. However, there is still disagreement on the optimal timing of the reconstruction procedure. METHODS: This is a multicenter analysis of data from the CERTAIN Registry. Included were 62 children aged 8.18 ± 4.90 years, with LUTD. Study endpoints were the duration of initial posttransplant hospitalization, febrile UTIs, and a composite failure endpoint comprising decline of eGFR, graft loss, or death up to 5 years posttransplant. Outcome was compared to matched controls without bladder dysfunction. RESULTS: Forty-one patients (66.1%) underwent pretransplant and 14 patients (22.6%) posttransplant reconstruction. Bladder augmentation was performed more frequently in the pretransplant (61%) than in the posttransplant group (21%, p = .013). Outcome in the pre- and posttransplant groups and in the subgroups of patients on pretransplant PD with major bladder surgery either pre- (n = 14) or posttransplant (n = 7) was comparable. Outcomes of the main study cohort and the matched control cohort (n = 119) were comparable during the first 4 years posttransplant; at year 5, there were more events of transplant dysfunction in the study cohort with LUTD than in controls (p = .03). CONCLUSIONS: This multicenter analysis of the current practice of LUTD reconstruction in pediatric KTx recipients shows that pre- or posttransplant surgical reconstruction of the lower urinary tract is associated with a comparable 5-year outcome.
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Trasplante de Riñón , Infecciones Urinarias , Niño , Estudios de Cohortes , Supervivencia de Injerto , Humanos , Receptores de Trasplantes , Vejiga Urinaria/cirugía , Infecciones Urinarias/etiologíaRESUMEN
BACKGROUND: Radiologic imaging is important for the detection, staging and follow-up of urological tumors. Basic therapy decisions for both oncological (surgical vs. systemic therapy, e.g. in testicular cancer) and non-oncological pathologies (interventional vs. conservative therapy, e.g. for ureteral stones) depend largely on the tomographic imaging performed. Due to its almost ubiquitous availability, speed and cost-effectiveness, computed tomography (CT) plays an important role not only in the clarification of abdominal trauma and non-traumatic emergencies, but also in staging and follow-up of oncological patients. However, the level of radiation exposure, impaired renal function and allergies to iodinated contrast media limit the use of CT. Magnetic resonance imaging (MRI) can be a good alternative for many areas of application in oncological and non-oncological imaging due to its high soft tissue differentiation and functional-specific protocols but without the use of ionizing radiation. AIM: In the following, the main indications of abdominal and pelvic CT and MRI in urology and their limitations are summarized. RESULTS: The areas of application between CT and MRI are increasingly overlapping, since the latest developments in CT continue to further reduce radiation exposure and increase contrast information, while the speed and robustness of MRI are significantly improving at the same time.
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Neoplasias Testiculares , Enfermedades Urológicas , Medios de Contraste , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Tomografía Computarizada por Rayos X/métodos , Enfermedades Urológicas/diagnóstico por imagenRESUMEN
Multiparametric magnetic resonance imaging (mpMRI) and MRI/ultrasound fusion-targeted prostate biopsy (FB) have excellent sensitivity in detecting significant prostate cancer (sPC). FB platforms can be distinguished by rigid (RTB) or elastic image registration (ETB). We compared RTB and ETB by analyzing sPC detection rates of both RTB and ETB at different stages of the surgeons' learning curve. Patients undergoing RTB between 2015-2017 (n = 502) were compared to patients undergoing ETB from 2017-2019 (n = 437). SPC detection rates were compared by Chi-square-test on patient-basis. Combination of transperineal systematic biopsy and each TB served as reference and sub-analyses were performed for different grades of surgeon's experience. In the RTB subgroup, 233 men (46%) had sPC, compared to 201 (46%) in the ETB subgroup. RTB alone detected 94% of men with sPC and ETB 87% (p = 0.02). However, for at least intermediate-experienced surgeons (>100 FB), no differences occurred between RTB and ETB. In the total cohort, at least intermediate-experienced surgeons detected significantly more sPC (10%, p = 0.008) than novices. Thus, targeted transperineal MRI/TRUS-FB with a RTB registration system showed a similar sPC detection rate to ETB in experienced surgeons but a superior sPC detection rate to ETB in the total cohort. Low-experienced surgeons seem to benefit from RTB.
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BACKGROUND: Mutations in DNA damage repair genes, in particular genes involved in homology-directed repair, define a subgroup of men with prostate cancer with a more unfavorable prognosis but a therapeutic vulnerability to PARP inhibition. In current practice, mutational testing of prostate cancer patients is commonly done late i.e., when the tumor is castration resistant. In addition, most sequencing panels do not include TP53, one of the most crucial tumor suppressor genes in human cancer. In this proof-of-concept study, we sought to extend the clinical use of these molecular markers by exploring the early prognostic impact of mutations in TP53 and DNA damage repair genes in men with primary, nonmetastatic prostate cancer undergoing radical prostatectomy (RPX). METHODS: Tumor specimens from a cohort of 68 RPX patients with intermediate (nâ¯=â¯11, 16.2%) or high-risk (nâ¯=â¯57, 83.8%) disease were analyzed by targeted next generation sequencing using a 37 DNA damage repair and checkpoint gene panel including TP53. Sequencing results were correlated to clinicopathologic variables as well as PSA persistence or time to PSA failure. In addition, the distribution of TP53 and DNA damage repair gene mutations was analyzed in three large publicly available datasets (TCGA, MSKCC and SU2C). RESULTS: Of 68 primary prostate cancers analyzed, 23 (33.8%) were found to harbor a mutation in either TP53 (nâ¯=â¯12, 17.6%) or a DNA damage repair gene (nâ¯=â¯11, 16.2%). The vast majority of these mutations (22 of 23, 95.7%) were detected in primary tumors from patients with high-risk features. These mutations were mutually exclusive in our cohort and additional data mining suggests an enrichment of DNA damage repair gene mutations in TP53 wild-type tumors. Mutations in either TP53 or a DNA damage repair gene were associated with a significantly worse prognosis after RPX. Importantly, the presence of TP53/DNA damage repair gene mutations was an independent risk factor for PSA failure or PSA persistence in multivariate Cox regression models. CONCLUSION: TP53 or DNA damage repair gene mutations are frequently detected in primary prostate cancer with high-risk features and define a subgroup of patients with an increased risk for PSA failure or persistence after RPX. The significant adverse impact of these alterations on patient prognosis may be exploited to identify men with prostate cancer who may benefit from a more intensified treatment.
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Reparación del ADN/genética , Mutación , Neoplasias de la Próstata/genética , Proteína p53 Supresora de Tumor/genética , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Prueba de Estudio ConceptualRESUMEN
OBJECTIVES: To assess differences in 24-month oncologic and functional outcomes in men with low to intermediate-risk prostate cancer treated with MRI-guided transurethral ultrasound ablation (TULSA) using intentionally conservative versus intensified treatment parameters. PATIENTS AND METHODS: Patients from a single center involved in two multicenter trials were included in this analysis. This included 14 of 30 patients with Gleason 3 + 3 from a Phase I study using intentionally conservative treatment parameters, and 15 of 115 patients with Gleason ≤ 3 + 4 from a pivotal study using intensified parameters. Follow-up data compared across these cohorts included 12-month biopsy and MRI for all patients, and 24-month PSA, micturition and quality of life (IIEF, IPSS, IPSS-QOL). The prognostic value of baseline parameters and PSA kinetics on 12-month histological recurrence was evaluated by logistic regression. RESULTS: 12-month biopsy revealed clinically significant residual disease in 4 (29%) and 2 (14%) patients from the Phase I and pivotal studies, respectively. PSA nadir was 0.7 ng/ml for Phase I and 0.5 ng/ml for pivotal study patients. Patient age at diagnosis, use of MRI fusion/systematic prostate biopsy, number of obtained cores at initial biopsy, PSA course, and PSA nadir were identified as prognostic factors for treatment success. All but one patient from each cohort maintained erection firmness sufficient for penetration. No cases of pad use were reported at 24 months. There were no Grade 4 or higher adverse events, and no late toxicity related to the procedure. CONCLUSION: Two-year follow-up demonstrated the efficacy of TULSA for the treatment of localized prostate cancer, and the durability of PSA and functional outcomes. Intensifying treatment parameters in the pivotal trial had no impact on safety or functional outcomes through 24 months, while reducing the recurrence rate for clinically significant disease. Careful patient selection by MRI fusion/systematic prostate biopsy and adequate follow-up through routine 12-month biopsy are recommended.
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There are currently five programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors approved for the treatment of locally advanced or metastatic urothelial carcinoma (UC) of the bladder. For platinum-ineligible patients, testing of tumor specimens for PD-L1 expression is required. However, scoring of PD-L1 immunohistochemistry is complex due to different antibodies used, the requirement to score expression in different cellular compartments and intratumoral heterogeneity. It can also be difficult to obtain and test longitudinal tumor samples, which would be desirable to monitor treatment responses and tumor evolution under treatment-induced selective pressure. In the present proof-of concept study, we provide evidence that PD-L1 can be detected in the urine of patients with non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Urine PD-L1 levels were significantly higher in NMIBC and MIBC patients when compared to patients with various non-malignant urological diseases. Further prospective and independent studies are required to assess the value of PD-L1 in the urine as a novel biomarker with potential for the early detection, prediction and therapeutic monitoring of patients with UC of the bladder.
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Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/orina , Receptor de Muerte Celular Programada 1/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/orina , Vejiga Urinaria/metabolismo , Femenino , Humanos , Inmunohistoquímica , MasculinoRESUMEN
Salvage radical prostatectomy (sRP) has evolved from open to minimally invasive approaches. sRP can be offered to patients with local recurrence to improve biochemical recurrence (BCR)-free and overall survival. We evaluate oncological outcome and continence after retropubic (RRP), conventional (cRARP), and Retzius-sparing robotic (rsRARP) surgery. MATERIALS/METHODS: A total of 53 patients undergoing sRP between 2010 and 2020 were included. Follow-up included oncological outcome and continence. RESULTS: sRP was done as RRP (n = 25), cRARP (n = 7), or rsRARP (n = 21). Median blood loss was 900 mL, 500 mL, and 300 mL for RRP, cRARP, and rsRARP, respectively. At 12 months, 5 (20%), 0, and 4 (19%) patients were continent, 9 (36%), 3 (43%), and 7 (33%) had grade 1 incontinence, 5 (20%), 2 (29%), and 3 (14%) had grade 2 incontinence, and 3 (12%), 2 (29%), and 4 (19%) had grade 3 incontinence for RRP, cRARP, or rsRARP, respectively. During a mean follow-up of 52.6 months, 16 (64%), 4 (57%), and 3 (14%) developed BCR in the RRP-, cRARP-, and rsRARP-group, respectively. CONCLUSIONS: Over the years, sRP has shifted from open to laparoscopic/robotic surgery. RARP shows good oncological and functional outcome. rsRARP ensures direct vision on the rectum during preparation and can therefore increase safety and surgeon's confidence, especially in the salvage setting.
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BACKGROUND: Contemporary selection criteria for men with prostate cancer (PC) suitable for active surveillance (AS) are unsatisfactory, leading to high disqualification rates based on tumor misclassification. Conventional biopsy protocols are based on standard 12-core transrectal ultrasound (TRUS) biopsy. OBJECTIVE: To assess the value of magnetic resonance imaging (MRI)/TRUS fusion biopsy over 4-yr follow-up in men on AS for low-risk PC. DESIGN, SETTING, AND PARTICIPANTS: Between 2010 and 2018, a total of 273 men were included. Of them, 157 men with initial 12-core TRUS biopsy and 116 with initial MRI/TRUS fusion biopsy were followed by systematic and targeted transperineal MRI/TRUS fusion biopsies based on Prostate Cancer Research International Active Surveillance criteria. MRI from follow-up MRI/TRUS fusion biopsy was assessed using the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) scoring system. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: AS-disqualification rates for patients on AS initially diagnosed by either 12-core TRUS biopsy or by MRI/TRUS fusion biopsy were compared using Kaplan-Meier estimates, log-rank tests, and regression analyses. We also analyzed the influence of negative primary MRI and PRECISE scoring to predict AS disqualification using Kaplan-Meier estimates, log-rank tests, and receiver operating characteristic (ROC) curve analysis. RESULTS AND LIMITATIONS: Of men diagnosed by 12-core TRUS biopsy, 59% were disqualified from AS based on the results of subsequent MRI/TRUS fusion biopsy. In the initial MRI fusion biopsy cohort, upgrading occurred significantly less frequently (19%, p<0.001). ROC curve analyses demonstrated good discrimination for the PRECISE score with an area under the curve of 0.83. No men with a PRECISE score of 1 or 2 (demonstrating absence or downgrading of lesions in follow-up MRI) were disqualified from AS. In our cohort, a negative baseline MRI scan was not a predictor of nondisqualification from AS. Limitations include transperineal approach and extended systematic biopsies used with MRI/TRUS fusion biopsy, which may not be representative of other centers. CONCLUSIONS: MRI/TRUS fusion biopsies allow a reliable risk classification for patients who are candidates for AS. The application of the PRECISE scoring system demonstrated good discrimination. PATIENT SUMMARY: In this study, we investigated the value of multiparametric magnetic resonance imaging (MRI) and MRI/transrectal ultrasound (TRUS) fusion biopsies for the assessment of active surveillance (AS) reliability using the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation criteria. Standard TRUS biopsies lead to significant underestimation of prostate cancer. In contrast, MRI/TRUS fusion biopsies allowed for a more reliable risk classification. For appropriate inclusion into AS, men should receive either an initial or a confirmatory MRI/TRUS fusion biopsy.
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Biopsia Guiada por Imagen/métodos , Imagen por Resonancia Magnética/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Ultrasonografía Intervencional/métodos , Espera Vigilante , Anciano , Biopsia , Humanos , Masculino , Persona de Mediana Edad , Perineo , Valor Predictivo de las Pruebas , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) has excellent sensitivity in detecting significant prostate cancer (sPC). Nevertheless, uncertainty exists regarding the management of Prostate Imaging-Reporting and Data System (PI-RADS) 3 lesions. OBJECTIVE: To investigate whether PI-RADS 3 lesions in combination with clinical parameters, especially prostate-specific antigen density (PSAD), can be used to exclude sPC. DESIGN, SETTING, AND PARTICIPANTS: A total of 455 consecutive biopsy-naïve men underwent MRI-guided transperineal prostate fusion biopsy at our department between 2017 and 2018. We identified 101 patients who had exclusively one or more PI-RADS 3 lesions on mpMRI. sPC was defined as intermediate- and high-risk PC (according to the D'Amico risk classification). OUTCOME MEASURES AND STATISTICAL ANALYSIS: Univariate logistic regression analysis was performed to test different clinical factors as predictors of sPC in men with PI-RADS 3 lesions. The probability of sPC prediction was calculated for different PSAD thresholds. RESULTS AND LIMITATIONS: Among patients with PI-RADS 3 lesions, PSAD was a significant predictor of sPC (p = 0.005). For a PI-RADS score of 3 the probability of excluding sPC was 85% (86/101), which increased to 98% (42/43) when combined with PSAD <0.1 ng/ml/ml. CONCLUSIONS: Inclusion of PSAD < 0.1 ng/ml/ml in the strategy for biopsy-naïve patients with equivocal mpMRI findings would allow a reduction in prostate biopsies in 43% (43/101) of cases at the cost of missing a very small number (2%, 1/43) of intermediate-risk PCs. PATIENT SUMMARY: At high-volume tertiary care centers with significant experience in prostate multiparametric magnetic resonance imaging, immediate biopsies could be safely omitted for men with lesions with a Prostate Imaging-Reporting and Data System score of 3 and prostate-specific antigen density of PSAD < 0.1 ng/ml/ml. Any decision to omit an immediate biopsy should be associated with close monitoring.
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Neoplasias de la Próstata , Biopsia , Humanos , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Masculino , Próstata/diagnóstico por imagen , Antígeno Prostático Específico , Neoplasias de la Próstata/diagnóstico por imagenRESUMEN
BACKGROUND: Fixed and adjustable male slings for the treatment of male urinary stress incontinence became increasingly popular during the last decade. Although fixed slings are recommended for the treatment of mild to moderate stress urinary incontinence, there is still a lack of evidence regarding the precise indication for an adjustable male sling. Furthermore, there is still no evidence that one type of male sling is superior to another. However, both, adjustable and fixed slings, are commonly utilized in daily clinical practice. This current investigation aims to evaluate the differences between fixed and adjustable male slings regarding indications, complication rates and functional outcome in the treatment of male stress urinary incontinence in current clinical practice. METHODS: A total of 294 patients with a fixed and 176 patients with an adjustable male sling were evaluated in a multicenter single arm cohort trial. Data collection was performed retrospectively according the medical record. Functional outcome was prospectively analyzed by standardized, validated questionnaires. Descriptive statistics was performed to present patient characteristics, complication rates and functional outcome. A chi2-test for categorical and independent t-test for continuous variables was performed to identify heterogeneity between the groups and to correlate preoperative characteristics with the outcome. A P value <0.05 was considered statistically significant. RESULTS: Patients with higher degree of urinary incontinence (P<0.001) and risk factors such as history of pelvic irradiation (P<0.001) or prior surgery for urethral stricture (P=0.032) were more likely to receive an adjustable MS. Complication rates were comparable except for infection (P=0.009, 0 vs. 2.3%) and pain (P=0.001, 1.7% vs. 11.3%) which occurred more frequently in adjustable slings. Functional outcome according validated questionnaires demonstrated no differences between fixed and adjustable male slings. CONCLUSIONS: Adjustable male slings are more frequently utilized in patients with higher degree of incontinence and risk factors compared to fixed slings. No differences could be identified between functional outcome which may imply an advantage for adjustability. However, pain and infection rates were significantly higher in adjustable MS and should be considered in the decision process for sling type.
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AIM: To analyze the influence of implantation volume of artificial sphincters (AMS 800) on outcome in a large central European multicenter cohort study. METHODS: As part of the DOMINO (Debates on Male Incontinence) project, the surgical procedures and outcomes were retrospectively analyzed in a total of 473 patients who received an artificial sphincter (AMS 800) between 2010 and 2012. Clinics that implanted at least 10 AMS 800 per year were defined as high-volume centers. RESULTS: Sixteen centers had a mean rate of 9.54 AMS 800/y of which five clinics were identified as high-volume centers. They implanted significantly more double cuffs (55% vs 12.1%; P < .001), used the perineal approach significantly more often (78% vs 67.7%; P = .003) and chose larger mean cuff sizes (4.63 cm vs 4.42 cm; P = .002). With a mean follow-up of 18 months, the revision rate was significantly higher at low-volume centers (38.5% vs 26.7%; P = .037), urethral erosion being the main reason for revision. Social continence (0-1 pads/24 h) was achieved significantly more often in high-volume centers (45.5% vs 24.2%; P = .002). CONCLUSIONS: Our study showed significantly better continence results and lower revision rates at high-volume centers, confirming earlier results that are still true in this decade. We, therefore, recommend surgery for male incontinence at qualified centers.
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Uretra/cirugía , Incontinencia Urinaria de Esfuerzo/cirugía , Esfínter Urinario Artificial , Anciano , Austria , Estudios de Cohortes , Alemania , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Defects in DNA damage repair genes characterize a subset of men with prostate cancer and provide an attractive opportunity for precision oncology approaches. The prevalence of such perturbations in newly diagnosed, treatment-naïve patients with a high risk for lethal disease outcome, however, has not been sufficiently explored. PATIENTS AND METHODS: Prostate cancer specimens from 67 men with newly diagnosed early onset, localized high-risk/locally advanced or metastatic prostate cancer were included in this prospective pilot study. Tumor samples, including 30 prostate biopsies, were analyzed by targeted next generation sequencing using a formalin-fixed, paraffin-embedded tissue-optimized 37 DNA damage repair and checkpoint gene panel. RESULTS: The drop-out rate due to an insufficient quantity of DNA was 4.5% (3 of 67 patients). In the remaining 64 patients, the rate of pathogenic DNA damage repair gene mutations was 26.6%. The highest rate of pathogenic DNA damage repair and checkpoint gene mutations was found in men with treatment-naïve metastatic prostate cancer (38.9%). In addition, a high number of likely pathogenic mutations and gene deletions were detected. Altogether, one or more pathogenic mutation, likely pathogenic mutation or gene deletion affected 43 of 64 patients (67.2%) including 29 of 36 patients (80.6%) with treatment-naïve metastatic prostate cancer. Men with metastatic prostate cancer showed a high prevalence of alterations in TP53 (36.1%). CONCLUSIONS: This pilot study demonstrates the feasibility, performance and clinical relevance of somatic targeted next generation sequencing using a unique 37 DNA damage repair and checkpoint gene panel under routine conditions. Our results indicate that this approach can detect actionable DNA repair gene alterations, uncommon mutations as well as mutations associated with therapy resistance in a high number of patients, in particular patients with treatment-naïve metastatic prostate cancer.
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Daño del ADN/genética , Reparación del ADN/genética , Metástasis de la Neoplasia/genética , Neoplasias de la Próstata/genética , Proteína p53 Supresora de Tumor/genética , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Prevalencia , Estudios Prospectivos , Neoplasias de la Próstata/patología , Resultado del TratamientoRESUMEN
AIMS: To comparatively analyse outcomes after ARGUS classic and ArgusT adjustable male sling implantation in a real-world setting. METHODS: Inclusion criteria encompassed: non-neurogenic, moderate-to-severe stress urinary incontinence (≥2 pads), implantation of an ARGUS classic or ArgusT male sling between 2010 and 2012 in a high-volume center (>150 previous implantations). Functional outcomes were assessed using daily pad usage, 24-hour pad testing, and International Consultation on Incontinence (ICIQ-SF) questionnaires. Continence was defined as zero pads per 24 hours. Complications were graded using Clavien-Dindo scale. For multivariate analysis, binary logistic regression models were used (P < .05). RESULTS: A total of 106 patients (n = 74 [ARGUS classic], n = 32 [ArgusT]) from four centers were eligible. Median follow-up was 44.0 months (24-64). Patient cohorts were well-balanced. We observed a statistical trend in favor of ARGUS classic regarding postoperative urine loss based on standardized 24-hour pad test (71 ± 162 g [ARGUS classic] vs 160 ± 180 g [ArgusT]); P = .066]. Dry rates were 33.3% (ARGUS classic) and 11.8% (ArgusT, P = .114). In multivariable analysis, ArgusT male sling could not be confirmed as an independent predictor of decreased success (OR, 0.587; 95% CI; 0.166-2.076, P = .408). There were no Clavien IV and V complications. Inguinal pain was significantly higher after ArgusT implantation (P = .033). Explantation rates were higher for ArgusT compared to ARGUS classic (14.0 vs 23.3%; P = .371). Longer device survival for the ARGUS classic male sling was observed in Kaplan-Meier analysis (P = .198). CONCLUSIONS: In the largest comparative analysis of ARGUS classic and ArgusT male sling with the longest follow-up to date, we observed low continence rates with superior functional outcomes and decreased explantation rates after ARGUS classic implantation.
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Remoción de Dispositivos/estadística & datos numéricos , Complicaciones Posoperatorias/cirugía , Prostatectomía , Cabestrillo Suburetral , Incontinencia Urinaria de Esfuerzo/cirugía , Procedimientos Quirúrgicos Urológicos Masculinos/métodos , Anciano , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Encuestas y Cuestionarios , Resultado del Tratamiento , Procedimientos Quirúrgicos Urológicos Masculinos/instrumentaciónRESUMEN
OBJECTIVE: To investigate the effect of perioperative complications involving artificial urinary sphincter (AUS) implantation on rates of explantation and continence as well as health-related quality of life (HRQOL). MATERIALS AND METHODS: Inclusion criteria encompassed non-neurogenic, moderate-to-severe stress urinary incontinence (SUI) post radical prostatectomy and primary implantation of an AUS performed by a high-volume surgeon (>100 previous implantations). Reporting complications followed the validated Clavien-Dindo scale and Martin criteria. HRQOL was assessed by the validated IQOL score, continence by the validated ICIQ-SF score. Statistical analysis included Chi (2) test, Mann-Whitney-U test, and multivariate regression models (p<0.05). RESULTS: 105 patients from 5 centers met the inclusion criteria. After a median follow-up of 38 months, explantation rates were 27.6% with a continence rate of 48.4%. In the age-adjusted multivariate analysis, perioperative urinary tract infection was confirmed as an independent predictor of postoperative explantation rates [OR 24.28, 95% CI 2.81-209.77, p=0.004). Salvage implantation (OR 0.114, 95% CI 0.02-0.67, p=0.016) and non-prostatectomy related incontinence (OR 0.104, 95% CI 0.02-0.74, p=0.023) were independent predictors for worse continence outcomes. Low visual analogue scale scores (OR 9.999, 95% CI 1,42-70.25, p=0.021) and ICIQ-SF scores, respectively (OR 0.674, 95% CI 0.51-0.88, p=0.004) were independent predictors for increased HRQOL outcomes. Perioperative complications did not significantly impact on continence and HRQOL outcomes. CONCLUSION: Findings show postoperative infections adversely affect device survival after AUS implantation. However, if explantation can be avoided, the comparative long-term functional results and HRQOL outcomes are similar between patients with or without perioperative complications.
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Incontinencia Urinaria de Esfuerzo , Esfínter Urinario Artificial , Anciano , Humanos , Masculino , Persona de Mediana Edad , Prostatectomía/efectos adversos , Calidad de Vida , Resultado del Tratamiento , Incontinencia Urinaria de Esfuerzo/etiología , Incontinencia Urinaria de Esfuerzo/cirugíaRESUMEN
BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) facilitates the detection of significant prostate cancer. Therefore, addition of mpMRI to clinical parameters might improve the prediction of extraprostatic extension (EPE) in radical prostatectomy (RP) specimens. OBJECTIVE: To investigate the accuracy of a novel risk model (RM) combining clinical and mpMRI parameters to predict EPE in RP specimens. DESIGN, SETTING, AND PARTICIPANTS: We added prebiopsy mpMRI to clinical parameters and developed an RM to predict individual side-specific EPE (EPE-RM). Clinical parameters of 264 consecutive men with mpMRI prior to MRI/transrectal ultrasound fusion biopsy and subsequent RP between 2012 and 2015 were retrospectively analysed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariate regression analyses were used to determine significant EPE predictors for RM development. The prediction performance of the novel EPE-RM was compared with clinical T stage (cT), MR-European Society of Urogenital Radiology (ESUR) classification for EPE, two established nomograms (by Steuber et al and Ohori et al) and a clinical nomogram based on the coefficients of the established nomograms, and was constructed based on the data of the present cohort, using receiver operating characteristics (ROCs). For comparison, models' likelihood ratio (LR) tests and Vuong tests were used. Discrimination and calibration of the EPE-RM were validated based on resampling methods using bootstrapping. RESULTS AND LIMITATIONS: International society of Urogenital Pathology grade on biopsy, ESUR criteria, prostate-specific antigen, cT, prostate volume, and capsule contact length were included in the EPE-RM. Calibration of the EPE-RM was good (error 0.018). The ROC area under the curve for the EPE-RM was larger (0.87) compared with cT (0.66), Memorial Sloan Kettering Cancer Center nomogram (0.73), Steuber nomogram (0.70), novel clinical nomogram (0.79), and ESUR classification (0.81). Based on LR and Vuong tests, the EPE-RM's model fit was significantly better than that of cT, all clinical models, and ESUR classification alone (p<0.001). Limitations include monocentric design and expert reading of MRI. CONCLUSIONS: This novel EPE-RM, incorporating clinical and MRI parameters, performed better than contemporary clinical RMs and MRI predictors, therefore providing an accurate patient-tailored preoperative risk stratification of side-specific EPE. PATIENT SUMMARY: Extraprostatic extension of prostate cancer can be predicted accurately using a combination of magnetic resonance imaging and clinical parameters. This novel risk model outperforms magnetic resonance imaging and clinical predictors alone and can be useful when planning nerve-sparing radical prostatectomy.
Asunto(s)
Modelos Estadísticos , Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Medición de Riesgo/métodos , Anciano , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Nomogramas , Planificación de Atención al Paciente , Valor Predictivo de las Pruebas , Pronóstico , Prostatectomía/métodos , Neoplasias de la Próstata/clasificación , Neoplasias de la Próstata/cirugía , Estudios RetrospectivosRESUMEN
PURPOSE: To analyze urinary continence outcome following robot-assisted radical prostatectomy (RARP) for aggressive prostate cancer in men aged ≥ 70 and < 70 years. METHODS: Retrospective analyses of prospectively collected long-term data from a monocentric cohort of 350 men with D'Amico high-risk prostate cancer undergone robot-assisted radical prostatectomy at a single institution between 2005 and 2016. The association between time since operation and zero-pad urinary continence recovery was comparatively analyzed by separate pre-operative and post-operative Cox proportional-hazard regression models. RESULTS: Median age in the age group ≥ 70 years was 73 years compared with 62 years in the < 70 year age group. Distribution of men receiving adjuvant and salvage radiotherapy/hormonal therapy was similar in both age groups. Urinary continence recovery rate at 12, 24, and 36 months after surgery of men aged ≥ 70 years was 66, 79 and 83%, respectively, and statistically similar to that of men < 70 years: 71, 81, and 85% (log-rank test p = 0.24). Multivariable analyses demonstrated no significant difference in return to continence between the two age groups (p = 0.28 and p = 0.17). In addition, clinical stage and type of nerve sparing (unilateral, bilateral or non-nerve sparing) were found to be independently predictive of pad-free continence recovery. CONCLUSIONS: Regardless of age, return to continence in men with aggressive prostate cancer undergoing RARP continues to improve way beyond the first 12 months after surgery. Considering the dire effects of post-operative radiotherapy on continence in this aggressive cancer cohort, advanced age alone should not discourage recommending multimodal therapy involving RARP.