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In up to two thirds of prostate-specific membrane antigen (PSMA) PET scans, unspecific bone uptake has been described. The aim of this study was to estimate the diagnostic accuracy of [68Ga]Ga-PSMA-11 PET/CT for bone metastases and the occurrence of equivocal lesions. Methods: We analyzed retrospectively 118 patients who underwent a [68Ga]Ga-PSMA-11 PET/CT for initial staging or recurrence evaluation. Lesions were interpreted according to the PSMA reporting and data system (PSMA-RADS) and the prostate cancer molecular imaging standardized evaluation (PROMISE) criteria. The SUVmax and the localization of each lesion were recorded. A combination of prior or follow-up examinations was used as a reference standard to categorize benign and malignant lesions. Correlation between the final diagnosis and imaging or clinicobiochemical parameters was tested. The diagnostic accuracy was calculated for different cutoffs of PSMA-RADS criteria, for PROMISE criteria, and the sequential combination of both. Results: In total, 265 bone abnormalities were identified in 70 of 118 patients. Among these, 148 (55.8%) lesions in 50 (42.4%) patients were classified as PSMA-RADS-3B. There were no PSMA-RADS-3D lesions in our cohort. Equivocal lesions were more frequent on the ribs (30.6%) followed by the pelvis (26.5%), but in the ribs, such an uptake was malignant in 33.3% of cases versus 66.7% in the pelvis. A significant association was found between the final diagnosis and the SUVmax, prostate-specific antigen (PSA), PSA doubling time, International Society of Urological Pathology score, and the number of foci. The sensitivity and specificity were 100% and 63.6% for the PSMA-RADS-3B cutoff, respectively; 40.5% and 100% for the PSMA-RADS-4 cutoff, respectively; and 89.3% and 96.6% for both the PROMISE criteria and the sequential PSMA-RADS/PROMISE strategy, respectively. In the sequential method, the number of equivocal lesions was reduced from 147 to 2. We found that 53% of PSMA-RADS-3B lesions were malignant; 95.5% of lesions classified positive by the sequential method were true positives, whereas 32.6% were false negatives. Conclusion: [68Ga]Ga-PSMA-11 PET/CT has high accuracy for the diagnosis of bone metastases. Equivocal lesions constitute nearly half of the lesions seen on PSMA PET. The sequential combination of PSMA-RADS and PROMISE criteria reduces the number of lesions classified as equivocal. PSMA-RADS-3B lesions which are positive according to the PROMISE criteria should be considered highly suggestive of malignancy.
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Neoplasias Óseas , Ácido Edético , Isótopos de Galio , Radioisótopos de Galio , Oligopéptidos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Neoplasias Óseas/secundario , Neoplasias Óseas/diagnóstico por imagen , Anciano , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Ácido Edético/análogos & derivados , Persona de Mediana Edad , Estudios Retrospectivos , Anciano de 80 o más Años , Estándares de ReferenciaRESUMEN
BACKGROUND: Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, identified through multiparametric magnetic resonance imaging (mpMRI), present a clinical challenge due to their equivocal nature in predicting clinically significant prostate cancer (csPCa). Aim of the study is to improve risk stratification of patients with PI-RADS 3 lesions and candidates for prostate biopsy. METHODS: A cohort of 4841 consecutive patients who underwent MRI and subsequent MRI-targeted and systematic biopsies between January 2016 and April 2023 were retrospectively identified from independent prospectively maintained database. Only patients who have PI-RADS 3 lesions were included in the final analysis. A multivariable logistic regression analysis was performed to identify covariables associated with csPCa defined as International Society of Urological Pathology (ISUP) grade group ≥2. Performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration, and net benefit. Significant predictors were then selected for further exploration using a Chi-squared Automatic Interaction Detection (CHAID) analysis. RESULTS: Overall, 790 patients had PI-RADS 3 lesions and 151 (19%) had csPCa. Significant associations were observed for age (OR: 1.1 [1.0-1.1]; p = 0.01) and PSA density (OR: 1643 [2717-41,997]; p < 0.01). The CHAID analysis identified PSAd as the sole significant factor influencing the decision tree. Cut-offs for PSAd were 0.13 ng/ml/cc (csPCa detection rate of 1% vs. 18%) for the two-nodes model and 0.09 ng/ml/cc and 0.16 ng/ml/cc for the three-nodes model (csPCa detection rate of 0.5% vs. 2% vs. 17%). CONCLUSIONS: For individuals with PI-RADS 3 lesions on prostate mpMRI and a PSAd below 0.13, especially below 0.09, prostate biopsy can be omitted, in order to avoid unnecessary biopsy and overdiagnosis of non-csPCa.
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PURPOSE: Magnetic resonance imaging (MRI) is a promising tool for risk assessment, potentially reducing the burden of unnecessary prostate biopsies. Risk prediction models that incorporate MRI data have gained attention, but their external validation and comparison are essential for guiding clinical practice. The aim is to externally validate and compare risk prediction models for the diagnosis of clinically significant prostate cancer (csPCa). METHODS: A cohort of 4606 patients across fifteen European tertiary referral centers were identified from a prospective maintained database between January 2016 and April 2023. Transrectal or transperineal image-fusion MRI-targeted and systematic biopsies for PI-RADS score of ≥ 3 or ≥ 2 depending on patient characteristics and physician preferences. Probabilities for csPCa, defined as International Society of Urological Pathology (ISUP) grade ≥ 2, were calculated for each patients using eight models. Performance was characterized by area under the receiver operating characteristic curve (AUC), calibration, and net benefit. Subgroup analyses were performed across various clinically relevant subgroups. RESULTS: Overall, csPCa was detected in 2154 (47%) patients. The models exhibited satisfactory performance, demonstrating good discrimination (AUC ranging from 0.75 to 0.78, p < 0.001), adequate calibration, and high net benefit. The model described by Alberts showed the highest clinical utility for threshold probabilities between 10 and 20%. Subgroup analyses highlighted variations in models' performance, particularly when stratified according to PSA level, biopsy technique and PI-RADS version. CONCLUSIONS: We report a comprehensive external validation of risk prediction models for csPCa diagnosis in patients who underwent MRI-targeted and systematic biopsies. The model by Alberts demonstrated superior clinical utility and should be favored when determining the need for a prostate biopsy.
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Imagen por Resonancia Magnética , Próstata , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Medición de Riesgo/métodos , Anciano , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Próstata/patología , Próstata/diagnóstico por imagen , Biopsia Guiada por Imagen/métodos , Valor Predictivo de las PruebasRESUMEN
PURPOSE: Utility of prostate-specific antigen density (PSAd) for risk-stratification to avoid unnecessary biopsy remains unclear due to the lack of standardization of prostate volume estimation. We evaluated the impact of ellipsoidal formula using multiparametric magnetic resonance (MRI) and semi-automated segmentation using tridimensional ultrasound (3D-US) on prostate volume and PSAd estimations as well as the distribution of patients in a risk-adapted table of clinically significant prostate cancer (csPCa). METHODS: In a prospectively maintained database of 4841 patients who underwent MRI-targeted and systematic biopsies, 971 met inclusions criteria. Correlation of volume estimation was assessed by Kendall's correlation coefficient and graphically represented by scatter and Bland-Altman plots. Distribution of csPCa was presented using the Schoots risk-adapted table based on PSAd and PI-RADS score. The model was evaluated using discrimination, calibration plots and decision curve analysis (DCA). RESULTS: Median prostate volume estimation using 3D-US was higher compared to MRI (49cc[IQR 37-68] vs 47cc[IQR 35-66], p < 0.001). Significant correlation between imaging modalities was observed (τ = 0.73[CI 0.7-0.75], p < 0.001). Bland-Altman plot emphasizes the differences in prostate volume estimation. Using the Schoots risk-adapted table, a high risk of csPCa was observed in PI-RADS 2 combined with high PSAd, and in all PI-RADS 4-5. The risk of csPCa was proportional to the PSAd for PI-RADS 3 patients. Good accuracy (AUC of 0.69 and 0.68 using 3D-US and MRI, respectively), adequate calibration and a higher net benefit when using 3D-US for probability thresholds above 25% on DCA. CONCLUSIONS: Prostate volume estimation with semi-automated segmentation using 3D-US should be preferred to the ellipsoidal formula (MRI) when evaluating PSAd and the risk of csPCa.
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Antígeno Prostático Específico , Próstata , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Antígeno Prostático Específico/sangre , Anciano , Persona de Mediana Edad , Tamaño de los Órganos , Próstata/patología , Próstata/diagnóstico por imagen , Medición de Riesgo , Biopsia Guiada por Imagen/métodos , Imagen por Resonancia Magnética/métodos , Toma de Decisiones Clínicas , Imágenes de Resonancia Magnética Multiparamétrica , Estudios ProspectivosRESUMEN
PURPOSE: Accurate prediction of extraprostatic extension (EPE) is crucial for decision-making in radical prostatectomy (RP), especially in nerve-sparing strategies. Martini et al. introduced a three-tier algorithm for predicting contralateral EPE in unilateral high-risk prostate cancer (PCa). The aim of the study is to externally validate this model in a multicentric European cohort of patients. METHODS: The data from 208 unilateral high-risk PCa patients diagnosed through magnetic resonance imaging (MRI)-targeted and systematic biopsies, treated with RP between January 2016 and November 2021 at eight referral centers were collected. The evaluation of model performance involved measures such as discrimination (AUC), calibration, and decision-curve analysis (DCA) following TRIPOD guidelines. In addition, a comparison was made with two established multivariable logistic regression models predicting the risk of side specific EPE for assessment purposes. RESULTS: Overall, 38%, 48%, and 14% of patients were categorized as low, intermediate, and high-risk groups according to Martini et al.'s model, respectively. At final pathology, EPE on the contralateral prostatic lobe occurred in 6.3%, 12%, and 34% of patients in the respective risk groups. The algorithm demonstrated acceptable discrimination (AUC 0.68), comparable to other multivariable logistic regression models (p = 0.3), adequate calibration and the highest net benefit in DCA. The limitations include the modest sample size, retrospective design, and lack of central revision. CONCLUSION: Our findings endorse the algorithm's commendable performance, supporting its utility in guiding treatment decisions for unilateral high-risk PCa patients.
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Prostatectomía , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Anciano , Persona de Mediana Edad , Medición de Riesgo , Prostatectomía/métodos , Estudios Retrospectivos , Invasividad Neoplásica , Algoritmos , Extensión Extranodal , Próstata/patologíaRESUMEN
BACKGROUND AND OBJECTIVE: Targeted biopsy of the index prostate cancer (PCa) lesion on multiparametric magnetic resonance imaging (MRI) is effective in reducing the risk of overdiagnosis of indolent PCa. However, it remains to be determined whether MRI-targeted biopsy can lead to a stage shift via overgrading of the index lesion by focusing only on the highest-grade component, and to a subsequent risk of overtreatment. Our aim was to assess whether overgrading on MRI-targeted biopsy may lead to overtreatment, using radical prostatectomy (RP) specimens as the reference standard. METHODS: Patients with clinically localized PCa who had positive MRI findings (Prostate Imaging-Reporting and Data System [PI-RADS] score ≥3) and Gleason grade group (GG) ≥2 disease detected on MRI-targeted biopsy were retrospectively identified from a prospectively maintained database that records all RP procedures from eight referral centers. Biopsy grade was defined as the highest grade detected. Downgrading was defined as lower GG for the RP specimen than for MRI-targeted biopsy. Overtreatment was defined as downgrading to RP GG 1 for cases with GG ≥2 on biopsy, or to RP low-burden GG 2 for cases with GG ≥3 on biopsy. KEY FINDINGS AND LIMITATIONS: We included 1020 consecutive biopsy-naïve patients with GG ≥2 PCa on MRI-targeted biopsy in the study. Pathological analysis of RP specimens showed downgrading in 178 patients (17%). The transperineal biopsy route was significantly associated with a lower risk of downgrading (odds ratio 0.364, 95% confidence interval 0.142-0.814; p = 0.022). Among 555 patients with GG 2 on targeted biopsy, only 18 (3.2%) were downgraded to GG 1 on RP. Among 465 patients with GG ≥3 on targeted biopsy, three (0.6%) were downgraded to GG 1 and seven were downgraded to low-burden GG 2 on RP. The overall risk of overtreatment due to targeted biopsy was 2.7% (28/1020). CONCLUSIONS AND CLINICAL IMPLICATIONS: Our multicenter study revealed no strong evidence that targeted biopsy results could lead to a high risk of overtreatment.
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Biopsia Guiada por Imagen , Clasificación del Tumor , Neoplasias de la Próstata , Humanos , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Masculino , Anciano , Biopsia Guiada por Imagen/métodos , Estudios Retrospectivos , Persona de Mediana Edad , Sobretratamiento , Prostatectomía , Imagen por Resonancia Magnética , Imágenes de Resonancia Magnética MultiparamétricaRESUMEN
BACKGROUND AND OBJECTIVE: A notable paradigm shift has emerged in the choice of prostate biopsy approach, with a transition from transrectal biopsy (TRBx) to transperineal biopsy (TPBx) driven by the lower risk of severe urinary tract infections. The impact of this change on detection of clinically significant prostate cancer (csPCa) remains a subject of debate. Our aim was to compare the csPCa detection rate of TRBx and TPBx. METHODS: Patients who underwent magnetic resonance imaging (MRI)-targeted and systematic biopsies for clinically localized PCa at 15 European referral centers from 2016 to 2023 were included. A propensity score matching (PSM) analysis was performed to minimize selection biases. Logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). KEY FINDINGS AND LIMITATIONS: Of 3949 patients who met the study criteria, 2187 underwent TRBx and 1762 underwent TPBx. PSM resulted in 1301 matched pairs for analysis. Patient demographics and tumor characteristics were comparable in the matched cohorts. TPBx versus TRBx was associated with greater detection of csPCa, whether defined as International Society of Urological Pathology grade group ≥2 (51% vs 45%; OR 1.37, 95% CI 1.15-1.63; p = 0.001) or grade group ≥3 (29% vs 23%; OR 1.38, 95% CI 1.13-1.67; p = 0.001). Similar results were found when considering MRI-targeted biopsy alone and after stratifying patients according to tumor location, Prostate Imaging-Reporting and Data System score, and clinical features. Limitations include the retrospective nature of the study and the absence of centralized MRI review. CONCLUSIONS: Our findings bolster existing understanding of the additional advantages offered by TPBx. Further randomized trials to fully validate these findings are awaited. PATIENT SUMMARY: We compared the rate of detection of clinically significant prostate cancer with magnetic resonance imaging (MRI)-guided biopsies in which the sample needle is passed through the perineum or the rectum. Our results suggest that the perineal approach is associated with better detection of aggressive prostate cancer.
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BACKGROUND: Systematic biopsy (SB) combined with magnetic resonance imaging (MRI)-targeted biopsy is still recommended considering the risk of missing clinically significant prostate cancer (csPCa). OBJECTIVE: To evaluate the added value in csPCa detection on side-specific SB relative to MRI lesion and to externally validate the Noujeim risk stratification model that predicts the risk of csPCa on distant SB cores relative to the index MRI lesion. DESIGN, SETTING, AND PARTICIPANTS: Overall, 4841 consecutive patients diagnosed by MRI-targeted biopsy and SB for Prostate Imaging Reporting and Data System score ≥3 lesions were identified from a prospectively maintained database between January 2016 and April 2023 at 15 European referral centers. A total of 2387 patients met the inclusion criteria and were included in the analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: McNemar's test was used to compare the csPCa detection rate between several biopsy strategies including MRI-targeted biopsy, side-specific SB, and a combination of both. Model performance was evaluated in terms of discrimination using area under the receiver operation characteristic curve (AUC), calibration plots, and decision curve analysis. Clinically significant prostate cancer was defined as International Society of Urological Pathology grade group ≥2. RESULTS AND LIMITATIONS: Overall, the csPCa detection rate was 49%. Considering MRI-targeted biopsy as reference, the added values in terms of csPCa detection were 5.8% (relative increase of 13%), 4.2% (relative increase of 9.8%), and 2.8% (relative increase of 6.1%) for SB, ipsilateral SB, and contralateral SB, respectively. Only 35 patients (1.5%) exclusively had csPCa on contralateral SB (p < 0.001). Considering patients with csPCa on MRI-targeted biopsy and ipsilateral SB, the upgrading rate was 2% (20/961) using contralateral SB (p < 0.001). The Noujeim model exhibited modest performance (AUC of 0.63) when tested using our validation set. CONCLUSIONS: The added value of contralateral SB was negligible in terms of cancer detection and upgrading rates. The Noujeim model could be included in the decision-making process regarding the appropriate prostate biopsy strategy. PATIENT SUMMARY: In the present study, we collected a set of patients who underwent magnetic resonance imaging (MRI)-targeted and systematic biopsies for the detection of prostate cancer. We found that biopsies taken at the opposite side of the MRI suspicious lesion have a negligible impact on cancer detection. We also validate a risk stratification model that predicts the risk of cancer on biopsies beyond 10 mm from the initial lesion, which could be used in daily practice to improve the personalization of the prostate biopsy.
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INTRODUCTION AND METHODS: Prostate biopsy (PB) is an essential step in the diagnosis and active surveillance of prostate cancer (PCa). Transperineal PB (TP-PB) is now the recommended approach and is mostly conducted under local anesthesia. However, this procedure can potentially cause anxiety for patients, given the oncological context and the fear of peri-procedural pain and complications. The objective of this narrative review is to summarize the currently available tools for the management of peri-interventional anxiety during TP-PB, with a particular emphasis on the potential role of virtual reality (VR) in this setting. RESULTS: In TP-PB, preoperative anxiety can lead to increased pain perception, longer procedure time, and decreased patient satisfaction. Pharmacological and non-pharmacological approaches have been explored to reduce anxiety, such as premedication, deep sedation, education, relaxation techniques, hypnosis, and music therapy, albeit with mixed results. VR has recently emerged in the technological armamentarium for managing pain and anxiety, and the efficiency of this technology has been evaluated in various medical fields, including pediatrics, gastroenterology, urology, gynecology, and psychiatry. CONCLUSION: Despite the paucity of available data, VR appears to be a safe and effective technique in reducing anxiety in many procedures, even in frail patients. No studies have evaluated the role of VR in TP-PB. Future research should thus explore the optimal way to implement VR technology and any potential benefits for TP-PB patients.
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Ansiedad , Biopsia , Próstata , Humanos , Masculino , Anestesia Local , Ansiedad/etiología , Ansiedad/prevención & control , Biopsia/efectos adversos , Biopsia/psicología , Dolor , Próstata/patologíaRESUMEN
Immersive technologies (IT) are undergoing significant expansion in medicine. Among them, virtual augmented or mixed reality offers an interactive or immersive virtual environments to its users, opening a wide array of applications in modern medicine. IT seem particularly interesting in urology, offering a real-time overlay of diagnostic information onto the surgical field and helping visualizing complex anatomical structures, potentially enhancing intraoperative decision-making. Training through realistic simulations with IT represent an excellent and secure tool for trainees and urologists. Finally, patient's comfort during procedures under local anesthesia could be optimized with the use of IT. Further studies are awaited to validate their effectiveness and evaluate their costs to permit their integration into routine medical practice.
Les technologies immersives (TI) connaissent une expansion significative dans le domaine médical. Parmi elles, la réalité virtuelle, augmentée ou mixte offre un environnement virtuel interactif ou immersif à ses utilisateurs, avec une vaste palette d'applications dans la médecine moderne. En urologie, elles sont particulièrement intéressantes, notamment dans la superposition d'informations diagnostiques en temps réel sur le champ opératoire ou la visualisation de structures anatomiques complexes, ce qui peut améliorer la prise de décision peropératoire. La formation à l'aide de simulations réalistes représente un excellent outil pour l'urologue. Enfin, le confort du patient lors des gestes techniques sous anesthésie locale peut être optimisé à l'aide des TI. Des études ultérieures sont nécessaires pour valider leur efficacité et évaluer leur coût avant une intégration dans la pratique médicale courante.
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Medicina , Urología , Humanos , TecnologíaRESUMEN
PURPOSE: Patients who undergo robot-assisted laparoscopic radical prostatectomy (RARP) may present concurrent or secondary inguinal hernia (IH). Surgical repair of IH simultaneously with RARP has been reported. We aimed to assess the long-term efficacy of concurrent prosthetic IH repair with RARP. METHODS: Data for consecutive patients undergoing concurrent IH repair with RARP for localized prostate cancer at our institution between 2006 and 2017 were retrospectively analysed. Patients were matched based on age, BMI, and year of surgery, with patients undergoing RARP alone. IH repair was performed with a polyester mesh. Efficacy of IH repair was the primary outcome. Patient characteristics, perioperative data, recurrence and treatment were recorded. RESULTS: A total of 136 men were included, 50% treated by RARP and concurrent IH, 50% by RARP alone. Mean age was 65 years (SD 6) and mean BMI 26.8 (SD 2.5). IH was diagnosed preoperatively in 42 patients (62%) or intraoperatively in 26 patients (38%). A total 18 patients (26%) had bilateral hernias and 50 patients had unilateral hernias (right 31%, left 43%). There was no significant difference between the two groups regarding perioperative data. The herniorrhaphy added 34 min to the operative time (p < 0.001). After a mean follow-up of 106 months [SD 38], 9 patients (13%) presented recurrence of IH, with a mean time to recurrence of 43 months [SD 35]. Age was significantly associated with IH recurrence (p = 0.0007). CONCLUSION: Concomitant IH repair and RARP appear to be a safe procedure with good long-term safety and efficacy, without significantly increasing morbidity.
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Hernia Inguinal , Laparoscopía , Neoplasias de la Próstata , Procedimientos Quirúrgicos Robotizados , Robótica , Masculino , Humanos , Anciano , Hernia Inguinal/complicaciones , Hernia Inguinal/cirugía , Hernia Inguinal/diagnóstico , Estudios Retrospectivos , Herniorrafia/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Prostatectomía/métodos , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/cirugía , Laparoscopía/métodosRESUMEN
INTRODUCTION: To determine associations between prostate cancer (PCa) tumor burden measured on biopsy or multiparametric magnetic resonance imaging (mpMRI) and outcomes in intermediate-risk (IR) International Society of Urological Pathology (ISUP) grade 2 men managed with primary radical prostatectomy (RP). METHODS: This retrospective, multicenter study was conducted in eight referral centers. The cohort included IR PCa patients who had ISUP 2 at biopsy. We defined biopsy tumor burden as low/high based on the absence/presence of more than 25% positive cores. Tumor burden on imaging was defined as low/high based on maximum lesion diameter, <15 mm and ≥15 mm at mpMRI, respectively. The histological endpoint of the study was adverse features at RP, defined as ≥pT3a stage and/or lymph node invasion and/or ISUP ≥3 at final pathology. The clinical endpoint was biochemical recurrence (BCR) after RP. RESULTS: A total of 698 IR patients was included, of whom 335 (48%) had adverse features. In multivariate logistic regression analysis, there was no statistical association between tumor burden at biopsy and adverse features (p = 0.7). Tumor size ≥15 mm at mpMRI was significantly associated with adverse pathology (OR 1.65, 95%CI 1.14-2.39; p = 0.01). No significant association was observed between tumor burden at biopsy and BCR (p = 0.4). Tumor size ≥15 mm at mpMRI was significantly associated with BCR (HR 1.96, 95% CI 1.01-3.80; p = 0.04). CONCLUSIONS: Our data support extending the inclusion criteria to ISUP 2 men with >25% positive cores, provided they have a low tumor size at mpMRI (<15 mm). Prospective studies should be performed to validate these findings.
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Renal cell carcinoma (RCC) and its principal subtype, clear cell RCC, are the most diagnosed kidney cancer. Despite substantial improvement over the last decades, current pharmacological intervention still fails to achieve long-term therapeutic success. RCC is characterized by a high intra- and inter-tumoral heterogeneity and is heavily influenced by the crosstalk of the cells composing the tumor microenvironment, such as cancer-associated fibroblasts, endothelial cells and immune cells. Moreover, multiple physicochemical properties such as pH, interstitial pressure or oxygenation may also play an important role. These elements are often poorly recapitulated in in vitro models used for drug development. This inadequate recapitulation of the tumor is partially responsible for the current lack of an effective and curative treatment. Therefore, there are needs for more complex in vitro or ex vivo drug screening models. In this review, we discuss the current state-of-the-art of RCC models and suggest strategies for their further development.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Células Endoteliales/patología , Neoplasias Renales/tratamiento farmacológico , Microambiente TumoralRESUMEN
BACKGROUND: Suitable selection criteria for focal therapy (FT) are crucial to achieve success in localized prostate cancer (PCa). OBJECTIVE: To develop a multivariable model that better delineates eligibility for FT and reduces undertreatment by predicting unfavorable disease at radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: Data were retrospectively collected from a prospective European multicenter cohort of 767 patients who underwent magnetic resonance imaging (MRI)-targeted and systematic biopsies followed by RP in eight referral centers between 2016 and 2021. The Imperial College of London eligibility criteria for FT were applied: (1) unifocal MRI lesion with Prostate Imaging-Reporting and Data System score of 3-5; (2) prostate-specific antigen (PSA) ≤20 ng/ml; (3) cT2-3a stage on MRI; and (4) International Society of Urological Pathology grade group (GG) 1 and ≥6 mm or GG 2-3. A total of 334 patients were included in the final analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was unfavorable disease at RP, defined as GG ≥4, and/or lymph node invasion, and/or seminal vesicle invasion, and/or contralateral clinically significant PCa. Logistic regression was used to assess predictors of unfavorable disease. The performance of the models including clinical, MRI, and biopsy information was evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis. A coefficient-based nomogram was developed and internally validated. RESULTS AND LIMITATIONS: Overall, 43 patients (13%) had unfavorable disease on RP pathology. The model including PSA, clinical stage on digital rectal examination, and maximum lesion diameter on MRI had an AUC of 73% on internal validation and formed the basis of the nomogram. Addition of other MRI or biopsy information did not significantly improve the model performance. Using a cutoff of 25%, the proportion of patients eligible for FT was 89% at the cost of missing 30 patients (10%) with unfavorable disease. External validation is required before the nomogram can be used in clinical practice. CONCLUSIONS: We report the first nomogram that improves selection criteria for FT and limits the risk of undertreatment. PATIENT SUMMARY: We conducted a study to develop a better way of selecting patients for focal therapy for localized prostate cancer. A novel predictive tool was developed using the prostate-specific antigen (PSA) level measured before biopsy, tumor stage assessed via digital rectal examination, and lesion size on magnetic resonance imaging (MRI) scans. This tool improves the prediction of unfavorable disease and may reduce the risk of undertreatment of localized prostate cancer when using focal therapy.
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Nomogramas , Neoplasias de la Próstata , Masculino , Humanos , Antígeno Prostático Específico , Estudios Retrospectivos , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Biopsia/métodos , Imagen por Resonancia Magnética/métodosRESUMEN
Background: Patient preferences for treatment outcomes are important to guide decision-making in clinical practice, but little is known about the preferences of patients with metastatic hormone-sensitive prostate cancer (mHSPC). Objective: To evaluate patient preferences regarding the attributed benefits and harms of systemic treatments for mHSPC and preference heterogeneity between individuals and specific subgroups. Design setting and participants: We conducted an online discrete choice experiment (DCE) preference survey among 77 patients with metastatic prostate cancer (mPC) and 311 men from the general population in Switzerland between November 2021 and August 2022. Outcome measurements and statistical analysis: We evaluated preferences and preference heterogeneity related to survival benefits and treatment-related adverse effects using mixed multinomial logit models and estimated the maximum survival time participants were willing to trade to avert specific adverse effects. We further assessed characteristics associated with different preference patterns via subgroup and latent class analyses. Results and limitations: Patients with mPC showed an overall stronger preference for survival benefits in comparison to men from the general population (p = 0.004), with substantial preference heterogeneity between individuals within the two samples (both p < 0.001). There was no evidence of differences in preferences for men aged 45-65 yr versus ≥65 yr, patients with mPC in different disease stages or with different adverse effect experiences, or general population participants with and without experiences with cancer. Latent class analyses suggested the presence of two groups strongly preferring either survival or the absence of adverse effects, with no specific characteristic clearly associated with belonging to either group. Potential biases due to participant selection, cognitive burden, and hypothetical choice scenarios may limit the study results. Conclusions: Given the relevant heterogeneity in participant preferences regarding the benefits and harms of treatment for mHSPC, patient preferences should be explicitly discussed during decision-making in clinical practice and reflected in clinical practice guidelines and regulatory assessment regarding treatment for mHSPC. Patient summary: We examined the preferences (values and perceptions) of patients and men from the general population regarding the benefits and harms of treatment for metastatic prostate cancer. There were large differences between men in how they balanced the expected survival benefits and potential adverse effects. While some men strongly valued survival, others more strongly valued the absence of adverse effects. Therefore, it is important to discuss patient preferences in clinical practice.
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PURPOSE: To summarize evidence regarding the use of neoadjuvant (NAC) and adjuvant chemotherapy (AC) among patients treated with radical nephroureterectomy (RNU). METHODS: A comprehensive literature search of PubMed (MEDLINE), EMBASE and the Cochrane library was performed to identify any original or review article on the role of perioperative chemotherapy for UTUC patients treated with RNU. RESULTS: With regards to NAC, retrospective studies consistently suggested that it may be associated with better pathological downstaging (pDS) ranging from 10.8 to 80% and complete response (pCR) ranging from 4.3 to 15%, while decreasing the risk of recurrence and death as compared to RNU alone. Even higher pDS ranging from 58 to 75% and pCR ranging from 14 to 38% were observed in single-arm phase II trials. With regards to AC, retrospective studies provided conflicting results although the largest report from the National Cancer Database suggested an overall survival benefit in pT3-T4 and/or pN + patients. In addition, a phase III randomized controlled trial showed that the use of AC was associated with a disease-free survival benefit (HR = 0.45; 95% CI = [0.30-0.68]; p = 0.0001) in pT2-T4 and/or pN + patients with acceptable toxicity profile. This benefit was consistent in all subgroups analyzed. CONCLUSIONS: Perioperative chemotherapy improves oncological outcomes associated with RNU. Given the impact of RNU on renal function, the rational is stronger for the use of NAC which impacts final pathology and potentially prolongs survival. However, the level of evidence is stronger for the use of AC that has been proven to decrease the risk of recurrence after RNU with a potential survival benefit.
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Carcinoma de Células Transicionales , Neoplasias Ureterales , Neoplasias de la Vejiga Urinaria , Humanos , Nefroureterectomía/métodos , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/cirugía , Carcinoma de Células Transicionales/patología , Neoplasias de la Vejiga Urinaria/cirugía , Estudios Retrospectivos , Quimioterapia Adyuvante/métodos , Neoplasias Ureterales/tratamiento farmacológico , Neoplasias Ureterales/cirugía , Neoplasias Ureterales/patología , Ensayos Clínicos Controlados Aleatorios como Asunto , Ensayos Clínicos Fase III como AsuntoRESUMEN
PURPOSE: To develop new selection criteria for active surveillance (AS) in intermediate-risk (IR) prostate cancer (PCa) patients. METHODS: Retrospective study including patients from 14 referral centers who underwent pre-biopsy mpMRI, image-guided biopsies and radical prostatectomy. The cohort included biopsy-naive IR PCa patients who met the following inclusion criteria: Gleason Grade Group (GGG) 1-2, PSA < 20 ng/mL, and cT1-cT2 tumors. We relied on a recursive machine learning partitioning algorithm developed to predict adverse pathological features (i.e., ≥ pT3a and/or pN + and/or GGG ≥ 3). RESULTS: A total of 594 patients with IR PCa were included, of whom 220 (37%) had adverse features. PI-RADS score (weight:0.726), PSA density (weight:0.158), and clinical T stage (weight:0.116) were selected as the most informative risk factors to classify patients according to their risk of adverse features, leading to the creation of five risk clusters. The adverse feature rates for cluster #1 (PI-RADS ≤ 3 and PSA density < 0.15), cluster #2 (PI-RADS 4 and PSA density < 0.15), cluster #3 (PI-RADS 1-4 and PSA density ≥ 0.15), cluster #4 (normal DRE and PI-RADS 5), and cluster #5 (abnormal DRE and PI-RADS 5) were 11.8, 27.9, 37.3, 42.7, and 65.1%, respectively. Compared with the current inclusion criteria, extending the AS criteria to clusters #1 + #2 or #1 + #2 + #3 would increase the number of eligible patients (+ 60 and + 253%, respectively) without increasing the risk of adverse pathological features. CONCLUSIONS: The newly developed model has the potential to expand the number of patients eligible for AS without compromising oncologic outcomes. Prospective validation is warranted.
Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Antígeno Prostático Específico/análisis , Estudios Retrospectivos , Imagen por Resonancia Magnética , Espera Vigilante , Biopsia Guiada por ImagenRESUMEN
PURPOSE: Despite surgical and anesthetic progress, radical cystectomy for bladder cancer remains one of the most morbid surgeries in urology. The objective of our study was to describe intraoperative complications and to assess the impact of surgical approach on morbidity. METHODS: We retrospectively reviewed medical records of patients treated by radical cystectomy for localized muscle invasive bladder cancer between 2015 and 2020, following the Martin et al. criteria for complications reports. All intraoperative adverse events were graded according to the EAUiaiC scores. Multivariate regression models were used to determine predicting factors of complications. RESULTS: A total of 318 patients were included for analysis. Among them, 17 patients (5.4%) presented an intraoperative complication. No preoperative oncological or clinical factor was associated with the occurrence of an intraoperative complication. Surgical approach had no impact on morbidity. Both overall survival (HR 2.02; CI95% 0.87-4.68; p = 0.101) and recurrence-free survival (HR 1.856; CI95% 0.804-4.284; p = 0.147) were not associated with intraoperative complication. CONCLUSION: Radical cystectomy remains a highly morbid surgery and surgical approach did not improve the complication rate. Perioperative morbidity has a significant impact on patient survival. The association between intraoperative and postoperative complications illustrates the cumulative effect of perioperative events that are associated with survival.
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Cistectomía , Neoplasias de la Vejiga Urinaria , Humanos , Cistectomía/efectos adversos , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Vejiga Urinaria , Músculos , Complicaciones Posoperatorias/etiologíaRESUMEN
Over the last year, urologic progress remains driven by evolutions in oncological and functionnal urology. Prostate cancer imaging modalities are improving, as well as treatment options for advanced stages. Kidney and bladder cancer are benefiting from new treatment modalities including immunotherapy, whose role in the peri-operative setting is still unclear. Surveillance startegies for testicular cancer has been greatly simplified, for the benefit of the patients. In functional urology, a new therapeutic class in now available for the treatment of overactive bladder. Mutliples alternatives to transurethral resection are emerging in the surgical treatment of benign prostatic hypertrophy, whose expected benefits will need to be validated by long-term studies.
Les progrès de cette année sont marqués par des avancées en uro-oncologie et urologie fonctionnelle. La prise en charge du cancer de la prostate s'améliore tant dans la qualité de son diagnostic que dans le traitement des stades avancés. Les cancers du rein et de la vessie bénéficient de nouvelles options de traitement incluant l'immunothérapie, qui cherche encore sa place en périopératoire. Quant au cancer des testicules, il a vu sa surveillance grandement simplifiée au bénéfice des patients. En urologie fonctionnelle, une nouvelle classe thérapeutique est désormais disponible pour le traitement de l'hyperactivité vésicale et de multiples alternatives à la résection endoscopique de la prostate émergent dans le traitement chirurgical de l'hypertrophie bénigne de la prostate. Il faudra toutefois valider les avantages espérés par des études à long terme.
Asunto(s)
Hiperplasia Prostática , Neoplasias de la Próstata , Neoplasias Testiculares , Urología , Masculino , Humanos , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/cirugía , Procedimientos Quirúrgicos Urológicos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/cirugíaRESUMEN
Background: Increasing use of multiparametric magnetic resonance imaging (mpMRI) has come with heterogeneity in image quality. The Prostate Imaging Quality (PI-QUAL) score is under scrutiny to assess its usefulness in predicting clinical outcomes. Objective: To compare upstaging of localized disease on mpMRI (mrT2) to locally invasive disease in radical prostatectomy (RP) specimens (≥pT3a) in relation to PI-QUAL. Design setting and participants: Patients treated with RP between 2015 and 2020 who underwent 1.5-3-T mpMRI within 6 mo before surgery and had systematic and mpMRI-US targeted biopsies were included. mpMRI scans were retrospectively assigned a PI-QUAL score, and prospectively acquired Prostate Imaging-Recording and Data System (PI-RADS) scores (version 2.0 or 2.1) were used. PI-QUAL scores were categorized as nondiagnostic (PI-QUAL <3), sufficient (PI-QUAL 3), or optimal (PI-QUAL >3). Outcome measurements and statistical analysis: We assessed the relationship between the PI-QUAL score and upstaging using multivariate logistic regression. mpMRI, clinical, and pathological findings were compared using χ2 tests and analysis of variance. Results and limitations: We identified 351 patients, of whom 40 (11.4%) had PI-QUAL <3, 57 (16.3%) had PI-QUAL 3, and 254 (72.3%) had PI-QUAL >3 scores. The distribution of PI-QUAL <3 (0-33.6%; p < 0.001) and PI-QUAL >3 (37.3-100%; p < 0.001) scores varied widely among centers. PI-QUAL ≥3 in comparison to PI-QUAL <3 was associated with a lower rate of upstaging (19% vs 35%; p = 0.02), greater detection of mrT3a and mrT3b prostate cancer (17.0% vs 2.5%; p = 0.016), a higher rate of PI-RADS 5 lesions (47% vs 27.5%; p = 0.002), a higher number of suspicious lesion (PI-RADS ≥3: 34.7% vs 15%; p = 0.012), and higher detection rates for aggregated (50.7% vs 22.5%; p = 0.001) and late (21.2% vs 0%; p < 0.001) extraprostatic extension. On multivariate analysis, PI-QUAL<3 was associated with more frequent upstaging in the RP specimen (odds ratio 3.4; p = 0.01). Conclusions: In comparison to PI-QUAL ≥3, PI-QUAL <3 was significantly associated with a higher rate of upstaging from organ-confined disease on mpMRI to locally advanced disease on pathology, lower detection rates for PI-RADS 5 lesions and extraprostatic extension, and a lower number of suspicious lesions. Patient summary: Poor image quality for magnetic resonance imaging (MRI) scans of the prostate is associated with underestimation of the stage of prostate cancer.