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BACKGROUND: Numerous studies have shown that magnetic resonance imaging (MRI)-targeted biopsy approaches are superior to traditional systematic transrectal ultrasound guided biopsy (TRUS-Bx). The optimal number of biopsy cores to be obtained per lesion identified on multiparametric MRI (mpMRI) images, however, remains a matter of debate. The aim of this study was to evaluate the incremental value of additional biopsy cores in an MRI-targeted "in-bore"-biopsy (MRI-Bx) setting. PATIENTS AND METHODS: Two hundred and forty-five patients, who underwent MRI-Bx between June 2014 and September 2021, were included in this retrospective single-center analysis. All lesions were biopsied with at least five biopsy cores and cumulative detection rates for any cancer (PCa) as well as detection rates of clinically significant cancers (csPCa) were calculated for each sequentially labeled biopsy core. The cumulative per-core detection rates are presented as whole numbers and as proportion of the maximum detection rate reached, when all biopsy cores were considered. CsPCa was defined as Gleason Score (GS) ≥ 7 (3 + 4). RESULTS: One hundred and thirty-two of 245 Patients (53.9%) were diagnosed with prostate cancer and csPCa was found in 64 (26.1%) patients. The first biopsy core revealed csPCa/ PCa in 76.6% (49/64)/ 81.8% (108/132) of cases. The second, third and fourth core found csPCa/ PCa not detected by previous cores in 10.9% (7/64)/ 8.3% (11/132), 7.8% (5/64)/ 5.3% (7/132) and 3.1% (2/64)/ 3% (4/132) of cases, respectively. Obtaining one or more cores beyond the fourth biopsy core resulted in an increase in detection rate of 1.6% (1/64)/ 1.5% (2/132). CONCLUSION: We found that obtaining five cores per lesion maximized detection rates. If, however, future research should establish a clear link between the incidence of serious complications and the number of biopsy cores obtained, a three-core biopsy might suffice as our results suggest that about 95% of all csPCa are detected by the first three cores.
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Biópsia Guiada por Imagem , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Estudos Retrospectivos , Idoso , Biópsia Guiada por Imagem/métodos , Pessoa de Meia-Idade , Próstata/patologia , Próstata/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Biópsia com Agulha de Grande Calibre/métodos , Gradação de Tumores , Imagem por Ressonância Magnética Intervencionista/métodos , Imageamento por Ressonância Magnética Multiparamétrica/métodosRESUMO
OBJECTIVES: To compare multiparametric magnetic resonance imaging (mpMRI) findings, US-MR fusion prostate biopsy results and whole-mount thin-section histopathology after radical prostatectomy. PATIENTS AND METHODS: Overall 259 patients, who had undergone mpMRI with lesions reported as PI-RADS 3-5, underwent a MR-US fusion biopsy between 2018 and 2020. Overall 186 biopsies yielded prostate cancer and 104 patients subsequently underwent endoscopic extraperitoneal radical prostatectomy. Histopathology of biopsies was compared to the final histopathology in whole mount thin sections after radical prostatectomy by means of descriptive statistics, and further, the lesions from mpMRT were compared to whole mount histology. RESULTS: Prostate cancer was diagnosed in 186 (71.8%) of 259 patients (median age 69.2 y, range 42-82 y, median PSA 7.8 ng/ml, range 2.1-31.3 ng/ml). Of those, 95 (51,1%) underwent radical endoscopic prostatectomy, and 80 (43%) chose radiotherapy or active surveillance. In 52/95 (54,7%) with RPE additional lesions were found in the final histological whole mount sections not described at mpMRI. 22/95 (23,2%) of RPE patients had ≥ 1 additional Gleason score ≥ 7 lesions, 23 /259 (8,4%) of biopsies, respectively. The Gleason score after surgery was upgraded in 37/95 (38,9%) and downgraded in 18/95 (18,9%) patients. CONCLUSION: If we compare all 259 performed biopsies with the final histological whole mount sections which showed additional lesions with Gleason ≥ 7 (23,2%), it can be assumed that up to 10% of clinical significant carcinomas are missed during primary assessment via mpMRI. The majority of additional findings after RP were intermediate/high risk tumors. Upgrades from low-risk to intermediate or high-risk occurred.
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Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Masculino , Humanos , Idoso , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética/métodos , Biópsia Guiada por Imagem/métodos , Biópsia , Prostatectomia/métodos , Gradação de Tumores , Estudos RetrospectivosRESUMO
The gene coding for histone methyltransferase KMT2D is found among the top mutated genes in upper tract urothelial carcinoma (UTUC); however, there is a lack of data regarding its association with clinicopathologic features as well as survival outcomes. Therefore, we aimed to investigate KMT2D expression, mutation patterns, and their utility as prognostic biomarkers in patients with UTUC. A single-center study was conducted on tumor specimens from 51 patients treated with radical nephroureterectomy (RNU). Analysis of KMT2D protein expression was performed using immunohistochemistry (IHC). Customized next-generation sequencing (NGS) was used to assess alterations in KMT2D exons. Cox regression was used to assess the relationship of KMT2D protein expression and mutational status with survival outcomes. KMT2D expression was increased in patients with a previous history of bladder cancer (25% vs. 0%, p = 0.02). The NGS analysis of KMT2D exons in 27 UTUC tumors revealed a significant association between pathogenic KMT2D variants and tumor location (p = 0.02). Pathogenic KMT2D variants were predominantly found in patients with non-pelvic or multifocal tumors (60% vs. 14%), while the majority of patients with a pelvic tumor location (81% vs. 20%) did not harbor pathogenic KMT2D alterations. Both IHC and NGS analyses of KMT2D failed to detect a statistically significant association between KMT2D protein or KMT2D gene alteration status and clinical variables such as stage/grade of the disease or survival outcomes (all p > 0.05). KMT2D alterations and protein expression were associated with UTUC features such as multifocality, ureteral location, and previous bladder cancer. While KMT2D protein expression and KMT2D mutational status do not seem to have prognostic value in UTUC, they appear to add information to improve clinical decision-making regarding the type of therapy.
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Androgen deprivation therapy (ADT) remains a key approach in the treatment of prostate cancer (PCa). However, PCa inevitably relapses and becomes ADT resistant. Besides androgens, there is evidence that thyroid hormone thyroxine (T4) and its active form 3,5,3'-triiodo-L-thyronine (T3) are involved in the progression of PCa. Epidemiologic evidences show a higher incidence of PCa in men with elevated thyroid hormone levels. The thyroid hormone binding protein µ-Crystallin (CRYM) mediates intracellular thyroid hormone action by sequestering T3 and blocks its binding to cognate receptors (TRα/TRß) in target tissues. We show in our study that low CRYM expression levels in PCa patients are associated with early biochemical recurrence and poor prognosis. Moreover, we found a disease stage-specific expression of CRYM in PCa. CRYM counteracted thyroid and androgen signaling and blocked intracellular choline uptake. CRYM inversely correlated with [18F]fluoromethylcholine (FMC) levels in positron emission tomography/magnetic resonance imaging of PCa patients. Our data suggest CRYM as a novel antagonist of T3- and androgen-mediated signaling in PCa. The role of CRYM could therefore be an essential control mechanism for the prevention of aggressive PCa growth.
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Cristalinas/genética , Cristalinas/metabolismo , Regulação para Baixo , Neoplasias da Próstata/patologia , Transdução de Sinais , Linhagem Celular Tumoral , Colina/administração & dosagem , Colina/análogos & derivados , Estudos de Coortes , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Metabolômica , Estadiamento de Neoplasias , Células PC-3 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Receptores dos Hormônios Tireóideos/genética , Análise de Sequência de RNA , Análise Serial de Tecidos , Tri-Iodotironina/antagonistas & inibidores , Tri-Iodotironina/metabolismo , Cristalinas muRESUMO
BACKGROUND: Bacillus Calmette-Guérin (BCG) immunotherapy, the standard adjuvant intravesical therapy for some intermediate and most high-risk non-muscle invasive bladder cancers (NMIBCs), suffers from a heterogenous response rate. Molecular markers to help guide responses are scarce and currently not used in the clinical setting. METHODS: To identify novel biomarkers and pathways involved in response to BCG immunotherapy, we performed a genome-wide DNA methylation analysis of NMIBCs before BCG therapy. Genome-wide DNA methylation profiles of DNA isolated from tumors of 26 BCG responders and 27 failures were obtained using the Infinium MethylationEPIC BeadChip. RESULTS: Distinct DNA methylation patterns were found by genome-wide analysis in the two groups. Differentially methylated CpG sites were predominantly located in gene promoters and gene bodies associated with bacterial invasion of epithelial cells, chemokine signaling, endocytosis, and focal adhesion. In total, 40 genomic regions with a significant difference in methylation between responders and failures were detected. The differential methylation state of six of these regions, localized in the promoters of the genes GPR158, KLF8, C12orf42, WDR44, FLT1, and CHST11, were internally validated by bisulfite-sequencing. GPR158 promoter hypermethylation was the best predictor of BCG failure with an AUC of 0.809 (p-value < 0.001). CONCLUSIONS: Tumors from BCG responders and BCG failures harbor distinct DNA methylation profiles. Differentially methylated DNA regions were detected in genes related to pathways involved in bacterial invasion of cells or focal adhesion. We identified candidate DNA methylation biomarkers that may help to predict patient prognosis after external validation in larger, well-designed cohorts.
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Adjuvantes Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Metilação de DNA , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Ilhas de CpG , Feminino , Estudo de Associação Genômica Ampla , Heterocromatina , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologiaRESUMO
Purpose: To assess the prognostic significance of the nuclear receptor binding SET protein 2 (NSD2), a co-activator of the NFkB-pathway, on tumour progression in patients with advanced prostate cancer (PCa).Methods: We retrospectively assessed NSD2 expression in 53 patients with metastatic and castration-resistant PCa. Immunohistochemical staining for NSD2 was carried out on specimen obtained from palliative resection of the prostate. Univariable and multivariable analyses were performed to assess the association between NSD2 expression and PCa progression.Results: Of the 53 patients, 41 had castration-resistant PCa and 48 men had metastases at time of tissue acquisition. NSD2 expression was increased in tumour specimen from 42 patients (79.2%). In univariable Cox regression analyses, NSD2 expression was associated with PSA progression, progression on imaging and overall survival (p = 0.04, respectively). In multivariable analyses, NSD2 expression did not retain its association with these endpoints.Conclusions: NSD2 expression is abnormal in almost 80% of patients with advanced PCa. Expression levels of this epigenetic regulator are easily detected by immunohistochemistry while this biomarker exhibited prognostic value for PCa progression and death in univariable analysis. Further studies on NSD2 involvement in PCa proliferation, progression, metastasis and resistance mechanisms are needed.
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Biomarcadores Tumorais/biossíntese , Histona-Lisina N-Metiltransferase/biossíntese , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Proteínas Repressoras/biossíntese , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Humanos , Imuno-Histoquímica/estatística & dados numéricos , Masculino , Prognóstico , Modelos de Riscos Proporcionais , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Estudos Retrospectivos , Análise de SobrevidaRESUMO
We document the case of a young adult female patient who presented with multiple intracerebral and extracerebral bone lesions, the latter most prominently along the vertebral column. The spatially distinct intracerebral lesions included a superficial frontal tumor nodule as well as diffuse enlargement of the pons. Differential diagnoses ranged from neoplastic to inflammatory conditions. Repeated bone biopsies yielded uncharacteristic reactive changes whereas cerebrospinal fluid cytology pointed towards a neoplastic disease. Resection of the superficial frontal tumor nodule prompted the diagnosis of an unusual "gliofibroma" with anaplastic features, WHO grade III. TMZ chemotherapy was initiated and led to intracranial disease stabilization, whereas the bone lesions were progressive. At 16 months after diagnosis, new brain lesions occurred, and further progression of the brain stem lesion led to clinical deterioration and patient death. Postmortem examination confirmed extensively disseminated intracranial disease with unusually striking morphologic heterogeneity across the various lesions ranging from diffuse spindle-celled areas to perivascular rosettes and embryonal-like areas. The morphologic heterogeneity was in contrast to shared epigenomic and copy number profiles supporting a common origin. Of note, molecular markers and DNA methylation-based classifier scores did not allow for unequivocal glioma classification. Ultimately, the bone lesions revealed scattered nests of GFAP-positive cells, thus confirming them as glioma-derived metastases. No other systemic organ involvement was found. In summary, this case 1) illustrates the strikingly heterogeneous morphological landscape of malignant gliomas, 2) serves as an example for rare cases that do not fit in any diagnostic category despite extensive molecular profiling, and 3) highlights the potential of gliomas for early systemic metastases - in the present case with selectivity for the bones.
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Neoplasias Ósseas/secundário , Neoplasias Encefálicas/secundário , Glioma/patologia , Adulto , Feminino , HumanosRESUMO
The aim of the present study was to identify and test a urine marker panel of genes involved in DNA methylation and histone modification for the detection of urothelial carcinoma of the bladder (UCB). RNA samples obtained from the voided urine of 227 patients with asymptomatic microscopic haematuria (AMH) were analysed. Gene array analysis was performed on 18 randomly selected cDNA samples, which revealed that histone deacetylase 9 (HDAC9), HDAC3, tRNA (cytosine-5-)-methyltransferase1 and DNA methyltransferase 1 were differentially expressed between patients with UCB and control subjects. Subsequently, reverse transcription-quantitative polymerase chain reaction analysis was employed to test the performance of the identified four-gene panel on the remaining 209 cDNA samples. In this targeted discovery cohort, all four genes were significantly associated with UCB on univariable analyses [each odds ratio (OR) >2, P<0.05], but only HDAC3 was significant following multivariable analysis (OR=2.8, P=0.011). The addition of HDAC3 to a base risk factor model improved its accuracy by 1.4%. These data suggest that urinary HDAC3 is associated with the presence of UCB in patients with AMH; however, HDAC3 improved the accuracy of the established risk factors only to a marginal extent.
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BACKGROUND: Commercial gene expression assays are guiding clinical decision making in patients with prostate cancer, particularly when considering active surveillance. Given heterogeneity and multifocality of primary prostate cancer, such assays should ideally be robust to the coexistence of unsampled higher grade disease elsewhere in the prostate in order to have clinical utility. Herein, we comprehensively evaluated transcriptomic profiles of primary multifocal prostate cancer to assess robustness to clinically relevant multifocality. METHODS: We designed a comprehensive, multiplexed targeted RNA-sequencing assay capable of assessing multiple transcriptional classes and deriving commercially available prognostic signatures, including the Myriad Prolaris Cell Cycle Progression score, the Oncotype DX Genomic Prostate Score, and the GenomeDX Decipher Genomic Classifier. We applied this assay to a retrospective, multi-institutional cohort of 156 prostate cancer samples. Derived commercial biomarker scores for 120 informative primary prostate cancer samples from 44 cases were determined and compared. RESULTS: Derived expression scores were positively correlated with tumor grade (rS = 0.53-0.73; all P < 0.001), both within the same case and across the entire cohort. In cases of extreme grade-discordant multifocality (co-occurrence of grade group 1 [GG1] and ≥GG4 foci], gene expression scores were significantly lower in low- (GG1) versus high-grade (≥GG4) foci (all P < 0.001). No significant differences in expression scores, however, were observed between GG1 foci from prostates with and without coexisting higher grade cancer (all P > 0.05). CONCLUSIONS: Multifocal, low-grade and high-grade prostate cancer foci exhibit distinct prognostic expression signatures. These findings demonstrate that prognostic RNA expression assays performed on low-grade prostate cancer biopsy tissue may not provide meaningful information on the presence of coexisting unsampled aggressive disease. FUNDING: Prostate Cancer Foundation, National Institutes of Health (U01 CA214170, R01 CA183857, University of Michigan Prostate Specialized Program of Research Excellence [S.P.O.R.E.] P50 CA186786-05, Weill Cornell Medicine S.P.O.R.E. P50 CA211024-01A1), Men of Michigan Prostate Cancer Research Fund, University of Michigan Comprehensive Cancer Center core grant (2-P30-CA-046592-24), A. Alfred Taubman Biomedical Research Institute, and Department of Defense.
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Neoplasias da Próstata/genética , Análise de Sequência de RNA/métodos , Transcriptoma/genética , Tomada de Decisão Clínica/métodos , Expressão Gênica/genética , Genômica/instrumentação , Humanos , Masculino , Técnicas de Diagnóstico Molecular/métodos , Gradação de Tumores , Prognóstico , Próstata/patologia , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Análise de Sequência de RNA/economiaRESUMO
INTRODUCTION: Bladder cancer (BC) is diagnosed by cystoscopy, which is invasive, costly and causes considerable patient discomfort. MicroRNAs (miR) are dysregulated in BC and may serve as non-invasive urine markers for primary diagnostics and monitoring. The purpose of this study was to identify a urinary miR signature that predicts the presence of BC. METHODS: For the detection of potential urinary miR markers, expression of 384 different miRs was analyzed in 16 urine samples from BC patients and controls using a Taqman™ Human MicroRNA Array (training set). The identified candidate gene signature was subsequently validated in an independent cohort of 202 urine samples of patients with BC and controls with microscopic hematuria. The final miR signature was developed from a multivariable logistic regression model. RESULTS: Analysis of the training set identified 14 candidate miRs for further analysis within the validation set. Using backward stepwise elimination, we identified a subset of 6 miRs (let-7c, miR-135a, miR-135b, miR-148a, miR-204, miR-345) that distinguished BC from controls with an area under the curve of 88.3%. The signature was most accurate in diagnosing high-grade non-muscle invasive BC (area under the curveâ¯=â¯92.9%), but was capable to identify both low-grade and high-grade disease as well as non-muscle and muscle-invasive BC with high accuracies. CONCLUSIONS: We identified a 6-gene miR signature that can accurately predict the presence of BC from urine samples, independent of stage and grade. This signature represents a simple urine assay that may help reducing costs and morbidity associated with invasive diagnostics.
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Biomarcadores Tumorais/urina , Regulação Neoplásica da Expressão Gênica , MicroRNAs/urina , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Idoso , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Neoplasias da Bexiga Urinária/urinaRESUMO
PURPOSE: Primary staging of prostate cancer relies on modalities, which are limited. We evaluate simultaneous [68Ga]Ga-PSMA-11 PET (PSMA-PET)/MRI as a new diagnostic method for primary tumor-node-metastasis staging compared with histology and its impact on therapeutic decisions. EXPERIMENTAL DESIGN: We investigated 122 patients with PSMA-PET/MRI prior to planned radical prostatectomy (RP). Primary endpoint was the accuracy of PSMA-PET/MRI in tumor staging as compared with staging-relevant histology. In addition, a multidisciplinary team reassessed the initial therapeutic approach to evaluate its impact on the therapeutic management. RESULTS: PSMA-PET/MRI correctly identified prostate cancer in 119 of 122 patients (97.5%). Eighty-one patients were treated with RP and pelvic lymphadenectomy. The accuracy for T staging was 82.5% [95% confidence interval (CI), 73-90; P < 0.001], for T2 stage was 85% (95% CI, 71-94; P < 0.001), for T3a stage was 79% (95% CI, 43-85; P < 0.001), for T3b stage was 94% (95% CI, 73-100; P < 0.001), and for N1 stage was 93% (95% CI, 84-98; P < 0.001). PSMA-PET/MRI changed the therapeutic strategy in 28.7% of the patients with either the onset of systemic therapy/radiotherapy (n = 16) or active surveillance (n = 19). CONCLUSIONS: PSMA-PET/MRI can provide an accurate staging of newly diagnosed prostate cancer. In addition, treatment strategies were changed in almost a third of the patients due to the information of this hybrid imaging technique.
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Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico , Pirrolidinas , Idoso , Biomarcadores Tumorais , Biópsia , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Imuno-Histoquímica , Ligantes , Linfonodos , Metástase Linfática , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/normas , Masculino , Glicoproteínas de Membrana , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organometálicos , Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons/normas , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/terapia , Compostos RadiofarmacêuticosRESUMO
OBJECTIVE: The aim of this study was to evaluate the potential of diffusion-weighted imaging-derived apparent diffusion coefficient (ADC) measurements to obviate unnecessary biopsies in multiparametric MRI-detected PI-RADS 4 and 5 lesions. MATERIALS AND METHODS: This retrospective, institutional review board-approved study investigated 101 PI-RADS 4 and 5 prostate lesions (52 malignant, 49 benign) verified by in-bore MRI-guided biopsy in 101 men (mean age, 62.8 years). Two readers, who were not aware of the biopsy results independently and repeatedly measured minimum, mean, and maximum ADC from diffusion-weighted imaging measurements (in line with PI-RADS v2 recommendations) using a 2-dimensional region of interest drawn around the biopsied lesions. Diagnostic performance was evaluated using receiver operating characteristic statistics and reproducibility statistics were calculated. RESULTS: The best diagnostic performance (overall area under the receiver operating characteristic curve [AUC] R1: 0.801; R2: 0.796 peripheral zone AUC R1:0.814, R2: 0.805; transitional zone AUC R1:0.786, R2:0.779) and the tightest limits of interreader agreement (-8.6% to 9.9%) were found in minimum ADC values. Rule-in and rule-out thresholds for diagnosis of prostate cancer were identified, demonstrating a potential to avoid unnecessary biopsies in 32.7% (16/49). CONCLUSIONS: Quantitative ADC measurement in multiparametric MRI-detected PI-RADS 4 and 5 lesions has the potential to avoid unnecessary MRI-guided biopsies in up to 33%.
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Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Sistemas de Informação em Radiologia , Procedimentos Desnecessários , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Humanos , Aumento da Imagem/métodos , Biópsia Guiada por Imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Próstata/diagnóstico por imagem , Próstata/patologia , Curva ROC , Radiologia Intervencionista , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
PURPOSE: To improve current prognostic models for the selection of patients with T1G3 urothelial bladder cancer who are more likely to fail intravesical therapy and progress to muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We performed a retrospective analysis of 1,289 patients with pT1G3 urothelial bladder cancer who were treated with transurethral resection of the bladder (TURB) and adjuvant intravesical bacillus-Calmette-Guérin (BCG). Random-split sample data and competing-risk regression were used to identify the independent impact of lymphovascular invasion (LVI) and variant histology (VH) on progression to MIBC. We developed a nomogram for predicting patient-specific probability of disease progression at 2 and 5 years after TURB. Decision curve analysis (DCA) was performed to evaluate the clinical benefit associated with the use of our nomogram. RESULTS: In the development cohort, within a median follow-up of 51.6 months (IQR: 19.3-92.5), disease progression occurred in 89 patients (13.8%). A total of 84 (13%) patients were found to have VH and 57 (8.8%) with LVI at TURB. Both factors were independently associated with disease progression on multivariable competing-risk analysis (HR: 4.4; 95% CI: 2.8-6.9; P<0.001 and HR: 3.5; 95% CI: 2.1-5.8; P<0.001, respectively). DCA showed superior net benefits for the nomogram within a threshold probability of progression between 5% and 55%. Limitations are inherent to the retrospective design. CONCLUSIONS: We demonstrated the clinical value of the integration of LVI and VH in a prognostic model for the prediction of MIBC. Indeed, our tool provides superior individualized risk estimation of progression facilitating decision-making regarding early RC.
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Tomada de Decisão Clínica , Neoplasias Musculares/patologia , Recidiva Local de Neoplasia/prevenção & controle , Nomogramas , Neoplasias da Bexiga Urinária/terapia , Idoso , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/epidemiologia , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Medição de Risco , Taxa de SobrevidaRESUMO
OBJECTIVE: To evaluate the diagnostic performance and complication rate of the in-bore magnetic resonance imaging-guided transrectal targeted prostate biopsy (MRGB) in a repeat biopsy population on the basis of a nearly 4-year learning curve (2014-2017). MATERIALS AND METHODS: A total of 142 consecutive males with previous biopsies and persistent suspicion of prostate cancer (PCa) due to high prostate-specific antigen level initially underwent MRGB in the case of prostate imaging reporting and data system (PI-RADS) 3-5 lesions. Cancer detection rate (CDR), number and length of cores, biopsy time, operator experience, complications, and prediction of clinically significant (cs) PCa (Gleason score ≥7) were investigated. RESULTS: PCa was found in 57% of patients. CDR in PI-RADS 3, 4, and 5 lesions were 46%, 52%, and 74%, respectively. csPCa was found in 9%, 25%, and 48% of patients. In univariate analysis the PI-RADS score (P = .0067) was a significant predictor of csPCa. In the multivariate logistic regression, age (P = .0007), number of previous biopsies (P = .0236), and prostate-specific antigen density (P = .0250) were significant predictors of csPCa. Location and size of the index lesion, number and length of cores obtained, and operator experience did not affect CDR. Concerning learning curve, biopsy time and number of cores obtained improved significantly after 10 procedures. Complications requiring medical intervention were seen in 6% (infections 2%). CONCLUSION: In a re-biopsy setting the MRGB showed sufficient diagnostic performance in detecting csPCa in PI-RADS 3-5 lesions, with low complication rate. The skill of performing biopsy is quickly acquired, and location of index lesion did not have an impact on CDR.
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Biópsia Guiada por Imagem , Imageamento por Ressonância Magnética , Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Fatores Etários , Idoso , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Biópsia Guiada por Imagem/normas , Curva de Aprendizado , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Duração da Cirurgia , Antígeno Prostático Específico/sangue , ReoperaçãoRESUMO
OBJECTIVES: To evaluate the concordance rate of lymphovascular invasion (LVI) and variant histology (VH) of transurethral resection (TUR) with radical cystectomy (RC) specimens. Furthermore, to evaluate the value of LVI and VH at TUR for predicting non-organ confined (NOC) disease, lymph node metastasis, and survival outcomes. PATIENTS AND METHODS: Two hundred and sixty-eight patients who underwent TUR and subsequent RC were reviewed. Logistic regression analyses were performed to evaluate the association of LVI and VH with NOC and lymph node metastasis at RC. Cox regression analyses were used to estimate recurrence-free survival (RFS) and cancer-specific survival (CSS). RESULTS: LVI and VH were detected in 13.8 and 11.2% of TUR specimens, and in 30.2 and 25.4% of RC specimens, respectively. The concordance rate between LVI and VH at TUR and subsequent RC was 69.8 and 83.6%, respectively. They were both associated with adverse pathological features such as lymph node metastasis and advanced stage. TUR LVI and VH were both independently associated with lymph node metastasis and TUR VH was independently associated with NOC. On univariable Cox regression analyses, TUR LVI was associated with RFS and CSS while TUR VH was only associated with RFS. Only TUR LVI was independently associated with RFS. CONCLUSION: Detection of LVI is missed in a third of TUR specimens while VH seems more accurately identified. TUR LVI and VH are associated with more advanced disease and LVI predicts disease recurrence. Assessment and reporting of LVI and VH on TUR specimen are important for risk stratification and decision-making.
Assuntos
Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/patologia , Idoso , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/cirurgia , Tomada de Decisão Clínica , Cistectomia , Cistoscopia , Intervalo Livre de Doença , Feminino , Humanos , Modelos Logísticos , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
HER2, a potential target for therapy, has been described to be amplified in urothelial carcinomas. As the topoisomerase II alpha (TOP2A) gene is located close to the HER2 gene on chromosome 17q12-q21, it is frequently either co-amplified or deleted with HER2 amplification. The purpose of this study was to assess the impact HER2 and TOP2A gene amplification as well as protein expression on outcomes of upper tract urothelial carcinoma (UTUC). HER2 and TOP2A gene amplification and protein expression were assessed in 81 patients with radical nephroureterectomy for UTUC. Immunohistochemistry and chromogenic in-situ hybridization was performed on formalin-fixed, paraffin-embedded samples. HER2 protein expression was observed in 27/81 (33%) cases, of which 8 cases exhibited amplification of HER2. One of them had an additional polysomy 17, whereas 6/67 HER2 non-amplified cases revealed a polysomy 17. Coamplification of HER2 and TOP2A was found in 4 cases, whereas 3 cases showed only HER2 amplification and 20 cases only TOP2A amplification. HER2 IHC overexpression was associated with higher-grade tumors (p = 0.001), non-organ confined carcinomas (p = 0.017), HER2 amplification (p < 0.00001) and TOP2A amplification (p = 0.016). HER2 amplification was association with higher tumor grade (p = 0.001) and lymphnode metastasis (p = 0.003). TOP2A IHC positivity was significantly associated with higher tumor grade (p = 0.0004), TOP2A amplification (p = 0.0003), polysomy 17 (p = 0.035) and HER2 IHC overexpression (p = 0.28), whereas all categories of tumor stage and HER2 amplification remained not related. TOP2A amplification was significantly more frequent in tumors with higher grade, higher tumor stage, polysomy 17 and distant metastasis (p = 0.015; p = 0.042; p = 0.032; p = 0.011), respectively. In univariate analyses HER2 IHC positivity, TOP2A amplification, and polysomy 17 were associated with poor clinical outcome after surgery. HER2 IHC overexpression and TOP2A amplification are associated with features of biologically aggressive UTUC. Overexpression and/or amplification of HER2 and TOP2A could help identify patients who may benefit from targeted therapy.
Assuntos
DNA Topoisomerases Tipo II/genética , DNA Topoisomerases Tipo II/metabolismo , Amplificação de Genes , Proteínas de Ligação a Poli-ADP-Ribose/genética , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Neoplasias Urológicas/genética , Neoplasias Urológicas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Urológicas/patologiaRESUMO
OBJECTIVES: To determine whether 3D acquisitions provide equivalent image quality, lesion delineation quality and PI-RADS v2 performance compared to 2D acquisitions in T2-weighted imaging of the prostate at 3 T. METHODS: This IRB-approved, prospective study included 150 consecutive patients (mean age 63.7 years, 35-84 years; mean PSA 7.2 ng/ml, 0.4-31.1 ng/ml). Two uroradiologists (R1, R2) independently rated image quality and lesion delineation quality using a five-point ordinal scale and assigned a PI-RADS score for 2D and 3D T2-weighted image data sets. Data were compared using visual grading characteristics (VGC) and receiver operating characteristics (ROC)/area under the curve (AUC) analysis. RESULTS: Image quality was similarly good to excellent for 2D T2w (mean score R1, 4.3 ± 0.81; R2, 4.7 ± 0.83) and 3D T2w (mean score R1, 4.3 ± 0.82; R2, 4.7 ± 0.69), p = 0.269. Lesion delineation was rated good to excellent for 2D (mean score R1, 4.16 ± 0.81; R2, 4.19 ± 0.92) and 3D T2w (R1, 4.19 ± 0.94; R2, 4.27 ± 0.94) without significant differences (p = 0.785). ROC analysis showed an equivalent performance for 2D (AUC 0.580-0.623) and 3D (AUC 0.576-0.629) T2w (p > 0.05, respectively). CONCLUSIONS: Three-dimensional acquisitions demonstrated equivalent image and lesion delineation quality, and PI-RADS v2 performance, compared to 2D in T2-weighted imaging of the prostate. Three-dimensional T2-weighted imaging could be used to considerably shorten prostate MRI protocols in clinical practice. KEY POINTS: ⢠3D shows equivalent image quality and lesion delineation compared to 2D T2w. ⢠3D T2w and 2D T2w image acquisition demonstrated comparable diagnostic performance. ⢠Using a single 3D T2w acquisition may shorten the protocol by 40%. ⢠Combined with short DCE, multiparametric protocols of 10 min are feasible.
Assuntos
Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Próstata/patologia , Neoplasias da Próstata/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROCRESUMO
AIM: To assess the predictive value of TGP on biochemical recurrence (BCR) and its association with clinicopathological outcomes in a large, multicenter cohort of patients with localized prostate cancer (PCa) treated with radical prostatectomy (RP). MATERIALS AND METHODS: Records of 6,041 patients who were treated with RP between 2000 and 2011 for clinically nonmetastatic PCa were, retrospectively, analyzed from prospectively collected datasets. BCR-free survival rates were assessed using univariable and multivariable cox-regression analyses. RESULTS: Median patient age was 61 years (interquartile range [IQR]: 57-66) with a median preoperative prostrate specific antigen of 6ng/ml (IQR: 4-9). Overall, 28% of patients had Gleason score (GS) 6, 0.3% GS 6 + TGP, 33% GS 7 (3 + 4), 0.2% GS 7 (3 + 4) + TGP, 22% GS 7 (4 + 3), 0.2% GS 7 (4 + 3) + TGP, 0.1% GS 8 and 0.4% GS 9 or 10. Median follow-up was 45 months (IQR: 31-57). Harboring a TGP was associated with higher rates of positive surgical margins, lymphovascular invasion, extraprostatic extension, and seminal vesicle invasion than their counterparts within the same GS group as well as in the next higher GS group (all P ≤ 0.05). At 5 years post-RP, BCR estimates were 5% for patients with GS 6, 13% for patients with GS 6 + TGP, 6% for patients with GS 7 (3 + 4), 22% for patients with GS 7 (3 + 4) + TGP, 16% for patients with GS 7 (4 + 3), 41% for patients with GS 7 (4 + 3) + TGP, 38% for patients with GS 8 (4 + 4) and 46% for patients with GS 9 or 10. Patients harboring a TGP had higher BCR rates than the patients in the next higher GS group: GS 6 + TGP vs. GS 7 (3 + 4), HR = 1.6, P = 0.02 and GS 7 (3 + 4)+TGP vs. GS 7 (4 + 3), HR = 1.4, P = 0.03. Patients with a TGP in the GS 7 (4 + 3) group had comparable BCR rates as patients with GS = 8 (P = 0.4) and GS 9 to 10 (P = 0.2). On multivariable analysis that adjusted for the effects of preoperative prostrate specific antigen, nodal involvement, positive surgical margin, extraprostatic disease (pT3a), seminal vesicle invasion (pT3b) and different institution, harboring a TGP showed higher risk of developing BCR within the same GS group and comparable risk of developing BCR with the next higher GS group. CONCLUSION: Patients with TGP at RP have adverse clinicopathological features when compared to their counterparts in the same and the next higher GS group without TGP. Risk of developing BCR increases with the presence of TGP within the same GS group. This risk seems to be comparable between patients with TGP and their counterparts in the next higher GS group without TGP. Knowledge of TGP in RP specimens is likely to improve risk stratification, patient counseling and follow-up scheduling. Further prospective studies that control significant clinical endpoints such as metastasis and mortality are necessary for more significant predictions.
Assuntos
Recidiva Local de Neoplasia/epidemiologia , Próstata/patologia , Prostatectomia , Neoplasias da Próstata/patologia , Idoso , Intervalo Livre de Doença , Seguimentos , Humanos , Calicreínas/sangue , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/sangue , Estudos Prospectivos , Próstata/cirurgia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The role of multi-parametric (mp)MRI in the diagnosis and treatment of prostate cancer has increased considerably. An alternative to visual inspection of mpMRI is the evaluation using histogram-based (first order statistics) parameters and textural features (second order statistics). The aims of the present work were to investigate the relationship between benign and malignant sub-volumes of the prostate and textures obtained from mpMR images. The performance of tumor prediction was investigated based on the combination of histogram-based and textural parameters. Subsequently, the relative importance of mpMR images was assessed and the benefit of additional imaging analyzed. Finally, sub-structures based on the PI-RADS classification were investigated as potential regions to automatically detect maligned lesions. Twenty-five patients who received mpMRI prior to radical prostatectomy were included in the study. The imaging protocol included T2, DWI, and DCE. Delineation of tumor regions was performed based on pathological information. First and second order statistics were derived from each structure and for all image modalities. The resulting data were processed with multivariate analysis, using PCA (principal component analysis) and OPLS-DA (orthogonal partial least squares discriminant analysis) for separation of malignant and healthy tissue. PCA showed a clear difference between tumor and healthy regions in the peripheral zone for all investigated images. The predictive ability of the OPLS-DA models increased for all image modalities when first and second order statistics were combined. The predictive value reached a plateau after adding ADC and T2, and did not increase further with the addition of other image information. The present study indicates a distinct difference in the signatures between malign and benign prostate tissue. This is an absolute prerequisite for automatic tumor segmentation, but only the first step in that direction. For the specific identified signature, DCE did not add complementary information to T2 and ADC maps.
Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/patologia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Prostatectomia , Neoplasias da Próstata/cirurgiaRESUMO
OBJECTIVE: Urothelial prostatic involvement (UPI) at the time of radical cystoprostatectomy (RCP) was found associated with worse survival outcomes by several previous reports. Our aim is to evaluate the impact of different levels of UPI on survival outcomes using a large series of male patients treated with RCP. METHODS: Whole step section specimens from 995 male BCa patients were assessed for UPI defined as: no involvement vs. prostatic urethral carcinoma in situ (CIS) vs. lamina propria involvement vs. ductal CIS vs. prostate stromal involvement. Primary end point of the study was predictors of prostatic involvement at RCP and its impact on overall survival after surgery. RESULTS: Prostatic involvement was recorded in 307 (30.9%) patients: 28% with prostatic urethral CIS, 12% with lamina propria involvement, 13% with ductal CIS and 47% with stromal involvement. Median follow-up was 70 months. Patients with stromal involvement had a worse 5-year survival (12%) than those with prostatic urethra CIS (40%), lamina propria involvement (36%), and ductal CIS (35%). Considering predictors of prostatic involvement, multifocal tumor (Odds Ratio [OR]: 6.60, pâ<â0.001), lymphovascular invasion (OR: 2.61, pâ<â0.001), lymph node metastases (OR: 2.02, pâ<â0.001) and CIS (OR: 2.02, pâ<â0.001) were found associated. Similar predictors were found assessing stromal involvement. CONCLUSIONS: Approximately one third of RCP patients harbor prostatic involvement of urothelial carcinoma. While all UPI are associated with worse overall survival, stromal involvement confers the worst outcome supporting its classification as T4 in the TNM staging.