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1.
J Urol ; 206(4): 854-865, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34032495

RESUMEN

PURPOSE: Sarcopenia, an age-related loss of muscle mass and function, may predict adverse outcomes for patients with urological cancers. However, the clinical implications and significance of sarcopenic obesity are not well understood. We systematically reviewed data on the prevalence and prognostic impact of sarcopenic obesity for patients with renal cell carcinoma, urothelial carcinoma and prostate cancer undergoing treatment. MATERIALS AND METHODS: We searched EMBASE®, PubMed®/MEDLINE® and Scopus® for relevant original articles and abstracts published between January 2010 and February 2021. Primary outcomes were overall survival (OS), cancer-specific survival (CSS) and progression-free survival. The secondary outcome was the prevalence of sarcopenic obesity. RESULTS: A total of 15 studies comprising 3,866 patients were included. Of the 10 studies that evaluated survival outcomes, the association between sarcopenic obesity and survival was mixed. One of 10 studies showed a significant association of sarcopenic obesity with OS (HR 0.7, 95% CI 0.51-0.98; p=0.04). One additional study showed reported a trend for shorter OS (p=0.05) associated with sarcopenic obesity. Others reported that it is an adverse prognostic factor for CSS (HR 5.0, 95% CI 1.4-16.7; p=0.01). All other studies did not demonstrate that sarcopenic obesity was of prognostic relevance with regard to OS, CSS and progression-free survival. Overall, its mean prevalence was 27% (range 11-63). CONCLUSIONS: There is considerable heterogeneity in methods used to define sarcopenic obesity in the literature, and current data are limited. Future studies are needed to further understand the relationship of obesity and sarcopenia on the clinical trajectory of patients with urological cancer.


Asunto(s)
Obesidad/epidemiología , Sarcopenia/epidemiología , Neoplasias Urológicas/mortalidad , Composición Corporal , Comorbilidad , Humanos , Obesidad/complicaciones , Obesidad/diagnóstico , Prevalencia , Pronóstico , Supervivencia sin Progresión , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Sarcopenia/complicaciones , Sarcopenia/diagnóstico
2.
Eur J Nucl Med Mol Imaging ; 48(6): 1795-1805, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33341915

RESUMEN

PURPOSE: Risk classification of primary prostate cancer in clinical routine is mainly based on prostate-specific antigen (PSA) levels, Gleason scores from biopsy samples, and tumor-nodes-metastasis (TNM) staging. This study aimed to investigate the diagnostic performance of positron emission tomography/magnetic resonance imaging (PET/MRI) in vivo models for predicting low-vs-high lesion risk (LH) as well as biochemical recurrence (BCR) and overall patient risk (OPR) with machine learning. METHODS: Fifty-two patients who underwent multi-parametric dual-tracer [18F]FMC and [68Ga]Ga-PSMA-11 PET/MRI as well as radical prostatectomy between 2014 and 2015 were included as part of a single-center pilot to a randomized prospective trial (NCT02659527). Radiomics in combination with ensemble machine learning was applied including the [68Ga]Ga-PSMA-11 PET, the apparent diffusion coefficient, and the transverse relaxation time-weighted MRI scans of each patient to establish a low-vs-high risk lesion prediction model (MLH). Furthermore, MBCR and MOPR predictive model schemes were built by combining MLH, PSA, and clinical stage values of patients. Performance evaluation of the established models was performed with 1000-fold Monte Carlo (MC) cross-validation. Results were additionally compared to conventional [68Ga]Ga-PSMA-11 standardized uptake value (SUV) analyses. RESULTS: The area under the receiver operator characteristic curve (AUC) of the MLH model (0.86) was higher than the AUC of the [68Ga]Ga-PSMA-11 SUVmax analysis (0.80). MC cross-validation revealed 89% and 91% accuracies with 0.90 and 0.94 AUCs for the MBCR and MOPR models respectively, while standard routine analysis based on PSA, biopsy Gleason score, and TNM staging resulted in 69% and 70% accuracies to predict BCR and OPR respectively. CONCLUSION: Our results demonstrate the potential to enhance risk classification in primary prostate cancer patients built on PET/MRI radiomics and machine learning without biopsy sampling.


Asunto(s)
Radioisótopos de Galio , Neoplasias de la Próstata , Ácido Edético , Humanos , Imagen por Resonancia Magnética , Masculino , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico por imagen , Aprendizaje Automático Supervisado
3.
J Urol ; 204(4): 649-660, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32105187

RESUMEN

PURPOSE: Studies exploring the association of cigarette smoking and long-term survival outcomes following radical cystectomy have yielded mixed results. We performed a systematic review and meta-analysis to investigate the impact of tobacco smoking exposure, duration, intensity and cessation on response to neoadjuvant chemotherapy and long-term survival outcomes in patients undergoing radical cystectomy for bladder cancer. MATERIALS AND METHODS: We systematically searched PubMed®, MEDLINE®, Embase® and Cochrane® Library databases for original articles published before April 2019. Primary end points were neoadjuvant chemotherapy response, overall and cancer specific mortality, and recurrence-free survival after radical cystectomy. Observational studies reporting Cox proportional hazards regression or logistic regression analysis were independently screened. Available multivariable hazard ratios and corresponding 95% CIs were included in the quantitative analysis. Sensitivity analyses were performed as appropriate. A risk of bias assessment was completed for nonrandomized studies. RESULTS: Our electronic search identified a total of 649 articles. After a detailed review we selected 17 studies that addressed the impact of smoking status on survival outcomes in 13,777 patients after radical cystectomy for bladder cancer. Pooled meta-analysis revealed that active smokers have an increased risk of overall mortality (HR 1.21, 95% CI 1.08-1.36; p=0.001, I2=0%), cancer specific mortality (HR 1.24, 95% CI 1.13-1.36; p <0.00001, I2=0%) and bladder cancer recurrence (HR 1.24, 95% CI 1.12-1.38; p <0.0001, I2=3%). Sensitivity analyses evaluating only patients who underwent neoadjuvant chemotherapy followed by radical cystectomy showed an advantage of non/never smokers in terms of neoadjuvant chemotherapy complete response rate (HR 0.47, 95% CI 0.29-0.75; p=0.001, I2=0%). CONCLUSIONS: Smoking status is associated with lower neoadjuvant chemotherapy response rates and higher overall and cancer specific mortality as well as bladder cancer recurrence after radical cystectomy. Appropriate preoperative counseling, together with tightened followup, may have a pivotal role in improving the smoking-related long-term survival outcomes in patients with bladder cancer.


Asunto(s)
Cistectomía , Fumar/efectos adversos , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/cirugía , Quimioterapia Adyuvante , Cistectomía/métodos , Humanos , Terapia Neoadyuvante , Tasa de Supervivencia , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico
4.
Clin Radiol ; 75(2): 157.e1-157.e7, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31690449

RESUMEN

AIM: To report prostate cancer (PCa) prevalence in Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) categories and investigate the potential to avoid unnecessary, magnetic resonance imaging (MRI)-guided in-bore biopsies by adding clinical and biochemical patient characteristics. MATERIALS AND METHODS: The present institutional review board-approved, prospective study on 137 consecutive men with 178 suspicious lesions on 3 T MRI was performed. Routine data collected for each patient included patient characteristics (age, prostate volume), clinical background information (prostate-specific antigen [PSA] levels, PSA density), and PI-RADS v2 scores assigned in a double-reading approach. RESULTS: Histopathological evaluation revealed a total of 93/178 PCa (52.2%). The mean age was 66.3 years and PSA density was 0.24 ng/ml2 (range, 0.04-0.89 ng/ml). Clinically significant PCa (csPCa, Gleason score >6) was confirmed in 50/93 (53.8%) lesions and was significantly associated with higher PI-RADS v2 scores (p=0.0044). On logistic regression analyses, age, PSA density, and PI-RADS v2 scores contributed independently to the diagnosis of csPCa (p=7.9×10-7, p=0.097, and p=0.024, respectively). The resulting area under the receiver operating characteristic curve (AUC) to predict csPCa was 0.76 for PI-RADS v2, 0.59 for age, and 0.67 for PSA density. The combined regression model yielded an AUC of 0.84 for the diagnosis of csPCa and was significantly superior to each single parameter (p≤0.0009, respectively). Unnecessary biopsies could have been avoided in 50% (64/128) while only 4% (2/50) of csPCa lesions would have been missed. CONCLUSIONS: Adding age and PSA density to PI-RADS v2 scores improves the diagnostic accuracy for csPCa. A combination of these variables with PI-RADS v2 can help to avoid unnecessary in-bore biopsies while still detecting the majority of csPCa.


Asunto(s)
Neoplasias de la Próstata/diagnóstico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Humanos , Biopsia Guiada por Imagen/métodos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Próstata/diagnóstico por imagen , Próstata/patología , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología
6.
Ann Oncol ; 30(11): 1697-1727, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31740927

RESUMEN

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.


Asunto(s)
Consenso , Oncología Médica/normas , Guías de Práctica Clínica como Asunto , Neoplasias de la Vejiga Urinaria/terapia , Urología/normas , Técnica Delphi , Europa (Continente) , Humanos , Cooperación Internacional , Oncología Médica/métodos , Estadificación de Neoplasias , Sociedades Médicas/normas , Participación de los Interesados , Encuestas y Cuestionarios , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/patología , Urología/métodos
7.
World J Urol ; 37(1): 165-172, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29882105

RESUMEN

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. PATIENTS AND METHODS: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. RESULTS: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the 'CIS' versus 'no-CIS' groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63-1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01-1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23-2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34-0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82-1.35; p = 0.70). CONCLUSION: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma in Situ/terapia , Cistectomía , Quimioterapia de Inducción , Terapia Neoadyuvante , Neoplasias de la Vejiga Urinaria/terapia , Anciano , Carcinoma in Situ/mortalidad , Carcinoma in Situ/patología , Cisplatino/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología
8.
Eur J Nucl Med Mol Imaging ; 45(2): 235-242, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29075832

RESUMEN

OBJECTIVE: To evaluate the diagnostic performance of [68Ga]Ga-PSMAHBED-CC conjugate 11 positron emission tomography (PSMA-PET) in the early detection of metastases in patients with biochemical recurrence (BCR) after radical prostatectomy (RP) for clinically non-metastatic prostate cancer, to compare it to CT/MRI alone and to assess its impact on further therapeutic decisions. MATERIAL AND METHODS: We retrospectively assessed 117 consecutive hormone-naïve BCR patients who had 68Ga-PSMA 11 PET/CT (n = 46) or PET/MRI (n = 71) between May 2014 and January 2017. BCR was defined as two PSA rises above 0.2 ng/ml. Two dedicated uro-oncological imaging experts (radiology/nuclear medicine) reviewed separately all images. All results were presented in a blinded sequential fashion to a multidisciplinary tumorboard in order to assess the influence of PSMA-PET imaging on decision-making. RESULTS: The median time from RP to BCR was 36 months (IQR 16-72). Overall, 69 (59%) patients received postoperative radiotherapy. Median PSA level at the time of imaging was 1.04 ng/ml (IQR 0.58-1.87). PSMA-positive lesions were detected in 100 (85.5%) patients. Detection rates were 65% for a PSA value of 0.2 to <0.5 ng/ml, 85.7% for 0.5 to <1, 85.7% for 1 to <2 and 100% for ≥2. PSMA-positive lesions could be confirmed by either histology (16%), PSA decrease in metastasis-directed radiotherapy (45%) or additional information in diffusion-weighted imaging when PET/MRI was performed (18%) in 79% of patients. PSMA-PET detected lesions in 67 patients (57.3%) who had no suspicious correlates according to the RECIST 1.1 criteria on MRI or CT. PSMA-PET changed therapeutic decisions in 74.6% of these 67 patients (p < 0.001), with 86% of them being considered for metastases-directed therapies. CONCLUSIONS: We confirm the high performance of PSMA-PET imaging for the detection of disease recurrence sites in patients with BCR after RP, even at relatively low PSA levels. Moreover, it adds significant information to standard CT/MRI, changing treatment strategies in a significant number of patients.


Asunto(s)
Toma de Decisiones , Ácido Edético/análogos & derivados , Oligopéptidos/metabolismo , Tomografía de Emisión de Positrones , Prostatectomía , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/metabolismo , Anciano , Ácido Edético/metabolismo , Isótopos de Galio , Radioisótopos de Galio , Humanos , Ligandos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Recurrencia , Estudios Retrospectivos
9.
World J Urol ; 36(10): 1621-1627, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29721611

RESUMEN

PURPOSE: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis to adequately stage and treat the patient. Persistent disease after TUR is not uncommon and is why re-TUR is recommended in T1G3 patients. When there is T1 tumor in the re-TUR specimen, very high risks of progression (82%) have been reported. We analyze the risks of recurrence, progression to muscle-invasive disease and cancer-specific mortality (CSM) according to tumor stage at re-TUR in T1G3 patients treated with BCG. METHODS: In our retrospective cohort of 2451 T1G3 patients, 934 patients (38.1%) underwent re-TUR. 667 patients had residual disease (71.4%): Ta in 378 (40.5%), T1 in 289 (30.9%) patients. Times to recurrence, progression and CSM in the three groups were estimated using cumulative incidence functions and compared using the Cox regression model. RESULTS: During a median follow-up of 5.2 years, 512 patients recurred. The recurrence rate was significantly higher in patients with a T1 at re-TUR (P < 0.001). Progression rates differed according to the pathology at re-TUR, 25.3% in T1, 14.6% in Ta and 14.2% in case of no residual tumor (P < 0.001). Similar trends were seen in both patients with and without muscle in the original TUR specimen. CONCLUSIONS: Patients with T1G3 tumors and no residual disease or Ta at re-TUR have better recurrence, progression and CSM rates than previously reported, with a CSM rate of 13.1 and a 25.3% progression rate in re-TUR T1 disease.


Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Vacuna BCG/uso terapéutico , Cistectomía/métodos , Neoplasias de la Vejiga Urinaria , Administración Intravesical , Anciano , Causas de Muerte , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Recurrencia Local de Neoplasia/mortalidad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Reoperación , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/terapia
10.
World J Urol ; 36(11): 1775-1781, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30171454

RESUMEN

PURPOSE: To evaluate the oncological impact of postponing radical cystectomy (RC) to allow further conservative therapies prior to progression in a large multicentre retrospective cohort of T1-HG/G3 patients initially treated with BCG. METHODS: According to the time of RC, the population was divided into 3 groups: patients who did not progress to muscle-invasive disease, patients who progressed before radical cystectomy and patients who experienced progression at the time of radical cystectomy. Clinical and pathological outcomes were compared across the three groups. RESULTS: Of 2451 patients, 509 (20.8%) underwent RC. Patients with tumors > 3 cm or with CIS had earlier cystectomies (HR = 1.79, p = 0.001 and HR = 1.53, p = 0.02, respectively). Patients with tumors > 3 cm, multiple tumors or CIS had earlier T3/T4 or N + cystectomies. In patients who progressed, the timing of cystectomy did not affect the risk of T3/T4 or N + disease at RC. Patients with T3/T4 or N + disease at RC had a shorter disease-specific survival (HR = 4.38, p < 0.001), as did patients with CIS at cystectomy (HR = 2.39, p < 0.001). Patients who progressed prior to cystectomy had a shorter disease-specific survival than patients for whom progression was only detected at cystectomy (HR = 0.58, p = 0.024) CONCLUSIONS: Patients treated with RC before experiencing progression to muscle-invasive disease harbor better oncological and survival outcomes compared to those who progressed before RC and to those upstaged at surgery. Tumor size and concomitant CIS at diagnosis are the main predictors of surgical treatment while tumor size, CIS and tumor multiplicity are associated with extravesical disease at surgery.


Asunto(s)
Vacuna BCG/uso terapéutico , Carcinoma de Células Transicionales/cirugía , Cistectomía/métodos , Recurrencia Local de Neoplasia/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/cirugía , Anciano , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/patología , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología
12.
World J Urol ; 35(6): 943-949, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27730305

RESUMEN

PURPOSE: This study aims to determine the significance of androgen receptor (AR) expression in urothelial carcinoma of the upper urinary tract (UTUC). METHODS: AR expression was assessed on tissue microarrays containing specimens of 737 patients with UTUC who underwent radical nephroureterectomy with curative intent. AR expression was correlated with clinical and pathological tumor features as well as recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS: Overall, AR was expressed in 11 % of tumors. AR expression was significantly associated with tumor necrosis as well as sessile and multifocal tumor growth but not with RFS, CSS or OS. AR was detected nearly twice as often in tumors of the ureter than of the pelvicalyceal system (p = 0.005). Subgroup analyses showed that the significant associations of AR with unfavorable pathologic features were exclusively attributable to tumors located in the ureter. However, in both ureteral and pelvicalyceal tumors, AR status was independent of RFS, CSS and OS. CONCLUSIONS: In this cohort of patients treated with RNU, AR expression was found in approximately 10 % of UTUCs, twice as often in ureteral than in pelvicalyceal tumors. While AR expression had no impact on postoperative prognosis, it was significantly associated with unfavorable pathologic features in ureteral tumors. Steroid hormone signaling might be relevant for future investigations of differences between ureteral and pelvicalyceal tumors.


Asunto(s)
Carcinoma de Células Transicionales/patología , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/patología , Receptores Androgénicos/genética , Neoplasias Ureterales/patología , Adulto , Anciano , Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/cirugía , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Renales/metabolismo , Neoplasias Renales/mortalidad , Neoplasias Renales/cirugía , Modelos Logísticos , Masculino , Persona de Mediana Edad , Nefrectomía/métodos , Nefrectomía/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Neoplasias Ureterales/metabolismo , Neoplasias Ureterales/mortalidad , Neoplasias Ureterales/cirugía
13.
World J Urol ; 35(12): 1891-1897, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28836063

RESUMEN

PURPOSE: Because the prognostic impact of the clinical and pathological features on cancer-specific survival (CSS) and overall survival (OS) in patients with papillary renal cell carcinoma (papRCC) is still controversial, we want to assess the impact of clinicopathological features, including Fuhrman grade and age, on survival in surgically treated papRCC patients in a large multi-institutional series. METHODS: We established a comprehensive multi-institutional database of surgically treated papRCC patients. Histopathological data collected from 2189 patients with papRCC after radical nephrectomy or nephron-sparing surgery were pooled from 18 centres in Europe and North America. OS and CSS probabilities were estimated using the Kaplan-Meier method. Multivariable competing risks analyses were used to assess the impact of Fuhrman grade (FG1-FG4) and age groups (<50 years, 50-75 years, >75 years) on cancer-specific mortality (CSM). RESULTS: CSS and OS rates for patients were 89 and 81% at 3 years, 86 and 75% at 5 years and 78 and 41% at 10 years after surgery, respectively. CSM differed significantly between FG 3 (hazard ratio [HR] 4.22, 95% confidence interval [CI] 2.17-8.22; p < 0.001) and FG 4 (HR 8.93, 95% CI 4.25-18.79; p < 0.001) in comparison to FG 1. CSM was significantly worse in patients aged >75 (HR 2.85, 95% CI 2.06-3.95; p < 0.001) compared to <50 years. CONCLUSIONS: FG is a strong prognostic factor for CSS in papRCC patients. In addition, patients older than 75 have worse CSM than patients younger than 50 years. These findings should be considered for clinical decision making.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Nefrectomía , Medición de Riesgo/métodos , Anciano , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Europa (Continente)/epidemiología , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/diagnóstico , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Mortalidad , Clasificación del Tumor , Estadificación de Neoplasias , Nefrectomía/efectos adversos , Nefrectomía/métodos , América del Norte/epidemiología , Tratamientos Conservadores del Órgano/efectos adversos , Tratamientos Conservadores del Órgano/métodos , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos
14.
Hell J Nucl Med ; 20 Suppl: 157, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29324927

RESUMEN

OBJECTIVE: We evaluated the impact of pre-therapeutic hematopoiesis on survival, hematotoxicity (HT) and number of 223Radium (223Ra) treatments in patients with metastatic castration-resistant prostate cancer. SUBJECTS AND METHOD: Hemoglobin-levels (Hb), the number of platelets (Plts), leukocytes (Leuk), and survival data were collected in 56 patients treated with 223Ra. Pre-therapeutic hematopoiesis as well as adverse events during and after therapy were scored (grade 0-4) according to the CTCAE recommendations. The association of pre-therapeutic hematopoiesis, survival, HT and numbers of 223Ra cycles was analyzed. RESULTS: Median survival in all patients was 69.9 weeks; 77% of patients had pre-existing impaired Hb (1.7% grade 3, 12.5% grade 2, 62.5% grade 1). 8/56 (14.3%) had impaired Plt (grade 1) Maximum toxicity (Tox) grades of patients during treatment were grade 4 (Hb 1.7%; Plt 1.7%), grade 3 (Hb 14.3%; Plt 7.1%; Leu 7.1%), grade 2 (Hb 33.9%; Plt 7.1%; Leu 23.2%), grade 1 (Hb 46.4%; Plt 17.9%; Leu 23.2%) and grade 0 (Hb 5.4%; Plt 66.1%; Leu 44.6%). Interestingly, patients with thrombocytopenia had a significantly shorter survival compared to those with normal Plt levels (21 weeks vs not reached; P<0.003). As expected patients with pre-therapeutic low Hb-level (<10g/dL) had a significantly shorter survival compared to those with Hb-level >10g/dL (28 weeks vs not reached, P<0.004), whereas survival of patients with mildly impaired Hb (>10 but <13.5g/dL) did not differ from patients with normal levels of Hb (X vs. Y, P=...). Also patients with impaired Hb also developed significantly more grade 3 and 4 HT (Hb <10g/dL: 42.9 vs 14.3%, P<0.001; Plt <150G/mL: 25.0% vs 6.3%; P=0.002) and received significantly fewer treatment cycles (Hb<10g/dL: 5.1 vs 5.8, P<0.04; Plt <150G/mL: 3.4 vs 5.6; P<0.001). Neither extent of bone metastases nor previous chemotherapy were associated with survival, number of 223Ra cycles and HT. CONCLUSION: Patients with metastatic castration-resistant prostate cancer and impaired hematopoiesis, in particular thrombocytopenia and anemia, before 223Ra therapy suffer from significantly more high-grade HT, shorter survival and receive significantly fewer 223Ra treatments. Therefore, Hb-levels and platelet counts are essential parameters for adequate patient selection for 223Ra therapy.


Asunto(s)
Hematopoyesis/efectos de la radiación , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Radio (Elemento)/efectos adversos , Radio (Elemento)/uso terapéutico , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Pronóstico , Análisis de Supervivencia
15.
Ann Oncol ; 27(7): 1311-6, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27091807

RESUMEN

BACKGROUND: Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer. Preclinical studies show that anti-FGFR3 treatment slows down tumor growth, suggesting that this tyrosine kinase receptor is a candidate for personalized bladder cancer treatment, particularly in patients with mutated FGFR3. We addressed tumor heterogeneity in a large multicenter, multi-laboratory study, as this may have significant impact on therapeutic response. PATIENTS AND METHODS: We evaluated possible FGFR3 heterogeneity by the PCR-SNaPshot method in the superficial and deep compartments of tumors obtained by transurethral resection (TUR, n = 61) and in radical cystectomy (RC, n = 614) specimens and corresponding cancer-positive lymph nodes (LN+, n = 201). RESULTS: We found FGFR3 mutations in 13/34 (38%) T1 and 8/27 (30%) ≥T2-TUR samples, with 100% concordance between superficial and deeper parts in T1-TUR samples. Of eight FGFR3 mutant ≥T2-TUR samples, only 4 (50%) displayed the mutation in the deeper part. We found 67/614 (11%) FGFR3 mutations in RC specimens. FGFR3 mutation was associated with pN0 (P < 0.001) at RC. In 10/201 (5%) LN+, an FGFR3 mutation was found, all concordant with the corresponding RC specimen. In the remaining 191 cases, RC and LN+ were both wild type. CONCLUSIONS: FGFR3 mutation status seems promising to guide decision-making on adjuvant anti-FGFR3 therapy as it appeared homogeneous in RC and LN+. Based on the results of TUR, the deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. We conclude that studies on the heterogeneity of actionable molecular targets should precede clinical trials with these drugs in the perioperative setting.


Asunto(s)
Biomarcadores de Tumor/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Adulto , Anciano , Toma de Decisiones Clínicas , Cistectomía , Femenino , Regulación Neoplásica de la Expresión Génica , Heterogeneidad Genética , Humanos , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Mutación , Periodo Perioperatorio , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/antagonistas & inhibidores , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugía
16.
J Urol ; 204(4): 660, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32648804
17.
Minerva Urol Nefrol ; 67(2): 103-15, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25604695

RESUMEN

Systemic chemotherapy is the standard treatment of advanced and metastatic urothelial carcinoma of the bladder (UCB). Unfortunately, systemic chemotherapy is ineffective in a significant number of patients, while side effects occur frequently. Detailed molecular-genetic investigations revealed a broad heterogeneity of underlying genomic mutations in UCB and led to the detection of cancer-specific therapeutic targets. These findings may allow a more tailored and individualized patient-based therapy, focusing on specific genomic variations, which may cause chemo-resistance in patients progressing or relapsing after standard chemotherapy. Targeted therapies hold the potential to be more effective in inhibiting cancer cell growth and progression, as well as to cause fewer side effects. While targeted therapies have been successfully established in the treatment of various malignancies including renal cell carcinoma, the clinical impact of these modern treatment strategies still remains unsettled for UCB. In this review, we comprehensively summarize the most current and relevant findings on targeted therapy in advanced and metastatic UCB, elucidating chances and limitations and discussing future perspectives.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/genética , Terapia Molecular Dirigida , Mutación , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacos , Quimioterapia Adyuvante/métodos , Ensayos Clínicos como Asunto , Medicina Basada en la Evidencia , Genómica , Humanos , Inmunoterapia/métodos , Terapia Molecular Dirigida/métodos , Estadificación de Neoplasias , Pronóstico , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/genética
18.
Br J Cancer ; 111(8): 1526-31, 2014 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-25117808

RESUMEN

BACKGROUND: Gamma-glutamyltransferase (GGT) regulates apoptotic balance and promotes cancer progression and invasion. Higher pretherapeutic GGT serum levels have been associated with worse outcomes in various malignancies, but there are no data for renal cell carcinoma (RCC). METHODS: Pretherapeutic GGT serum levels and clinicopathological parameters were retrospectively evaluated in 921 consecutive RCC patients treated with nephrectomy at a single institution between 1998 and 2013. Gamma-glutamyltransferase was analysed as continuous and categorical variable. Associations with RCC-specific survival were assessed with Cox proportional hazards models. Discrimination was measured with the C-index. Decision-curve analysis was used to evaluate the clinical net benefit. The median postoperative follow-up was 45 months. RESULTS: Median pretherapeutic serum GGT level was 25 U l(-1). Gamma-glutamyltransferase levels increased with advancing T (P<0.001), N (P=0.006) and M stages (P<0.001), higher grades (P<0.001), and presence of tumour necrosis (P<0.001). An increase of GGT by 10 U l(-1) was associated with an increase in the risk of death from RCC by 4% (HR 1.04, P<0.001). Based on recursive partitioning-based survival tree analysis, we defined four prognostic categories of GGT: normal low (<17.5 U l(-1)), normal high (17.5 to <34.5 U l(-1)), elevated (34.5 to <181.5 U l(-1)), and highly elevated (⩾181.5 U l(-1)). In multivariable analyses that adjusted for the effect of standard features, both continuously and categorically coded GGT were independent prognostic factors. Adding GGT to a model that included standard features increased the discrimination by 0.9% to 1.8% and improved the clinical net benefit. CONCLUSIONS: Pretherapeutic serum GGT is a novel and independent prognostic factor for patients with RCC. Stratifying patients into prognostic subgroups according to GGT may be used for patient counselling, tailoring surveillance, individualised treatment planning, and clinical trial design.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Células Renales/enzimología , Neoplasias Renales/enzimología , gamma-Glutamiltransferasa/sangre , Anciano , Carcinoma de Células Renales/patología , Femenino , Humanos , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos
19.
Br J Cancer ; 111(2): 213-9, 2014 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-25003663

RESUMEN

BACKGROUND: Pelvic lymph node dissection in patients undergoing radical prostatectomy for clinically localised prostate cancer is not without morbidity and its therapeutical benefit is still a matter of debate. The objective of this study was to develop a model that allows preoperative determination of the minimum number of lymph nodes needed to be removed at radical prostatectomy to ensure true nodal status. METHODS: We analysed data from 4770 patients treated with radical prostatectomy and pelvic lymph node dissection between 2000 and 2011 from eight academic centres. For external validation of our model, we used data from a cohort of 3595 patients who underwent an anatomically defined extended pelvic lymph node dissection. We estimated the sensitivity of pathological nodal staging using a beta-binomial model and developed a novel clinical (preoperative) nodal staging score (cNSS), which represents the probability that a patient has lymph node metastasis as a function of the number of examined nodes. RESULTS: In the development and validation cohorts, the probability of missing a positive lymph node decreases with increase in the number of nodes examined. A 90% cNSS can be achieved in the development and validation cohorts by examining 1-6 nodes in cT1 and 6-8 nodes in cT2 tumours. With 11 nodes examined, patients in the development and validation cohorts achieved a cNSS of 90% and 80% with cT3 tumours, respectively. CONCLUSIONS: Pelvic lymph node dissection is the only reliable technique to ensure accurate nodal staging in patients treated with radical prostatectomy for clinically localised prostate cancer. The minimum number of examined lymph nodes needed for accurate nodal staging may be predictable, being strongly dependent on prostate cancer characteristics at diagnosis.


Asunto(s)
Neoplasias de la Próstata/patología , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prostatectomía , Neoplasias de la Próstata/cirugía , Medición de Riesgo
20.
Prog Urol ; 24(15): 1021-9, 2014 Nov.
Artículo en Francés | MEDLINE | ID: mdl-25158323

RESUMEN

PURPOSE: To review current knowledge about techniques of radical nephroureterectomy (RNU) for the treatment of the upper urinary tract cancer (UTUC). MATERIAL AND METHOD: A systematic review of the literature search was performed from the database Medline (NLM, Pubmed), focused on the following key-words; nephroureterectomy; renal pelvis; ureter; bladder-cuff excision; urothelial carcinoma; surgery; lymph-node dissection; laparoscopy. RESULTS: The removal of a bladder-cuff during RNU is mandatory. After the surgical procedure, intravesical instillation of ametycine reduces significantly the risk of recurrence into the bladder. Ureteral stripping should not be practiced and continuity of the bladder wall must be restored to avoid compromising the post-operative instillation. Lymphadenectomy during RNU is of prognostic and therapeutic interests. However, the anatomic sites of lymphadenectomy and the number of nodes to be analyzed are not consensual. The oncological results of laparoscopic approach are similar to those of open surgery. CONCLUSION: The RNU must include a lymphadenectomy and an excision of a bladder-cuff and restore the sealing of the bladder to allow practicing of a EPOI. Laparoscopic or open surgery may be used equally, and must respect these rules to avoid compromising the oncological outcome.


Asunto(s)
Carcinoma de Células Transicionales/cirugía , Nefrectomía , Uréter/cirugía , Neoplasias Urológicas/cirugía , Urotelio/patología , Carcinoma de Células Transicionales/patología , Humanos , Laparoscopía , Escisión del Ganglio Linfático , Ureteroscopía , Neoplasias Urológicas/patología
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