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1.
BJU Int ; 132(5): 591-599, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37410659

RESUMEN

OBJECTIVES: To study the safety and efficacy of a personalised indocyanine-guided pelvic lymph node dissection (PLND) against extended PLND (ePLND) during radical prostatectomy (RP). PATIENTS AND METHODS: Patients who were candidates for RP and lymphadenectomy, with intermediate- or high-risk prostate cancer (PCa) according to the National Comprehensive Cancer Network guidelines, were enrolled in this randomised clinical trial. Randomisation was made 1:1 to indocyanine green (ICG)-PLND (only ICG-stained LNs) or ePLND (obturator fossa, external, internal, and common iliac and presacral LNs). The primary endpoint was the complication rate within 3 months after RP. Secondary endpoints included: rate of major complications (Clavien-Dindo Grade III-IV), time to drainage removal, length of stay, percentage of patients classified as pN1, number of LNs removed, number of metastatic LNs, rate of patients with undetectable prostate-specific antigen (PSA), biochemical recurrence (BCR)-free survival, and rate of patients with androgen-deprivation therapy at 24 months. RESULTS: A total of 108 patients were included with a median follow-up of 16 months. In all, 54 were randomised to ICG-PLND and 54 to ePLND. The postoperative complication rate was higher in the ePLND (70%) vs the ICG-PLND group (32%) (P < 0.001). Differences between major complications in both groups were not statically significant (P = 0.7). The pN1 detection rate was higher in the ICG-PLND group (28%) vs the ePLND group (22%); however, this difference was not statistically significant (P = 0.7). The rate of undetectable PSA at 12 months was 83% in the ICG-PLND vs 76% in the ePLND group, which was not statistically significant. Additionally, there were no statistically significant differences in BCR-free survival between groups at the end of the analysis. CONCLUSIONS: Personalised ICG-guided PLND is a promising technique to stage patients with intermediate- and high-risk PCa properly. It has shown a lower complication rate than ePLND with similar oncological outcomes at short-term follow-up.


Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/patología , Antígeno Prostático Específico , Antagonistas de Andrógenos , Metástasis Linfática , Escisión del Ganglio Linfático/efectos adversos , Escisión del Ganglio Linfático/métodos , Pelvis/cirugía , Prostatectomía/efectos adversos , Prostatectomía/métodos
2.
Medicina (Kaunas) ; 58(8)2022 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-36013525

RESUMEN

Background and Objectives: Patients with seminal vesicle invasion (SVI) are a highly heterogeneous group. Prognosis can be affected by many clinical and pathological characteristics. Our aim was to study whether bilateral SVI (bi-SVI) is associated with worse oncological outcomes. Materials and Methods: This is an observational retrospective study that included 146 pT3b patients treated with radical prostatectomy (RP). We compared the results between unilateral SVI (uni-SVI) and bi-SVI. The log-rank test and Kaplan-Meier curves were used to compare biochemical recurrence-free survival (BCR), metastasis-free survival (MFS), and additional treatment-free survival. Cox proportional hazard models were used to identify predictors of BCR-free survival, MFS, and additional treatment-free survival. Results: 34.93% of patients had bi-SVI. The median follow-up was 46.84 months. No significant differences were seen between the uni-SVI and bi-SVI groups. BCR-free survival at 5 years was 33.31% and 25.65% (p = 0.44) for uni-SVI and bi-SVI. MFS at 5 years was 86.03% vs. 75.63% (p = 0.1), and additional treatment-free survival was 36.85% vs. 21.93% (p = 0.09), respectively. In the multivariate analysis, PSA was related to the development of BCR [HR 1.34 (95%CI: 1.01-1.77); p = 0.03] and metastasis [HR 1.83 (95%CI: 1.13-2.98); p = 0.02]. BCR was also influenced by lymph node infiltration [HR 2.74 (95%CI: 1.41-5.32); p = 0.003]. Additional treatment was performed more frequently in patients with positive margins [HR: 3.50 (95%CI: 1.65-7.44); p = 0.001]. Conclusions: SVI invasion is an adverse pathology feature, with a widely variable prognosis. In our study, bilateral seminal vesicle invasion did not predict worse outcomes in pT3b patients despite being associated with more undifferentiated tumors.


Asunto(s)
Carcinoma , Neoplasias de la Próstata , Carcinoma/patología , Humanos , Masculino , Recurrencia Local de Neoplasia/patología , Pronóstico , Próstata/patología , Antígeno Prostático Específico , Prostatectomía , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Vesículas Seminales/patología
3.
Int J Urol ; 28(5): 566-572, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33675069

RESUMEN

OBJECTIVES: To evaluate whether indocyanine green guidance can improve the quality of extended pelvic lymph node dissection in patients undergoing radical prostatectomy. METHODS: A total of 214 patients underwent laparoscopic radical prostatectomy with indocyanine green-guided lymph node dissection plus extended pelvic lymph node dissection. These patients (group A) were matched 1:1 for clinical risk groups according to the National Comprehensive Cancer Network classification with patients who underwent the same procedure without fluorescence guidance (group B). Biochemical recurrence was defined as two consecutive prostate-specific antigen rises of at least 0.2 ng/mL. The Kaplan-Meier method and Cox regression models were used to identify predictors of biochemical recurrence. RESULTS: The median number of retrieved nodes was significantly higher in group A (22 vs 14, P < 0.001). The rate of lymph node metastases was higher in group A (65.9% vs 34.1%, P = 0.01). Increasing the yield of lymph node dissection was independently and negatively correlated with the biochemical recurrence risk in both overall and pN-positive patients (hazard ratio 0.97, P = 0.03; and hazard ratio 0.95, P = 0.02). The 5-year biochemical recurrence-free survival rates were (75.8% vs 65.9, P = 0.09) and (54.1% vs 24.9%, P = 0.023) for group A and group B in the overall cohort and pN-positive cohort, respectively. CONCLUSION: Indocyanine green-guided lymph node dissection plus extended pelvic lymph node dissection improves identification of lymphatic drainage, resulting in a higher number of lymph nodes and retrieved lymph node metastases, and allowing a more accurate local staging and a prolonged biochemical recurrence-free survival.


Asunto(s)
Laparoscopía , Neoplasias de la Próstata , Humanos , Verde de Indocianina , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Masculino , Pelvis/cirugía , Prostatectomía , Neoplasias de la Próstata/cirugía
4.
Int J Mol Sci ; 22(12)2021 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-34200878

RESUMEN

Prostate cancer (PCa) is the most commonly diagnosed cancer in men. The diagnosis is currently based on PSA levels, which are associated with overdiagnosis and overtreatment. Moreover, most PCas are localized tumours; hence, many patients with low-/very low-risk PCa could benefit from active surveillance (AS) programs instead of more aggressive, active treatments. Heterogeneity within inclusion criteria and follow-up strategies are the main controversial issues that AS presently faces. Many biomarkers are currently under investigation in this setting; however, none has yet demonstrated enough diagnostic ability as an independent predictor of pathological or clinical progression. This work aims to review the currently available literature on tissue, blood and urine biomarkers validated in clinical practice for the management of AS patients.


Asunto(s)
Biomarcadores/análisis , Neoplasias de la Próstata/diagnóstico , Espera Vigilante/estadística & datos numéricos , Progresión de la Enfermedad , Humanos , Masculino , Neoplasias de la Próstata/prevención & control , Espera Vigilante/métodos
5.
J Proteome Res ; 19(10): 4082-4092, 2020 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-32924497

RESUMEN

Prostate cancer (PCa) is a hormone-dependent tumor characterized by an extremely heterogeneous prognosis. Despite recent advances in partially uncovering some of the biological processes involved in its progression, there is still an urgent need for identifying more accurate and specific prognostic procedures to differentiate between disease stages. In this context, targeted approaches, focused on mapping dysregulated metabolic pathways, could play a critical role in identifying the mechanisms driving tumorigenesis and metastasis. In this study, a targeted analysis of the nuclear magnetic resonance-based metabolomic profile of PCa patients with different tumor grades, guided by transcriptomics profiles associated with their stages, was performed. Serum and urine samples were collected from 73 PCa patients. Samples were classified according to their Gleason score (GS) into low-GS (GS < 7) and high-GS PCa (GS ≥ 7) groups. A total of 36 metabolic pathways were found to be dysregulated in the comparison between different PCa grades. Particularly, the levels of glucose, glycine and 1-methlynicotinamide, metabolites involved in energy metabolism and nucleotide synthesis were significantly altered between both groups of patients. These results underscore the potential of targeted metabolomic profiling to characterize relevant metabolic changes involved in the progression of this neoplastic process.


Asunto(s)
Neoplasias de la Próstata , Humanos , Masculino , Metabolómica , Clasificación del Tumor , Pronóstico , Neoplasias de la Próstata/diagnóstico
6.
Prostate ; 80(6): 500-507, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32077525

RESUMEN

BACKGROUND: A 2-gene urine-based molecular test that targets messenger RNAs known to be overexpressed in aggressive prostate cancer (PCa) has been described as a helpful method for detecting clinically significant prostate cancer (grade group [GG] ≥2). We performed an external validation of this test in men undergoing initial prostate biopsy (Bx) within a Spanish opportunistic screening scenario. METHODS: We analyzed archived samples from 492 men who underwent prostate Bx in an opportunistic screening scenario, with prostate-specific antigen (PSA) 3 to 10 ng/mL and/or suspicious digital rectal exploration (DRE) and without previous multi-parametric magnetic resonance imaging (mpMRI). Urinary biomarker measurements were combined with clinical risk factors to determine a risk score, and accuracy for GG ≥ 2 PCa detection was compared with PCA3, European randomized screening in prostate cancer (ERSPC), and prostate biopsy collaborative group (PBCG) risk calculators in a validation workup that included calibration, discrimination, and clinical utility analysis. RESULTS: In our cohort, the detection rates for GG1 and GG ≥ 2 PCa were 20.3% and 14.0%, respectively. The median PSA level was 3.9 ng/mL and 13.4% of subjects had suspicious DRE findings. The median risk score for men with GG ≥ 2 PCa was 21 (interquartile range: 14-28), significantly higher than benign+GG1 PCa (10, 6-18), P < .001, achieving the highest area under the curve among the models tested, 0.749 (95% confidence interval: 0.690-0.807). The urine test was well-calibrated, while ERSPC showed a slight underestimation and PBCG a slight overestimation of risk. Assuming a GG2 non-detection rate of 11% without using mpMRI, use of the urinary biomarker-based clinical model could have helped avoid 37.2% of excess biopsies while delaying the diagnosis of eight patients (1.6% of the entire cohort) with GG ≥ 2 PCa. CONCLUSIONS: In this first evaluation in an opportunistic screening population, the urinary biomarker-based test improved the detection of clinically significant PCa. Facing men with elevated PSA and/or suspicious DRE, it could be a useful tool to help avoid excess initial Bx and to identify patients most likely to benefit from Bx.


Asunto(s)
Neoplasias de la Próstata/orina , ARN Mensajero/orina , Anciano , Antígenos de Neoplasias/orina , Detección Precoz del Cáncer , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Ensayos Clínicos Controlados Aleatorios como Asunto , Reproducibilidad de los Resultados
7.
Int J Mol Sci ; 21(8)2020 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-32316350

RESUMEN

The purpose of this study is to clinically validate a series of circulating miRNAs that distinguish between the 4 most prevalent tumor types (lung cancer (LC); breast cancer (BC); colorectal cancer (CRC); and prostate cancer (PCa)) and healthy donors (HDs). A total of 18 miRNAs and 3 housekeeping miRNA genes were evaluated by qRT-PCR on RNA extracted from serum of cancer patients, 44 LC, 45 BC, 27 CRC, and 40 PCa, and on 45 HDs. The cancer detection performance of the miRNA expression levels was evaluated by studying the area under the curve (AUC) of receiver operating characteristic (ROC) curves at univariate and multivariate levels. miR-21 was significantly overexpressed in all cancer types compared with HDs, with accuracy of 67.5% (p = 0.001) for all 4 tumor types and of 80.8% (p < 0.0001) when PCa cases were removed from the analysis. For each tumor type, a panel of miRNAs was defined that provided cancer-detection accuracies of 91%, 94%, 89%, and 77%, respectively. In conclusion, we have described a series of circulating miRNAs that define different tumor types with a very high diagnostic performance. These panels of miRNAs would constitute the basis of different approaches of cancer-detection systems for which clinical utility should be validated in prospective cohorts.


Asunto(s)
Neoplasias de la Mama/genética , MicroARN Circulante/sangre , Neoplasias Colorrectales/genética , Neoplasias Pulmonares/genética , Neoplasias de la Próstata/genética , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Detección Precoz del Cáncer , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Curva ROC
8.
BJU Int ; 124(5): 758-767, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31063245

RESUMEN

OBJECTIVES: To test whether using disease prognosis can inform a rational approach to active surveillance (AS) for early prostate cancer. PATIENTS AND METHODS: We previously developed the Cambridge Prognostics Groups (CPG) classification, a five-tiered model that uses prostate-specific antigen (PSA), Grade Group and Stage to predict cancer survival outcomes. We applied the CPG model to a UK and a Swedish prostate cancer cohort to test differences in prostate cancer mortality (PCM) in men managed conservatively or by upfront treatment in CPG2 and 3 (which subdivides the intermediate-risk classification) vs CPG1 (low-risk). We then applied the CPG model to a contemporary UK AS cohort, which was optimally characterised at baseline for disease burden, to identify predictors of true prognostic progression. Results were re-tested in an external AS cohort from Spain. RESULTS: In a UK cohort (n = 3659) the 10-year PCM was 2.3% in CPG1, 1.5%/3.5% in treated/untreated CPG2, and 1.9%/8.6% in treated/untreated CPG3. In the Swedish cohort (n = 27 942) the10-year PCM was 1.0% in CPG1, 2.2%/2.7% in treated/untreated CPG2, and 6.1%/12.5% in treated/untreated CPG3. We then tested using progression to CPG3 as a hard endpoint in a modern AS cohort (n = 133). During follow-up (median 3.5 years) only 6% (eight of 133) progressed to CPG3. Predictors of progression were a PSA density ≥0.15 ng/mL/mL and CPG2 at diagnosis. Progression occurred in 1%, 8% and 21% of men with neither factor, only one, or both, respectively. In an independent Spanish AS cohort (n = 143) the corresponding rates were 3%, 10% and 14%, respectively. CONCLUSION: Using disease prognosis allows a rational approach to inclusion criteria, discontinuation triggers and risk-stratified management in AS.


Asunto(s)
Neoplasias de la Próstata , Anciano , Progresión de la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Estudios Retrospectivos , Espera Vigilante
9.
World J Urol ; 37(1): 195-200, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29948042

RESUMEN

PURPOSE: To evaluate the efficacy of the Advance® and AdvanceXP® slings in men with stress urinary incontinence (SUI) post-radical prostatectomy and to identify predictive factors for outcome. METHODS: Included were male patients with SUI following radical prostatectomy who had a positive "repositioning test", 24 h-pad weight (PW) test < 400 g and who were continent at night and at rest. Urgency was defined as a sudden compelling desire to pass urine, which was difficult to defer. The cure rate was defined as no pad use. RESULTS: From February 2008 to October 2014, 24 AdVance® and 70 AdVance XP® were implanted. The median (range) follow-up was 49 (12-102) months. The overall cure rate was 77%. The preoperative 24 h PW was significantly related to the continence outcome (p = 0.044). A total of 12 patients (13%) presented with postoperative AUR, which was significantly related to abnormal voiding detrusor activity (p = 0.036). Twenty-two patients (23%) had postoperative urgency (16% "de novo"), which was significantly related to preoperative urgency (p = 0.003). During follow-up, a degree of deterioration of continence was observed in five patients who were classed as cured initially. To date, no reports of urethral sling erosion have been made. CONCLUSIONS: The AdVance® and AdVanceXP® slings are safe and effective in relieving SUI following post-radical prostatectomy. There were no differences between the two slings in terms of efficacy, urgency or postoperative AUR. There was a moderate rate of "de novo "urgency and low rate of loss of continence during follow-up.


Asunto(s)
Complicaciones Posoperatorias/cirugía , Prostatectomía , Cabestrillo Suburetral , Incontinencia Urinaria de Esfuerzo/cirugía , Anciano , Anciano de 80 o más Años , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/fisiopatología , Neoplasias de la Próstata/cirugía , Resultado del Tratamiento , Incontinencia Urinaria de Esfuerzo/fisiopatología , Retención Urinaria/epidemiología
10.
Neurourol Urodyn ; 38(6): 1616-1624, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31090095

RESUMEN

AIMS: The aim of this study was to compare magnetic resonance imaging (MRI) parameters in patients with mild incontinence after radical prostatectomy, who had undergone treatment with a suburethral sling. The objective was to compare patients who had been successfully treated with unsuccessful patients. METHODS: This observational cohort study at a single institution evaluated consecutive patients treated with an AdVance XP sling. MRI was performed using a 1.5 Tesla system. Preoperative urodynamic assessment and flexible cystoscopy were performed. The qualitative analysis was based on sling indentation (complete vs incomplete). The quantitative analysis comprised the following three parameters: the sling-pubis distance, the thickness of the proximal urethral bulb, and the sling backward distance (SBD), defined as the distance between the prolongation of a line through the major axis of the pubis (the line-segment joining the vertices of the pubis) and the sling indentation. The primary outcome was pad count at 3 months; cure as zero pads. A logistic univariate regression model was employed to assess the potential predictors of successful outcomes. An adjusted multivariate logistic regression model using the significant univariate factors was developed. RESULTS: Of the 83 patients enrolled, the univariate analysis revealed a relationship between failure and adverse urodynamics and between success and sling indentation, thickness of the proximal bulb and SBD. Only the association with SBD persisted in the multivariate analysis. CONCLUSIONS: MRI revealed a strong relationship between proper positioning of the sling (small SBD) and continence outcome. These data have important implications for a second surgery following initial sling failure.


Asunto(s)
Imagen por Resonancia Magnética , Próstata/cirugía , Prostatectomía/efectos adversos , Cabestrillo Suburetral , Incontinencia Urinaria/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Incontinencia Urinaria/etiología , Incontinencia Urinaria/cirugía
11.
BMC Cancer ; 17(1): 367, 2017 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-28545426

RESUMEN

BACKGROUND: Prostate cancer (PCa) is characterized by clinical and biological heterogeneity and has differential outcomes and mortality rates. Therefore, it is necessary to identify molecular alterations to define new therapeutic strategies based on the risk of progression. In this study, the prognostic relevance of the insulin-like growth factor (IGF) system was examined in molecular subtypes defined by TMPRSS2-ERG (T2E) gene fusion within a series of patients with primary localized PCa. METHODS: A cohort of 270 formalin-fixed and paraffin-embedded (FFPE) primary PCa samples from patients with more than 5 years' follow-up was collected. IGF-1R, IGF-1, IGFBP-3 and INSR expression was analyzed using quantitative RT-PCR. The T2E status and immunohistochemical ERG findings were considered in the analyses. The association with both biochemical and clinical progression-free survival (BPFS and PFS, respectively) was evaluated for the different molecular subtypes using the Kaplan-Meier proportional risk log-rank test and the Cox proportional hazards model. RESULTS: An association between IGF-1R overexpression and better BPFS was found in T2E-negative patients (35.3% BPFS, p-value = 0.016). Multivariate analysis demonstrated that IGF-1R expression constitutes an independent variable in T2E-negative patients [HR: 0.41. CI 95% (0.2-0.82), p = 0.013]. These data were confirmed using immunohistochemistry of ERG as subrogate of T2E. High IGF-1 expression correlated with prolonged BPFS and PFS independent of the T2E status. CONCLUSIONS: IGF-1R, a reported target of T2E, constitutes an independent factor for good prognosis in T2E-negative PCa. Quantitative evaluation of IGF-1/IGF-1R expression combined with molecular assessment of T2E status or ERG protein expression represents a useful marker for tumor progression in localized PCa.


Asunto(s)
Proteínas de Fusión Oncogénica , Neoplasias de la Próstata/metabolismo , Receptores de Somatomedina/metabolismo , Serina Endopeptidasas/genética , Anciano , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/mortalidad , Receptor IGF Tipo 1 , Receptores de Somatomedina/análisis , Receptores de Somatomedina/genética , Regulador Transcripcional ERG/genética
12.
Neurourol Urodyn ; 36(5): 1387-1394, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27654121

RESUMEN

AIMS: Artificial urinary sphincter (AUS) AMS-800® is an effective treatment for male stress urinary incontinence. The aim of the study was to assess the long-term effectiveness and complications of artificial urinary sphincter placement preserving the bulbospongiosus muscle. METHODS: From April 2004 to March 2014, all consecutive male patients with urinary incontinence who underwent an AUS prosthesis insertion were prospectively evaluated. Surgical technique consisted of a perineal incision for cuff placement around the bulbous urethra preserving the bulbospongiosus muscle. Cure rate was defined as no pad use. RESULTS: A total of 82 consecutive patients (median age 68 years, range: 54-78) were prospectively evaluated (median follow-up 46 months, range: 12-135). Bulbospongiosus muscles were preserved intact in all cases with no intraoperative complications. Postoperative complications were reported in 14 patients (1 urethral erosion). The overall cure rate (dry rate) was 76.8% and the median ICIQ-UI score improved from 18 (range: 8-21) to 4 (range: 0-17) (P < 0.001). Artificial urinary sphincter survival rate was 95.5% (95%CI 89.4-100%) at 24 months and 62.6% (95%CI 45.5-79.6%) at 60 months. The mechanical failure rate was 6.3% (median 46.1 months, range: 22.2-100.9) and urethral atrophy and/or inadequate compression rate was 9.5% (median 58.6 months, range: 39-101.4 months). CONCLUSIONS: Our study suggests that placement of AUS preserving the bulbospongiosus muscle is technically easy and efficient, reports excellent continence rates and lower urethral erosion rates, and could delay the onset of urethral atrophy compared to other surgical procedures used for sphincter placement.


Asunto(s)
Implantación de Prótesis/métodos , Incontinencia Urinaria de Esfuerzo/cirugía , Esfínter Urinario Artificial , Anciano , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Uretra/cirugía
13.
J Urol ; 196(5): 1429-1435, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27235788

RESUMEN

PURPOSE: We evaluated the effectiveness of indocyanine green guided pelvic lymph node dissection for the optimal staging of prostate cancer and analyzed whether the technique could replace extended pelvic lymph node dissection. MATERIALS AND METHODS: A solution of 25 mg indocyanine green in 5 ml sterile water was transperineally injected. Pelvic lymph node dissection was started with the indocyanine green stained nodes followed by extended pelvic lymph node dissection. Primary outcome measures were sensitivity, specificity, predictive value and likelihood ratio of a negative test of indocyanine green guided pelvic lymph node dissection. RESULTS: A total of 84 patients with a median age of 63.55 years and a median prostate specific antigen of 8.48 ng/ml were included in the study. Of these patients 60.7% had intermediate risk disease and 25% had high or very high risk disease. A median of 7 indocyanine green stained nodes per patient was detected (range 2 to 18) with a median of 22 nodes excised during extended pelvic lymph node dissection. Lymph node metastasis was identified in 25 patients, 23 of whom had disease properly classified by indocyanine green guided pelvic lymph node dissection. The most frequent location of indocyanine green stained nodes was the proximal internal iliac artery followed by the fossa of Marcille. The negative predictive value was 96.7% and the likelihood ratio of a negative test was 8%. Overall 1,856 nodes were removed and 603 were stained indocyanine green. Pathological examination revealed 82 metastatic nodes, of which 60% were indocyanine green stained. The negative predictive value was 97.4% but the likelihood ratio of a negative test was 58.5%. CONCLUSIONS: Indocyanine green guided pelvic lymph node dissection correctly staged 97% of cases. However, according to our data it cannot replace extended pelvic lymph node dissection. Nevertheless, its high negative predictive value could allow us to avoid extended pelvic lymph node dissection if we had an accurate intraoperative lymph fluorescent analysis.


Asunto(s)
Colorantes , Verde de Indocianina , Escisión del Ganglio Linfático/métodos , Prostatectomía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Cirugía Asistida por Computador , Anciano , Humanos , Masculino , Persona de Mediana Edad , Pelvis , Estudios Prospectivos , Prostatectomía/métodos
14.
BMC Cancer ; 15: 633, 2015 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-26362197

RESUMEN

BACKGROUND: PCA3 has been included in a nomogram outperforming previous clinical models for the prediction of any prostate cancer (PCa) and high grade PCa (HGPCa) at the initial prostate biopsy (IBx). Our objective is to validate such IBx-specific PCA3-based nomogram. We also aim to optimize the use of this nomogram in clinical practice through the definition of risk groups. METHODS: Independent external validation. Clinical and biopsy data from a contemporary cohort of 401 men with the same inclusion criteria to those used to build up the reference's nomogram in IBx. The predictive value of the nomogram was assessed by means of calibration curves and discrimination ability through the area under the curve (AUC). Clinical utility of the nomogram was analyzed by choosing thresholds points that minimize the overlapping between probability density functions (PDF) in PCa and no PCa and HGPCa and no HGPCa groups, and net benefit was assessed by decision curves. RESULTS: We detect 28% of PCa and 11 % of HGPCa in IBx, contrasting to the 46 and 20% at the reference series. Due to this, there is an overestimation of the nomogram probabilities shown in the calibration curve for PCa. The AUC values are 0.736 for PCa (C.I.95%:0.68-0.79) and 0.786 for HGPCa (C.I.95%:0.71-0.87) showing an adequate discrimination ability. PDF show differences in the distributions of nomogram probabilities in PCa and not PCa patient groups. A minimization of the overlapping between these curves confirms the threshold probability of harboring PCa >30 % proposed by Hansen is useful to indicate a IBx, but a cut-off > 40% could be better in series of opportunistic screening like ours. Similar results appear in HGPCa analysis. The decision curve also shows a net benefit of 6.31% for the threshold probability of 40%. CONCLUSIONS: PCA3 is an useful tool to select patients for IBx. Patients with a calculated probability of having PCa over 40% should be counseled to undergo an IBx if opportunistic screening is required.


Asunto(s)
Antígenos de Neoplasias/metabolismo , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/metabolismo , Anciano , Biomarcadores/orina , Biomarcadores de Tumor , Biopsia , Estudios de Cohortes , Técnicas de Apoyo para la Decisión , Humanos , Masculino , Persona de Mediana Edad , Nomogramas , Tamaño de los Órganos , Medición de Riesgo/métodos , Factores de Riesgo
15.
J Urol ; 192(1): 252-9, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24518785

RESUMEN

PURPOSE: miRNAs are noncoding RNAs that negatively regulate target mRNA gene expression. Aberrant miRNA expression is associated with prostate cancer pathogenesis. We identified miRNAs as potential biomarkers for prostate cancer diagnosis and prognosis. MATERIALS AND METHODS: Total RNA was obtained from 10 normal prostate and 50 prostate cancer samples, and analyzed using the GeneChip® miRNA 2.0 Array. At a median followup of 92 months (range 2 to 189) an independent cohort of 273 paraffin embedded prostate cancer samples was used for validation by quantitative reverse transcriptase-polymerase chain reaction. Another 92 urine samples from patients undergoing prostate biopsy were evaluated for these miRNAs. RESULTS: miR-182 and 187, the miRNAs most differentially expressed between normal and tumor tissue, were selected for further validation. miR-187 inversely correlated with cT (p = 0.125) and pT (p = 0.0002) stages, Gleason score (p = 0.003) and TMPRSS2-ERG status (p = 0.003). The log rank test showed associations of miR-182 with biochemical (p = 0.026) and clinical (p = 0.043) progression-free survival, as also noted on multivariate analysis. A significant independent improvement in the definition of risk of progression was achieved by combining miR-182 expression with Gleason score (p <0.0001). miR-187 detection in urine provided an independent predictive value for positive biopsy. A prediction model including serum prostate specific antigen, urine PCA3 and miR-187 provided 88.6% sensitivity and 50% specificity (AUC 0.711, p = 0.001). CONCLUSIONS: Results show that miR-182 and 187 are promising biomarkers for prostate cancer prognosis to identify patients at risk for progression and for diagnosis to improve the predictive capability of existing biomarkers.


Asunto(s)
Biomarcadores de Tumor , MicroARNs , Prostatectomía , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/cirugía , Anciano , Biomarcadores de Tumor/orina , Diagnóstico Precoz , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , MicroARNs/genética , MicroARNs/orina , Pronóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/orina , Estudios Retrospectivos
16.
BJU Int ; 113(6): 878-86, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24529282

RESUMEN

OBJECTIVES: To implement the use of nomograms in clinical practice showing how to choose thresholds in nomograms' predictions to select risk groups. To validate and compare the predictive ability and clinical utility of the Hospital Universitario 'Miguel Servet' (HUMS) and the updated Partin Tables 2012 (PT-2012) nomograms to predict organ-confined disease (OCD) after radical prostatectomy (RP). PATIENTS AND METHODS: Cohort of 1285 patients with prostate cancer treated with RP at Instituto Valenciano de Oncología (IVO) between 1986 and 2011. The predictive value of the nomograms was assessed by means of calibration curves, discrimination ability (area under the receiver operating characteristic (ROC) curve (AUC) and probability density functions). The clinical utility was evaluated through Vickers' decision curves and thresholds were chosen through probability density functions. RESULTS: The calibration curves showed a minimal underestimation in low probabilities (<20%), a minimal overestimation in high probabilities (>50%) in the HUMS nomogram and a regular minimal overestimation in the PT-2012. Their AUC of 0.7285 (95% confidence interval [CI] 0.7010-0.7559) and 0.7288 (95%CI 0.7013-0.7562) respectively, show an adequate discrimination ability for both predictive models in the IVO cohort. The decision curves show similar net benefits for both models. In this study we advocate for a threshold of 53% for the identification of OCD. CONCLUSIONS: The HUMS-nomogram and the PT-2012 predictions of OCD confirm their utility in a contemporary cohort of patients. Patients with a probability of OCD >53% should be classified as OCD, helping physicians to better counsel their patients. A selection of adequate thresholds, as presented in this paper, makes nomograms more accessible tools.


Asunto(s)
Modelos Estadísticos , Nomogramas , Neoplasias de la Próstata/patología , Humanos , Masculino , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Antígeno Prostático Específico/sangre , Prostatectomía , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/cirugía
17.
Arch Esp Urol ; 67(5): 419-30, 2014 Jun.
Artículo en Español | MEDLINE | ID: mdl-24914841

RESUMEN

In the present review we detail the more universally accepted selection criteria in the various protocols of active surveillance in prostate cancer; we also identify and classify twenty nomograms/predictive models useful for decision making in active surveillance for prostate cancer. These models are classified in accordance to their prediction (High grade prostate cancer in radical prostatectomy specimen [Gleason grade > 7], understaging on biopsy compared to prostatectomy specimen, pathological stage, indolent cancer or progression after expectant therapy). We also detail the predictive variables used in each model for estimations, their internal validation parameters, the samples used to generate them, and the external validations if they were done. Many of them are presented with their URL address, where they may be consulted on line, this making easier their implementation. Finally we expose our thoughts about the use of probability density functions as a useful tool for validation of these predictive models that help in the definition of cut points facilitating their clinical use and credibility.


Asunto(s)
Selección de Paciente , Neoplasias de la Próstata/diagnóstico , Humanos , Masculino , Perineo , Neoplasias de la Próstata/clasificación , Neoplasias de la Próstata/patología , Espera Vigilante
18.
Arch Esp Urol ; 67(5): 462-72, 2014 Jun.
Artículo en Español | MEDLINE | ID: mdl-24914846

RESUMEN

Identification of biomarkers that, at the time of diagnosis of prostate cancer (PCa), are associated with presence of disease or a more aggressive behavior will transform the clinical management of this disease. If both patients and clinicians would have reproducible and valid tools to estimate the specific risk of morbidity associated with PCa, then many patients would opt to and join active surveillance (AS) protocols, and consequently costs and comorbidities associated with the current overtreatment of prostate cancer would be reduced. Thus, a biomarker, or a panel of biomarkers, with high specificity to identify patients at risk for progression in AS protocols, would identify those men who could benefit from less intensive AS protocols with less repeated biopsies, so reducing the risk and cost of these invasive procedures. In this review we try to offer an overview of the new markers identified by genomic techniques and to discuss their potential role in an AS context. Moreover, the AS protocol offers an adequate setting for validation of biomarkers associated to disease progression.


Asunto(s)
Biomarcadores de Tumor/sangre , Selección de Paciente , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/terapia , Progresión de la Enfermedad , Humanos , Masculino , Neoplasias de la Próstata/genética , Espera Vigilante
19.
Int Urol Nephrol ; 56(4): 1323-1333, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37980689

RESUMEN

PURPOSE: A re-transurethral resection of the bladder (re-TURB) is a well-established approach in managing non-muscle invasive bladder cancer (NMIBC) for various reasons: repeat-TURB is recommended for a macroscopically incomplete initial resection, restaging-TURB is required if the first resection was macroscopically complete but contained no detrusor muscle (DM) and second-TURB is advised for all completely resected T1-tumors with DM in the resection specimen. This study assessed the long-term outcomes after repeat-, second-, and restaging-TURB in T1-NMIBC patients. METHODS: Individual patient data with tumor characteristics of 1660 primary T1-patients (muscle-invasion at re-TURB omitted) diagnosed from 1990 to 2018 in 17 hospitals were analyzed. Time to recurrence, progression, death due to bladder cancer (BC), and all causes (OS) were visualized with cumulative incidence functions and analyzed by log-rank tests and multivariable Cox-regression models stratified by institution. RESULTS: Median follow-up was 45.3 (IQR 22.7-81.1) months. There were no differences in time to recurrence, progression, or OS between patients undergoing restaging (135 patients), second (644 patients), or repeat-TURB (84 patients), nor between patients who did or who did not undergo second or restaging-TURB. However, patients who underwent repeat-TURB had a shorter time to BC death compared to those who had second- or restaging-TURB (multivariable HR 3.58, P = 0.004). CONCLUSION: Prognosis did not significantly differ between patients who underwent restaging- or second-TURB. However, a worse prognosis in terms of death due to bladder cancer was found in patients who underwent repeat-TURB compared to second-TURB and restaging-TURB, highlighting the importance of separately evaluating different indications for re-TURB.


Asunto(s)
Neoplasias Vesicales sin Invasión Muscular , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patología , Pronóstico , Procedimientos Quirúrgicos Urológicos , Vejiga Urinaria/cirugía , Vejiga Urinaria/patología , Cistectomía , Estadificación de Neoplasias
20.
Biomolecules ; 13(11)2023 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-38002324

RESUMEN

BACKGROUND: Androgen deprivation therapy (ADT) is a mainstay of prostate cancer in both adjuvant and palliative settings. Since androgens are crucial for functional status and psychological functions, we evaluated whether blood testosterone, androstenedione, or DHEA concentrations were associated with functional status and psychological alterations in patients with localised (PCa) or metastatic prostate cancer (mPCa) receiving ADT with analogues of luteinising hormone-releasing hormone (LHRH). METHODS: The five Fried criteria were considered to identify frailty syndrome. In addition, complementary evaluations were carried out to measure other variables of interest. Sleep quality was assessed using the Athens Insomnia Scale, cognitive functions were assessed using the Mini-Mental State Examination, and symptoms of depression were measured using the Yesavage Geriatric Depression Scale. Logistic regression analysis was performed to determine if the androgens level could be related to frailty syndrome, sleep impairment, depressive symptoms, and cognitive functions. RESULTS: The results of the multivariate analyses show that high concentrations of androstenedione were significantly associated with frailty syndrome in both groups (p = 0.018; odds ratio = 4.66, 95% confidence interval [1.30-16.6]). There were significant relationships between frailty syndrome and the systemic concentration of androstenedione (p = 0.01), but not the concentration of testosterone (p = 0.60) or DHEA (p = 0.42). In addition, the results of the non-parametric tests show significant results between a decreased gait speed in the two groups (metastatic and localised) and the concentration of androstenedione (p = 0.015). High androstenedione levels were associated with a slow walking speed in the mCaP group (p = 0.016), while high testosterone levels were associated with a better walking speed in the localised CaP group (p = 0.03). For the concentration of androstenedione in plasma, the area under the curve was 0.72, with a 95% CI of 0.55-0.88 with acceptable values, and with a cut-off point of 4.51 pg/mL, a sensitivity of 82.9%, and specificity of 53.8%. No relationships between the concentration of androgens in plasma and sleep quality, cognitive functions, or symptoms of depression suggest that the changes were specific to frailty syndrome. CONCLUSIONS: Further research into the role of androstenedione should be evaluated in follow-up studies in order to recommend its use as a suitable biomarker of frailty syndrome in prostate cancer patients.


Asunto(s)
Fragilidad , Neoplasias de la Próstata , Masculino , Anciano , Humanos , Neoplasias de la Próstata/patología , Andrógenos , Androstenodiona , Antagonistas de Andrógenos , Anciano Frágil , Testosterona , Deshidroepiandrosterona
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