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OBJECTIVES: To determine whether 6 months of preoperative apalutamide for intermediate-risk prostate cancer (IRPCa) reduces the aggregate postoperative radiotherapy risk and to evaluate associations of molecular perturbations with clinical outcomes in this study cohort. PATIENTS AND METHODS: Between May 2018 and February 2020, eligible patients with IRPCa (Gleason 3 + 4 or 4 + 3 and clinical T2b-c or prostate-specific antigen level of 10-20 ng/mL) were treated with apalutamide 240 mg/day for 6 months followed by radical prostatectomy (RP) in this single-arm, phase II trial. The primary endpoint was presence of any adverse pathological feature at risk of pelvic radiation (pathological T stage after neoadjuvant therapy [yp]T3 or ypN1 or positive surgical margins). Translational studies, including germline and somatic DNA alterations and RNA and protein expression, were performed on post-apalutamide RP specimens, and assessed for associations with clinical outcomes. RESULTS: A total of 40 patients underwent a RP, and only one patient discontinued apalutamide prior to 6 months. In all, 40% had adverse pathological features at time of RP, and the 3-year biochemical recurrence (BCR) rate was 15%, with 27.5% being not evaluable. Genomic alterations frequently seen in metastatic PCas, such as androgen receptor (AR), tumour protein p53 (TP53), phosphatase and tensin homologue (PTEN), or BReast CAncer associated gene (BRCA1/2) were underrepresented in this localised cohort. Adverse pathological features and BCR at 3-years were associated with increased expression of select cell cycle (e.g., E2F targets: adjusted P value [Padj] < 0.001, normalised enrichment score [NES] 2.47) and oxidative phosphorylation (Padj < 0.001, NES 1.62) pathways. CONCLUSIONS: Preoperative apalutamide did not reduce the aggregate postoperative radiation risk to the pre-specified threshold in unselected men with IRPCa. However, transcriptomic analysis identified key dysregulated pathways in tumours associated with adverse pathological outcomes and BCR, which warrant future study. Further investigation of preoperative therapy is underway for men with high-risk PCa.
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Prostatectomía , Neoplasias de la Próstata , Tiohidantoínas , Humanos , Masculino , Tiohidantoínas/uso terapéutico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/tratamiento farmacológico , Persona de Mediana Edad , AncianoRESUMEN
BACKGROUND: The Mediterranean diet (MD) may be beneficial for men with localized prostate cancer (PCa) on active surveillance (AS) because of its anti-inflammatory, antilipidemic, and chemopreventive properties. This study prospectively investigated adherence to the MD with Gleason score progression and explored associations by diabetes status, statin use, and other factors. METHODS: Men with newly diagnosed PCa on an AS protocol (n = 410) completed a baseline food frequency questionnaire, and the MD score was calculated across 9 energy-adjusted food groups. Cox proportional hazards models were fit to evaluate multivariable-adjusted associations of the MD score with progression-free survival; progression was defined as an increase in the Gleason grade group (GG) score over a biennial monitoring regimen. RESULTS: In this cohort, 15% of the men were diabetic, 44% of the men used statins, and 76 men progressed (median follow-up, 36 months). After adjustments for clinical factors, higher adherence to the MD was associated with a lower risk of GG progression among all men (hazard ratio [HR] per 1-unit increase in MD score, 0.88; 95% confidence interval [CI], 0.77-1.01), non-White men (HR per 1-unit increase in MD score, 0.64; 95% CI, 0.45-0.92; P for interaction = .07), and men without diabetes (HR per 1-unit increase in MD score, 0.82; 95% CI, 0.71-0.96; P for interaction = .03). When joint effects of the MD score and statin use were examined, a similar risk reduction was observed among men with high MD scores who did not use statins in comparison with men with low/moderate MD scores with no statin use. CONCLUSIONS: The MD is associated with a lower risk of GG progression in men on AS, and this is consistent with prior reports about the MD and reduced cancer morbidity and mortality.
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Dieta Mediterránea , Neoplasias de la Próstata/patología , Anciano , Estudios de Cohortes , Progresión de la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Modelos de Riesgos Proporcionales , Estudios ProspectivosRESUMEN
PURPOSE: Radiation refractory prostate cancer (RRPCa) is common and salvage cryotherapy for RRPCa is emerging as a viable local treatment option. However, there is a paucity of long-term data. The purpose of this study is to determine long-term outcomes following salvage cryotherapy for RRPca. MATERIALS AND METHODS: Patients undergoing salvage cryotherapy for biopsy-proven, localized RRPCa from 1992 through 2004 were prospectively accrued at two centers. Preoperative characteristics, perioperative morbidity and postoperative data were reviewed from our database. The primary outcomes were overall survival (OS) and disease-specific survival (DSS). The secondary outcomes were freedom from castration-resistant prostate cancer (CRPC) and freedom from androgen deprivation therapy (ADT). RESULTS: A total of 268 patients were identified with a median followup of 10.3 years. A total of 223 complication events were recorded; of them, 168 were Clavien I-II events and 55 Clavien III events. At 10 years, 69% had freedom from ADT and 76% had freedom from CRPC. The 10-year DSS rate was 81%, and the 10-year OS rate was 77%. A pre-salvage prostate specific antigen level of >10 ng/ml was associated with an increased risk of developing CRPC and initiation of ADT but was not associated with DSS or OS. The use of neoadjuvant ADT was associated with improved OS and DSS but did not affect freedom from CRPC or adjuvant ADT. CONCLUSIONS: Salvage cryotherapy for RRPCa provides excellent long-term freedom from ADT, CRPC and DSS with acceptable morbidity. OS at 10 years was 77%. Prospective trials are required for validation.
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Criocirugía/efectos adversos , Terapia Neoadyuvante/métodos , Recurrencia Local de Neoplasia/terapia , Complicaciones Posoperatorias/epidemiología , Neoplasias de la Próstata Resistentes a la Castración/terapia , Terapia Recuperativa/efectos adversos , Anciano , Antagonistas de Andrógenos/farmacología , Antagonistas de Andrógenos/uso terapéutico , Quimioterapia Adyuvante/estadística & datos numéricos , Estudios de Seguimiento , Humanos , Calicreínas/sangre , Masculino , Terapia Neoadyuvante/estadística & datos numéricos , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/mortalidad , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Próstata/patología , Próstata/efectos de la radiación , Próstata/cirugía , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata Resistentes a la Castración/sangre , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Tolerancia a Radiación , Radioterapia Adyuvante/estadística & datos numéricos , Estudios Retrospectivos , Terapia Recuperativa/métodos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: Evidence suggests that visceral fat quantity may be associated with post-prostatectomy outcomes and risk of prostate cancer related death. We evaluated whether increased fat volume, normalized to prostate size, is associated with decreased risk of disease progression. MATERIALS AND METHODS: Patients enrolled on a prospective active surveillance trial for at least 6 months who had magnetic resonance imaging within 2 years of enrollment were eligible. The surveillance protocol included a standardized followup regimen consisting of biennial prostate specific antigen and examination and yearly biopsy. Clinicopathological characteristics were collected at baseline. Three fat measurements were taken using prostate magnetic resonance imaging, including subcutaneous, linear periprostatic (pubic symphysis to prostate) and volumetrically defined periprostatic. Progression was defined as increase in Gleason grade group. Multivariable Cox proportional hazards models were used to evaluate fat volumes normalized by prostate size (stratified into tertiles). RESULTS: A total of 175 patients were included in the study. Average age was 62.5 years (SD 7.4) and average prostate specific antigen was 5.4 ng/dl (SD 3.9). Median followup was 42 months (IQR 18-60) and 50 patients (28.6%) had progression. Compared to the lowest tertile, the highest tertile of volumetric periprostatic fat measurement (HR 2.63, 95% CI 1.23-5.60, p=0.01) and linear periprostatic fat measurement (HR 2.30, 95% CI 1.01-5.22, p=0.05) were associated with worsened progression-free survival, while subcutaneous fat measurement (p=0.97) was not. Importantly, the model did not substantively change when accounting for patient body mass index and other factors. CONCLUSIONS: Increased periprostatic fat volume, normalized to prostate size, may be associated with shortened progression-free survival in men with prostate cancer on active surveillance.
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Adiposidad/fisiología , Grasa Intraabdominal/fisiopatología , Próstata/patología , Neoplasias de la Próstata/mortalidad , Espera Vigilante/estadística & datos numéricos , Anciano , Biopsia/estadística & datos numéricos , Progresión de la Enfermedad , Estudios de Seguimiento , Humanos , Grasa Intraabdominal/diagnóstico por imagen , Calicreínas/sangre , Imagen por Resonancia Magnética/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Tamaño de los Órganos , Supervivencia sin Progresión , Estudios Prospectivos , Próstata/diagnóstico por imagen , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Grasa Subcutánea/diagnóstico por imagen , Grasa Subcutánea/fisiopatologíaRESUMEN
OBJECTIVES: To evaluate the ability of magnetic resonance imaging (MRI)-targeted biopsy combined with systematic biopsy (MRI-biopsy) to reduce negative biopsies and detect clinically significant prostate cancer compared to systematic biopsy (SB) alone in the confirmatory biopsy setting using matched cohorts. PATIENTS AND METHODS: Patients were identified from an active surveillance database who had a previously positive transrectal ultrasonography-guided SB followed by a confirmatory biopsy at a single institution between 2006 and 2019. Patients were divided into two cohorts based on confirmatory biopsy technique: SB alone or MRI-biopsy (which included MRI-targeted and systematic biopsies). Cohorts were then matched on age, prostate-specific antigen (PSA) level, number of positive cores on initial biopsy and initial biopsy Gleason grade group (GG). Logistic regression was performed to identify associations with confirmatory biopsy upgrading. RESULTS: After matching, 514 patients were identified (257 per cohort). PSA, prostate volume and PSA density prior to initial biopsy, in addition to total number of initial biopsy positive cores and GG, were similar between the matched cohorts. After confirmatory biopsy, 118/257 patients (45.9%) in the MRI-biopsy cohort were upgraded compared to 46/257 patients (17.9%) in the SB cohort (P < 0.001). The rate of negative confirmatory biopsy was 32/257 (12.5%) compared to 97/257 (37.7%) in the MRI-biopsy and SB cohorts, respectively (P < 0.001). Confirmatory MRI-biopsy was associated with greater odds of confirmatory biopsy upgrade from GG 1 to ≥GG 2 compared to SB alone (odds ratio 3.62, 95% confidence interval 1.97-6.63; P < 0.001). CONCLUSION: The addition of MRI-targeted biopsies to SB in the confirmatory biopsy setting among men with previously detected prostate cancer resulted in fewer negative confirmatory biopsies and detection of more clinically significant prostate cancer compared to SB alone.
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Biopsia con Aguja Gruesa/métodos , Biopsia Guiada por Imagen , Neoplasias de la Próstata/patología , Anciano , Reacciones Falso Negativas , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/terapia , Espera VigilanteRESUMEN
PURPOSE: To report long-term follow-up of the efficacy of subtotal prostate ablation using a "hockey-stick" template, including oncologic control and quality of life (QoL) impact. METHODS: We performed a prospective controlled trial to evaluate the efficacy of subtotal prostate ablation in selected men with baseline and confirmatory biopsy showing grade group (GG) 1-2 prostate cancer. "Hockey-stick" cryoablation that included the ipsilateral hemi-gland and contralateral anterior prostate was performed. Prostate biopsies and QOL queries were performed at 6, 18 and 36 months following regional ablation, and follow-up was updated to include subsequent clinic visits. RESULTS: Between August 2009 and January 2012, 72 men were screened for eligibility and 47 opted to undergo confirmatory biopsy. Of these, 23 were deemed eligible and treated with regional cryoablation. Median age was 64 years. Median follow-up was 74 months. A single patient had < 1 mm of in-field viable tumor with therapy effect on 36-month biopsy. At time of last follow-up, a total of 12/23 (52%) patients did not have evidence of disease, all patients had preserved urinary control with no patients requiring pads for urinary incontinence. Sexual decline was significant at 3 and 6 months (P < 0.01 for both), though improvement was seen at subsequent time points. CONCLUSION: Subtotal (hockey-stick template) cryoablation of the prostate provides oncologic control to targeted tissue in a generally low-risk group with minimal impact on sexual and urinary function. Further studies are needed to evaluate this ablation template in the MRI-targeted era and higher risk populations.
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Criocirugía/métodos , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Calidad de Vida , Anciano , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Focal therapy is growing as an alternative management options for men with clinically localized prostate cancer. Parallel to the increasing popularity of active surveillance (AS) as a treatment for low-risk disease, there has been an increased interest towards providing focal therapy for patients with intermediate-risk disease. Focal therapy can act as a logical "middle ground" in patients who seek treatment while minimizing potential side effects of definitive whole-gland treatment. The aim of the current review is to define the rationale of focal therapy in patients with intermediate-risk prostate cancer and highlight the importance of patient selection in focal therapy candidacy.
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Técnicas de Ablación , Neoplasias de la Próstata/cirugía , Técnicas de Ablación/métodos , Ensayos Clínicos como Asunto , Humanos , Masculino , Tratamientos Conservadores del Órgano , Guías de Práctica Clínica como Asunto , Medición de RiesgoRESUMEN
BACKGROUND: Postchemotherapy retroperitoneal lymphadenectomy (PC-RPLND) is an essential, yet potentially morbid, therapy for the management of patients with advanced germ cell tumors. In the current study, the authors sought to define the complication profile of PC-RPLND using validated grading systems for intraoperative adverse events (iAEs) and early postoperative complications. METHODS: Between 2000 and 2018, all patients who underwent PC-RPLND were analyzed for iAEs and early postoperative complications using the Kaafarani and Clavien-Dindo classifications, respectively. Logistic regression models were conducted to assess patient and tumor factors associated with iAEs and postoperative complications. RESULTS: Of the 453 patients identified, 115 patients (25%) and 252 patients (56%), respectively, experienced an iAE and postoperative complication. Major iAEs (grade ≥3) were observed in 15 patients (3%) and major postoperative complications (grade ≥3) were noted in 80 patients (18%). The most common iAE was vascular injury (112 of 132 events; 85%), which occurred in 92 patients (20%), and the most frequent postoperative complication was ileus, which occurred in 121 patients (27%). Original and postchemotherapy retroperitoneal mass size, nonretroperitoneal metastases, intermediate and/or poor International Germ Cell Cancer Collaborative Group classification, previous RPLND, elevated tumor markers at the time of RPLND, and anticipated adjuvant surgical procedures increased the risk of both iAEs and postoperative complications. Patients who experienced an iAE were significantly more likely to experience a postoperative complication (odds ratio, 2.50; 95% confidence interval, 1.58-3.97 [P < .001]). CONCLUSIONS: In what to the authors' knowledge is the first analysis of PC-RPLND using validated classifications for both iAEs and postoperative complications, advanced disease and surgical complexity significantly increased the risks of major iAEs and postoperative complications. Standardized reporting of adverse perioperative events allows providers and patients to appreciate the consequences of PC-RPLND during counseling and decision making.
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Clasificación del Tumor/clasificación , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/cirugía , Complicaciones Posoperatorias/etiología , Adulto , Femenino , Humanos , Escisión del Ganglio Linfático/métodos , Masculino , Adulto JovenRESUMEN
Background Prostate MRI is used widely in clinical care for guiding tissue sampling, active surveillance, and staging. The Prostate Imaging Reporting and Data System (PI-RADS) helps provide a standardized probabilistic approach for identifying clinically significant prostate cancer. Despite widespread use, the variability in performance of prostate MRI across practices remains unknown. Purpose To estimate the positive predictive value (PPV) of PI-RADS for the detection of high-grade prostate cancer across imaging centers. Materials and Methods This retrospective cross-sectional study was compliant with the HIPAA. Twenty-six centers with members in the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel submitted data from men with suspected or biopsy-proven untreated prostate cancer. MRI scans were obtained between January 2015 and April 2018. This was followed with targeted biopsy. Only men with at least one MRI lesion assigned a PI-RADS score of 2-5 were included. Outcome was prostate cancer with Gleason score (GS) greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2). A mixed-model logistic regression with institution and individuals as random effects was used to estimate overall PPVs. The variability of observed PPV of PI-RADS across imaging centers was described by using the median and interquartile range. Results The authors evaluated 3449 men (mean age, 65 years ± 8 [standard deviation]) with 5082 lesions. Biopsy results showed 1698 cancers with GS greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2) in 2082 men. Across all centers, the estimated PPV was 35% (95% confidence interval [CI]: 27%, 43%) for a PI-RADS score greater than or equal to 3 and 49% (95% CI: 40%, 58%) for a PI-RADS score greater than or equal to 4. The interquartile ranges of PPV at these same PI-RADS score thresholds were 27%-44% and 27%-48%, respectively. Conclusion The positive predictive value of the Prostate Imaging and Reporting Data System was low and varied widely across centers. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Milot in this issue.
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Imagen por Resonancia Magnética/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Sistemas de Información Radiológica , Anciano , Estudios Transversales , Humanos , Masculino , Valor Predictivo de las Pruebas , Próstata/diagnóstico por imagen , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sociedades MédicasRESUMEN
OBJECTIVES: To evaluate the role of caveolin-1 (Cav-1) as a predictor of disease reclassification (DR) in men with early prostate cancer undergoing active surveillance (AS). PATIENTS AND METHODS: We analysed archived plasma samples prospectively collected from patients with early prostate cancer in a single-institution AS study. Of 825 patients enrolled, 542 had ≥1 year of follow-up. Baseline and longitudinal plasma Cav-1 levels were measured using an enzyme-linked immunosorbent assay. Tumour volume or Gleason grade increases were criteria for DR. Logistic regression analyses were used to assess associations between clinicopathological characteristics and reclassification risk. RESULTS: In 542 patients, 480 (88.6%) had stage cT1c disease, 542 (100.0%) had a median prostate-specific antigen level of 4.1 ng/mL, and 531 (98.0%) had a median Cancer of the Prostate Risk Assessment score of 1. In all, 473 (87.3%) had a Gleason score of 3+3. After a median of 3.1 years of follow-up, disease was reclassified in 163 patients (30.1%). The mean baseline Cav-1 level was 2.2 ± 8.5 ng/mL and the median 0.2 ng/mL (range, 0-85.5 ng/mL). In univariate analysis, baseline Cav-1 was a significant predictor for risk of DR (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.24-2.65; P = 0.002). In multivariate analysis, with adjustments for age, tumour length, group risk stratification and number of positive cores, reclassification risk associated with Cav-1 remained significant (OR 1.91, 95% CI 1.28-2.84; P = 0.001). CONCLUSION: Baseline plasma Cav-1 level was an independent predictor of disease classification. New methods for refining AS and intervention may result.
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Biomarcadores de Tumor/sangre , Caveolina 1/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Espera Vigilante/métodos , Anciano , Análisis de Varianza , Estudios de Cohortes , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Humanos , Modelos Logísticos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Clasificación del Tumor , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/fisiopatologíaRESUMEN
OBJECTIVE: To provide comparative data on quality of life (QoL) after prostate cancer treatment to help patients make an informed decision regarding their choice of treatment. METHODS: Patients with pathologically proven, non-metastatic, T1-T3bN0 prostate cancer were included in this prospective non-randomized study if they were to receive treatment with curative intent. Sample size was at least 181 patients per cohort/treatment type. QoL was recorded at baseline and at each follow-up using the Expanded Prostate Cancer Index Composite (EPIC) instrument. The minimal clinically important difference was defined as half of the standard deviation of the baseline score for each domain. A mixed effects model was used to compare the different treatments. Data are presented on the brachytherapy and the bilateral nerve-sparing robot-assisted radical prostatectomy (RARP) cohorts. Hormonotherapy was not allowed. RESULTS: Between November 2007 and January 2013, 181 patients who received brachytherapy and 210 patients who underwent RARP were included. Of the patients who underwent RARP, 178 had bilateral nerve-sparing and were included in the present analysis. Response rate to EPIC questionnaires were higher in the brachytherapy than in the RARP arm: 82% vs 57% at 2 years after treatment and 55% vs 45% at 4 years after treatment. In the mixed effects model, patients in the RARP arm had better QoL with regard to urinary irritation/obstruction or bother and bowel function, and lower QoL regarding sexual function and urinary incontinence. Results were confirmed in a propensity score-matched model. Patient satisfaction was significantly higher in the brachytherapy group at 1, 2 and 3 years after treatment. CONCLUSION: This prospective non-randomized study shows long-term differences in QoL domains after bilateral nerve-sparing RARP and brachytherapy. Differences in patient satisfaction should be further explored. These results could be used to counsel patients in the decision-making process.
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Braquiterapia , Prostatectomía , Neoplasias de la Próstata , Calidad de Vida , Anciano , Braquiterapia/efectos adversos , Braquiterapia/métodos , Braquiterapia/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente/estadística & datos numéricos , Estudios Prospectivos , Prostatectomía/efectos adversos , Prostatectomía/métodos , Prostatectomía/estadística & datos numéricos , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/terapia , Procedimientos Quirúrgicos RobotizadosRESUMEN
OBJECTIVE: To report the oncological outcome of salvage high-intensity focused ultrasound (S-HIFU) for locally recurrent prostate cancer after external beam radiotherapy (EBRT) from a multicentre database. PATIENTS AND METHODS: This retrospective study comprises patients from nine centres with local recurrent disease after EBRT treated with S-HIFU from 1995 to 2009. The biochemical failure-free survival (bFFS) rate was based on the 'Phoenix' definition (PSA nadir + 2 ng/mL). Secondary endpoints included progression to metastasis and cancer-specific death. Kaplan-Meier analysis was performed examining overall (OS), cancer-specific (CSS) and metastasis-free survival (MFS). Adverse events and quality of life status are reported. RESULTS: In all, 418 patients with a mean (SD) follow-up of 3.5 (2.5) years were included. The mean (SD) age was 68.6 (5.8) years and the PSA level before S-HIFU was 6.8 (7.8) ng/mL. The median PSA nadir after S-HIFU was 0.19 ng/mL. The OS, CSS and MFS rates at 7 years were 72%, 82% and 81%, respectively. At 5 years the bFFS rate was 58%, 51% and 36% for pre-EBRT low-, intermediate- and high-risk patients, respectively. The 5-year bFFS rate was 67%, 42% and 22% for pre-S-HIFU PSA level ≤4, 4-10 and ≥10 ng/mL, respectively. Complication rates decreased after the introduction of specific post-RT parameters: incontinence (grade II or III) from 32% to 19% (P = 0.002); bladder outlet obstruction or stenosis from 30% to 15% (P = 0.003); recto-urethral fistula decreased from 9% to 0.6% (P < 0.001). Study limitations include being a retrospective analysis from a registry with no control group. CONCLUSION: S-HIFU for locally recurrent prostate cancer after failed EBRT is associated with 7-year CSS and MFS rates of >80% at a price of significant morbidity. S-HIFU should be initiated early following EBRT failure.
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Recurrencia Local de Neoplasia/cirugía , Neoplasias de la Próstata/cirugía , Ultrasonido Enfocado Transrectal de Alta Intensidad , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Pronóstico , Neoplasias de la Próstata/radioterapia , Estudios Retrospectivos , Terapia Recuperativa , Insuficiencia del Tratamiento , Ultrasonido Enfocado Transrectal de Alta Intensidad/efectos adversosRESUMEN
BACKGROUND: Intratumoral heterogeneity presents a major obstacle to the widespread implementation of precision medicine. The authors assessed the origin of intratumoral heterogeneity in nonseminomatous germ cell tumor of the testis (NSGCT) and identified distinct tumor subtypes and a potentially lethal phenotype. METHODS: In this retrospective study, all consecutive patients who had been diagnosed with an NSGCT between January 2000 and December 2010 were evaluated. The histologic makeup of primary tumors and the clinical course of disease were determined for each patient. A Fine and Gray proportional hazards regression analysis was used to determine the prognostic risk factors, and the Gray test was used to detect differences in the cumulative incidence of cancer death. In a separate prospective study, next-generation sequencing was performed on tumor samples from 9 patients to identify any actionable mutations. RESULTS: Six hundred fifteen patients were included in this study. Multivariate analysis revealed that the presence of yolk sac tumor in the primary tumor (P = .0003) was associated with an unfavorable prognosis. NSGCT could be divided into 5 subgroups. Patients in the yolk sac-seminoma subgroup had the poorest clinical outcome (P = .0015). These tumors tended to undergo somatic transformation (P < .0001). Among the 9 NSGCTs that had a yolk sac tumor phenotype, no consistent gene mutation was detected. CONCLUSIONS: The current data suggest that intratumoral heterogeneity is caused in part by differentiation of pluripotent progenitor cells. Integrated or multimodal therapy may be effective at addressing intratumoral heterogeneity and treating distinct subtypes as well as a potentially lethal phenotype of NSGCT. Cancer 2016;122:1836-43. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias Testiculares/genética , Neoplasias Testiculares/patología , Adolescente , Adulto , Anciano , Diferenciación Celular/fisiología , Niño , Heterogeneidad Genética , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Células Madre Neoplásicas/patología , Fenotipo , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Adulto JovenAsunto(s)
Biopsia Guiada por Imagen/métodos , Curva de Aprendizaje , Grupo de Atención al Paciente , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Anciano , Endosonografía , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Imagen Multimodal , Próstata/diagnóstico por imagen , Próstata/patología , RectoRESUMEN
OBJECTIVES: To evaluate prospectively the associations between illness uncertainty, anxiety, fear of progression and general and disease-specific quality of life (QoL) in men with favourable-risk prostate cancer undergoing active surveillance (AS). PATIENTS AND METHODS: After meeting stringent enrollment criteria for an AS cohort study at a single tertiary care cancer centre, 180 men with favourable-risk prostate cancer completed questionnaires at the time of enrollment and every 6 months for up to 30 months. Questionnaires assessed illness uncertainty, anxiety, prostate-specific QoL (using the Expanded Prostate Cancer Index Composite [EPIC] scale) and general QoL (using the 12-time short-form health survey [SF-12]) and fear of progression. We used linear mixed-model analyses and multilevel mediation analyses. RESULTS: Sexual scores on the EPIC scale significantly declined over time (P < 0.05). Illness uncertainty was a significant predictor of all EPIC summary scores, SF-12 physical component summary (PCS) scores, mental component summary (MCS) scores and fear of progression scores (all P < 0.05), after controlling for demographic and clinicopathological factors. Anxiety predicted all EPIC summary, MCS and fear of progression scores (all P < 0.05) but not PCS scores (P = 0.08). Scores on PCS, MCS, EPIC summary scales (except sexual scale), and fear of progression did not change significantly over the study period (all P > 0.10). CONCLUSION: Over the 2.5-year follow-up, QoL remained stable; only sexual function scores significantly declined. Illness uncertainty and anxiety were significant predictors of general and prostate-specific QoL and fear of progression. Interventions to reduce uncertainty and anxiety may enhance QoL for men with prostate cancer on AS.
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Trastornos de Ansiedad/etiología , Miedo/psicología , Neoplasias de la Próstata/psicología , Espera Vigilante , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Factores de Riesgo , IncertidumbreRESUMEN
OBJECTIVES: To determine the frequency of disease reclassification and to identify clinicopathological variables associated with it in patients with favourable-risk prostate cancer undergoing active surveillance (AS). PATIENTS AND METHODS: We assessed 191 men, selected by what may be the most stringent criteria used in AS studies yet conducted, who were enrolled in a prospective cohort AS trial. Clinicopathological characteristics were analysed in a multivariate Cox proportional hazards regression model. Key features were an extended biopsy with a single core positive for Gleason score (GS) 3 + 3 (<3 mm) or 3 + 4 (<2 mm) and a prostate-specific antigen (PSA) level <4 ng/mL (adjusted for prostate volume). Biopsies were repeated every 1-2 years and clinical evaluations every 6 months. Disease was reclassified when PSA level increased by 30% from baseline, or when biopsy tumour length increased beyond the enrolment criteria, more than one positive core was detected or any grade increased to a dominant 4 pattern or any 5 pattern. RESULTS: Disease was reclassified in 32 patients (16.8%) including upgrading to GS 4 + 3 in five patients (2.6%). The median (interquartile range) follow-up time among survivors was 3 (1.9-4.6) years. Overall, 13 of the 32 (40.6%) had incremental increases in GS. Tumour length (hazard ratio 2.95, 95% confidence interval [CI] 1.34-6.46; P = 0.007) and older age (hazard ratio 1.05, 95% CI 1.00-1.09; P = 0.05) were identified as significant and marginally significant predictors of disease reclassification, respectively. Disease remained stable in 83.2% of patients. CONCLUSION: The need persists for improvements in risk stratification and predictive indicators of cancer progression.
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Neoplasias de la Próstata/clasificación , Neoplasias de la Próstata/terapia , Espera Vigilante , Anciano , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico , Medición de RiesgoRESUMEN
INTRODUCTION: To describe immediate perioperative outcomes of robot-assisted laparoscopic salvage radical prostatectomy for recurrent cancer following radiation therapy, and compare outcomes to a contemporary open surgical cohort. MATERIALS AND METHODS: A total of 39 patients underwent salvage radical prostatectomy with pelvic lymphadenectomy (20 robotic, 19 open) for local recurrence following radiation therapy at a single institution between 2007 and 2011. Intraoperative parameters, postoperative complications, and oncological outcomes, were recorded. Wilcoxon rank-sum test and Fisher's exact test were used for comparison of continuous and categorical variables respectively. Mean values of numeric variables are reported with standard deviation. RESULTS: The cohorts were similar with respect to age, ethnicity, and American Society of Anesthesiologists Score classification. Estimated blood loss was lower in the robotic group versus the open group (381.3 mL versus 865.0 mL, p = 0.001). There was no difference in the rate of intraoperative complications, postoperative Clavien = 3 complications (30% versus 15.7%), anastomotic leak (40% versus 42.1%), or wound infection (0% versus 15.7%) in the robotic and open groups. Mean node yield (10.4 versus 11.8), positive surgical margins (15.0% versus 15.7%), and undetectable prostate-specific antigen rate (78% versus 60%) were also similar between the robotic and open groups. CONCLUSIONS: Robotic salvage prostatectomy appears to have no significant difference to the open approach with respect to safety and surgical quality as measured by complications, node yield and surgical margins in this retrospective single-institution series.
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Escisión del Ganglio Linfático/métodos , Recurrencia Local de Neoplasia/cirugía , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Terapia Recuperativa/métodos , Infección de la Herida Quirúrgica/etiología , Anciano , Fuga Anastomótica/etiología , Pérdida de Sangre Quirúrgica , Humanos , Complicaciones Intraoperatorias/etiología , Laparoscopía , Metástasis Linfática , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/patología , Pelvis , Antígeno Prostático Específico/sangre , Prostatectomía/efectos adversos , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Procedimientos Quirúrgicos Robotizados , Resultado del TratamientoRESUMEN
BACKGROUND: The aim of the study was to assess the morbidity and efficacy of repeat cryoablation (CA) in the treatment of localized prostate cancer. METHODS: Twenty-seven patients with median age of 71 years (range 48-80) who underwent repeat CA between April 2003 and April 2011 at a single institution were included. The median initial prostate-specific antigens (PSA) and Gleason values were 6.2 ng/ml (range 4-23.6) and 7 (range 6-9), respectively. Twenty-four patients underwent two CA treatments, and three patients underwent three CA treatments. Pre- and perioperative parameters and oncological and functional outcomes were evaluated. RESULTS: No intraoperative complications occurred. After the first CA, PSA was undetectable in 10 patients, and the median nadir PSA value was 0.65 ng/ml (range 0.1-4.9). After the second CA, 4 patients had undetectable PSA, and the median nadir PSA value was 1.25 ng/ml (range 0.2-7.9). For patients who underwent a third CA treatment, no patients had undetectable PSA, and the subsequent median nadir PSA value was 1.6 ng/ml (range 0.4-4.5). Two patients had incontinence (1 pad per day) following repeat CA. One patient had urinary retention after the third CA treatment, and one had urethral stricture. The mean hospitalization and follow-up periods were 1 day (range 0-2) and 51.5 months (range 11-96), respectively. CONCLUSIONS: Repeat CA successfully reduced PSA levels, and complications were modest. We conclude that repeat CA is a feasible, safe, and effective treatment option for localized prostate cancer.
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Criocirugía/métodos , Neoplasias de la Próstata/cirugía , Anciano , Anciano de 80 o más Años , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Neoplasias de la Próstata/patología , Reoperación , Estudios Retrospectivos , SeguridadRESUMEN
OBJECTIVE: To assess the oncological and functional outcomes of primary prostate cryoablation for men with clinical stage T3 (cT3) prostate cancer, as although radical prostatectomy (RP) or external beam radiotherapy (EBRT) are the standard treatments for locally advanced cT3 prostate cancer some patients opt for nonextirpative prostate cryoablation instead. PATIENTS AND METHODS: The Cryo-On-Line Database (COLD) Registry was queried to identify patients with cT3 prostate cancer treated with whole-gland cryoablation (366 patients). We assessed biochemical disease-free survival (bDFS) using the Phoenix definition and determined reported rates of urinary incontinence and retention, sexual activity, and rectourethral fistulisation after treatment. Patients were subsequently assessed according to whether they were administered neoadjuvant androgen-deprivation therapy or not (ADT; 115 patients, 31.4%). RESULTS: For the entire cohort, the 36- and 60-month bDFS rates were 65.3% and 51.9%, respectively. Patients who received neoadjuvant ADT had statistically nonsignificantly higher 36- and 60-month bDFS rates (68.0% and 55.4%, respectively) than patients who did not receive neoadjuvant ADT (55.3% and 36.9%, respectively). The after treatment urinary incontinence rate was 2.6%; urinary retention rate, 6.0%; sexual activity rate, 30.4%; and rectourethral fistulisation rate, 1.1%. CONCLUSIONS: Cryoablation for patients with cT3 prostate cancer leads to less favourable bDFS than that after RP or RT for the same group of men. The after treatment rectourethral fistulisation rates for patients with cT3 disease are higher than in those with organ-confined prostate cancer treated with cryoablation; however, urinary dysfunction and sexual activity rates are similar for men with cT3 to those reported from this same registry in men with cT2 disease. The addition of neoadjuvant ADT (though not studied prospectively here) should be strongly considered if a patient with cT3 prostate cancer is to be treated with cryoablation.