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The genomic and immune landscapes of prostate cancer differ by self-identified race. However, few studies have examined the genome-wide copy number landscape and immune content of matched cohorts with genetic ancestry data and clinical outcomes. Here, we assessed prostate cancer somatic copy number alterations (sCNA) and tumor immune content of a grade-matched, surgically treated cohort of 145 self-identified Black (BL) and 145 self-identified White (WH) patients with genetic ancestry estimation. A generalized linear model adjusted with age, preoperative prostate-specific antigen (PSA), and Gleason Grade Group and filtered for germline copy number variations (gCNV) identified 143 loci where copy number varied significantly by percent African ancestry, clustering on chromosomes 6p, 10q, 11p, 12p, and 17p. Multivariable Cox regression models adjusted for age, preoperative PSA levels, and Gleason Grade Group revealed that chromosome 8q gains (including MYC) were significantly associated with biochemical recurrence and metastasis, independent of genetic ancestry. Finally, Treg density in BL and WH patients was significantly correlated with percent genome altered, and these findings were validated in the TCGA cohort. Taken together, our findings identify specific sCNA linked to genetic ancestry and outcome in primary prostate cancer and demonstrate that Treg infiltration varies by global sCNA burden in primary disease.
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Neoplasias de la Próstata , Humanos , Masculino , Variaciones en el Número de Copia de ADN , Clasificación del Tumor , Modelos de Riesgos Proporcionales , Antígeno Prostático Específico/genética , Neoplasias de la Próstata/etnología , Neoplasias de la Próstata/genética , Grupos RacialesRESUMEN
We present the case of a 38-year-old male with a past presumed history of traumatic genitourinary injury. Twenty-one years later, he presented with dysuria, urinary frequency, and urinary urgency and was found to have membranous stricture as well as a urethral diverticulum filled with calculi. For this rare case, we elected surgical management via urethroplasty and a urethral diverticulectomy. We present his clinical course and brief review of the diagnosis and management of male urethral diverticula.
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Introduction: Procedure-specific guidelines for postsurgical opioid use can decrease overprescribing and facilitate opioid stewardship. Initial recommendations were based on feasibility data from limited pilot studies. This study aims to refine opioid prescribing recommendations for endourological and minimally invasive urological procedures by integrating emerging clinical evidence with a panel consensus. Materials and Methods: A multistakeholder panel was convened with broad subspecialty expertise. Primary literature on opioid prescribing after 16 urological procedures was systematically assessed. Using a modified Delphi technique, the panel reviewed and revised procedure-specific recommendations and opioid stewardship strategies based on additional evidence. All recommendations were developed for opioid-naive adult patients after uncomplicated procedures. Results: Seven relevant studies on postsurgical opioid prescribing were identified: four studies on ureteroscopy, two studies on robotic prostatectomy including a combined study on robotic nephrectomy, and one study on transurethral prostate surgery. The panel affirmed prescribing ranges to allow tailoring quantities to anticipated need. The panel noted that zero opioid tablets would be potentially appropriate for all procedures. Following evidence review, the panel reduced the maximum recommended quantities for 11 of the 16 procedures; the other 5 procedures were unchanged. Opioids were no longer recommended following diagnostic endoscopy and transurethral resection procedures. Finally, data on prescribing decisions supported expanded stewardship strategies for first-time prescribing and ongoing quality improvement. Conclusion: Reductions in initial opioid prescribing recommendations are supported by evidence for most endourological and minimally invasive urological procedures. Shared decision-making before prescribing and periodic reevaluation of individual prescribing patterns are strongly recommended to strengthen opioid stewardship.
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Analgésicos Opioides , Trastornos Relacionados con Opioides , Adulto , Analgésicos Opioides/uso terapéutico , Humanos , Masculino , Procedimientos Quirúrgicos Mínimamente Invasivos , Dolor Postoperatorio/tratamiento farmacológico , Pautas de la Práctica en MedicinaRESUMEN
This study leveraged a gene-protein assay to assess MYC and PTEN status at prostate cancer biopsy and examined the association with adverse outcomes after surgery. MYC gain and PTEN loss were simultaneously assessed by chromogenic in situ hybridization and immunohistochemistry, respectively, using 277 Grade Group 2 needle biopsies that were followed by prostatectomy. The maximal size of cribriform Gleason pattern 4 carcinoma (CRIB), the presence of intraductal carcinoma (IDC), and percentage of Gleason pattern 4 carcinoma at biopsy were also annotated. MYC gain or PTEN loss was present in 19% and 18% of biopsies, respectively, whereas both alterations were present in 9% of biopsies. Tumors with one or both alterations were significantly more likely to have non-organ-confined disease (NOCD) at radical prostatectomy. In logistic regression models, including clinical stage, tumor volume on biopsy, and presence of CRIB/IDC, cases with MYC gain and PTEN loss remained at higher risk for NOCD (odds ratio, 6.23; 95% CI, 1.74-24.55; P = 0.005). The area under the curve for a baseline model using CAPRA variables (age, prostate-specific antigen, percentage of core involvement, clinical stage) was increased from 0.68 to 0.69 with inclusion of CRIB/IDC status and to 0.75 with MYC/PTEN status. Dual MYC/PTEN status can be assessed in a single slide and is independently associated with increased risk of NOCD for Grade Group 2 biopsies.
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Biomarcadores de Tumor , Técnicas de Diagnóstico Molecular , Fosfohidrolasa PTEN/metabolismo , Próstata/patología , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Adulto , Anciano , Humanos , Inmunohistoquímica/métodos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , Clasificación del Tumor , Estadificación de Neoplasias , Fosfohidrolasa PTEN/genética , Pronóstico , Próstata/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/mortalidad , Unión Proteica , Proteínas Proto-Oncogénicas c-myc/genética , Reproducibilidad de los ResultadosRESUMEN
Black men die more often of prostate cancer yet, interestingly, may derive greater survival benefits from immune-based treatment with sipuleucel-T. Since no signatures of immune-responsiveness exist for prostate cancer, we explored race-based immune-profiles to identify vulnerabilities. Here we show in multiple independent cohorts comprised of over 1,300 patient samples annotated with either self-identified race or genetic ancestry, prostate tumors from Black men or men of African ancestry have increases in plasma cell infiltrate and augmented markers of NK cell activity and IgG expression. These findings are associated with improved recurrence-free survival following surgery and nominate plasma cells as drivers of prostate cancer immune-responsiveness.
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Células Plasmáticas/inmunología , Neoplasias de la Próstata/inmunología , Negro o Afroamericano/genética , Anciano , Movimiento Celular , Estudios de Cohortes , Humanos , Inmunoglobulina G/genética , Inmunoglobulina G/inmunología , Células Asesinas Naturales/inmunología , Masculino , Persona de Mediana Edad , Próstata/inmunología , Próstata/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/fisiopatologíaRESUMEN
BACKGROUND: Homeobox B13 (HOXB13) expression regulates normal prostate development and mutations are associated with prostate cancer (PCa) formation. OBJECTIVE: To assess the role of HOXB13 mRNA expression in PCa progression following radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide expression profiles were queried from two retrospective prostatectomy cohorts with follow-up data (Mayo Clinic, n=780; Johns Hopkins Medical Institute [JHMI], n=355), and a prospective genomic registry (n=5239). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable Cox regressions were used to analyze metastasis-free survival (MFS). RESULTS AND LIMITATIONS: HOXB13 expression in primary PCa increased with increasing tumor grade and with high metastatic potential based on a genomic signature. The highest quartile of HOXB13 expression was associated with worse MFS compared with the lowest quartile (Mayo Clinic: adjusted hazard ratio [AHR] 1.46, 95% confidence interval [CI] 1.03-2.06, and JHMI: AHR 1.80, 95% CI 1.02-3.19). The combinations of high HOXB13 expression and low expression of its binding partner, MEIS1 (AHR 2.03, 95% CI 1.54-2.66) or MEIS2 (AHR 1.73, 95% CI 1.33-2.26), portended worse MFS. Additionally, high HOXB13 expression in combination with low MEIS1/2 expression correlated with high expression of androgen receptor-mediated genes. The retrospective nature of this study subjects the findings to a bias due to unmeasured variables. CONCLUSIONS: Primary PCa tumors with increased HOXB13 expression have an increased propensity for metastases following prostatectomy, particularly in the setting of low MEIS1/2 expression. High androgen receptor output may account for worse outcomes for these tumors and suggests heightened sensitivity to androgen suppression. PATIENT SUMMARY: Using genomic data from a large number of prostate cancer (PCa) tumors, we found that increased expression of homeobox B13 (HOXB13), a gene related to normal prostate development, was associated with worse outcomes following surgery for PCa. A biomarker signature suggests that these tumors would be more susceptible to androgen suppression, a common treatment for PCa. Take Home Messagece:: In multiple large cohorts, prostate cancer tumors with high homeobox B13 (HOXB13) expression and low expression of its binding partner MEIS1/2 were enriched with high androgen receptor output and had an increased propensity for metastases following surgery.
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Genes Homeobox , Neoplasias de la Próstata , Proteínas de Homeodominio/genética , Humanos , Masculino , Estudios Prospectivos , Próstata , Prostatectomía , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: Small cell neuroendocrine (NE) carcinomas of the prostate classically lose androgen receptor (AR) expression, may harbor loss of the RB1, TP53, and PTEN tumor suppressor genes, and are associated with a poor prognosis. However usual-type adenocarcinomas may also contain areas of NE differentiation, and in this context the molecular features and biological significance are less certain. METHODS: We examined the molecular phenotype and oncologic outcomes of primary prostate adenocarcinomas with ≥5% NE differentiation (≥5% chromogranin A-positive NE cells in any given tumor spot on tissue microarray) using three independent study sets: a set of tumors with paneth cell-like NE differentiation (n = 26), a retrospective case-cohort of intermediate- and high-risk patients enriched for adverse outcomes (n = 267), and primary tumors from a retrospective series of men with eventual castration-resistant metastatic prostate cancer (CRPC) treated with abiraterone or enzalutamide (n = 55). RESULTS: Benign NE cells expressed significantly lower quantified AR levels compared with paired benign luminal cells (P < .001). Similarly, paneth-like NE carcinoma cells or carcinoma cells expressing chromogranin A expressed significantly lower quantified AR levels than paired non-NE carcinoma cells (P < .001). Quantified ERG protein expression, was also lower in chromogranin A-labeled adenocarcinoma cells compared with unlabeled cells (P < .001) and tumors with NE differentiation showed lower gene expression scores for AR activity compared with those without. Despite evidence of lower AR signaling, adenocarcinomas with NE differentiation did not differ by prevalence of TP53 missense mutations, or PTEN or RB1 loss, compared with those without NE differentiation. Finally, NE differentiation was not associated with time to metastasis in intermediate- and high-risk patients (P = .6 on multivariate analysis), nor with progression-free survival in patients with CRPC treated with abiraterone or enzalutamide (P = .9). CONCLUSION: NE differentiation in usual-type primary prostate adenocarcinoma is a molecularly and clinically distinct form of lineage plasticity from that occurring in small cell NE carcinoma.
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Células Neuroendocrinas/patología , Tumores Neuroendocrinos/patología , Neoplasias de la Próstata/patología , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Carcinoma de Células Pequeñas/genética , Carcinoma de Células Pequeñas/metabolismo , Carcinoma de Células Pequeñas/patología , Diferenciación Celular/fisiología , Estudios de Cohortes , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Células Neuroendocrinas/metabolismo , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/metabolismo , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , Receptores Androgénicos/biosíntesis , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Proteínas de Unión a Retinoblastoma/genética , Proteínas de Unión a Retinoblastoma/metabolismo , Estudios Retrospectivos , Transducción de Señal , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
Hemorrhage after robotic-assisted partial nephrectomy (RAPN) is uncommon but can cause significant morbidity. We present a case of acute hemorrhage isolated to the collecting system that was managed with renal artery embolization (RAE). A 76-year-old male developed sudden onset transfusion-dependent hematuria and hypotension following uncomplicated RAPN. He had no signs of intra-abdominal bleeding and his hypotension was responsive to volume resuscitation. Renal angiography identified a segmental artery with extravasation into the collecting system. RAE eliminated the patient's hematuria, the need for further transfusion, and allowed preservation of renal function. RAE is a viable option for collecting system hemorrhage following RAPN.
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BACKGROUND: Direct high-quality evidence is lacking evaluating perioperative pharmacologic prophylaxis (PP) after radical prostatectomy (RP) to prevent venous thromboembolism (VTE) leading to significant practice variation. OBJECTIVE: To study the impact of in-hospital PP on symptomatic VTE incidence and adverse events after RP at 30 d, with the secondary objective of evaluating overall VTE in a screening subcohort. DESIGN, SETTING, AND PARTICIPANTS: A prospective, phase 4, single-center, randomized trial of men with prostate cancer undergoing open or robotic-assisted laparoscopic RP was conducted (July 2017-November 2018). INTERVENTION: PP (subcutaneous heparin) plus routine care versus routine care alone. The screening subcohort was offered lower extremity duplex ultrasound at 30 d. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: The primary efficacy outcome was symptomatic VTE incidence (pulmonary embolism [PE] or deep venous thrombosis [DVT]). Primary safety outcomes included the incidence of symptomatic lymphocele, hematoma, or bleeding after surgery. Secondary outcomes were overall VTE, estimated blood loss, total surgical drain output, complications, and surveillance imaging bias. Fisher's exact test and modified Poisson regression were performed. RESULTS AND LIMITATIONS: A total of 501 patients (75% robotic) were randomized and >99% (500/501) completed follow-up. At second interim analysis (N = 445), the symptomatic VTE rate was 2.3% (four PE + DVT and one DVT) for routine care versus 0.9% (one PE + DVT and one DVT) for PP (relative risk 0.40 [95% confidence interval 0.08-2.03], p = 0.3) meeting a futility threshold for early stopping. In the screening subcohort, the overall VTE rate was 3.3% versus 2.4% (p = 0.7). Results were similar at the final analysis (symptomatic VTE: 2.0% vs 0.8%, p = 0.3; overall VTE: 2.9% vs 2.8%, p = 1). No differences were observed in safety or secondary outcomes. All VTE events (seven symptomatic and three asymptomatic) occurred in patients undergoing pelvic lymph node dissection. CONCLUSIONS: This study was not able to demonstrate a statistically significant reduction in symptomatic VTE associated with PP. There was no increase in the development of symptomatic lymphoceles, bleeding, or other adverse events. Given that the event rate was lower than powered for, further research is needed among high-risk patients (Caprini score ≥8) or patients receiving pelvic lymph node dissection. PATIENT SUMMARY: In this report, we randomized patients undergoing radical prostatectomy to perioperative pharmacologic prophylaxis or routine care alone. We found that pharmacologic prophylaxis did not reduce postoperative symptomatic venous thromboembolism significantly for men at routine risk. Importantly, pharmacologic prophylaxis did not increase adverse events, such as formation of lymphoceles or bleeding, and can safely be implemented when indicated for patients with risk factors undergoing radical prostatectomy.
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Anticoagulantes/administración & dosificación , Heparina/administración & dosificación , Complicaciones Posoperatorias/prevención & control , Prostatectomía , Embolia Pulmonar/prevención & control , Tromboembolia Venosa/prevención & control , Trombosis de la Vena/prevención & control , Anciano , Quimioprevención , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Periodo Preoperatorio , Estudios Prospectivos , Prostatectomía/métodosRESUMEN
PURPOSE: The potential biological determinants of aggressive prostate cancer in African American (AA) men are unknown. Here we characterize prostate cancer genomic alterations in the largest cohort to date of AA men with clinical follow-up for metastasis, with the aim to elucidate the key molecular drivers associated with poor prognosis in this population. EXPERIMENTAL DESIGN: Targeted sequencing was retrospectively performed on 205 prostate tumors from AA men treated with radical prostatectomy (RP) to examine somatic genomic alterations and percent of the genome with copy-number alterations (PGA). Cox proportional hazards analyses assessed the association of genomic alterations with risk of metastasis. RESULTS: At RP, 71% (145/205) of patients had grade group ≥3 disease, and 49% (99/202) were non-organ confined. The median PGA was 3.7% (IQR = 0.9%-9.4%) and differed by pathologic grade (P < 0.001) and stage (P = 0.02). Median follow-up was 5 years. AA men with the highest quartile of PGA had increased risks of metastasis (multivariable: HR = 13.45; 95% CI, 2.55-70.86; P = 0.002). The most common somatic mutations were SPOP (11.2%), FOXA1 (8.3%), and TP53 (3.9%). The most common loci altered at the copy number level were CDKN1B (6.3%), CHD1 (4.4%), and PTEN (3.4%). TP53 mutations and deep deletions in CDKN1B were associated with increased risks of metastasis on multivariable analyses (TP53: HR = 9.5; 95% CI, 2.2-40.6; P = 0.002; CDKN1B: HR = 6.7; 95% CI, 1.3-35.2; P = 0.026). CONCLUSIONS: Overall, PGA, somatic TP53 mutations, and a novel finding of deep deletions in CDKN1B were associated with poor prognosis in AA men. These findings require confirmation in additional AA cohorts.
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Biomarcadores de Tumor/genética , Negro o Afroamericano/estadística & datos numéricos , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Eliminación de Gen , Recurrencia Local de Neoplasia/patología , Prostatectomía/métodos , Neoplasias de la Próstata/patología , Estudios de Seguimiento , Genómica , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/terapia , Pronóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/terapia , Estudios Retrospectivos , Tasa de Supervivencia , Población Blanca/estadística & datos numéricosRESUMEN
PURPOSE: Few groups have investigated the combined effects of PTEN loss and ERG expression on the outcomes of metastasis of or death from prostate cancer in surgically treated patients. We examined the association of PTEN/ERG status with lethal prostate cancer in patients treated with radical prostatectomy. MATERIALS AND METHODS: Included in analysis were 791 patients with clinically localized prostate cancer treated with radical prostatectomy at a single institution. Genetically validated immunohistochemistry assays for PTEN and ERG were performed on tissue microarrays. Multivariable Cox proportional hazard models were used to assess the association of PTEN/ERG status with lethal prostate cancer (defined as metastasis or prostate cancer specific death), adjusting for patient age, race, pathological grade and stage, and surgical margin status. RESULTS: Median followup in the cohort was 12.8 years. Of 791 cases 203 (25%) demonstrated PTEN loss and 330 of 776 (43%) were ERG positive. On multivariable analysis PTEN loss (HR 1.9, 95% CI 1.2-3.0, p=0.012) but not ERG expression (HR 0.6, 95% CI 0.4-1.1, p=0.11) was associated with an increased risk of lethal prostate cancer. The association of PTEN loss with lethal disease only remained among men with ERG negative tumors (HR 2.3, 95% CI 1.3-4.1, p=0.005) and not ERG positive tumors (HR 1.1, 95% CI 0.6-2.1, p=0.81). CONCLUSIONS: PTEN loss is associated with an increased risk of lethal prostate cancer after radical prostatectomy and this risk is most pronounced in the subgroup of patients with ERG negative tumors. This work corroborates the use of PTEN and ERG status for risk stratification in surgically treated patients.
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Fosfohidrolasa PTEN/análisis , Prostatectomía , Neoplasias de la Próstata/química , Neoplasias de la Próstata/cirugía , Humanos , Masculino , Persona de Mediana Edad , Prostatectomía/métodos , Regulador Transcripcional ERG/análisis , Resultado del TratamientoRESUMEN
Prostate cancer (PCa) is the most common noncutaneous malignancy affecting American men and the second most common cause of cancer death. The traditional risk classification schemes for PCa are limited due to the vast clinical and molecular heterogeneity of the disease. Fortunately, recent advancements in sequencing technologies have provided us with valuable insight into the genomics of PCa. To date, a wide array of recurrent genomic alterations in PCa have been identified. Incorporating these distinct molecular subtypes of PCa into prediction models provides opportunities for improved risk stratification and ultimately better patient outcomes. In this review, we summarize the key molecular subtypes of PCa and focus on those genomic alterations that have clinical implications for diagnosis, prognosis, and therapeutic response.
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Neoplasias de la Próstata/genética , Biomarcadores de Tumor , Humanos , Masculino , Terapia Molecular Dirigida , Pronóstico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/terapiaRESUMEN
OBJECTIVES: To evaluate the effect of a prospective opioid reduction intervention after radical prostatectomy (RP; based on a surgery-specific guideline and education) on post-discharge opioid prescribing, use, disposal, and need for additional opioid medication. PATIENTS AND METHODS: A prospective, non-randomised, pre-post interventional trial of patients undergoing RP for prostate cancer (August 2017-November 2018) was conducted as part of the Opioid Reduction Intervention for Open, Laparoscopic, and Endoscopic Surgery (ORIOLES) Initiative. An evidence-based intervention including: a discharge sheet, nursing education, and standardised prescribing guideline, was applied with the primary outcome of total oral morphine equivalents (OMEQ) used after RP. Secondary outcomes included opioid prescribing, opioid disposal, need for additional opioid medication, and presence of incisional/post-surgical abdominal pain at 30 days after RP. RESULTS: A total of 214 (Pre-Intervention arm) and 229 (Post-Intervention arm) adult patients were enrolled (100% follow-up). The intervention reduced post-discharge opioid prescribing (from 224.3 to 120.3 mg; -46.4%, P = 0.01), reduced opioid use (from 52.1 to 38.3 mg; -26.5%, P < 0.01), and increased opioid disposal (+13.5%, P < 0.01). Greater prescribing of opioids at discharge, higher body mass index, and use of opioid medication prior to surgery, were independently associated with greater post-discharge opioid use, while history of a chronic pain diagnosis was not statistically significant. In the Post-Intervention cohort, 2.2% of patients needed additional medication for post-surgical pain (0.9% obtained a prescription) and 1.3% initiated long-term use. CONCLUSIONS: A prospective, evidence-based intervention reduced post-discharge opioid prescribing and use, while increasing disposal after RP. Risk factors for increased opioid use were identified. The results support expanding the use of evidence-based opioid reduction interventions to other surgical specialties.
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Analgésicos Opioides/uso terapéutico , Prescripciones de Medicamentos/estadística & datos numéricos , Utilización de Medicamentos/estadística & datos numéricos , Dolor Postoperatorio/tratamiento farmacológico , Programas de Monitoreo de Medicamentos Recetados , Prostatectomía , Adulto , Humanos , Masculino , Estudios Prospectivos , Prostatectomía/métodosRESUMEN
PURPOSE: Opioids are frequently overprescribed after surgery. The 2018 AUA position statement on opioid use suggests using the lowest dose and potency to achieve pain control but the lack of procedure specific prescribing guidelines contributes to wide variation in prescribing patterns. To address this gap we aimed to develop opioid prescribing recommendations through an expert panel consensus. MATERIALS AND METHODS: The 15-member multidisciplinary expert panel included representatives from 5 stakeholder groups. A 3-step modified Delphi method was used to develop recommendations for postoperative opioid prescribing. Recommendations were made for opioid naïve patients without chronic pain conditions. The panel used oxycodone 5 mg equivalents to define the number of prescribed tablets. RESULTS: Procedure specific recommendations were developed for 16 endourological and minimally invasive urological procedures. The panel agreed that not all patients desire or require opioids and, thus, the minimum recommended number of opioid tablets for all procedures was 0. Consensus ranges were identified to allow prescribed quantities to be aligned with expected needs. The maximum recommended quantity varied by procedure from 0 tablets (3 procedures) to 15 tablets (6 procedures) with a median of 10 tablets. Attending urologists typically voted for higher opioid quantities than nonattending panel members. The panel identified 8 overarching strategies for opioid stewardship, including contextualizing postoperative pain management with patient goals and preferences, and maximizing nonopioid therapies. CONCLUSIONS: Procedure specific guidelines for postoperative opioid prescribing may help align individual urologist prescribing habits with consensus recommendations. These guidelines can aid quality improvement efforts to reduce overprescribing in urology.
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Analgésicos Opioides/uso terapéutico , Manejo del Dolor/métodos , Dolor Postoperatorio/tratamiento farmacológico , Pautas de la Práctica en Medicina/normas , Procedimientos Quirúrgicos Urológicos , Técnica Delphi , Humanos , Estados UnidosRESUMEN
BACKGROUND: The SPINK1 molecular subtype is more common in African-American (AA) men with prostatic adenocarcinoma (PCa) than European Americans (EA). Studies have suggested that SPINK1 expression is associated with more aggressive disease. However, the size, follow-up, and racial diversity of prior patient cohorts have limited our understanding of SPINK1 expression in AA men. The objective was to determine the associations between SPINK1 subtype, race, and oncologic outcomes after radical prostatectomy (RP). METHODS: A total of 186 AA and 206 EA men who underwent RP were matched according to pathologic grade. We examined SPINK1 status by immunohistochemistry on tissue microarrays using a genetically validated assay. Cox proportional hazard analyses assessed the association of SPINK1 status with oncologic outcomes in race-specific multivariate models. A second objective was to determine the correlation between CD3/CD8 T cell densities with SPINK1 status and race, using immunostaining and automated image analysis. RESULTS: SPINK1-positive subtype was present in 25% (45/186) of AA and 15% (30/206) of EA men (p = 0.013). There were no differences in pathologic grade, pathologic stage, biochemical recurrence (BCR)-free survival, or metastasis-free survival between SPINK1-positive and SPINK1-negative tumors in the overall cohort or by race. In multivariate analyses, SPINK1 expression was not associated with BCR (AA: HR 0.99, 95% CI 0.56-1.75, p = 0.976; EA: HR 0.88, 95% CI 0.43-1.77, p = 0.720) or metastasis (AA: HR 0.79, 95% CI 0.25-2.49, p = 0.691; EA: HR 1.55, 95% CI 0.58-4.11, p = 0.381) in either AA or EA men. There were no significant differences in surrounding CD3/CD8 lymphocyte densities between SPINK1-positive and SPINK1-negative tumors in either race. CONCLUSIONS: SPINK1-positive subtype is more prevalent in AA than EA men with PCa. Contrary to previous studies, we found that SPINK1 protein expression was not associated with worse pathologic or oncologic outcomes after RP in either AA men or EA men.
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Adenocarcinoma/mortalidad , Negro o Afroamericano/estadística & datos numéricos , Próstata/patología , Neoplasias de la Próstata/mortalidad , Inhibidor de Tripsina Pancreática de Kazal/metabolismo , Adenocarcinoma/inmunología , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Anciano , Supervivencia sin Enfermedad , Estudios de Seguimiento , Humanos , Calicreínas/sangre , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , Persona de Mediana Edad , Pronóstico , Próstata/inmunología , Próstata/cirugía , Antígeno Prostático Específico/sangre , Prostatectomía , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Análisis de Matrices Tisulares , Población Blanca/estadística & datos numéricosRESUMEN
PURPOSE: Prostatic adenocarcinoma with extraprostatic extension detected on prostate needle biopsy is an uncommon finding. We describe clinical and pathological findings in a large cohort of patients with prostatic adenocarcinoma who were treated with radical prostatectomy and in whom extraprostatic extension was identified on prostate needle biopsy. MATERIALS AND METHODS: Using our institutional pathology database we identified 83 patients with prostatic adenocarcinoma and with extraprostatic extension on prostate needle biopsy between 2000 to 2018 who underwent radical prostatectomy and had clinical followup information. Clinical and pathological outcomes were examined. RESULTS: Of the 83 patients 54 (65%) presented with clinical stage T2 or greater disease. On biopsy 50 of the 83 patients (60%) had Grade Group 4-5 and 66 (81%) had perineural invasion. Extraprostatic extension was confirmed in the radical prostatectomy specimen in 81 of 83 cases (98%). At radical prostatectomy 49 of 83 patients (59%) had positive surgical margins, 37 (45%) had seminal vesicle invasion and 30 (37%) had lymph node involvement. Median followup after radical prostatectomy was 2 years. Overall 34 of 76 men (45%) received postoperative radiation a median of 1 year after radical prostatectomy and 8 (11%) received chemotherapy a median of 2 years after radical prostatectomy. The 3-year biochemical recurrence-free survival rate was 48.4% (95% CI 0.345-0.610) and the 3-year metastasis-free survival rate was 75.2% (95% CI 0.603-0.851). CONCLUSIONS: Patients in whom extraprostatic extension is detected on prostate needle biopsy almost always have extraprostatic disease and markedly adverse pathology findings at radical prostatectomy. Many of them experience biochemical recurrence and most will require multimodal therapy. These data can be useful to counsel such patients in regard to the treatment approach and the expected outcomes after surgery.
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Adenocarcinoma/patología , Adenocarcinoma/cirugía , Prostatectomía/métodos , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Adenocarcinoma/mortalidad , Anciano , Biopsia con Aguja , Estudios de Cohortes , Bases de Datos Factuales , Supervivencia sin Enfermedad , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Cuidados Preoperatorios/métodos , Pronóstico , Neoplasias de la Próstata/mortalidad , Estudios Retrospectivos , Medición de Riesgo , Análisis de SupervivenciaRESUMEN
Opioid pain medications are overprescribed, but few data are available to help in appropriate tailoring of postdischarge opioid prescriptions after surgery. Prior studies are retrospective and based on incomplete responses (<50%) to questionnaires, with small sample sizes for any particular surgery. The ORIOLES initiative was a prospective cohort study (2017-2018) designed to measure postdischarge opioid prescribing and use and clinical predictors of use for consecutive patients after radical prostatectomy. The objectives were to establish a postdischarge opioid reference value to meet the needs of >80% of patients and compare open and robotic surgery. A total of 205 adult patients were enrolled, with 100% completing follow-up. In units of oral morphine equivalents (OMEQ), a median of 225mg was prescribed and 22.5mg used. There was no difference by surgical approach or among patients with a history of pain-related diagnoses. Overall, 77% of postdischarge opioid medication was unused, with 84% of patients requiring ≤112.5mg OMEQ. Only 9% of patients appropriately disposed of leftover medication. Approximately 5% reported continued incisional pain due to surgery at 30d, but none required continued opioid medication use. Prescribing more opioids was independently associated with greater opioid use in adjusted models. PATIENT SUMMARY: In this report, we looked at opioid medication use following discharge after radical prostatectomy. We found that 77% of opioid pain medication prescribed was unused, with 84% of patients using less than half of their prescription. Prescribing more opioids was associated with greater use; only 9% of patients appropriately disposed of leftover medication.
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Analgésicos Opioides/administración & dosificación , Manejo del Dolor/tendencias , Dolor Postoperatorio/prevención & control , Alta del Paciente , Pautas de la Práctica en Medicina/tendencias , Prostatectomía/efectos adversos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Analgésicos Opioides/efectos adversos , Baltimore , Prescripciones de Medicamentos , Humanos , Masculino , Manejo del Dolor/efectos adversos , Dimensión del Dolor , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Estudios Prospectivos , Prostatectomía/métodos , Eliminación de Residuos/métodos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
The use of neoadjuvant chemotherapy or radiation for borderline resectable pancreatic adenocarcinoma (BL-PDAC) is increasing. However, the impact of neoadjuvant chemotherapy and radiation therapy on the outcome of BL-PDAC remains to be elucidated. We performed a retrospective analysis of 93 consecutive patients who were diagnosed with BL-PDAC and primarily followed at Johns Hopkins Hospital between February 2007 and December 2012. Among 93 patients, 62% received upfront neoadjuvant chemotherapy followed by chemoradiation, whereas 20% received neoadjuvant chemoradiation alone and 15% neoadjuvant chemotherapy alone. Resectability following all neoadjuvant therapy was 44%. Patients who underwent resection with a curative intent had a median overall survival (mOS) of 25.8 months, whereas those who did not undergo surgery had a mOS of 11.9 months. However, resectability and overall survival were not significantly different between the three types of neoadjuvant therapy. Nevertheless, 22% (95% CI, 0.13-0.36) of the 58 patients who received upfront chemotherapy followed by chemoradiation remained alive for a minimum of 48 months compared to none of the 19 patients who received upfront chemoradiation. Among patients who underwent curative surgical resection, 32% (95% CI, 0.19-0.55) of those who received upfront chemotherapy remained disease free at least 48 months following surgical resection, whereas none of the eight patients who received upfront chemoradiation remained disease free beyond 24 months following surgical resection. Neoadjuvant therapy with upfront chemotherapy may result in long-term survival in a subpopulation of patients with BL-PDAC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores de Tumor , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Oportunidad Relativa , Neoplasias Pancreáticas/diagnóstico , Modelos de Riesgos Proporcionales , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
UNLABELLED: Prostate cancer (PCa) subtypes based on ETS gene expression have been described. Recent studies suggest there are racial differences in tumor location, with PCa located anteriorly more often among African-American (AA) compared to Caucasian-American (CA) men. In this retrospective analysis of a multi-institutional cohort treated by radical prostatectomy (179 CA, 121 AA), we evaluated associations among molecular subtype, race, anatomic tumor location, and androgen receptor (AR) signaling. Subtype (m-ERG(+), m-ETS(+), m-SPINK1(+), or triple-negative) was determined using distribution-based outlier analysis. AR signaling was investigated using gene expression profiling of canonical AR targets. m-ERG(+) was more common in CA than AA men (47% vs 22%, p<0.001). AA men were more likely to be m-SPINK1(+) (13% vs 7%; p=0.069) and triple-negative (50% vs 37%; p=0.043). Racial differences in molecular subtypes did not persist when tumors were analyzed by location, suggesting a biologically important relationship between tumor location and subtype. Accordingly, anterior tumor location was associated with higher Decipher scores and lower global AR signaling. PATIENT SUMMARY: This study demonstrates associations among patient race, prostate cancer molecular subtypes, and tumor location. Location-specific differences in androgen regulation may further underlie these relationships.