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PURPOSE: Asian, Black, and Hispanic men are underrepresented in prostate cancer (PCa) clinical trials. Few novel prostate cancer biomarkers have been validated in diverse cohorts. We aimed to determine if Stockholm3 can improve prostate cancer detection in a diverse cohort. METHODS: An observational prospective multicentered (17 sites) clinical trial (2019-2023), supplemented by prospectively recruited participants (2008-2020) in a urology clinic setting included men with suspicion of PCa and underwent prostate biopsy. Before biopsy, sample was collected for measurement of the Stockholm3 risk score. Parameters include prostate-specific antigen (PSA), free PSA, KLK2, GDF15, PSP94, germline risk (single-nucleotide polymorphisms), age, family history, and previous negative biopsy. The primary endpoint was detection of International Society of Urological Pathology (ISUP) Grade ≥2 cancer (clinically significant PCa, csPC). The two primary aims were to (1) demonstrate noninferior sensitivity (0.8 lower bound 95% CI noninferiority margin) in detecting csPC using Stockholm3 compared with PSA (relative sensitivity) and (2) demonstrate superior specificity by reducing biopsies with benign results or low-grade cancers (relative specificity). RESULTS: A total of 2,129 biopsied participants were included: Asian (16%, 350), Black or African American (Black; 24%, 505), Hispanic or Latino and White (Hispanic; 14%, 305), and non-Hispanic or non-Latino and White (White; 46%, 969). Overall, Stockholm3 showed noninferior sensitivity compared with PSA ≥4 ng/mL (relative sensitivity: 0.95 [95% CI, 0.92 to 0.99]) and nearly three times higher specificity (relative specificity: 2.91 [95% CI, 2.63 to 3.22]). Results were consistent across racial and ethnic subgroups: noninferior sensitivity (0.91-0.98) and superior specificity (2.51-4.70). Compared with PSA, Stockholm3 could reduce benign and ISUP 1 biopsies by 45% overall and between 42% and 52% across racial and ethnic subgroups. CONCLUSION: In a substantially diverse population, Stockholm3 significantly reduces unnecessary prostate biopsies while maintaining a similar sensitivity to PSA in detecting csPC.
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BACKGROUND: Multiquadrant procedures are technically more demanding than sequential operations. The new single port (SP) system allows to work in every abdominal quadrant maintaining an adequate triangulation without the need for changes in the port positioning. METHODS: In February 2020, two patients underwent a robotic SP partial nephrectomy for malignancy combined with a cholecystectomy and a left inguinal hernia repair respectively. RESULTS: Both procedures were successfully completed with one robotic docking and without the need for conversion. The operative time was 213 minutes for the right partial nephrectomy (126 min) with cholecystectomy (18 min), and 257 minutes for the left partial nephrectomy (161 min) with inguinal hernia repair (35 min). Estimated blood loss was 200 (150-250) mL, while the total warm ischemia time was 15 minutes for the right partial nephrectomy and 53 minutes for the left partial nephrectomy. There were no intraoperative complications or perioperative transfusions. The postoperative course was uneventful, and the postoperative hospital stay was 1 and 2 days. Both resections had free margins and the median tumor size was 2.5 (1.5-3.5) cm. Histopathology analysis revealed chronic cholecystitis and renal cell carcinomas with free margins and a median tumor size of 2.5 (1.5-3.5) cm. After a mean follow-up of 24 months, no surgical-related complications or recurrence were detected. CONCLUSIONS: The robotic SP approach facilitates the completion of combined surgical procedures in multiple abdominal quadrants through a single 25mm incision.
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Carcinoma de Células Renales , Hernia Inguinal , Neoplasias Renales , Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/patologíaRESUMEN
OBJECTIVES: This study sought to prospectively investigate a novel quantitative biparametric prostate magnetic resonance imaging (MRI) protocol to detect prostate cancer (PCa) in biopsy-naïve men. Secondarily, this study reports the accuracy of fractional order calculus (FROC) diffusion and quantitative T2 compared with the Prostate Imaging Reporting & Data System (PI-RADS). METHODS: This prospective pilot study (NCT04175730) enrolled 50 prostate biopsy-naïve men who met eligibility criteria. All men received 3T MRI with T2 and diffusion-weighted imaging (DWI) (b-values: 50-4,000 s/mm2). Men with PI-RADS lesions ≥3 underwent targeted and systematic prostate biopsy, omitting systematic biopsy cores in peripheral zone lesions. DWI series images were fit to signal decay to calculate ADC (mm2/s) and the FROC model for coefficient DF (mm2/s). The primary end point was detection of Gleason grade group ≥2 (GG≥2) PCa. Receiver operating characteristic regression and area under the curve (AUC) were reported. RESULTS: Forty-eight men underwent MRI and biopsy. Mean age was 61.5 years (56-68), 29% were White, 52% were African American, mean PSA was 6.0 ng/mL (4.9-8.0), and mean PSA density was 0.14 ng/mL2. In total, 61 PI-RADS ≥3 lesions were targeted for biopsy. GG≥2 PC was found in 7% (1/14) of PI-RADS 3 lesions, 28% (10/36) of PI-RADS 4 lesions, and 36% (4/11) of PI-RADS 5 lesions. The AUC for detection of GG≥2 PC was 0.63 (0.5-0.76) for PI-RADS, 0.82 (0.68-0.96) for ADC, and 0.87 (0.77-0.97) for the FROC model. CONCLUSION: This small prospective pilot study demonstrates the feasibility of a novel quantitative biparametic MRI protocol to detect prostate cancer in biopsy-naïve men.
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Neoplasias de la Próstata , Masculino , Humanos , Persona de Mediana Edad , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Próstata/patología , Imagen por Resonancia Magnética/métodos , Antígeno Prostático Específico/análisis , Estudios Prospectivos , Proyectos Piloto , Biopsia Guiada por Imagen/métodosRESUMEN
Background: Total pelvic exenteration (TPE) in men is a surgical procedure to treat genitourinary and colorectal malignancies. Despite improvement in multimodal strategies and technology, mortality is still high and literature is limited about perioperative outcomes comparison to other radical procedures. Methods: We analyzed National Surgical Quality Improvement Program (NSQIP) baseline database of all male patients undergoing cystectomy, low anterior resection/abdominoperineal resection (LAR/APR) or TPE from January 1, 2005 to December 31, 2016. Postoperative complications within 30 days after surgery were measured including: Wound infection, septic complications, deep vein thrombosis, cardiovascular events, and return to the operating room or mortality, etc. Differences between groups were analyzed using analysis of variance (ANOVA) tests. Results: A total of 7,375 patients underwent radical cystectomy, 49,762 underwent LAR/APR and 792 underwent TPE. Cystectomy patients were on average older compared to TPE or LAR/APR patients (P<0.001). In univariable and multivariable analysis, patients undergoing TPE had greater infectious and septic complications compared to cystectomy (odds ratio =1.09; 95% confidence interval (CI): 1.06-1.12) and LAR/APR (odds ratio =1.08; 95% CI: 1.05-1.11). Moreover, TPE had a slightly higher mortality within the 30-day postoperatively than those who underwent LAR/APR (odds ratio =1.01; 95% CI: 1.00-1.02) and cystectomy (odds ratio =1.01; 95% CI: 1.00-1.01). Conclusions: Men undergoing TPE had greater rates of infections and postoperative complications compared to those undergoing radical cystectomy and LAR/APR. From a clinical standpoint, TPE has high morbidity that could provide opportunity for quality improvement projects with the goal of mitigating high complication rates.
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PURPOSE: Renal function outcomes between radical nephroureterectomy (RNU) and nephron-sparing surgery (NSS) for upper tract urothelial carcinoma (UTUC) patients are not well established. We sought to compare the incidence and factors associated with development of advanced chronic kidney disease (CKD) between RNU and NSS and examine the role of acute kidney injury (AKI) on renal function outcomes. METHODS: We retrospectively analyzed an institutional database for patients who underwent either RNU or NSS for UTUC. Cumulative incidence of postoperative advanced CKD, defined as eGFR < 30 ml/min/1.73 m2, was compared between groups. Fine-Gray competing risk regression was used to identify predictors of advanced CKD. Locally weight scatterplot smoothing was used to assess postoperative eGFR trends. AKI events were counted, staged, and assessed for influence of progression to advanced CKD. RESULTS: Four hundred and twenty-six patients were included in analysis, with a median follow up of 6.68 years (IQR 3.4-12.2). Median preoperative eGFR was similar between the groups (NSS: 68 ml/min/1.73 m2, RNU: 65 ml/min/1.73 m2,Pâ¯=â¯0.220). Cumulative incidence of advanced CKD was significantly lower in the NSS cohort (Pâ¯=â¯0.009). Factors associated with advanced CKD included age, diabetes, recurrent AKI and RNU. Percent of patients with an AKI event differed between the groups (51.5% NSS, 72.7% RNU, Pâ¯=â¯<0.001), there was no between group difference in percentage of patients with recurrent AKI (25.6% NSS, 25.9% RNU, P =1). CONCLUSION: NSS provides a renal function benefit in UTUC. AKI is common among UTUC patients and recurrent AKI is a risk factor for development of advanced CKD.
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Lesión Renal Aguda , Carcinoma de Células Transicionales , Insuficiencia Renal Crónica , Neoplasias Ureterales , Neoplasias de la Vejiga Urinaria , Humanos , Nefroureterectomía/efectos adversos , Carcinoma de Células Transicionales/patología , Neoplasias de la Vejiga Urinaria/cirugía , Estudios Retrospectivos , Neoplasias Ureterales/patología , Insuficiencia Renal Crónica/etiología , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Nefronas/cirugíaRESUMEN
Objective: To report early institutional experience with the single-port robotic platform and compare perioperative outcomes between single-port robot-assisted partial nephrectomies (SP-RAPN) and multiport robot-assisted partial nephrectomies (MP-RAPN) when utilizing a retroperitoneal approach. Methods: A retrospective chart review of patients who underwent SP-RAPN or MP-RAPN at our institution between November 1, 2013 and May 30, 2021 was performed. Surgical platforms were compared through univariate analysis using the Kruskal-Wallis test for continuous variables and χ2 test for categorical variables. Results: A total of 20 SP-RAPN and 42 MP-RAPN were performed utilizing a retroperitoneal approach. Patients who underwent SP-RAPN were more likely to have a lower radius, endophytic/exophytic, nearness, anterior/posterior, location score (4 vs 6; p = 0.0084) and their masses tended to be more exophytic, although this was not statistically significant (p = 0.0535). Patients undergoing SP-RAPN had a shorter postoperative length of hospital stay (1 vs 2 days; p < 0.0001). There were no significant differences in operative time, estimated blood loss, ischemia time, positive margin rate, malignant histology, postoperative complication rate, or Clavien-Dindo complication grade. Conclusion: Retroperitoneal SP-RAPN appear to be safe without compromising perioperative outcomes when compared with MP-RAPN for low-complexity renal masses. Further studies are recommended to assess the role of the SP for higher-complexity renal masses and to characterize variables that influence the observed difference in length of hospital stay.
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Robótica , Humanos , Estudios Retrospectivos , Proyectos de InvestigaciónRESUMEN
There is uncertainty with how to proceed when targeted prostate biopsy of suspicious multiparametric magnetic resonance imaging (mpMRI) lesions return without clinically significant prostate cancer (csPCa). While possible, there are error sources that could contribute to such discordance including the mpMRI read, mpMRI-ultrasound fusion, biopsy technique, and histologic classification. Consequences are potentially significant; mistakenly missing csPCa can lead to delays in curative treatment. Conversely, in cases of incorrect mpMRI interpretation, the patient may be subjected to unnecessary workup/burden. At our institution, we implemented a quality improvement (QI) initiative triggered after a discordant case occurs. This multidisciplinary review process incorporates mpMRI re-review and assessment of accurate lesion-sampling, termed "reverse-fusion." Herein, we describe the protocol, present sample cases, and discuss clinical implications.
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Próstata , Neoplasias de la Próstata , Biopsia , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Clasificación del Tumor , Próstata/diagnóstico por imagen , Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Mejoramiento de la CalidadRESUMEN
There are currently few situations in which genomic testing is actionable for genitourinary tumors. Without clear indications or treatment paradigms, genomic sequencing cannot be recommended as a standard of care for genitourinary tumors.
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Neoplasias Urogenitales , Neoplasias Urológicas , Genómica , Humanos , Nivel de Atención , Neoplasias Urogenitales/diagnóstico , Neoplasias Urogenitales/genética , Neoplasias Urogenitales/terapia , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/genética , Neoplasias Urológicas/terapiaRESUMEN
OBJECTIVES: To evaluate the differences in prostate cancer characteristics and treatment between Hispanic Americans with different countries of origin using the National Cancer Database. METHODS: We performed a retrospective analysis of 54,947 adult Hispanic Americans diagnosed with prostate cancer between 2004 and 2015. Origin was Mexican (Nâ¯=â¯7844; 14.3%), South/Central American (Nâ¯=â¯4010; 7.3%), Puerto Rican (Nâ¯=â¯2938; 5.4%), Cuban (Nâ¯=â¯2549; 4.6%), Dominican (Nâ¯=â¯1535; 2.8%), Hispanic not specified (Nâ¯=â¯36,269; 65.7%). Comparison between characteristics among Hispanic American sub-groups' categories was performed using chi-square and Kruskal-Wallis tests for categorical and continuous variables respectively. RESULTS: Mexicans had overall worse disease at presentation including highest median PSA (7.8 ng/mL), most prevalent T3/T4 stage (6.7%), M1 stage (8.9%), and high-grade Gleason scores (24.0%) when compared to all other Hispanic American groups. Cubans were most likely to receive hormone therapy and radiation therapy and least likely to receive surgical treatment. Compared to Mexicans, Cubans (hazards ratio [HR]â¯=â¯1.30, 95% confidence intervalâ¯=â¯[1.16-1.44]) had worse overall survival, while Puerto Ricans (HRâ¯=â¯1.08 [0.95-1.19] had similar overall survival, and Dominicans (HRâ¯=â¯0.63 [0 0.53-0.75]), South/Central Americans (HRâ¯=â¯0.75, [0.66-0.84]) and not specified (HRâ¯=â¯0.84 [0.79-0.91]) had better survival. CONCLUSION: Among Hispanic Americans with different countries of origin, disparities in prostate cancer characteristics, treatment choice, and survival do exist. Mexicans had the least favorable prostate cancer characteristics at presentation. Cubans had the worst overall survival while they were also most likely to receive hormone and/or radiation as first-line treatment. Our analysis demonstrates significant heterogeneity in the Hispanic American population.
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Hispánicos o Latinos , Neoplasias de la Próstata , Adulto , Hormonas , Humanos , Masculino , Neoplasias de la Próstata/terapia , Puerto Rico/epidemiología , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Several studies evaluated prostate cancer (PCa) outcomes in Black men on active surveillance (AS); most studies contained few Black men and results were conflicting. We performed a systematic review and meta-analyze of race and outcomes on AS. METHODS: A systematic search was performed for articles of men with Grade Group 1 or 2 (GG1 or GG2) PCa on AS. All studies required race-specific comparative progression data. Progression to treatment, PSA, or biopsy progression were considered and relative risk (RR) estimates of Black men progressing were extracted and pooled using random-effects models. Differences by study-level characteristics were evaluated using subgroup and a cumulative meta-analysis by time. RESULTS: In total, 12 studies were included (3137 Black and 12,206 non-Black men); eight prospective (27%, n = 4210) and four retrospectives (73%, n = 11,133) cohorts. The overall RR of progression for Black men was 1.62 (95%CI, 1.21-2.17), I2 = 64% (95% CI, 32-80%), (χ2 = 30.23; P = 0.001; τ2 = 0.16). Black men with GG1 PCa alone had a higher pooled progression: RR = 1.81 (95% CI, 1.23-2.68). Including only studies with clinical progression (excluding progression to treatment), potentiated results: RR = 1.82 (95%CI, 1.27-2.60). However, a cumulative meta-analysis demonstrated decreasing pooled effect over time, with contemporary studies after 2019 showing a tempered effect (RR: 1.29, 95% CI: 1.20-1.39). CONCLUSIONS: Many studies attribute racial disparity in PCa to delayed presentation of disease, however, AS is unique since all AS eligible men have a low grade and stage PCa. Our findings suggest Black men may have an increased risk of progression during AS, but the association is not so strong that Black men should be discouraged from undergoing AS. Indeed, contemporary evidence suggests stricter inclusion, better confirmatory testing or better access to care may temper these findings. Importantly, these results utilize self-reported race, a social construct that has many limitations.
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Neoplasias de la Próstata , Biopsia , Humanos , Masculino , Clasificación del Tumor , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/terapia , Espera VigilanteRESUMEN
BACKGROUND: The aim of this paper was to evaluate the safety and feasibility of robotic-assisted laparoscopic partial nephrectomy (RAPN) performed using the da Vinci Single-Port (SP) platform. METHODS: A retrospective review was conducted from December 2018 to December 2019 of 14 consecutive patients with localized renal cancer who underwent SP robot-assisted partial nephrectomy at a single institution. The procedures were performed by 2 experienced robotic surgeons, reproducing the steps of the standard multiport robotic approach to partial nephrectomy. A transperitoneal approach was utilized with a 2.5 cm para-rectus incision with one assistant 12 mm laparoscopic port. RESULTS: No conversions to open or laparoscopic surgery occurred and no additional laparoscopic assistant ports were required. The median total operative time was 202 (162-231) minutes and the median total room time was 258 (215-295) minutes. The warm ischemia time averaged 20±8 minutes. 2 patients required angioembolization due to postoperative acute bleeding (Clavien-Dindo Grade 3a complication). Trifecta outcome (<25 min warm ischemia, no perioperative complications and negative margins) was achieved in 79% of patients. In one case, a positive margin was present. The median length of stay was of 1 day (Interquartile Range 1-2) with a median pain score on post-operative day 1 of 3.5 (Interquartile Range 2.4-5); 1/14 (7%) patient needed narcotic use at one week from discharge. At a median follow up of 5.0 (4.0-8.0) months, no patients have had evidence of disease recurrence. CONCLUSIONS: In this initial cohort, considering the introduction of a new technology, we observed satisfactory outcomes for several key perioperative variables including operative time, warm ischemia time, surgical margins, hospital stay, pain requirements in patients undergoing RAPN with the SP platform. For experienced robotic surgeons, RAPN with the SP platform is a safe and feasible approach for single site partial nephrectomy.
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Neoplasias Renales , Nefrectomía , Procedimientos Quirúrgicos Robotizados , Humanos , Neoplasias Renales/cirugía , Laparoscopía/efectos adversos , Nefrectomía/efectos adversos , Nefrectomía/métodos , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/efectos adversosRESUMEN
Although studies have investigated cadmium and prostate cancer (PC) incidence and mortality, the role of cadmium in PC progression might be more clinically relevant. In this observational study, we assessed the association between air cadmium exposure and PC aggressiveness, with PC stage defined as metastatic or localized and Gleason grade defined as high (Gleason score ≥ 8) or low (Gleason score ≤ 6) among PC patients from the 2010-2014 US Surveillance, Epidemiology, and End Results database. The 2005 and 2011 National Air Toxics Assessment provided county-level air cadmium concentrations. Results were presented as odds ratios (OR) with 95% confidence intervals (CI) and were calculated using random intercept mixed effects logistic regression, comparing the 80th to 20th percentile of exposure. We adjusted for age, sociodemographic status, smoking prevalence, and overall air quality at the county level, and stratified by race, age, and degree of urbanization. The cohort consisted of 230,540 cases from 493 counties. Strong associations were observed in nonmetropolitan, urban areas: (OR 1.26, CI 1.14-1.39) for metastatic vs. localized and (OR 1.41, CI 1.27-1.57) for high- vs. low-grade PC where 40 million Americans reside. This study may be hypothesis-generating to inform future studies and public health measures.
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Cadmio , Neoplasias de la Próstata , Cadmio/toxicidad , Estudios de Cohortes , Humanos , Masculino , Neoplasias de la Próstata/epidemiología , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
[This corrects the article DOI: 10.1016/j.isci.2020.101974.].
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BACKGROUND: Prostate cancer (PC) etiology is up to 57% heritable, with the remainder attributed to environmental exposures. There are limited studies regarding national level environmental exposures and PC aggressiveness, which was the focus of this study METHODS: SEER was queried to identify PC cases between 2010 and 2014. The environmental quality index (EQI) is a county-level metric for 2000-2005 combining data from 18 sources and reports an overall ambient environmental quality index, as well as 5 environmental quality sub-domains (air, water, land, built, and sociodemographic) with higher values representing lower environmental quality. PC stage at diagnosis was determined and, multivariable logistic regression models which adjusted for age at diagnosis (years) and self-reported race (White, Black, Other, Unknown) were used to test associations between quintiles of EQI scores and advanced PC stage at diagnosis. RESULTS: The study cohort included 252,164 PC cases, of which 92% were localized and 8% metastatic at diagnosis. In the adjusted regression models, overall environmental quality EQI (OR 1.20, CI 1.15-1.26), water EQI (OR: 1.34, CI: 1.27-1.40), land EQI (OR: 1.35, CI: 1.29-1.42) and sociodemographic EQI (OR: 1.29, CI: 1.23-1.35) were associated with metastatic PC at diagnosis. For these domains there was a dose response increase in the OR from the lowest to the highest quintiles of EQI. Black race was found to be an independent predictor of metastatic PC at diagnosis (OR: 1.36, CI: 1.30-1.42) and in stratified analysis by race; overall EQI was more strongly associated with metastatic PC in Black men (OR: 1.53, CI: 1.35-1.72) compared to White men (OR: 1.18, CI: 1.12-1.24). CONCLUSION(S): Lower environmental quality was associated with advanced stage PC at diagnosis. The water, land and sociodemographic domains showed the strongest associations. More work should be done to elucidate specific modifiable environmental factors associated with aggressive PC.
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Exposición a Riesgos Ambientales/efectos adversos , Neoplasias de la Próstata/etiología , Neoplasias de la Próstata/patología , Anciano , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Factores de Riesgo , Programa de VERF , Estados UnidosRESUMEN
PURPOSE: The Genomic Prostate Score (GPS), performed on biopsy tissue, predicts adverse outcome in prostate cancer (PCa) and has shown promise for improving patient selection for active surveillance (AS). However, its impact on treatment choice in high-risk populations of African Americans is largely unknown and, in general, the effect of the GPS on this difficult decision has not been evaluated in randomized trials. METHODS: Two hundred men with National Comprehensive Cancer Network very low to low-intermediate PCa from three Chicago hospitals (70% Black, 16% college graduates) were randomly assigned at diagnosis to standard counseling with or without a 12-gene GPS assay. The primary end point was treatment choice at a second postdiagnosis visit. The proportion of patients choosing AS was compared, and multivariable modeling was used to estimate the effects of various factors on AS acceptance. RESULTS: AS acceptance was high overall, although marginally lower in the intervention group (77% v 88%; P = .067), and lower still when men with inadequate specimens were excluded (P = .029). Men with lower health literacy who received a GPS were seven-fold less likely to choose AS compared with controls, whereas no difference was seen in men with higher health literacy (Pinteraction = .022). Among men with low-intermediate risk, 69% had GPS values consistent with unfavorable intermediate or high-risk cancer. AS choice was also independently associated with a family history of PCa and having health insurance. CONCLUSION: In contrast to other studies, the net effect of the GPS was to move patients away from AS, primarily among men with low health literacy. These findings have implications for our understanding of how prognostic molecular assays that generate probabilities of poor outcome can affect treatment decisions in diverse clinical populations.
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Genómica/métodos , Negro o Afroamericano , Anciano , Humanos , Masculino , Factores de RiesgoRESUMEN
Vitamin D is an essential steroid hormone that regulates systemic calcium homeostasis and cell fate decisions. The prostate gland is hormonally regulated, requiring steroids for proliferation and differentiation of secretory luminal cells. Vitamin D deficiency is associated with an increased risk of lethal prostate cancer, which exhibits a dedifferentiated pathology, linking vitamin D sufficiency to epithelial differentiation. To determine vitamin D regulation of prostatic epithelial differentiation, patient-derived benign prostate epithelial organoids were grown in vitamin D-deficient or -sufficient conditions. Organoids were assessed by phenotype and single-cell RNA sequencing. Mechanistic validation demonstrated that vitamin D sufficiency promoted organoid growth and accelerated differentiation by inhibiting canonical Wnt activity and suppressing Wnt family member DKK3. Wnt and DKK3 were also reduced by vitamin D in prostate tissue explants by spatial transcriptomics. Wnt dysregulation is a known contributor to aggressive prostate cancer, thus findings further link vitamin D deficiency to lethal disease.
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BACKGROUND: The Stockholm3 test improves Gleason Grade Group ≥2 (GG ≥ 2) prostate cancer (PC) detection, however it has not been evaluated in an American cohort where clinical practice patterns and ethnicity differ. We aimed to identify subgroups within a Stockholm population with PC risk profiles matching American ethnicity-specific subgroups and compare the detection of PC and describe Stockholm3 performance within these subgroups. METHODS: All men age 49-70 years presenting for prostate biopsies were evaluated at UIC from 2016 to 2019, as well as men in Stockholm from 2012 to 2014 in the STHLM3 study. Propensity scores (PS) were estimated for each person using logistic regression for age, PSA, prostate volume, family history of PC, 5-alpha reductase inhibitor use, and prior biopsy. 3:1 PS matching was performed for Stockholm to Chicago ethnicity-specific cohorts and odds ratios (OR) were computed to compare detection of GG ≥ 2 PC between groups. RESULTS: 504 Chicago men and 6980 Stockholm men were included. In African American (AA) men, 51% had GG ≥ 2 PC detected, while in risk-matched Stockholm men, 34% had GG ≥ 2 PC detected (OR: 2.1, p < 0.001). There was no statistical difference in GG ≥ 2 PC detected when matching Stockholm men to non-Hispanic Caucasian men (31% vs. 24%, OR: 0.7, p = 0.30) or Hispanic Caucasian men (31% vs. 27%, OR: 1.2, p = 0.42). The AUC for the Stockholm3 test of the matched Stockholm cohorts for AA, non-Hispanic Caucasian, and Hispanic Caucasian men was 0.85, 0.89, and 0.90, respectively. CONCLUSIONS: Using statistical techniques to simulate a multi-ethnic Chicago cohort within the STHLM3 population, we found an excess risk of GG ≥ 2 PC among AA men. Our hypothesis that the Stockholm3 may have good predictive value in a multiethnic cohort is strengthened, and that recalibration to at least AA men seems likely to be needed to obtain well-calibrated predictions.
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Etnicidad , Clasificación del Tumor/métodos , Próstata/patología , Neoplasias de la Próstata/diagnóstico , Medición de Riesgo/métodos , Anciano , Biopsia , Estudios de Factibilidad , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias de la Próstata/etnología , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Total pelvic exenterations (TPEs) for malignancies are complex operations often performed by multidisciplinary teams. The differences among primary cancer for TPE and multicentered results are not well described. We aimed to describe TPE outcomes for different malignant origins in a national multicentered sample. METHODS: Patients from the National Surgical Quality Improvement Program (NSQIP) database who underwent TPE between 2005 and 2016 for all malignant indications (colorectal, gynecologic, urologic, or other) were included. Chi square and Kruskal-Wallis tests were used to compare patient characteristics by primary malignancy. Multivariate logistic and linear regression models were used to determine factors associated with any 30-day Clavien-Dindo grade 3 or higher complication, length of hospital stay (LOS; days), 30-day wound infection, and 30-day mortality. RESULTS: Overall, 2305 patients underwent TPE. Indications for surgery included 33% (749) colorectal, 15% (335) gynecologic, 9% (196) other, and 45% (1025) urologic malignancies. Median LOS decreased from 10 to 8 days during the study period (p < 0.001), 36% were males, and 50% required blood transfusion. High-grade complications occurred in 15% of patients and were associated with bowel diversion [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.1-2.4], disseminated cancer (OR 1.8, 95% CI 1.4-2.3), and gynecologic cancers (OR 2.9, 95% CI 1.8-4.7). Mortality was 2% and was associated with disseminated cancer (OR 2.2, 95% CI 1.1-4.3) and male sex (OR 2.4, 95% CI 1.3-4.4). CONCLUSIONS: TPE is associated with high rates of complications, however mortality rates remain low. Preoperative and perioperative outcomes differ depending on the origin of the primary malignancy.
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Neoplasias de los Genitales Femeninos , Exenteración Pélvica , Transfusión Sanguínea , Femenino , Neoplasias de los Genitales Femeninos/cirugía , Humanos , Masculino , Morbilidad , Complicaciones Posoperatorias , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Active surveillance (AS) provides appropriate prostate cancer (PCa)-specific survival while minimizing morbidity, but underlying worry of PCa can generate anxiety. The aim of the study is to evaluate anxiety levels in men on AS and how anxiety relates to disease characteristics and treatment decision-making. METHODS: A retrospective analysis was conducted using all 302 subjects from the Reduction by Dutasteride of clinical progression Events in Expectant Management (REDEEM) study. Prostate biopsies were obtained at 18 and 36 months. Anxiety was measured at baseline and 3, 6, 12, 18, and 36 months post-randomization using the MAX-PC (Memorial general anxiety scale for PCa) questionnaire. Univariable and multivariable analysis of the association of disease aggressiveness (PSA levels, percentage of positive cores, and maximum core involvement) and anxiety levels were performed. Cox regression was used to analyze time to progression to discontinuation of active surveillance as a function of baseline anxiety. RESULTS: Overall, MAX-PC scores decreased from moderate at baseline with slight increases after receiving PSA results at 18 months, followed by more decline. Percentage of positive cores was associated with baseline anxiety (P = 0.02). The association remained when controlling for age, race, number of cores sampled, body mass index, prostate volume, and maximum core length (P = 0.003). In univariable and multivariable analysis, baseline anxiety was not significantly associated with time to progression to discontinuation of active surveillance. CONCLUSIONS: In evaluating the natural history of anxiety levels among patients with prostate cancer undergoing active surveillance, there was a decline of anxiety levels over time, with increases after receiving PSA results. Moreover, we found that disease aggressiveness measured by percentage of positive biopsy cores was associated with baseline levels of anxiety. However, anxiety had no impact on clinical or therapeutic progression.
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Ansiedad/patología , Neoplasias de la Próstata/complicaciones , Espera Vigilante/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Ansiedad/etiología , Ansiedad/psicología , Progresión de la Enfermedad , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/psicología , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
The da Vinci single port (SP) robotic system (Intuitive Surgical, Sunnyvale, CA, USA) is a recently approved robotic platform designed with several modifications to the previously available multi-port robotic systems. This article describes the technique performed utilizing the SP robotic system for radical robotic-assisted laparoscopic prostatectomy (RALP) with or without bilateral pelvic lymph node dissection from a single institution. In this report we describe our step-by-step approach, technical modifications from the multi-port technique and initial results for performing single port robotic-assisted laparoscopic prostatectomy (SP-RALP). We describe our initial experience and technique with the SP robotic system consisting of 23 consecutive patients who underwent SP-RALP between December 2018 and May 2019. The median patient age was 62 years with approximately half of the patients undergoing pelvic lymphadenectomy. The median operative time was 236 minutes, median estimated blood loss was 50 mL and median length of hospital stay was 1 day. No unplanned port placements occurred and no conversions to open surgery occurred. We demonstrate the safety and feasibility of performing a transperitoneal prostatectomy with either a posterior or anterior approach.