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1.
J Urol ; 211(5): 669-676, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38591701

RESUMEN

PURPOSE: Partial nephrectomy is standard-of-care treatment for small renal masses. As utilization of partial nephrectomy increases and includes larger and complex tumors, the risk of conversion to radical nephrectomy likely increases. We evaluated incidence and reason for conversion to radical nephrectomy in patients scheduled for partial nephrectomy by surgeons participating in MUSIC (the Michigan Urologic Surgery Improvement Collaborative). MATERIALS AND METHODS: All patients in whom robotic partial nephrectomy was planned were stratified by completed procedure (robotic partial nephrectomy vs radical nephrectomy). Preoperative and intraoperative records were reviewed for preoperative assessment of difficulty and reason for conversion. Patient, tumor, pathologic, and practice variables were compared between cohorts. RESULTS: Of 650 patients scheduled for robotic partial nephrectomy, conversion to radical nephrectomy occurred in 27 (4.2%) patients. No conversions to open were reported. Preoperative documentation indicated a plan for possible conversion in 18 (67%) patients including partial with possible radical (n = 8), partial vs radical (n = 6), or likely radical nephrectomy (n = 4). Intraoperative documentation indicated that only 5 (19%) conversions were secondary to bleeding, with the remaining conversions due to tumor complexity and/or oncologic concerns. Patients undergoing conversion had larger (4.7 vs 2.8 cm, P < .001) and higher-complexity tumors (64% vs 6%, P < .001) with R.E.N.A.L. (for radius, exophytic/endophytic, nearness of tumor to collecting system, anterior/posterior, location relative to polar line) nephrometry score ≥ 10. The converted cases had a higher rate of ≥ pT3 (27% vs 8.4%, P = .008). CONCLUSIONS: There was a low rate of conversion from robotic partial to radical nephrectomy in the MUSIC-KIDNEY (Kidney mass: Identifying and Defining Necessary Evaluation and therapY) collaborative, and an even lower risk of conversion due to uncontrolled bleeding. Targeted review of each conversion identified appropriate decision-making based on oncologic risk in most cases.


Asunto(s)
Neoplasias Renales , Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Procedimientos Quirúrgicos Robotizados/efectos adversos , Procedimientos Quirúrgicos Robotizados/métodos , Resultado del Tratamiento , Nefrectomía/efectos adversos , Nefrectomía/métodos , Estudios Retrospectivos
2.
Prostate ; 83(1): 64-70, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36120850

RESUMEN

INTRODUCTION AND OBJECTIVE: The prognostic significance of a "second" biochemical recurrence (sBCR) after salvage radiation therapy (sRT) with/without hormonal therapy following primary radical prostatectomy in men with prostate cancer has not been examined. We hypothesized that a shorter time to sBCR will be associated with worse cancer control outcomes. METHODS: The RTOG 9601 study included 760 patients with tumor stage pT2/T3, pN0, who had either persistently elevated prostate-specific antigen (PSA) postradical prostatectomy or developed subsequent biochemical recurrence with PSA levels between 0.2 and 4.0 ng/ml. All patients received sRT (with or without 2 years of Bicalutamide) from 1998 to 2015. For our study, we focused on 421 patients who had sBCR after sRT-which was defined as a PSA increase of at least 0.3 ng/ml over the first nadir. Patients were divided into two categories: early sBCR (n = 210) and late sBCR (n = 211) using median time to sBCR (3.51 years). All patients who experienced sBCR received salvage hormonal therapy. Competing-risk analysis was used to examine the impact of early versus late sBCR on prostate cancer specific mortality (CSM), after accounting for available covariates. RESULTS: The majority of patients were age 60 years or older (75.8%), had pT3 disease (74.8%), and Gleason score 7 (75.2%). Overall, 13.8% had persistent PSA initially after surgery. At 10 years, starting at the time of sBCR, CSM rate was 31.3% in the early sBCR group versus 20.0% in the late sBCR group. In competing-risk analysis, time to sBCR was an independent predictor of CSM, where patients with early sBCR had 1.7-fold higher CSM risk (p = 0.026) than their counterparts with late sBCR. CONCLUSIONS: Time to sBCR after sRT (with or without concomitant Bicalutamide) is a significant predictor of CSM following initial radical prostatectomy. This information can be used to guide subsequent treatments, and to counsel patients.


Asunto(s)
Neoplasias de la Próstata , Humanos , Persona de Mediana Edad , Masculino , Pronóstico , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía
3.
Prostate ; 83(13): 1238-1246, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37290911

RESUMEN

PURPOSE: To investigate the conditional overall survival (OS) of metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel chemotherapy. METHODS: We used deidentified patient-level data from the Prostate Cancer DREAM Challenge database and the control arm of the ENTHUSE 14 trial. We identified 2158 chemonaïve mCRPC patients undergoing docetaxel chemotherapy in the five randomized clinical trials. The 6-month conditional OS was calculated at times 0, 6, 12, 18, and 24 months from randomization. Survival curves of each group were compared using the log-rank test. Patients were then stratified into low- and high-risk groups based on the median predicted value of our recently published nomogram predicting OS in mCRPC patients. RESULTS: Nearly half (45%) of the study population was aged between 65 and 74 years. Median interquartile range prostate-specific antigen for the overall cohort was 83.2 (29.6-243) ng/mL, and 59% of patients had bone metastasis with or without lymph node involvement. The 6-month conditional survival rates at 0, 6, 12, 18, and 24 months for the entire cohort were 93% (95% confidence interval [CI]: 92-94), 82% (95% CI: 81-84), 76% (95% CI: 73-78), 75% (95% CI: 71-78), and 71% (95% CI: 65-76). These rates were, respectively, 96% (95% CI: 95-97), 92% (95% CI: 90-93), 84% (95% CI: 81-87), 81% (95% CI: 77-85), and 79% (95% CI: 72-84) in the low-risk group and 89% (95% CI: 87-91), 73% (95% CI: 70-76), 65% (95% CI: 60-69), 64% (95% CI: 58-70), and 58% (95% CI: 47-67) in the high-risk group. CONCLUSION: The conditional OS for patients undergoing docetaxel chemotherapy tends to plateau over time, with the main drop in conditional OS happening during the first year from initiating docetaxel treatment. That is the longer a patient survives, the more likely they are to survive further. This prognostic information could be a useful tool for a more accurate tailoring of both follow-up and therapies. PATIENT SUMMARY: In this report, we looked at the future survival in months of patients with metastatic castration resistant prostate cancer on chemotherapy who have already survived a certain period. We found that the longer time that a patient survives, the more likely they will continue to survive. We conclude that this information will help physicians tailor follow-ups and treatments for patients for a more accurate personalized medicine.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Anciano , Humanos , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Docetaxel/uso terapéutico , Pronóstico , Antígeno Prostático Específico/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/patología , Taxoides/uso terapéutico , Resultado del Tratamiento
4.
J Urol ; 210(1): 79-87, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36947795

RESUMEN

PURPOSE: Renal masses can be characterized as "indeterminate" due to lack of differentiating imaging characteristics. Optimal management of indeterminate renal lesions remains nebulous and poorly defined. We assess management of indeterminate renal lesions within the MUSIC-KIDNEY (Michigan Urological Surgery Improvement Collaborative-Kidney mass: Identifying and Defining Necessary Evaluation and therapY) collaborative. MATERIALS AND METHODS: Each renal mass is classified as suspicious, benign, or indeterminate based on radiologist and urologist assessment. Objectives were to assess initial management of indeterminate renal lesions and the impact of additional imaging and biopsy on characterization prior to treatment. RESULTS: Of 2,109 patients, 444 (21.1%) had indeterminate renal lesions on their initial imaging, which included CT without contrast (36.2%), CT with contrast (54.1%), and MRI (9.7%). Eighty-nine patients (20.0%) underwent additional imaging within 90 days, 8.3% (37/444) underwent renal mass biopsy, and 3.6% (16/444) had reimaging and renal mass biopsy. Additional imaging reclassified 58.1% (61/105) of indeterminate renal lesions as suspicious and 21.0% (22/105) as benign, with only 20.9% (22/105) remaining indeterminate. Renal mass biopsy yielded a definitive diagnosis for 87%. Treatment was performed for 149 indeterminate renal lesions (33.6%), including 117 without reimaging and 123 without renal mass biopsy. At surgery for indeterminate renal lesions, benign pathology was more common in patients who did not have repeat imaging (9.9%) than in those who did (6.7%); for ≤4 cm indeterminate renal lesions, these rates were 11.8% and 4.3%. CONCLUSIONS: About 33% of patients diagnosed with an indeterminate renal lesion underwent immediate treatment without subsequent imaging or renal mass biopsy, with a 10% rate of nonmalignant pathology. This highlights a quality improvement opportunity for patients with cT1 renal masses: confirmation that the lesion is suspicious for renal cell carcinoma based on high-quality, multiphase, cross-sectional imaging and/or histopathological features prior to surgery, even if obtaining subsequent follow-up imaging and/or renal mass biopsy is necessary. When performed, these steps lead to reclassification in 79% and 87% of indeterminate renal lesions, respectively.


Asunto(s)
Neoplasias Renales , Música , Humanos , Neoplasias Renales/diagnóstico , Neoplasias Renales/terapia , Neoplasias Renales/patología , Sensibilidad y Especificidad , Riñón/diagnóstico por imagen , Riñón/patología , Biopsia , Estudios Retrospectivos
5.
Prostate ; 82(12): 1186-1195, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35579026

RESUMEN

BACKGROUND: To identify the periprostatic structures associated with early return of urinary continence after radical prostatectomy (RP). METHODS: We compared total continence results between four different techniques of robot-assisted radical prostatectomy (RARP). Specifically, we studied 1-week and 1-month zero-pad continence rates of anterior (n = 60), posterior (n = 59), a novel hybrid posterior-anterior (n = 12), and transvesical (n = 12) approaches of RARP. Each technique preserved a unique set of periprostatic anatomic structures, thereby, allowing evaluation of the individual impact of preservation of nerves, bladder neck, and space of Retzius with associated anterior support structures on early continence. Urethral length was preserved in all approaches. The space of Retzius was preserved in posterior and transvesical approaches, while the bladder neck was preserved in posterior and hybrid approaches. Nerve sparing was done per preoperative oncological risk. For all patients, 24-h pad usage rates and 24-h pad weights were noted at 1 week and 1 month after catheter removal. Multivariable logistic regression analysis was performed to identify predictors of early continence. Data were obtained from prospective studies conducted between 2015 and 2021. RESULTS: At 1 week, 15%, 42%, 45%, and 8% of patients undergoing anterior, posterior, hybrid, and transvesical RARP approaches, respectively, were totally continent (p = 0.003). These rates at 1 month were 35%, 66%, 64%, and 25% (p = 0.002), respectively. The transvesical approach, which preserved the space of Retzius but not the bladder neck, was associated with the poorest continence rates, while the posterior and hybrid approaches in which the bladder neck was preserved with or without space of Retzius preservation were associated with quickest urinary continence recovery. Bladder neck preservation was the only significant predictor of 1-week and 1-month total continence recovery in adjusted analysis, Odds ratios 9.06 (p = 0.001) and 5.18 (p = 0.004), respectively. CONCLUSIONS: The beneficial effect of the Retzius-sparing approach on early continence recovery maybe associated with bladder neck preservation rather than space of Retzius preservation.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Incontinencia Urinaria , Humanos , Masculino , Estudios Prospectivos , Próstata , Prostatectomía/efectos adversos , Prostatectomía/métodos , Recuperación de la Función/fisiología , Procedimientos Quirúrgicos Robotizados/efectos adversos , Procedimientos Quirúrgicos Robotizados/métodos , Resultado del Tratamiento , Incontinencia Urinaria/etiología , Incontinencia Urinaria/prevención & control
6.
Curr Opin Urol ; 32(2): 152-157, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-34930885

RESUMEN

PURPOSE OF REVIEW: The purpose of this review article is to discuss the impact of Coronavirus Disease 2019 (COVID-19) on the evolution of telemedicine use for urology office visits. RECENT FINDINGS: The COVID-19 pandemic has caused a dramatic change in the delivery of healthcare. Fraught with numerous barriers previously, the need for healthcare delivery during a time of social distancing and increased healthcare requirements drove the adoption of telemedicine forward. This 'trial period' over the last year has allowed us to appreciate the potential utility of telehealth-associated services in practice and consider its role even after the pandemic. Multiple studies equating its utility to in-person visits whereas simultaneously providing added convenience and cost-related savings have been published in the urologic literature. Permanent regulatory changes will need to be implemented to allow us the flexibility to use telehealth in the future. SUMMARY: It is clear that telemedicine is an effective strategy for delivery of healthcare under the right circumstances. Although it initially started to fill a need out of necessity, it can help us effectively deliver healthcare as long as the regulations surrounding telemedicine allow us to continue to use it. This period has been challenging for healthcare delivery and led to policy changes that served as a catalyst to help us better understand this previously underutilized resource.


Asunto(s)
COVID-19 , Telemedicina , Urología , Humanos , Visita a Consultorio Médico , Pandemias , SARS-CoV-2
7.
Cancer ; 127(17): 3156-3162, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34160824

RESUMEN

BACKGROUND: Ensuring representative data accrual in clinical trials is important to safeguard the generalizability of results and to minimize disparities in care. This study's goal was to evaluate differences in gender representation in trials leading to US Food and Drug Administration (FDA) cancer drug approvals. METHODS: An observational study was conducted from January 2014 to April 2019 using PubMed and the National Institutes of Health trials registry for primary trial reports. The National Cancer Institute's Surveillance, Epidemiology, and End Results program and US Census were consulted for national cancer incidence. The outcome was an enrollment incidence disparity (EID), which was calculated as the difference between male and female trial enrollment and national incidence, with positive values representing male overrepresentation. RESULTS: There were 149 clinical trials with 59,988 participants-60.3% and 39.7% were male and female, respectively-leading to 127 oncology drug approvals. The US incidence rates were 55.4% for men versus 44.6% for women. Gender representation varied by specific tumor type. Most notably, women were underrepresented in thyroid cancer (EID, +27.4%), whereas men were underrepresented in soft tissue cancer (EID, -26.1%). Overall, women were underrepresented when compared with expected incidence (EID, +4.9%; 42% of trials). CONCLUSIONS: For many specific tumor types, women are underrepresented in clinical trials leading to FDA oncology drug approvals. It is critical to better align clinical trial cohort demographics and the populations to which these data will be extrapolated. LAY SUMMARY: This study assesses whether gender disparities exist in clinical trials leading to US Food and Drug Administration (FDA) cancer drug approvals. From January 2014 to April 2019, 149 clinical trials leading to FDA oncology drug approvals showed 60.3% and 39.7% of the enrollees were male and female, respectively. Gender representation varied by specific tumor when compared with the expected incidence rate of cancer in the United States, although women were more often underrepresented. Increased efforts are needed with regard to ensuring equitable representation in oncology clinical trials.


Asunto(s)
Oncología Médica , Neoplasias , Estudios de Cohortes , Aprobación de Drogas , Femenino , Humanos , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/epidemiología , Estudios Observacionales como Asunto , Estados Unidos/epidemiología , United States Food and Drug Administration
8.
J Urol ; 206(1): 115-123, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33683936

RESUMEN

PURPOSE: The purpose of this study was to establish the feasibility of performing a urinary bladder vascularized composite allograft transplantation for either bladder augmentation or neobladder creation. MATERIALS AND METHODS: Six adult cadavers were studied. Cadavers were excluded for any previous pelvic surgery, radiation, vascular surgery or history of pelvic malignancy. An intravascular colored silicone and barium mixture was injected and both computerized tomography scans and gross dissections were performed. Contrast enhanced computerized tomography imaging was used to delineate urinary bladder vascular anatomy variability. Bladders were explanted en bloc from 2 cadavers with bilateral vascular pedicles based on the external iliac vessels and "transplanted" to replicate a bladder transplant. RESULTS: Contrast enhanced 3-D-computerized tomography reconstructions and cadaver dissections revealed distal vascular variability with proximal blood supply based primarily on the internal iliac artery. Urinary bladder vascularized composite allograft transplantation was successfully performed during 2 mock transplants with the vascular anastomosis done to the recipient external iliac artery and vein. CONCLUSIONS: Urinary bladder vascularized composite allograft transplantation is technically and anatomically feasible. This procedure may obviate the use of intestinal segments for bladder reconstruction in select patients. A phase 1 clinical trial is in progress.


Asunto(s)
Vejiga Urinaria/irrigación sanguínea , Vejiga Urinaria/trasplante , Adulto , Cadáver , Estudios de Factibilidad , Femenino , Humanos , Masculino
9.
J Urol ; 204(6): 1312-1317, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32799727

RESUMEN

PURPOSE: In 2012 the American Urological Association published vasectomy guidelines to promote best practices, including when to obtain post-vasectomy semen analyses. In this study we assessed practice patterns of post-vasectomy semen analysis since this guideline publication. MATERIALS AND METHODS: We retrospectively analyzed a database of men who underwent post-vasectomy semen analysis between 2013 and 2017. Vasectomies were performed by urologist and nonurologist providers in academic and community settings. RESULTS: A total of 4,827 men underwent post-vasectomy semen analysis with 22.3% undergoing 1 or more repeat analyses. On initial analysis 58.2% were azoospermic, 28.3% had less than 100,000/ml rare nonmotile sperm, 8.7% had greater than 100,000/ml nonmotile sperm and 4.8% had motile sperm. The rate of repeat post-vasectomy semen analysis decreased from 30.7% in 2013 to 18.6% in 2016. Overall 72% of repeat post-vasectomy semen analyses were performed for patients with azoospermia or rare nonmotile sperm on initial post-vasectomy semen analysis. Of the 421 men with greater than 100,000/ml nonmotile sperm, 61.3% did not obtain a repeat analysis. Among cases of repeat analysis after initially having greater than 100,000/ml nonmotile sperm, 67.5% were downgraded to rare nonmotile sperm or azoospermia, 32.5% had a persistent count greater than 100,000/ml nonmotile sperm and none developed motile sperm. CONCLUSIONS: The rate of repeat post-vasectomy semen analysis is decreasing, likely highlighting a decrease in unnecessary testing. However, there is ongoing discordance between vasectomy guidelines and practice patterns, with 72% of repeat post-vasectomy semen analyses obtained unnecessarily based on guideline recommendations. Interestingly, no men with greater than 100,000/ml nonmotile sperm went on to have motile sperm on repeat post-vasectomy semen analysis. Further provider education is warranted and subsequent studies may allow for guideline modification wherein all nonmotile sperm are characterized similarly.


Asunto(s)
Azoospermia/diagnóstico , Adhesión a Directriz/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Análisis de Semen/estadística & datos numéricos , Vasectomía , Adulto , Azoospermia/etiología , Humanos , Masculino , Periodo Posoperatorio , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/normas , Estudios Retrospectivos , Análisis de Semen/normas , Sociedades Médicas/normas , Factores de Tiempo , Estados Unidos , Urología/normas
10.
Jpn J Clin Oncol ; 50(7): 800-809, 2020 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-32083295

RESUMEN

BACKGROUND: Targeting the programmed death ligand 1 (PD-L1) pathway has become standard for many advanced malignancies. Whether PD-L1 expression predicts response is unclear. We assessed the association between PD-L1 expression and immunotherapy response using stratified meta-analysis. METHODS: We performed a systematic review of randomized clinical trials published prior to October 2018 comparing overall survival (OS) in patients with advanced solid organ malignancies treated with immunotherapy or standard treatment. Pooled hazard ratios were calculated among patients with high and low PD-L1 levels independently. Differences between the two estimates were assessed using meta-analysis of study-level differences. Our primary analysis assessed a 1% threshold while secondary analyses utilized 5, 10 and 50%. RESULTS: 14 eligible trials reporting on 8887 patients were included. While there was a significant OS benefit for immunotherapy compared with standard treatment for all patients, the magnitude of benefit was significantly larger among those with high PD-L1 expression (P = 0.006). This finding persisted regardless of threshold used and across subgroup analyses according to PD-L1 assay type, tumor histology, line of therapy, type of inhibitor and study methodology. CONCLUSIONS: PD-L1 levels have important predictive value in determining the response to immunotherapy. However, patients with low PD-L1 levels also experience improved survival with immunotherapy compared with standard treatment.


Asunto(s)
Antígeno B7-H1/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de Supervivencia
12.
World J Urol ; 37(7): 1239-1249, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30003375

RESUMEN

INTRODUCTION: Conventional imaging modalities have been poor in characterizing the true extent of disease in men with biochemical recurrence following primary treatment for prostate cancer. Functional imaging with positron emission tomography (PET) has shown promise of being a superior imaging modality. We conducted a systematic review and meta-analysis to define the diagnostic accuracy of PET/CT using 11C-choline, 18F-FACBC, or 68Ga-PSMA in detecting recurrent prostate cancer. METHODS: We searched multiple databases in line with the preferred reporting items for systematic review and meta-analysis (PRISMA) statement to define the diagnostic accuracy of 11C-choline, 18F-FACBC, or 68Ga-PSMA PET/CT. Only studies secondarily staging participants with biochemical recurrence and those with an appropriate reference standard (pathology, further imaging, and/or clinical response) were eligible for analysis. RESULTS: Twenty-one studies with 3202 participants met the inclusion criteria. Of these, 11C-choline, 18F-FACBC, and 68Ga-PSMA were the tracer investigated in 16, 5, and 1 studies, respectively. The summary sensitivity for each tracer was 80.9% (95% CI 70.4-88.3%), 79.7% (95% CI 51.9-93.4%), and 76.4% (95% CI 68.3-82.9%), respectively. The corresponding summary specificity was 84.1% (95% CI 70.2-92.2%), 61.9% (95% CI 41.1-79.0%), and 99.8% (95% CI 97.5-100%), respectively. Detection rates ranged between 58.6 and 82.8%. All included studies were judged to be at high risk of bias primarily due to study limitations pertaining to the reference standard. CONCLUSION: There is a lack of high-quality data to verify the accuracy of PET-based imaging using 11C-choline, 18F-FACBC, or 68Ga-PSMA. The early results are encouraging that these techniques are superior to conventional imaging modalities, which would allow salvage therapies to be optimized.


Asunto(s)
Recurrencia Local de Neoplasia/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/diagnóstico por imagen , Radioisótopos de Carbono , Ácidos Carboxílicos , Colina , Ciclobutanos , Isótopos de Galio , Radioisótopos de Galio , Humanos , Masculino , Glicoproteínas de Membrana , Recurrencia Local de Neoplasia/sangre , Compuestos Organometálicos , Neoplasias de la Próstata/sangre , Radiofármacos
13.
Nature ; 483(7391): 613-7, 2012 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-22425996

RESUMEN

Targeted therapies have demonstrated efficacy against specific subsets of molecularly defined cancers. Although most patients with lung cancer are stratified according to a single oncogenic driver, cancers harbouring identical activating genetic mutations show large variations in their responses to the same targeted therapy. The biology underlying this heterogeneity is not well understood, and the impact of co-existing genetic mutations, especially the loss of tumour suppressors, has not been fully explored. Here we use genetically engineered mouse models to conduct a 'co-clinical' trial that mirrors an ongoing human clinical trial in patients with KRAS-mutant lung cancers. This trial aims to determine if the MEK inhibitor selumetinib (AZD6244) increases the efficacy of docetaxel, a standard of care chemotherapy. Our studies demonstrate that concomitant loss of either p53 (also known as Tp53) or Lkb1 (also known as Stk11), two clinically relevant tumour suppressors, markedly impaired the response of Kras-mutant cancers to docetaxel monotherapy. We observed that the addition of selumetinib provided substantial benefit for mice with lung cancer caused by Kras and Kras and p53 mutations, but mice with Kras and Lkb1 mutations had primary resistance to this combination therapy. Pharmacodynamic studies, including positron-emission tomography (PET) and computed tomography (CT), identified biological markers in mice and patients that provide a rationale for the differential efficacy of these therapies in the different genotypes. These co-clinical results identify predictive genetic biomarkers that should be validated by interrogating samples from patients enrolled on the concurrent clinical trial. These studies also highlight the rationale for synchronous co-clinical trials, not only to anticipate the results of ongoing human clinical trials, but also to generate clinically relevant hypotheses that can inform the analysis and design of human studies.


Asunto(s)
Bencimidazoles/farmacología , Ensayos Clínicos Fase II como Asunto , Modelos Animales de Enfermedad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Farmacogenética/métodos , Taxoides/uso terapéutico , Proteínas Quinasas Activadas por AMP , Animales , Protocolos de Quimioterapia Combinada Antineoplásica , Bencimidazoles/uso terapéutico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Docetaxel , Evaluación Preclínica de Medicamentos , Fluorodesoxiglucosa F18 , Genes p53/genética , Humanos , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Mutación/genética , Tomografía de Emisión de Positrones , Proteínas Serina-Treonina Quinasas/deficiencia , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Ensayos Clínicos Controlados Aleatorios como Asunto , Reproducibilidad de los Resultados , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Proteínas ras/genética , Proteínas ras/metabolismo
14.
J Urol ; 207(1): 51, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34633222
17.
Nat Rev Urol ; 21(7): 406-421, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38365895

RESUMEN

Small renal masses (SRMs) are a heterogeneous group of tumours with varying metastatic potential. The increasing use and improving quality of abdominal imaging have led to increasingly early diagnosis of incidental SRMs that are asymptomatic and organ confined. Despite improvements in imaging and the growing use of renal mass biopsy, diagnosis of malignancy before treatment remains challenging. Management of SRMs has shifted away from radical nephrectomy, with active surveillance and nephron-sparing surgery taking over as the primary modalities of treatment. The optimal treatment strategy for SRMs continues to evolve as factors affecting short-term and long-term outcomes in this patient cohort are elucidated through studies from prospective data registries. Evidence from rapidly evolving research in biomarkers, imaging modalities, and machine learning shows promise in improving understanding of the biology and management of this patient cohort.


Asunto(s)
Neoplasias Renales , Nefrectomía , Humanos , Neoplasias Renales/terapia , Neoplasias Renales/diagnóstico , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Carcinoma de Células Renales/terapia , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/patología
18.
Investig Clin Urol ; 65(4): 411-419, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38978221

RESUMEN

PURPOSE: The Open Payments Program (OPP), established in 2013 under the Sunshine Act, mandated medical device and pharmaceutical manufacturers to submit records of financial incentives given to physicians for public availability. The study aims to characterize the gap in real general and real research payments between man and woman urologists. MATERIALS AND METHODS: The study sample included all urologists in the United States who received at least one general or research payment in the OPP database from 2015 to 2021. Recipients were identified using the National Provider Identifier and National Downloadable File datasets. Payments were analyzed by geography, year, payment type, and years since graduation. Multivariable analysis on odds of being in above the median in terms of money received was done with gender as a covariate. This analysis was also completed for all academic urologists. RESULTS: There was a total of 15,980 urologists; 13.6% were woman, and 86.4% were man. Compared to man urologists, woman urologists were less likely to be in the top half of total payments received (odds ratio [OR] 0.62) when adjusted for other variables. When looking at academic urologists, 18.1% were woman and 81.9% were man. However, woman academic urologists were even less likely to be in the top 50% of payments received (OR 0.55). CONCLUSIONS: This study is the first to characterize the difference in industry payments between man and woman urologists. The results should be utilized to educate physicians and industry, in order to achieve equitable engagement and funding for woman urologists.


Asunto(s)
Urología , Humanos , Femenino , Masculino , Urología/economía , Estados Unidos , Industria Farmacéutica/economía , Médicos Mujeres/economía , Médicos Mujeres/estadística & datos numéricos , Urólogos/estadística & datos numéricos , Urólogos/economía
19.
J Endourol ; 38(6): 559-563, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38429913

RESUMEN

Introduction: Retzius-sparing prostatectomy was promoted with the early continence result. The long-term oncologic outcome is still unknown. In this study, we aimed to compare the intermediate-term oncologic outcomes of these two approaches in patients' cohort who were treated as part of a randomized controlled trial. Methods: A total of 120 patients were previously randomized equally to receive Retzius-sparing robot-assisted laparoscopic radical prostatectomy (RS-RARP) vs standard robot-assisted laparoscopic radical prostatectomy (S-RARP) between January 2015 and April 2016. Baseline, surgical, and pathologic characteristics as well as oncologic outcomes were assessed. The analysis was done based on the treatment received. Result: Sixty-three patients underwent S-RARP, whereas 57 patients underwent RS-RARP. There was no statistically significant difference in the baseline nor surgical characteristics. The median follow-up was 71.24 (interquartile range: 59.75-75.75) months. There were more pathologic T3 diseases in RS-RARP. There was no significant difference in the positive margin status nor in the biochemical recurrence (BCR) rate among both groups. After S-RARP and RS-RARP, 6 and 10 patients had BCR, and the 5 years BCR-free survival was 91% and 85%, respectively (p = 0.21). Conclusion: In this cohort, there was no difference in BCR in the patients who received either technique. Further multi-institutional studies with a larger sample size and longer follow-up are required.


Asunto(s)
Prostatectomía , Neoplasias de la Próstata , Procedimientos Quirúrgicos Robotizados , Humanos , Masculino , Prostatectomía/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Persona de Mediana Edad , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Resultado del Tratamiento , Anciano , Tratamientos Conservadores del Órgano/métodos , Estudios de Cohortes , Laparoscopía/métodos
20.
Urol Pract ; : 101097UPJ0000000000000710, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39302182

RESUMEN

INTRODUCTION: How renal mass biopsy (RMB) impacts patient management with T1 renal masses (T1RM) is unclear. We explore the association between RMB and utilization of active surveillance (AS), nephron-sparing interventions (NSI), and radical nephrectomy (RN). METHODS: Data were analyzed retrospectively using the MUSIC-KIDNEY registry. Treatment received was analyzed using a fitted mixed-effects multinomial logistic-regression model. RESULTS: Of 4062 patients, 19.6% underwent RMB. Factors associated with RMB included younger age, higher Charlson comorbidity score, tumor size > 2.0 cm and higher complexity tumors. AS was selected by 88%, 68%, and 27% of patients with benign, indeterminate, and malignant RMB findings. Non-malignant pathology at surgery was significantly (P < .0001) more common without RMB (vs after RMB): 14.8% vs 7.2% of PN and 10.2% vs 1.7% of RN. Patients with T1bRM managed without or with RMB, AS was chosen by 22% vs 34%, NSI by 31% vs 35%, and RN by 47% vs 32% (P = .0027). An interaction between tumor stage (T1a vs T1b) and RMB remained in multivariable analyses accounting for practice-level variation and other confounding variables. The risk-adjusted RN rate for T1bRM was 41.4% without RMB vs 27.8% with RMB; 7.4 RMB are needed to avoid one RN (number needed to treat) for benign or indolent disease. CONCLUSIONS: Treatments received by T1RM patients undergoing RMB are different than when RMB is omitted, based on RMB results and several confounders. T1RM patients benefit from reduction in intervention for non-malignant disease, particularly when RN is planned. For every 7 biopsies of T1bRM performed, one RN was avoided.

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