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1.
Can J Urol ; 27(1): 10118-10124, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32065869

RESUMO

INTRODUCTION: To describe the incidence, contemporary management, risk factors and outcomes of urinary leak following open and robotic partial nephrectomy at a tertiary care, comprehensive cancer center. MATERIALS AND METHODS: We reviewed 975 patients who underwent partial nephrectomy at Moffitt Cancer Center from January 2009 to May 2017. Patient demographic, perioperative and follow up data was recorded and compared stratified for postoperative urine leak. Fisher's exact and Wilcoxon sum-rank testing were performed for categorical and continuous variables as indicated. RESULTS: Twenty-three of 975 (2.3%) patients experienced a urine leak after partial nephrectomy. Median nephrometry score for urine leak patients was 8 (SD +/- 1.3). Median postoperative days to detection was 3.5 and most leaks were discovered due to high drain output. Operative factors associated with urinary leak included open surgery, estimated blood loss, and not using a sliding-clip renorrhaphy (p < 0.05). Ten (44%) were managed conservatively, 9 (39%) patients required ureteral stent placement, 3 (13%) needed a percutaneous nephrostomy tube, one patient (4%) required percutaneous drainage for urinoma (4%). One patient ultimately failed conservative management and required nephrectomy 45 days after the original surgery. Mean time to stent and drain removal was 40 +/- 17 and 24 +/- 7 days, respectively. Five patients with symptomatic leaks were readmitted with a mean length of stay of 3.2 +/- 1.8 days. CONCLUSIONS: The overall incidence of urinary leak after partial nephrectomy remains low regardless of surgical approach. Perioperative characteristics such as tumor complexity and high blood loss, in addition to open surgery and not using a sliding-clip bolstered renorrhaphy are associated with urine leak.

2.
J Urol ; 203(1): 159-163, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31441673

RESUMO

PURPOSE: Patients who undergo cystectomy due to bladder cancer can elect an ileal conduit or a neobladder for urinary diversion. Decision regret related to this choice is an important and undesirable patient reported outcome. Our objective was to compare the severity of decision regret experienced by patients with a neobladder vs an ileal conduit. MATERIALS AND METHODS: We analyzed data from a longitudinal cohort study of patients who underwent cystectomy from 2013 to 2015. We applied multivariable linear regression to examine associations of the urinary diversion method (neobladder vs ileal conduit) with decision regret measured with the DRS (Decision Regret Scale) 6 and 18 months after cystectomy. Covariates included demographic and clinical characteristics, health care utilization and complications after cystectomy, quality of life and factors related to the decision making process, including informed and shared decision making, and goal concordance. RESULTS: Of the 192 patients in our cohort 141 received an ileal conduit and 51 received a neobladder. We observed no significant difference in the DRS score in patients with a neobladder vs an ileal conduit at 6 or 18 months (b=-1.28, 95% CI -9.07-6.53, vs b=-1.55, 95% CI -12.48-9.38). However, informed decision making was negatively related to decision regret at 6 and 18 months (b=-13.08, 95% CI -17.05--9.11, and b=-8.54, 95% CI -4.26--2.63, respectively). Quality of life was negatively associated with decision regret at 18 months (b=-5.50, 95% CI -8.95--2.03). CONCLUSIONS: Patients treated with cystectomy who were more informed about bladder reconstruction options experienced less regret independent of the method selected. Efforts to inform and prepare patients for the bladder reconstruction decision may help prevent decision regret.


Assuntos
Cistectomia , Tomada de Decisões , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/métodos , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Qualidade de Vida , Neoplasias da Bexiga Urinária/patologia
3.
Urol Oncol ; 38(1): 7.e9-7.e18, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31704139

RESUMO

OBJECTIVES: Primary tumor size (PTS) is the main prognostic factor for relapse in clinical stage (CS) IA testicular seminoma (T1N0M0S0) and the 8th edition of the Tumor-Node-Metastasis staging system now subcategorizes pT1 tumors into pT1a and pT1b based on PTS (<3 cm and ≥3 cm, respectively). We attempted to assess PTS as a prognosticator for overall survival (OS) in CS IA seminoma and to evaluate the comparative effectiveness of active surveillance (AS) versus adjuvant therapy (AT) in patients with large primary tumors (LPT). METHODS AND MATERIALS: In the National Cancer Database (2004-2014), 2455 (47.7%) and 2685 (52.3%) patients with CS IA seminoma were treated with AS and AT, respectively. AT was defined as the receipt of chemotherapy or radiation within 3 months after orchiectomy. A cut-point analysis was performed to determine the optimal PTS threshold predicting OS at 5 years after orchiectomy. Inverse-probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and Cox regression analyses were used to compare OS of patients with LPT (using the optimal PTS cut-point) treated with AS versus AT. RESULTS: In adjusted analysis, pathologic T-stage (pT1a vs. pT1b) did not predict OS and no OS benefit was noted in pT1b patients treated with AT. The optimal PTS cut-point was 4.5 cm. In multivariable analysis, patients with LPT (≥4.5 cm) had an increased risk of overall mortality (HR = 1.87, P = 0.003). Kaplan-Meier curves revealed that OS was superior in patients with LPT treated with AT (IPTW-adjusted log-rank P = 0.029). In IPTW-adjusted Cox regression analysis, AT was associated with an OS benefit in patients with LPT (HR = 0.59, 95%CI: 0.39-0.91, P = 0.017). CONCLUSIONS: In this National Cancer Database analysis, PTS was a predictor of OS in CS IA seminoma. An OS benefit was noted for individuals with LPT (defined as PTS ≥4.5 cm) managed with AT. These findings may warrant refinement of Tumor-Node-Metastasis staging system.

4.
Eur Urol Focus ; 5(5): 704-705, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31564641

RESUMO

While there is still debate and uncertainty regarding the best management strategy for clinical stage IB nonseminoma germ cell tumor, adjuvant treatment with chemotherapy or surgery is associated with a markedly lower risk of recurrence for men with high-risk features and provides more definitive disease control and lower overall exposure to chemotherapy for patients who do experience recurrence.

5.
BJU Int ; 124(6): 955-961, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31313473

RESUMO

OBJECTIVE: To examine predictors of early readmissions after radical cystectomy (RC). Factors associated with preventable readmissions may be most evident in readmissions that occur within 3 days of discharge, commonly termed 'bounce-back' readmissions, and identifying such factors may inform efforts to reduce surgical readmissions. PATIENTS AND METHODS: We utilised the Healthcare Cost and Utilization Project's State Inpatient Databases to examine 1867 patients undergoing RC in 2009 and 2010, and identified all patients readmitted within 30 days of discharge. We assessed differences between patients experiencing bounce-back readmission compared to those readmitted 8-30 days after discharge using logistic regression models and also calculated abbreviated LACE scores to assess the utility of common readmissions risk stratification algorithms. RESULTS: The 30-day and bounce-back readmission rates were 28.4% and 5.6%, respectively. Although no patient or index hospitalisation characteristics were significantly associated with bounce-back readmissions in adjusted analyses, bounce-back patients did have higher rates of gastrointestinal (14.3% vs 6.7%, P = 0.02) and wound (9.5% vs 3.0%, P < 0.01) diagnoses, as well as increased index and readmission length of stay (5 vs 4 days, P = 0.01). Overall, the median abbreviated LACE score was 7, which fell into the moderate readmission risk category, and no difference was observed between readmitted and non-readmitted patients. CONCLUSION: One in five readmissions after RC occurs within 3 days of initial discharge, probably due to factors present at discharge. However, sociodemographic and clinical factors, as well as traditional readmission risk tools were not predictive of this bounce-back. Effective strategies to reduce bounce-back readmission must identify actionable clinical factors prior to discharge.

6.
J Urol ; 202(5): 913-919, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31219762

RESUMO

PURPOSE: To our knowledge the reliability of administrative claims codes to report postoperative radical cystectomy complications has not been examined. We compared complications identified by claims data to those abstracted from clinical chart review following radical cystectomy. METHODS: We manually reviewed the charts of 268 patients treated with radical cystectomy between 2014 and 2016 for 30-day complications and queried administrative complication coding using 805 ICD-9/10 codes. Complications were categorized. Using Cohen κ statistics we assessed agreement between the 2 methods of complication reporting for 1 or more postoperative complications overall, categorical complications and complications stratified by the top quartile length of hospital stay and patients who were readmitted. RESULTS: At least 1 or more complications were recorded in 122 patients (45.5%) through manual chart review and 80 (29.9%) were recorded via claim coding data with a concordance rate of κ=0.16, indicating weak agreement. Concordance was generally weak for categorical complication rates (range 0.05 to 0.36). However, when examining only the top length of stay quartile, 1 or more complications were reported in 32 patients (65%) by the manual chart review and in 12 (25%) via coding data with a concordance rate of κ=-0.2. Agreement was weak, similar to the total cohort. CONCLUSIONS: Manual chart review and claim code identification of complications are not highly concordant even when stratified by patients with an extended length of stay, who are known to have more frequent complications. Researchers and administrators should be aware of these differences and exercise caution when interpreting complication reports.


Assuntos
Cistectomia/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia , Neoplasias da Bexiga Urinária/diagnóstico
8.
J Urol ; 202(1): 83-89, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30835627

RESUMO

PURPOSE: Patient centered care aims to align treatment with patient goals, especially when treatment options have equivalent clinical outcomes. For surgeries with lasting impacts that alignment is critical. To our knowledge no psychometrically tested preference elicitation measures exist to support patients with bladder cancer treated with cystectomy, who can often choose between ileal conduit and neobladder diversions. In this study we created a scale to measure how patient goals align with each type of urinary diversion and the associated surgical outcomes. MATERIALS AND METHODS: We performed formative research through focus groups and clinician outreach to adapt a goal dissonance measure. We mailed a survey to adult Kaiser Permanente® members who underwent cystectomy for bladder cancer between January 2013 and June 2015. Eligible patients were identified through electronic health records and chart review. Surveys were mailed 5 to 7 months postoperatively. We administered our 10-item decision dissonance scale along with other decision making measures. We explored goal alignment as well as dissonance. Psychometric analysis included factor analysis, evaluation of scale scores between surgery groups and evaluation with other decision making scores. RESULTS: We identified 10 goals associated with ileal conduit or neobladder diversion. Using survey data on 215 patients our scale differentiated patient goals associated with each diversion choice. On average patients with a neobladder strongly valued neobladder aligned goals such as maintaining body integrity and volitional voiding through the urethra. Patients with an ileal conduit had neutral values on average across all goals. CONCLUSIONS: Our measure lays the foundation for a simple value elicitation approach which could facilitate shared decision making about urinary diversion choice.


Assuntos
Tomada de Decisão Clínica/métodos , Tomada de Decisões , Preferência do Paciente , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/psicologia , Idoso , Cistectomia/efeitos adversos , Feminino , Grupos Focais , Metas , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Inquéritos e Questionários , Derivação Urinária/efeitos adversos , Derivação Urinária/métodos
9.
Eur Urol ; 76(1): 4-6, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30833139

RESUMO

It has been demonstrated that immune checkpoint blockade has efficacy similar to chemotherapy in the neoadjuvant setting. Biomarkers such as PD-L1 expression levels can be used to rationally design clinical trials aimed at personalizing systemic therapy for patients with muscle-invasive bladder cancer.

10.
Bladder Cancer ; 5(1): 51-61, 2019 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-30854413

RESUMO

Background: Bladder cancer patients who undergo cystectomy and urinary diversion face functional and quality-of-life challenges. Little is known about these patients' experiences during decision-making, surgery, and recovery, or how they vary by treatment setting. Objective: To learn about patients' experiences with treatment choice, surgical care, and recovery across health settings. Understanding patient experiences is essential to closing care gaps and developing patient-reported measures. Methods: We conducted focus groups with cystectomy patients and family caregivers at a large comprehensive health care system (N = 32 patients) and an NCI-designated comprehensive cancer center (N = 25 patients and 5 caregivers). Using standard qualitative methods, we identified themes that are not well-represented in existing research. Results: Across both systems, patients described variable experiences in decision-making about their cystectomy and urinary diversion. Some felt overwhelmed by information; others felt poorly informed. Many found self-care equipment challenging; many felt they knew little about what to expect regarding chemotherapy, recovery, and transitioning home. At times, health care personnel could not help manage patients' ostomies or catheterization equipment. Our study also contributes a grounded theoretical framework for describing meaningful domains of patient experience with cystectomy and urinary diversion. We identified a common trajectory that includes decision-making, surgery and post-operative recovery, mastery of self-care, and reintegration. Conclusions: Patients with radical cystectomy and urinary diversion report a wide variety of experiences not captured by quantitative measures. These findings demonstrate that many cystectomy patients could benefit from additional post-operative support. We offer a framework to measure patient-centered domains in future research.

11.
Urology ; 125: 152-153, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30798964
12.
World J Urol ; 37(10): 2017-2029, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30535583

RESUMO

INTRODUCTION: Intravesical therapy has been an important aspect of the management of non-muscle invasive bladder cancer (NMIBC) for 40 years. Bacillus Calmette-Guerin (BCG) is considered standard of care for intermediate and high-grade non-invasive disease, yet understanding the nuances of subsequent intravesical therapy is important for any provider managing bladder cancer. Herein, we review the literature and describe optimal use of intravesical therapies for NMIBC. METHODS: A comprehensive search of the medical literature was performed and highlighted in this review of intravesical therapy for NMIBC. RESULTS: Post-resection intravesical Mitomycin C therapy for low-risk disease remains an important component of care, and gemcitabine now has level-one evidence demonstrating efficacy in this setting but is not yet a guideline recommendation. BCG intravesical therapy remains the most effective therapy preventing recurrence and progression of intermediate and high-risk NMIBC. Adequately characterizing BCG-failure is critical in determining the next step in management which includes radical cystectomy, additional intravesical immunotherapy, chemotherapy with intravesical gemcitabine ± docetaxel and clinical trials. CONCLUSIONS: Intravesical therapy remains the mainstay of treatment for NMIBC and bladder preservation. Intravesical induction BCG followed by maintenance therapy remains standard of care for intermediate and high-risk patients. Detailing the timing and characteristics of recurrence after intravesical therapy is crucial in determining subsequent treatment recommendations. Current clinical trials focus on systemic immunotherapy and enhancing the intravesical immune response by augmenting the delivery mechanism.

13.
World J Urol ; 37(1): 85-93, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30238399

RESUMO

PURPOSE: To provide a comprehensive overview and update of the joint consultation of the International Consultation on Urological Diseases (ICUD) and Société Internationale d'Urologie on Bladder Cancer Urinary Diversion (UD). METHODS: A detailed analysis of the literature was conducted reporting on the different modalities of UD. For this updated publication, an exhaustive search was conducted in PubMed for recent relevant papers published between October 2013 and August 2018. Via this search, a total of 438 references were identified and 52 of them were finally eligible for analysis. An international, multidisciplinary expert committee evaluated and graded the data according to the Oxford System of Evidence-based Medicine. RESULTS: The incidence of early complications has been reported retrospectively in the range of 20-57%. Unfortunately, only a few randomized controlled studies exist within the field of UD. Consequently, almost all studies used in this report are of level 3-4 evidence including expert opinion based on "first principles" research. CONCLUSIONS: Complications rates overall following RC and UD are significant, and when strict reporting criteria are incorporated, they are much higher than previously published. Complications can occur up to 20 years after surgery, emphasizing the need for lifelong follow-up. Progress has been made to prevent complications implementing robotic surgery and fast track protocols. Preoperative patient information, patient selection, surgical techniques, and careful postoperative follow-up are the cornerstones to achieve good results.


Assuntos
Carcinoma de Células de Transição/cirurgia , Cistectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/métodos , Carcinoma de Células de Transição/patologia , Humanos , Músculo Liso/patologia , Invasividade Neoplásica , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias da Bexiga Urinária/patologia , Coletores de Urina
14.
Urology ; 125: 222-229, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30471370

RESUMO

OBJECTIVE: To assess the relative contributions of patient and surgeon factors for predicting selection of ileal conduit (IC), neobladder (NB), or continent pouch (CP) urinary diversions (UD) for patients diagnosed with muscle-invasive/high-risk nonmuscle invasive bladder cancer. This information is needed to enhance research comparing cancer survivors' outcomes across different surgical treatment options. METHODS: Bladder cancer patients' age ≥21 years with cystectomy/UD performed from January 2010 to June 2015 in 3 Kaiser Permanente regions were included. All patient and surgeon data were obtained from electronic health records. A mixed effects logistic regression model was used treating surgeon as a random effect and region as a fixed effect. RESULTS: Of 991 eligible patients, 794 (80%) received IC. One hundred sixty-nine surgeons performed the surgeries and accounted for a sizeable proportion of the variability in patient receipt of UD (intraclass correlation coefficient = 0.26). The multilevel model with only patient factors showed good fit (area under the curve = 0.93, Hosmer-Lemeshow test P = .44), and older age, female sex, estimated glomerular filtration rate <45, 4+ comorbidity index score, and stage III/IV tumors were associated with higher odds of receiving an IC vs neobladder/continent pouch. However, including surgeon factors (annual cystectomy volume, specialty training, clinical tenure) had no association (P = .29). CONCLUSION: In this community setting, patient factors were major predictors of UD received. Surgeons also played a substantial role, yet clinical training and experience were not major predictors. Surgeon factors such as beliefs about UD options and outcomes should be explored.


Assuntos
Cistectomia , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária , Idoso , Serviços de Saúde Comunitária , Prestação Integrada de Cuidados de Saúde , Feminino , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Seleção de Pacientes , Complicações Pós-Operatórias/epidemiologia , Neoplasias da Bexiga Urinária/patologia , Derivação Urinária/métodos , Derivação Urinária/estatística & dados numéricos
15.
J Urol ; 201(4): 709-714, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30342063

RESUMO

PURPOSE: The BCI (Bladder Cancer Index) is a validated, condition specific health questionnaire assessing urinary, bowel and sexual function and quality of life among patients with bladder cancer. We aimed to establish minimally important difference score thresholds that signal clinical importance. MATERIALS AND METHODS: For 1 year after surgery we followed a prospective cohort of 150 patients who underwent radical cystectomy between 2013 and 2016. Usable data on 138 patients were analyzed. The BCI and the Medical Outcomes Study SF-36 (36-Item Short Form Health Survey) questionnaires were completed prior to cystectomy, and 3, 6 and 12 months postoperatively. Distribution based, minimally important differences were estimated at ⅓ and ½ SD for each index domain across time points. Changes in index domain scores anchored to changes in a SF-36 overall health assessment question were used to estimate anchor based, minimally important differences. Pooled averages are reported between time points and methods. RESULTS: The distribution based, minimally important difference of ⅓ SDs for urinary, bowel and sexual domains ranged between 5.3 and 7.3, 4.6 and 5.6, and 6.0 and 8.9 points, respectively. Ranges of ½ SDs were 8.8 and 10.9, 6.8 and 8.4, and 8.9 and 13.5 points, respectively. The anchor based approach resulted in minimally important difference estimates of 6.2, 7.3 and 6.8 points, respectively. Aggregated results across the 2 approaches resulted in minimally important differences of 6 to 9, 5 to 8 and 7 to 11 points for urinary, bowel and sexual domains, respectively. CONCLUSIONS: Using 2 independent approaches to our knowledge we established the first minimally important difference estimates for the BCI. Defining patient reported outcome thresholds is important to interpret changes or differences in BCI scores.


Assuntos
Autoavaliação Diagnóstica , Qualidade de Vida , Neoplasias da Bexiga Urinária , Idoso , Cistectomia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/fisiopatologia , Neoplasias da Bexiga Urinária/cirurgia
17.
BMC Anesthesiol ; 18(1): 157, 2018 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-30390636

RESUMO

BACKGROUND: The perioperative period can be a critical period with long-term implications on cancer-related outcomes. In this study, we evaluate the influence of regional anesthesia on cancer-specific outcomes in a radical cystectomy (RC) cohort of patients. METHODS: We performed a retrospective analysis of patients with clinically-nonmetastatic urothelial carcinoma of the bladder who underwent RC at our institution from 2008 to 2012. Patients were retrospectively registered and stratified based on two anesthetic techniques: perioperative epidural analgesia with general anesthesia (epidural) versus general anesthesia alone (GA). Epidural patients received a sufentanil-based regimen (median intraoperative sufentanil dose 50 mcg (45,85). Propensity-score was used to make 1:1 case-control matching. Cumulative risk of recurrence with competing risks was calculated based on anesthetic technique. Kaplan-Meier curves were used to compare recurrence-free (RFS) and cancer-specific survival (CSS). Univariable and multivariable analyses were performed with Cox proportional hazard regression models for RFS and CSS. RESULTS: Only patients with complete data on anesthetic technique were included. Out of 439 patients, 215-pair samples with complete follow-up were included in the analysis. Median follow-up was 41.4 months (range: 0.20-101). Patients with epidurals received higher median total intravenous morphine equivalents (ivMEQ) versus those in the GA group (75 (11-235) vs. 50 ivMEQ (7-277), p < 0.0001). Cumulative risk of recurrence at two years was 25.2% (19.6, 31.2) for epidural patients vs. 20.0% (15.0, 25.7) for GA patients (Gray test p = 0.0508). Epidural analgesic technique was a significant predictor of worse RFS (adjusted HR = 1.67, 1.14-2.45; p = 0.009) and CSS (HR = 1.53, 1.04-2.25; p = 0.030) on multivariable analyses. CONCLUSIONS: Epidural anesthesia using sufentanil was associated with worse recurrence and disease-free survival in bladder cancer patients treated with surgery. This may be due use of epidural sufentanil or due to the increased total morphine equivalents patient received as a consequence of this drug.


Assuntos
Anestesia Epidural/métodos , Carcinoma de Células de Transição/cirurgia , Cistectomia/métodos , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Anestesia Geral/métodos , Carcinoma de Células de Transição/patologia , Estudos de Casos e Controles , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem , Recidiva Local de Neoplasia , Pontuação de Propensão , Estudos Retrospectivos , Centros de Atenção Terciária , Neoplasias da Bexiga Urinária/patologia
18.
Oncoimmunology ; 7(9): e1476816, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30228944

RESUMO

Advanced bladder cancer patients have limited therapeutic options resulting in a median overall survival (OS) between 12 and 15 months. Adoptive cell therapy (ACT) using tumor infiltrating lymphocytes (TIL) has been used successfully in treating patients with metastatic melanoma, resulting in a median OS of 52 months. In this study, we investigated the feasibility of expanding TIL from the tumors of bladder cancer patients. Primary bladder tumors and lymph node (LN) metastases were collected. Tumor specimens were minced into fragments, placed in individual wells of a 24-well plate, and propagated in high dose IL-2 for four weeks. Expanded TIL were phenotyped by flow cytometry and anti-tumor reactivity was assessed after co-culture with autologous tumor digest and IFN-gamma ELISA. Of the 28 transitional cell bladder or LN tumors collected, 14/20 (70%) primary tumors and all of the LN metastases demonstrated TIL expansion. Expanded TIL were predominantly CD3+ (median 63%, range 10-87%) with a median of 30% CD8 + T cells (range 5-70%). TIL secreted IFN-gamma in response to autologous tumor. Addition of agonisitic 4-1BB antibody improved TIL expansion from primary bladder tumors regardless of pre-treatment with chemotherapy. This study establishes the practical first step towards an autologous TIL therapy process for therapeutic testing in patients with bladder cancer.

19.
JAMA Oncol ; 4(11): 1535-1542, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30178038

RESUMO

Importance: Neoadjuvant chemotherapy (NAC) followed by radical cystectomy improves survival compared with cystectomy alone for patients with bladder cancer. Although gemcitabine with cisplatin has become a standard NAC regimen, a dose-dense combination of methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) is being adopted at some institutions. Objective: To assess the association of neoadjuvant ddMVAC vs standard regimens with downstaging and overall survival among patients treated with radical cystectomy for bladder cancer. Design, Setting, and Participants: Cross-sectional analysis of data extracted from the medical records of a consecutive sample, after exclusions, of 1113 patients with bladder cancer of whom 824 had disease stage T2 or greater, who were treated with cystectomy at the Moffitt Cancer Center in Tampa, Florida, a tertiary care cancer center, between January 1, 2007, and May 31, 2017. Data were collected between November 14, 2016, and July 21, 2017, and analyzed between August 21, 2017, and December 8, 2017. Patients were compared based on type of NAC. Those who did not receive NAC were included as controls. Main Outcomes and Measures: Comparative rates and the association of any downstaging, complete response, and overall survival with ddMVAC and other NAC regimens and surgery alone. Outcomes were examined using Kaplan-Meier, adjusted logistic, Cox regression, and propensity-weighted models. Results: Of the 1113 patients who underwent cystectomy for bladder cancer, 861 (77.4%) were male, the median (interquartile range) age was 67 (60-74) years, 1051 (94.4%) were white, 27 (2.4%) black, 37 (3.3%) Hispanic/Latino, and 35 (3.1%) other race/ethnicity. Of 824 patients with muscle-invasive bladder cancer, 332 (40%) received NAC. Downstaging rates were 52.2% for ddMVAC, 41.3% for gemcitabine-cisplatin, and 27.0% for gemcitabine with carboplatin, and complete response (pT0N0) rates were 41.3% for ddMVAC, 24.5% for gemcitabine-cisplatin, and 9.4% for gemcitabine-carboplatin (2-sided P < .001). Adjusted analysis comparing ddMVAC with gemcitabine-cisplatin demonstrated a higher likelihood of downstaging (odds ratio [OR], 1.84; 95% CI, 1.10-3.09) and complete response (OR, 2.67; 95% CI, 1.50-4.77) with ddMVAC. Similar results were achieved with propensity score matching (OR, 1.52; 95% CI, 0.99-2.35). Patients who received ddMVAC had better overall survival than those treated with other chemotherapy regimens, although the observed survival benefit did not reach statistical significance in adjusted or propensity-matched models (hazard ratio, 0.44; 95% CI, 0.14-1.38; P = .16). Conclusions and Relevance: This study suggest that neoadjuvant ddMVAC followed by cystectomy is associated with a higher complete response (ypT0N0) rate than standard NAC. These data highlight and suggest the need to further investigate ddMVAC vs standard NAC in a prospective, randomized fashion.


Assuntos
Cistectomia/métodos , Terapia Neoadjuvante/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/mortalidade
20.
Clin Genitourin Cancer ; 16(5): e1003-e1013, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29859736

RESUMO

BACKGROUND: Primary urethral carcinoma (PUC) is rare, and standard treatment recommendations are lacking. We examined the variation in treatments and survival outcomes of female PUC at a single, tertiary referral cancer center. METHODS: Records of women with PUC referred to our multidisciplinary genitourinary oncology service between 2003 and 2017 were reviewed. Clinical, demographic, pathologic, primary and salvage therapy details, and overall (OS) and recurrence-free survival (RFS) were recorded. Survival outcomes were analyzed for the entire cohort, and cases of locally-advanced (≥ T2 tumor), non-metastatic PUC were evaluated according to treatment intensity. Multimodal treatment (cystourethrectomy + concomitant therapy) was compared with non-multimodal therapy. Contingency analyses and Kaplan-Meier estimates were performed. RESULTS: Thirty-nine women with PUC were identified. In total, median OS was 36 months (95% confidence interval, 10.6-61.4 months). Twenty-four had T3 to T4 disease, 12 were node-positive, and 3 had distant metastases. Histology included 22 adenocarcinomas, 11 urothelial, 5 squamous, and 1 neuroendocrine. Patients with locally advanced, non-metastatic disease (n = 25) had significantly reduced OS (36 vs. 99 months; P = .016) and RFS (46 months vs. unmet; P = .011) compared with patients with locally confined tumors. Approximately one-half of locally advanced cases were managed with multimodal therapy (4 with neoadjuvant therapy + cystourethrectomy, 8 with cystourethrectomy + adjuvant therapy, and 1 with chemoradiation + consolidative cystourethrectomy). Multimodal therapy had nonsignificant longer OS (36 vs. 16 months) and RFS (58 vs. 16 months), P > .05. CONCLUSIONS: Locally advanced female PUC has relatively poor survival outcomes. Although we observed a nonsignificant interval improvement in survival with multimodality therapy, the treatment paradigm is inconsistent. Because it is a rare disease, collaborative multi-institutional studies are needed.


Assuntos
Terapia Combinada/métodos , Neoplasias Uretrais/terapia , Idoso , Quimiorradioterapia , Cistectomia , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Análise de Sobrevida , Resultado do Tratamento , Ureteroscopia , Neoplasias Uretrais/patologia
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