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PURPOSE: Urinary comprehensive genomic profiling (uCGP) uses next-generation sequencing to identify mutations associated with urothelial carcinoma and has the potential to improve patient outcomes by noninvasively diagnosing disease, predicting grade and stage, and estimating recurrence risk. EXPERIMENTAL DESIGN: This is a multicenter case-control study using banked urine specimens collected from patients undergoing initial diagnosis/hematuria workup or urothelial carcinoma surveillance. A total of 581 samples were analyzed by uCGP: 333 for disease classification and grading algorithm development, and 248 for blinded validation. uCGP testing was done using the UroAmp platform, which identifies five classes of mutation: single-nucleotide variants, copy-number variants, small insertion-deletions, copy-neutral loss of heterozygosity, and aneuploidy. UroAmp algorithms predicting urothelial carcinoma tumor presence, grade, and recurrence risk were compared with cytology, cystoscopy, and pathology. RESULTS: uCGP algorithms had a validation sensitivity/specificity of 95%/90% for initial cancer diagnosis in patients with hematuria and demonstrated a negative predictive value (NPV) of 99%. A positive diagnostic likelihood ratio (DLR) of 9.2 and a negative DLR of 0.05 demonstrate the ability to risk-stratify patients presenting with hematuria. In surveillance patients, binary urothelial carcinoma classification demonstrated an NPV of 91%. uCGP recurrence-risk prediction significantly prognosticated future recurrence (hazard ratio, 6.2), whereas clinical risk factors did not. uCGP demonstrated positive predictive value (PPV) comparable with cytology (45% vs. 42%) with much higher sensitivity (79% vs. 25%). Finally, molecular grade predictions had a PPV of 88% and a specificity of 95%. CONCLUSIONS: uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Hematuria/diagnóstico , Hematuria/genética , Estudios de Casos y Controles , Biomarcadores de Tumor/genética , Sensibilidad y Especificidad , GenómicaRESUMEN
The clinical standard of care for urothelial carcinoma (UC) relies on invasive procedures with suboptimal performance. To enhance UC treatment, we developed a urinary comprehensive genomic profiling (uCGP) test, UroAmplitude, that measures mutations from tumor DNA present in urine. In this study, we performed a blinded, prospective validation of technical sensitivity and positive predictive value (PPV) using reference standards, and found at 1% allele frequency, mutation detection performs at 97.4% sensitivity and 80.4% PPV. We then prospectively compared the mutation profiles of urine-extracted DNA to those of matched tumor tissue to validate clinical performance. Here, we found tumor single-nucleotide variants were observed in the urine with a median concordance of 91.7% and uCGP revealed distinct patterns of genomic lesions enriched in low- and high-grade disease. Finally, we retrospectively explored longitudinal case studies to quantify residual disease following bladder-sparing treatments, and found uCGP detected residual disease in patients receiving bladder-sparing treatment and predicted recurrence and disease progression. These findings demonstrate the potential of the UroAmplitude platform to reliably identify and track mutations associated with UC at each stage of disease: diagnosis, treatment, and surveillance. Multiple case studies demonstrate utility for patient risk classification to guide both surgical and therapeutic interventions.
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Importance: Low-grade non-muscle-invasive urothelial cancer frequently recurs after excision by transurethral resection of bladder tumor (TURBT). Objective: To determine whether immediate post-TURBT intravesical instillation of gemcitabine reduces recurrence of suspected low-grade non-muscle-invasive urothelial cancer compared with saline. Design, Setting, and Participants: Randomized double-blind clinical trial conducted at 23 US centers. Patients with suspected low-grade non-muscle-invasive urothelial cancer based on cystoscopic appearance without any high-grade or without more than 2 low-grade urothelial cancer episodes within 18 months before index TURBT were enrolled between January 23, 2008, and August 14, 2012, and followed up every 3 months with cystoscopy and cytology for 2 years and then semiannually for 2 years. Patients were monitored for tumor recurrence, progression to muscle invasion, survival, and toxic effects. The final date of follow-up was August 14, 2016. Interventions: Participants were randomly assigned to receive intravesical instillation of gemcitabine (2 g in 100 mL of saline) (n = 201) or saline (100 mL) (n = 205) for 1 hour immediately following TURBT. Main Outcomes and Measures: The primary outcome was time to recurrence of cancer. Secondary end points were time to muscle invasion and death due to any cause. Results: Among 406 randomized eligible patients (median age, 66 years; 84.7% men), 383 completed the trial. In the intention-to-treat analysis, 67 of 201 patients (4-year estimate, 35%) in the gemcitabine group and 91 of 205 patients (4-year estimate, 47%) in the saline group had cancer recurrence within 4.0 years (hazard ratio, 0.66; 95% CI, 0.48-0.90; P<.001 by 1-sided log-rank test for time to recurrence). Among the 215 patients with low-grade non-muscle-invasive urothelial cancer who underwent TURBT and drug instillation, 34 of 102 patients (4-year estimate, 34%) in the gemcitabine group and 59 of 113 patients (4-year estimate, 54%) in the saline group had cancer recurrence (hazard ratio, 0.53; 95% CI, 0.35-0.81; P = .001 by 1-sided log-rank test for time to recurrence). Fifteen patients had tumors that progressed to muscle invasion (5 in the gemcitabine group and 10 in the saline group; P = .22 by 1-sided log-rank test) and 42 died of any cause (17 in the gemcitabine group and 25 in the saline group; P = .12 by 1-sided log-rank test). There were no grade 4 or 5 adverse events and no significant differences in adverse events of grade 3 or lower. Conclusions and Relevance: Among patients with suspected low-grade non-muscle-invasive urothelial cancer, immediate postresection intravesical instillation of gemcitabine, compared with instillation of saline, significantly reduced the risk of recurrence over a median of 4.0 years. These findings support using this therapy, but further research is needed to compare gemcitabine with other intravesical agents. Trial Registration: clinicaltrials.gov Identifier: NCT00445601.
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Antimetabolitos Antineoplásicos/administración & dosificación , Carcinoma Papilar/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Recurrencia Local de Neoplasia/prevención & control , Cloruro de Sodio/administración & dosificación , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Administración Intravesical , Anciano , Antimetabolitos Antineoplásicos/efectos adversos , Carcinoma Papilar/patología , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia/epidemiología , Neoplasias de la Vejiga Urinaria/patología , Urotelio , GemcitabinaRESUMEN
INTRODUCTION: Urinary tract infections (UTI) and sepsis contribute significantly to the morbidity associated with cystectomy and urinary diversion in the first 30 days. We hypothesized that continuous antibiotic prophylaxis decreased UTIs in the first 30 days following radical cystectomy. METHODS: Patients with urothelial carcinoma of the bladder who underwent a radical cystectomy with urinary diversion for bladder cancer at Oregon Health and Science University from January 2014 to May 2015 were included in the study. The ureteral stents were kept for 3 weeks in both groups. In October 2014, we enacted a Department Quality Initiative to reduce UTIs. Following the initiative, all radical cystectomy patients were discharged home on antibiotic prophylaxis following a postoperative urine culture obtained during hospitalization. To evaluate the effectiveness of the initiative, the last 42 patients before the initiative were compared to the first 42 patients after the initiative with regard to the rate of UTI in the first 30 days following surgery. We used a combination of comprehensive chart review and the American College of Surgeons' National Surgical Quality Improvement Program (NSQIP) to determine UTI and readmission for urosepsis in the first 30 days following surgery. This ensured accurate capture of all patients developing a UTI. RESULTS: A total of 12% in the prophylactic antibiotic group had a documented UTI, whereas 36% in the no antibiotic group had a urinary tract infection (P<0.004). A total of 1 (2%) patient in the antibiotic group was readmitted for urosepsis whereas 7 (17%) patients in the no antibiotic group were admitted for urosepsis (P = 0.02). There was no association noted between urine culture at discharge and the development of UTI in the 30-day postdischarge period (P = 0.75). The median time to UTI was 19 days and the most common organism was Enterococcus (32%). Thirty-percent of patients not receiving prophylaxis developed a UTI 1 day after ureteral stent removal. No patients had a UTI following stent removal in the prophylaxis group. No adverse antibiotic related events were noted. CONCLUSION: Prophylactic antibiotics in the 30 days following radical cystectomy is associated with a significant decrease in urinary tract infections and readmission from urosepsis after surgery.
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Antibacterianos/uso terapéutico , Profilaxis Antibiótica/métodos , Cistectomía/efectos adversos , Complicaciones Posoperatorias/prevención & control , Sepsis/prevención & control , Neoplasias de la Vejiga Urinaria/cirugía , Infecciones Urinarias/prevención & control , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Mejoramiento de la Calidad , Sepsis/etiología , Infecciones Urinarias/etiologíaRESUMEN
BACKGROUND: Renal cell carcinoma forming a venous tumor thrombus (VTT) in the inferior vena cava (IVC) has a poor prognosis. Recent investigations have been focused on prognostic markers of survival. Thrombus consistency (TC) has been proposed to be of significant value but yet there are conflicting data. The aim of this study is to test the effect of IVC VTT consistency on cancer specific survival (CSS) in a multi-institutional cohort. METHODS: The records of 413 patients collected by the International Renal Cell Carcinoma-Venous Thrombus Consortium were retrospectively analyzed. All patients underwent radical nephrectomy and tumor thrombectomy. Kaplan-Meier estimate and Cox regression analyses investigated the impact of TC on CSS in addition to established clinicopathological predictors. RESULTS: VTT was solid in 225 patients and friable in 188 patients. Median CSS was 50 months in solid and 45 months in friable VTT. TC showed no significant association with metastatic spread, pT stage, perinephric fat invasion, and higher Fuhrman grade. Survival analysis and Cox regression rejected TC as prognostic marker for CSS. CONCLUSIONS: In the largest cohort published so far, TC seems not to be independently associated with survival in RCC patients and should therefore not be included in risk stratification models. J. Surg. Oncol. 2016;114:764-768. © 2016 Wiley Periodicals, Inc.
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Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Vena Cava Inferior/patología , Trombosis de la Vena/etiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Trombosis de la Vena/patologíaRESUMEN
The identification of the molecular drivers of cancer by sequencing is the backbone of precision medicine and the basis of personalized therapy; however, biopsies of primary tumors provide only a snapshot of the evolution of the disease and may miss potential therapeutic targets, especially in the metastatic setting. A liquid biopsy, in the form of cell-free DNA (cfDNA) sequencing, has the potential to capture the inter- and intra-tumoral heterogeneity present in metastatic disease, and, through serial blood draws, track the evolution of the tumor genome. In order to determine the clinical utility of cfDNA sequencing we performed whole-exome sequencing on cfDNA and tumor DNA from two patients with metastatic disease; only minor modifications to our sequencing and analysis pipelines were required for sequencing and mutation calling of cfDNA. The first patient had metastatic sarcoma and 47 of 48 mutations present in the primary tumor were also found in the cell-free DNA. The second patient had metastatic breast cancer and sequencing identified an ESR1 mutation in the cfDNA and metastatic site, but not in the primary tumor. This likely explains tumor progression on Anastrozole. Significant heterogeneity between the primary and metastatic tumors, with cfDNA reflecting the metastases, suggested separation from the primary lesion early in tumor evolution. This is best illustrated by an activating PIK3CA mutation (H1047R) which was clonal in the primary tumor, but completely absent from either the metastasis or cfDNA. Here we show that cfDNA sequencing supplies clinically actionable information with minimal risks compared to metastatic biopsies. This study demonstrates the utility of whole-exome sequencing of cell-free DNA from patients with metastatic disease. cfDNA sequencing identified an ESR1 mutation, potentially explaining a patient's resistance to aromatase inhibition, and gave insight into how metastatic lesions differ from the primary tumor.
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ADN de Neoplasias/genética , Receptor alfa de Estrógeno/genética , Exoma , Mutación Missense , Proteínas de Neoplasias/genética , Fosfatidilinositol 3-Quinasas/genética , Sarcoma/genética , Sustitución de Aminoácidos , Fosfatidilinositol 3-Quinasa Clase I , ADN de Neoplasias/sangre , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Sarcoma/sangre , Sarcoma/patologíaRESUMEN
PURPOSE: Metastatic renal cell carcinoma can be clinically diverse in terms of the pattern of metastatic disease and response to treatment. We studied the impact of metastasis and location on cancer specific survival. MATERIALS AND METHODS: The records of 2,017 patients with renal cell cancer and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 centers in the United States and Europe were analyzed. Number and location of synchronous metastases were compared with respect to patient cancer specific survival. Multivariable Cox regression models were used to quantify the impact of covariates. RESULTS: Lymph node metastasis (155) or distant metastasis (725) was present in 880 (44%) patients. Of the patients with distant disease 385 (53%) had an isolated metastasis. The 5-year cancer specific survival was 51.3% (95% CI 48.6-53.9) for the entire group. On univariable analysis patients with isolated lymph node metastasis had a significantly worse cancer specific survival than those with a solitary distant metastasis. The location of distant metastasis did not have any significant effect on cancer specific survival. On multivariable analysis the presence of lymph node metastasis, isolated distant metastasis and multiple distant metastases were independently associated with cancer specific survival. Moreover higher tumor thrombus level, papillary histology and the use of postoperative systemic therapy were independently associated with worse cancer specific survival. CONCLUSIONS: In our multi-institutional series of patients with renal cell cancer who underwent radical nephrectomy and tumor thrombectomy, almost half of the patients had synchronous lymph node or distant organ metastasis. Survival was superior in patients with solitary distant metastasis compared to isolated lymph node disease.
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Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/cirugía , Neoplasias Renales/mortalidad , Neoplasias Renales/cirugía , Células Neoplásicas Circulantes , Nefrectomía , Trombectomía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/secundario , Humanos , Neoplasias Renales/patología , Persona de Mediana Edad , Nefrectomía/métodos , Tasa de Supervivencia , Adulto JovenRESUMEN
OBJECTIVES: No guidelines exist for the management of micropapillary bladder cancer (MPBC) and most reports of this variant of urothelial carcinoma are case series comprising small numbers of patients. We sought to determine current practice patterns for MPBC using a survey sent to the Society of Urologic Oncology (SUO) and to present those results in the setting of a comprehensive review of the existing literature. MATERIALS AND METHODS: A survey developed by the Translational Science Working Group of the Bladder Cancer Advocacy Network-sponsored Think Tank meeting was distributed to members of the SUO. The results from 118 respondents were analyzed and presented with a literature review. RESULTS: Most survey respondents were urologists, with 80% considering bladder cancer their primary area of interest. Although 78% of the respondents reported a dedicated genitourinary pathologist at their institution, there were discrepant opinions on how a pathologic diagnosis of MPBC is determined as well as variability on the proportion of MPBC that is clinically significant. Among them, 78% treat MPBC differently than conventional urothelial carcinoma, with 81% reporting that they would treat cT1 MPBC with upfront radical cystectomy. However, the respondents had split opinions regarding the sensitivity of MPBC to cisplatin-based chemotherapy, which affected utilization of neoadjuvant chemotherapy in muscle-invasive disease. CONCLUSIONS: The management of MPBC is diverse among members of the SUO. Although most favors early cystectomy for cT1 MPBC, there is no consensus on the use of neoadjuvant chemotherapy for muscle-invasive MPBC.
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Carcinoma de Células Transicionales/terapia , Oncología Médica/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Neoplasias de la Vejiga Urinaria/terapia , Carcinoma de Células Transicionales/patología , Quimioterapia Adyuvante , Terapia Combinada , Cistectomía/métodos , Humanos , Terapia Neoadyuvante , Radioterapia/métodos , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: Neoadjuvant chemotherapy (NACT) for the treatment of muscle-invasive bladder cancer (MIBC) remains underutilized in the United States despite evidence supporting its use. OBJECTIVES: To examine the perioperative chemotherapy management of patients with MIBC by medical oncologists (MedOncs) to move toward standardization of practice PARTICIPANTS AND METHODS: A 26-question survey was emailed to 92 MedOncs belonging to the Bladder Cancer Advocacy Network or the American Society of Clinical Oncology for completion from May to October 2011 RESULTS: A total of 83 MedOncs completed the survey: 52% were based in academic centers. Most referrals were from urologists (79%). NACT for treatment of MIBC and high-grade upper-tract urothelial carcinoma is offered by 80% and 46% of respondents, respectively. Adjuvant chemotherapy for treatment of MIBC and upper-tract urothelial carcinoma is offered by 46% and 42% of respondents, respectively. NACT was not offered by 49%, 29%, and 35% of respondents if Eastern Cooperative Oncology Group performance status was 3 or greater, if patients had T2 lesions without lymphovascular invasion, and if the glomerular filtration rate was<50ml/min, respectively. Chemotherapy regimens included gemcitabine/cisplatin (90%), methotrexate/vinblastine/adriamycin/cisplatin (30%), dose-dense methotrexate, vinblastine, adriamycin, and cisplatin (20%), and gemcitabine/carboplatin (37%). CONCLUSIONS: Most MedOncs (79%) in this survey offer perioperative chemotherapy to all patients with MIBC. This increased use of NACT is higher than previously reported, suggesting an increase in the adoption of recommendations that follow best evidence.
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Quimioterapia Adyuvante/estadística & datos numéricos , Músculos/patología , Terapia Neoadyuvante/estadística & datos numéricos , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/terapia , Anciano , Anciano de 80 o más Años , Humanos , Oncología Médica , Persona de Mediana Edad , Invasividad Neoplásica , Encuestas y Cuestionarios , Estados Unidos , UrologíaRESUMEN
Renal cell carcinoma (RCC) extension into the renal vein or the inferior vena cava occurs in 4%-10% of all kidney cancer cases. This entity shows a wide range of different clinical and surgical scenarios, making natural history and oncological outcomes variable and poorly characterized. Infrequency and variability make it necessary to share the experience from different institutions to properly analyze surgical outcomes in this setting. The International Renal Cell Carcinoma-Venous Tumor Thrombus Consortium was created to answer the questions generated by competing results from different retrospective studies in RCC with venous extension on current controversial topics. The aim of this article is to summarize the experience gained from the analysis of the world's largest cohort of patients in this unique setting to date.
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Carcinoma de Células Renales/cirugía , Neoplasias Renales/cirugía , Células Neoplásicas Circulantes/patología , Nefrectomía/efectos adversos , Trombectomía/métodos , Vena Cava Inferior , Trombosis de la Vena , Carcinoma de Células Renales/patología , Humanos , Cooperación Internacional , Neoplasias Renales/patología , Trombosis de la Vena/etiología , Trombosis de la Vena/patología , Trombosis de la Vena/cirugíaRESUMEN
OBJECTIVES: Upper tract urothelial carcinoma (UTUC) is a rare disease in Western countries and garners little focused attention in urologic and oncologic circles. We report highlights from the first symposium on UTUC. METHODS: All participants were asked to provide a summary of their presentation to be included as part of these proceedings. Submitted summaries were synthesized into this document. All contributors reviewed and provided input on the final draft. RESULTS: Five highlights are included in this report, including landmark research that not only reveals the likely cause of Balkan endemic nephropathy and associated UTUC but also links it directly to UTUC in Taiwan. Because of the ubiquitous use of Aristolochia plants in these herbal remedies, a public health problem of considerable magnitude is anticipated in Asian countries. Gene expression signatures reveal some differential expression in bladder carcinoma, such as CLCA2 and GABRE. Few urinary markers have proven utility for the diagnosis and follow-up of UTUC, and no tissue or blood-based markers are currently undergoing clinical application. Novel endoscopic therapies provide some hope of improving tissue sampling, diagnosis, and kidney-sparing therapeutics, but the greatest potential lies in improving clinical (preoperative) risk stratification, which is critically limited in this disease. Biomarkers, currently untested, hold promise in identifying patients most likely to benefit from perioperative chemotherapy and at high risk from cisplatin-induced nephrotoxicity. CONCLUSIONS: Despite its rarity in the West, UTUC is reaching potentially epidemic proportions in the East because of exposure to carcinogenic herbal remedies. Critical trials are needed to improve our understanding and treatment of UTUC. Because of the broad range of comorbid conditions in patients suffering from this disease, it is the consensus of the participants that future clinical trials should be practical in design and applicable to a broad range of patients, diverging from the current dogma of narrow patient selection criteria in clinical trials. Practical designs would maximize accrual for a still uncommon disease, and their findings would be applicable to a larger proportion of patients than current narrowly selected designs.
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Carcinoma de Células Transicionales , Neoplasias Urológicas , Congresos como Asunto , HumanosRESUMEN
BACKGROUND: Although different prognostic factors for patients with renal cell carcinoma (RCC) and vena cava tumor thrombus (TT) have been studied, the prognostic value of histologic subtype in these patients remains unclear. OBJECTIVE: We analyzed the impact of histologic subtype on cancer-specific survival (CSS). DESIGN, SETTINGS, AND PARTICIPANTS: We retrospectively analyzed the records of 1774 patients with RCC and TT who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 US and European centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable ordered logistic and Cox regression models were used to quantify the impact of tumor histology on CSS. RESULTS AND LIMITATIONS: Overall 5-yr CSS was 53.4% (confidence interval [CI], 50.5-56.2) in the entire group. TT level (according to the Mayo classification of macroscopic venous invasion in RCC) was I in 38.5% of patients, II in 30.6%, III in 17.3%, and IV in 13.5%. Histologic subtypes were clear cell renal cell carcinoma (cRCC) in 89.9% of patients, papillary renal cell carcinoma (pRCC) in 8.5%, and chromophobe RCC in 1.6%. In univariable analysis, pRCC was associated with a significantly worse CSS (p<0.001) compared with cRCC. In multivariable analysis, the presence of pRCC was independently associated with CSS (hazard ratio: 1.62; CI, 1.01-2.61; p<0.05). Higher TT level, positive lymph node status, distant metastasis, and fat invasion were also independently associated with CSS. CONCLUSIONS: In our multi-institutional series, we found that patients with pRCC and vena cava TT who underwent radical nephrectomy and tumor thrombectomy had significantly worse cancer-specific outcomes when compared with patients with other histologic subtypes of RCC. We confirmed that higher TT level and fat invasion were independently associated with reduced CSS.
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Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Venas Cavas/patología , Trombosis de la Vena/patología , Tejido Adiposo/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/secundario , Carcinoma de Células Renales/cirugía , Femenino , Humanos , Neoplasias Renales/cirugía , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Nefrectomía , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Trombosis de la Vena/cirugía , Adulto JovenRESUMEN
PURPOSE: Patients undergoing radical cystectomy for bladder cancer are at high risk for venous thromboembolism. Recent data have demonstrated that the risk of venous thromboembolism often extends beyond hospital discharge in nonurological surgical populations. To our knowledge the timing of venous thromboembolism in patients who have undergone radical cystectomy during a 30-day postoperative period has not been assessed. Therefore, we evaluated the timing, incidence and risk factors for venous thromboembolism for patients undergoing radical cystectomy for malignancy. MATERIALS AND METHODS: In this descriptive, observational, retrospective study data from 1,307 patients who underwent radical cystectomy for malignancy from 2005 to 2011 were collected using the American College of Surgeons NSQIP (National Surgical Quality Improvement Program) database. Venous thromboembolism occurrences were evaluated by postoperative day and whether they occurred while an inpatient or after discharge home. Univariate and multivariate Cox regression and logistic regression models were used to evaluate risk factors associated with venous thromboembolism. RESULTS: Of 1,307 patients 78 (6%) were diagnosed with venous thromboembolism. The mean time to venous thromboembolism diagnosis was 15.2 days postoperatively. Of all venous thromboembolism events 55% were diagnosed after patient discharge home. The 30-day mortality rate from venous thromboembolism was 6.4%. Risk factors for the development of venous thromboembolism on multivariate analysis were age (p = 0.024), operative time (p = 0.004) and sepsis or septic shock (p = 0.0001). CONCLUSIONS: More than half of all venous thromboembolisms (55%) in patients undergoing radical cystectomy for malignancy occurred after discharge home and the mean time to venous thromboembolism diagnosis was 15.2 days postoperatively. It is reasonable to consider extended duration pharmacological prophylaxis (4 weeks) in this high risk surgical population.
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Cistectomía/efectos adversos , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/prevención & control , Anciano , Quimioprevención , Cistectomía/métodos , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Neoplasias de la Vejiga Urinaria/cirugía , Tromboembolia Venosa/etiologíaRESUMEN
PURPOSE: Previous studies of the impact of renal cell carcinoma histopathology on survival are conflicting and generally limited to institutional analyses. Thus, we determined the role of renal cell carcinoma histopathology on the stage specific survival rate in a large population based cohort. MATERIALS AND METHODS: We used the 2000 to 2005 National Cancer Institute SEER (Surveillance, Epidemiology and End Results) database to identify 17,605 patients who underwent surgery for renal cell carcinoma and met study inclusion criteria. Patients were stratified by histological subtype (clear cell, papillary, chromophobe, collecting duct and sarcomatoid differentiation) and pathological stage. We performed Cox proportional hazard modeling and Kaplan-Meier survival analysis to determine overall and cancer specific survival. RESULTS: Patients with papillary and chromophobe pathology were less likely to present with T3 or greater disease (17.6% and 16.9%, respectively) while patients with collecting duct and sarcomatoid variants were more likely to present with T3 or greater disease (55.7% and 82.8%, respectively) compared to those with clear cell histology (p <0.001). On multivariate analysis histology was significantly associated with overall and cancer specific survival. Patients with chromophobe pathology had improved survival (HR 0.56, 95% CI 0.40-0.78) while those with collecting duct and sarcomatoid variants had worse survival (HR 2.07, 95% CI 1.44-2.97 and 2.26, 95% CI 1.93-2.64, respectively). CONCLUSIONS: Renal cell carcinoma histological subtype predicts overall and cancer specific survival. Patients with collecting duct and sarcomatoid variants of renal cell carcinoma have poor survival, even those who present with low stage disease. These data suggest inherent differences in renal cell carcinoma biology and may ultimately form the basis of future histologically targeted therapies.
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Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/clasificación , Carcinoma de Células Renales/mortalidad , Estudios de Cohortes , Femenino , Humanos , Estimación de Kaplan-Meier , Riñón/patología , Neoplasias Renales/clasificación , Neoplasias Renales/mortalidad , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Programa de VERF , Tasa de SupervivenciaRESUMEN
PURPOSE: We aimed to validate and improve prognostic signatures for high-risk urothelial carcinoma of the bladder. EXPERIMENTAL DESIGN: We evaluated microarray data from 93 patients with bladder cancer managed by radical cystectomy to determine gene expression patterns associated with clinical and prognostic variables. We compared our results with published bladder cancer microarray data sets comprising 578 additional patients and with 49 published gene signatures from multiple cancer types. Hierarchical clustering was utilized to identify subtypes associated with differences in survival. We then investigated whether the addition of survival-associated gene expression information to a validated postcystectomy nomogram utilizing clinical and pathologic variables improves prediction of recurrence. RESULTS: Multiple markers for muscle invasive disease with highly significant expression differences in multiple data sets were identified, such as fibronectin 1 (FN1), NNMT, POSTN, and SMAD6. We identified signatures associated with pathologic stage and the likelihood of developing metastasis and death from bladder cancer, as well as with two distinct clustering subtypes of bladder cancer. Our novel signature correlated with overall survival in multiple independent data sets, significantly improving the prediction concordance of standard staging in all data sets [mean ΔC-statistic: 0.14; 95% confidence interval (CI), 0.01-0.27; P < 0.001]. Tested in our patient cohort, it significantly enhanced the performance of a postoperative survival nomogram (ΔC-statistic: 0.08, 95% CI, -0.04-0.20; P < 0.005). CONCLUSIONS: Prognostic information obtained from gene expression data can aid in posttreatment prediction of bladder cancer recurrence. Our findings require further validation in external cohorts and prospectively in a clinical trial setting.
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Perfilación de la Expresión Génica , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Reproducibilidad de los Resultados , Análisis de Supervivencia , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: The clinical course of pT3 upper tract urothelial carcinoma (UTUC) is highly variable. OBJECTIVES: The aim of the current study was to validate the clinical and prognostic importance of pT3 subclassification in the renal pelvicalyceal system in a large international cohort of patients. DESIGN, SETTING, AND PARTICIPANTS: From a multi-institutional international database, 858 renal pelvicalyceal tumors treated with radical nephroureterectomy (RNU) were systematically reevaluated by genitourinary pathologists. Category pT3 pelvic tumors were categorized as pT3a (infiltration of the renal parenchyma on a microscopic level only) versus pT3b (macroscopic infiltration of the renal parenchyma and/or infiltration of peripelvic adipose tissue). INTERVENTION: RNU. MEASUREMENTS: Associations of pT3 subclassifications with clinicopathologic features were assessed with the chi-square test. Prognostic impact was assessed with the log-rank test and multivariable Cox regression analyses. RESULTS AND LIMITATIONS: Of 858 patients with renal pelvicalyceal tumors, 266 (31%) had pT3 disease. Of these, 146 (54.9%) were classified as pT3a and 120 (45.1%) as pT3b. Compared with pT3a, pT3b cancers were associated with higher tumor grade, nodal disease, and tumor necrosis. Ten-year recurrence-free (pT3a 58% vs pT3b 38%; p<0.001) and cancer-specific (pT3a 60% vs pT3b 39%; p=0.002) survival rates were lower for patients with pT3b disease. In multivariable analyses, classification pT3b was an independent predictor of both disease recurrence (hazard ratio [HR]: 1.8, p=0.003) and cancer-specific mortality (HR: 1.7; p=0.02). The major limitation is the retrospective character of the study. CONCLUSIONS: Subclassification of pT3 renal pelvicalyceal UTUC helps identify patients who are at increased risk of disease progression and cancer-related death. Further research may help assess the value of subclassification and its inclusion in future editions of the American Joint Committee on Cancer-International Union Against Cancer TNM classification system.
Asunto(s)
Carcinoma/clasificación , Carcinoma/patología , Neoplasias Renales/clasificación , Neoplasias Renales/patología , Urotelio/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Renales/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Nefrectomía/métodos , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Novel prognostic factors for patients after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) have recently been described. OBJECTIVE: We tested the prognostic value of pathologic characteristics and developed models to predict the individual probabilities of recurrence-free survival (RFS) and cancer-specific survival (CSS) after RNU. DESIGN, SETTING, AND PARTICIPANTS: Our study included 2244 patients treated with RNU without neoadjuvant or adjuvant therapy at 23 international institutions. Tumor characteristics included T classification, grade, lymph node status, lymphovascular invasion, tumor architecture, location, and concomitant carcinoma in situ (CIS). The cohort was randomly split for development (12 centers, n=1273) and external validation (11 centers, n=971). INTERVENTIONS: All patients underwent RNU. MEASUREMENTS: Univariable and multivariable models addressed RFS, CSS, and comparison of discrimination and calibration with American Joint Committee on Cancer (AJCC) stage grouping. RESULTS AND LIMITATIONS: At a median follow-up of 45 mo, 501 patients (22.3%) experienced disease recurrence and 418 patients (18.6%) died of UTUC. On multivariable analysis, T classification (p for trend <0.001), lymph node metastasis (hazard ratio [HR]: 1.98; p=0.002), lymphovascular invasion (HR: 1.66; p<0.001), sessile tumor architecture (HR: 1.76; p<0.001), and concomitant CIS (HR: 1.33; p=0.035) were associated with disease recurrence. Similarly, T classification (p for trend<0.001), lymph node metastasis (HR: 2.23; p=0.001), lymphovascular invasion (HR: 1.81; p<0.001), and sessile tumor architecture (HR: 1.72; p=0.001) were independently associated with cancer-specific mortality. Our models achieved 76.8% and 81.5% accuracy for predicting RFS and CSS, respectively. In contrast to these well-calibrated models, stratification based upon AJCC stage grouping resulted in a large degree of heterogeneity and did not improve discrimination. CONCLUSIONS: Using standard pathologic features, we developed highly accurate prognostic models for the prediction of RFS and CSS after RNU for UTUC. These models offer improvements in calibration over AJCC stage grouping and can be used for individualized patient counseling, follow-up scheduling, risk stratification for adjuvant therapies, and inclusion criteria for clinical trials.
Asunto(s)
Carcinoma/cirugía , Nefrectomía , Uréter/cirugía , Neoplasias Ureterales/cirugía , Neoplasias Urológicas/cirugía , Procedimientos Quirúrgicos Urológicos , Anciano , Carcinoma/mortalidad , Carcinoma/secundario , Supervivencia sin Enfermedad , Europa (Continente) , Femenino , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia , América del Norte , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Uréter/patología , Neoplasias Ureterales/mortalidad , Neoplasias Ureterales/patología , Neoplasias Urológicas/mortalidad , Neoplasias Urológicas/patología , Urotelio/patología , Urotelio/cirugíaRESUMEN
OBJECTIVE: Carcinoma in situ (CIS) is associated with increased risk of progression when found with high-grade non-muscle-invasive bladder cancer, yet its impact is less clear in the upper urinary tract. In the current study, we evaluated the impact of concomitant CIS on recurrence-free survival and cancer-specific survival following radical nephroureterectomy for upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: A multi-institutional retrospective cohort of 1,387 patients undergoing radical nephroureterectomy was identified. Concomitant CIS was defined as the presence of CIS in association with another pathologic stage; patients with CIS alone were excluded from the analysis. The presence of concomitant CIS served as the exposure variable with disease recurrence and cancer-specific mortality as the outcomes. Organ-confined disease was defined as AJCC/UICC stage II or lower. RESULTS: Concomitant CIS was identified in 371 of 1,387 (26.7%) patients and was significantly more common in patients with a previous bladder cancer history, high grade, and high stage tumors. In a multivariable analysis, concomitant CIS was a predictor of disease recurrence (HR = 1.25, P = 0.04) and cancer specific mortality (HR = 1.34, P = 0.05) for patients with organ-confined UTUC, but not in the entire cohort. Other prognostic variables, such as grade, stage, lymphovascular invasion, and lymph node status, were associated with poorer overall and recurrence-free survival for all patients. CONCLUSION: The presence of concomitant CIS in patients with organ-confined UTUC is associated with a higher risk of recurrent disease and cancer-specific mortality. This information may be useful in refining surveillance protocols and in more appropriate selection of patients for adjuvant chemotherapy.
Asunto(s)
Carcinoma in Situ/cirugía , Palpación/métodos , Uréter/cirugía , Neoplasias de la Vejiga Urinaria/cirugía , Urotelio/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/diagnóstico , Carcinoma/mortalidad , Carcinoma/cirugía , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/mortalidad , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Nefrectomía/métodos , Pronóstico , Recurrencia , Estudios Retrospectivos , Riesgo , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/mortalidad , Sistema Urinario/cirugíaRESUMEN
OBJECTIVE: Although CT is most commonly used for guidance of radiofrequency ablation (RFA) of renal masses, other publications have shown that ultrasound alone may be used. Therefore, we compared the complications and technical effectiveness of renal RFA guided by ultrasound alone versus combined CT and ultrasound guidance. MATERIALS AND METHODS: We retrospectively analyzed outcomes and complications of percutaneous renal RFA in two groups of patients for whom RFA was guided by either ultrasound alone (group 1) or combined CT and ultrasound (group 2). The sole factor in determining the method of guidance was preablation imaging. All other technical factors were consistent between the two groups. RESULTS: There were 28 masses in 27 patients in group 1 and 32 masses in 29 patients in group 2. There was an overall major complication rate of 3.3% (2/60). Major complications occurred equally in group 2 (3.1% [1/32]) compared with group 1 (3.6% [1/28]). Overall ablative effectiveness was 93% (26/28) in group 1 and 84% (27/32) in group 2. There was no statistical difference between the two groups. CONCLUSION: In proper hands, sonography guidance alone is a safe and effective method for performance of renal RFA in preselected cases and can decrease CT utilization. The use of CT is reserved for situations in which pretreatment RFA imaging suggests difficulty in ultrasound mass visualization or when the mass is in close proximity to structures that may be injured by thermal ablation.
Asunto(s)
Ablación por Catéter , Neoplasias Renales/cirugía , Radiografía Intervencional , Tomografía Computarizada por Rayos X , Ultrasonografía Intervencional , Adulto , Anciano , Anciano de 80 o más Años , Medios de Contraste/administración & dosificación , Gadolinio DTPA/administración & dosificación , Humanos , Yohexol/administración & dosificación , Neoplasias Renales/diagnóstico por imagen , Modelos Logísticos , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
OBJECTIVES: To determine the effect of age on the disease characteristics, treatment administered, and disease-specific survival (DSS) for patients with upper tract urothelial carcinoma. The effect of advancing age on the disease extent and survival has not been well delineated in patients with upper tract urothelial carcinoma. METHODS: Using the Surveillance, Epidemiology, and End Results database from the National Cancer Institute, we identified patients diagnosed with UTUC from 1984 to 2004. The data were analyzed for age (40-49, 50-59, 60-69, 70-79, and ≥80 years), sex, race, disease extent, treatment type, and cause of death. Relationships among age, clinicopathologic features, and treatment were tabulated. The effect of age on overall and DSS were calculated using Cox proportional hazards ratio analyses. RESULTS: The final cohort consisted of 12 639 patients. Advancing age was associated with greater T stage and grade at presentation. Of those 40-49 years old, 41% presented with invasive tumors (T2-T4) compared with 50% of octogenarians. Poor or undifferentiated tumors increased in frequency from 42% among those 40-49 years old to 59% among those≥80 years old. Extirpative surgery was less likely among those with Stage T1 or less disease (88.3% vs 92.8%). Octogenarians were less likely to have undergone extirpative surgery than those 40-49 years old (86% vs 95%). Despite adjustments for T stage, grade, and treatment, DSS (hazard ratio 2.64) worsened with increasing age. CONCLUSIONS: With advancing age, we found a corresponding increase in stage and grade at presentation. After adjustment for stage, grade, and treatment type, older patients still had worse DSS.