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BACKGROUND AND OBJECTIVE: The rationale for oophorectomy during female cystectomy is not adequately supported. The co-occurrence and timing of bladder cancer (BC) and ovarian cancer (OC) in females harboring OC germline mutations remain unclear. Our objective was to determine the frequency and temporal occurrence of OC germline variants among females with BC. METHODS: We used genetic and phenotypic data from the UK Biobank (UKB). The study cohort was defined using ICD-10/ICD-9 codes for BC and further stratified to identify 1347 females. Analysis was restricted to variants with high/moderate impact for initial regression. ClinVar was used to interpret pathogenicity. Pathogenic/likely pathogenic (P/LP) variants were assessed by age of presentation, family history, and concomitant malignancies. Statistical analysis was performed using UKB DNAnexus JupyterLab and RStudio. KEY FINDINGS AND LIMITATIONS: Some 3.4% of the patients had at least one of 15 variants for OC. CHEK2 and PALB2 mutations represented the highest ratio of overall/pathogenic variants (15.8% and 6.6%). Although females with P/LP OC mutations had a higher risk of OC, diagnosis of OC preceded BC by 11.3 yr (±12.5 yr) in the group with mutations and by 15.6 yr (±11.3 yr) in the group without mutations. The group with P/LP variants had higher rates of maternal (14.63% vs 8.12%; p = 0.04) and sibling (9.76% vs 3.98%; p = 0.02) breast cancer and of maternal colon cancer (9.76% vs 4.21%), and lower maternal life expectancy (75.34 vs 68.15 yr; p = 0.0014). UKB provides limited staging/treatment history and its exome sequencing platform may miss variants or provide insufficient coverage for genotyping. CONCLUSIONS AND CLINICAL IMPLICATIONS: This study provides evidence against routine oophorectomy for reducing OC risk in females with BC. The results highlight that the development of OC occurred 11 yr before diagnosis of BC for patients with OC mutations and 15 yr before diagnosis of BC for patients without OC mutations. PATIENT SUMMARY: Although removal of the ovaries in women with bladder cancer is common, no studies have shown that this strategy has a benefit. Our study of women diagnosed with bladder cancer who had genetic mutations associated with ovarian cancer shows that their risk of developing ovarian cancer after bladder cancer is low. These findings provide evidence against removal of the ovaries when the bladder is being removed as treatment for bladder cancer.
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Neoplasias Ovarianas , Neoplasias da Bexiga Urinária , Humanos , Feminino , Neoplasias da Bexiga Urinária/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/epidemiologia , Pessoa de Meia-Idade , Idoso , Estudos de Coortes , Ovariectomia , Mutação em Linhagem Germinativa , Medição de Risco , Reino Unido/epidemiologia , Predisposição Genética para Doença , AdultoRESUMO
PURPOSE: Technetium-99m-sestamibi single-photon emission CT/x-ray CT is an emerging clinical tool to differentiate oncocytic tumors from renal cell carcinomas. We report data from a large institutional cohort of patients who underwent technetium-99m-sestamibi scans during evaluation of renal masses. MATERIALS AND METHODS: Patients who underwent technetium-99m-sestamibi single-photon emission CT/x-ray CT between February 2020 and December 2021 were included in the analysis. Scans were defined as "hot" for oncocytic tumor when technetium-99m-sestamibi uptake was qualitatively equivalent or higher between the mass of interest and normal renal parenchyma, suggesting oncocytoma, hybrid oncocytic/chromophobe tumor, or chromophobe renal cell carcinoma. Demographic, pathological, and management strategy data were compared between "hot" and "cold" scans. For individuals who underwent diagnostic biopsy or extirpative procedures, the concordance between radiological findings and pathology was indexed. RESULTS: A total of 71 patients (with 88 masses) underwent technetium-99m-sestamibi imaging with 60 (84.5%) patients having at least 1 "cold" mass on imaging and 11 (15.5%) patients exhibiting only "hot" masses. Pathology was available for 7 "hot" masses, with 1 biopsy specimen (14.3%) being discordant (clear cell renal cell carcinoma). Five patients with "cold" masses underwent biopsy. Out of 5 biopsied masses, 4 (80%) were discordant oncocytomas. Of the extirpated specimens, 35/40 (87.5%) harbored renal cell carcinoma and 5/40 (12.5%) yielded discordant oncocytomas. In sum, 20% of pathologically sampled masses that were "cold" on technetium-99m-sestamibi imaging still harbored oncocytoma/hybrid oncocytic/chromophobe tumor/chromophobe renal cell carcinoma. CONCLUSIONS: Further work is needed to define utility of technetium-99m-sestamibi in real-world clinical practice. Our data suggest this imaging strategy is not yet ready to replace biopsy.
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Adenoma Oxífilo , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Tecnécio Tc 99m Sestamibi , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Adenoma Oxífilo/diagnóstico por imagem , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Compostos RadiofarmacêuticosRESUMO
INTRODUCTION: Treatment naïve patients with high-risk non-muscle invasive bladder cancer (NMIBC) are treated with bacillus Calmette-Guérin (BCG) therapy as the standard of care. Recently, intravesical sequential gemcitabine-docetaxel in the BCG-naïve setting was shown to be well-tolerated and effective, raising the possibility of a new first line intravesical therapy. Cost effectiveness of this intervention remains unknown; therefore, we designed a cost effectiveness study evaluating BCG vs. sequential gemcitabine-docetaxel in patients with high risk NMIBC. METHODS: Using TreeAgePro 2019 software, we developed a Markov model to evaluate BCG vs. gemcitabine-docetaxel from the U.S. Medicare perspective with a 2-year time horizon. Model probabilities and utilities were derived from published literature. Direct costs were obtained from Medicare cost databases. Our primary outcomes were effectiveness (measured in quality adjusted life years [QALYs]), cost and the incremental cost-effectiveness ratio with a willingness to pay threshold of $100,000. RESULTS: Our results indicate that while both treatments resulted in similar QALYs of 1.76, the mean costs per patient at 2 years were $12,363 and $7,090 for BCG and gemcitabine-docetaxel, respectively. Therefore, the BCG strategy was dominated by the gemcitabine-docetaxel strategy as it was equally effective and less costly. One way sensitivity analyses were completed and gemcitabine-docetaxel remained a cost-effective strategy. CONCLUSIONS: The findings of this preliminary cost-effectiveness analysis are novel in that they highlight a well tolerated, efficacious drug that is less expensive than the traditional gold standard therapy. In modern medicine, we are more often challenged by agents with marginally increased efficacy but at significantly higher costs; gemcitabine-docetaxel represents a rare entity which is a success for both patients and healthcare systems alike.
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Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Idoso , Humanos , Estados Unidos , Gencitabina , Docetaxel/uso terapêutico , Vacina BCG/uso terapêutico , Análise de Custo-Efetividade , Medicare , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Adjuvantes Imunológicos/uso terapêutico , Invasividade NeoplásicaRESUMO
INTRODUCTION: While abiraterone acetate (AA) has demonstrated survival benefit in advanced prostate cancer (APC), meaningful cardiotoxicity is observed. It is unclear whether the magnitude differs based on disease indication and concurrent steroid administration. METHODS: We performed a systematic review and meta-analysis of phase II/III RCTs of AA in APC published as of August 11, 2020. Primary outcomes examined were all- and high-grade (grade ≥ 3) hypokalemia and fluid retention, and secondary outcomes included hypertension and cardiac events. We performed random effects meta-analysis comparing intervention (AA + steroid) and control (placebo ± steroid), stratified by treatment indication and whether patients received steroids. RESULTS: Among 2,739 abstracts, we included 6 relevant studies encompassing 5901 patients. Hypokalemia and fluid retention were observed more frequently among patients receiving AA (odds ratio [OR] 3.10 [95% CI 1.69-5.67] and 1.41 [95% CI 1.19-1.66]). This was modified by whether patients in the control received steroids: trials where control patients did not demonstrated a larger association between AA and hypokalemia (OR 6.88 [95% CI 1.48-2.36] versus OR 1.86 [95% CI 4.97-9.54], P < .0001) and hypertension (OR 2.53 [95% CI 1.91-3.36] vs. OR 1.55 [95% CI 1.17-2.04], P = .1) than those where steroids were administered. We observed heterogeneity due to indication: there were greater effects on hypokalemia (P < 0001), hypertension (P = .03), and cardiac disorders (P = .01) among patients treated for mHSPC than mCRPC. CONCLUSIONS: The magnitude of cardiotoxicity with AA differs based on trial design and disease indication. These data are valuable in treatment decisions and highlight utilization of appropriate data for counseling.
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Hipertensão , Hipopotassemia , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Acetato de Abiraterona/efeitos adversos , Mineralocorticoides/uso terapêutico , Prednisona/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Hipopotassemia/induzido quimicamente , Cardiotoxicidade/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
INTRODUCTION: Radical cystectomy and trimodal therapy are both accepted options in the management of muscle-invasive bladder cancer. As such, we sought to evaluate the micro-level costs associated with both modalities. METHODS: All patients undergoing trimodal therapy or radical cystectomy for primary treatment of urothelial muscle-invasive bladder cancer at a single academic center between 2008 and 2012 were included. Direct costs associated with each phase of a patient's clinical course were collected from the hospital's financial department, and physician costs were calculated based on the provincial fee schedule. Costs of radiation treatments were derived from previously published literature. RESULTS: A total of 137 patients were included. The mean (±SD) patient age was 69 (±12) years. Overall, 89 (65%) patients underwent radical cystectomy and 48 (35%) were treated with trimodal therapy. The radical cystectomy group had higher rates of cT3/T4 compared to those in the trimodal therapy group (51% vs 26%, P < .001). The median cost in the treatment phase for radical cystectomy was $30,577 (IQR: $23,908-$38,837) vs $18,979 ($17,271-$23,519) for trimodal therapy (P < .001). There was no significant difference between treatment groups with respect to cost of diagnosis or workup. However, the cost of follow-up care was numerically higher for patients undergoing trimodal therapy compared to radical cystectomy ($3,096/y vs $1,974/y, P = .09). CONCLUSIONS: In appropriately selected patients with muscle-invasive bladder cancer trimodal therapy costs are not prohibitive and are lower than in radical cystectomy. With increasing follow-up time after primary treatment, the cost difference between modalities may be mitigated by the need for bladder surveillance and salvage therapy in the trimodal therapy cohort.
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Neoplasias da Bexiga Urinária , Bexiga Urinária , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Cistectomia/efeitos adversos , Terapia Combinada , Invasividade Neoplásica , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
BACKGROUND: The application of next-generation sequencing techniques has enabled characterization of urinary tract microbiome. Although many studies have demonstrated associations between the human microbiome and bladder cancer (BC), these have not always reported consistent results, thereby necessitating cross-study comparisons. Thus, the fundamental questions remain how we can utilize this knowledge. OBJECTIVE: The aim of our study was to examine the disease-associated changes in urine microbiome communities globally utilizing a machine learning algorithm. DESIGN, SETTING, AND PARTICIPANTS: Raw FASTQ files were downloaded for the three published studies in urinary microbiome in BC patients, in addition to our own prospectively collected cohort. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Demultiplexing and classification were performed using the QIIME 2020.8 platform. De novo operational taxonomic units were clustered using the uCLUST algorithm and defined by 97% sequence similarity and classified at the phylum level against the Silva RNA sequence database. The metadata available from the three studies included were used to evaluate the differential abundance between BC patients and controls via a random-effect meta-analysis using the metagen R function. A machine learning analysis was performed using the SIAMCAT R package. RESULTS AND LIMITATIONS: Our study includes 129 BC urine and 60 healthy control samples across four different countries. We identified a total of 97/548 genera to be differentially abundant in the BC urine microbiome compared with that of healthy patients. Overall, while the differences in diversity metrics were clustered around the country of origin (Kruskal-Wallis, p < 0.001), collection methodology was a driver of microbiome composition. When assessing dataset from China, Hungary, and Croatia, data demonstrated no discrimination capacity to distinguish between BC patients and healthy adults (area under the curve [AUC] 0.577). However, inclusion of samples with catheterized urine improved the diagnostic accuracy of prediction for BC to AUC 0.995, with precision-recall AUC = 0.994. Through elimination of contaminants associated with the collection methodology among all cohorts, our study identified increased abundance of polycyclic aromatic hydrocarbon (PAH)-degrading bacteria Sphingomonas, Acinetobacter, Micrococcus, Pseudomonas, and Ralstonia to be consistently present in BC patients. CONCLUSIONS: The microbiota of the BC population may be a reflection of PAH exposure from smoking, environmental pollutants, and ingestion. Presence of PAHs in the urine of BC patients may allow for a unique metabolic niche and provide necessary metabolic resources where other bacteria are not able to flourish. Furthermore, we found that while compositional differences are associated with geography more than with disease, many are driven by the collection methodology. PATIENT SUMMARY: The goal of our study was to compare the urine microbiome of bladder cancer patients with that of healthy controls and evaluate any potential bacteria that may be more likely to be found in patients with bladder cancer. Our study is unique as it evaluates this across multiple countries, to find a common pattern. After we removed some of the contamination, we were able to localize several key bacteria that are more likely to be found in the urine of bladder cancer patients. These bacteria all share their ability to break down tobacco carcinogens.
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Microbiota , Neoplasias da Bexiga Urinária , Adulto , Humanos , Bactérias/genética , Neoplasias da Bexiga Urinária/urina , Microbiota/genética , Motivação , RNA Ribossômico 16S/genéticaRESUMO
PURPOSE OF REVIEW: Cytoreductive nephrectomy has had a variable role in the management of metastatic renal cell carcinoma (RCC) through the different systemic therapy eras. Initially felt to be beneficial with interferon, the utility of cytoreductive nephrectomy was called into question in the tyrosine kinase inhibitor (TKI) era. However, with the advent of immunotherapy for metastatic RCC, the role of cytoreductive nephrectomy continues to be debated. This study sought to evaluate the recent literature and discuss cytoreductive nephrectomy within the context of an improved systemic therapy era. RECENT FINDINGS: The literature that exists on the use of cytoreductive nephrectomy with immunotherapy is retrospective in nature and largely derived from large, institutional databases. Although smaller, single-institution articles exist and provide more granular data, issues concerning selection bias and unmeasured confounders persist. Overall, the available studies demonstrate that patient selection is paramount, and cytoreductive nephrectomy should be reserved for patients with no more than one risk factor, those requiring palliation of local symptoms and for those patients with stable, low volume disease or with a complete response following systemic therapy exposure. SUMMARY: The optimal use of cytoreductive nephrectomy in metastatic RCC remains unclear, but certain subgroups of patients, on evaluation of post hoc and retrospective data, seem to benefit from surgical intervention.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Estudos Retrospectivos , Imunoterapia/efeitos adversos , Nefrectomia/efeitos adversosRESUMO
PURPOSE: We evaluated oncologic risks in a large cohort of patients with radiographic cystic renal masses who underwent active surveillance or intervention. MATERIALS AND METHODS: A single-institutional database of 4,340 kidney lesions managed with either active surveillance or intervention between 2000-2020 was queried for radiographically cystic renal masses. Association of radiographic tumor characteristics and high-grade pathology was evaluated. RESULTS: We identified 387 radiographically confirmed cystic lesions in 367 patients. Of these, 247 were resected (n=240) or ablated (n=7; n=247, 203 immediate vs 44 delayed intervention). Pathologically, 23% (n=56) demonstrated high-grade pathology. Cystic features were explicitly described by pathology in only 18% (n=33) of all lesions and in 7% (n=4) of high-grade lesions. Of the intervention cohort, African American race, male gender, and Bosniak score were associated with high-grade pathology (P < .05). On active surveillance (n=184), Bosniak IV lesions demonstrated faster growth rates than IIF and III lesions (2.7 vs 0.6 and 0.5 mm/y, P ≤ .001); however, growth rates were not associated with high-grade pathology (P = .5). No difference in cancer-specific survival was identified when comparing intervention vs active surveillance at 5 years (99% vs 100%, P = .2). No difference in recurrence was observed between immediate intervention vs delayed intervention (P > .9). CONCLUSIONS: A disconnect between "cystic" designation on imaging and pathology exists for renal lesions. Over 80% of radiographic Bosniak cystic lesions are not described as "cystic" on pathology reports. More than 1 in 5 resected cystic renal lesions demonstrated high-grade disease. Despite this finding, judiciously managed active surveillance ± delayed intervention is a safe and effective management option for most radiographic cystic renal masses.
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Carcinoma de Células Renais , Doenças Renais Císticas , Neoplasias Renais , Humanos , Masculino , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Doenças Renais Císticas/diagnóstico por imagem , Doenças Renais Císticas/cirurgia , Tomografia Computadorizada por Raios X/métodos , Rim/patologia , Carcinoma de Células Renais/patologia , Estudos RetrospectivosRESUMO
While multiple mechanisms have been hypothesized to explain the therapeutic effect of lymph node (LN) yield in patients with urothelial cell carcinoma (UCC) undergoing radical cystectomy (RC), the effect of stage migration, commonly known as the Will Rogers effect, is often discounted. We reviewed the National Cancer Database for patients with UCC undergoing RC with pathologically node-negative (pN0) disease from 2004 to 2016. We tested for an adjusted association between LN yield and overall survival using multivariable Cox proportional-hazard models. Median survival was estimated using the Kaplan-Meier method. We identified 19 939 patients with pN0 UCC treated with RC. After adjustment, patients in the highest quantile for LN yield (≥26 LNs) had a 34% lower risk of death in comparison to patients in the lowest quantile (≤5 LNs). As we increased the threshold for LN yield for dichotomization from >5 to >15 to >25 LNs, median survival increased from 83 to 95 to 103 mo. The pN0 group with higher LN yield appeared to live longer in this analysis owing to the mathematical artifact of how patients are indexed. Resection of a greater number of negative LNs will lead to higher fidelity for pN0 cohorts being evaluated, as the likelihood of contamination by pN+ cases that were missed will be lower. Patient summary: A strategy to dissect a high number of lymph nodes in patients undergoing removal of their bladder for bladder cancer can be associated with side effects, and the benefit in terms of cancer control or survival remains uncertain. Urologists and their patients should engage in shared decision-making and consider the risks and benefits of more extensive lymph node dissection during surgery.
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Carcinoma de Células Renais , Neoplasias Renais , Radiocirurgia , Humanos , Carcinoma de Células Renais/radioterapia , Carcinoma de Células Renais/cirurgia , Sobretratamento , Radiocirurgia/efeitos adversos , Neoplasias Renais/radioterapia , Neoplasias Renais/cirurgia , Neoplasias Renais/patologiaRESUMO
INTRODUCTION: A clear and well-documented gender bias exists in the evaluation of sexual outcomes for women undergoing urologic surgery. Due to the anatomic template of anterior exenteration, women are commonly left with side effects that include sexual dysfunction and the perpetuated effects of surgical menopause. OBJECTIVES: To present evaluation and treatment recommendations for female sexual dysfunction treatment and evaluation, in addition to surgical templates during radical cystectomy (RC). METHODS: This article reviews current literature regarding sexual function and RC with urinary diversion in female bladder cancer patients. Furthermore, this review will provide a review of techniques for organ and neurovascular preservation, along with novel vaginal reconstruction templates. Our review will further focus on emerging technology, including minimally invasive surgery and organ and nerve preservation, directed at preservation of female sexual function. RESULTS: Clinically, studies have demonstrated that females who have undergone genitalia-sparing and neurovascular preservation during RC regained sexual activity earlier than patients undergoing traditional RC. If organ and nerve preservation is not feasible due to involvement of trigone or bladder neck, vaginal reconstruction can mitigate the sexual dysfunction that results from a loss of the anterior vagina during a standard RC. CONCLUSION: Female sexual dysfunction is associated with high levels of patient distress and is best comanaged with a multidisciplinary treatment approach, including preoperative counseling, intraoperative nerve, and organ preservation, and postoperative interventions to mitigate sexual side effects. Davis L, Isali I, Prunty M, et al. Female Sexual Function Following Radical Cystectomy in Bladder Cancer. Sex Med Rev 2022;10:231-239.
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Disfunções Sexuais Fisiológicas , Neoplasias da Bexiga Urinária , Derivação Urinária , Cistectomia/efeitos adversos , Feminino , Humanos , Masculino , Sexismo , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Fisiológicas/cirurgia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/efeitos adversosRESUMO
Importance: Surgeon sex is associated with differential postoperative outcomes, though the mechanism remains unclear. Sex concordance of surgeons and patients may represent a potential mechanism, given prior associations with physician-patient relationships. Objective: To examine the association between surgeon-patient sex discordance and postoperative outcomes. Design, Setting, and Participants: In this population-based, retrospective cohort study, adult patients 18 years and older undergoing one of 21 common elective or emergent surgical procedures in Ontario, Canada, from 2007 to 2019 were analyzed. Data were analyzed from November 2020 to March 2021. Exposures: Surgeon-patient sex concordance (male surgeon with male patient, female surgeon with female patient) or discordance (male surgeon with female patient, female surgeon with male patient), operationalized as a binary (discordant vs concordant) and 4-level categorical variable. Main Outcomes and Measures: Adverse postoperative outcome, defined as death, readmission, or complication within 30-day following surgery. Secondary outcomes assessed each of these metrics individually. Generalized estimating equations with clustering at the level of the surgical procedure were used to account for differences between procedures, and subgroup analyses were performed according to procedure, patient, surgeon, and hospital characteristics. Results: Among 1â¯320â¯108 patients treated by 2937 surgeons, 602â¯560 patients were sex concordant with their surgeon (male surgeon with male patient, 509â¯634; female surgeon with female patient, 92â¯926) while 717â¯548 were sex discordant (male surgeon with female patient, 667â¯279; female surgeon with male patient, 50â¯269). A total of 189â¯390 patients (14.9%) experienced 1 or more adverse postoperative outcomes. Sex discordance between surgeon and patient was associated with a significant increased likelihood of composite adverse postoperative outcomes (adjusted odds ratio [aOR], 1.07; 95% CI, 1.04-1.09), as well as death (aOR, 1.07; 95% CI, 1.02-1.13), and complications (aOR, 1.09; 95% CI, 1.07-1.11) but not readmission (aOR, 1.02; 95% CI, 0.98-1.07). While associations were consistent across most subgroups, patient sex significantly modified this association, with worse outcomes for female patients treated by male surgeons (compared with female patients treated by female surgeons: aOR, 1.15; 95% CI, 1.10-1.20) but not male patients treated by female surgeons (compared with male patients treated by male surgeons: aOR, 0.99; 95% CI, 0.95-1.03) (P for interaction = .004). Conclusions and Relevance: In this study, sex discordance between surgeons and patients negatively affected outcomes following common procedures. Subgroup analyses demonstrate that this is driven by worse outcomes among female patients treated by male surgeons. Further work should seek to understand the underlying mechanism.
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Relações Médico-Paciente , Complicações Pós-Operatórias , Cirurgiões , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Readmissão do Paciente/estatística & dados numéricos , Médicas , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Fatores SexuaisAssuntos
Carcinoma de Células Renais , Neoplasias Renais , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , NefrectomiaRESUMO
INTRODUCTION: Radical cystectomy (RC) is the historic gold standard treatment for muscle-invasive bladder cancer (MIBC), but trimodal therapy (TMT) has emerged as a valid therapeutic option for select patients. Given that prospective clinical trials have been difficult to perform in this area, our aim was to compare these two primary treatment strategies using decision analytic methods. METHOD: A two-dimensional Markov microsimulation model was constructed using TreeAge Pro to compare RC and TMT for patients with newly diagnosed MIBC. A comprehensive literature search was used to populate model probabilities and utilities. Our primary outcome was quality-adjusted life expectancy (QALE). Secondary outcomes included crude life expectancy (LE) and bladder cancer recurrences. The simulated patient for our model was an adult with MIBC (pT2-4 N0 M0) who was a candidate for either RC or TMT. RESULTS: A total of 500 000 patients were simulated. TMT resulted in an estimated mean QALE of 7.48 vs. 7.41 for RC. However, the average LE for patients treated with TMT was lower compared with RC (10.20 vs. 10.74 years). A sensitivity analysis evaluating the impact of age showed that younger patients treated with RC had greater QALE and longer LE than those treated with TMT; inverse findings were observed for elderly patients. Overall, 39.4% of patients treated with TMT experienced a bladder recurrence. CONCLUSIONS: RC results in a longer LE compared to TMT (0.54 years), but with a lower QALE (-0.07 years). The preferred treatment strategy varied with patient age.
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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.
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Oncologia , Neoplasias , Estudos de Coortes , Aprovação de Drogas , Feminino , Humanos , Masculino , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Estudos Observacionais como Assunto , Estados Unidos/epidemiologia , United States Food and Drug AdministrationRESUMO
While focal therapy (FT) is increasingly endorsed for treating localized prostate cancer in the appropriately selected patient, management of recurrences following FT is not well-established in the literature. This case series describes three patients who received high-intensity focal ultrasound (HIFU) for primary treatment followed by focal laser interstitial thermal therapy (FLTT) for salvage therapy treated in the context of an ongoing clinical trial. Evaluation of these reported patients demonstrates that FLTT is feasible in the salvage setting with promising short-term oncologic outcomes and with the potential to preserve functional outcomes. Repeat focal therapy for previous failures is feasible however, it requires sophisticated imaging modalities for the accurate identification of recurrence and treatment of the tumor.