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OBJECTIVES: To compare clinical outcomes with programmed-death ligand-1 immune checkpoint inhibitors (ICIs) in patients with advanced urothelial carcinoma (aUC) who have vs have not undergone radical surgery (RS) or radiation therapy (RT) prior to developing metastatic disease. PATIENTS AND METHODS: We performed a retrospective cohort study collecting clinicopathological, treatment and outcomes data for patients with aUC receiving ICIs across 25 institutions. We compared outcomes (observed response rate [ORR], progression-free survival [PFS], overall survival [OS]) between patients with vs without prior RS, and by type of prior locoregional treatment (RS vs RT vs no locoregional treatment). Patients with de novo advanced disease were excluded. Analysis was stratified by treatment line (first-line and second-line or greater [second-plus line]). Logistic regression was used to compare ORR, while Kaplan-Meier analysis and Cox regression were used for PFS and OS. Multivariable models were adjusted for known prognostic factors. RESULTS: We included 562 patients (first-line: 342 and second-plus line: 220). There was no difference in outcomes based on prior locoregional treatment among those treated with first-line ICIs. In the second-plus-line setting, prior RS was associated with higher ORR (adjusted odds ratio 2.61, 95% confidence interval [CI]1.19-5.74]), longer OS (adjusted hazard ratio [aHR] 0.61, 95% CI 0.42-0.88) and PFS (aHR 0.63, 95% CI 0.45-0.89) vs no prior RS. This association remained significant when type of prior locoregional treatment (RS and RT) was modelled separately. CONCLUSION: Prior RS before developing advanced disease was associated with better outcomes in patients with aUC treated with ICIs in the second-plus-line but not in the first-line setting. While further validation is needed, our findings could have implications for prognostic estimates in clinical discussions and benchmarking for clinical trials. Limitations include the study's retrospective nature, lack of randomization, and possible selection and confounding biases.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Inibidores de Checkpoint Imunológico , Estudos Retrospectivos , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológicoRESUMO
PURPOSE: NonHispanic Black (NHB) and Hispanic/Afro-Caribbean men have the highest risk of prostate cancer (PCa) compared to nonHispanic White (NHW) men. However, ethnicity-specific outcomes of targeted fusion biopsy (FB) for the detection of PCa are poorly characterized. We compared the outcomes of FB by Prostate Imaging Reporting and Data System (PI-RADS®) score and race/ethnicity among a diverse population. MATERIALS AND METHODS: We evaluated all men who underwent image-guided FB for suspicious lesions on prostate magnetic resonance imaging (≥PI-RADS 3) over a 2-year period. We examined associations of race/ethnicity and PI-RADS score with risk of PCa or clinically significant PCa (cs-PCa, Gleason Group ≥2) on FB using mixed-effects logistic regression models. RESULTS: A total of 410 men with 658 lesions were analyzed, with 201 (49.0%) identified as NHB and 125 (30.5%) identified as Hispanic. NHB men had a twofold increase in the odds of detecting cs-PCa (OR=2.7, p=0.045), while Hispanic men had similar odds of detecting cs-PCa compared to NHW men. With regard to all PCa, NHB men had a similar increase in the odds of detecting all PCa (OR=2.4, p=0.050), which was borderline statistically significant compared to NHW men on FB. When we excluded men on active surveillance, NHB men had even stronger associations with detection of cs-PCa (OR=3.10, p=0.047) or all PCa (OR=2.77, p=0.032) compared to NHW men. CONCLUSIONS: NHB men have higher odds for overall PCa and cs-PCa on FB compared to NHW men. Further work may clarify differences per PI-RADS score. Clinicians should interpret prostate magnetic resonance imaging lesions with more caution in NHB men.
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Imagem por Ressonância Magnética Intervencionista/estatística & dados numéricos , Próstata/patologia , Neoplasias da Próstata/epidemiologia , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Hispânico ou Latino/estatística & dados numéricos , Humanos , Biópsia Guiada por Imagem/métodos , Biópsia Guiada por Imagem/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , População Branca/estatística & dados numéricosRESUMO
OBJECTIVES: To compare clinical outcomes between patients with locally advanced (unresectable) or metastatic urothelial carcinoma (aUC) in the upper and lower urinary tract receiving immune checkpoint inhibitors (ICIs). PATIENTS AND METHODS: We performed a retrospective cohort study collecting clinicopathological, treatment, and outcome data for patients with aUC receiving ICIs from 2013 to 2020 across 24 institutions. We compared the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) between patients with upper and lower tract UC (UTUC, LTUC). Uni- and multivariable logistic and Cox regression were used to assess the effect of UTUC on ORR, OS, and PFS. Subgroup analyses were performed stratified based on histology (pure, mixed) and line of treatment (first line, subsequent line). RESULTS: Out of a total of 746 eligible patients, 707, 717, and 738 were included in the ORR, OS, and PFS analyses, respectively. Our results did not contradict the hypothesis that patients with UTUC and LTUC had similar ORRs (24% vs 28%; adjusted odds ratio [aOR] 0.73, 95% confidence interval [CI] 0.43-1.24), OS (median 9.8 vs 9.6 months; adjusted hazard ratio [aHR] 0.93, 95% CI 0.73-1.19), and PFS (median 4.3 vs 4.1 months; aHR 1.01, 95% CI 0.81-1.27). Patients with mixed-histology UTUC had a significantly lower ORR and shorter PFS vs mixed-histology LTUC (aOR 0.20, 95% CI 0.05-0.91 and aHR 1.66, 95% CI 1.06-2.59), respectively). CONCLUSION: Overall, patients with UTUC and LTUC receiving ICIs have comparable treatment response and outcomes. Subgroup analyses based on histology showed that those with mixed-histology UTUC had a lower ORR and shorter PFS compared to mixed-histology LTUC. Further studies and evaluation of molecular biomarkers can help refine patient selection for immunotherapy.
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Carcinoma de Células de Transição/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Urológicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/patologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Urológicas/patologiaRESUMO
BACKGROUND: Immune checkpoint inhibitors (ICIs) represent an appealing treatment for patients with advanced urothelial cancer (aUC) and a poor performance status (PS). However, the benefit of ICIs for patients with a poor PS remains unknown. It was hypothesized that a poor Eastern Cooperative Oncology Group (ECOG) PS (≥2 vs 0-1) would correlate with shorter overall survival (OS) in patients receiving ICIs. METHODS: In this retrospective cohort study, clinicopathologic, treatment, and outcome data were collected for patients with aUC who were treated with ICIs at 18 institutions (2013-2019). The overall response rate (ORR) and OS were compared for patients with an ECOG PS of 0 to 1 and patients with an ECOG PS ≥ 2 at ICI initiation. The association between a new ICI in the last 30 and 90 days of life (DOL) and death location was also tested. RESULTS: Of the 519 patients treated with ICIs, 395 and 384 were included in OS and ORR analyses, respectively, with 26% and 24% having a PS ≥ 2. OS was higher in those with a PS of 0 to 1 than those with a PS ≥ 2 who were treated in the first line (median, 15.2 vs 7.2 months; hazard ratio [HR], 0.62; P = .01) but not in subsequent lines (median, 9.8 vs 8.2 months; HR, 0.78; P = .27). ORRs were similar for patients with a PS of 0 to 1 and patients with a PS ≥ 2 in both lines. Of the 288 patients who died, 10% and 32% started ICIs in the last 30 and 90 DOL, respectively. ICI initiation in the last 30 DOL was associated with increased odds of death in a hospital (odds ratio, 2.89; P = .04). CONCLUSIONS: Despite comparable ORRs, ICIs may not overcome the negative prognostic role of a poor PS, particularly in the first-line setting, and the initiation of ICIs in the last 30 DOL was associated with hospital death location.
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Antígeno B7-H1/antagonistas & inibidores , Imunoterapia/métodos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Índice de Gravidade de Doença , Neoplasias Urológicas/tratamento farmacológico , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologiaRESUMO
PURPOSE: Urinary tract cancer can be pure urothelial carcinoma, pure nonurothelial carcinoma or variant urothelial carcinoma (defined here as mixed urothelial carcinoma). Little is known regarding outcomes for patients with variant urothelial carcinoma receiving immune checkpoint inhibitors. We hypothesized that variant urothelial carcinoma does not compromise immune checkpoint inhibitor efficacy in patients with advanced urothelial carcinoma. MATERIALS AND METHODS: We performed a retrospective cohort study across 18 institutions. Demographic, clinicopathological, treatment and outcomes data were collected for patients with advanced urothelial carcinoma who received immune checkpoint inhibitors. Patients were divided into pure vs variant urothelial carcinoma subgroups, with variant urothelial carcinoma further divided by type of variant (ie squamous, neuroendocrine etc). We compared overall response rate using univariate and multivariate logistic regression and progression-free survival and overall survival using Kaplan-Meier and univariate and multivariate Cox proportional hazards. RESULTS: Overall 519 patients were identified, with 395, 406 and 403 included in overall response rate, overall survival and progression-free survival analyses, respectively. Overall response rate to immune checkpoint inhibitors between patients with pure vs variant urothelial carcinoma was comparable (28% vs 29%, p=0.90) without significant differences for individual subtypes vs pure urothelial carcinoma. Median overall survival for patients with pure urothelial carcinoma was 11.0 months vs 10.1 months for variant urothelial carcinoma (p=0.60), but only 4.6 months for patients with neuroendocrine features (9 patients, HR 2.75, 95% CI 1.40-5.40 vs pure urothelial carcinoma, p=0.003). Median progression-free survival was 4.1 months for pure vs 5.2 months for variant urothelial carcinoma (p=0.43) and 3.7 months for neuroendocrine features (HR 1.87, 95% CI 0.92-3.79 vs pure urothelial carcinoma, p=0.09). CONCLUSIONS: Overall response rate to immune checkpoint inhibitors was comparable across histological types. However, overall survival was worse for patients with tumors containing neuroendocrine features. Variant urothelial carcinoma should not exclude patients from receiving immune checkpoint inhibitors.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma/patologia , Carcinoma/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Urológicas/patologia , Neoplasias Urológicas/terapia , Idoso , Carcinoma/mortalidade , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias Urológicas/mortalidadeRESUMO
OBJECTIVE: To investigate the cadence of recurrence in patients with low grade intermediate-risk non-muscle invasive bladder cancer (LG IR-NMIBC) based on clinical determinants. We aim to describe patterns in rates of recurrence to better inform surveillance regimens for this chronic, burdensome, and costly disease. METHODS: Using baseline and follow-up data from participants in the West Midlands' (United Kingdom, UK) Bladder Cancer Prognosis Programme (BCPP), we assessed overall recurrence rate and recurrence-free intervals throughout the follow-up period for IR-NMIBC participants. Recurrence-free intervals were calculated using the Kaplan-Meier method. RESULTS: We identified 379 patients with G1/G2 pTa tumors classified as intermediate risk. Median age was 70 and 284/379 (75%) were male. The median follow-up time was 4.2 years (95% CI: 3.9-4.8). After 5 years of follow-up, 53% of patients had at least one recurrence. One-year recurrence-free survival (RFS) was 75% and 4-year RFS was 50%. The median time to or between 1st, 2nd, 3rd, 4th, and 5th sequential recurrences was 49, 19, 12, 14, and 10 months, respectively. CONCLUSION: Over half of patients with IR-NMIBC are destined to recur. Our data suggest that a subset of patients experience acceleration of recurrence over time and that this acceleration may serve as a potential kinetic biomarker for these individuals that could inform surveillance intervals and future treatment strategies.
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OBJECTIVE: To investigate the impact of a holistic review of urology residency applications on interview selection at our institution during the COVID-19 pandemic. METHODS: In the 2019-2020 cycle, applicants were filtered by a Step 1 score of 230 and whether they applied from selected east coast medical schools. For the 2020-2021 and 2021-2022 cycles, we implemented a scoring system which focused on desirable attributes based on our program training needs and resources. We compared applicant and interviewee demographics and United States Medical Licensing Examination (USMLE) scores using descriptive statistics and 1-way analysis of variance tests. RESULTS: A total of 282, 300, and 367 students applied to our residency program with 50, 45, and 52 selected for interviews during the 2019-2020, 2020-2021, and 2021-2022 cycles, respectively. Compared to 2019-2020, the 2020-2021 and 2021-2022 interviewee cohorts comprised of more non-tri-state applicants (36%, 55.6%, and 46.2%, respectively). Underrepresented minority representation increased for the 2020-2021 interviewee cohort; however, this was not observed in 2021-2022 (16%, 24.4%, 15.4%, respectively). Additionally, USMLE Step 1 and 2 scores were similar between interviewee cohorts in 2019-2020, 2020-2021 and 2021-2022, respectively (Step 1: 244.2 ± 8.8, 242 ± 12.1, 242.8 ± 12.4, Pâ¯=â¯.624) (Step 2: 249.1 ± 11.5, 251.5 ± 10.5, 254.4 ± 10.8, Pâ¯=â¯.143). CONCLUSION: Utilizing a comprehensive review resulted in a geographically diverse interview pool and no significant difference in academic performance among interviewees. Holistic review provides an alternative, balanced evaluation of residency applicants which may increase diversity in urology.
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COVID-19 , Internato e Residência , Urologia , Humanos , Estados Unidos , Pandemias , COVID-19/epidemiologia , Critérios de Admissão EscolarRESUMO
BACKGROUND: A lack of standardization is pervasive in procedural application and reporting templates for TURBT with the use of a surgical checklist proposed as a means for quality improvement. OBJECTIVE: To introduce a TURBT checklist to assess surgeon prediction accuracy and the impact of standardized documentation on quality of resection and oncologic outcomes. METHODS: Nine critical elements of a high-quality TURBT identified by literature review were incorporated into a prospectively implemented checklist for operative reports. The checklist included both visualized and predicted tumor characteristics. A retrospective single-institution analysis compared quality of dictation pre- and post-checklist implementation. Surgeon predictions were compared to final pathology reports to determine rates of concordance. Kaplan-Meier curves examined the association of checklist use with recurrence free survival (RFS). RESULTS: 333 operative reports were included in this analysis, of which 107 (32.1%) were completed pre-checklist implementation. The average number of critical elements reported was 8.69 with checklist use compared to 4.99 without (pâ<â0.001). There was no significant difference in RFS between the pre- and post-checklist cohorts (log-rank test pâ=â0.53). Surgeons were least and most accurate in predicting low grade tumor (43.5%) and absence of muscle invasion (96.6%), respectively. CONCLUSIONS: Incorporation of a TURBT surgical checklist improves operative dictation and quality of reporting but did not directly impact RFS. With quality of initial resection a proven correlate to recurrence rates, checklist implementation to improve surgical performance and long-term oncologic outcomes reveals an interesting area of exploration highlighting the need for more standardized methodology when performing these procedures.
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INTRODUCTION: Active surveillance (AS) is the standard for very low- and low-risk prostate cancer. Although risk factors for pathologic reclassification while on AS have been identified, results are mixed for non-Hispanic Black (NHB) and Hispanic ethnicity. We aim to further explore how race and ethnicity may be affecting AS participation and outcomes in a primarily urban, diverse, and vulnerable population. MATERIALS AND METHODS: Patients eligible for AS from 2005-2020 were reviewed. Demographics, race/ethnicity, prostate specific antigen (PSA), prostate volume, and pathologic characteristics were analyzed between patients enrolled in AS and those that underwent immediate therapy. Kaplan-Meier survival analysis was used to compare biochemical recurrence (BCR) rates. Cox proportional hazards models were used to develop prediction models for clinical reclassification. RESULTS: A total of 471 men were eligible for AS. Of those, 188 (39.9%) enrolled in AS while 283 (60.1%) underwent immediate radical therapy. No significant differences were found in racial/ethnic composition between the AS and immediate treatment groups. In our AS cohort, 79 (42.0%) experienced clinical reclassification and underwent deferred treatment. BCR rates were similar between treatment groups. Race/ethnicity were not found to be predictors of clinical reclassification, while metrics at diagnostic biopsy such as elevated PSA, higher PSA density, and lower prostate volume increased reclassification odds. CONCLUSIONS: In our diverse population, NHB race and Hispanic ethnicity were not significant predictors of adverse reclassification while on AS. Our findings support utilizing other metrics taken at initial biopsy to identify high-risk patients such as PSA, prostate volume, and PSA density.
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Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Etnicidade , Conduta Expectante/métodos , Gradação de Tumores , Neoplasias da Próstata/patologia , Fatores de RiscoRESUMO
INTRODUCTION: The use of urine cytology in the surveillance of non-muscle invasive bladder cancer (NMIBC) is widely variable in clinical practice. We studied the impact of surveillance urine cytology on clinical decision making during NMIBC surveillance. METHODS: A retrospective chart review was conducted on patients surveilled for clinical NMIBC from 2013 to 2020 with at least one follow-up cytology result after diagnosis. Patients were classified into risk categories according to American Urological Association (AUA) NMIBC guidelines. Data were obtained regarding tumor recurrence pathology and the frequency and findings of surveillance cystoscopies and urine cytologies. Positive (suspicious, malignant) and negative (atypical or negative for malignant cells) cytology results were correlated with cystoscopy and pathology findings when obtained within 3 months of the cytology specimen to determine if cytology impacted plan of care. RESULTS: Two hundred fourteen patients with NMIBC were followed for a median of 34 months, with 1045 urine cytologies collectively obtained over the surveillance period. There were no positive urine cytologies among patients with low-risk NMIBC; therefore, cytology did not change management in this cohort. The potential for cytology to escalate management for patients of any risk group (ie, positive cytology in the absence of positive cystoscopy or pathology findings) occurred in 30 (2.9%) cases. However, clinical decision making was only altered in 4 cases (0.4% of all cytologies). CONCLUSIONS: Less than 1% of urine cytology specimens collected during NMIBC surveillance impacted clinical management, none of whom had low-risk disease. The use of urine cytology for surveillance of low-risk NMIBC should continue to be strongly discouraged, as it did not change management in any such cases.
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Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Humanos , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/patologia , Citodiagnóstico , Cistoscopia/métodos , Invasividade Neoplásica/patologiaRESUMO
BACKGROUND: Bacille Calmette-Guérin (BCG) is the standard therapy after transurethral resection of bladder tumour for high-risk non-muscle-invasive bladder cancer (NMIBC). However, post-BCG recurrence/progression occurs frequently, and noncystectomy options are limited. OBJECTIVE: To evaluate the safety and clinical activity of atezolizumab ± BCG in high-risk BCG-unresponsive NMIBC. DESIGN, SETTING, AND PARTICIPANTS: This phase 1b/2 GU-123 study (NCT02792192) treated patients with BCG-unresponsive NMIBC who had carcinoma in situ with atezolizumab ± BCG. INTERVENTION: Patients in cohorts 1A and 1B received atezolizumab 1200 mg IV q3w for ≤96 wk. Those in cohort 1B also received standard BCG induction (six weekly doses) and maintenance courses (three doses weekly starting at month 3) with optional maintenance at 6, 12, 18, 24, and 30 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Coprimary endpoints were safety and 6-mo complete response (CR) rate. Secondary endpoints included 3-mo CR rate and duration of CR; 95% confidence intervals were calculated using the Clopper-Pearson method. RESULTS AND LIMITATIONS: At data cut-off (September 29, 2020), 24 patients were enrolled (cohort 1A, n = 12; cohort 1B, n = 12), and the recommended BCG dose was 50 mg in cohort 1B. Four patients (33%) had adverse events (AEs) leading to BCG dose modification/interruption. Three patients (25%) in cohort 1A reported atezolizumab-related grade 3 AEs; cohort 1B had no atezolizumab- or BCG-related grade ≥3 AEs. No grade 4/5 AEs were reported. The 6-mo CR rate was 33% in cohort 1A (median duration of CR, 6.8 mo) and 42% in cohort 1B (median duration of CR, not reached [≥12 mo]). These results are limited by the small sample size of GU-123. CONCLUSIONS: In this first report of the atezolizumab-BCG combination in NMIBC, atezolizumab ± BCG was well tolerated, with no new safety signals or treatment-related deaths. Preliminary results suggested clinically meaningful activity; the combination favoured a longer duration of response. PATIENT SUMMARY: We studied atezolizumab with and without bacille Calmette-Guérin (BCG) to determine whether this combination was safe and had clinical activity in patients with high-risk noninvasive bladder cancer (high-grade bladder tumours that affect the outermost lining of the bladder wall) that has previously been treated with BCG and is still present or occurred again. Our results suggest that atezolizumab with or without BCG was generally safe and could be used to treat patients unresponsive to BCG.
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Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Humanos , Vacina BCG/uso terapêutico , Neoplasias da Bexiga Urinária/patologia , Administração IntravesicalRESUMO
INTRODUCTION: Small renal masses (SRMs) are often incidentally diagnosed, and a large proportion are malignant. However, there is a paucity of data describing predictors of malignancy in minority patients with SRMs. Thus, our goal was to examine clinical risk factors associated with SRM malignant histology in patients undergoing partial nephrectomy (PN) a diverse, urban academic center. MATERIALS AND METHODS: Patients with a SRM undergoing PN at a single institution between 2010 to 2018 were reviewed. Demographic, clinical, and imaging characteristics were compared to pathology results. Logistic regression was used to examine associations between demographic/clinical variables for malignant and high-grade histology. RESULTS: In total, 331 patients who underwent PN for SRM were included. Of those, 264 (79.8%) had malignant histology while 67 (20.2%) had benign histology. The proportions of men and of current smokers were significantly higher among patients with malignant histology. In multivariate models, non-Hispanic Black (NHB) patients had increased odds of having malignant histology (OR 2.46, 95% CI: 1.01-5.99, P = .048) and current smokers (OR = 4.02; 95% CI 1.14-14.18, P = .031). Hispanic patients had a 3-fold increased risk of high-grade RCC (OR 3.06, 95% CI: 1.19-7.87, P = 0.02) compared to Non-Hispanic White patients. CONCLUSION: In our population, male sex, smoking, and NHB race/ethnicity was associated with an increased risk of malignancy in patients undergoing partial nephrectomy for SRM. Older age and Hispanic race/ethnicity were associated with high grade RCC. Our results suggest that urologists should exercise a higher level of vigilance in managing and treating SRM among NHB and Hispanic patients.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Masculino , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Etnicidade , Nefrectomia/métodos , Fatores de RiscoRESUMO
BACKGROUND: Immune checkpoint inhibitors (ICI) improve overall survival (OS) in patients with locally advanced, unresectable, or metastatic urothelial carcinoma (aUC), but response rates can be modest. We compared outcomes between patients with and without prior intravesical Bacillus Calmette-Guerin (BCG), who received ICI for aUC, hypothesizing that prior intravesical BCG would be associated with worse outcomes. PATIENTS AND METHODS: We performed a retrospective cohort study across 25 institutions in US and Europe. We compared observed response rate (ORR) using logistic regression; progression-free survival (PFS) and OS using Kaplan-Meier and Cox proportional hazards. Analyses were stratified by treatment line (first line/salvage) and included multivariable models adjusting for known prognostic factors. RESULTS: A total of 1026 patients with aUC were identified; 614, 617, and 638 were included in ORR, OS, PFS analyses, respectively. Overall, 150 pts had history of prior intravesical BCG treatment. ORR to ICI was similar between those with and without prior intravesical BCG exposure in both first line and salvage settings (adjusted odds radios 0.55 [P= .08] and 1.65 [P= .12]). OS (adjusted hazard ratios 1.05 [P= .79] and 1.13 [P= .49]) and PFS (adjusted hazard ratios 1.12 [P= .55] and 0.87 [P= .39]) were similar between those with and without intravesical BCG exposure in first line and salvage settings. CONCLUSION: Prior intravesical BCG was not associated with differences in response and survival in patients with aUC treated with ICI. Limitations include retrospective nature, lack of randomization, presence of selection and confounding biases. This study provides important preliminary data that prior intravesical BCG exposure may not impact ICI efficacy in aUC.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Adjuvantes Imunológicos , Administração Intravesical , Vacina BCG/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/patologiaRESUMO
BACKGROUND: Early progression on first-line (1L) platinum-based therapy or between therapy lines may be a surrogate of more aggressive disease and poor outcomes in advanced urothelial carcinoma (aUC), but its prognostic role regarding immune checkpoint inhibitor (ICI) response and survival is unclear. We hypothesized that shorter time until start of second-line (2L) ICI would be associated with worse outcomes in aUC. PATIENTS AND METHODS: We performed a retrospective multi-institution cohort study in patients with aUC treated with 1L platinum-based chemotherapy, who received 2L ICI. Patients receiving switch maintenance ICI were excluded. We defined time to 2L ICI therapy as the time between the start of 1L platinum-based chemotherapy to the start of 2L ICI and categorized patients a priori into 1 of 3 groups: less than 3 months versus 3-6 months versus more than 6 months. We calculated overall response rate (ORR) with 2L ICI, progression-free survival (PFS) and overall survival (OS) from the start of 2L ICI. ORR was compared among the 3 groups using multivariable logistic regression, and PFS, OS using cox regression. Multivariable models were adjusted for known prognostic factors. RESULTS: We included 215, 215, and 219 patients in the ORR, PFS, and OS analyses, respectively, after exclusions. ORR difference did not reach statistical significance between patients with less than 3 months versus 3-6 months versus more than 6 months to 2L ICI. However, PFS (HR 1.64; 95% CI 1.02-2.63) and OS (HR 1.77; 95% CI 1.10-2.84) was shorter among those with time to 2L ICI less than 3 months compared to those who initiated 2L ICI more than 6 months. CONCLUSION: Among patients with aUC treated with 2L ICI, time to 2L ICI less than 3 months was associated with lower, but not significantly different ORR, but shorter PFS and OS compared to 2L ICI more than 6 months. This highlights potential cross resistance mechanisms between ICI and platinum-based chemotherapy.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Estudos Retrospectivos , Estudos de Coortes , Resultado do TratamentoRESUMO
BACKGROUND: Sites of metastasis have prognostic significance in advanced urothelial carcinoma (aUC), but more information is needed regarding outcomes based on metastatic sites in patients treated with immune checkpoint inhibitors (ICI). We hypothesized that presence of liver/bone metastases would be associated with worse outcomes with ICI. METHODS: We identified a retrospective cohort of patients with aUC across 26 institutions, collecting demographics, clinicopathological, treatment, and outcomes information. Outcomes were compared with logistic (observed response rate; ORR) and Cox (progression-free survival; PFS, overall survival; OS) regression between patients with/without metastasis beyond lymph nodes (LN) and those with/without bone/liver/lung metastasis. Analysis was stratified by 1st or 2nd+ line. RESULTS: We identified 917 ICI-treated patients: in the 1st line, bone/liver metastases were associated with shorter PFS (Hazard ratio; HR: 1.65 and 2.54), OS (HR: 1.60 and 2.35, respectively) and lower ORR (OR: 0.48 and 0.31). In the 2nd+ line, bone/liver metastases were associated with shorter PFS (HR: 1.71 and 1.62), OS (HR: 1.76 and 1.56) and, for bone-only metastases, lower ORR (OR: 0.29). In the 1st line, LN-confined metastasis was associated with longer PFS (HR: 0.53), OS (HR:0.49) and higher ORR (OR: 2.97). In the 2nd+ line, LN-confined metastasis was associated with longer PFS (HR: 0.47), OS (HR: 0.54), and higher ORR (OR: 2.79); all associations were significant. CONCLUSION: Bone and/or liver metastases were associated with worse, while LN-confined metastases were associated with better outcomes in patients with aUC receiving ICI. These findings in a large population treated outside clinical trials corroborate data from trial subset analyses.
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Carcinoma de Células de Transição , Neoplasias Hepáticas , Neoplasias da Bexiga Urinária , Carcinoma de Células de Transição/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/tratamento farmacológicoRESUMO
BACKGROUND: The immune system plays an important role in the pathogenesis of Alzheimer disease (AD), but it remains unclear whether bacillus Calmette-Guérin (BCG) may affect the risk of AD or not. METHODS: Using retrospective chart review, we collected data regarding demographics, comorbidities, cancer diagnosis, BCG treatment, and subsequent diagnosis of AD or other dementia in a racially/ethnically diverse cohort of patients with non-muscle-invasive bladder cancer (NIMBC) receiving treatment between 1984 and 2020 in the Bronx, New York. We used Cox proportional hazard models to examine association between BCG treatment and risk of incident AD or other dementia, adjusting for age, gender, race/ethnicity, and major comorbidities. RESULTS: In our cohort of 1290 patients with NMIBC, a total of 99 (7.7%) patients developed AD or other dementia during follow-up. Patients who received BCG treatment (25%) had a 60% lowered incidence of AD or other dementia (adjusted hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.21-0.80) in comparison to those who did not receive BCG. There was also suggestive evidence that the reduction in risk of AD or other dementia associated with BCG treatment was stronger in men (adjusted HR, 0.34; 95% CI, 0.15-0.81) but not in women (adjusted HR, 0.75; 95% CI 0.25-2.24). When we stratified the patients who received BCG by type of treatments, patients who received both induction and maintenance rounds of BCG had a further lowered incidence of AD or other dementia (HR, 0.23; 95% CI, 0.06-0.96) than patients who did not receive BCG. CONCLUSIONS: To our knowledge, our study is one of the first to suggest that BCG treatment is associated with a reduced risk of developing AD or other dementia in a multiethnic population, independent of significant comorbidities. Larger cohort studies are needed to corroborate our findings.
Assuntos
Doença de Alzheimer , Neoplasias da Bexiga Urinária , Adjuvantes Imunológicos , Administração Intravesical , Doença de Alzheimer/epidemiologia , Vacina BCG/uso terapêutico , Feminino , Humanos , Masculino , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/epidemiologiaRESUMO
BACKGROUND: While immune checkpoint inhibitors (ICIs) are approved in the first-line (1L) setting for cisplatin-unfit patients with programmed death-ligand 1 (PD-L1)-high tumors or for platinum (cisplatin/carboplatin)-unfit patients, response rates remain modest and outcomes vary with no clinically useful biomarkers (except for PD-L1). OBJECTIVE: We aimed to develop a prognostic model for overall survival (OS) in patients receiving 1L ICIs for advanced urothelial cancer (aUC) in a multicenter cohort study. DESIGN, SETTING, AND PARTICIPANTS: Patients treated with 1L ICIs for aUC across 24 institutions and five countries (in the USA and Europe) outside clinical trials were included in this study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used a stepwise, hypothesis-driven approach using clinician-selected covariates to develop a new risk score for patients receiving ICIs in the 1L setting. Demographics, clinicopathologic data, treatment patterns, and OS were collected uniformly. Univariate Cox regression was performed on 18 covariates hypothesized to be associated with OS based on published data. Variables were retained for multivariate analysis (MVA) if they correlated with OS (p < 0.2) and were included in the final model if p < 0.05 on MVA. Retained covariates were assigned points based on the beta coefficient to create a risk score. Stratified median OS and C-statistic were calculated. RESULTS AND LIMITATIONS: Among 984 patients, 357 with a mean age of 71 yr were included in the analysis, 27% were female, 68% had pure UC, and 13% had upper tract UC. Eastern Cooperative Oncology Group performance status ≥2, albumin <3.5 g/dl, neutrophil:lymphocyte ratio >5, and liver metastases were significant prognostic factors on MVA and were included in the risk score. C index for new 1L risk score was 0.68 (95% confidence interval 0.65-0.71). Limitations include retrospective nature and lack of external validation. CONCLUSIONS: We developed a new 1L ICI risk score for OS based on data from patients with aUC treated with ICIs in the USA and Europe outside of clinical trials. The score components highlight readily available factors related to tumor biology and treatment response. External validation is being pursued. PATIENT SUMMARY: With multiple new treatments under development and approved for advanced urothelial carcinoma, it can be difficult to identify the best treatment sequence for each patient. The risk score may help inform treatment discussions and estimate outcomes in patients treated with first-line immune checkpoint inhibitors, while it can also impact clinical trial design and endpoints. TAKE HOME MESSAGE: A new risk score was developed for advanced urothelial carcinoma treated with first-line immune checkpoint inhibitors. The score assigned Eastern Cooperative Oncology Group performance status ≥2, albumin <3.5 g/dl, neutrophil:lymphocyte ratio >5, and liver metastases each one point, with a higher score being associated with worse overall survival.
Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Idoso , Carcinoma de Células de Transição/tratamento farmacológico , Estudos de Coortes , Feminino , Humanos , Inibidores de Checkpoint Imunológico , Prognóstico , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/tratamento farmacológicoRESUMO
OBJECTIVE: To perform a systematic review and meta-analysis comparing overall prostate cancer detection rate and clinically-significant prostate cancer detection rate between MRI-ultrasound image guided fusion biopsy (MRI-US FB) and cognitive biopsy (CB). METHODS: A systematic review of Pubmed, EMBASE, MEDLINE, and Cochrane library databases was performed. Identified studies were assessed for clinical relevance and excluded based on a set of predefined criteria. Final articles included in the analysis comprised only prospective trials that compared CB vs. MRI-US FB in men with MRI-identifiable lesions (Prostate Imaging Reporting and Data System score 2+). Articles were reviewed for patient demographics, MRI protocol, and rates of overall and clinically significant prostate cancer detection by both modalities. RESULTS: Nine studies were analyzed. A composite 1,714 men with mean age 64.6 years and mean PSA 8.2 ng/dL were reviewed. When comparing FB to CB, the odds ratio for overall and for clinically significant prostate cancer detection was 1.11 (95%CI 0.91-1.36, Pâ¯=â¯0.30) and 1.13 (95%CI 0.89-1.44, Pâ¯=â¯0.32), respectively. Heterogeneity among the studies was moderate but not significant for either overall (X2â¯=â¯14.67; I2â¯=â¯45%; Pâ¯=â¯0.07) or clinically significant prostate cancer detection (X2â¯=â¯11.81; I2â¯=â¯49%; Pâ¯=â¯0.07). CONCLUSION: MRI-US FB demonstrates a trend toward improved rates of prostate cancer detection compared to CB, although this is not statistically significant. Further comparative studies may help to further elucidate whether one of these modalities is superior over the other.
Assuntos
Próstata/patologia , Neoplasias da Próstata/patologia , Humanos , Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética , Masculino , Ultrassonografia de IntervençãoRESUMO
PURPOSE: To report our experience with sequential maintenance intravesical gemcitabine/docetaxel (GEM/DOCE) for patients with nonmuscle-invasive bladder cancer. MATERIALS AND METHODS: Fifty-nine patients who received full GEM/DOCE for nonmuscle-invasive bladder cancer between 2013 and 2018, per the protocol adapted from University of Iowa, were identified and characterized. Patients were treated with 6 weekly instillations of GEM/DOCE and subsequent monthly maintenance installations for those with no evidence of disease at the first surveillance. Student's t test and χ2 test were used to compare continuous and categorical variables as appropriate. For survival analyses, Kaplan-Meier (KM) curves were created to assess disease-free survival (DFS). Overall comparisons of KM survival analysis were conducted using the Wilcoxon test. RESULTS: Among all patients, median follow-up was 24 months. Sixty-six percent of patients received ≥2 intravesical induction therapies prior to receiving GEM/DOCE. Thirty-one patients (63%) failed ≥2 induction courses of Bacillus Calmette-Guérin (BCG) before receiving GEM/DOCE. Overall DFS was 49% at 1 year and 29% at 2 years. For patients who failed ≥1 induction courses of BCG, overall DFS was 48% at 1 year and 32% at 2 years. GEM/DOCE appears to be effective for therapy naïve and patients who have failed previous intravesical therapies (Pâ¯=â¯0.39). There were 41 (69.5%) patients who had no evidence of disease at the first surveillance and were eligible for maintenance therapy. Among these patients, 24 were managed with observation alone and 17 with monthly maintenance. Median follow-up for observed patients was 36 months and 26 months for patients with maintenance. DFS at 1 year was 42% for observed patients and 81% for patients receiving maintenance (Pâ¯=â¯0.04). DFS at 2 years was 32% for observed patients and 59% for patients receiving maintenance therapy (Pâ¯=â¯0.45). For maintenance eligible patients who received ≥1 induction courses of BCG, DFS was 42% for observed patients and 81% for patients receiving maintenance therapy at 1 year and 34% for observed patients and 59% for patients receiving maintenance therapy at 2 years. Pathologic stage at recurrence was similar between observed patients and those receiving maintenance (Pâ¯=â¯0.83). KM analyses showed greater DFS for patients receiving maintenance therapy compared to observed patients (Pâ¯=â¯0.04). CONCLUSION: Patients who demonstrate initial complete response to GEM/DOCE may benefit from maintenance GEM/DOCE.