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1.
Int J Cancer ; 154(7): 1309-1323, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38009868

RESUMO

Renal cell carcinoma (RCC) represents 2% of all diagnosed malignancies worldwide, with disease recurrence affecting 20% to 40% of patients. Existing prognostic recurrence models based on clinicopathological features continue to be a subject of controversy. In this meta-analysis, we summarized research findings that explored the correlation between clinicopathological characteristics and post-surgery survival outcomes in non-metastatic RCC patients. Our analysis incorporates 99 publications spanning 140 568 patients. The study's main findings indicate that the following clinicopathological characteristics were associated with unfavorable survival outcomes: T stage, tumor grade, tumor size, lymph node involvement, tumor necrosis, sarcomatoid features, positive surgical margins (PSM), lymphovascular invasion (LVI), early recurrence, constitutional symptoms, poor performance status (PS), low hemoglobin level, high body-mass index (BMI), diabetes mellitus (DM) and hypertension. All of which emerged as predictors for poor recurrence-free survival (RFS) and cancer-specific survival. Clear cell (CC) subtype, urinary collecting system invasion (UCSI), capsular penetration, perinephric fat invasion, renal vein invasion (RVI) and increased C-reactive protein (CRP) were all associated with poor RFS. In contrast, age, sex, tumor laterality, nephrectomy type and approach had no impact on survival outcomes. As part of an additional analysis, we attempted to assess the association between these characteristics and late recurrences (relapses occurring more than 5 years after surgery). Nevertheless, we did not find any prediction capabilities for late disease recurrences among any of the features examined. Our findings highlight the prognostic significance of various clinicopathological characteristics potentially aiding in the identification of high-risk RCC patients and enhancing the development of more precise prediction models.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Rim/patologia , Prognóstico , Nefrectomia , Estudos Retrospectivos , Estadiamento de Neoplasias
2.
Int J Cancer ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958288

RESUMO

The overall survival (OS) improvement after the advent of several novel systemic therapies, designed for treatment of metastatic urothelial carcinoma of the urinary bladder (mUCUB), is not conclusively studied in either contemporary UCUB patients and/or non-UCUB patients. Within the Surveillance, Epidemiology, and End Results database, contemporary (2017-2020) and historical (2000-2016) systemic therapy-exposed metastatic UCUB and, subsequently, non-UCUB patients were identified. Separate Kaplan-Meier and multivariable Cox regression (CRM) analyses first addressed OS in mUCUB and, subsequently, in metastatic non-UCUB (mn-UCUB). Of 3443 systemic therapy-exposed patients, 2725 (79%) harbored mUCUB versus 709 (21%) harbored mn-UCUB. Of 2725 mUCUB patients, 582 (21%) were contemporary (2017-2020) versus 2143 (79%) were historical (2000-2016). In mUCUB, median OS was 11 months in contemporary versus 8 months in historical patients (Δ = 3 months; p < .0001). After multivariable CRM, contemporary membership status (2017-2020) independently predicted lower overall mortality (OM; hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.60-0.76; p < .001). Of 709 mn-UCUB patients, 167 (24%) were contemporary (2017-2020) and 542 (76%) were historical (2000-2016). In mn-UCUB, median OS was 8 months in contemporary versus 7 months in historical patients (Δ = 1 month; p = .034). After multivariable CRM, contemporary membership status (2017-2020) was associated with HR of 0.81 (95% CI = 0.66-1.01; p = .06). In conclusion, contemporary systemic therapy-exposed metastatic patients exhibited better OS in UCUB. However, the magnitude of survival benefit was threefold higher in mUCUB and approximated the survival benefits recorded in prospective randomized trials of novel systemic therapies.

3.
Prostate ; 84(8): 731-737, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38506561

RESUMO

BACKGROUND: In incidental prostate cancer (IPCa), elevated other-cause mortality (OCM) may obviate the need for active treatment. We tested OCM rates in IPCa according to treatment type and cancer grade and we hypothesized that OCM is significantly higher in not-actively-treated patients. METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2015), IPCa patients were identified. Smoothed cumulative incidence plots as well as multivariable competing risks regression models were fitted to address OCM after adjustment for cancer-specific mortality (CSM). RESULTS: Of 5121 IPCa patients, 3655 (71%) were not-actively-treated while 1466 (29%) were actively-treated. Incidental PCa not-actively-treated patients were older and exhibited higher proportion of Gleason sum (GS) 6 and clinical T1a stage. In smoothed cumulative incidence plots, 5-year OCM was 20% for not-actively-treated versus 8% for actively-treated patients. Conversely, 5-year CSM was 5% for not-actively-treated versus 4% for actively-treated patients. No active treatment was associated with 1.4-fold higher OCM, even after adjustment for age, cancer characteristics, and CSM. According to GS, OCM reached 16%, 27%, and 35% in GS 6, 7, and 8-10 not-actively-treated IPCa patients, respectively and exceeded CSM recorded for the same three groups (2%, 6%, and 28%, respectively). CONCLUSION: Our results quantified OCM rates, confirming that in not-actively-treated IPCa patients OCM is indeed significantly higher than in their actively-treated counterparts (HR: 1.4). These observations validate the use of no active treatment in IPCa patients, in whom OCM greatly surpasses CSM (20% vs. 5%).


Assuntos
Achados Incidentais , Neoplasias da Próstata , Programa de SEER , Humanos , Masculino , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/tratamento farmacológico , Idoso , Pessoa de Meia-Idade , Causas de Morte , Gradação de Tumores , Idoso de 80 Anos ou mais , Estados Unidos/epidemiologia , Incidência
4.
N Engl J Med ; 384(22): 2102-2114, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34077643

RESUMO

BACKGROUND: The role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery is not clear. METHODS: In a phase 3, multicenter, double-blind, randomized, controlled trial, we assigned patients with muscle-invasive urothelial carcinoma who had undergone radical surgery to receive, in a 1:1 ratio, either nivolumab (240 mg intravenously) or placebo every 2 weeks for up to 1 year. Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. The primary end points were disease-free survival among all the patients (intention-to-treat population) and among patients with a tumor programmed death ligand 1 (PD-L1) expression level of 1% or more. Survival free from recurrence outside the urothelial tract was a secondary end point. RESULTS: A total of 353 patients were assigned to receive nivolumab and 356 to receive placebo. The median disease-free survival in the intention-to-treat population was 20.8 months (95% confidence interval [CI], 16.5 to 27.6) with nivolumab and 10.8 months (95% CI, 8.3 to 13.9) with placebo. The percentage of patients who were alive and disease-free at 6 months was 74.9% with nivolumab and 60.3% with placebo (hazard ratio for disease recurrence or death, 0.70; 98.22% CI, 0.55 to 0.90; P<0.001). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 74.5% and 55.7%, respectively (hazard ratio, 0.55; 98.72% CI, 0.35 to 0.85; P<0.001). The median survival free from recurrence outside the urothelial tract in the intention-to-treat population was 22.9 months (95% CI, 19.2 to 33.4) with nivolumab and 13.7 months (95% CI, 8.4 to 20.3) with placebo. The percentage of patients who were alive and free from recurrence outside the urothelial tract at 6 months was 77.0% with nivolumab and 62.7% with placebo (hazard ratio for recurrence outside the urothelial tract or death, 0.72; 95% CI, 0.59 to 0.89). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 75.3% and 56.7%, respectively (hazard ratio, 0.55; 95% CI, 0.39 to 0.79). Treatment-related adverse events of grade 3 or higher occurred in 17.9% of the nivolumab group and 7.2% of the placebo group. Two treatment-related deaths due to pneumonitis were noted in the nivolumab group. CONCLUSIONS: In this trial involving patients with high-risk muscle-invasive urothelial carcinoma who had undergone radical surgery, disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression level of 1% or more. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 274 ClinicalTrials.gov number, NCT02632409.).


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Nivolumabe/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/metabolismo , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Nivolumabe/efeitos adversos , Placebos/uso terapêutico , Qualidade de Vida , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
5.
Cancer Immunol Immunother ; 73(2): 38, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38289361

RESUMO

Immune checkpoint inhibitor (ICI)-based combination therapies are the recommended first-line treatment for metastatic renal cell carcinoma (mRCC). However, no head-to-head phase-3 randomized controlled trials (RCTs) have compared the efficacy of different ICI-based combination therapies. Here, we compared the efficacy of various first-line ICI-based combination therapies in patients with mRCC using updated survival data from phase-3 RCTs. Three databases were searched in June 2023 for RCTs that analyzed oncologic outcomes in mRCC patients treated with ICI-based combination therapies as first-line treatment. A network meta-analysis compared outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and complete response (CR) rate. Subgroup analyses were based on the International mRCC Database Consortium risk classification. The treatment ranking analysis of the entire cohort showed that nivolumab + cabozantinib (81%) had the highest likelihood of improving OS, followed by nivolumab + ipilimumab (75%); pembrolizumab + lenvatinib had the highest likelihood of improving PFS (99%), ORR (97%), and CR (86%). These results remained valid even when the analysis was limited to patients with intermediate/poor risk, except that nivolumab + ipilimumab had the highest likelihood of achieving CR (100%). Further, OS benefits of ICI doublets were not inferior to those of ICI + tyrosine kinase inhibitor combinations. Recommendation of combination therapies with ICIs and/or tyrosine kinase inhibitors based on survival benefits and patient pretreatment risk classification will help advance personalized medicine for mRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Seguimentos , Ipilimumab , Metanálise em Rede , Nivolumabe , Resposta Patológica Completa , Neoplasias Renais/tratamento farmacológico
6.
BMC Med ; 22(1): 264, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38915094

RESUMO

BACKGROUND: Ureteral cancer is a rare cancer. This study aimed to provide an up-to-date and comprehensive analysis on the global trends of ureteral cancer incidence and its association with lifestyle and metabolic risk factors. METHODS: The incidence of ureteral cancer was estimated from the Cancer Incidence in Five Continents Plus and Global Cancer Observatory databases. We analyzed the (1) global incidence of ureteral cancer by region, country, sex, and age group by age-standardized rates (ASR); (2) associated risk factors on a population level by univariable linear regression with logarithm transformation; and (3) incidence trend of ureteral cancer by sex and age group in different countries by Average Annual Percentage Change (AAPC). RESULTS: The global age-standardized rate of ureteral cancer incidence in 2022 was 22.3 per 10,000,000 people. Regions with higher human development index (HDI), such as Europe, Northern America, and East Asia, were found to have a higher incidence of ureteral cancer. Higher HDI and gross domestic product (GDP) and a higher prevalence of smoking, alcohol drinking, physical inactivity, unhealthy dietary, obesity, hypertension, diabetes, and lipid disorder were associated with higher incidence of ureteral cancer. An overall increasing trend of ureteral cancer incidence was observed for the past decade, especially among the female population. CONCLUSIONS: Although ureteral cancer was relatively rare, the number of cases reported was rising over the world. The rising trends among females were more evident compared with the other subgroups, especially in European countries. Further studies could be conducted to examine the reasons behind these epidemiological changes and confirm the relationship with the risk factors identified.


Assuntos
Sistema de Registros , Neoplasias Ureterais , Humanos , Fatores de Risco , Feminino , Masculino , Incidência , Pessoa de Meia-Idade , Idoso , Neoplasias Ureterais/epidemiologia , Adulto , Saúde Global , Adulto Jovem , Adolescente , Idoso de 80 Anos ou mais , Carga Global da Doença/tendências
7.
Ann Surg Oncol ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773038

RESUMO

BACKGROUND: In contemporary surgically treated patients with localized high-grade (G3 or G4) clear-cell renal cell carcinoma (ccRCC), it is not known whether presence of sarcomatoid dedifferentiation is an independent predictor and/or an effect modifier, when cancer-specific mortality (CSM) represents an endpoint. METHODS: Within the Surveillance, Epidemiology, and End Results database, all surgically treated localized high-grade ccRCC patients treated between 2010 and 2020 were identified. Univariable and multivariable Cox-regression models were used. RESULTS: In 18,853 surgically treated localized high-grade (G3 or G4) ccRCC patients, 5-year CSM-free survival was 87% (62% vs. 88% with vs. without sarcomatoid dedifferentiation, p < 0.001). Presence of sarcomatoid dedifferentiation was an independent predictor of higher CSM (hazard ratio [HR] 1.8, p < 0.001). In univariable survival analyses predicting CSM, presence versus absence of sarcomatoid dedifferentiation in G3 versus G4 yielded the following hazard ratios: HR 1.0 in absent sarcomatoid dedifferentiation in G3; HR 2.7 (p < 0.001) in absent sarcomatoid dedifferentiation in G4; HR 3.9 (p < 0.001) in present sarcomatoid dedifferentiation in G3; HR 5.1 (p < 0.001) in present sarcomatoid dedifferentiation in G4. Finally, in multivariable Cox-regression analyses, the interaction terms defining present versus absent sarcomatoid dedifferentiation in G3 versus G4 represented independent predictors of higher CSM. CONCLUSIONS: In contemporary surgically treated patients with localized high-grade ccRCC, sarcomatoid dedifferentiation is not only an independent multivariable predictor of higher CSM, but also interacts with tumor grade and results in even better ability to predict CSM.

8.
Ann Surg Oncol ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526833

RESUMO

BACKGROUND: In-hospital mortality and complication rates after partial and radical nephrectomy in patients with history of heart-valve replacement are unknown. PATIENTS AND METHODS: Relying on the National Inpatient Sample (2000-2019), kidney cancer patients undergoing partial or radical nephrectomy were stratified according to presence or absence of heart-valve replacement. Multivariable logistic and Poisson regression models addressed adverse hospital outcomes. RESULTS: Overall, 39,673 patients underwent partial nephrectomy versus 94,890 radical nephrectomy. Of those, 248 (0.6%) and 676 (0.7%) had a history of heart-valve replacement. Heart-valve replacement patients were older (median partial nephrectomy 69 versus 60 years; radical nephrectomy 71 versus 63 years), and more frequently exhibited Charlson comorbidity index ≥ 3 (partial nephrectomy 22 versus 12%; radical nephrectomy 32 versus 23%). In partial nephrectomy patients, history of heart-valve replacement increased the risk of cardiac complications [odds ratio (OR) 4.33; p < 0.001), blood transfusions (OR 2.00; p < 0.001), intraoperative complications (OR 1.53; p = 0.03), and longer hospital stay [rate ratio (RR) 1.25; p < 0.001], but not in-hospital mortality (p = 0.5). In radical nephrectomy patients, history of heart-valve replacement increased risk of postoperative bleeding (OR 4.13; p < 0.001), cardiac complications (OR 2.72; p < 0.001), intraoperative complications (OR 1.53; p < 0.001), blood transfusions (OR 1.27; p = 0.02), and longer hospital stay (RR 1.12; p < 0.001), but not in-hospital mortality (p = 0.5). CONCLUSIONS: History of heart-valve replacement independently predicted four of twelve adverse outcomes in partial nephrectomy and five of twelve adverse outcomes in radical nephrectomy patients including intraoperative and cardiac complications, blood transfusions, and longer hospital stay. Conversely, no statistically significant differences were observed in in-hospital mortality.

9.
Ann Surg Oncol ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802714

RESUMO

BACKGROUND: Deterioration of renal function is associated with increased all-cause mortality. In renal masses larger than 4 cm, whether partial versus radical nephrectomy (PN vs. RN) might affect long-term functional outcomes is unknown. This study tested the association between PN versus RN and postoperative acute kidney injury (AKI), recovery of at least 90% of the preoperative estimated glomerular filtration rate (eGFR) at 1 year, upstaging of chronic kidney disease (CKD) one stage or more at 1 year, and eGFR decline of 45 ml/min/1.73 m2 or less at 1 year. METHODS: Data from 23 high-volume institutions were used. The study included only surgically treated patients with single, unilateral, localized, clinical T1b-2 renal masses. Multivariable logistic regression analyses were performed. RESULTS: Overall, 968 PN patients and 325 RN patients were identified. The rate of AKI was lower in the PN versus the RN patients (17% vs. 58%; p < 0.001). At 1 year after surgery, for the PN versus the RN patients, the rate for recovery of at least 90% of baseline eGFR was 51% versus 16%, the rate of CKD progression of ≥ 1 stage was 38% versus 65%, and the rate of eGFR decline of 45 ml/min/1.73 m2 or less was 10% versus 23% (all p < 0.001). Radical nephrectomy independently predicted AKI (odds ratio [OR], 7.61), 1-year ≥ 90% eGFR recovery (OR, 0.30), 1-year CKD upstaging (OR, 1.78), and 1-year eGFR decline of 45 ml/min/1.73 m2 or less (OR, 2.36) (all p ≤ 0.002). CONCLUSIONS: For cT1b-2 masses, RN portends worse immediate and 1-year functional outcomes. When technically feasible and oncologically safe, efforts should be made to spare the kidney in case of large renal masses to avoid the hazard of glomerular function loss-related mortality.

10.
Histopathology ; 85(1): 92-103, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38477374

RESUMO

AIMS: We aimed to assess the oncological impact of micrometric extent of invasion in patients with pT1 bladder cancer (BCa) who underwent en-bloc resection for bladder tumour (ERBT). METHODS AND RESULTS: We retrospectively analysed the records and specimens of 106 pT1 high-grade BCa patients who underwent ERBT. The extent of invasion, such as depth from basal membrane, number of invasive foci, maximum width of invasive focus, muscularis mucosae invasion and infiltration pattern (pattern A: solid sheet-like, nodular or nested growth, pattern B: trabecular, small cluster or single-cell pattern) were evaluated by a single genitourinary pathologist. The end-points were recurrence-free (RFS) and progression-free survival (PFS). Within a median follow-up of 23 months, overall, 36 patients experienced recurrence and 13 patients experienced disease progression. The 2-year PFS differed significantly depending on depth from basal membrane (< 1.3 mm: 94.8% versus ≧ 1.3 mm: 65.2%, P = 0.005), maximum width of invasive focus (< 4 mm: 91.7% versus ≧ 4 mm: 62.3%, P < 0.001), muscularis mucosae (MM) invasion (above MM = 96.1% versus into or beyond MM = 64.8%, P = 0.002) and infiltration pattern (pattern A: 100% versus pattern B: 83.3%, P = 0.037). In a multivariable analysis, MM invasion [hazard ratio (HR) = 4.54, 95% confidence interval (CI) = 1.25-16.5] and maximum width of invasive focus ≧ 4 mm (HR = 4.79, 95% CI = 1.25-16.5) were independent prognostic factors of progression. CONCLUSIONS: En-bloc resection facilitates the evaluation of pathologic variables that might be useful in predicting disease recurrence and progression. In particular, not only the MM invasion but also the maximum width of invasion focus, reflecting the invasive volume, appear to be reliable prognosticators for disease progression.


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/mortalidade , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Idoso de 80 Anos ou mais , Recidiva Local de Neoplasia/patologia , Cistectomia/métodos , Adulto , Estadiamento de Neoplasias , Invasividade Neoplásica , Progressão da Doença , Intervalo Livre de Doença
11.
Eur J Clin Invest ; 54(6): e14192, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38445798

RESUMO

BACKGROUND: High-intensity focused ultrasound (HIFU) emerged as a novel approach for the treatment of localized prostate cancer (PCa). However, prospective studies on HIFU-related outcomes and predictors of treatment failure (TF) remain scarce. MATERIALS AND METHODS: We conducted a multinational prospective cohort study among patients undergoing HIFU therapy for localized, low- to intermediate-risk PCa. Follow-up data on serial prostate specific antigen (PSA), multi-parametric magnetic resonance imaging (mpMRI), targeted/systematic biopsies, adverse events and functional outcomes were collected. The primary endpoint was TF, defined as histologically confirmed PCa requiring whole-gland salvage treatment. Uni- and multi-variable adjusted hazard ratios (HRs) were calculated using Cox proportional hazard regression models. RESULTS: At baseline, mean (standard deviation) age was 64.14 (7.19) years, with the majority of patients showing T-stage 1 (73.9%) and International Society of Urological Pathology grading system Grade 2 (58.8%). PSA nadir (median, 1.70 ng/mL) was reached after 6 months. Of all patients recruited, 16% had clinically significant PCa, as confirmed by biopsy, of which 13.4% had TF. Notably, T-stage and number of positive cores at initial biopsy were independent predictors of TF during follow-up (HR [95% CI] 1.27 [1.02-1.59] and 5.02 [1.80-14.03], respectively). Adverse events were minimal (17% and 8% early and late adverse events, respectively), with stable or improved functional outcomes in the majority of patients. CONCLUSIONS: This interim analysis of a multinational study on HIFU therapy for the management of low-to-intermediate-risk PCa reveals good functional outcomes, minimal adverse events and low incidence of TF over the short-term. Data on long-term outcomes, specifically as it relates to oncological outcomes, are awaited eagerly.


Assuntos
Antígeno Prostático Específico , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Pessoa de Meia-Idade , Idoso , Antígeno Prostático Específico/metabolismo , Antígeno Prostático Específico/sangue , Estudos Prospectivos , Ultrassom Focalizado Transretal de Alta Intensidade , Falha de Tratamento , Modelos de Riscos Proporcionais , Terapia de Salvação/métodos , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Imageamento por Ressonância Magnética Multiparamétrica , Gradação de Tumores , Estudos de Coortes
12.
Artigo em Inglês | MEDLINE | ID: mdl-38693454

RESUMO

BACKGROUND: Circulating-tumor DNA (ctDNA) and prostate-specific membrane antigen (PSMA) ligand positron-emission tomography (PET) enable minimal-invasive prostate cancer (PCa) detection and survival prognostication. The present study aims to compare their tumor discovery abilities and prognostic values. METHODS: One hundred thirty men with confirmed PCa (70.5 ± 8.0 years) who underwent [68Ga]Ga-PSMA-11 PET/CT (184.8 ± 19.7 MBq) imaging and plasma sample collection (March 2019-August 2021) were included. Plasma-extracted cell-free DNA was subjected to whole-genome-based ctDNA analysis. PSMA-positive tumor lesions were delineated and their quantitative parameters extracted. ctDNA and PSMA PET/CT discovery rates were compared, and the prognostic value for overall survival (OS) was evaluated. RESULTS: PSMA PET discovery rates according to castration status and PSA ranges did differ significantly (P = 0.013, P < 0.001), while ctDNA discovery rates did not (P = 0.311, P = 0.123). ctDNA discovery rates differed between localized and metastatic disease (P = 0.013). Correlations between ctDNA concentrations and PSMA-positive tumor volume (PSMA-TV) were significant in all (r = 0.42, P < 0.001) and castration-resistant (r = 0.65, P < 0.001), however not in hormone-sensitive patients (r = 0.15, P = 0.249). PSMA-TV and ctDNA levels were associated with survival outcomes in the Logrank (P < 0.0001, P < 0.0001) and multivariate Cox regression analysis (P = 0.0023, P < 0.0001). CONCLUSION: These findings suggest that PSMA PET imaging outperforms ctDNA analysis in detecting prostate cancer across the whole spectrum of disease, while both modalities are independently highly prognostic for survival outcomes.

13.
BJU Int ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658172

RESUMO

OBJECTIVE: To compare the value of flexible blue-light cystoscopy (BLC) vs flexible white-light cystoscopy (WLC) in the surveillance setting of non-muscle-invasive bladder cancer (NMIBC). METHODS: All major databases were searched for articles published before May 2023 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome was the accuracy of flexible BLC vs WLC in detecting bladder cancer recurrence among suspicious bladder lesions. RESULTS: A total of 10 articles, comprising 1634 patients, were deemed eligible for the quantitative synthesis. In the meta-analysis focusing on the detection of disease recurrence, there was no difference between flexible BLC and WLC (odds ratio [OR] 1.08, 95% confidence interval [CI] 0.82-1.41)]; the risk difference (RD) showed 1% of flexible BLC, corresponding to a number needed to treat (NNT) of 100. In the subgroup meta-analysis of detection of carcinoma in situ (CIS) only, there was again no significant difference between flexible BLC and WLC (OR 1.19, 95% CI 0.82-1.69), BLC was associated with a RD of 2% (NNT = 50). The positive predictive values for flexible BLC and WLC in detecting all types of recurrence were 72% and 66%, respectively, and for CIS they were 39% and 29%, respectively. CONCLUSION: Surveillance of NMIBC with flexible BLC could detect more suspicious lesions and consequently more tumour recurrences compared to flexible WLC, with a increase in the rate of false positives leading to overtreatment. A total of 100 and 50 flexible BLC procedures would need to be performed to find on additional tumor and CIS recurences, respectively. A risk-stratified strategy for patient selection could be considered when using flexible BLC for the surveillance of NMIBC patients.

14.
BJU Int ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483124

RESUMO

OBJECTIVES: To evaluate the impact of incorporating neoadjuvant chemotherapy (NAC) into the 'quadrifecta' outcomes composite for reporting outcomes of radical cystectomy (RC) creating a pentafecta score. PATIENTS AND METHODS: This is a retrospective multicentre analysis of patients treated with RC, with or without NAC, for bladder cancer between 2002 and 2023. The primary outcome was the effect of adding NAC to a quadrifecta outcomes composite on cancer-specific (CSS) and overall survival (OS). The quadrifecta outcomes composite included a yield of ≥16 lymph nodes, negative soft tissue surgical margin, absence of major complication within 30 days from surgery, and no delay in RC. RESULTS: A total of 590 patients were included in the analyses. A total of 233 (39.5%) patients achieved all quadrifecta outcomes and 82 (13.9%) patients were additionally treated with NAC, achieving the pentafecta. Achieving the quadrifecta outcomes composite was significantly associated with better CSS (hazard ratio [HR] 0.49, 95% confidence interval [CI] 0.32-0.75; P = 0.001) and OS (HR 0.48, 95% CI 0.34-0.69; P < 0.01). The addition of NAC to the quadrifecta composite outcomes significantly improved the discrimination of patients more likely to have better CSS (HR 0.21, 95% CI 0.08-0.57; P = 0.002) and OS (HR 0.26, 95% CI 0.12-0.55; P < 0.01). CONCLUSION: We propose a new pentafecta that may serve as a tool for standardising outcomes reporting and measuring the quality of RC.

15.
BJU Int ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733321

RESUMO

OBJECTIVE: To investigate long-term and patient-reported outcomes, including sexual function, in women undergoing urogenital fistula (UGF) repair, addressing the lack of such data in Western countries, where fistulas often result from iatrogenic causes. PATIENTS AND METHODS: We conducted a retrospective analysis at a tertiary referral centre (2010-2023), classifying fistulas based on World Health Organisation criteria and evaluating surgical approaches, aetiology, and characteristics. Both objective (fistula closure, reintervention rates) and subjective outcomes (validated questionnaires) were assessed. A scoping review of patient-reported outcome measures in UGF repair was also performed. RESULTS: The study included 50 patients: 17 (34%) underwent transvaginal and 33 (66%) transabdominal surgery. History of hysterectomy was present in 36 patients (72%). The median (interquartile range [IQR]) operating time was 130 (88-148) min. Fistula closure was achieved in 94% of cases at a median (IQR) follow-up of 50 (16-91) months and reached 100% after three redo fistula repairs. Seven patients (14%) underwent reinterventions for stress urinary incontinence after transvaginal repair (autologous fascial slings). Patient-reported outcomes showed median (IQR) scores on the International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms Modules (ICIQ-FLUTS) of 5 (3-7) for filling symptoms, 1 (0-2) for voiding symptoms and 4.5 (1-9) for incontinence symptoms. The median (IQR) score on the ICIQ Female Sexual Matters Associated with Lower Urinary Tract Symptoms Module (ICIQ-FLUTSsex) was 3 (1-5). The median (IQR) ICIQ Satisfaction (ICIQ-S) outcome score and overall satisfaction with surgery item score was 22 (18.5-23.5) and 10 (8.5-10), respectively. Higher scores indicate higher symptom burden and treatment satisfaction, respectively. Our scoping review included 1784 women, revealing mixed aetiology and methodological and aetiological heterogeneity, thus complicating cross-study comparisons. CONCLUSIONS: Urogenital fistula repair at a specialised centre leads to excellent outcomes and high satisfaction. Patients with urethrovaginal fistulas are at increased risk of stress urinary incontinence, possibly due to the original trauma site of the fistula.

16.
BJU Int ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38659099

RESUMO

OBJECTIVE: To compare the differential efficacy of first-line immune checkpoint inhibitor (ICI)-based combined therapies among patients with intermediate- and poor-risk metastatic renal cell carcinoma (mRCC), as recently, the efficacy of triplet therapy comprising nivolumab plus ipilimumab plus cabozantinib has been published. PATIENTS AND METHODS: Three databases were searched in December 2022 for randomised controlled trials (RCTs) analysing oncological outcomes in patients with mRCC treated with first-line ICI-based combined therapies. We performed network meta-analysis (NMA) to compare the outcomes, including progression-free survival (PFS) and objective response rates (ORRs), in patients with intermediate- and poor-risk mRCC; we also assessed treatment-related adverse events. RESULTS: Overall, seven RCTs were included in the meta-analyses and NMAs. Treatment ranking analysis revealed that pembrolizumab + lenvatinib (99%) had the highest likelihood of improved PFS, followed by nivolumab + cabozantinib (79%), and nivolumab + ipilimumab + cabozantinib (77%). Notably, compared to nivolumab + cabozantinib, adding ipilimumab to nivolumab + cabozantinib did not improve PFS (hazard ratio 1.02, 95% confidence interval 0.72-1.43). Regarding ORRs, treatment ranking analysis also revealed that pembrolizumab + lenvatinib had the highest likelihood of providing better ORRs (99.7%). The likelihoods of improved PFS and ORRs of pembrolizumab + lenvatinib were true in both International Metastatic RCC Database Consortium (IMDC) risk groups. CONCLUSIONS: Our analyses confirmed the robust efficacy of pembrolizumab + lenvatinib as first-line treatment for patients with intermediate or poor IMDC risk mRCC. Triplet therapy did not result in superior efficacy. Considering both toxicity and the lack of mature overall survival data, triplet therapy should only be considered in selected patients.

17.
BJU Int ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627025

RESUMO

OBJECTIVE: To evaluate the impact of adjuvant therapy on oncological outcomes in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC), as due to the poorly-defined and overlapping diagnostic criteria optimal decision-making remains challenging in these patients. PATIENTS AND METHODS: In this multicentre study, patients treated with transurethral resection of bladder tumour for Ta disease were retrospectively analysed. All patients with low- or high-risk NMIBC were excluded from the analysis. Associations between adjuvant therapy administration with recurrence-free survival (RFS) and progression-free survival (PFS) rates were assessed in Cox regression models. RESULTS: A total of 2206 patients with intermediate-risk NMIBC were included in the analysis. Among them, 1427 patients underwent adjuvant therapy, such as bacille Calmette-Guérin (n = 168), or chemotherapeutic agents, such as mitomycin C or epirubicin (n = 1259), in different regimens up to 1 year. The median (interquartile range) follow-up was 73.3 (38.4-106.9) months. The RFS at 1 and 5 years in patients treated with adjuvant therapy and those without were 72.6% vs 69.5% and 50.8% vs 41.3%, respectively. Adjuvant therapy was associated with better RFS (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.70-0.89, P < 0.001), but not with PFS (P = 0.09). In the subgroup of patients aged ≤70 years with primary, single Ta Grade 2 <3 cm tumours (n = 328), adjuvant therapy was not associated with RFS (HR 0.71, 95% CI 0.50-1.02, P = 0.06). While in the subgroup of patients with at least one risk factor including patient age >70 years, tumour multiplicity, recurrent tumour and tumour size ≥3 cm (n = 1878), adjuvant intravesical therapy was associated with improved RFS (HR 0.78, 95% CI 0.68-0.88, P < 0.001). CONCLUSION: In our study, patients with intermediate-risk NMIBC benefit from adjuvant intravesical therapy in terms of RFS. However, in patients without risk factors, adjuvant intravesical therapy did not result in a clear reduction in the recurrence rate.

18.
BJU Int ; 133(3): 246-258, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37562831

RESUMO

OBJECTIVES: To determine and summarize the available data on urinary, sexual, and health-related quality-of-life (HRQOL) outcomes after traditional radical cystectomy (RC), reproductive organ-preserving RC (ROPRC) and nerve-sparing RC (NSRC) for bladder cancer (BCa) in female patients. METHODS: The PubMed, SCOPUS and Web of Science databases were searched to identify studies reporting functional outcomes in female patients undergoing RC and urinary diversion for the treatment of BCa. The outcomes of interest were voiding function (for orthotopic neobladder [ONB]), sexual function and HRQOL. The following independent variables were derived and included in the meta-analysis: pooled rate of daytime and nighttime continence/incontinence, and intermittent self-catheterization (ISC) rates. Analyses were performed separately for traditional, organ- and/or nerve-sparing surgical approaches. RESULTS: Fifty-three studies comprising 2740 female patients (1201 traditional RC and 1539 organ-/nerve-sparing RC, and 264 nerve-sparing-alone RC) were eligible for qualitative synthesis; 44 studies comprising 2418 female patients were included in the quantitative synthesis. In women with ONB diversion, the pooled rates of daytime continence after traditional RC, ROPRC and NSRC were 75.2%, 79.3% and 71.2%, respectively. The pooled rate of nighttime continence after traditional RC was 59.5%; this rate increased to 70.7% and 71.7% in women who underwent ROPRC and NSRC, respectively. The pooled rate of ISC after traditional RC with ONB diversion in female patients was 27.6% and decreased to 20.6% and 16.8% in patients undergoing ROPRC and NSRC, respectively. The use of different definitions and questionnaires in the assessment of postoperative sexual and HRQOL outcomes did not allow a systematic comparison. CONCLUSIONS: Female organ- and nerve-sparing surgical approaches during RC seem to result in improved voiding function. There is a significant need for well-designed studies exploring sexual and HRQOL outcomes to establish evidence-based management strategies to support a shared decision-making process tailored towards patient expectations and satisfaction. Understanding expected functional, sexual and quality-of-life outcomes is necessary to allow individualized pre- and postoperative counselling and care delivery in female patients planned to undergo RC.


Assuntos
Neoplasias da Bexiga Urinária , Derivação Urinária , Incontinência Urinária , Humanos , Feminino , Cistectomia/efeitos adversos , Bexiga Urinária/cirurgia , Incontinência Urinária/epidemiologia , Incontinência Urinária/etiologia , Incontinência Urinária/prevenção & controle , Micção , Derivação Urinária/efeitos adversos , Resultado do Tratamento
19.
BJU Int ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38494989

RESUMO

OBJECTIVE: To address cancer-specific mortality free-survival (CSM-FS) differences in patients with urothelial carcinoma of the urinary bladder (UCUB) vs non-UCUB who underwent trimodal therapy (TMT), according to organ confined (OC: T2N0M0) vs non-organ confined (NOC: T3-4NanyM0 or TanyN1-3M0) clinical stages. PATIENTS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified patients with cT2-T4N0-N3M0 bladder cancer treated with TMT, defined as the combination of transurethral resection of bladder tumour, chemotherapy, and radiotherapy. Temporal trends described TMT use over time. Kaplan-Meier plots and multivariable Cox regression (MCR) models addressed CSM in UCUB vs non-UCUB according to OC vs NOC stages. RESULTS: Of 5130 assessable TMT-treated patients, 425 (8%) harboured non-UCUB vs 4705 (92%) who had UCUB. The TMT rates increased for patients with OC UCUB from 92.4% to 96.8% (estimated annual percentage change of 0.4%, P < 0.001), but not in the NOC stages (P = 0.3). In the OC stage, the median CSM-FS was 36 months in patients with non-UCUB vs 60 months in those with UCUB, respectively (P = 0.01). Conversely, in the NOC stage, the median CSM-FS was 23 months both in UCUB and non-UCUB (P = 0.9). In the MCR models addressing OC stage, non-UCUB histology independently predicted higher CSM (hazard ratio 1.45, P = 0.004), but not in the NOC stage (P = 0.9). CONCLUSION: In OC UCUB, TMT rates have increased over time in a guideline-consistent fashion. Patients with OC non-UCUB treated with TMT showed a CSM disadvantage relative to OC UCUB. In the NOC stage, use of TMT resulted in dismal CSM, regardless of UCUB vs non-UCUB histology.

20.
BJU Int ; 133(3): 341-350, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37904652

RESUMO

OBJECTIVE: To determine the oncological impact of extended pelvic lymph node dissection (ePLND) vs standard PLND (sPLND) during radical cystectomy (RC) in clinically lymph node-positive (cN+) bladder cancer (BCa). PATIENTS AND METHODS: In this retrospective, multicentre study we included 969 patients who underwent RC with sPLND (internal/external iliac and obturator lymph nodes) or ePLND (sPLND plus common iliac and presacral nodes) with or without platin-based peri-operative chemotherapy for cTany N1-3 M0 BCa between 1991 and 2022. We assessed the impact of ePLND on recurrence-free survival (RFS) and the distribution of recurrences (locoregional and distant recurrences). The secondary endpoint was overall survival (OS). We performed propensity-score matching using covariates associated with the extent of PLND in univariable logistic regression analysis. The association of the extent of PLND with RFS and OS was investigated using Cox regression models. RESULTS: Of 969 cN+ patients, 510 were 1:1 matched on propensity scores. The median (interquartile range [IQR]) time to recurrence was 8 (4-16) months, and median (IQR) follow-up of alive patients was 30 (13-51) months. Disease recurrence was observed in 104 patients in the ePLND and 107 in the sPLND group. Of these, 136 (27%), 47 (9.2%) and 19 patients (3.7%) experienced distant, locoregional, or both distant and locoregional disease recurrence, respectively. When stratified by the extent of PLND, we did not find a difference in recurrence patterns (P > 0.05). ePLND improved neither RFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.70-1.19; P = 0.5) nor OS (HR 0.78, 95% CI 0.60-1.01; P = 0.06) compared to sPLND. Stratification by induction chemotherapy did not change outcomes. CONCLUSION: Performing an ePLND at the time of RC in cN+ patients improved neither RFS nor OS compared to sPLND, regardless of induction chemotherapy status. Pretreatment risk stratification is paramount to identify ideal candidates for RC with ePLND as part of a multimodal treatment approach.


Assuntos
Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária , Humanos , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Excisão de Linfonodo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Linfonodos/cirurgia , Linfonodos/patologia , Cistectomia
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