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1.
World J Urol ; 42(1): 307, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38722418

ABSTRACT

PURPOSE: To explore pre-treatment risk factors for overall survival (OS) in advanced urothelial carcinoma (UC) patients treated with first-line (1L) chemotherapy in sequential therapy (ST) era. Additionally, to evaluate the proportion of patients who were not able to undergo subsequent immune checkpoint inhibitor (ICI) therapy according to the subgroups stratified by the risk factors. METHODS: A multicenter retrospective study was conducted. Metastatic or locally advanced UC patients treated between 2017 and 2022 were included. The Kaplan-Meier method with the log-rank test and multivariate Cox regression models were used to address OS. RESULTS: Three hundred and fourteen patients treated with 1L chemotherapy were included in the study and 57 (18.2%) patients were not able to proceed to subsequent ICI therapy. Pre-chemotherapy risk factors for OS in 314 patients were ECOG-PS 1 or more, having no primary site resection, C-reactive protein (CRP) level of 3 mg/dL or more, and non-cisplatin-based regimen. Patients having 3 or 4 risk factors had higher risk for not being able to receive ST (Mann-Whitney U test, P < 0.001). As risk factors for OS in 230 patients who were able to receive ST, having no primary site resection, a neutrophil to lymphocyte ratio of 3 or more, and the presence of liver metastasis were identified. CONCLUSION: We reported the risk factors for OS in advanced UC patients treated with 1L chemotherapy in ST era. Patients with high risk for OS may not be able to proceed to subsequent ICI therapy even in the ST era.


Subject(s)
Carcinoma, Transitional Cell , Humans , Male , Retrospective Studies , Female , Aged , Middle Aged , Risk Assessment , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Survival Rate , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/mortality , Neoplasm Staging , Urologic Neoplasms/drug therapy , Urologic Neoplasms/mortality , Urologic Neoplasms/pathology , Immune Checkpoint Inhibitors/therapeutic use , Risk Factors
2.
PLoS One ; 19(5): e0302548, 2024.
Article in English | MEDLINE | ID: mdl-38728337

ABSTRACT

BACKGROUND: This study evaluated the cost-effectiveness of avelumab first-line (1L) maintenance therapy plus best supportive care (BSC) versus BSC alone for adults with locally advanced or metastatic urothelial carcinoma (la/mUC) that had not progressed following platinum-based chemotherapy in France. METHODS: A three-state partitioned survival model was developed to assess the lifetime costs and effects of avelumab plus BSC versus BSC alone. Data from the phase 3 JAVELIN Bladder 100 trial (NCT02603432) were used to inform estimates of clinical and utility values considering a 10-year time horizon and a weekly cycle length. Cost data were estimated from a collective perspective and included treatment acquisition, administration, follow-up, adverse event-related hospitalization, transport, post-progression, and end-of-life costs. Health outcomes were measured in quality-adjusted life-years (QALYs) and life-years gained. Costs and clinical outcomes were discounted at 2.5% per annum. Incremental cost-effectiveness ratios (ICERs) were used to compare cost-effectiveness and willingness to pay in France. Uncertainty was assessed using a range of sensitivity analyses. RESULTS: Avelumab plus BSC was associated with a gain of 2.49 QALYs and total discounted costs of €136,917; BSC alone was associated with 1.82 QALYs and €39,751. Although avelumab plus BSC was associated with increased acquisition costs compared with BSC alone, offsets of -€20,424 and -€351 were observed for post-progression and end-of-life costs, respectively. The base case analysis ICER was €145,626/QALY. Sensitivity analyses were consistent with the reference case and showed that efficacy parameters (overall survival, time to treatment discontinuation), post-progression time on immunotherapy, and post-progression costs had the largest impact on the ICER. CONCLUSIONS: This analysis demonstrated that avelumab plus BSC is associated with a favorable cost-effectiveness profile for patients with la/mUC who are eligible for 1L maintenance therapy in France.


Subject(s)
Antibodies, Monoclonal, Humanized , Cost-Benefit Analysis , Humans , Antibodies, Monoclonal, Humanized/economics , Antibodies, Monoclonal, Humanized/therapeutic use , France , Male , Female , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/economics , Urinary Bladder Neoplasms/pathology , Quality-Adjusted Life Years , Aged , Middle Aged , Adult , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/economics , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Neoplasm Metastasis , Urologic Neoplasms/drug therapy , Urologic Neoplasms/mortality , Urologic Neoplasms/economics , Urologic Neoplasms/pathology , Maintenance Chemotherapy/economics
3.
Front Immunol ; 15: 1401214, 2024.
Article in English | MEDLINE | ID: mdl-38799450

ABSTRACT

Background: Avelumab maintenance after first-line platinum-based chemotherapy represents a cornerstone for the treatment of metastatic urothelial carcinoma (mUC). However, identifying prognostic biomarkers is paramount for optimizing patients' benefits while minimizing toxicity. Cytokines represent circulating mediators of the complex interaction between cancer, the immune system, and inflammation. Inflammation, a hallmark of cancer, can be expressed by circulating factors. In different tumor subtypes, peripheral blood biomarkers, such as circulating cytokines, and systemic inflammatory indexes, have been addressed as potential prognostic factors for immune checkpoint inhibitors. However, their role in mUC still needs to be determined. Methods: Between February 2021 and April 2023, we prospectively collected plasma cytokines and inflammation indexes in 28 patients with mUC before starting avelumab as first-line maintenance. The primary endpoint was the relationship between baseline cytokines and inflammatory indexes with the clinical benefit (CB), defined as the number of Responders. Secondary endpoints included the correlation of baseline cytokines and inflammatory indexes with progression-free survival (PFS), overall survival (OS), and the number and grade of immune-related adverse events. Results: High pre-treatment levels of interferon (IFN)-γ and interleukin (IL)-2, and low levels of IL-6, IL-8, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and systemic-inflammation index (SII) were associated with clinical benefit and longer survival. In the multivariate analysis, low IL-8, NLR, and SII levels maintained a positive prognostic value for OS. Conclusion: Our data suggest that, in mUC patients receiving avelumab, pre-treatment levels of plasma cytokines and inflammatory indexes may serve as potential prognostic biomarkers for response and efficacy. In particular, patients with signs of pre-therapeutic inflammation showed a significantly lower response and survival to avelumab. On the contrary, low systemic inflammation and high levels of cytokines characterized responders and longer survivors.


Subject(s)
Antibodies, Monoclonal, Humanized , Cytokines , Humans , Male , Antibodies, Monoclonal, Humanized/therapeutic use , Female , Cytokines/blood , Aged , Middle Aged , Prognosis , Inflammation/drug therapy , Inflammation/blood , Inflammation/immunology , Biomarkers, Tumor/blood , Aged, 80 and over , Prospective Studies , Antineoplastic Agents, Immunological/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/blood , Carcinoma, Transitional Cell/immunology , Carcinoma, Transitional Cell/mortality , Urologic Neoplasms/drug therapy , Urologic Neoplasms/blood , Urologic Neoplasms/mortality , Urologic Neoplasms/immunology , Urologic Neoplasms/pathology , Maintenance Chemotherapy , Neoplasm Metastasis
4.
Pharmacoepidemiol Drug Saf ; 33(5): e5798, 2024 May.
Article in English | MEDLINE | ID: mdl-38680111

ABSTRACT

PURPOSE: Although recent trials involving first-line immune checkpoint inhibitors have expanded treatment options for patients with advanced urothelial carcinoma (aUC) who are ineligible for standard cisplatin-based chemotherapy, there exists limited evidence for whether trial efficacy translates into real-world effectiveness for patients seen in routine care. This retrospective cohort study compares differences in overall survival (OS) between KEYNOTE-052 trial participants and routine-care patients receiving first-line pembrolizumab monotherapy. METHODS: A routine-care patient cohort was constructed from the Flatiron Health database using trial eligibility criteria and was weighted to balance EHR and trial patient characteristics using matching-adjusted indirect comparisons. RESULTS: The routine-care cohort was older, more likely to be female, and more often cisplatin-ineligible due to renal dysfunction. ECOG performance status was comparable between the cohorts. Median OS was 9 months (95% CI 7-16) in the weighted routine-care cohort and 11.3 months (9.7-13.1) in the trial cohort. No significant differences between the Kaplan-Meier OS curves were detected (p = 0.76). Survival probabilities were similar between the weighted routine-care and trial cohorts at 12-, 24-, and 36- months (0.45 vs. 0.47, 0.31 vs. 0.31, 0.26 vs. 0.23, respectively). Notably, routine care patients had modestly lower survival at 3 months compared to trial participants (0.69 vs. 0.83, respectively). CONCLUSION: Our results provide reassurance that cisplatin-ineligible aUC patients receiving first-line immunotherapy in routine care experience similar benefits to those observed in trial patients.


Subject(s)
Antibodies, Monoclonal, Humanized , Immune Checkpoint Inhibitors , Humans , Immune Checkpoint Inhibitors/therapeutic use , Female , Male , Aged , Retrospective Studies , Antibodies, Monoclonal, Humanized/therapeutic use , Middle Aged , Urologic Neoplasms/drug therapy , Urologic Neoplasms/mortality , Aged, 80 and over , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/mortality , Cohort Studies , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/mortality , Databases, Factual
5.
Anticancer Res ; 44(5): 2117-2123, 2024 May.
Article in English | MEDLINE | ID: mdl-38677745

ABSTRACT

BACKGROUND/AIM: Evidence suggests that serum magnesium levels are associated with outcomes of immune checkpoint inhibitors (ICIs). However, this association remains under-explored in patients with metastatic urothelial carcinoma (UC) treated with ICIs. PATIENTS AND METHODS: This prognostic study used individual participant-level data from 1,281 patients with locally advanced or metastatic UC treated with atezolizumab (N=855) or chemotherapy (N=426) who participated in the IMvigor210 and the IMvigor211 trials. Multivariable Cox proportional hazards regression and Fine-Gray subdistribution hazards regression models were used to examine the association of baseline serum magnesium levels with overall survival (OS), progression-free survival (PFS), and immune-related adverse events (irAEs). RESULTS: No evidence of an association was found between baseline serum magnesium levels and PFS or OS in patients treated with atezolizumab [PFS, hazard ratio (HR)=1.03, 95% confidence interval (CI)=0.78-1.35; OS, HR=1.13, 95%CI=0.84-1.51] or chemotherapy (PFS, HR=0.93, 95%CI=0.62-1.40; OS, HR=0.91, 95%CI=0.59-1.40). We also found no evidence of association with irAEs (subdistribution HR=1.29, 95%CI=0.81-2.07) in patients receiving atezolizumab. CONCLUSION: This study found no evidence of an association between baseline serum magnesium levels and treatment outcomes or irAEs in patients with metastatic UC receiving atezolizumab. Contrary to previous research suggesting a role for magnesium in cancer therapy, these results indicate that serum magnesium levels may not serve as a biomarker to predict outcomes in these patients.


Subject(s)
Antibodies, Monoclonal, Humanized , Magnesium , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Male , Female , Magnesium/blood , Aged , Middle Aged , Neoplasm Metastasis , Treatment Outcome , Prognosis , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/adverse effects , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/blood , Urinary Bladder Neoplasms/pathology , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/blood , Carcinoma, Transitional Cell/secondary , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/mortality , Aged, 80 and over , Urologic Neoplasms/drug therapy , Urologic Neoplasms/blood , Urologic Neoplasms/pathology , Urologic Neoplasms/mortality
6.
Crit Rev Oncol Hematol ; 197: 104352, 2024 May.
Article in English | MEDLINE | ID: mdl-38614269

ABSTRACT

C-reactive protein (CRP) may reflect a pro-inflammatory tumor microenvironment and could represent a biomarker to select patients with urothelial carcinoma more likely to benefit from therapies directed at modulating tumor-promoting inflammation. We performed a systematic review to evaluate survival outcomes based on pre-treatment CRP values in urothelial carcinoma. The hazard ratios (HRs) of survival such as overall survival (OS) and progression-free survival (PFS) between groups with high versus low CRP values were pooled by the random-effect model meta-analyses. Overall, 28 studies comprising 6789 patients were identified for meta-analyses. High CRP levels were associated with shorter OS (HR=1.96 [95% CI: 1.64-2.33], p < 0.01), particularly in advanced disease treated with immune checkpoint blockade (ICB, HR=1.78 [1.47-2.15], p < 0.01). Similar findings were observed in ICB-treated patients with PFS. These findings suggest that CRP could be an attractive biomarker to select patients with urothelial carcinoma for strategies seeking to modulate tumor-promoting inflammation.


Subject(s)
Biomarkers, Tumor , C-Reactive Protein , Humans , Biomarkers, Tumor/blood , C-Reactive Protein/analysis , Carcinoma, Transitional Cell/blood , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/diagnosis , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/drug therapy , Prognosis , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/blood , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/diagnosis , Urologic Neoplasms/mortality , Urologic Neoplasms/pathology , Urologic Neoplasms/diagnosis , Urologic Neoplasms/blood
7.
Int J Clin Oncol ; 29(5): 612-619, 2024 May.
Article in English | MEDLINE | ID: mdl-38430304

ABSTRACT

BACKGROUND: This study aims to investigate the relationship between comorbidities and survival in patients with mUC treated with pembrolizumab as a second-line treatment. METHODS: From February 2018 to October 2021, we analyzed the data of 185 consecutive patients with metastatic UC who received pembrolizumab as second-line therapy at The Jikei University Hospital and five affiliated hospitals. We used the Charlson Comorbidity Index (CCI) to assess the comorbidities. The outcomes of interest were progression-free survival (PFS) and overall survival (OS). To compare the survival differences, inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and the IPTW-adjusted Cox regression hazards model were used. RESULTS: After IPTW adjustment, patient characteristics were well-balanced between patients with high CCI and those with low CCI. The IPTW-adjusted Kaplan-Meier curves of PFS and OS based on CCI revealed that the patients with high CCI (2 or more) had a shorter PFS (median, 1.6 vs. 2.8 months) and a shorter OS (median, 12.4 vs. 18.8 months) (0-1). Similarly, in the IPTW-adjusted Cox regression hazards model, patients with high CCI had significantly shorter PFS [HR, 1.84 (95% CI 1.26-2.68; p = 0.002)] and OS [HR, 1.98 (95% CI 1.20-3.27; p = 0.008)] than those with lower CCI. CONCLUSIONS: High CCI was associated with a higher risk of disease progression as well as overall mortality in mUC patients treated with second-line pembrolizumab.


Subject(s)
Antibodies, Monoclonal, Humanized , Comorbidity , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Male , Female , Aged , Middle Aged , Antineoplastic Agents, Immunological/therapeutic use , Retrospective Studies , Aged, 80 and over , Progression-Free Survival , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/secondary , Kaplan-Meier Estimate , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology , Urologic Neoplasms/drug therapy , Urologic Neoplasms/mortality , Urologic Neoplasms/pathology
8.
Eur Urol Oncol ; 7(3): 313-315, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38485615

ABSTRACT

Recent findings reported for the phase 3 EV-302 trial indicate a survival benefit from enfortumab vedotin plus pembrolizumab versus chemotherapy in metastatic urothelial carcinoma. We discuss several key points regarding post-protocol therapies, extending the duration of therapy, toxicity, and costs, all of which may have a bearing on how physicians and patients balance the benefit against the potential harms associated with this regimen.


Subject(s)
Antibodies, Monoclonal, Humanized , Antibodies, Monoclonal , Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Antibodies, Monoclonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology , Standard of Care , Urologic Neoplasms/drug therapy , Urologic Neoplasms/mortality , Urologic Neoplasms/pathology , Neoplasm Metastasis , Survival Rate , Antineoplastic Agents, Immunological/therapeutic use
9.
Int J Urol ; 31(5): 552-559, 2024 May.
Article in English | MEDLINE | ID: mdl-38303567

ABSTRACT

OBJECTIVES: Immune checkpoint inhibitors and enfortumab vedotin have opened new avenues for sequential treatment strategies for locally advanced/metastatic urothelial carcinoma (la/mUC). In the pre-enfortumab vedotin era, many patients could not receive third-line treatment owing to rapid disease progression and poor general status. This study aimed to analyze real-world sequential treatment practices for la/mUC in Japan, with a focus on patients who do not receive third-line treatment. METHODS: We analyzed data for 1023 la/mUC patients diagnosed between January 2020 and December 2021 at 54 institutions from a Japanese nationwide cohort. RESULTS: At the median follow-up of 28.5 months, the median overall survival from first-line initiation for 905 patients who received systemic anticancer treatment was 19.1 months. Among them, 81% and 32% received second- and third-line treatment. Notably, 52% had their treatment terminated before the opportunity for third-line treatment. Multivariate logistic regression analysis revealed that low performance status (≥1), elevated neutrophil-to-lymphocyte ratio (≥3), and low body mass index (<21 kg/m2) at the start of first-line treatment were independent risk factors for not proceeding to third-line treatment (p = 0.0024, 0.0069, and 0.0058, respectively). In this cohort, 33% had one of these factors, 36% had two, and 15% had all three. CONCLUSIONS: This study highlights the high frequency of factors associated with poor tolerance to anticancer treatment in la/mUC patients. The findings suggest the need to establish optimal sequential treatment strategies, maximizing efficacy within time and tolerance constraints, while concurrently providing strong supportive care, considering immunological and nutritional aspects.


Subject(s)
Carcinoma, Transitional Cell , Humans , Male , Female , Aged , Japan/epidemiology , Middle Aged , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/mortality , Aged, 80 and over , Immune Checkpoint Inhibitors/therapeutic use , Treatment Outcome , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/mortality , Retrospective Studies , Urologic Neoplasms/drug therapy , Urologic Neoplasms/pathology , Urologic Neoplasms/mortality , Disease Progression , Practice Patterns, Physicians'/statistics & numerical data
10.
J Clin Oncol ; 42(13): 1466-1471, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38350047

ABSTRACT

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.POUT was a phase III, randomized, open-label trial, including 261 patients with muscle-invasive or lymph node-positive, nonmetastatic upper tract urothelial cancer (UTUC) randomly assigned after radical nephroureterectomy to platinum-based chemotherapy (132) or surveillance (129). Primary outcome analysis demonstrated that chemotherapy improved disease-free survival (DFS). At that time, the planned secondary outcome analysis of overall survival (OS) was immature. By February 2022, 50 and 67 DFS events had occurred in the chemotherapy and surveillance groups, respectively, at a median follow-up of 65 months. The 5-year DFS was 62% versus 45%, univariable hazard ratio (HR), 0.55 (95% CI, 0.38 to 0.80, P = .001). The restricted mean survival time (RMST) was 18 months longer (95% CI, 6 to 30) in the chemotherapy arm. There were 46 and 60 deaths in the chemotherapy and control arms, respectively. The 5-year OS was 66% versus 57%, with univariable HR, 0.68 (95% CI, 0.46 to 1.00, P = .049) and RMST difference 11 months (95% CI, 1 to 21). Treatment effects were consistent across chemotherapy regimens (carboplatin or cisplatin) and disease stage. Toxicities were similar to those previously reported, and there were no clinically relevant differences in quality of life between arms. In summary, although OS was not the primary outcome measure, the updated results add further support for the use of adjuvant chemotherapy in patients with UTUC, suggesting long-term benefits.


Subject(s)
Nephroureterectomy , Humans , Nephroureterectomy/methods , Chemotherapy, Adjuvant , Female , Disease-Free Survival , Male , Aged , Middle Aged , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/surgery , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Urologic Neoplasms/drug therapy , Urologic Neoplasms/mortality , Urologic Neoplasms/surgery , Urologic Neoplasms/pathology , Ureteral Neoplasms/drug therapy , Ureteral Neoplasms/mortality , Ureteral Neoplasms/surgery , Ureteral Neoplasms/pathology , Kidney Neoplasms/drug therapy , Kidney Neoplasms/mortality , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology
11.
Actas urol. esp ; 46(5): 268-274, jun. 2022. tab, graf
Article in Spanish | IBECS | ID: ibc-208674

ABSTRACT

Introducción En el año 2020, en España, se diagnosticaron 282.421 nuevos casos de cáncer, encontrándose las neoplasias urológicas (NU) entre las más frecuentes. El tratamiento del cáncer en personas mayores es todo un reto, debido a su fragilidad y comorbilidades. Para responder a las necesidades que plantean las NU en las personas mayores, es necesaria una adecuada planificación de la enfermedad, comenzando por analizar los registros de cáncer. El objetivo fue, considerando a la población española de más de 65 años, proporcionar un análisis detallado de incidencia y mortalidad de las NU en el año 2020, así como las estimaciones para el año 2040. Material y métodos Las NU que se incluyeron fueron: testículo, vejiga, pene, riñón y próstata. Las estimaciones de incidencia y mortalidad fueron obtenidas de la base de datos GLOBOCAN. Resultados En el año 2020 se diagnosticaron en España 63.278 NU. Exceptuando la neoplasia de testículo, todas las neoplasias se diagnosticaron con mucha mayor frecuencia en el grupo de mayores de 65 años. Para el año 2040 se estima un aumento del 41,5%, alcanzando los 89.507 nuevos casos por año, de los cuales aproximadamente tres cuartas partes tendrán lugar en mayores de 65. El número de fallecidos mayores de 65 aumentará un 60,15% en 2040. Conclusión En las próximas 2 décadas es esperable que los nuevos casos de NU en mayores de 65 años aumenten por encima del 50%. Mayores recursos económicos y humanos, además de equipos multidisciplinares con experiencia y formación geriátrica, serán necesarios (AU)


Introduction In 2020, 282,421 new cases of cancer were diagnosed in Spain, and urological neoplasms (UN) were among the most frequent ones. Cancer treatment in elderly people is challenging due to frailty and comorbidities. Healthcare resources must be optimized in order to meet the needs of treating UN in the elderly, and deep analysis of cancer registries becomes mandatory. The objective of this work was to provide a detailed analysis of the incidence and mortality of UN in patients over 65 years old in the last year 2020 in Spain, as well as the estimates for the year 2040. Material and methods Incidence and mortality estimates were obtained from the GLOBOCAN database. The UN included were testicle, bladder, penis, kidney, and prostate. Results In 2020, 63,278 cases of UN were diagnosed in Spain. Most UN were much more frequent among patients > 65 years old, except for testicular cancers. For the year 2040, an increased incidence of 41.5% is estimated, reaching 89,507 new cases of UN per year, with approximately 3 out of 4 patients over 65 years of age. Deaths in people over 65 will increase by 60.15% in 2040. Conclusion In the next two decades, it is expected that new cases of UN in people over 65 years will rise above 50%. More financial and human resources, as well as multidisciplinary teams with experience and geriatric training, will be necessary (AU)


Subject(s)
Humans , Male , Aged , Urologic Neoplasms/mortality , Aging , Retrospective Studies , Spain/epidemiology , Age Factors , Incidence
12.
PLoS One ; 17(1): e0261124, 2022.
Article in English | MEDLINE | ID: mdl-34982793

ABSTRACT

Survival has improved in bladder cancer but few studies have considered extended periods or covered populations for which medical care is essentially free of charge. We analyzed survival in urothelial cancer (UC, of which vast majority are bladder cancers) in Finland and Sweden over a 50-year period (1967-2016) using data from the NORDCAN database. Finland and Sweden are neighboring countries with largely similar health care systems but higher economic resources and health care expenditure in Sweden. We present results on 1- and 5-year relative survival rates, and additionally provide a novel measure, the difference between 1- and 5-year relative survival, indicating how well survival was maintained between these two periods. Over the 50-year period the median diagnostic age has increased by several years and the incidence in the very old patients has increased vastly. Relative 1- year survival rates increased until early 1990s in both countries, and with minor gains later reaching about 90% in men and 85% in women. Although 5-year survival also developed favorably until early 1990s, subsequent gains were small. Over time, age specific differences in male 1-year survival narrowed but remained wide in 5-year survival. For women, age differences were larger than for men. The limitations of the study were lack of information on treatment and stage. In conclusion, challenges are to improve 5-year survival, to reduce the gender gap and to target specific care to the most common patient group, those of 70 years at diagnosis. The most effective methods to achieve survival gains are to target control of tobacco use, emphasis on early diagnosis with prompt action at hematuria, upfront curative treatment and awareness of high relapse requiring regular cystoscopy follow up.


Subject(s)
Urinary Bladder Neoplasms/mortality , Urologic Neoplasms/mortality , Aged , Aged, 80 and over , Databases, Factual , Female , Finland/epidemiology , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Survival Rate/trends , Sweden/epidemiology , Tobacco Use , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/epidemiology , Urologic Neoplasms/diagnosis , Urologic Neoplasms/epidemiology
13.
Anticancer Drugs ; 33(1): e61-e68, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34387596

ABSTRACT

We performed a systematic review and meta-analysis to evaluate the role of platinum-based adjuvant chemotherapy (AC) in upper tract urothelial carcinoma. Eligible studies were identified using Pubmed/Medline, Cochrane library, Embase and meeting abstracts. Outcomes of interest included: overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS). Platinum-based AC was associated with improved DFS, while the benefit in OS and CSS was not statistically significant compared to observation. Conversely, platinum-based AC showed a modest OS benefit in an analysis combing multivariable HRs with estimated HRs from Kaplan-Meier curves. Our results suggest that platinum-based AC is associated with improved DFS and a modest OS benefit in patients with locally advanced urothelial carcinomas.


Subject(s)
Carcinoma, Transitional Cell/drug therapy , Chemotherapy, Adjuvant/methods , Platinum Compounds/therapeutic use , Urologic Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/surgery , Humans , Kaplan-Meier Estimate , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Platinum Compounds/administration & dosage , Platinum Compounds/adverse effects , Survival Analysis , Urologic Neoplasms/mortality , Urologic Neoplasms/surgery
14.
Biomed Res Int ; 2021: 5311828, 2021.
Article in English | MEDLINE | ID: mdl-34660791

ABSTRACT

BACKGROUND: Conflicting results exist between the potential protective effects of metformin and the prognosis of urologic cancers. This meta-analysis summarized the effects of metformin exposure on the recurrence, progression, cancer-specific survival (CSS), and overall survival (OS) of the three main urologic cancers (kidney cancer, bladder cancer, and prostate cancer). METHODS: We systematically searched PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure databases (January 2010 to December 2019), which identified studies regarding metformin users and nonusers with urologic cancers and extracted patient data. A random effect model or fixed effect model was used to analyze hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among the 1883 confirmed studies, 27 eligible studies were identified, including 123,212 participants. In prostate cancer, patients using metformin have significant benefits for recurrence (HR = 0.74; 95% CI: 0.61-0.90; P = 0.007; I 2 = 56%), CSS (HR = 0.74; 95% CI: 0.61-0.91; P = 0.002; I 2 = 79%), and OS (HR = 0.76; 95% CI: 0.65-0.90; P < 0.001; I 2 = 86%). Moreover, further subgroup analysis showed that the beneficial effects of metformin may be more significant for patients receiving radical radiotherapy. For kidney cancer, metformin was beneficial for progression (HR = 0.80; 95% CI: 0.65-0.98; P = 0.14; I 2 = 46%). Analysis revealed that the effect of metformin on the overall survival of kidney cancer patients may be related to nationality (American: HR = 0.76; 95% CI: 0.59-0.98; P = 0.88; I 2 = 0%). For bladder cancer, no obvious benefits of metformin use were identified. However, subgroup analysis indicated that metformin may improve the recurrence of bladder cancer, but this improvement was only found in patients with a median follow-up time of more than 4 years (HR = 0.43; 95% CI: 0.28-0.67; P = 0.61; I 2 = 0%).


Subject(s)
Kidney Neoplasms/mortality , Metformin/therapeutic use , Prostatic Neoplasms/mortality , Urinary Bladder Neoplasms/mortality , Urologic Neoplasms/mortality , China , Humans , Hypoglycemic Agents/therapeutic use , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Male , Prognosis , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Survival Rate , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Urologic Neoplasms/drug therapy , Urologic Neoplasms/pathology
15.
Ann Med ; 53(1): 1827-1838, 2021 12.
Article in English | MEDLINE | ID: mdl-34647517

ABSTRACT

OBJECTIVE: Systemic immune-inflammation index (SII) has been reported in numerous studies to effectively predict the survival outcomes of urinary system cancers; however no agreement has been reached. This meta-analysis aimed to explore the prognostic significance of pre-treatment SII in tumours of the urinary system. METHODS: Relevant published articles were selected from Web of Science, PubMed, Embase, and the Cochrane Library up to 30 August 2020. The hazard ratios (HRs) with 95% confidence intervals (CIs) were computed to estimate the associations of pre-treatment SII with overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS) in urinary system cancers. RESULTS: 13 papers were included in our meta-analysis. From the combined data, we found that a high pre-treatment SII indicated a markedly worse OS (HR = 1.98; 95% CI: 1.75-2.23; p < .001), PFS (HR: 2.08; 95% CI: 1.32-3.26; p = .002), and CSS (HR: 2.41, 95% CI: 1.73-3.35, p < .001). Additionally, patients with an elevated SII value might have undesirable pathological characteristics, including a large tumour size, a poor differentiation grade, and an advanced tumour stage (all p < .001). CONCLUSIONS: Pre-treatment SII could be used as a non-invasive and promising biomarker to indicate the prognosis of urinary system cancer patients.KEY MESSAGES:This meta-analysis evaluates the predictive value of systemic immune-inflammation index (SII) for patients with urinary system cancer.A high pre-treatment SII indicates a poor prognosis.SII can serve as a promising non-invasive biomarker to help clinicians assess the prognosis and develop treatment strategies for urinary system cancer patients.


Subject(s)
Inflammation/diagnosis , Urologic Neoplasms/immunology , Urologic Neoplasms/mortality , Biomarkers/blood , Humans , Predictive Value of Tests , Prognosis , Proportional Hazards Models , Urologic Neoplasms/blood
16.
Future Oncol ; 17(31): 4145-4156, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34467778

ABSTRACT

Background: Bioinformatic analysis has revealed that OXR1 is significantly downregulated in muscle-invasive bladder cancer. Patients & methods: The expression of OXR1 in patients with urothelial carcinoma was evaluated by immunohistochemistry, including 340 cases with urothelial carcinoma in the upper urinary tract and 295 in the urinary bladder. Results: Low expression of OXR1 was significantly correlated with adverse pathological parameters including high primary tumor (pT) stage, high node stage, high histological grade, high mitotic activity and increased vascular or perineural invasion (all p < 0.05). Low expression of OXR1 independently predicted worse metastasis-free survival (p = 0.033) in urothelial carcinoma of the upper urinary tract and worse disease-specific survival (p = 0.022) and metastasis-free survival (p < 0.001) in urothelial carcinoma of the urinary bladder. Conclusion: Low expression of OXR1 is an adverse prognostic factor in urothelial carcinoma.


Subject(s)
Carcinoma, Transitional Cell/mortality , Mitochondrial Proteins/analysis , Urologic Neoplasms/mortality , Adult , Aged , Carcinoma, Transitional Cell/chemistry , Carcinoma, Transitional Cell/pathology , Female , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Staging , Prognosis , Urologic Neoplasms/chemistry , Urologic Neoplasms/pathology
17.
Future Oncol ; 17(32): 4343-4353, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34350778

ABSTRACT

Aim: To investigate real-world overall survival (rwOS) and real-world progression-free survival (rwPFS) in locally advanced/metastatic urothelial carcinoma postplatinum and postprogrammed death receptor-1/death ligand 1 inhibitors. Patients & methods: Adult patients diagnosed with locally advanced/metastatic urothelial carcinoma from 1 January 2011 to 31 December 2018 and treated with taxane monotherapy or any therapy postplatinum and post-PD-1/L1 inhibitors were included from a nationwide electronic health record-derived oncology database. Results: Median rwOS among 72 patients treated with taxane monotherapy was 7.6 months (95% CI: 5.2-14.4) and rwPFS was 2.9 months (95% CI: 2.4-4.0). Among 208 patients treated with any therapy, median rwOS was 8.9 months (95% CI: 7.3-10.6) and rwPFS was 3.6 months (95% CI: 2.7-4.7). Conclusion: Short duration of rwOS and rwPFS were observed, highlighting the need for effective and safe treatments in this patient population.


Lay abstract Few studies have evaluated survival outcomes in patients with advanced urothelial cancer who have disease relapse after chemotherapy and PD-1/L1 inhibitor therapy in clinical practice. In this study, we used electronic health records from a nationwide cancer database to assess survival in adult patients who received further treatment in this setting from 2011 to 2018. Among 72 patients who were treated with taxane monotherapy after chemotherapy and a PD-1/L1 inhibitor, average overall survival was 7.6 months and progression-free survival was 2.9 months. Among 208 patients who were treated with any therapy, average overall survival was 8.9 months and progression-free survival was 3.6 months. These results highlight the need for safer and more effective therapies in patients with advanced urothelial cancer who have disease relapse after chemotherapy and PD-1/L1 inhibitor therapy.


Subject(s)
Carcinoma, Transitional Cell/mortality , Immune Checkpoint Inhibitors/therapeutic use , Urologic Neoplasms/mortality , Aged , Aged, 80 and over , Bridged-Ring Compounds/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/pathology , Female , Humans , Male , Neoplasm Metastasis , Platinum/therapeutic use , Taxoids/therapeutic use , Urologic Neoplasms/drug therapy , Urologic Neoplasms/pathology
18.
Comput Math Methods Med ; 2021: 5515218, 2021.
Article in English | MEDLINE | ID: mdl-34335862

ABSTRACT

Urologic cancers, comprising prostate carcinoma (PCa), renal cell carcinoma (RCC), and bladder carcinoma (BCa), were the commonly occurred carcinoma amid males. Long noncoding RNAs (lncRNAs) with the length of more than 200 nt functioned importantly in physiological and pathological advancement. Nevertheless, further investigation regarding lncRNA expression feature and function in urologic cancers should be essential. This study is aimed at uncovering the roles of the differently expressed lncRNAs in urologic cancers. The data of gene expression levels was downloaded from lncRNAtor datasets. The lncRNA expression pattern existing in different urologic cancers was assessed by hierarchical clustering analysis. Gene Ontology (GO) analysis and KEGG pathway analysis were separately applied to evaluate the biological function and process and the biological pathways involving differently expressed lncRNAs. Our results indicated that 18 lncRNA expressions were increased, and 16 lncRNA expressions were reduced in urologic cancers after comparison with that in normal tissues. Moreover, our results demonstrated 61, 422, 137, and 281 lncRNAs were specifically dysregulated in bladder cancer (BLCA), kidney renal clear cell cancer (KIRC), kidney renal papillary cell cancer (KIRP), and prostate adenocarcinoma (PRAD), respectively. Bioinformatics analysis showed that differently expressed lncRNAs displayed crucially in urologic cancers. The prognostic value of common and cancer-specific differently expressed lncRNAs, such as PVT1, in cancer outcomes, was emphasized here. Our research has deeply unearthed the mechanism of differently expressed lncRNAs in urologic cancers development.


Subject(s)
RNA, Long Noncoding/genetics , Urologic Neoplasms/genetics , Adenocarcinoma/genetics , Carcinoma, Papillary/genetics , Carcinoma, Renal Cell/genetics , Computational Biology , Female , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/genetics , Male , Prognosis , Prostatic Neoplasms/genetics , Urinary Bladder Neoplasms/genetics , Urologic Neoplasms/mortality
19.
Prostate ; 81(15): 1149-1158, 2021 11.
Article in English | MEDLINE | ID: mdl-34402086

ABSTRACT

BACKGROUND: To test the effect of urological primary cancers (bladder, kidney, testis, upper tract, penile, urethral) on overall mortality (OM) after secondary prostate cancer (PCa). METHODS: Within the Surveillance, Epidemiology and End Results (SEER) database, patients with urological primary cancers and concomitant secondary PCa (diagnosed 2004-2016) were identified and were matched in 1:4 fashion with primary PCa controls. OM was compared between secondary and primary PCa patients and stratified according to primary urological cancer type, as well as to time interval between primary urological cancer versus secondary PCa diagnoses. RESULTS: We identified 5,987 patients with primary urological and secondary PCa (bladder, n = 3,287; kidney, n = 2,127; testis, n = 391; upper tract, n = 125; penile, n = 47; urethral, n = 10) versus 531,732 primary PCa patients. Except for small proportions of Gleason grade group and age at diagnosis, PCa characteristics between secondary and primary PCa were comparable. Conversely, proportions of secondary PCa patients which received radical prostatectomy were smaller (29.0 vs. 33.5%), while no local treatment rates were higher (34.2 vs. 26.3%). After 1:4 matching, secondary PCa patients exhibited worse OM than primary PCa patients, except for primary testis cancer. Here, no OM differences were recorded. Finally, subgroup analyses showed that the survival disadvantage of secondary PCa patients decreased with longer time interval since primary cancer diagnosis. CONCLUSIONS: After detailed matching for PCa characteristics, secondary PCa patients exhibit worse survival, except for testis cancer patients. The survival disadvantage is attenuated, when secondary PCa diagnosis is made after longer time interval, since primary urological cancer diagnosis.


Subject(s)
Prostatic Neoplasms/mortality , Urologic Neoplasms/mortality , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Neoplasm Grading , Prostatectomy , Prostatic Neoplasms/secondary , Prostatic Neoplasms/surgery , SEER Program , Survival Rate , Treatment Outcome , Urologic Neoplasms/pathology
20.
J Immunother ; 44(7): 248-253, 2021 09 01.
Article in English | MEDLINE | ID: mdl-34081050

ABSTRACT

Eosinophils influence antitumor immunity and may predict response to treatment with immune checkpoint inhibitors (ICIs). To examine the association between blood eosinophil counts and outcomes in patients with advanced or metastatic urothelial carcinoma (mUC) treated with ICIs, we identified 2 ICI-treated cohorts: discovery (n=60) and validation (n=111). Chemotherapy cohorts were used as comparators (first-line platinum-based chemotherapy, n=75; second-line or more pemetrexed, n=77). The primary endpoint was overall survival (OS). Secondary endpoints were time on treatment (ToT) and progression-free survival. Univariate and multivariate analyses were performed using Cox proportional hazard models. Associations between changes in eosinophil count at weeks 2/3 and 6 after the start of ICI treatment were analyzed using landmark analyses. Baseline characteristics of the ICI cohorts were similar. In the discovery cohort, an optimal cutoff for pretreatment eosinophil count was determined [Eos-Lo: <100 cells/µL; n=9 (15%); Eos-Hi: ≥100 cells/µL; n=51 (85%)]. Eos-Lo was associated with inferior outcomes [OS: hazard ratio (HR), 3.98; 95% confidence interval (CI), 1.85-8.56; P<0.013; ToT: HR, 2.45; 95% CI, 1.17-5.10; P=0.017]. This was confirmed in the validation cohort [Eos-Lo: n=17 (15%); Eos-Hi: n=94 (85%)] (OS: HR, 2.51; 95% CI, 1.31-4.80; P=0.006; ToT: HR, 2.22; 95% CI, 1.2-3.80; P=0.004), and remained significant after adjustment for other prognostic factors. Changes in eosinophil counts at weeks 2/3 and 6 were not clearly associated with outcomes. In chemotherapy cohorts, eosinophil counts were not associated with outcomes. In conclusion, low pretreatment eosinophil count was associated with poorer outcomes in patients with mUC treated with ICIs, and may represent a new predictive biomarker.


Subject(s)
B7-H1 Antigen/antagonists & inhibitors , Eosinophils/immunology , Immune Checkpoint Inhibitors/therapeutic use , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Urologic Neoplasms/drug therapy , Aged , Female , Humans , Kaplan-Meier Estimate , Leukocyte Count , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Treatment Outcome , Urologic Neoplasms/immunology , Urologic Neoplasms/mortality , Urologic Neoplasms/pathology , Urothelium/pathology
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