RESUMO
Survival outcomes after radical cystectomy (RC) for bladder cancer (BCa) have not improved in recent decades; nevertheless, RC remains the standard treatment for patients with localized muscle-invasive BCa. Identification of the patients most likely to benefit from RC only versus a combination with systemic therapy versus systemic therapy first/only and bladder-sparing is needed. This systematic review and meta-analysis pools the data from published studies on blood-based biomarkers to help prognosticate disease recurrence after RC. A literature search on PubMed and Scopus was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Articles published before November 2022 were screened for eligibility. A meta-analysis was performed on studies investigating the association of the neutrophil-to-lymphocyte ratio (NLR), the only biomarker with sufficient data, with recurrence-free survival. The systematic review identified 33 studies, and 7 articles were included in the meta-analysis. Our results demonstrated a statistically significant correlation between elevated NLR and an increased risk of disease recurrence (HR 1.26; 95% CI 1.09, 1.45; p = 0.002) after RC. The systematic review identified various other inflammatory biomarkers, such as interleukin-6 or the albumin-to-globulin ratio, which have been reported to have a prognostic impact on recurrence after RC. Besides that, the nutritional status, factors of angiogenesis and circulating tumor cells, and DNA seem to be promising tools for the prognostication of recurrence after RC. Due to the high heterogeneity between the studies and the different cut-off values of biomarkers, prospective and validation trials with larger sample sizes and standardized cut-off values should be conducted to strengthen the approach in using biomarkers as a tool for risk stratification in clinical decision-making for patients with localized muscle-invasive BCa.
Assuntos
Neoplasias da Bexiga Urinária , Bexiga Urinária , Humanos , Bexiga Urinária/patologia , Cistectomia/métodos , Prognóstico , Estudos Prospectivos , Recidiva Local de Neoplasia/patologia , Neoplasias da Bexiga Urinária/patologia , BiomarcadoresRESUMO
INTRODUCTION: Two randomized trials demonstrated a survival benefit of triplet therapy (androgen deprivation therapy [ADT]) plus androgen receptor pathway inhibitor [ARPI] plus docetaxel) over doublet therapy (ADT plus docetaxel), thus changing treatment strategies in metastatic hormonesensitive prostate cancer (mHSPC). PATIENTS AND METHODS: We conducted the first real-world analysis comprising 97 mHSPC patients from 16 Austrian medical centers, among them 79.4% of patients received abiraterone and 17.5% darolutamide treatment. Baseline characteristics and clinical parameters during triplet therapy were documented. Mann-Whitney U test for continuous or X²-test for categorical variables was used. Variables on progression were tested using logistic regression analysis and tabulated as hazard ratios (HR), 95% confidence interval (CI). RESULTS: Of 83.5% patients with synchronous and 16.5% with metachronous disease were included. 83.5% had high-volume disease diagnosed by conventional imaging (48.9%) or PSMA PET-CT (51.1%). While docetaxel and ARPI were administered consistent with pivotal trials, prednisolone, prophylactic gCSF and osteoprotective agents were not applied guideline conform in 32.5%, 37%, and 24.3% of patients, respectively. Importantly, a nonsimultaneous onset of chemotherapy and ARPI, performed in 44.3% of patients, was associated with significantly worse treatment response (P = .015, HR 0.245). Starting ARPI before chemotherapy was associated with significantly higher probability for progression (P = .023, HR 15.781) than vice versa. Strikingly, 15.6% (abiraterone) and 25.5% (darolutamide) low-volume patients as well as 14.4% (abiraterone) and 17.6% (darolutamide) metachronous patients received triplet therapy. Adverse events (AE) occurred in 61.9% with grade 3 to 5 in 15% of patient without age-related differences. All patients achieved a PSA decline of 99% and imaging response was confirmed in 88% of abiraterone and 75% of darolutamide patients. CONCLUSIONS: Triplet therapy arrived in clinical practice primarily for synchronous high-volume mHSPC. Regardless of selected therapy regimen, treatment is highly effective and tolerable. Preferably therapy should be administered simultaneously, however if not possible, chemotherapy should be started first.
Assuntos
Neoplasias da Próstata , Humanos , Masculino , Antagonistas de Androgênios/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Áustria , Docetaxel/uso terapêutico , Hormônios , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND AND OBJECTIVE: There are limited data on real-world outcomes for patients with advanced or metastatic urothelial cancer (mUC) since immune checkpoint inhibitors (ICIs) became available. Our objective was to analyze outcomes for patients with mUC since ICIs became available. METHODS: We performed a retrospective analysis of 131 patients with mUC attending the outpatient clinic of a single tertiary care center who received systemic therapy between June 2017 and July 2021 with follow-up up to December 2022. Summary and descriptive statistics were calculated for categorical and continuous variables. The Kaplan-Meier method was applied to calculate survival, and a Cox proportional-hazards model was used to explore associations between clinical variables and outcomes. KEY FINDINGS AND LIMITATIONS: The median patient age was 68 yr (range 35-90). The first systemic therapy administered was platinum-based in 79% of cases and ICI-based in 21%. Some 61% of the cohort received a second systemic treatment, with 75% of these an ICI. Median overall survival for the entire cohort was 24 mo (interquartile range 9-35). Patients on ICI therapy for ≥6 mo had median overall survival of 59 mo (95% confidence interval 39 mo-not reached). Metastatic sites on initiation of ICI therapy and C-reactive protein kinetics were prognostic in patients receiving ICIs. Limitations include the retrospective design and inherent selection bias. CONCLUSIONS AND CLINICAL IMPLICATIONS: More than 60% of patients with mUC received second-line treatment, and 75% of these received an ICI. Patients staying on immunotherapy for more than 6 mo have substantially better outcomes in comparison to patients with less time on immunotherapy and historical cohorts. PATIENT SUMMARY: We looked at the lines of therapy and outcomes for patients with advanced or metastatic cancer of the urinary tract, starting from when immunotherapy drugs called immune checkpoint inhibitors (ICIs) became available. We found that 60% of patients have received second-line therapy, which is a double the rate in comparison to historical groups of patients. Patients with long-term ICI therapy (>6 months) had significantly better outcomes, with a median survival of more than 3 years.