BACKGROUND: Triplet therapy, androgen receptor signaling inhibitors (ARSIs) plus docetaxel plus androgen-deprivation therapy (ADT), is a novel guideline-recommended treatment for metastatic hormone-sensitive prostate cancer (mHSPC). However, the optimal selection of the patient most likely to benefit from triplet therapy remains unclear. METHODS: We performed a systematic review, meta-analysis, and network meta-analysis to assess the oncologic benefit of triplet therapy in mHSPC patients stratified by disease volume and compare them with doublet treatment regimens. Three databases and meeting abstracts were queried in March 2023 for randomized controlled trials (RCTs) evaluating patients treated with systemic therapy for mHSPC stratified by disease volume. Primary interests of measure were overall survival (OS). We followed the PRISMA guideline and AMSTAR2 checklist. RESULTS: Overall, eight RCTs were included for meta-analyses and network meta-analyses (NMAs). Triplet therapy outperformed docetaxel plus ADT in terms of OS in both patients with high-(pooled HR: 0.73, 95%CI 0.64-0.84) and low-volume mHSPC (pooled HR: 0.71, 95%CI 0.52-0.97). There was no statistically significant difference between patients with low- vs. high-volume in terms of OS benefit from adding ARSI to docetaxel plus ADT (p = 0.9). Analysis of treatment rankings showed that darolutamide plus docetaxel plus ADT (90%) had the highest likelihood of improved OS in patients with high-volume disease, while enzalutamide plus ADT (84%) had the highest in with low-volume disease. CONCLUSIONS: Triplet therapy improves OS in mHSPC patients compared to docetaxel-based doublet therapy, irrespective of disease volume. However, based on treatment ranking, triplet therapy should preferably be considered for patients with high-volume mHSPC while those with low-volume are likely to be adequately treated with ARSI + ADT.
- Klíčová slova
- Androgen receptor signaling inhibitor, Docetaxel, High-volume, Low-volume, Metastatic hormone-sensitive prostate cancer,
- MeSH
- antagonisté androgenních receptorů terapeutické užití MeSH
- antagonisté androgenů * terapeutické užití MeSH
- docetaxel * terapeutické užití aplikace a dávkování MeSH
- lidé MeSH
- nádory prostaty * farmakoterapie mortalita patologie MeSH
- protokoly antitumorózní kombinované chemoterapie * terapeutické užití MeSH
- randomizované kontrolované studie jako téma MeSH
- síťová metaanalýza * MeSH
- tumor burden MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
- Názvy látek
- antagonisté androgenních receptorů MeSH
- antagonisté androgenů * MeSH
- docetaxel * MeSH
Pembrolizumab is the standard for the first and second lines in treating metastatic urothelial carcinoma (UC). This systematic review and meta-analysis aimed to assess the value of pretreatment clinical characteristics and hematologic biomarkers for prognosticating response to pembrolizumab in patients with metastatic UC. PUBMED®, Web of Science™, and Scopus® databases were searched for articles published before May 2021 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were deemed eligible if they evaluated overall survival (OS) in patients with metastatic urothelial carcinoma treated with pembrolizumab and pretreatment clinical characteristics or laboratory examination. Overall, 13 studies comprising 1311 patients were eligible for the meta-analysis. Several pretreatment patients' demographics and hematologic biomarkers were significantly associated with worse OS as follows: Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≥ 2 (Pooled hazard ratio [HR]: 3.24, 95% confidence interval [CI] 2.57-4.09), presence of visceral metastasis (Pooled HR: 1.84, 95% CI 1.42-2.38), presence of liver metastasis (Pooled HR: 4.23, 95% CI 2.18-8.20), higher neutrophil-lymphocyte ratio (NLR) (Pooled HR: 1.29, 95% CI 1.07-1.55) and, higher c-reactive protein (CRP) (Pooled HR: 2.49, 95% CI 1.52-4.07). Metastatic UC patients with poor PS, liver metastasis, higher pretreatment NLR and/or CRP have a worse survival despite pembrolizumab treatment. These findings might help to guide the prognostic tools for clinical decision-making; however, they should be interpreted carefully, owing to limitations regarding the retrospective nature of primary data.
- Klíčová slova
- Metastatic urothelial carcinoma, Pembrolizumab, Prognostic factor,
- MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- karcinom z přechodných buněk * farmakoterapie MeSH
- lidé MeSH
- nádory močového měchýře * farmakoterapie MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
- Názvy látek
- humanizované monoklonální protilátky MeSH
- pembrolizumab MeSH Prohlížeč
PURPOSE: To evaluate the potential predictive value of the preoperative serum albumin to globulin ratio (AGR) for oncological outcomes in patients treated with radical prostatectomy (RP) for clinically non-metastatic prostate cancer (PCa). METHODS: Pre-operative AGR was assessed in a multi-institutional cohort of 6041 patients treated with RP. Logistic regression analyses were performed to assess the association of the AGR with advanced disease. We performed Cox regression analyses to determine the relationship between AGR and biochemical recurrence (BCR). RESULTS: The optimal cut-off value was determined to be 1.31 according to receiver operating curve analysis. Compared to patients with a higher AGR, those with a lower preoperative AGR had worse BCR-free survival (P < 0.01) in the Kaplan-Meier analysis. Pre- and post-operative multivariable models that adjusted for the effects of established clinicopathologic features, confirmed its independent association with BCR [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.31-1.75, P < 0.01, HR 1.55, 95% CI 1.34-1.79, P < 0.01, respectively]. However, the addition of AGR to established prognostic models did not improve their discrimination. CONCLUSION: While AGR is significantly associated with BCR, in the present study, the clinical impact of AGR was not large enough to affect patient management. Longer follow-up is necessary to observe the true effect of AGR.
- Klíčová slova
- Albumin, Globulin, Prostate cancer, Radical prostatectomy,
- Publikační typ
- časopisecké články MeSH
AIMS: The European Association of Urology guideline for upper tract urothelial carcinoma (UTUC) relies on two grading system: 1973 World Health Organization (WHO) and 2004/2016 WHO. No consensus has been made which classification should supersede the other and both are recommended in clinical practice. We hypothesized that one may be superior to the other. METHODS: Newly diagnosed non-metastatic UTUC patients treated with radical nephroureterectomy were abstracted from the Surveillance, Epidemiology, and End Results database (2010-2016). Kaplan-Meier plots and multivariable Cox regression models (CRMs) tested cancer-specific mortality (CSM), according to 1973 WHO (G1 vs. G2 vs. G3) or to 2004/2016 WHO (low-grade vs. high-grade) grading systems. Haegerty's C-index quantified accuracy. RESULTS: Of 4271 patients, according to 1973 WHO grading system, 134 (3.1%) were G1, 436 (10.2%) were G2 and 3701 (86.7%) were G3; while according to 2004/2016 WHO grading system, 508 (11.9%) were low grade vs 3763 (88.1%) high grade. In multivariable CRMs, high grade predicted higher CSM (Hazard ratio: 1.70, p < 0.001). Conversely, neither G2 (p = 0.8) nor G3 (p = 0.1) were independent predictors of worse survival. The multivariable models without consideration of either grading system were 74% accurate in predicting 5-year CSM. Accuracy increased to 76% after either addition of the 1973 WHO or 2004/2016 WHO grade. CONCLUSIONS: From a statistical standpoint, either 1973 WHO or 2004/2016 WHO grading system improves the accuracy of CSM prediction to the same extent. In consequence, other considerations such as intra- and interobserver variability may represent additional metrics to consider in deciding which grading system is better.
This systematic review and meta-analysis aimed to assess and compare the perioperative and oncological outcomes of intracorporeal (ICUD) and extracorporeal (ECUD) urinary diversion following robot-assisted radical cystectomy (RARC). A systematic literature search of articles was performed in PubMed®, Web of Science®, and Scopus® databases according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. We included studies that compared patients who underwent RARC with ICUD to those with ECUD. Twelve studies including 3067 patients met the eligibility criteria. There were no significant differences between ICUD and ECUD in overall and major complications, regardless of the period (short-term [≤ 30 days] or mid-term [> 30 days]). Subgroup analyses demonstrated that ICUD performed by high-volume centers exhibited a significantly reduced risk of major complications (short-term: OR 0.57, 95% CI 0.37-0.86, p = 0.008, mid-term: OR 0.66, 95% CI 0.46-0.94, p = 0.02). Patients who underwent ICUD had lower estimated blood loss (MD -102.3 ml, 95% CI - 132.8 to - 71.8, p < 0.00001), less likely to receive blood transfusion rates (OR 0.36, 95% CI 0.20-0.62, p = 0.00003); and these findings were consistent in subgroup analyses by low-volume centers (MD-121.6 ml, 95% CI - 160.9 to - 82.3, p < 0.00001 and OR 0.36, 95% CI 0.20-0.62, p = 0.00003, respectively). ICUD had a higher lymph node yield (MD 3.68, 95% CI 0.80-6.56, p = 0.01). Patients receiving ICUD provided comparable complications, superior perioperative outcomes, and similar oncological outcomes compared with ECUD. Centralization of patients may contribute to a reduction of postoperative complications, while maintaining the advantages.
- Klíčová slova
- Complication, Extracorporeal urinary diversion, Hospital volume, Intracorporeal urinary diversion, Meta-analysis, Robot-assisted radical cystectomy,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Management of non-metastatic castration-resistant prostate cancer (nmCRPC) has undergone a paradigm shift with next-generation androgen receptor inhibitors. However, direct comparative data are not available to inform treatment decisions and/or guideline recommendations. Therefore, we performed network meta-analysis to indirectly compare the efficacy and safety of currently available treatments. Multiple databases were searched for articles published before June 2020. Studies that compared overall and/or metastasis-free and/or prostate-specific antigen (PSA) progression-free survival (OS/MFS/PSA-PFS) and/or adverse events (AEs) in nmCRPC patients were considered eligible. Three studies (n = 4117) met our eligibility criteria. Formal network meta-analyses were conducted. For MFS, apalutamide, darolutamide, and enzalutamide were significantly more effective than placebo, and apalutamide emerged as the best option (P score: 0.8809). Apalutamide [hazard ratio (HR): 0.85, 95% credible interval (CrI): 0.77-0.94] and enzalutamide (HR: 0.86, 95% CrI: 0.78-0.95) were both significantly more effective than darolutamide. For PSA-PFS, all three agents were statistically superior to placebo, and apalutamide emerged as the likely preferred option (P score: 1.000). Apalutamide (HR: 0.71, 95% CrI: 0.69-0.74) and enzalutamide (HR: 0.76, 95% CrI: 0.74-0.79) were both significantly more effective than darolutamide. For AEs (including all AEs, grade 3 or grade 4 AEs, grade 5 AEs, and discontinuation rates), darolutamide was the likely best option. Apalutamide and enzalutamide appear to be more efficacious agents for therapy of nmCRPC, while darolutamide appears to have the most favorable tolerability profile. These findings may facilitate individualized treatment strategies and inform future direct comparative trials.
- Klíčová slova
- Apalutamide, Darolutamide, Enzalutamide, Network meta-analysis, Non-metastatic castration-resistant prostate cancer,
- MeSH
- antagonisté androgenních receptorů terapeutické užití MeSH
- antitumorózní látky terapeutické užití MeSH
- benzamidy MeSH
- doba přežití bez progrese choroby MeSH
- fenylthiohydantoin analogy a deriváty terapeutické užití MeSH
- kalikreiny metabolismus MeSH
- lidé MeSH
- nádory prostaty rezistentní na kastraci farmakoterapie mortalita patologie MeSH
- nitrily MeSH
- proporcionální rizikové modely MeSH
- prostatický specifický antigen metabolismus MeSH
- pyrazoly terapeutické užití MeSH
- síťová metaanalýza MeSH
- thiohydantoiny terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
- Názvy látek
- antagonisté androgenních receptorů MeSH
- antitumorózní látky MeSH
- apalutamide MeSH Prohlížeč
- benzamidy MeSH
- darolutamide MeSH Prohlížeč
- enzalutamide MeSH Prohlížeč
- fenylthiohydantoin MeSH
- kalikreiny MeSH
- KLK3 protein, human MeSH Prohlížeč
- nitrily MeSH
- prostatický specifický antigen MeSH
- pyrazoly MeSH
- thiohydantoiny MeSH
INTRODUCTION: This systematic review and meta-analysis aimed to assess the prognostic value of testosterone in patients with castration-resistant prostate cancer (CRPC). MATERIALS AND METHODS: PubMed, Web of Science, and Scopus databases were systematically searched until December 2019, according to the Preferred Reporting Items for Systemic Review and Meta-analysis statement. The endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: We identified 11 articles with 4206 patients for systematic review and nine articles with 4136 patients for meta-analysis. Higher testosterone levels were significantly associated with better OS (pooled HR 0.74, 95% CI 0.58-0.95) and better PFS (pooled HR 0.51, 95% CI 0.30-0.87). Subgroup analyses based on the treatment type revealed that higher testosterone levels were significantly associated with better OS in CRPC patients treated with androgen receptor-targeted agents (ARTAs) (pooled HR 0.64, 95% CI 0.55-0.75), but not in those treated with chemotherapy (pooled HR 0.78, 95% CI 0.53-1.14). CONCLUSION: This meta-analysis demonstrated that the PFS and OS were significantly greater in patients with CRPC in those with higher testosterone levels than that of those with lower testosterone levels. In the subgroup analyses, lower testosterone levels were a consistently poor prognostic factor for OS in patients treated with ARTAs, but not in those treated with chemotherapy. Therefore, higher testosterone levels could be a useful biomarker to identify patient subgroups in which ARTAs should be preferentially recommended in the CRPC setting.
- Klíčová slova
- Androgen receptor-targeted agents, Castration-resistant, Meta-analysis, Prostate cancer, Testosterone,
- MeSH
- androgenní receptory metabolismus MeSH
- lidé MeSH
- nádory prostaty rezistentní na kastraci krev farmakoterapie mortalita MeSH
- prognóza MeSH
- testosteron krev MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
- Názvy látek
- androgenní receptory MeSH
- AR protein, human MeSH Prohlížeč
- testosteron MeSH
This systematic review and meta-analysis aimed to assess the prognostic value of preoperative hematologic biomarkers in patients with urothelial carcinoma of the bladder treated with radical cystectomy. PUBMED, Web of Science, Cochrane Library, and Scopus databases were searched in September 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared cancer-specific survival in patients with urothelial carcinoma of the bladder with and without pretreatment laboratoryabnormalities. Formal meta-analyses were performed for this outcome. The systematic review identified 36 studies with 23,632 patients, of these, 32 studies with 22,224 patients were eligible for the meta-analysis. Several preoperative hematologic biomarkers were significantly associated with cancer-specific survival as follows: neutrophil - lymphocyte ratio (pooled hazard ratio [HR]: 1.20, 95% confidence interval [CI]: 1.11-1.29), hemoglobin (pooled HR: 0.87, 95% CI 0.82-0.94), C-reactive protein (pooled HR: 1.44, 95% CI 1.26-1.66), De Ritis ratio (pooled HR: 2.18, 95% CI 1.37-3.48), white blood cell count (pooled HR: 1.05, 95% CI 1.02-1.07), and albumin-globulin ratio (pooled HR: 0.26, 95% CI 0.14-0.48). Several pretreatment laboratory abnormalities in patients with urothelial carcinoma of the bladder were associated with cancer-specific mortality. Therefore, it might be useful to incorporate such hematologic biomarkers into prognostic tools for urothelial carcinoma of the bladder. However, given the study limitations including heterogeneity and retrospective nature of the primary data, the conclusions should be interpreted with caution.
- Klíčová slova
- Hematologic biomarker, Meta-analysis, Urothelial carcinoma of the bladder,
- MeSH
- biologické markery krev MeSH
- C-reaktivní protein analýza MeSH
- cystektomie metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfocyty patologie MeSH
- nádory močového měchýře krev mortalita chirurgie MeSH
- neutrofily patologie MeSH
- počet leukocytů MeSH
- počet trombocytů MeSH
- předoperační období MeSH
- prognóza MeSH
- proporcionální rizikové modely MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
- Názvy látek
- biologické markery MeSH
- C-reaktivní protein MeSH
The objectives of this study are to evaluate the available literature regarding the oncologic effect of neoadjuvant and adjuvant chemotherapy in the treatment of patients with clinically non-metastatic upper tract urothelial carcinoma (UTUC) and locally advanced UTUC. We searched PubMed, Cochrane Library, and Scopus databases in November 2019, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We included studies that compared patients with non-metastatic UTUC who received either neoadjuvant or adjuvant chemotherapy with patients who underwent surgery alone. Subgroup meta-analyses were also performed for studies that investigated only locally advanced UTUC. Overall, 36 studies were included in the review of which 22 studies and 15,378 patients were eligible for the meta-analysis. Neoadjuvant chemotherapy (NAC) was associated with higher rates of pathological downstaging (pDS) (RR 6.48, 95% CI 2.05-20.44, p = 0.001) and pathological complete response (RR 18.46, 95% CI 3.34-99.24, p = 0.001); and this was also proven in a subgroup analysis of studies that evaluated pDS in locally advanced UTUC (RR 3.18, 95% CI 2.0-5.07, p < 0.001). The association of NAC with overall survival (OS) and cancer-specific survival (CSS) was also statistically significant in all patients and in patients with locally advanced UTUC. Adjuvant chemotherapy (AC) was associated with improved metastasis-free survival (HR 0.65, 95% CI 0.55-0.76, p < 0.001) and CSS (HR 0.66, 95% CI 0.57-0.77, p < 0.001), which continued to be true for the patients with locally advanced UTUC. The association of AC with OS was only significant in patients with locally advanced UTUC. Perioperative chemotherapy might provide better survival outcomes in patients with clinically non-metastatic UTUC treated with radical nephroureterectomy. Neoadjuvant chemotherapy seems to have promising results, although high level of evidence is still lacking. Despite the low level, the body of evidence suggests a need for multimodal therapy of invasive UTUC.
- Klíčová slova
- Adjuvant, Chemotherapy, Neoadjuvant, Nephroureterectomy, Upper urinary tract urothelial carcinoma,
- MeSH
- adjuvantní chemoterapie MeSH
- karcinom z přechodných buněk farmakoterapie patologie chirurgie MeSH
- lidé MeSH
- nefroureterektomie MeSH
- neoadjuvantní terapie MeSH
- urologické nádory farmakoterapie patologie chirurgie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- srovnávací studie MeSH
- systematický přehled MeSH
PURPOSE: To assess the prognostic value of alkaline phosphatase in patients with hormone-sensitive prostate cancer. METHODS: A systematic review and meta-analysis was performed using the PUBMED, Web of Science, Cochrane Library, and Scopus in April 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared hormone-sensitive prostate cancer patients with high vs. low alkaline phosphatase to determine its predictive value for overall survival, cancer-specific survival, and progression-free survival. We performed a formal meta-analysis of these outcomes. RESULTS: 42 articles with 7938 patients were included in the systematic review and 28 studies with 5849 patients for the qualitative assessment. High alkaline phosphatase was associated with worse overall survival (pooled HR 1.72; 95% CI 1.37-2.14) and progression-free survival (pooled HR 1.30; 95% CI 1.10-1.54). In subgroup analyses of patients with "high-volume" and "low-volume", alkaline phosphatase was associated with the overall survival (pooled HR 1.41; 95% CI 1.21-1.64 and pooled HR 1.64; 95% CI, 1.06-2.52, respectively). CONCLUSIONS: In this meta-analysis, elevated serum levels of alkaline phosphatase were associated with an increased risk of overall mortality and disease progression in patients with hormone-sensitive prostate cancer. In contrast, those were not associated with an increased risk of cancer-specific mortality. Alkaline phosphatase was independently associated with overall survival in both patients with "high-volume" and "low-volume" hormone-sensitive prostate cancer. Alkaline phosphatase may be useful for being integrated into prognostic tools that help guide treatment strategy, thereby facilitating the shared decision making process.
- Klíčová slova
- Alkaline phosphatase (ALP), Hormone-sensitive prostate cancer (HSPC), Meta-analysis,
- MeSH
- alkalická fosfatasa krev metabolismus MeSH
- analýza přežití MeSH
- hormony metabolismus MeSH
- lidé MeSH
- nádorové biomarkery krev MeSH
- nádory prostaty mortalita MeSH
- prognóza MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
- Názvy látek
- alkalická fosfatasa MeSH
- hormony MeSH
- nádorové biomarkery MeSH
