Despite currently used intravesical therapies in non-muscle-invasive bladder cancer (NMIBC), the rate of intravesical recurrence remains very high. We aimed to evaluate the effectiveness of adding nonintravesical interventions to standard intravesical therapies to prevent intravesical recurrence. In April 2024, 3 databases were queried for prospective studies evaluating nonintravesical interventions in addition to standard intravesical therapies for NMIBC (CRD42024490988). The primary outcome was intravesical recurrence-free survival (iRFS). Standard pairwise meta-analyses were performed using hazard ratios (HR) and 95% confidence intervals (95% CI) with a random-effects model. We identified 18 eligible studies (14 RCTs and 4 prospective trials) comprising 4,593 NMIBC patients, which investigated pharmacological interventions (eg, selenium, vitamins, Lactobacillus casei, celecoxib, metformin, mistletoe lectin) and lifestyle modifications (diet). The addition of Lactobacillus casei significantly improved iRFS (HR: 0.50; 95% CI: 0.34-0.73; P < .001). A high western diet pattern significantly worsened iRFS (HR:1.48, 95%CI:1.06-2.06, P = .03). The other nonintravesical interventions were not associated with iRFS. Our comprehensive review of the published literature highlights the need for further research into the efficacy of nonvesical interventions for NMIBC. While Lactobacillus was shown to improve iRFS in 2 RCTs, additional high-quality randomized studies are required to evaluate the effectiveness of other interventions.
- Klíčová slova
- Celecoxib, Diet, Lactobacillus casei, Non-muscle-invasive bladder cancer, Vitamins,
- MeSH
- aplikace intravezikální MeSH
- celekoxib aplikace a dávkování terapeutické užití MeSH
- Lactobacillus casei MeSH
- lidé MeSH
- lokální recidiva nádoru * prevence a kontrola MeSH
- metformin terapeutické užití aplikace a dávkování MeSH
- nádory močového měchýře * patologie farmakoterapie MeSH
- probiotika aplikace a dávkování terapeutické užití MeSH
- randomizované kontrolované studie jako téma MeSH
- selen aplikace a dávkování terapeutické užití MeSH
- vitaminy aplikace a dávkování terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
- Názvy látek
- celekoxib MeSH
- metformin MeSH
- selen MeSH
- vitaminy MeSH
BACKGROUND: Androgen-receptor signaling inhibitors (ARSIs) significantly improve survival in systemic therapy for advanced/metastatic prostate cancer (PCa) patients; however possible central nervous system (CNS) toxicity is an unaddressed concern. We aimed to assess and compare the incidence of CNS-related adverse events (AEs) secondary to the treatment of PCa patients with different ARSIs. MATERIALS: In August 2023, a comprehensive seach was conducted in three databases for randomized controlled trials (RCTs) of PCa patients receiving ARSIs plus ADT. The primary endpoints included mental impairment, cognitive impairment, seizure, fatigue, and falls. RESULTS: Twenty-six RCTs, comprising 20,328 patients, were included in meta-analyses and network meta-analyses (NMAs). ARSIs increased the risk of mental impairment (RR: 1.72; 95% CI, 1.09-2.71), cognitive impairment (RR: 2.25; 95% CI, 1.78-2.86), seizure (RR: 2.20, 95% CI, 1.09-4.45), fatigue (RR: 1.31, 95% CI, 1.20-1.43), and falls (RR: 2.07, 95% CI, 1.60-2.67) compared to standard of care (SOC). Based on NMAs, Enzalutamide showed a significant increase in risk for all assessed CNS-related AEs, while Abiraterone demonstrated significant risk increases in cognitive impairment, fatigue, and falls. Conversely, Darolutamide did not exhibit significant increases in risk for any CNS-related AEs, except for fatigue. CONCLUSIONS: The addition of ARSIs to ADT increased all examined CNS-related AEs compared to SOC. Each ARSI is associated with a distinct profile of CNS-related AEs. Careful patient selection and monitoring for CNS sequelae is necessary to achieve the best quality of life in patients on ARSI + ADT for PCa.
- Klíčová slova
- ARSI, Central Nervous System, Meta-analysis, Network Meta-analysis, Prostate Cancer,
- MeSH
- antagonisté androgenních receptorů * škodlivé účinky MeSH
- lidé MeSH
- nádory prostaty * farmakoterapie MeSH
- nemoci centrálního nervového systému * chemicky indukované epidemiologie MeSH
- randomizované kontrolované studie jako téma MeSH
- síťová metaanalýza MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
- Názvy látek
- antagonisté androgenních receptorů * MeSH
Although immune checkpoint inhibitors (ICI) and/or tyrosine kinase inhibitors (TKI) are the standard treatment of advanced unresectable or metastatic renal cell carcinoma (RCC), the impact of concomitant medications remains unclear. We aimed to evaluate the impact of concomitant medications on survival outcomes in patients treated with systemic therapy for advanced unresectable or metastatic RCC. In August 2024, PubMed, Scopus, and Web of Science were queried for studies evaluating concomitant medications in patients with advanced unresectable or metastatic RCC (PROSPERO: CRD42024573252). The primary outcome was overall survival (OS). A fixed- or random-effects model was used for meta-analysis according to heterogeneity. We identified 22 eligible studies (5 prospective and 17 retrospective) comprising 16,072 patients. Concomitant medications included proton pump inhibitors (PPI) (n = 3959), antibiotics (n = 571), statins (n = 5466), renin-angiotensin system inhibitors (RASi) (n = 6615), and beta-blockers (n = 1964). Both concomitant PPI and antibiotics were significantly associated with worse OS in patients treated with ICI (PPI: HR: 1.22, P = .01, and antibiotics: HR: 2.09, P < .001). Concomitant statins, RASi, or beta-blocker were significantly associated with improved OS in patients treated with TKI (statins: HR: 0.81, P = .03, RASi: HR: 0.63, P < .001, beta-blocker: HR: 0.69, P < .001, respectively). In patients treated with ICI, RASi was significantly associated with improved OS (HR: 0.64, P = .02). Concomitant use of antibiotics or PPI with ICI can reduce its oncologic efficacy. Conversely, concomitant statins, RASi, or beta-blockers can enhance the oncologic efficacy of TKI. When initiating systemic therapy for metastatic RCC, it may be important for clinicians to assess baseline co-medications and recognize their possible positive or negative effects.
- Klíčová slova
- Chemotherapy, Concomitant medications metastatic renal cell carcinoma, Immune checkpoint inhibitors,
- MeSH
- analýza přežití MeSH
- beta blokátory terapeutické užití MeSH
- inhibitory kontrolních bodů terapeutické užití MeSH
- inhibitory proteinkinas terapeutické užití MeSH
- inhibitory protonové pumpy terapeutické užití aplikace a dávkování MeSH
- karcinom z renálních buněk * farmakoterapie mortalita sekundární MeSH
- lékové interakce MeSH
- lidé MeSH
- nádory ledvin * farmakoterapie mortalita patologie MeSH
- statiny terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
- Názvy látek
- beta blokátory MeSH
- inhibitory kontrolních bodů MeSH
- inhibitory proteinkinas MeSH
- inhibitory protonové pumpy MeSH
- statiny MeSH
OBJECTIVE: Sparse data exist on the impact of upper urinary tract (UUT) decompression on the risk of UUT recurrence in patients with bladder cancer (BCa). This study aims to evaluate whether Double J stenting (DJS) can increase the risk of UUT recurrence compared to percutaneous nephrostomy (PCN) placement. MATERIALS AND METHODS: We retrospectively analyzed data from 1550 patients with cTa-T3NanyM0 BCa who underwent radical cystectomy (RC) between at 12 tertiary care centers (1990-2020). Patients with complete follow-up, no prior history of UUT cancer, and who required UUT decompression for preoperative hydronephrosis were selected. Hydronephrosis grade was defined according to established scoring systems. UUT recurrence was diagnosed through imaging, urinary cytology, and confirmed by selective cytology and ureteroscopy when possible. Propensity scores were computed to determine overlap weights and balance groups. Kaplan-Meier analyses estimated UUT recurrence-free survival (RFS), cancer-specific (CSS), and overall survival (OS) before and after weighting. Cox regression analyses before and after weighting were fitted to predict UUT recurrence. RESULTS: Of 524 included patients, 132 (25%) and 392 (75%) patients were managed with DJS and PCN placement, respectively. Patients who received PCN had higher grade (≥ 3) of obstruction (34% vs. 14%) and pT3-4 tumors (70% vs. 36%) than patients with DJS. During a median follow-up of 19 months, 2-years UUT-RFS did not differ between groups (95% for PCN vs 92% for DJS, weighted HR 1.41, 95% CI, 0.55-3.59). There was no difference in 2-years weighted CSS (74% vs. 74%) and OS (67% vs 69%). Main limitations were the short follow-up and inclusion of patients uniquely undergoing RC. CONCLUSIONS: These results suggest that ureteral DJS does not increase the risk of developing UUT recurrence in BCa patients with hydronephrosis requiring UUT decompression. However, UUT recurrence was rare, and associations were weak, with findings susceptible to bias. Randomized trials are needed to validate these results.
- Klíčová slova
- Double J, Hydronephrosis, Radical cystectomy, UUT recurrence, percutaneous nephrostomy,
- MeSH
- cystektomie MeSH
- hydronefróza etiologie MeSH
- karcinom z přechodných buněk chirurgie patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory močového měchýře * chirurgie patologie MeSH
- nádory močovodu chirurgie patologie MeSH
- následné studie MeSH
- perkutánní nefrostomie MeSH
- retrospektivní studie MeSH
- sekundární malignity chirurgie patologie MeSH
- senioři MeSH
- stenty * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: We evaluate the predictive and prognostic value of insulin-like growth factor-I (IGF-1), IGF binding protein-2 (IGFBP-2) and -3 (IGFBP-3) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: This is a retrospective analysis of a multi-institutional database comprising 753 patients who underwent RNU for UTUC and had a preoperative plasma available. Logistic and Cox regression analyses were performed. The discriminative ability and clinical utility of the models was calculated using the lasso regression test, area under receiver operating characteristics curves, C-index, and decision curve analysis (DCA). RESULTS: Lower preoperative plasma levels of IGFBP-2 and -3 independently correlated with increased risks of lymph node metastasis, pT3/4 disease, nonorgan confined disease, and worse recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) (all P ≤ .004). The addition of both IGFBP-2 and -3 to a postoperative multivariable model, that included standard clinicopathologic characteristics, improved the model's concordance index by 10%, 9%, and 8% for RFS, CSS, and OS, respectively. On DCA, addition of both IGFBP-2 and -3 to base models improved their performance for RFS, CSS, and OS by a statistically and clinically significant margin. Plasma IGF-1 was not associated with any of outcomes. CONCLUSIONS: We confirmed that a lower plasma levels of IGFBP-2 and -3 both are independent and clinically significant predictors of adverse pathological features and survival outcomes in UTUC patients treated with RNU. These findings might help guide the clinical decision-making regarding perioperative systemic therapy and follow-up scheduling.
- Klíčová slova
- IGF-1, IGFBP-2, IGFBP-3, Upper tract, Urothelial carcinoma,
- MeSH
- hodnocení rizik metody MeSH
- IGFBP-3 krev MeSH
- insulinu podobný růstový faktor I * metabolismus MeSH
- karcinom z přechodných buněk chirurgie krev patologie mortalita MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery krev MeSH
- nefroureterektomie * metody MeSH
- peptidy podobné insulinu MeSH
- předoperační období MeSH
- prognóza MeSH
- protein 2 vázající insulinu podobné růstové faktory * krev MeSH
- retrospektivní studie MeSH
- senioři MeSH
- urologické nádory chirurgie krev patologie mortalita MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Názvy látek
- IGF1 protein, human MeSH Prohlížeč
- IGFBP-3 MeSH
- IGFBP2 protein, human MeSH Prohlížeč
- IGFBP3 protein, human MeSH Prohlížeč
- insulinu podobný růstový faktor I * MeSH
- nádorové biomarkery MeSH
- peptidy podobné insulinu MeSH
- protein 2 vázající insulinu podobné růstové faktory * MeSH
INTRODUCTION AND OBJECTIVES: We examined the impact of preoperative plasma potassium levels (PPLs) on outcomes in patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB), hypothesizing that potassium imbalances might influence outcomes. PATIENTS AND METHODS: In this retrospective study, 501 UCB patients undergoing RC from 2009 to 2017 at a tertiary center were analyzed. Blood samples collected a week prior to surgery defined normal and abnormal PPL based on institutional standards. We assessed overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), postoperative complications, 30-day mortality, and non-organ confined disease. Kaplan-Meier estimates, Cox proportional hazards, logistic regression, and decision curve analyses (DCA) were employed. RESULTS: 63 (13%) patients had abnormal preoperative PPLs, with 50 (10%) elevated and 13 (2.5%) decreased. In a 59 months median follow-up, 152 (31%) had disease recurrence, 197 (39%) died from any cause, and 119 (24%) from UCB. Multivariable cox regression analyses adjusting for perioperative parameters demonstrated abnormal PPL was associated with worse OS (HR=1.9, P=0.009), CSS (HR=2.8, P<0.001) and RFS (HR=2.1; P=0.007). Elevated preoperative PPLs also demonstrated significant associations with adverse outcomes in OS, CSS, and RFS (all P<0.05). In multivariable logistic regression analyses, abnormal and elevated PPLs were not associated with 30-day mortality, major 30-day postoperative complications, positive nodal disease, pT3/4 stage, and non-organ confined disease (all P>0.05). CONCLUSION: Abnormal and elevated preoperative PPLs correlate with adverse oncologic outcomes in UCB patients treated with RC. Pending external validation, preoperative PPLs might be a cost-effective, easily obtainable supplemental biomarker for enriching accuracy of outcome prediction in this highly variable maladie.
- Klíčová slova
- Bilateral pelvic lymph node dissection, Electrolyte disorder, Oncologic outcome, Urothelial bladder cancer,
- MeSH
- cystektomie * mortalita MeSH
- draslík * krev MeSH
- karcinom z přechodných buněk chirurgie mortalita krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru krev mortalita MeSH
- nádory močového měchýře * chirurgie mortalita krev MeSH
- pooperační komplikace * mortalita epidemiologie krev MeSH
- předoperační období * MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- draslík * MeSH
BACKGROUND: We aimed to assess the prognostic value of tumor infiltrating lymphocytes (TILs) in patients with bladder cancer (BC) after radical cystectomy (RC). MATERIALS AND METHODS: We searched Pubmed, Web of Science and Scopus in April 2022 to identify studies assessing the prognostic value of TILs, including a subset of lymphocytes (eg, CD3, CD8, FOXP3), after RC. The endpoints were overall survival and recurrent free survival. Subgroup analyses were performed based on the evaluation method for TILs (ie, CD3, CD8, FOXP3, HE staining). RESULTS: Overall, 9 studies comprising 1413 patients were included in this meta-analysis. The meta-analysis revealed that elevated expressions of TILs were significantly associated with favorable OS (pooled hazard ratio [HR]: 0.65, 95% confidence interval [CI]: 0.51-0.83) and RFS (pooled HR: 0.48, 95% CI: 0.35-0.64). In subgroup analyses, high CD8+ TILs were also associated with favorable OS (HR: 0.51, 95% CI: 0.33-0.80) and RFS (pooled HR: 0.53, 95% CI: 0.36-0.76). Among 3 studies comprising 146 patients, high intratumoral TILs were significantly associated with favorable OS (pooled HR: 0.34, 95% CI: 0.19-0.60). CONCLUSION: TILs are useful prognostic markers in patients treated with RC for BC. Although the prognostic value of TILs is varied, depending on the subset and infiltration site, CD8+ TILs and intratumoral TILs are associated with oncologic outcomes. Further studies are warranted to explicate the predictive value of TILs on the response to perioperative systemic therapy to help clinical decision-making in patients with BC.
- Klíčová slova
- MIBC, TIL,
- MeSH
- cystektomie MeSH
- forkhead transkripční faktory metabolismus MeSH
- lidé MeSH
- nádory močového měchýře * patologie MeSH
- prognóza MeSH
- tumor infiltrující lymfocyty * metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- systematický přehled MeSH
- Názvy látek
- forkhead transkripční faktory MeSH
BACKGROUND: Systemic treatment with immune combinations is the gold standard for metastatic renal cell carcinoma (mRCC) worldwide. The systemic immune-inflammation index (SII) is a prognostic marker for several types of malignant neoplasms, including mRCC, in the era of tyrosine kinase inhibitor (TKI) treatment. Data regarding the prognostic value of the SII in patients with mRCC treated with immunotherapy are scarce and controversial. METHODS: We retrospectively collected the data of patients with mRCC from 56 centers in 18 countries. SII (Platelet × Neutrophil/Lymphocyte count) was calculated prior to the first systemic treatment and cut-off was defined by a survival receiver operating characteristic (ROC) analysis. The primary objective of our retrospective study was to assess the outcomes of patients treated with first-line immunotherapy. RESULTS: Data from 1034 mRCC patients was collected and included in this analysis. The SII cut-off value was 1265. After a follow-up of 26.7 months, and the overall survival (OS) and progression-free survival (PFS) were 39.8 and 15.7 months, respectively. According to SII (low vs. high), patients with low-SII had longer OS (55.7 vs. 22.2 months, P < .001), better PFS (20.8 vs. 8.5 months, P < .001), and higher overall response rate (52 vs. 37%, P = .033). CONCLUSION: A high SII is associated with poor oncological outcomes in patients with mRCC. SII could be an easily accessible prognostic indicator for use in clinical practice.
- Klíčová slova
- Immune checkpoint inhibitors, Prognostic biomarker,
- MeSH
- analýza přežití MeSH
- karcinom z renálních buněk * patologie MeSH
- lidé MeSH
- nádory ledvin * patologie MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- zánět patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: In the era of standardized outcome reporting, it remains unclear if widely used comorbidity and health status indices can enhance predictive accuracy for morbidity and long-term survival outcomes after radical cystectomy (RC). PATIENTS AND METHODS: In this monocentric study, we included 468 patients undergoing open RC with pelvic lymph node dissection for bladder cancer between January 2009 and December 2017. Postoperative complications were meticulously assessed according to the EAU guideline criteria for standardized outcome reporting. Multivariable regression models were fitted to evaluate the ability of ASA physical status (ASA PS), Charlson comorbidity index (± age-adjustment) and the combination of both to improve prediction of (A) 30-day morbidity key estimates (major complications, readmission, and cumulative morbidity as measured by the Comprehensive Complication index [CCI]) and (B) secondary mortality endpoints (overall [OM], cancer-specific [CSM], and other-cause mortality [OCM]). RESULTS: Overall, 465 (99%) and 52 (11%) patients experienced 30-day complications and major complications (Clavien-Dindo grade ≥IIIb), respectively. Thirty-seven (7.9%) were readmitted within 30 days after discharge. Comorbidity and health status indices did not improve the predictive accuracy for 30-day major complications and 30-day readmission of a reference model but were associated with 30-day CCI (all P < .05). When ASA PS and age-adjusted Charlson index were combined, ASA PS was no longer associated with 30-day CCI (P = .1). At a median follow-up of 56 months (IQR 37-86), OM, CSM, and 90-day mortality were 37%, 24%, and 2.9%, respectively. Both Charlson and age-adjusted Charlson index accurately predicted OCM (all P < .001) and OM (all P ≤ .002) but not CSM (all P ≥ .4) and 90-day mortality (all P > .05). ASA PS was not associated with oncologic outcomes (all P ≥ .05). CONCLUSION: While comorbidity and health status indices have a role in predicting OCM and OM after RC, their importance in predicting postoperative morbidity is limited. Especially ASA PS performed poorly. This highlights the need for procedure-specific comorbidity assessment rather than generic indices.
- Klíčová slova
- ASA physical status, Charlson Comorbidity index, Comorbidity indices, Mortality, Urinary Bladder Neoplasms,
- MeSH
- cystektomie * škodlivé účinky MeSH
- komorbidita MeSH
- lidé MeSH
- morbidita MeSH
- nádory močového měchýře * patologie MeSH
- pooperační komplikace etiologie MeSH
- retrospektivní studie MeSH
- ukazatele zdravotního stavu MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Obesity has been associated with improved response to immunotherapy in cancer patients. We investigated the role of body mass index (BMI) in patients from the ARON-1 study (NCT05287464) treated by dual immuno-oncology agents (IO+IO) or a combination of immuno-oncology drug and a tyrosine kinase inhibitors (TKI) as first-line therapy for metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Medical records of patients with documented mRCC treated by immuno-oncology combinations were reviewed at 47 institutions from 16 countries. Patients were assessed for overall survival (OS), progression-free survival (OS), and overall clinical benefit (OCB), defined as the sum of the rate of partial/complete responses and stable disease. Univariate and multivariate analyses were used to explore the association of variables of interest with survival. RESULTS: A total of 675 patients were included; BMI was >25 kg/m2 in 345 patients (51%) and was associated with improved OS (55.7 vs. 28.4 months, P < .001). The OCB of patients with BMI >25 kg/m2 versus those with BMI ≤25 kg/m2 was significantly higher only in patients with nonclear cell histology (81% vs. 65%, P = .011), and patients with liver metastases (76% vs. 58%, P = .007), Neutrophil to lymphocyte ratio >4 (77% vs 62%, P = .022) or treated by nivolumab plus ipilimumab (77% vs. 64%, P = .044). In the BMI ≤25 kg/m2 subgroup, significant differences were found between patients with NLR >4 versus ≤4 (62% vs. 82%, P = .002) and patients treated by IO+IO versus IO+TKIs combinations (64% vs. 83%, P = .002). CONCLUSION: Our study suggests that the prognostic significance and the association of BMI with treatment outcome varies across clinico-pathological mRCC subgroups.
- Klíčová slova
- Immunocombo, Immunotherapy, NCT05287464, Obesity, Survival, Tumor Response, mRCC,
- MeSH
- index tělesné hmotnosti MeSH
- inhibitory proteinkinas terapeutické užití MeSH
- karcinom z renálních buněk * patologie MeSH
- lidé MeSH
- nádory ledvin * patologie MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- inhibitory proteinkinas MeSH