BACKGROUND: There might be differential sensitivity to neoadjuvant chemotherapy (NAC) in patients with primary muscle-invasive bladder cancer (MIBC) in comparison to patients with secondary MIBC after a history of non-muscle-invasive disease. OBJECTIVE: To investigate pathologic response rates and survival associated with primary versus secondary MIBC among patients treated with cisplatin-based NAC for cT2-4N0M0 MIBC. DESIGN SETTING AND PARTICIPANTS: Oncologic outcomes were compared for 350 patients with primary MIBC and 64 with secondary MIBC treated with NAC and radical cystectomy between 1992 and 2021 at 11 academic centers. Genomic analyses were performed for 476 patients from the Memorial Sloan Kettering/The Cancer Genome Atlas cohort. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcome measures were pathologic objective response (pOR; ≤ypT1 N0), pathologic complete response (pCR; ypT0 N0), overall mortality, and cancer-specific mortality. RESULTS AND LIMITATIONS: The primary MIBC group had higher pOR (51% vs 34%; p = 0.02) and pCR (33% vs 17%; p = 0.01) rates in comparison to the secondary MIBC group. On multivariable logistic regression analysis, primary MIBC was independently associated with both pOR (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.26-0.87; p = 0.02) and pCR (OR 0.41, 95% CI 0.19-0.82; p = 0.02). However, on multivariable Cox regression analysis, primary MIBC was not associated with overall mortality (hazard ratio 1.70, 95% CI 0.84-3.44; p = 0.14) or cancer-specific mortality (hazard ratio 1.50, 95% CI 0.66-3.40; p = 0.3). Genomic analyses revealed a significantly higher ERCC2 mutation rate in primary MIBC than in secondary MIBC (12.4% vs 1.3%; p < 0.001). CONCLUSIONS: Patients with primary MIBC have better pathologic response rates to NAC in comparison to patients with secondary MIBC. Chemoresistance might be related to the different genomic profile of primary versus secondary MIBC. PATIENT SUMMARY: We investigated the treatment response to neoadjuvant chemotherapy (NAC; chemotherapy received before the primary course of treatment) and survival for patients with a primary diagnosis of muscle-invasive bladder cancer (MIBC) in comparison to patients with a history of non-muscle-invasive bladder cancer that progressed to MIBC. Patients with primary MIBC had a better response to NAC but this did not translate to better survival after accounting for other tumor characteristics.

• Klíčová slova
• Bladder cancer, Neoadjuvant chemotherapy, Primary, Response, Secondary, Survival,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Preoperative plasma levels of Interleukin 6 (IL6) and its soluble receptor (IL6sR) have previously been associated with oncologic outcomes in urothelial carcinoma of the bladder (UCB); however, external validation in patients treated with radical cystectomy (RC) for UCB is missing. PATIENTS/METHODS: We prospectively collected preoperative plasma from 1,036 consecutive patients at two institutes. These plasma specimens were assessed for levels of IL6 and IL6sR. Logistic and Cox regression analyses were used to assess the correlation of plasma levels with pathologic and survival outcomes. The additional clinical net benefits of preoperative IL6 and IL6sR were evaluated using decision curve analysis (DCA). RESULTS: Median IL6 and IL6sR plasma levels were significantly higher in patients with adverse pathologic features. Elevated biomarker levels were independently associated with an increased risk for lymph node metastasis and ≥ pT3 disease. Both biomarkers were independently associated with recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). The addition to, respectively, fitted pre- and postoperative prognostic models improved the predictive accuracy for lymph node metastasis, ≥ pT3 disease, RFS and CSS on DCA. INTERPRETATION: We confirmed that elevated preoperative plasma levels of IL6 and IL6sR levels are associated with worse oncological disease survival in patients treated with RC for UCB in a large multicenter study. Both biomarkers hold potential in identifying patients with adverse pathological features that may benefit from intensified/multimodal therapy and warrant inclusion into predictive/prognostic models. They demonstrated the ability to improve the discriminatory power of such models and thus guide clinical decision making.

• Klíčová slova
• Biomarker, Bladder cancer, Interleukin 6, Interleukin 6 soluble receptor, MIBC, Urothelial carcinoma,
• MeSH
• biologické markery metabolismus   MeSH
• cystektomie metody   MeSH
• interleukin-6 krev   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• multivariační analýza MeSH
• nádory močového měchýře krev   chirurgie   MeSH
• pooperační období MeSH
• předoperační období MeSH
• proporcionální rizikové modely MeSH
• prospektivní studie MeSH
• receptory interleukinu-6 krev   MeSH
• regresní analýza MeSH
• rozhodování MeSH
• senioři MeSH
• systémy pro podporu klinického rozhodování MeSH
• urotel patologie   chirurgie   MeSH
• výsledek terapie MeSH
• zánět MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• IL6 protein, human MeSH Prohlížeč
• IL6R protein, human MeSH Prohlížeč
• interleukin-6 MeSH
• receptory interleukinu-6 MeSH

Elevated preoperative plasma level of endoglin has been associated with worse oncologic outcomes in various malignancies. The present large-scale study aimed to determine the predictive and prognostic values of preoperative endoglin with regard to clinicopathologic and survival outcomes in patients treated with radical cystectomy (RC) for nonmetastatic urothelial carcinoma of the bladder (UCB). We prospectively collected preoperative blood samples from 1036 consecutive patients treated with RC for UCB. Logistic and Cox regression analyses were undertaken to assess the correlation of endoglin levels with pathologic and survival outcomes, respectively. The AUC and C-index were used to assess the discrimination. Patients with adverse pathologic features had significantly higher median preoperative endoglin plasma levels than their counterparts. Higher preoperative endoglin level was independently associated with an increased risk for lymph node metastasis, ≥pT3 disease, and nonorgan confined disease (NOCD; all p < 0.001). Plasma endoglin level was also independently associated with cancer-specific and overall survival in both pre- and postoperative models (all p < 0.05), as well as with recurrence-free survival (RFS) in the preoperative model (p < 0.001). The addition of endoglin to the preoperative standard model improved its discrimination for prediction of lymph node metastasis, ≥pT3 disease, NOCD, and RFS (differential increases in C-indices: 10%, 5%, 5.8%, and 4%, respectively). Preoperative plasma endoglin is associated with features of biologically and clinically aggressive UCB as well as survival outcomes. Therefore, it seems to hold the potential of identifying UCB patients who may benefit from intensified therapy in addition to RC such as extended lymphadenectomy or/and preoperative systemic therapy.

• Klíčová slova
• biomarker, bladder cancer, endoglin, radical cystectomy,
• MeSH
• analýza přežití MeSH
• cystektomie MeSH
• endoglin krev   MeSH
• karcinom z přechodných buněk krev   patologie   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfadenektomie MeSH
• nádorové biomarkery krev   MeSH
• nádory močového měchýře krev   patologie   chirurgie   MeSH
• předoperační období MeSH
• prognóza MeSH
• prospektivní studie MeSH
• regulace genové exprese u nádorů MeSH
• senioři MeSH
• staging nádorů 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
• práce podpořená grantem MeSH
• Názvy látek
• endoglin MeSH
• ENG protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH

PURPOSE: We assessed the prognostic value of systemic immune-inflammation index (SII) to refine risk stratification of the heterogeneous spectrum of patients with non-muscle-invasive bladder cancer (NMIBC) METHODS: In this multi-institutional cohort, preoperative blood-based SII was retrospectively assessed in 1117 patients with NMIBC who underwent transurethral resection of bladder (TURB) between 1996 and 2007. The optimal cut-off value of SII was determined as 580 using the best Youden index. Cox regression analyses were performed. The concordance index (C-index) and decision curve analysis (DCA) were used to assess the discrimination of the predictive models. RESULTS: Overall, 309 (28%) patients had high SII. On multivariable analyses, high SII was significantly associated with worse PFS (hazard ratio [HR] 1.84; 95% confidence interval [CI] 1.23-2.77; P = 0.003) and CSS (HR 2.53; 95% CI 1.42-4.48; P = 0.001). Subgroup analyses, according to the European Association of Urology guidelines, demonstrated the main prognostic impact of high SII, with regards to PFS (HR 3.39; 95%CI 1.57-7.31; P = 0.002) and CSS (HR 4.93; 95% CI 1.70-14.3; P = 0.005), in patients with intermediate-risk group; addition of SII to the standard predictive model improved its discrimination ability both on C-index (6% and 12%, respectively) and DCA. In exploratory intergroup analyses of patients with intermediate-risk, the improved discrimination ability was retained the prediction of PFS and CSS. CONCLUSION: Preoperative SII seems to identify NMIBC patients who have a worse disease and prognosis. Such easily available and cheap standard biomarkers may help refine the decision-making process regarding adjuvant treatment in patients with intermediate-risk NMIBC.

• Klíčová slova
• Biomarker, Intermediate-risk, NMIBC, SII, Survival,
• MeSH
• hodnocení rizik MeSH
• invazivní růst nádoru MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory močového měchýře komplikace   imunologie   patologie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři MeSH
• zánět etiologie   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

PURPOSE: To investigate the prognostic value of preoperative serum albumin to globulin ratio (AGR) in patients with non-muscle-invasive bladder cancer (NMIBC) treated with transurethral resection of bladder tumor (TURB) with or without intravesical therapy (IVT). MATERIALS AND METHODS: We retrospectively reviewed 1,096 consecutive patients with NMIBC. Levels of albumin and globulin were obtained before TURB and used to calculate the preoperative AGR level. Multivariable Cox regression analyses were performed to assess the prognostic effect of preoperative AGR on oncologic outcomes. Subgroup analyses were performed in patients based on the European Association of Urology (EAU) risk groups for NMIBC. RESULTS: Low AGR levels were observed in 389 (35.5%) patients. The median follow-up was 63.7 months (IQR 25.3-111). On multivariable Cox regression analysis, low AGR was associated with increased risk of progression to muscle-invasive BCa (MIBC) (HR 1.81, 95% CI 1.22-2.68, P = 0.003). The addition of AGR only minimally improved the discrimination ability of a base model that included established clinicopathologic features (C-index = 0.7354 vs. C-index = 0.7162). Low preoperative AGR was not significantly associated with the risk of disease recurrence (P = 0.31). In subgroup analyses based on patients' EAU risk groups, low preoperative AGR was not associated with recurrence-free survival (RFS) (P = 0.59) or progression-free survival (PFS) (P = 0.22) in any of the risk groups. Additionally, in patients treated with Bacillus Calmette-Guerin (BCG) for intermediate- or high-risk NMIBC, low AGR failed to predict disease recurrence or progression. CONCLUSION: Preoperative serum AGR levels independently predicted the risk of disease progression in patients with NMIBC. However, it was not found to be associated with either RFS or PFS in NMIBC patients based on their EAU risk group. This marker seems to have a limited role in NMIBC at the present time. However, further research is needed to investigate this marker in combination with other systemic inflammatory markers to help improve prediction in this heterogeneous group of patients.

• Klíčová slova
• AGR, Albumin, BCG, Bladder cancer, Globulin, Non-muscle-invasive, Progression,
• MeSH
• cystektomie * metody   MeSH
• invazivní růst nádoru MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory močového měchýře krev   patologie   chirurgie   MeSH
• předoperační období MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři MeSH
• sérové globuliny analýza   MeSH
• sérový albumin analýza   MeSH
• uretra MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• sérové globuliny MeSH
• sérový albumin MeSH

BACKGROUND: Radical cystectomy (RC) is the standard treatment for muscle invasive bladder cancer, but approximately half of all patients will ultimately succumb to disease progression despite apparent cure with extirpative surgery. Elderly patients are at especially high risk of advanced disease and may benefit from perioperative systemic therapy. OBJECTIVE: To assess the real-world benefit of adjuvant chemotherapy (AC) in patients ≥75 years old. METHODS: We retrospectively reviewed patients who underwent RC for non-metastatic urothelial carcinoma of the bladder (UCB) from 12 participating international medical institutions. Kaplan-Meier survival curves and Cox regression models were used to assess the association between age groups, administration of AC and oncological outcome parameters such as recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS: 4,335 patients were included in the analyses, of which 820 (18.9%) were ≥75 years old. These elderly patients had a higher rate of adverse pathologic features. In an univariable subgroup analysis in patients ≥75 years with lymph node metastasis, 5-year OS was significantly higher in patients who had received AC (41% vs. 30.9%, p = 0.02). In a multivariable Cox model that was adjusted for several established outcome predictors, there was a significant favorable association between the administration of AC in elderly patients and OS, but no RFS or CSS. CONCLUSIONS: In this large observational study, the administration of AC was associated with improved OS, but not RFS or CSS, in elderly patients treated with RC for UCB. This is of clinical importance, as elderly patients are more likely to have adverse pathologic features and experience worse survival outcomes. Treatment of UCB should include both a multidisciplinary approach and a geriatric evaluation to identify patients who are most likely to tolerate and benefit from AC.

• Klíčová slova
• MIBC, NMIBC, adjuvant chemotherapy, bladder cancer, elderly, systemic therapy, transitional cell carcinoma,
• Publikační typ
• časopisecké články MeSH

PURPOSE: The Plasminogen Activation System (PAS) plays a role in tumor growth, invasion and metastasis and has been associated with oncological outcomes in urinary bladder carcinoma (UBC). The use of the different components of this system as molecular markers could improve our understanding of the heterogeneous behavior of UBC and might enable earlier disease detection, individual risk stratification, more accurate outcome prediction and be a rationale for new targeted therapies. METHODS: A comprehensive literature search including relevant articles up to October 2020 was performed using the MEDLINE/PubMed database. RESULTS: The components of the PAS axis are involved in tumor progression through their signaling processes during angiogenesis, cell migration, metastasis and adhesion. The body of evidence shows an association of PAS component overexpression with adverse pathological features and clinical outcome in UBC. Overexpressed PAS components correlate with a higher pathological tumor grade and advanced tumor stage. In non-muscle-invasive bladder cancer (NMIBC), the PAS components were associated with disease outcome while in muscle-invasive bladder cancer (MIBC), it was associated with disease outcome and pathological features. Possible therapeutic approaches in the PAS for the treatment of UBC have only been sparsely investigated in in vitro and in vivo studies. Intravesical plasminogen activator inhibitor 1 (PAI-1) instillation in animal models yielded interesting results and warrant further exploration in Phase II studies. CONCLUSION: The overexpression of PAS components in UBC tumor tissue is associated with adverse pathological features and worse oncological outcomes. These findings are mainly based on preclinical studies and retrospective series, which requires further prospective studies to translate the PAS into clinically useful biomarkers and therapeutic targets.

• Klíčová slova
• PAI, review, therapy, uPA, uPAR, urothelial cancer,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH