BACKGROUND: The aim of this study is to investigate the differential stage-dependent outcomes of patients undergoing radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC). METHODS: We performed a retrospective analysis of 1422 patients with cT2-4N0 MIBC treated with RC, with/without cisplatin-based NAC, from our multicenter cooperation program (treated period: 1992-2021). Patients were stratified according to their pathologic stage at RC. Cancer-specific survival (CSS) and overall survival (OS) were calculated using mixed-effects Cox analysis. RESULTS: Analysis was conducted on 761 patients treated with NAC followed by RC and 661 treated with RC only (median follow-up 19 months). Of 337 (24%) patients who died, 259 (18%) died of bladder cancer. On univariable analyses, increased pathologic stage was significantly associated with worse CSS (HR=1.59, 95% CI 1.46-1.73; P<0.01) and OS (HR=1.58, 95% CI 1.47-1.71; P<0.001). On multivariable mixed-effects model, patients after RC only had significantly worse CSS with stage pT≥3/N1-3 and OS with stage pT≥2/N0-3 compared to those with stage pT≤1N0. Patients after RC and NAC had significantly worse CSS and OS already at stage ypT≥2/N0-3 compared to those with ypT≤1N0. On subgroup analyses, CSS (HR=4.26; 95% CI 2.03-8.95; P<0.001) but not OS (HR=1.1; 95% CI 0.5-2.4; P=0.81) was worse for pT2N0 patients after NAC versus no-NAC. This difference was not maintained on multivariable analysis. CONCLUSIONS: NAC improves pathologic stage at the time of RC. Patients with residual MIBC after NAC have worse survival outcomes compared to those with the same pathologic stage who did not receive NAC, suggesting a need for better adjuvant therapy in these patients.
PURPOSE: We investigated the pathological response rates and survival associated with 3 vs 4 cycles of cisplatin-based neoadjuvant chemotherapy (NAC) in patients with cT2-4N0M0 muscle invasive bladder cancer. MATERIALS AND METHODS: In this cohort study we analyzed clinical data of 828 patients treated with NAC and radical cystectomy between 2000 and 2020. A total of 384 and 444 patients were treated with 3 and 4 cycles of NAC, respectively. Pathological objective response (pOR; ypT0-Ta-Tis-T1 N0), pathological complete response (pCR; ypT0 N0), cancer-specific survival and overall survival were investigated. RESULTS: pOR and pCR were achieved in 378 (45%; 95% CI 42, 49) and 207 (25%; 95% CI 22, 28) patients, respectively. Patients treated with 4 cycles of NAC had higher pOR (49% vs 42%, p=0.03) and pCR (28% vs 21%, p=0.02) rates compared to those treated with 3 cycles. This effect was confirmed on multivariable logistic regression analysis (pOR OR 1.46 p=0.008, pCR OR 1.57, p=0.007). On multivariable Cox regression analysis, 4 cycles of NAC were significantly associated with overall survival (HR 0.68; 95% CI 0.49, 0.94; p=0.02) but not with cancer-specific survival (HR 0.72; 95% CI 0.50, 1.04; p=0.08). CONCLUSIONS: Four cycles of NAC achieved better pathological response and survival compared to 3 cycles. These findings may aid clinicians in counseling patients and serve as a benchmark for prospective trials. Prospective validation of these findings and assessment of cumulative toxicity derived from an increased number of cycles are needed.
- MeSH
- cystektomie MeSH
- invazivní růst nádoru MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- nádory močového měchýře farmakoterapie mortalita patologie chirurgie MeSH
- neoadjuvantní terapie statistika a číselné údaje 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
- multicentrická studie MeSH
BACKGROUND: To date it is unknown whether renal vs. ureteral urothelial carcinoma affects the type and the distribution of metastatic sites, and whether survival differs according to renal vs. ureteral location in metastatic patients. METHODS: Two datasets were used, namely Surveillance, Epidemiology and End Results (SEER) and National Inpatients Sample (NIS). Multivariable logistic regression models tested whether renal pelvis vs. ureteral location predicts site-specific metastases. Kaplan-Meier plots and multivariable Cox regression models (CRMs) tested overall mortality (OM) according to renal pelvis vs. ureteral location. RESULTS: In SEER (2010-2016), 623 (71.1%) metastatic renal pelvis urothelial carcinoma (RPUC) vs. 253 (28.9%) ureteral urothelial carcinoma (UUC) patients were identified. Patients with RPUC more frequently harbored lung (46.1% vs. 35.2%, P < 0.01; Odds ratio [OR]: 1.57, P < 0.01), but less frequently liver metastases (27.9% vs. 36.4%, P = 0.02; OR:0.66, P = 0.01). In RPUC, lung, liver, bone, and brain metastases independently predicted higher OM. Only liver metastases independently predicted higher OM in UUC. In NIS (2005-2015), 818 (61.0%) RPUC vs. 522 (39.0%) UUC patients were identified. Patients with RPUC more frequently harbored lung (34.0% vs. 17.2%, P < 0.001; OR:2.36, P < 0.001), as well as brain (4.4% vs. 1.9%, P = 0.02; OR:2.00, P = 0.049) metastases, but less frequently harbored retroperitoneal and/or peritoneal (12.3% vs. 21.8%, P < 0.001; OR:0.51, P < 0.001), urinary tract (9.3% vs. 14.0%, P = 0.01; OR:0.65, P = 0.01) and multiple metastatic sites (62.6% vs. 70.7%, P < 0.01; OR:0.69, P < 0.01). CONCLUSIONS: In both databases lung metastases were more frequent in RPUC and abdominal metastases were more frequent in UUC. Moreover, liver metastases independently predicted worse survival, regardless of primary site.
- MeSH
- karcinom z přechodných buněk * MeSH
- lidé MeSH
- nádory jater * MeSH
- nádory ledvin * MeSH
- nádory močového měchýře * MeSH
- nádory močovodu * MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
A trend towards greater benefit from adjuvant chemotherapy (ACT) in pN+ bladder cancer (BCa) has been observed in multiple randomized controlled trials. However, it is still unclear which patients might benefit the most from this approach. We retrospectively analyzed a multicenter cohort of 1381 patients with pTany pN1-3 cM0 R0 urothelial BCa treated with radical cystectomy (RC) with or without cisplatin-based ACT. The main endpoint was overall survival (OS) after RC. We performed 1:1 propensity score matching to adjust for baseline characteristics and conducted a classification and regression tree (CART) analysis to assess postoperative risk groups and Cox regression analyses to predict OS. Overall, 391 patients (28%) received cisplatin-based ACT. After matching, two cohorts of 281 patients with pN+ BCa were obtained. CART analysis stratified patients into three risk groups: favorable prognosis (≤pT2 and positive lymph node [PLN] count ≤2; odds ratio [OR] 0.43), intermediate prognosis (≥pT3 and PLN count ≤2; OR 0.92), and poor prognosis (pTany and PLN count ≥3; OR 1.36). Only patients with poor prognosis benefitted from ACT in terms of OS (HR 0.51; p < 0.001). We created the first algorithm that stratifies patients with pN+ BCa into prognostic classes and identified patients with pTany BCa with PLN ≥3 as the most suitable candidates for cisplatin-based ACT. PATIENT SUMMARY: We found that overall survival among patients with bladder cancer and evidence of lymph node involvement depends on cancer stage and the number of positive lymph nodes. Patients with more than three nodes affected by metastases seem to experience the greatest overall survival benefit from cisplatin-based chemotherapy after bladder removal. Our study suggests that patients with the highest risk should be prioritized for cisplatin-based chemotherapy after bladder removal.
- MeSH
- adjuvantní chemoterapie MeSH
- cisplatina terapeutické užití MeSH
- cystektomie * škodlivé účinky MeSH
- lidé MeSH
- močový měchýř patologie MeSH
- nádory močového měchýře * farmakoterapie chirurgie patologie MeSH
- retrospektivní studie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
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.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Identifying those of patients with metastatic renal cell carcinoma (mRCC) who are most likely to benefit from cytoreductive nephrectomy (CN) is challenging. We tested the association between preoperative value of Systemic Immune-Inflammation Index (SII) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN. METHODS: mRCC patients treated with CN at different institutions were included. After assessing for the optimal pretreatment SII cut‐off value, we found 710 to have the maximum Youden Index value. The overall population was therefore divided into two SII groups using this cut‐off (low, <710 vs. high, ≥710). Univariable and multivariable Cox regression analyses tested the association SII and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's Concordance Index (C-Index). The clinical value of the SII was evaluated with decision curve analysis (DCA). RESULTS: Among 613 mRCC patients, 298 (49%) patients had a SII≥710. Median follow-up was 31 (IQR 16-58) months. On univariable analysis, high preoperative serum SII was significantly associated with worse OS (HR: 1.28, 95% CI: 1.07-1.54, P=0.01) and CSS (HR: 1.29, 95% CI: 1.08-1.55, P=0.01). On multivariable analysis, which adjusted for the effect of established clinicopathologic features, SII≥710 was associated with OS (HR: 1.25, 95% CI: 1.04-1.50, P=0.02) and CSS (HR: 1.26, 95% CI: 1.05-1.52, P=0.01). The addition of SII only slightly improved the discrimination of a base model that included established clinicopathologic features (C-index: 0.637 vs. 0.629). On DCA, the inclusion of SII did not improve the net-benefit of the prognostic model. On multivariable analyses, SII≥710 remained independently associated with the worse OS and CSS in IMDC intermediate risk group (both: HR: 1.31, 95% CI: 1.02-1.67, P=0.03). In the subgroup analyses based on the BMI, among patients with BMI ≥ 25, SII was significantly associated with OS (HR: 1.29, 95% CI: 1.04-1.61, P=0.02) and CSS (HR: 1.31, 95% CI: 1.05-1.63, P=0.02). CONCLUSIONS: We found an independent association of high SII prior to CN with unfavorable clinical outcomes, particularly in patients with intermediate risk mRCC and patients with increased BMI. Despite these results, it does not seem to add any prognostic or clinical benefit beyond that obtained by currently available clinicopathologic characteristics as sole worker.
- MeSH
- cytoredukční chirurgie * MeSH
- karcinom z renálních buněk * imunologie patologie chirurgie MeSH
- lidé MeSH
- nádory ledvin * imunologie patologie chirurgie MeSH
- nefrektomie * metody MeSH
- předoperační péče MeSH
- prognóza MeSH
- zánět imunologie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: To test contemporary rates and predictors of open conversion at minimally invasive partial nephrectomy (MIPN: laparoscopic or robotic partial nephrectomy). MATERIALS AND METHODS: Within the National Inpatient Sample database (2008-2015) we identified all MIPN patients and patients that underwent open conversion at MIPN. First, estimated annual percentage changes (EAPC) tested temporal trends of open conversion. Second, univariable and multivariable logistic regression models predicted open conversion at MIPN. All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics. RESULTS: Of 7649 MIPN patients, 287 (3.8%) underwent open conversion. The rates of open conversion decreased over time (from 12 to 2.4%; EAPC: 24.8%; p = 0.004). In multivariable logistic regression models predicting open conversion, patient obesity achieved independent predictor status (OR:1.80; p < 0.001). Moreover, compared to high volume hospitals, medium volume (OR:1.48; p = 0.02) and low volume hospitals (OR:2.11; p < 0.001) were associated with higher rates of open conversion. Last but not least, when the effect of obesity was tested according to hospital volume, the rates of open conversion ranged from 2.2 (non obese patients treated at high volume hospitals) to 9.8% (obese patients treated at low volume hospitals). CONCLUSION: Overall contemporary (2008-2015) rate of open conversion at MIPN was 3.8% and it was strongly associated with patient obesity and hospital surgical volume. In consequence, these two parameters should be taken into account during preoperative patients counselling, as well as in clinical and administrative decision making.
- MeSH
- karcinom z renálních buněk patologie chirurgie MeSH
- konverze na otevřenou operaci statistika a číselné údaje MeSH
- laparoskopie metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- miniinvazivní chirurgické výkony metody MeSH
- nádory ledvin patologie chirurgie MeSH
- následné studie MeSH
- nefrektomie metody MeSH
- obezita patofyziologie MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- robotika metody MeSH
- senioři MeSH
- specializovaná centra se zvyšujícím se počtem výkonů a tím zvyšující se kvalitou léčby statistika a číselné údaje MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: The Albumin-Globulin Ratio (AGR; albumin/total protein - albumin) has been associated with oncological outcome in various malignancies. However, its role in urothelial carcinoma of the bladder (UCB) has not been clearly established. In this study, we assessed the association of preoperative AGR (pAGR) with survival in patients who underwent radical cystectomy (RC) for UCB. MATERIAL AND METHODS: We conducted a retrospective analysis of an established multicenter database of 4.335 patients who were treated with RC for UCB. The cohort was divided into 2 groups according to the pAGR status. Binominal logistic regression as well as uni- and multivariable Cox regression analyses were used. The predictive value of the models was assessed by calculating receiver operating characteristics curves and concordance-indices (C-Index). The additional clinical value was assessed using the decision curve analysis (DCA). RESULTS: Overall, 1.670 patients (38.5%) had a low pAGR. On multivariable logistic regression analyses, low pAGR was associated with an increased risk of ≥pT3 disease at RC (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.01-1.31, P= 0.04). On multivariable Cox regression analyses, low pAGR remained associated with worse recurrence-free survival (RFS, HR 1.24, 95% CI 1.1-1.37, P< 0.001), cancer-specific survival (CSS, HR 1.23, 95% CI 1.1-1.38, P< 0.001) and overall survival (OS, HR 1.17, 95% CI 1.07-1.28, P< 0.001). The addition of pAGR to multiple prognostic models that were respectively fitted for clinical and postoperative variables did not improve the predictive accuracy. CONCLUSION: pAGR status is an independent predictor of ≥pT3 disease, therefore it could help identify patients who have a higher likelihood to benefit from neoadjuvant systemic therapy. While pAGR was independently associated with RFS, CSS, and OS, it did not improve the predictive accuracy and clinical value beyond obtained by information already available. The predictive value of this biomarker in the age of immunotherapy needs further evaluation.
- MeSH
- cystektomie * metody MeSH
- karcinom z přechodných buněk krev chirurgie MeSH
- lidé MeSH
- nádory močového měchýře krev chirurgie MeSH
- předoperační období MeSH
- sérové globuliny analýza MeSH
- sérový albumin analýza MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
PURPOSE: Management of metastatic renal cell cancer (mRCC) has undergone a paradigm shift with immune-checkpoint inhibitors (ICI) in the first-line setting. However, direct comparative data are inadequate to inform treatment decisions. Therefore, we aimed to assess first-line therapy for mRCC and indirectly compare the efficacy and safety of currently available treatments. MATERIALS AND METHODS: Multiple databases were searched for articles published before June 2020. Studies that compared overall and/or progression-free survival (OS/PFS) and/or adverse events (AEs) in mRCC patients were considered eligible. RESULTS: Six studies matched our eligibility criteria. For OS, pembrolizumab plus axitinib [hazard ratio (HR) 0.85, 95% credible interval (CrI) 0.73-0.98] and nivolumab plus ipilimumab (HR 0.86, 95% CrI 0.75-0.99) were significantly more effective than sunitinib, and pembrolizumab plus axitinib was probably the best option based on analysis of the treatment ranking. For PFS, pembrolizumab plus axitinib (HR 0.86, 95% CrI 0.76-0.97) and avelumab plus axitinib (HR 0.85, 95% CrI 0.74-0.98) were statistically superior to sunitinib, and avelumab plus axitinib was likely to be the preferred option based on analysis of the treatment ranking, closely followed by pembrolizumab plus axitinib. Nivolumab plus ipilimumab had significantly lower rates of serious AEs than sunitinib. CONCLUSION: Pembrolizumab plus axitinib seemed to be the most efficacious first-line agents, while nivolumab plus ipilimumab had the most favorable efficacy-tolerability equilibrium. These findings may facilitate individualized treatment strategies and inform future direct comparative trials in an expanding treatment options without direct comparison between approved drugs.
BACKGROUND: Recent data showed that North America has the highest incidence of renal cell carcinoma (RCC) worldwide. OBJECTIVE: To assess contemporary gender-, race-, and stage-specific incidence; survival rates; and trends of RCC patients in the USA. DESIGN, SETTING, AND PARTICIPANTS: Within the Surveillance, Epidemiology, and End Results database (2001-2016), all patients aged ≥18 yr with histologically confirmed renal parenchymal tumors were included. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Age-adjusted incidence rates and 5-yr cancer-specific survival (CSS) rates were estimated. Temporal trends were calculated through Joinpoint regression analyses to describe the average annual percent change (AAPC). RESULTS AND LIMITATIONS: The age-adjusted incidence rate of RCC was 11.3/100 000 person years (AAPC+2.0%, p<0.001). Five-year CSS rates increased from 78.4% to 84.5% (AAPC +0.8%, p<0.001). Male incidence was double that of females (15.5 and 7.7, respectively). CSS marginally favored females (84.5% vs 82.0%), but improved equally in both genders (both AAPC +0.8%). The highest incidence (14.1/100 000 person years, AAPC +2.8%) and lowest survival (80.1%) were recorded in non-Hispanic American Indian/Alaska Native populations. T1aN0M0 had the highest incidence rates (4.6/100 000 person years), the highest increase over time (AAPC +3.6%), and the highest CSS (97.6%) of all stages. Limitations include retrospective nature and lack of information on risk factors. CONCLUSIONS: The incidence of RCC increased significantly from 2001 to 2016, and 5-yr CSS after RCC improved. This was mainly due to T1aN0M0 tumors that showed the highest increase in the incidence and highest CSS. Unfavorable outcomes in specific ethnic groups warrant further research. PATIENT SUMMARY: We examined contemporary incidence and cancer-specific survival rates of kidney cancer. Males had double the incidence rates of females, but lower survival. Natives showed the highest incidence rates and the lowest survival rates. Small renal masses showed the highest incidence and survival rates.
- MeSH
- incidence MeSH
- karcinom z renálních buněk * patologie MeSH
- ledviny patologie MeSH
- lidé MeSH
- nádory ledvin * patologie MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
