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.
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.
- Klíčová slova
- Adjuvant chemotherapy, Bladder cancer, Cisplatin, Nodal metastases, Radical cystectomy, Urothelial cancer,
- 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
- Názvy látek
- cisplatina 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.
- Klíčová slova
- Metastatic, NIS, SEER, Tumor location, UTUC,
- 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
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: 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
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.
- Klíčová slova
- drug administration schedule, neoadjuvant therapy, survival, urinary bladder neoplasms,
- 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
OBJECTIVES: Metabolic syndrome (MetS) and its components (high blood pressure, BMI≥30, altered fasting glucose, low HDL cholesterol and high triglycerides) may undermine early perioperative outcomes after radical prostatectomy (RP). We tested this hypothesis. MATERIALS & METHODS: Within the National Inpatient Sample database (2008-2015) we identified RP patients. The effect of MetS was tested in four separate univariable analyses, as well as in multivariable regression models predicting: 1) overall complications, 2) length of stay, 3) total hospital charges and 4) non-home based discharge. All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics. RESULTS: Of 91,618 patients: 1) 50.2% had high blood pressure, 2) 8.0% had BMI≥30, 3) 13.0% had altered fasting glucose, 4) 22.8% had high triglycerides and 5) 0.03% had low HDL cholesterol. Respectively, one vs. two vs. three vs. four MetS components were recorded in 36.2% vs. 19.0% vs. 5.5% vs. 0.8% patients. Of all patients, 6.3% exhibited ≥3 components and qualified for MetS diagnosis. The rates of MetS increased over time (EAPC:+9.8%; p < 0.001). All four tested MetS components (high blood pressure, BMI≥30, altered fasting glucose and high triglycerides) achieved independent predictor status in all four examined endpoints. Moreover, a highly statistically significant dose-response was also confirmed for all four tested endpoints. CONCLUSION: MetS and its components consistently and strongly predict early adverse outcomes after RP. Moreover, the strength of the effect was directly proportional to the number of MetS components exhibited by each individual patient, even if formal MetS diagnosis of ≥3 components has not been met.
- Klíčová slova
- Altered fasting glucose, High blood pressure, High triglycerides, Metabolic syndrome, National inpatient sample, Obesity,
- MeSH
- databáze faktografické MeSH
- dospělí MeSH
- hypertenze komplikace epidemiologie MeSH
- index tělesné hmotnosti MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolický syndrom komplikace epidemiologie MeSH
- metastázy nádorů MeSH
- nádory prostaty komplikace chirurgie MeSH
- pooperační komplikace epidemiologie MeSH
- prostatektomie MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Spojené státy americké epidemiologie MeSH
BACKGROUND: Optimal management of metastatic non-clear cell renal cell carcinoma (non-ccmRCC) remains largely unknown. OBJECTIVE: To test the effect of systemic therapy (ST) and/or cytoreductive nephrectomy (CNT) on overall mortality (OM) in patients with non-ccmRCC. DESIGN, SETTING, AND PARTICIPANTS: Within the Surveillance, Epidemiology and End Results (SEER) registry (2006-2015), we identified patients with papillary, chromophobe, sarcomatoid, and collecting duct metastatic renal cell carcinoma (mRCC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Temporal trends (estimated annual percentage change [EAPC]), Kaplan-Meier plots, and multivariable Cox regression models were used. RESULTS AND LIMITATIONS: Of 1573 patients with non-ccmRCC, 22%, 25%, 25%, and 28% underwent no treatment, ST, CNT, and CNT with ST, respectively. Between 2006 and 2015, rates of CNT and the combination of CNT and ST decreased (EAPC: -6.3% and -3.2%, respectively). Conversely, rates of no treatment and ST increased over time (EAPC: 4.6% and 7.5%, respectively). In multivariable Cox regression models, relative to no treatment, ST (hazard ratio [HR]: 0.5; p < 0.001), CNT (HR: 0.4; p < 0.001), and CNT with ST (HR: 0.3; p < 0.001) were associated with lower OM. Histological subtypes were associated with OM, relative to papillary renal cell carcinoma (RCC): chromophobe (HR: 0.7; p < 0.01), sarcomatoid (HR: 2.1; p < 0.001), and collecting duct RCC (HR: 1.9; p < 0.001). Limitations include the impossibility to stratify patients according to mRCC risk groups. CONCLUSIONS: Most non-ccmRCC patients are treated with a combination of CNT and ST or CNT alone or ST alone. The rates of ST alone are increasing. Conversely, the rates of combined CNT and ST and CNT alone are decreasing. These observed temporal patterns of treatment rates are counterintuitive with respect to associated OM benefits, where combination of CNT and ST, as well as CNT alone, resulted in the lowest absolute OM, relative to ST alone, or, even worse, no treatment. PATIENT SUMMARY: We investigated the effect of treatment modalities on survival of patients with metastatic non-clear cell renal cell carcinoma. The combination of cytoreductive nephrectomy and systemic therapy confers greater benefit with respect to single treatments alone.
- Klíčová slova
- Cytoreductive nephrectomy *, Histological subtypes *, Metastases *, Non–clear cell renal cell carcinoma *, Overall mortality *, Systemic therapy *,
- MeSH
- cytoredukční chirurgie metody MeSH
- karcinom z renálních buněk * patologie chirurgie MeSH
- lidé MeSH
- nádory ledvin * patologie chirurgie MeSH
- nefrektomie metody 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.
- Klíčová slova
- Hospital volume, National inpatient sample, Obesity, Open conversion, Partial nephrectomy,
- 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
BACKGROUND: Accurate identification of ideal candidates for cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is an unmet need. We tested the association between preoperative value of systemic albumin to globulin ratio (AGR) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN. METHODS: mRCC patients treated with CN were included. The overall population was therefore divided into two AGR groups using cut-off of 1.43 (low, <1.43 vs. high, ≥1.43). Univariable and multivariable Cox regression analyses tested the association between AGR 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 AGR was evaluated with decision curve analysis (DCA). RESULTS: Among 613 mRCC patients, 159 (26%) patients had an AGR <1.43. Median follow-up was 31 (IQR: 16-58) months. On univariable analysis, low preoperative serum AGR was significantly associated with both OS (HR: 1.55, 95% CI: 1.26-1.89, P<0.001) and CSS (HR: 1.55, 95% CI: 1.27-1.90, P<0.001). On multivariable analysis, AGR <1.43 was associated with worse OS (HR: 1.51, 95% CI: 1.23-1.85, P<0.001) and CSS (HR: 1.52, 95% CI: 1.24-1.86, P<0.001). The addition of AGR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index=0.640 vs. C-index=0.629). On DCA, the inclusion of AGR marginally improved the net benefit of the prognostic model. Low AGR remained independently associated with OS and CSS in the IMDC intermediate risk group (HR: 1.52, 95% CI: 1.16-1.99, P=0.002). CONCLUSIONS: In our study, low AGR before CN was associated with worse OS and CSS, particularly in intermediate risk patients.
