Independent Risk Factor For Disease-specific Survival Research Articles

Dedifferentiated liposarcoma of the extremities: a Korean multi-center study of 107 cases

BackgroundDedifferentiated liposarcoma of the extremities (DDL-E) is rare in comparison to that of the retroperitoneum. Its clinical features and surgical principle for resection margins at the dedifferentiated and the well-differentiated components are yet to be elucidated.MethodsThis retrospective multi-center study examined patients diagnosed with DDL-E from August 2004 to May 2023 at 5 sarcoma centers. Clinical features, oncologic outcomes, and prognostic factors were analyzed.ResultsA total of 107 patients were reviewed. The 5-year local recurrence free survival (LRFS), metastasis-free survival (MFS) and disease specific survival (DSS) were 84.7%, 78.6%, and 87.8%, respectively. Other primary malignancies and extrapulmonary metastasis were observed in 27 and 4 patients, respectively. The independent risk factor for local recurrence was R1/2 margin at the dedifferentiated component of the tumor. Metastasis was associated with tumor size in univariate analysis. The independent risk factor for DSS was tumor grade. Previous unplanned excision, de novo presentation, tumor depth, absence of the well-differentiated component, infiltrative border, R1/2 margin at the well-differentiated component were not associated with oncologic outcomes.ConclusionsThis is the largest study examining DDL-E to-date. Localized DDL-E has low potential for metastasis and carries an excellent prognosis. Other primary malignancy and extrapulmonary metastasis are more frequent in DDL-E, thus close monitoring of other sites during follow-up is recommended. While wide resection margin is the standard surgical approach for DDL-E, further investigation into moderated wide resection margin at the well-differentiated component is warranted.

Development and Validation of a Nomogram for Patients with Lung Large Cell Neuroendocrine Carcinoma

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rarely high-grade neuroendocrine carcinoma of the lung with features of both small cell and non-small cell lung cancer. We aim to construct a prognostic nomogram combined with the clinical features and treatment options to predict disease-specific survival (DSS), meanwhile, evaluating the role of prophylactic cranial irradiation (PCI) in LCNEC by subgroup analysis. A total of 713 patients diagnosed with LCNEC from the US National Cancer Institute's Surveillance Epidemiology and End Results (SEER) registry between 2010 and 2016. Cox proportional hazards analysis was conducted to choose the significant predictors of DSS. External validation was performed using 77 patients with LCNEC in the West China Hospital Sichuan University between 2010 and 2018, subgroup analysis was carried out for the whole brain radiotherapy (WBRT) and PCI population. The predictive accuracy and discriminative capability were estimated by the concordance index (C-index), calibration curve and receiver operating characteristic (ROC) curve. The clinical applicability of the nomogram was verified through the decision curve analysis (DCA). Six independent risk factors for DSS were identified and integrated into the nomogram. The nomogram achieved good C- indexes of 0.803 and 0.767 in the training and validation group respectively. Moreover, the calibration curves of both cohorts for the probability of survival showed good agreement between prediction by nomogram and actual observation in 1-, 3- and 5-year DSS. The ROC curves demonstrated the prediction accuracy of the established nomogram (all AUC>0.8). DCA confirmed the better potential clinical practicality of the nomogram in the prediction of LCNEC survival than AJCC staging. A risk classification system was built which could perfectly classify LCNEC patients into high- and low-risk groups(p<0.001). Subgroup analysis showed that WBRT did not bring survival benefits, PCI appeared to have survival benefits in LCNEC patients without brain metastases (p>0.05). The prognostic nomogram developed in this study has certain prognostic value and clinical practicality for LCNEC patients. PCI might be investigated as a means of improving prognosis.

Lung Large Cell Neuroendocrine Carcinoma: A Population-Based Retrospective Cohort Study.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rarely high-grade neuroendocrine carcinoma of the lung with features of both small cell and non-small cell lung cancer. In this study, we aim to construct a prognostic nomogram that integrates the clinical features and treatment options to predict disease-specific survival (DSS). A total of 713 patients diagnosed with LCNEC were from the US National Cancer Institute's Surveillance Epidemiology and End Results (SEER) registry between 2010-2016. Cox proportional hazards analysis was conducted to choose the significant predictors of DSS. External validation was performed using 77 patients with LCNEC in the West China Hospital Sichuan University between 2010-2018. The predictive accuracy and discriminative capability were estimated by the concordance index (C-index), calibration curve, and receiver operating characteristic (ROC) curve. The clinical applicability of the nomogram was verified through the decision curve analysis (DCA). Additionally, we conducted a subgroup analysis of data available in the external cohort that may impact prognosis but was not recorded in the SEER database. Six independent risk factors for DSS were identified and integrated into the nomogram. The nomogram achieved good C- indexes of 0.803 and 0.767 in the training and validation group, respectively. Moreover, the calibration curves for the probability of survival showed good agreement between prediction by nomogram and actual observation in 1-, 3- and 5-year DSS. The ROC curves demonstrated the prediction accuracy of the established nomogram (all Area Under Curve (AUC) > 0.8). DCA exhibited the favorable clinical applicability of the nomogram in the prediction of LCNEC survival. A risk classification system was built which could perfectly classify LCNEC patients into high-, medium- and low-risk groups (p < 0.001). The survival analysis conducted on the West China Hospital cohort indicated that whole brain radiation therapy (WBRT), prophylactic cranial irradiation (PCI), surgical procedures, tumor grade, Ki-67, and PD-L1 expression were not significantly associated with DSS. This study has effectively developed a prognostic nomogram and a corresponding risk stratification system, which demonstrate promising potential for predicting the DSS of patients with LCNEC.

Prognostic impact of desmoplastic reaction in esophageal squamous cell carcinoma patients with neoadjuvant therapy

This study aimed to examine the prognostic value of desmoplastic reaction (DR) in esophageal squamous cell carcinoma (ESCC), particularly in patients who received neoadjuvant therapy, such as chemotherapy (NAC) or chemoradiotherapy (NACRT). In total, 153 patients with pStage II/III ESCC were included in this study. Ninety-one patients received neoadjuvant therapy (NAC, 70; NACRT, 21). Patients were classified according to three DR categories based on the presence of keloid-like collagen and/or myxoid stroma. In total, 50, 50, and 53 patients were classified as having mature, intermediate, and immature DR, respectively. The weighted kappa coefficient was 0.623 in the patients with preoperative treatments and 0.782, in those without. The 5-year disease-specific survival (DSS) rates in patients with intermediate/immature DR was significantly worse than those with mature DR (40.7% vs. 73.3%, p < 0.001). Similarly, the 5-year DSS rate in patients with intermediate/immature DR was significantly worse than those with mature DR in a study of patients who received neoadjuvant therapy (46.7% vs. 71.2%, p = 0.009). Multivariate analysis revealed that DR (hazard ratio [HR]: 3.15, 95% confidence interval [CI] 1.58-6.27, p = 0.001), along with N factors, was an independent risk factor for DSS. Moreover, multivariate analysis of patients who received neoadjuvant therapy revealed only DR (HR: 2.47, 95% CI 1.02-5.96, p = 0.045) as independent risk factors for DSS. The DR classification was a valuable prognostic factor not only in the ESCC patients without neoadjuvant therapy but also in those with neoadjuvant therapy.

Sarcobesity Index Predicts Poor Disease-Specific Survival After Resection for Colorectal Cancer

IntroductionSarcobesity (SO) is traditionally defined as the association between low muscle mass and obesity and has been reported to worsen prognosis after curative resection for colorectal cancer (CRC). This study aimed to propose a new definition of SO based on computed tomography measurements of the skeletal muscle area (SMA) and visceral adipose tissue (VAT) and to assess its implications on long-term survival after curative resection for stage I-III CRC. MethodsWe retrospectively analyzed 506 patients with stage I–III CRC who underwent surgery between January 2010 and December 2019. Preoperative computed tomography images were analyzed and the sarcobesity index (SI) was calculated for each patient as the VAT/SMA ratio. The optimal cutoff value for predicting survival was determined using time-dependent receiver operating characteristic analysis. Overall survival and disease-specific survival (DSS) were compared between SO (SI > 1.25) and non-SO (SI ≤ 1.25) patients. The rates and modes of recurrence were also compared between the two groups. ResultsThree hundred (59.3%) patients were identified to be sarcobese. No differences in short-term outcomes and administration of adjuvant chemotherapy were found, except for a longer length of stay in patients with SO. In a univariable analysis, SO was associated with a worse 5-y overall survival and DSS, considering the whole population and stages II and III separately. A multivariable analysis confirmed SO to be an independent risk factor for DSS (hazard ratio 2.29; 95% confidence interval 1.13-4.62, P = 0.02). Although the overall recurrence rate did not differ between the groups, a significantly higher rate of recurrence at multiple sites was observed in patients with SO (P = 0.01). ConclusionsThe SI, defined as per the VAT/SMA ratio, seems to be a reliable tool for identifying patients with worse DSS after potentially curative surgery for stage I-III CRC.

Prognostic Value of Pretreatment Overweight/Obesity and Adipose Tissue Distribution in Resectable Gastric Cancer: A Retrospective Cohort Study.

BackgroundThis is a study aimed at exploring the relationship between pretreatment overweight/obesity, adipose tissue distribution, and long-term prognosis of gastric cancer.MethodsA total of 607 gastric cancer patients were involved in the retrospective cohort study. Overweight/obese patients were defined as body mass index (BMI) greater than 25 kg/m2, and adipose tissue distribution parameters, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratio were measured at the level of the third lumbar vertebra using computerized tomography images within 15 days before the surgery. Multiple Cox regression models were applied to evaluate the association between overweight/obesity and disease-specific survival (DSS) of gastric cancer, and covariates including age, gender, T stage, N stage, and chemotherapy were adjusted. Furthermore, multiple Cox regression models were performed to evaluate the association between adipose tissue distribution parameters and DSS of gastric cancer; except for covariates mentioned above, overweight/obesity was adjusted additionally.ResultsOverweight/obesity was a predictive factor (HR = 0.61, 95% CI: 0.37–0.99) for the prognosis of gastric cancer. After additionally adjusting for overweight/obesity, high SAT percentage was an independent protective factor (HR = 0.59, 95% CI: 0.36–0.96), while high VAT percentage (HR = 1.68, 95% CI: 1.06–2.68) and high VAT/SAT ratio (HR = 1.99, 95% CI: 1.19–3.34) were independent risk factors for DSS of gastric cancer. Compared with other patients (overweight/obesity with low VAT/SAT ratio group, non-overweight/obesity or high VAT/SAT ratio group), patients in the non-overweight/obesity with high VAT/SAT ratio group had a worse prognosis (HR = 1.89, 95% CI: 1.28–2.77).ConclusionThese results suggest that overweight/obesity is a predictive factor for the prognosis of gastric cancer. The VAT/SAT ratio could be used as a promising prognostic factor for gastric cancer. Therefore, in preoperative evaluation of gastric cancer patients, attention should be paid not only to BMI but also to adipose tissue distribution.

Clinical Implication of World Health Organization Classification in Patients with Follicular Thyroid Carcinoma in South Korea: A Multicenter Cohort Study.

BackgroundThe study aimed to compare the prognostic value of the 4th edition of World Health Organization classification (WHO-2017) with the previous WHO classification (WHO-2004) for follicular thyroid carcinoma (FTC).MethodsThis multicenter retrospective cohort study included 318 patients with FTC from five tertiary centers who underwent thyroid surgery between 1996 and 2009. We evaluated the prognosis of patients with minimally invasive (MI), encapsulated angioinvasive (EA), and widely invasive (WI) FTC according to WHO-2017. Further, we evaluated the proportion of variation explained (PVE) and Harrell’s C-index to compare the predictability of disease-free survival (DFS) and disease-specific survival (DSS).ResultsIn total, 227, 58, and 33 patients had MI-, EA-, and WI-FTC, respectively. During a median follow-up of 10.6 years, 46 (14.5%) patients had disease recurrence and 20 (6.3%) patients died from FTC. The 10-year DFS rates of patients with MI-, EA-, and WI-FTC were 91.1%, 78.2%, and 54.9%, respectively (P<0.001, PVE=7.1%, C-index=0.649). The corresponding 10-year DSS rates were 95.9%, 93.5%, and 73.5%, respectively (P<0.001, PVE=2.6%, C-index=0.624). The PVE and C-index values were higher using WHO-2017 than using WHO-2004 for the prediction of DFS, but not for DSS. In multivariate analysis, older age (P=0.02), gross extrathyroidal extension (ETE) (P=0.003), and distant metastasis (P<0.001) were independent risk factors for DSS.ConclusionWHO-2017 improves the predictability of DFS, but not DSS, in patients with FTC. Distant metastasis, gross ETE and older age (≥55 years) were independent risk factors for DSS.

Binary grading may be more appropriate for endometrial cancer

Objective:To elucidate the survival consequences of the prognostic factors for endometrial cancer.Material and Methods:This was a retrospective study of 276 patients diagnosed with endometrial cancer who admitted for staging surgery. The extent of the surgery was determined by clinical staging and preoperative evaluation. The pathology specimens were reassessed by a gynecopathologist. Independent risk factors were revealed for the progression-free survival (PFS), overall survival (OS) and disease-specific survival (DSS) utilizing Kaplan-Meier and “Cox” proportional analysis.Results:The median follow up of the patients was 50 months. Of the 29 patients who died, 15 (5.43%) died because of endometrial cancer. Multivariate analysis revealed that independent risk factors for OS and PFS were stage (p=0.002, 0.002, respectively) and grade 3 (G3) histology (p=0.013, 0.015, respectively). Positive peritoneal cytology was an independent risk factor for OS (p=0.024), but not for PFS (p=0.050). Stage (p=0.005) was found to be the only independent risk factor for DSS. Patients with G1 and G2 histology had a similar and more favorable prognosis than patients with G3 histology.Conclusion:Advanced stage, high-grade tumor and the presence of positive peritoneal cytology were ascertained as independent prognostic factors for endometrial cancer. A binary histological grading system could be simpler and as effective as the current three grade system because grade 1 and 2 patients showed similar prognosis.

Survival study of patients with stage N1-3 testicular seminoma

Objective To explore the independent predictors for disease-specific survival (DSS) rate in patients with stage N1-3 testicular seminoma (TS), and establish a nomogram to predict individual 5-year DSS. Methods The data of N1-3 TS patients registered in the SEER database of National Cancer Institute (USA) from January 2004 to December 2015 were retrospectively analyzed. The 5-year overall survival (OS) rate and DSS rate were calculated using Kaplan-Meier method and the differences among different subgroups were assessed using log-rank test. Besides, the independent predictors of DSS were defined using multivariate Cox regression analysis, and nomogram was drawn using R software. Furthermore, the predictive performance of the nomogram was internally validated using the C-index and calibration plot. Results TNM stage ⅢA (HR=5.604, 95%CI: 1.252-25.083, P=0.024), ⅢB (HR=6.710, 95%CI: 1.923-23.410, P=0.003) and ⅢC (HR=13.189, 95%CI: 3.916-44.420, P<0.001), age at diagnosis ≥45 years old (HR=3.575, 95%CI: 2.014-6.344, P<0.001), and patients without spouse (HR=2.346, 95%CI: 1.406-3.914, P=0.001) were identified as independent risk factors for DSS. On internal validation, the predictive accuracy of our nomogram was 0.751 (C-index: 0.751, 95%CI: 0.694-0.808). Besides, the calibration plot showed that the predicted survival outcomes were highly consistent with the actual survival outcomes. Conclusion The study confirms that age at diagnosis ≥45 years old, TNM stage ≥ⅢA and patients without spouse are the independent risk factors for DSS in TS patients with stage N1-3, and the nomogram for predicting individual 5-year DSS is established. Key words: Seminoma; Lymphatic metastasis; Prognosis; Nomogram

Prognostic Nomogram for Disease-Specific Survival in Patients with Non-metastatic Ampullary Carcinoma After Surgery

ObjectiveThe aim of this study was to establish and validate an individualized nomogram for predicting disease-specific survival (DSS) in patients with non-metastatic ampullary carcinoma after surgery.MethodsThe nomogram was prepared using retrospective data from the Surveillance, Epidemiology, and End Results database, and included 2022 patients (training dataset: 1276; validation dataset: 746 patients) with non-metastatic ampullary carcinoma who were surgically treated between 2004 and 2014. Cox multivariate regression was performed to identify independent risk factors. The predictive accuracy was determined using the concordance index (C-index) and calibration curves. Results were validated internally using bootstrap resampling, and externally against the validation dataset.ResultsThe median follow-up for the training dataset was 25.5 months (range 1–143), the median survival time was 52 months [95% confidence interval (CI) 41.67–62.33], and the postoperative 1-, 3-, and 5-year DSS rates were 86.7%, 57.3%, and 47.2%, respectively. Univariate and multivariate regression analysis demonstrated that age, grade, tumor size, lymph node ratio, extension range, and histology were independent risk factors for DSS. The C-index of the internal validation dataset for predicting DSS was 0.70 (95% CI 0.68–0.72), which was superior to that of the American Joint Committee on Cancer staging, i.e. 0.64 (95% CI 0.62–0.66; p < 0.001). The 5-year DSS and median DSS time for the low-risk group were significantly greater than those for the high-risk group (p < 0.001).ConclusionOur nomogram reliably and accurately predicted DSS in patients with non-metastatic ampullary carcinoma after surgery. This model may help clinicians in their decision making.

Clinical significance and biological function of WD repeat domain 54 as an oncogene in colorectal cancer.

In recent years, protein-protein interactions have become an attractive candidate for identifying biomarkers and drug targets for various diseases. However, WD40 repeat (WDR) domain proteins, some of the most abundant mediators of protein interactions, are largely unexplored. In our study, 57 of 361 known WDR proteins were identified as hub nodes, and a hub (WDR54) with elevated mRNA in colorectal cancer (CRC) was selected for further study. Immunohistochemistry of specimens from 945 patients confirmed the elevated expression of WDR54 in CRC, and we found that patients with WDR54-high tumors typically had a shorter disease-specific survival (DSS) than those with WDR54-low tumors, especially for the subgroup without well-differentiated tumors. Multivariate analysis showed that WDR54-high tumors were an independent risk factor for DSS, with a hazard ratio of 2.981 (95% confidence interval, 1.425-6.234; p = 0.004). Knockdown of WDR54 significantly inhibited the growth and aggressiveness of CRC cells and reduced tumor growth in a xenograft model. Each WDR54 isoform (a, b, and c) was found to reverse the inhibitory effect of WDR54 knockdown; however, only isoform c, which exhibited the highest expression, was increased in CRC cells. Sensitization of WDR54 knockdown to an SHP2 inhibitor was consistently found in CRC cells, and the underlying mechanism involved their common function in regulating AKT and ERK signaling. In conclusion, the present study is the first to investigate the significance of WDR54 in cancer and to conclude that WDR54 serves as an oncogene in CRC and may be a potential prognostic marker and therapeutic target.

Significance of hydroxymethylglutaryl-CoA synthase 2 on prognosis of esophageal squamous cell carcinoma

Objective: To explore the roll and function of hydroxymethylglutaryl-CoA synthase 2 (HMGCS2) in the development and progression of human esophageal squamous cell carcimoma(ESCC). Method: Using immunohistochemistry, the expression of HMGCS2 was determined in 150 primary ESCC patients from July 2002 to December 2005 in the People's Hospital of Linzhou City, Henan Province. And HMGCS2 over-expression ESCC cell lines were established to verify HMGCS2 gene function. Result: In 150 cases of ESCCs, the expression rate of HMGCS2 was 58% (87/150), which was lower than 72% (108/150) in paired normal tissues, the difference was statistically significant (P=0.013). HMGCS2 down-regulated expression was associated with tumor cell differentiation (P=0.022), pT status (P=0.036), pN status (P=0.017) and TNM stage(P=0.012). The 5-years disease-specific survival (DSS) in down HMGCS2 expression group (14 months) was poorer than those in normal expression group (20 months; P=0.002). In addition, multivariate Cox regression analysis showed that HMGCS2 expression (Wald=7.136, P=0.008) was an independent risk factor for DSS. Furthermore, functional studies demonstrated that HMGCS2 gene could suppress the tumorigenic ability of ESCC cells (OD: 0.79±0.04 vs 1.25±0.68; P=0.01), the formation of colone (number of colones: 30±10 vs 189±15, P=0.002), and cell motility (number of cells: 27±14 vs 222±40, P=0.009). Conclusion: HMGCS2 can inhibit the proliferation and migration of ESCC cells, and could be an important candidate tumor suppressor gene for ESCC.

A Prognostic Nomogram for Disease-Specific Survival in Patients with Pancreatic Ductal Adenocarcinoma of the Head of the Pancreas Following Pancreaticoduodenectomy.

BackgroundThis study developed and validated a nomogram to predict patient prognosis for pancreatic ductal adenocarcinoma (PDAC) of the head of the pancreas following pancreaticoduodenectomy.Material/MethodsRetrospective data were obtained from 4,383 patients with PDAC of the head of the pancreas who underwent pancreaticoduodenectomy between 2004–2013 from 11 Registries Research Data of the Surveillance, Epidemiology,and End Results (SEER) database. Cox proportional hazards model was used to identify independent risk factors. The predictive accuracy of the nomogram was determined by the concordance index (C-index) and calibration curve. The results were externally validated by comparison with data from 1,743 patients from 7 other Registries Research Data.ResultsOf the 4,383 patients in the training dataset, median disease-specific survival (DSS) was 17.0 months (range, 1.0–131 months), and postoperative 1-year, 3-year, and 5-year DSS rates were 70.3%, 26.1%, and 16.8%, respectively. Multivariate analysis showed that patient sex, age, tumor grade, regional lymph nodes examined, positive regional lymph nodes, tumor size, extent of local invasion, and tumor metastases were independent risk factors for DSS. The C-index of the internal validation dataset for prediction of DSS was 0.64 (95% CI, 0.63–0.65), which was superior to the American Joint Committee on Cancer (AJCC) staging, 0.57 (95% CI, 0.56–0.58) (P<0.001). The 5-year DSS rates and median DSS time for patients in the low-risk group were significantly greater compared with high-risk group (P<0.001).ConclusionsA validated prognostic disease-specific nomogram for patient survival in PDAC of the head of the pancreas following pancreaticoduodenectomy was developed.

Melanoma in Mexico: Clinicopathologic Features in a Population with Predominance of Acral Lentiginous Subtype.

The aim of this study was to analyze the clinicopathologic features of melanoma in México as the demographics of melanoma are not well known in Mexican and Latin American people. A total of 1219 patients with cutaneous melanoma were analyzed through a retrospective database collected from a cancer referral institute, and the results were compared with developed countries. Median age was 57years, and 713 (58.5%) were females. The most common melanoma subtype was acral lentiginous melanoma (ALM), which was observed in 538 (44.1%) patients. Median Breslow thickness was 5.2mm. Among 837 patients with complete data, the 5-year disease-specific survival (DSS) was 52.3%. Factors associated with worse DSS on univariate analysis were Breslow thickness (p<0.001), recurrence (p<0.001), ulceration (p<0.001), positive margin (p<0.001), ALM (p=0.001), and male sex (p=0.001). Multivariate analysis demonstrated Breslow thickness [hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.27-1.65; p<0.001], positive margin (HR 1.25, 95% CI 1.03-1.57; p=0.018), recurrence (HR 9.56, 95% CI 6.89-9.87; p=0.002), ALM (HR 8.07, 95% CI 6.77-8.95; p=0.004), and male sex (HR 1.33, 95% CI 1.06-1.68; p=0.013) as independent risk factors for DSS. Our patients had worse prognosis compared with data from the US Surveillance, Epidemiology, and End Results database. We found male sex and ALM as independent risk factors for worse survival, in addition to known risk factors.

Sex differences in bladder cancer outcomes among smokers with advanced bladder cancer

To study the effect of smoking on bladder cancer presentation and outcome in a large cystectomy population. A database including 546 patients from the University Health Network (Toronto, Canada) and Turku University Hospital (Turku, Finland) was studied. In addition to the association of smoking with clinicopathological parameters, the effect of smoking on survival was analyzed. Categorical data were analyzed by the chi-squared test and numerical data were analyzed by Student's t-test. The Kaplan-Meier method, log-rank test and a proportional hazards model were used to estimate the effect of smoking on survival. In total, 352 patients (64%) were smokers and 194 (36%) were non-smokers. Smokers had more frequently advanced tumours and nodal metastasis. The 10-year disease-specific survival (DSS) was 52% vs 66% for smokers and non-smokers, respectively (P = 0.039). Smokers also had significantly worse overall survival (10-year overall survival 37% vs 62%; P = 0.015). Smoking affected significant DSS among men (P = 0.012), although no effect was observed among women. In a univariate model smoking was associated with a hazard ratio (HR) of 1.4 (95% confidence interval, CI, 1.0-1.9) for bladder cancer specific mortality and 1.4 (95% CI, 1.1-1.8) for overall mortality. In a multivariate model, smoking did not impact on DSS (HR, 1.1; 95% CI, 0.8-1.6; P = 0.41). In addition to advanced stage and nodal metastasis, female sex was an independent risk factor for DSS (HR, 1.6; 95% CI, 1.1-2.3; P = 0.007). Smokers appear to have worse outcomes after radical cystectomy for bladder cancer; however, it does not appear to be an independent prognostic factor for survival. Smoking affected survival only among men. Women had poorer survival but smoking was not a contributing factor to this.

Hydronephrosis Is an Independent Predictor of Poor Clinical Outcome in Patients Treated for Muscle-Invasive Transitional Cell Carcinoma With Radical Cystectomy

The purpose of this study was to assess the prognostic significance of hydronephrosis on pathologic and clinical outcomes in muscle-invasive bladder cancer. We performed a retrospective evaluation of a prospectively maintained cystectomy database and identified patients with hydronephrosis on preoperative imaging. Of a total of 306 patients, 57 (19%) had unilateral hydronephrosis and 17 (6%) had bilateral hydronephrosis. We constructed multivariate Cox regression analysis and Kaplan Meier tables to evaluate the association between preoperative hydronephrosis and clinical outcomes. In patients without hydronephrosis, 41.4% had extravesical disease compared with 56.1% and 64.7% in patients with unilateral or bilateral hydronephrosis, respectively. Mean overall survival (OS) among patients without hydronephrosis, with unilateral hydronephrosis, and with bilateral hydronephrosis was 55.5, 42.1, and 22.2 months, respectively. Five-year OS and disease-specific survival (DSS) was 46%, 35%, and 22% (P = .001) and 68%, 54%, and 35% (P = .002), respectively. Multivariate analysis demonstrated that both unilateral and bilateral hydronephrosis are significant independent risk factors for DSS and OS. Bilateral hydronephrosis was found to have a hazard ratio of 3.87 (95% confidence interval [CI] = 1.71-8.78, P = .001) and 2.75 (95% CI = 1.45-5.18, P = .002) for DSS and OS, respectively. The hazard ratios for unilateral hydronephrosis were 1.7 (95% CI = 1.05-2.87, P = .03) and 1.5 (95% CI = 1.03-2.23, P = .04) for DSS and OS, respectively. Preoperative hydronephrosis is associated with a significantly poorer prognosis in patients with muscle-invasive bladder cancer. These patients should be appropriately counseled with regard to overall prognosis and the potential benefit of neoadjuvant chemotherapy.