Dynamic Prognostication Using Conditional Recurrence and Progression Estimates for Patients with Nonmuscle Invasive Bladder Cancer.

PURPOSE: Conditional estimates provide a dynamic prediction of outcomes but to our knowledge there are no data on nonmuscle invasive bladder cancer. We assessed changes in conditional recurrence and progression rates after transurethral resection of the bladder and explored the prognostic impact of established factors and risk groups with time. MATERIALS AND METHODS: We retrospectively analyzed data on 1,292 consecutive patients with newly diagnosed Ta/T1 bladder cancer who underwent transurethral resection of the bladder. Study end points were time to first recurrence and time to progression. RESULTS: The 2-year recurrence rate at baseline was 36%, which improved as a function of the time that patients were free of disease recurrence. After 6, 12, 24, 36 and 48 months the 2-year conditional recurrence rate improved to 31% (14% improvement vs baseline), 22% (39% improvement), 16% (56% improvement), 13% (64% improvement) and 11% (69% improvement), respectively. Comparably, conditional progression rates improved with increasing followup, although relative differences were less distinct. The prognostic impact of established factors and nonmuscle invasive bladder cancer risk groups progressively decreased with time and finally disappeared. However, bacillus Calmette-Guérin had a protective effect on progression even after 3 years. We provide tables with dynamic prognostic information at all analyzed time points. CONCLUSIONS: In patients with primary Ta/T1 bladder cancer recurrence and progression rates improve with time. The prognostic impact of established factors and risk groups decreases and finally disappears. The effect of bacillus Calmette-Guérin on progression is long-lasting. Conditional outcome estimates may improve patient counseling and individualize surveillance planning.

Preoperative serum cholesterol is an independent prognostic factor for patients with renal cell carcinoma (RCC).

OBJECTIVE: To assess the prognostic role of preoperative serum cholesterol in patients with renal cell carcinoma (RCC), as increasing evidence suggests that alterations in the lipid profile are associated with the development, progression and prognosis of various cancers. PATIENTS AND METHODS: We analysed 867 patients, who underwent radical or partial nephrectomy for RCC between 2002 and 2012. Preoperative total cholesterol levels were determined in serum using colorimetric analysis (CHOD-PAP method). The association with cancer-specific survival (CSS) was assessed with Cox models. Discrimination was quantified with the C-index. The median follow-up was 52 months. RESULTS: The median (interquartile range) serum cholesterol was 195 (166-232) mg/dL. Decreasing serum cholesterol was associated with more advanced T, N and M stages (P < 0.001), higher grades (P = 0.001) and presence of tumour necrosis (P = 0.002). Continuously coded cholesterol was associated with CSS in both univariable (hazard ratio [HR] 0.87, P < 0.001) and multivariable analyses (HR 0.93, P = 0.001). The discrimination of a multivariable base model increased significantly from 88.3% to 89.2% following inclusion of cholesterol (P = 0.006). In patients with clinically localised disease (T1-3N0/+M0), cholesterol remained associated with CSS in multivariable analysis (HR 0.90, P = 0.002) and increased the discrimination from 74.6% to 76.9% (P = 0.002). CONCLUSIONS: Preoperative serum cholesterol is an independent prognostic factor for patients with RCC, with lower levels being associated with worse survival. Its use increases the discrimination of established prognostic factors. As cholesterol is a broadly available routine marker, its use may provide a meaningful adjunct in clinical practice. The biological rationale underlying this association remains to be clarified.

Perioperative Allogenic Blood Transfusion in Renal Cell Carcinoma: Risk Factors and Effect on Long-term Outcomes.

BACKGROUND: We sought to create a preoperative model to predict the risk of perioperative blood transfusion (PBT) in patients with renal cell carcinoma (RCC) undergoing nephrectomy and to evaluate the effect of PBT on long-term outcomes. PATIENTS AND METHODS: The present retrospective study included 648 consecutive patients who had undergone radical or partial nephrectomy for RCC at a single institution. The risk factors for PBT were analyzed using logistic regression analysis. Cox proportional hazards models addressed the effect of PBT on overall and RCC-specific mortality. RESULTS: A total of 62 patients (10%) received a median of 2 red blood cell units (interquartile range, 2-3; range 1-20). On multivariable logistic regression analysis, 2 preoperative factors were independently associated with receipt of PBT: preoperative anemia (odds ratio, 6.28; P < .001) and open surgery (odds ratio, 3.40; P < .001). The risk of receiving PBT was high with both risk factors present (34%), intermediate with 1 risk factor present (7%-12%), and low with 0 risk factors present (2%). Within a median follow-up period of 63 months (interquartile range, 32-91), 108 patients (17%) had died of RCC and 177 (27%) had died of any cause. In the multivariable Cox models, PBT remained independently associated with overall mortality (hazard ratio [HR], 1.86; P = .004) and RCC-specific mortality (HR, 1.79; P = .007). A dose-dependent association of PBT with RCC-specific mortality was observed (HR, 1.14; P = .01). CONCLUSION: In patients undergoing surgery for RCC, PBT was associated with adverse overall and RCC-specific mortality. Patients with preoperative anemia and those scheduled to undergo open surgery are at an increased risk of PBT and could be candidates for perioperative optimization techniques.

Serum Adiponectin Predicts Cancer-specific Survival of Patients with Renal Cell Carcinoma.

BACKGROUND: Prediction of outcomes in patients with renal cell carcinoma (RCC) is crucial for clinical decision-making. The limited accuracy of conventional prognostic factors such as stage and grade may be increased by the use of biomarkers. OBJECTIVE: To evaluate the association of serum adiponectin and leptin and polymorphisms in the leptin and leptin receptor genes with RCC histopathology and prognosis. DESIGN, SETTING, AND PARTICIPANTS: Adiponectin and leptin levels were measured in preoperative serum samples from 131 consecutive patients with sporadic unilateral RCC. The polymorphisms G-2548A (rs7799039) in the leptin gene (LEP) and Gln223Arg (Q223R, A668G, rs1137101) in the leptin receptor gene (LEPR) were genotyped in 233 patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable associations with RCC-specific survival were analyzed using Cox models. RESULTS AND LIMITATIONS: Median preoperative serum adiponectin was 15.8µg/ml (interquartile range 10.0-23.1). Adiponectin was lower in patients with distant metastases (p=0.017) or histologic tumor necrosis (p=0.015). On multivariable analysis adjusted for the effects of variables in the Karakiewicz nomogram, each 1-µg/ml increase in adiponectin was associated with a 8% decrease in the hazard of death from RCC (hazard ratio 0.92, 95% confidence interval 0.86-0.98; p=0.007). The discrimination of the Karakiewicz nomogram increased by 0.6% on inclusion of adiponectin. Leptin levels, LEP G-2548A and LEPR Q223R were not associated with either RCC pathology or outcomes. Limitations include the retrospective study design, the low numbers of patients, and a lack of standardized follow-up. CONCLUSIONS: This study suggests that lower preoperative serum adiponectin is associated with features of biologically aggressive RCC, metastasis, and survival. PATIENT SUMMARY: We assessed the relationship between outcomes and blood levels of adiponectin and leptin and genetic changes in leptin and leptin receptor genes. We found that patients with lower adiponectin levels have more aggressive tumors and poorer survival.

Development of a Preoperative Nomogram Incorporating Biomarkers of Systemic Inflammatory Response to Predict Nonorgan-confined Urothelial Carcinoma of the Bladder at Radical Cystectomy.

OBJECTIVE: To develop a preoperative multivariable decision-making tool to predict nonorgan-confined urothelial carcinoma of the bladder (NOC-UCB) using standard clinical and pathological factors as well as biomarkers of systemic inflammatory response. MATERIALS AND METHODS: We retrospectively analyzed a prospectively maintained single-institutional database comprising 310 patients with clinically N0 M0 UCB who underwent radical cystectomy (RC) with pelvic lymph node dissection without neoadjuvant cisplatin-based chemotherapy (NAC). NOC-UCB was defined as pT3-4/Nany or pTany/N + disease. A predictive nomogram was built based on significant variables in a bootstrap-corrected multivariable logistic regression model. The accuracy was measured by the area under the curve. Decision-curve analysis was used to evaluate the clinical net benefit. RESULTS: NOC-UCB was found in 147 (47%) of the 310 patients. On multivariable analysis, T stage at transurethral resection of the bladder, lymphovascular invasion, abnormal imaging, and Glasgow prognostic score (GPS) were all independent predictors of NOC-UCB and formed the basis of the nomogram. By adding the GPS, the accuracy of the nomogram improved by 4.7% to 81.7%. The decision curve analysis showed a net benefit of this model compared with the Green model and the strategies of treating all patients or no patient with NAC. Limitations include the retrospective design and the lack of a validation cohort. CONCLUSION: NOC-UCB at radical cystectomy can be accurately predicted. The accuracy of preoperative models can be improved by adding biomarkers of systemic inflammatory response, such as the GPS. The use of this nomogram may help physicians to accurately identify patients with NOC-UCB who may benefit from NAC.