A Preoperative Prognostic Model for Patients Treated with Nephrectomy for Renal Cell Carcinoma

Karakiewicz, Pierre I.; Suardi, Nazareno; Capitanio, Umberto; Jeldres, Claudio; Ficarra, Vincenzo; Cindolo, Luca; Taille, Alexandre de la; Tostain, Jacques; Mulders, Peter F.A.; Bensalah, Karim; Artibani, Walter; Salomon, Laurent; Zigeuner, Richard; Valéri, Antoine; Descotes, J; Rambeaud, J.J.; Méjean, A.; Montorsi, Francesco; Bertini, Roberto; Patard, Jean Jacques

doi:10.1016/j.eururo.2008.07.037

Cited by 124 publications

(105 citation statements)

References 31 publications

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“…No evidence was observed for association of cathepsin D with CSS (LRT P ¼ 0.291) or DFS (LRT P ¼ 0.103). Metastatic disease, sex, and CT T stage showed independently prognostic value (Po0.050), and for other variables HRs were within the 95% CIs reported earlier in a much larger dataset (Karakiewicz et al, 2009). The power to show independent prognostic value in this pilot study is low as there are a large number of variables included in the model (nine when considering all levels in categorical variables) and simulation experiments based on this model show that 200 patients would be required at observed event rates to attain a power of approximately 50% and 500 patients to attain a power of approximately 90% with similar HRs to those observed at standard significance levels (Cairns et al, in preparation).…”

Section: Immunoassay Of Urinary Cathepsin Dsupporting

confidence: 52%

“…To examine further the utility of urinary cathepsin D as a preoperative marker, the association of cathepsin D with the variables used in the pre-operative nomogram developed by Karakiewicz et al (n ¼ 2474) (Karakiewicz et al, 2009), that is CT tumour size, CT T stage and symptoms at presentation was also examined Refers to test comparing control (normal and benign) with RCC group. c Spearman's rank correlation coefficient.…”

Section: Immunoassay Of Urinary Cathepsin Dmentioning

confidence: 99%

“…However, estimates of risk are relatively wide for individual patients (Leibovich et al, 2003;Sorbellini et al, 2005) and some elements such as nuclear grade are subject to intra-and inter-observer variability (Al Aynati et al, 2003). The possibility of determining outcome pre-operatively has also recently been highlighted, with the definition of six pre-operative variables that predict risk of RCC-specific mortality with a high degree of accuracy (Raj et al, 2008;Karakiewicz et al, 2009). Such nomograms may influence patient management in terms of treatment modality, surgical strategy and neoadjuvant treatment using suninib or sorafenib for example.…”

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Pre-operative urinary cathepsin D is associated with survival in patients with renal cell carcinoma

et al. 2009

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BACKGROUND: No circulating markers are routinely used for renal cancer. The objective of this pilot study was to investigate whether conditioned media (CM) from renal cancer cell lines contains potential biomarkers that, when measured in clinical fluids, have diagnostic or prognostic utility. METHODS: Comparative 2D PAGE profiling of CM from renal cell carcinoma (RCC) and normal renal cultures identified cathepsin D that was subsequently validated in urine samples from 239 patients and healthy and benign disease subjects. RESULTS: Urinary cathepsin D was found to be significantly associated with overall (OS) (hazard ratio, HR, 1.33, 95%CI [1.09 -1.63], P ¼ 0.005) and cancer-specific survival (HR 1.36, 95%CI [1.07 -1.74], P ¼ 0.013) in RCC patients on univariate analysis. An optimal cut point (211 ng ml À1 mmolCr À1 ) around which to stratify patients by OS was determined. Five-year OS equal to/above and below this value was 47.0% (95%CI 35.4%, 62.4%) and 60.9% (48.8%, 76.0%), respectively. On multivariable analysis using pre-operative variables, cathepsin D showed some evidence of independent prognostic value for OS (likelihood ratio test P-value ¼ 0.056) although requiring further validation in larger patient numbers with sufficient statistical power to determine independent significance. CONCLUSION: These data establish an important proof of principle and show the potential of proteomics-based studies. Cathepsin D may be of value as a pre-operative urinary biomarker for RCC, alone or in combination.

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Section: Immunoassay Of Urinary Cathepsin Dsupporting

confidence: 52%

Section: Immunoassay Of Urinary Cathepsin Dmentioning

confidence: 99%

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Pre-operative urinary cathepsin D is associated with survival in patients with renal cell carcinoma

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“…However, the prognostic information provided by RCC subtype is lost when stratified to tumour stage (LE 3) [43]. For localised RCC, several risk scores and nomograms can be used, including the Stage, Size, Grade, and Necrosis Score (SSIGN) [44], a modified version of the SSIGN score (Leibovich score) [45], the University of California Los Angeles Integrated Staging System (UISS) [46], and Karakiewicz's nomogram (LE 3) [47]; Section 3.7 provides further details. Clinical factors include patient PS, localised symptoms, cachexia, anaemia, elevated neutrophil and platelet counts, and other laboratory parameters, and are predominantly used in prognostic risk models in mRCC (LE 3) [48,49].…”

Section: Prognostic Factorsmentioning

confidence: 99%

EAU Guidelines on Renal Cell Carcinoma: The 2010 Update

Ljungberg¹,

Cowan²,

Hanbury³

et al. 2010

European Urology

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Context: The European Association of Urology Guideline Panel for Renal Cell Carcinoma (RCC) has prepared evidence-based guidelines and recommendations for RCC management. Objectives: To provide an update of the 2010 RCC guideline based on a standardised methodology that is robust, transparent, reproducible, and reliable. Evidence acquisition: For the 2014 update, the panel prioritised the following topics: percutaneous biopsy of renal masses, treatment of localised RCC (including surgical and nonsurgical management), lymph node dissection, management of venous thrombus, systemic therapy, and local treatment of metastases, for which evidence synthesis was undertaken based on systematic reviews adhering to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Relevant databases (Medline, Cochrane Library, trial registries, conference proceedings) were searched (January 2000 to November 2013) including randomised controlled trials (RCTs) and retrospective or controlled studies with a comparator arm. Risk of bias (RoB) assessment and qualitative and quantitative synthesis of the evidence were performed. The remaining sections of the document were updated following a structured literature assessment. Evidence synthesis: All chapters of the RCC guideline were updated. For the various systematic reviews, the search identified a total of 10 862 articles. A total of 151 studies reporting on 78 792 patients were eligible for inclusion; where applicable, data from RCTs were included and meta-analyses were performed. For RCTs, there was low RoB across studies; however, clinical and methodological heterogeneity prevented data pooling for most studies. The majority of studies included were retrospective with matched or unmatched cohorts based on single or multi-institutional data or national registries. The exception was for systemic treatment of metastatic RCC, in which several RCTs have been performed, resulting in recommendations based on higher levels of evidence.

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“…4 we believe that this clinical variable-based nomogram might be a better tool with which to stratify preoperatively nonmetastatic patients, and to identify those at increased risk who are potentially suitable for enrollment in rCts designed to evaluate the efficacy of neoadjuvant therapies.…”

Section: In 2009 Karakiewicz Et Almentioning

confidence: 99%