Abstract
Objectives
Karakiewicz et al. and Green et al. created pre-cystectomy nomograms to predict lymph node involvement. The aim of the study was to externally validate these two nomograms in intermediate-volume institutions in Europe.
Patients and methods
Data from a Serbian single-centre cystectomy series comprising 183 patients with bladder cancer were used for the validation of two US nomograms, which were originally based on data from 726 and 201 patients, respectively. A multivariate regression model assessed the value of the clinical parameters integrated in the two nomograms. The expected predictive accuracy, calibration and clinical utility according to the nomograms were calculated.
Results
Comparison of our dataset with the previously published data shows differences in nearly all underlying risk variables. Overall, 109 (59.6 %) patients had lymph node metastases. The analysis demonstrated that hydronephrosis and status of lymph nodes on computed tomography have independent prognostic value. The performance of the nomograms deteriorated from the development set, and the predictive accuracies for the two models showed moderate discriminatory ability (61.2–69.1 %). In the decision curve analysis, only the Green et al. model predicting lymph node positivity provided net benefit.
Conclusions
The Green et al. nomogram seems applicable to patients from Europe, despite varying risk factors in the validation dataset. Acceptance of such a tool into daily clinical management may lead to more appropriate decision-making. Nevertheless, further improvement and implementation of novel statistical models with enhanced predictive accuracy is needed.
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Abbreviations
- AUC:
-
Area under the receiver operating characteristic curve
- BC:
-
Bladder cancer
- CI:
-
Confidential interval
- CIS:
-
Carcinoma in situ
- CT:
-
Computed tomography
- LN:
-
Lymph node
- LN+ :
-
Positive lymph node
- LR:
-
Logistic regression
- LVI:
-
Lymphovascular invasion
- MRI:
-
Magnetic resonance imaging
- NC:
-
Neoadjuvant chemotherapy
- NOC:
-
Non organ-confined
- NPV:
-
Negative predictive value
- OR:
-
Odds ratio
- PLND:
-
Pelvic lymph node dissection
- PPV:
-
Positive predictive value
- RC:
-
Radical cystectomy
- ROC:
-
Receiver operating characteristic curve
- TUR:
-
Transurethral resection
References
Karl A, Carroll PR, Gschwend JE et al (2009) The impact of lymphadenectomy and lymph node metastasis on the outcomes of radical cystectomy for bladder cancer. Eur Urol 55:826–835
Youssef RF, Raj GV (2011) Lymphadenectomy in management of invasive bladder cancer. Int J Surg Oncol 2011:758189. doi:10.1155/2011/758189
Shariat SF, Ehdaie B, Rink M et al (2012) Clinical nodal staging scores for bladder cancer: a proposal for preoperative risk assessment. Eur Urol 61:237–242
Xie HY, Zhu Y, Yao XD et al (2012) Development of a nomogram to predict non-organ-confined bladder urothelial cancer before radical cystectomy. Int Urol Nephrol 44:1711–1719
Green DA, Rink M, Hansen J et al (2012) Accurate preoperative prediction of non-organ-confined bladder urothelial carcinoma at cystectomy. BJU Int 111(3):404–411
Karakiewicz PI, Shariat SF, Palapattu GS et al (2006) Precystectomy nomogram for prediction of advanced bladder cancer stage. Eur Urol 50:1254–1262
Ahmadi H, Mitra AP, Abdelsayed GA et al (2012) Principal component analysis based pre-cystectomy model to predict pathological stage in patients with clinical organ-confined bladder cancer. BJU Int 111(4 Pt B):E167–E172
Margel D, Harel A, Yossepowitch O, Baniel J (2009) A novel algorithm to improve pathologic stage prediction of clinically organ-confined muscle-invasive bladder cancer. Cancer 115:1459–1464
Mitra AP, Skinner EC, Miranda G, Daneshmand S (2013) A precystectomy decision model to predict pathological upstaging and oncological outcomes in clinical stage T2 bladder cancer. BJU Int 111:240–248
Shariat SF, Karakiewicz PI, Suardi N et al (2008) Comparison of nomograms with other methods for predicting outcomes in prostate cancer: a critical analysis of the literature. Clin Cancer Res 15(14):4400–4407
Sylvester RJ, van der Meijden AP, Oosterlinck W et al (2006) Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol 49:466–477
Margulis V, Lotan Y, Montorsi F et al (2008) Predicting survival after radical cystectomy for bladder cancer. BJU Int 102:15–22
El-Mekresh M, Akl A, Mosbah A, Abdel-Latif M et al (2009) Prediction of survival after radical cystectomy for invasive bladder carcinoma: risk group stratification, nomograms or artificial neural networks? J Urol 182:466–472
International Bladder Cancer Nomogram Consortium (2006) Postoperative nomogram predicting risk of recurrence after radical cystectomy for bladder cancer. J Clin Oncol 24:3967–3972
Karakiewicz PI, Shariat SF, Palapattu GS et al (2006) Nomogram for predicting disease recurrence after radical cystectomy for transitional cell carcinoma of the bladder. J Urol 176:1354–1361
Nuhn P, May M, Sun M et al (2012) External validation of postoperative nomograms for prediction of all-cause mortality, cancer-specific mortality, and recurrence in patients with urothelial carcinoma of the bladder. Eur Urol 61:58–64
Zaak D, Burger M, Otto W et al (2010) Predicting individual outcomes after radical cystectomy: an external validation of current nomograms. BJU Int 106:342–348
May M, Burger M, Brookman-May S et al (2011) Validation of pre-cystectomy nomograms for the prediction of locally advanced urothelial bladder cancer in a multicentre study: are we able to adequately predict locally advanced tumour stages before surgery? Der Urologe Ausg A 50:706–713
Stenzl A, Cowan NC, De Santis M et al (2009) The updated EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol 55:815–825
Rink M, Hansen J, Cha EK et al (2013) Outcomes and prognostic factors in patients with a single lymph node metastasis at time of radical cystectomy. BJU Int 111:74–84
Haleblian GE, Skinner EC, Dickinson MG et al (1998) Hydronephrosis as a prognostic indicator in bladder cancer patients. J Urol 160:2011–2014
Sobin LH, Gospodariwicz M, Wittekind C (2009) TNM classification of malignant tumors. UICC International Union Against Cancer, 7th edn. Wiley, London
Mostofi FK, Sobin LH, Torloni H (1973) Histological typing of urinary bladder tumours. World Health Organization, Geneva
Quek ML, Stein JP, Nichols PW et al (2005) Prognostic significance of lymphovascular invasion of bladder cancer treated with radical cystectomy. J Urol 174:103–106
Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247
DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44:837–845
Vickers AJ, Elkin EB (2006) Decision curve analysis: a novel method for evaluating prediction models. Med Decis Making 26(6):565–574
Turker P, Bostrom PJ, Wroclawski ML et al (2012) Upstaging of urothelial cancer at the time of radical cystectomy: factors associated with upstaging and its effect on outcome. BJU Int 110(6):804–811
McLaughlin S, Shephard J, Wallen E et al (2007) Comparison of the clinical and pathologic staging in patients undergoing radical cystectomy for bladder cancer. Int Braz J Urol 33:25–31
Matsumoto K, Shariat SF, Casella R et al (2003) Preoperative plasma soluble E-cadherin predicts metastases to lymph nodes and prognosis in patients undergoing radical cystectomy. J Urol 170:2248–2252
Suzuki K, Morita T, Tokue A (2005) Vascular endothelial growth factor-C (VEGF-C) expression predicts lymph node metastasis of transitional cell carcinoma of the bladder. Int J Urol 12:152–158
Smith SC, Baras AS, Dancik G et al (2011) A 20-gene model for molecular nodal staging of bladder cancer: development and prospective assessment. Lancet Oncol 12:137–143
Stimson CJ, Cookson MS, Barocas DA et al (2010) Preoperative hydronephrosis predicts extravesical and node positive disease in patients undergoing cystectomy for bladder cancer. J Urol 183:1732–1737
Taylor JM, Ankerst DP, Andridge RR (2008) Validation of biomarker-based risk prediction models. Clin Cancer Res 14(19):5977–5983
Shariat SF, Rink M, Ehdaie B et al (2013) Pathologic nodal staging score for bladder cancer: a decision tool for adjuvant therapy after radical cystectomy. Eur Urol 63:371–378
Mertens LS, Meijer RP, Meinhardt W et al (2013) Occult lymph node metastases in patients with carcinoma invading bladder muscle: incidence after neoadjuvant chemotherapy and cystectomy vs after cystectomy alone. BJU Int. doi:10.1111/bju.12447
Acknowledgments
The authors were financially supported through a research Grant N0175014 of the Ministry of Science and Technological Development of Serbia. The authors thank the Ministry for this support.
Conflict of interest
None declared.
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Stojadinovic, M.M., Prelevic, R.I. External validation of existing nomograms predicting lymph node metastases in cystectomized patients. Int J Clin Oncol 20, 164–170 (2015). https://doi.org/10.1007/s10147-014-0693-3
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DOI: https://doi.org/10.1007/s10147-014-0693-3