Prediction of Cancer Specific Survival After Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: Development of an Optimized Postoperative Nomogram Using Decision Curve Analysis

Rouprêt, Morgan; Hupertan, Vincent; Seisen, Thomas; Colin, P.; Xylinas, Évanguelos; Yates, David R.; Fajković, Harun; Lotan, Yair; Raman, Jay D.; Zigeuner, Richard; Remzi, Mesut; Bolenz, Christian; Novara, Giacomo; Kassouf, Wassim; Ouzzane, A.; Rozet, François; Cussenot, Olivier; Martínez-Salamanca, Juan Ignacio; Fritsche, Hans Martin; Walton, Thomas J.; Wood, Christopher G.; Bensalah, Karim; Karakiewicz, Pierre I.; Montorsi, Francesco; Margulis, Vitaly; Shariat, Shahrokh F.

doi:10.1016/j.juro.2012.10.057

Cited by 151 publications

(109 citation statements)

References 27 publications

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“…Approximately 60% of UTUCs are invasive at diagnosis, compared with 15-25% of all bladder tumors, and thus this disease has a comparatively poor prognosis (6). The European Association of Urology Guidelines reviewed several published studies and reported that four different nomograms are available for predicting survival rates postoperatively, based on standard pathological features (17)(18)(19)(20). Recently, several papers reported a number of clinicopathological features and gene promoter methylation statuses of UTUC patients that might affect the probability of bladder recurrence, including patient gender, smoking status, tumor multifocality, surgical management, and GDF15 and RASSF1A promoter methylation (11,(21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

Predictive value of gene methylation for second recurrence following surgical treatment of first bladder recurrence of a primary upper‑tract urothelial carcinoma

et al. 2018

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Abstract. The clinical relevance of aberrant DNA promoter methylation is being increasingly recognized in urothelial carcinoma. The present study was conducted to explore the methylation status of patients with upper-tract urothelial carcinoma (UTUC) who experienced bladder recurrence, and to evaluate the predictive value of gene methylation for second bladder recurrence and tumor progression. A total of 85 patients with primary UTUC, who experienced bladder recurrence after radical nephroureterectomy, were enrolled between January 2001 and December 2013. Using methylation-sensitive polymerase chain reaction, the promoter methylation statuses of 10 genes were analyzed in the bladder tumor specimens. Among the patient group, 32 patients experienced second bladder recurrence, and bladder progression was detected in 16. With the exception of BRCA1, the methylation rate of the majority of genes tended to gradually increase to varying extents with the number of recurrences; a smaller proportion of primary tumors exhibited gene methylation when compared with the first recurrent tumors and second recurrent tumors. Univariate and multivariate Cox regression analyses revealed that unmethylated GDF15 [hazard ratio (HR)=0.36; 95% confidence interval (CI), 0.14-0.92] and methylated VIM (HR=2.91; 95% CI, 1.11-7.61) in the first recurrent bladder tumor, as well as male gender (HR=2.28; 95% CI, 1.06-4.87), first recurrence interval <8 months (HR=2.34; 95% CI, 1.15-4.78) and primary UTUC tumor size ≥5 cm (HR=3.48; 95% CI, 1.43-8.45) were independent risk factors for a second bladder recurrence after surgery for the first bladder recurrence; the Harrell's concordance index (c-index) for the related nomogram was 0.71 (95% CI: 0.61-0.81). Furthermore, methylated CDH1 (HR=2.91; 95% CI, 1.08-7.77) and VIM (HR=4.91; 95% CI, 1.11-21.7) in the first recurrent bladder tumor, male gender (HR=3.6; 95% CI, 1.1-11.73), and primary tumor stage T2-T4 (HR=4.57; 95% CI, 1.22-17.13), multifocality (HR=3.64; 95% CI, 1.19-11.16) and size ≥5 cm (HR=3.1; 95% CI, 1.91-10.54) for the primary UTUC were considered to be predictors of tumor progression; the c-index for the nomogram was 0.88 (95% CI, 0.69-0.92). The present findings demonstrated that promoter methylation of cancer-related genes was frequently observed in patients with urothelial carcinoma, and that the gene methylation rate of certain genes tended to gradually increase with the number of bladder recurrences. This may be used as a predictive factor for a second bladder recurrence and tumor progression after the surgical treatment of the first bladder recurrence.

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Section: Discussionmentioning

confidence: 99%

Predictive value of gene methylation for second recurrence following surgical treatment of first bladder recurrence of a primary upper‑tract urothelial carcinoma

et al. 2018

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“…Despite enormous progress in the identification of genetic and molecular alterations in UTUC, including gene mutations, non-coding RNA expression, and chromosomal aberrations achieved over the last years [23,24] , the routine prognostic risk assessment of UTUC patients currently still relies on well-established clinicopathological prognostic variables, such as pathologic T-stage and tumor grade [4,5] .…”

Section: Discussionmentioning

confidence: 99%

“…Pathologic T-stage and tumor grade are currently regarded as representing the most important pathological prognostic factors in UTUC [4,5] . Additionally, the presence of lymphovascular invasion and histologic tumor necrosis represent independent predictors of UTUC patient's survival [6,7] .…”

Section: Introductionmentioning

confidence: 99%

“…The identification of risk factors that are able to accurately predict the clinical outcome of UTUC patients is paramount, since they allow the assessment of patient's individualized risk profiles. Several groups of authors developed pre-and postoperative prognostic models to better predict UTUC patient's clinical outcomes [5,8] . For instance, Margulis et al [8] integrated patient's disease-related symptoms, histologic subtype, tumor size, and pathologic T-stage into a pretreatment multivariable prognostic model to predict non-organ confined UTUC.…”

Section: Introductionmentioning

confidence: 99%

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Validation of the Preoperative Platelet-to-Lymphocyte Ratio as a Prognostic Factor in a European Cohort of Patients with Upper Tract Urothelial Carcinoma

Dalpiaz¹,

Krieger²,

Ehrlich³

et al. 2016

Urol Int

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Introduction: This study is aimed at investigating the potential prognostic impact of the preoperatively assessed platelet-to-lymphocyte ratio (PLR) in a European cohort of patients with non-metastatic upper tract urothelial carcinoma (UTUC). Materials and Methods: Clinicopathological data from 180 consecutive non-metastatic UTUC patients, operated between 1990 and 2012 at a single tertiary academic center, were evaluated retrospectively. The preoperative PLR was assessed one day before surgery. Patients were categorized using a PLR cut-off value according to receiver-operating curve analysis. Cancer-specific survival (CSS) and overall survival (OS) were assessed using the Kaplan-Meier method. Additionally, multivariate proportional Cox regression models were applied. Results: In multivariate analyses, age at the date of surgery (<65 vs. ≥65 years, hazard ratio (HR) 1.827, 95% CI 1.051-3.175, p = 0.033), pathologic T-stage (pT1 vs. pT2-4, HR 1.873, 95% CI 1.066-3.292, p = 0.029), and pretreatment PLR (<150.0 vs. ≥150.0, HR 1.782, 95% CI 1.041-3.050, p = 0.035) were independent predictors of OS. Regarding CSS, pathologic T-stage (pT1 vs. pT2-4, HR 2.176, 95% CI 1.062-4.460, p = 0.034) and pretreatment PLR (<150.0 vs. ≥150.0, HR 2.026, 95% CI 1.045-3.930, p = 0.037) were considered independent predictors. Conclusions: In the cohort studied, patients with an elevated (≥150.0) preoperative PLR had a higher cancer-specific mortality and overall mortality after radical surgery for UTUC, compared with those with a low pretreatment PLR.

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“…To date, no randomized controlled trial has evaluated the utility of LND for patients with UTUC. Although previous retrospective studies have suggested that the presence of lymph node (LN) metastasis is a negative prognostic factor (7)(8)(9)(10), the therapeutic role of LND is still controversial. The objective of the current study was to clarify the therapeutic impact of the implementation and extent of LND on clinical outcomes using the nationwide database of the JUA.…”

Section: Introductionmentioning

confidence: 99%

Impact of lymph node dissection on clinical outcomes during nephroureterectomy in patients with clinically node-negative upper urinary tract urothelial cancer: subanalysis of a multi-institutional nationwide case series of the Japanese Urological Association

Inokuchi

Eto

Hara

et al. 2017

Japanese Journal of Clinical Oncology

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Objective: To evaluate the impact of lymph node dissection (LND) on the clinical outcomes during radical nephroureterectomy (RNU) in patients with clinically node-negative upper urinary tract urothelial cancer (UTUC). Methods: Within the nationwide case series of the Japanese Urological Association, which comprises 1509 patients with UTUC diagnosed in 2005, we identified 823 patients with clinically nodenegative UTUC who underwent RNU. The extent of limited LND was defined as the renal hilar region only for renal pelvic cancer and as either the pelvic region or para-aortic/paracaval region only for ureteral cancer, while the extent of wider LND was defined as at least one perilesional LND region in addition to limited LND. Multivariate analysis with a Cox regression hazard model was used to evaluate the survival benefit. Results: Among the 823 patients, LND was performed in 197 (23.9%) patients, and 26 (13.2%) of them had pathologically node-positive disease. Of 197 patients who underwent LND, limited and wider LND was performed in 119 (60.4%) and 78 (39.6%) patients, respectively. Patients with node-positive disease showed significantly shorter overall survival than those with node-negative disease. No LND-associated survival improvement was observed in a direct comparison between patients with and without LND. In addition, limited or wider LND was not associated with overall survival or cancer-specific survival. Conclusions: The therapeutic benefit obtained by LND remains unclear regardless of the extent of LND, although LND has diagnostic value with respect to the prediction of a poor prognosis especially in patients with clinically muscle-invasive disease.

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Prediction of Cancer Specific Survival After Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: Development of an Optimized Postoperative Nomogram Using Decision Curve Analysis

Cited by 151 publications

References 27 publications

Predictive value of gene methylation for second recurrence following surgical treatment of first bladder recurrence of a primary upper‑tract urothelial carcinoma

Predictive value of gene methylation for second recurrence following surgical treatment of first bladder recurrence of a primary upper‑tract urothelial carcinoma

Validation of the Preoperative Platelet-to-Lymphocyte Ratio as a Prognostic Factor in a European Cohort of Patients with Upper Tract Urothelial Carcinoma

Impact of lymph node dissection on clinical outcomes during nephroureterectomy in patients with clinically node-negative upper urinary tract urothelial cancer: subanalysis of a multi-institutional nationwide case series of the Japanese Urological Association

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