Endoscopic management of upper tract urothelial carcinoma: Improved prediction of invasive cancer using a ureteroscopic scoring model

Background

The aim of this study was to investigate clinical and ureteroscopic factors considered as important for the prediction of invasive upper tract urothelial carcinoma (UTUC) and establish a model using a new ureteroscopic scoring.

An audit of nephroureterectomy for upper tract urothelial carcinoma

Background

The boundary of nephroureterctomy has been revisited and lymph node dissection has been recommended recently. We investigated the role of synchronous ipsilateral adrenalectomy in treating patients with upper tract urothelial carcinoma.

Methods

110 patients with clinically localized upper tract urothelial carcinoma treated by nephroureterectomy and bladder cuff resection were retrospectively evaluated. 70 patients underwent nephroureterectomy without concomitant ipsilateral adrenalectomy, whereas nephroureterectomy and ipsilateral adrenalectomy was performed in other 40 patients. Cancer specific, metastasis and local recurrence free survival during a follow-up of median 46 months were analyzed.

Results

No patient had adrenal metastasis among the 40 adrenalectomized patients. A total of 4 patients developed local recurrences; including 1 of the 70 adrenalectomy-sparing and 3 of the 40 adrenalectomized patients (p = 0.102, chi-square test). Five patients with adrenalectomy and four without adrenalectomy had distant metastases (p = 0.212, chi-square test). The five-year local recurrence free survival (p = 0.09, log-rank test), metastasis-free survival (p = 0.292, log-rank test), and cancer-specific survival (p = 0.117, log-rank test) did not have significant difference between both groups.

Conclusions

This is the only study in recent 2 decades to evaluate the necessity of synchronous adrenalectomy in treating localized upper tract urothelial carcinoma. Adrenal-sparing nephroureterectomy seems justified for clinically localized upper tract urothelial carcinoma.     

Contralateral upper tract urothelial carcinoma after nephroureterectomy: the predictive role of DNA methylation

Background

Aberrant methylation of genes is one of the most common epigenetic modifications involved in the development of urothelial carcinoma. However, it is unknown the predictive role of methylation to contralateral new upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). We retrospectively investigated the predictive role of DNA methylation and other clinicopathological factors in the contralateral upper tract urothelial carcinoma (UTUC) recurrence after radical nephroureterectomy (RNU) in a large single-center cohort of patients.

Methods

In a retrospective design, methylation of 10 genes was analyzed on tumor specimens belonging to 664 consecutive patients treated by RNU for primary UTUC. Median follow-up was 48 mo (range: 3–144 mo). Gene methylation was accessed by methylation-sensitive polymerase chain reaction, and we calculated the methylation index (MI), a reflection of the extent of methylation. The log-rank test and Cox regression were used to identify the predictor of contralateral UTUC recurrence.

Results

Thirty (4.5%) patients developed a subsequent contralateral UTUC after a median follow-up time of 27.5 (range: 2–139) months. Promoter methylation for at least one gene promoter locus was present in 88.9% of UTUC. Fewer methylation and lower MI (P = 0.001) were seen in the tumors with contralateral UTUC recurrence than the tumors without contralateral recurrence. High MI (P = 0.007) was significantly correlated with poor cancer-specific survival. Multivariate analysis indicated that unmethylated RASSF1A (P = 0.039), lack of bladder recurrence prior to contralateral UTUC (P = 0.009), history of renal transplantation (P < 0.001), and preoperative renal insufficiency (P = 0.002) are independent risk factors for contralateral UTUC recurrence after RNU.

Conclusions

Our data suggest a potential role of DNA methylation in predicting contralateral UTUC recurrence after RNU. Such information could help identify patients at high risk of new contralateral UTUC recurrence after RNU who need close surveillance during follow up.     

Association of perioperative blood transfusion with oncologic outcomes after radical nephroureterectomy for upper tract urothelial carcinoma

BackgroundTo test the hypothesis that perioperative blood transfusion (PBT)impacts oncologic outcomes of patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).MethodsRetrospective analysis of 2492 patients with UTUC treated at 23 institutions with RNU between 1987 and 2007.Cox regression models addressed the association of PBT with disease recurrence, cancer-specific mortality and any-cause mortality.ResultsA total of 510 patients (20.5%) patients received PBT. Within a median follow-up of 36 months (Interquartile range: 55 months), 663 (26.6%) patients experienced disease recurrence, 545 patients (21.9%) died of UTUC and 884 (35.5%) patients died from any cause. Patients who received PBT were at significantly higher risk of disease recurrence, cancer-specific mortality and overall mortality than patients not receiving PBT in univariable Cox regression analyses. In multivariable Cox regression analyses that adjusted for the effects of standard clinicopathologic features, PBT did not remain associated with disease recurrence (HR: 1.11; 95% CI 0.92–1.33, p = 0.25), cancer-specific mortality (HR: 1.09; 95% CI 0.89–1.33, p = 0.41) or overall mortality (HR: 1.09; 95% CI 0.93–1.28, p = 0.29).ConclusionsIn patients undergoing RNU for UTUC, PBT is associated with disease recurrence, cancer-specific survival or overall survival in univariable, but not in multivariable Cox regression analyses.     

Prognostic relevance of postoperative platelet count in upper tract urothelial carcinoma after radical nephroureterectomy

Aim of the studyTo assess the impact of perioperative platelet count (PLT) kinetics on recurrence-free survival (RFS) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).MethodsFrom three prospectively maintained databases of three tertiary care centres a total of 269 patients undergoing RNU without perioperative treatment between 1996 and 2011 were considered for this analysis. Pre- and postoperatively elevated PLT count was defined as >400 × 10⁹/L. PLT levels were measured 1–3 days preoperatively and 7–10 days postoperatively. The median follow-up was 24 months (Interquartile range (IQR): 10–52). A new weighted scoring model was developed to predict recurrence after RNU based on significant parameters of multivariable analysis.ResultsThe 5-year RFS in patients with preoperatively normal and elevated PLT count was 58.3% and 29.3%, respectively (p < 0.001). The 5-year-RFS was 57.6% in patients with normal postoperative PLT count and 29.7% in those with elevated PLT levels (p < 0.001). In multivariable analysis, pT-stage, lymphovascular invasion, ureteral margin status and postoperative thrombocytosis remained independent predictors for RFS. The 5-year RFS in patients with a score of 0 (low-risk), 1 (intermediate-risk) and 2–4 (high-risk) was 77.7%, 47.5% and 12.3%, respectively (p < 0.001). Consideration of the variable postoperative thrombocytosis in the final model increased its predictive accuracy by 1.9% with a concordance index of 0.758 (p = 0.015).ConclusionPLT kinetics is significantly associated with RFS after RNU for UTUC. We constructed a simple, PLT-based prognostic model for recurrence after RNU.     

Prolonged pneumoperitoneum time is an independent risk factor for intravesical recurrence after laparoscopic radical nephroureterectomy in upper tract urothelial carcinoma

Objective

To evaluate the impact of pneumoperitoneum time on intravesical recurrence (IVR) in upper tract urothelial carcinoma (UTUC) patients who underwent laparoscopic radical nephroureterectomy (LRNU).

上尿路尿路上皮癌淋巴结清扫的研究进展

上尿路尿路上皮癌(UTUC)指发生于肾盂及输尿管的尿路上皮恶性肿瘤，约占全部尿路上皮癌的 5%～10%。目前，UTUC淋巴引流的解剖范围暂不明确，一些研究表明淋巴结清扫范围对患者生存的影响可能大于清扫淋巴结数量的影响，但这一观点尚未得到证实。近年来，由于微创手术的快速发展，虽然在技术操作方面和标准化方面取得了重大进展，但对于淋巴结清扫的意义和范围仍缺乏共识。本文就UTUC淋巴结清扫的意义、范围、适应证、并发症及微创手术地位的研究进展作一综述。     

Management of upper urinary tract urothelial carcinoma

Upper urinary tract urothelial carcinoma (UTUC) is relatively uncommon. In this article, we review prognostic factors, criteria and indications for treatment with the available modalities using contemporary data. A systematic search on PubMed was performed using the keywords ‘upper tract urothelial carcinoma’, ’upper tract transitional cell carcinoma’, ’nephroureterectomy’, ‘laparoscopic’, ‘endoscopic’ and ‘prognostic factor’. The literature on UTUC is scarce. No prognostic factors have been formally validated in either the diagnosis or treatment of UTUC. The gold-standard management for invasive UTUC is radical nephroureterectomy with a bladder-cuff excision. Laparoscopic and endoscopic approaches represent alternatives in properly selected individuals. Segmental ureterectomy may also be considered. The extent and role of lymph node dissection remains to be validated. Chemotherapy may also be considered in select patients. Additional multi-institutional studies are needed to identify and validate prognostic factors that can predict the outcomes of patients diagnosed with UTUC. Randomized controlled trials are needed to assess the efficacy of the treatment modalities.     

Highly predictive survival nomogram after upper urinary tract urothelial carcinoma

BACKGROUND:

Nephroureterectomy is the surgical standard of care for patients with upper urinary‐tract urothelial carcinoma. The objectives of the current study were to identify the most informative predictors of cancer‐specific mortality after nephroureterectomy, to devise an algorithm capable of predicting the individual probability of cancer‐specific mortality, and to compare its prognostic accuracy to that of the International Union Against Cancer (UICC) staging system.

METHODS:

Within the Surveillance, Epidemiology, and End Results database, the authors identified 5918 patients who had been treated with nephroureterectomy. Within the development cohort (n = 2959), multivariate Cox regression models predicting cancer‐specific mortality were fitted by using age, stage, nodal status, sex, grade, race, type of surgery (nephroureterectomy with or without bladder‐cuff removal), and tumor location (renal pelvis vs ureter). Backward variable elimination according to the Akaike information criterion identified the most accurate and parsimonious model. Model validation and calibration were performed within the external validation cohort (n = 2959). External validation was also applied to the UICC staging system.

RESULTS:

The 5‐year freedom from cancer‐specific mortality rates in both the development and external validation cohorts was 77.3%. The most informative and parsimonious nomogram for cancer‐specific‐mortality–free survival relied on age, pT and pN stages, and tumor grade. In external validation, nomogram prediction of 5‐year cancer‐specific‐mortality–free rate was 75.4% accurate and was significantly better (P < .001) than the UICC staging system (64.8%).

CONCLUSIONS:

The current nomogram is capable of predicting the prognosis in patients with upper urinary‐tract urothelial carcinoma treated by nephroureterectomy with better accuracy than the UICC staging system. The authors recommend the application of this nomogram to routine clinical practice when counseling or making clinical decisions. Cancer 2010. © 2010 American Cancer Society.     

腔内激光手术治疗肾盂输尿管肿瘤

目的:通过对无法行根治性手术的上尿路上皮肿瘤患者进行腔内红激光治疗情况进行总结,评价该术式的有效性与安全性.方法:对于我院2013年1月到2016年6月期间收治的肾盂、输尿管肿瘤,其中13例行腔内激光手术治疗,分别就术中情况、术后并发症及疗效进行总结.结果:13例患者中,肾盂肿瘤行经皮肾镜激光手术9例,输尿管肿瘤行输尿管镜激光手术4例,平均手术时间分别为(47.22±6.25)min、(25.0±4.84)min;平均出血量分别约为(133.33±24.94)ml、(40.0±7.07)ml;血尿及肾积水情况得到控制,5/13例呈现局部进展,1/13例术后10个月死亡;未出现严重并发症.结论:对于特殊情况下的肾盂、输尿管肿瘤患者,腔内激光手术具有创伤小,止血效果好,可以姑息性切除肿瘤,降低肿瘤负荷,保护肾脏功能,也能减缓肿瘤进展,可以作为这一类患者的首选治疗方案.     

Anatomical templates of lymph node dissection for upper tract urothelial carcinoma: a systematic review of the literature

Introduction: Indications and techniques of lymph node dissection (LND) for upper tract urothelial carcinoma (UTUC) are still controversial.

Areas covered: In this study, a systematic review of the English-language literature was performed up to 1 July 2016 using the Medline, Scopus, Cochrane Library and Web of Sciences databases to provide a detailed overview of the most commonly dissected surgical templates of LND for UTUC according to laterality and location of the tumor. Overall, sixteen studies were analyzed. Based on the shared experiences in the scientific literature, the LND template typically included: for right-sided tumors of the renal pelvis, upper third and middle third of the ureter, the renal hilar, paracaval, precaval and retrocaval nodes, while for left-sided tumors the renal hilar, paraaortic and preaortic nodes. For tumors of the lower ureter, an extended pelvic LND was performed in most cases; however, the paracaval, paraaortic or presacral nodes were dissected in selected series.

Expert commentary: LND is not routinely performed at the time of surgery for UTUC and both indication and extent of LND vary among surgeons and institutions. Future high-quality studies are needed to define the most accurate LND templates and to assess their oncological efficacy and surgical morbidity.     

Novel strategies for treating relapsed/refractory urothelial carcinoma

Advanced urothelial cancer is associated with a poor prognosis and there has been no substantial progress over the past three decades since the development of platinum-based multiagent chemotherapy. Clinical trials evaluating novel agents and combinations including chemotherapeutic drugs, as well as targeted inhibitors, are desperately needed. With a better understanding of the complex molecular alterations that drive urothelial tumorigenesis, new targets for novel therapeutics are being defined. This article will describe the current state of advanced urothelial cancer treatment and provide a comprehensive discussion of novel agents in development.     

Molecular classification and diagnostics of upper urinary tract urothelial carcinoma

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External validation of an online nomogram in patients undergoing radical nephroureterectomy for upper urinary tract urothelial carcinoma

Background:

The objective was to validate an online nomogram developed based on the French collaborative national database on upper urinary tract urothelial carcinoma (UUT-UC) using a different cohort.

Methods:

The study comprised 328 patients with UUT-UC who underwent radical nephroureterectomy. The discrimination of models was quantified using Harrell''s concordance index. The relationship between the model-derived and actuarial cancer-specific mortality was graphically explored within calibration plots. Calibration was also assessed using the quartiles of the predicted survival at 3 and 5 years and calculation of the corresponding observed Kaplan–Meier estimates. Clinical net benefit was evaluated constructing decision curve analysis.

Results:

The discrimination accuracy of the nomograms at 3 and 5 years was 71.6% and 71.8%, respectively. Although nomograms discriminated well by Kaplan–Meier curves, and log-rank tests were all highly significant, the calibration plots tended to exaggerate the overestimation of mortality between predicted and observed probabilities at 3 and 5 years for survival. When compared with the AJCC/UICC staging system, the nomograms performed well across a wide range of threshold probabilities using decision curve analysis.

Conclusion:

The online nomogram is a highly accurate prognostic tool for patients with UUT-UC treated with radical nephroureterectomy. The model can provide an accurate estimate of the individual risk of cancer-specific mortality. Further improvement and implementation of novel molecular marker is needed.     

High visfatin expression predicts poor prognosis of upper tract urothelial carcinoma patients

Visfatin, a newly discovered adipocytokine, is a pro-inflammatory cytokine. This study aimed to evaluate the predictive value of visfatin on prognosis of patients with upper tract urothelial carcinoma. One-hundred and five patients (median age=64, range=24-84 years) were included in this study. Visfatin expression in upper tract urothelial carcinoma tissues was analyzed by immunohistochemistry. Visfatin expression was correlated with clinicopathologic variables using the χ² test. The prognostic value of visfatin for recurrence-free and cancer-specific survival was evaluated by Kaplan-Meier estimates, and the significance of differences between curves was evaluated by the log-rank test. Cox regression model was also used to evaluate the hazard ratios of visfatin on survival. High visfatin expression in upper tract urothelial carcinoma tissues was significantly correlated with tumor stage (P=0.001), grade (P=0.007) and p53 expression (P=0.07). High visfatin expression was associated with poor recurrence-free and cancer-specific survival. Cox regression analysis also revealed that visfatin is an independent predictor of recurrence-free (HR=3.22, P=0.009) and cancer-specific survival (HR=5.74, P=0.023). Our findings indicated that higher visfatin expression is a potential biomarker to predict patient survival. Further study is necessary to investigate the role of visfatin in the carcinogenesis of upper tract urothelial carcinoma.     

Diagnostic accuracy of ureteroscopic biopsy in predicting stage and grade at final pathology in upper tract urothelial carcinoma: Systematic review and meta-analysis

ObjectiveTo assess the accuracy of ureteroscopic (URS) biopsies in predicting stage and grade at final pathology in upper tract urothelial carcinoma (UTUC).Materials and methodsThe meta-analysis was performed in accordance with the PRISMA statement. Studies providing data on tumor stage and grade at URS biopsy and surgical specimens were included. The negative predictive value (NPV) implies concordance between the absence of subepithelial connective tissue invasion or the presence of low-grade tumors at URS biopsy and the absence of a muscle-invasive disease in the final pathology.ResultsA total of 23 studies were included (3547 patients). The stage-to-stage match between URS biopsy/final pathology showed a positive predictive value (PPV) for cT1+/muscle-invasive disease of 94% (95% CI: 84%–100%) and a NPV for cTa-Tis/non-muscle-invasive disease of 60% (95% CI: 52%–68%). The grade-to-grade match between URS biopsy/final pathology was 66% (95% CI: 55%–77%) for low-grade (cLG/pLG) tumors and 97% (95% CI: 94%–98%) for high-grade (cHG/pHG) tumors. The PPV for cHG/muscle-invasive disease was 60% (95% CI: 54%–66%) and the NPV for cLG/non-muscle-invasive disease was 77% (95% CI: 73%–82%). The undergrading and understaging rates were 32% (95%CI: 25%–38%) and 46% (95% CI: 38%–54%), respectively.ConclusionsThere is a substantial correlation between tumor grade at URS biopsy and the final pathology. The identification of cHG tumors and subepithelial connective tissue invasion (cT1+) in URS biopsy showed a moderate and a strong correlation with invasive UTUC, respectively. Nevertheless, a certain risk of undergrading and understaging should be assumed.     

The clinicopathological characteristics of muscle-invasive bladder recurrence in upper tract urothelial carcinoma

This study aimed to clarify the clinical characteristics and oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who developed muscle-invasive bladder cancer (MIBC) after radical nephroureterectomy (RNU). We identified 966 pTa-4N0-2M0 patients with UTUC who underwent RNU and clarified the risk factors for MIBC progression after initial intravesical recurrence (IVR). We also identified 318 patients with primary pT2-4N0-2M0 MIBC to compare the oncological outcomes with those of patients with UTUC who developed or progressed to MIBC. Furthermore, immunohistochemical examination of p53 and FGFR3 expression in tumor specimens was performed to compare UTUC of MIBC origin with primary MIBC. In total, 392 (40.6%) patients developed IVR after RNU and 46 (4.8%) developed MIBC at initial IVR or thereafter. As a result, pT1 stage on the initial IVR specimen, concomitant carcinoma in situ on the initial IVR specimen, and no intravesical adjuvant therapy after IVR were independent factors for MIBC progression. After propensity score matching adjustment, primary UTUC was a favorable indicator for cancer-specific death compared with primary MIBC. Subgroup molecular analysis revealed high FGFR3 expression in non-MIBC and MIBC specimens from primary UTUC, whereas low FGFR3 but high p53 expression was observed in specimens from primary MIBC tissue. In conclusion, our study demonstrated that patients with UTUC who develop MIBC recurrence after RNU exhibited the clinical characteristics of subsequent IVR more than those of primary UTUC. Of note, MIBC subsequent to UTUC may have favorable outcomes, probably due to the different molecular biological background compared with primary MIBC.