Prognostic value of lymph node dissection in patients with muscle-invasive transitional cell carcinoma of the upper urinary tract

OBJECTIVES: To analyze the prognostic role of lymphadenectomy (LND) in patients with muscle-invasive transitional cell carcinoma (TCC) of the upper urinary tract (UUT) managed with radical surgery. METHODS: From 1986 to 2003, 132 consecutive patients with muscle-invasive TCC of the UUT underwent radical surgery. LND was performed in 95 cases. Patients were stratified according to the presence of LND and lymph node (LN) status. Univariable and multivariable Cox regression models determined the effect of age, pT, grade, nodal status (pN), number of LNs removed, year of surgery, and postoperative chemotherapy on disease-free survival (DFS) and cancer-specific survival (CSS) in the overall population and in patients who underwent LND. RESULTS: The actuarial 5-yr CSS in pNx patients was significantly worse than in pN0 patients (48% vs. 73%, p=0.001) and comparable to pN+ outcome (48% vs. 39%, p=0.476). In the entire population, multivariable Cox regression analyses indicated that pT and pN status were independent predictors of DFS (p=0.04, hazard ratio [HR]=1.82 and p<0.01, HR=1.34, respectively) and CSS (p<0.01, HR=2.42 and p=0.04, HR=1.32, respectively). In patients who underwent LND, the number of LNs removed was an independent predictor of DFS (p=0.03, HR=0.928) and of CSS (p=0.007, HR=0.903). The extent of LND again resulted in an independent predictor either of DFS or CSS (p=0.04, HR=0.904 and p=0.01, HR=0.867, respectively) in the subgroup of pN0 patients. CONCLUSIONS: LND emerged as a strong independent predictor of DFS and CSS in patients surgically managed for a muscle-invasive TCC of the UUT.     

Prognostic value of lymph node yield during nephroureterectomy for upper tract urothelial carcinoma

Introduction

Lymph node dissection (LND) performed during radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) remains controversial and difficult to evaluate. The aim of this study was to investigate whether removal of more lymph nodes during RNU is safe and improves oncologic outcomes.

The emerging role of lymphadenectomy in upper tract urothelial carcinoma

Within the last decade, there has been an increased focus on lymphadenectomy or lymph node dissection (LND) in patients with upper tract urothelial carcinoma (UTUC). Although the data with regards to LND in UTUC are sparse, investigators are beginning to evaluate the role and define the anatomy to understand how LND may affect outcomes in patients with UTUC. This article reviews the history of LND for UTUC, outlines the relative anatomy, and evaluates the arguments and evidence for, and against, LND in patients with UTUC.     

Risk factors for intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma: A meta-analysis

PurposeAfter radical nephroureterectomy (RNU), approximately 22% to 47% of patients with upper tract urothelial carcinoma (UTUC) develop a subsequent intravesical recurrence (IVR). Considering this high incidence of occurrence, several risk factors were reported as predictive of IVR after RNU. Until recently, most of the risk factors were still under debate. The aim of study was to conduct a meta-analysis based on the recent literature to explore the risk factors for IVR after RNU for UTUC.Patients and methodsAn electronic search of the Medline, Embase, Cochrane Library, CancerLit, and ClinicalTrials.gov databases was performed to identify relevant studies published before May 2013. The studies were included if they reported risk factors related to bladder or IVR after RNU for UTUC.ResultsOverall, 40 studies, with 12,010 patients, were included in our meta-analysis. Our study indicated that a statistically significant difference in IVR after RNU was found in the male vs. female patients (odds ratio [OR] = 0.72, 95% CI: 0.59–0.85), ureteral vs. renal pelvis (OR = 1.18, 95% CI: 1.00–1.36), T2–4 vs. Tis, Ta, and T1 (OR = 0.53, 95% CI: 0.40–0.66), larger vs. smaller tumor size (OR = 1.02, 95% CI: 1.01–1.03), and previous/synchronous bladder cancer vs. the absence of bladder cancer (OR = 1.59, 95% CI: 1.26–1.9). No significant differences in IVR after RNU were found in the younger vs. older age groups, multifocal tumors vs. single tumor, G3 vs. G1 and G2, high vs. low grade, N0 vs. N+, concomitant carcinoma in situ vs. the absence of carcinoma in situ, positive vs. negative lymphovascular invasion, open vs. laparoscopic nephroureterectomy, and endoscopic vs. transvesical technique.ConclusionsOur study showed that female patient; ureteral tumor; larger tumor; Tis, Ta, and T1; and the history of bladder cancer were significant risk factors related to IVR after RNU.     

Comparative analysis of comorbidity and performance indices for prediction of oncological outcomes in patients with upper tract urothelial carcinoma who were treated with radical nephroureterectomy

ObjectiveComorbidity and performance indices (CPIs) are useful tools to evaluate patient?s risk of comorbidities and thus may guide clinical decision making regarding surgery or multimodal therapy approaches. Hence, the aim of the current study was to assess the predictive capacity of CPIs comprising the American Society of Anaesthesiologists (ASA)-score, the Charlson comorbidity index (CCI), the age-adjusted CCI (ACCI), and the Eastern Cooperative Oncology Group performance status (ECOG-PS) in patients with upper tract urothelial carcinoma (UTUC) who were treated with radical nephroureterectomy (RNU).Methods and materialsA total of 242 patients with UTUC underwent RNU without neoadjuvant chemotherapy between 1992 and 2012 at 3 German academic centers. Patients were stratified according to the pre-RNU CPIs dichotomized as ASA 1/2 vs.≥3, CCI 0 to 2 vs.>2, ACCI 0 to 5 vs. >5, and ECOG-PS 0 to 1 vs. >1. We assessed the associations of CPIs with clinicopathologic features, as well as the prognostic effect on recurrence-free survival, cancer-specific survival (CSS), overall survival, and cancer-independent mortality (CIM), using univariable and multivariable Cox regression analyses.ResultsSixty-two patients (25.6%) had an ASA-score≥3, 71 patients (29.3%) a CCI>2, 50 patients (20.7%) an ACCI>5, and 122 (50.4%) patients an ECOG-PS>1. The ASA-score (P = 0.001), CCI (P = 0.029), and the ECOG-PS (P<0.001) were significantly associated with age. In addition, the ECOG-PS was associated with pelvicalyceal tumors (P = 0.012), and the CCI with preoperative hydronephrosis (P = 0.026). The median follow-up was 30 months. In Kaplan-Meier analyses, ACCI>5 (P≤0.025) and ECOG-PS>1 (P≤0.042) were associated with recurrence-free survival, CSS, and overall survival, and ASA-score≥3 (P = 0.011) and ACCI>5 (P = 0.006) with CIM. In multivariable analysis that adjusted for standard clinicopathologic parameters, an ECOG-PS>1 was an independent predictor for CSS (hazard ratio = 1.89, P = 0.019), and an ASA-score≥3 (hazard ratio = 1.86, P = 0.026) was a predictor for CIM.ConclusionCPIs are easy assessable predictors for outcome in patients with UTUC who were treated with RNU. CPIs have carefully to be taken into account in patient counseling regarding operative decision making and multimodal treatment.     

Neoadjuvant and adjuvant chemotherapy use in upper tract urothelial carcinoma

Objective

To determine trends in neoadjuvant and adjuvant chemotherapy use for upper tract urothelial cancer and assess its effects on survival.

Preoperative prognostic nutritional index is a significant predictor of survival in patients with localized upper tract urothelial carcinoma after radical nephroureterectomy

Background

Patient's nutritional and immunological status have a potentially significant role in survival outcome in patients with malignant tumors. We investigated the prognostic value of preoperative prognostic nutritional index (PNI) in patients with localized upper tract urothelial carcinoma (UTUC) undergoing radical nephrouretectomy (RNU).

机器人辅助技术在双侧上尿路尿路上皮癌治疗中的应用和研究进展

上尿路尿路上皮癌(Upper tract urothelial carcinoma,UTUC)是一种泌尿系相对罕见的疾病,其双侧发病则更为罕见。病因学上,UTUC和膀胱癌有一些共同的致病因素,但两种疾病在临床特征和外科治疗上则不尽相同。随着泌尿外科腹腔镜手术的普及,腹腔镜下根治性肾-输尿管切除术和膀胱袖口状切除术(Laparoscopic nephroureterectomy with bladder cuff excision,LNUBCE)已经成为泌尿外科治疗UTUC的主流方法。机器人外科手术系统因其直观清晰的手术视觉效果和较高的灵敏度,弥补了腹腔镜手术存在的缺陷,使机器人根治性肾-输尿管切除术和膀胱袖口状切除术(Robotic nephroureterectomy with bladder cuff excision,RNUBCE)逐渐被大家所接受。本文对近年机器人手术系统在双侧上尿路尿路上皮癌治疗中的应用和研究进展进行综述。     

Variant histology as a significant predictor of survival after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma

Objectives

To investigate the effect of variant histology (VH) on survival after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma (UTUC) and the effect of adjuvant chemotherapy on the survival of patients with UTUC with VH.

Overall survival in patients with metastatic renal cell carcinoma and clinical N1 disease undergoing cytoreductive nephrectomy and lymph node dissection

Background

Patients with metastatic renal cell carcinoma (mRCC) have limited treatment options. Cytoreductive nephrectomy (CN) in select patients has been associated with improved survival. We aim to assess the survival in patients with mRCC and cN1 disease who underwent CN with and without lymph node dissection (LND).

Risk stratification of patients with nodal involvement in upper tract urothelial carcinoma: value of lymph-node density

OBJECTIVE

To determine the risk factors associated with clinical outcome in patients with lymph node (LN)‐positive urothelial carcinoma of the upper urinary tract (UTUC) treated with radical nephroureterectomy (RNU) and lymphadenectomy, focusing on the concept of LN density (LND).

PATIENTS AND METHODS

Patients undergoing RNU with regional lymphadenectomy were identified through multi‐institutional databases. All pathology slides were re‐evaluated by genitourinary pathologists unaware of the clinical data. The exposure variable used was LND (continuously coded and that of all possible thresholds) with recurrence‐free and disease‐specific survival (DSS) serving as the outcome measures.

RESULTS

Of 432 patients undergoing RNU with lymphadenectomy, 135 (31%) had LN metastases. Within a median follow‐up of 4.1 years, 90 of the 135 patients with LN metastases (68%) had disease recurrence and 76 (58%) died from UTUC. The mean (sem ) 5‐year recurrence‐free and DSS probabilities were 27 (4)% and 33 (5)%, respectively. The median (range) LND was 50 (3–100)%. The most informative threshold for LND in relation to outcome was 30%. In multivariable analyses that adjusted for the effects of tumour stage and grade, patients with a LND of ≥30% were at greater risk of both cancer recurrence, with 5‐year rates of 25 (5)% vs 38 (8)% (hazard ratio 1.8, P = 0.021) and mortality, with 5‐year rates of 30 (6)% vs 48 (9)% (1.7, P = 0.032) compared to those with a LND of <30%. Our results are primarily limited by a lack of standardization in the lymphadenectomy template.

CONCLUSION

We evaluated the concept of LND for the first time in UTUC. LND provides additional prognostic information in patients with node‐positive disease after RNU. The use of LND in clinical trials might provide an additional insight into the value of LN dissection in patients undergoing RNU.     

Laparoscopic versus open nephroureterectomy for the treatment of upper urinary tract urothelial carcinoma: a systematic review and cumulative analysis of comparative studies

Context

Laparoscopic nephroureterectomy (LNU) has increasingly been used as a minimally invasive alternative to open nephroureterectomy (ONU), but studies comparing the efficacy and safety of the two surgical procedures are still limited.

Objective

Evaluate the oncologic and perioperative outcomes of LNU versus ONU in the treatment of upper urinary tract urothelial carcinoma.

Evidence acquisition

A systematic review and cumulative analysis of comparative studies reporting both oncologic and perioperative outcomes of LNU and ONU was performed through a comprehensive search of the Medline, Embase, and the Cochrane Library electronic databases. All analyses were performed using the Review Manager (RevMan) v.5 (Nordic Cochrane Centre, Copenhagen, Denmark) and Meta-analysis In eXcel (MIX) 2.0 Pro (BiostatXL) software packages.

Evidence synthesis

Twenty-one eligible studies (1235 cases and 3093 controls) were identified. A significantly higher proportion of pTa/Tis was observed in LNU compared to ONU (27.52% vs 22.59%; p = 0.047), but there were no significant differences in other stages and pathologic grades (all p > 0.05). For patients who underwent LNU, the 5-yr cancer-specific survival (CSS) rate was significantly higher, at 9% (p = 0.03), compared to those who underwent ONU, while the overall recurrence rate and bladder recurrence rate were notably lower, at 15% (p = 0.01) and 17% (p = 0.02), respectively. However, there were no statistically significant differences in 2-yr CSS, 5-yr recurrence-free survival (RFS), 5-yr overall survival (OS), 2-yr OS, and metastasis rates between LNU and ONU (all p > 0.05). Moreover, there were no significant differences between LNU and ONU in terms of intraoperative complications, postoperative complications, and perioperative mortality (all p > 0.05). The results of our study were mainly limited by the retrospective design of most of the individual studies included as well as selection biases based on different management of regional lymph nodes and pathologic characteristics.

Conclusions

Our data suggest that LNU offers reliable perioperative safety and comparable oncologic efficacy when compared to ONU. Given that some limitations cannot be overcome, well-designed prospective trials are needed to confirm our findings.     

Optimizing management of upper tract urothelial carcinoma

Upper tract urothelial cancer (UTUC) is a rare cancer of the urothelium, comprising only a fraction of cases as compared to urothelial tumors of the bladder. As a result, systemic treatment approaches in bladder cancer are often applied to patients with UTUC. Given the anatomical location of these tumors, the age, the comorbid conditions of these patients with UTUC, and the need for radical nephroureterectomy for treatment, most patients have substantial impairment of renal reserve. There is growing evidence for the benefit of perioperative chemotherapy in this disease. Patients with UTUC have high rates of microsatellite instability and fibroblast growth factor receptor 3 mutations as compared to their bladder counterparts presenting unique, important subsets in UTUC. Immune checkpoint inhibitors targeting the programmed death receptor 1 and ligand have provided a new second-line treatment option for patients with UTUC and appear particularly well suited for patients with microsatellite instability. More work in understanding the molecular gene signatures and its relationship to response to chemotherapy, immunotherapy, and targeted therapy is needed to continually optimize care for patients with all stages of disease. Advances in UTUC are possible, when one accounts for the unique clinical and biological features of this disease.     

Degree of hydronephrosis predicts adverse pathological features and worse oncologic outcomes in patients with high-grade urothelial carcinoma of the upper urinary tract

ObjectiveTo evaluate degree of hydronephrosis (HN) as a surrogate for adverse pathological features and oncologic outcomes in patients with high-grade (HG) and low-grade (LG) upper tract urothelial carcinomas (UTUCs).MethodsWe retrospectively reviewed 141 patients with localized UTUCs that underwent extirpative surgery at a tertiary referral center. Preoperative imaging was used to evaluate presence and degree of ipsilateral HN. We evaluated degree of HN (none/mild vs. moderate/severe), pathological findings, and oncologic outcomes.ResultsHG UTUC was present in 113 (80%) patients, muscle-invasive disease (≥pT2) in 49 (35%), and non–organ-confined disease (≥pT3) in 41 (29%). At a median follow-up of 34 months, 49 (35%) patients experienced intravesical recurrence, 28 (20%) developed local/systemic recurrence, and 24 (17%) died of UTUC. HN was graded as none/mild in 77 (55%) patients and moderate/severe in 64 (45%). In patients with HG UTUC, but not LG, degree of HN was associated with advanced pathological stage (P<0.001), positive lymph nodes (P = 0.01), local/systemic recurrence-free survival (hazard ratio [HR] = 5.5, P = 0.02), and cancer-specific survival (HR = 5.2, P = 0.02). On multivariable analysis of preoperative factors, degree of HN in patients with HG UTUC was associated with muscle invasion (HR = 9.3; 95% CI: 3.08–28.32; P<0.001), non–organ-confined disease (HR = 4.5; 95% CI: 1.66–12.06; P = 0.003), local/systemic recurrence-free survival (HR = 2.5; 95% CI: 1.07–5.64; P = 0.04), and cancer-specific survival (HR = 2.6; 95% CI: 1.05–6.22; P = 0.04).ConclusionsDegree of HN can serve as a surrogate for advanced disease and predict worse oncologic outcomes in HG UTUC. Degree of HN was not predictive of intravesical or local/systemic recurrence in LG UTUC.     

The role of lymph node dissection in renal cell carcinoma

The role of lymph node dissection (LND) in the staging and treatment of renal cell carcinoma has long been a topic of debate. The controversy has focused on whether LND is purely an adjunctive staging procedure or has a therapeutic role in the management of this disease. Potential benefits include enhanced staging, better selection for adjuvant therapies/clinical trials, a decrease in recurrence rates, and improved disease-specific and overall survival. This article reviews the available literature on LND in renal cell carcinoma and discusses the potential benefits of aggressive surgical resection in select high-risk patients.     

Retroperitoneal lymph node dissection in patients with interaortocaval lymph node metastases of transitional cell carcinoma of the urinary tract

Three patients suffered from renal pelvic, ureteral and bladder cancers that were treated with both standard surgical treatments and two adjuvant cycles of cisplatin-based combination chemotherapy. Metastases of interaortocaval lymph nodes were detected in all patients between 9 and 33 months from the surgery for primary lesions. All patients received three cycles of cisplatin-based combination chemotherapy and retroperitoneal lymph node dissection (RPLND). The chemotherapy achieved partial response (62-98%). Two patients with viable cancer cells died with hepatic metastases; the first 15 months and the second 25 months from the date of diagnosis of distant lymph node metastasis. The third patient, who had no viable cancer cells, remains alive and disease-free 36 months later. Therefore, RPLND after chemotherapy provides prognostic information that helps to define patients who might benefit from additional systemic chemotherapy.     

Effect of tumor size on recurrence-free survival of upper tract urothelial carcinoma following surgical resection

ObjectiveTo identify predictors of recurrence-free survival (RFS) based on the clinicopathological features of patients with upper tract urothelial carcinoma (UTUC) who have undergone radical nephroureterectomy (RNU) with bladder cuff resection.Materials and methodsWe retrospectively reviewed the records of patients from October 1998 to July 2012 at our tertiary institution and identified 120 patients with sufficient data who underwent RNU for UTUC. We recorded various clinical and histopathological parameters as potential predictors of outcome. Recurrence was defined as any occurrence of urothelial carcinoma after RNU either intravesically, local/regionally, or at distant sites. Univariate, multivariate, and RFS analyses were conducted using the Cox regression and Kaplan-Meier methods.ResultsThe median age of our cohort was 71 years (interquartile range: 64–78). Median RNU-specimen tumor size was 3.0 cm (interquartile range: 2.0–5.0 cm). Fifty-four patients (45%) had a tumor<3.0 cm and 66 (55%) had a tumor≥3.0 cm. Eighty patients (66.7%) had organ-confined UTUC (≤pT2) and 40 (33.3%) had non–organ-confined UTUC (≥pT3). Sixty-five patients (54.2%) experienced at least 1 recurrence. Forty-three patients (35.8%) had at least 1 episode of intravesical recurrence and 28 (23.3%) had distant recurrence. A multivariate analysis revealed non–organ-confined disease (hazard ratio [HR] = 3.62, P<0.001), tumor diameter≥3 cm (HR = 1.97, P = 0.011), and male gender (HR = 1.81, P = 0.047) to be significant independent predictors of disease recurrence. The 5-year RFS rate was 46.9% and 25.8% for patients with tumor size<3 and≥3 cm, respectively.ConclusionsFollowing RNU, the incidence of recurrence remains high among patients with UTUC. In our cohort of patients, tumor diameter≥3.0 cm, non–organ-confined UTUC, and male gender constitute important risk factors for poor RFS outcomes following RNU. These patients require diligent postoperative surveillance and may potentially benefit from perioperative systemic therapy.     

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目的 分析进展期胃癌胃周淋巴结转移及淋巴结清除与病人预后的关系。方法 对1982－1992年间收治并行手术治疗的进展期胃癌299例进行统计分析。结果 肿瘤进展与淋巴结转移的程度显著相关（P＜0.05）。淋巴结转移有无、淋巴结清扫与术后生存直接相关，对于侵及浆膜下或侵出浆膜并伴有远处淋巴结转移的病例，淋巴结清扫仍能提高术后生存率（P＜0.05）。结论 严格的淋巴结清扫可以提高胃癌病人术后生存率。     

Urothelial carcinoma of the upper urinary tract: surgical approach and prognostic factors

OBJECTIVES: Open radical nephroureterectomy (O-RNU) has been the gold standard for the treatment of upper urinary tract urothelial carcinoma (UUT-UC) for decades. With the advances in laparoscopic techniques and endourologic procedures, this concept has been increasingly challenged. Oncologic outcome prediction is mainly based on stage and grade. With progress in medical treatment, adjuvant therapies may gain importance in the future. This review assesses the values of the variety of available treatments as well as prognostic factors that may become relevant regarding patient selection for future adjuvant treatment trials. METHODS: We performed a systematic literature research using MEDLINE with emphasis on open surgical, laparoscopic, and endourologic (ureteroscopic or percutaneous) techniques and prognostic contents. RESULTS: Overall, no evidence level 1 information from prospective randomised trials is available for treatment of UUT-UC. Laparoscopic radical nephroureterectomy (L-RNU) is increasingly challenging open surgery. Currently, L-RNU should be reserved for low-stage, low-grade tumours. Ureteroscopy and percutaneous nephron-sparing techniques show favourable survival data but high local recurrence rates. Regarding prognosis, estimation of outcome still relies mainly on stage and grade because no additional parameters have been introduced in a routine clinical setting. CONCLUSIONS: O-RNU still represents the gold standard for the treatment of UUT-UC. The laparoscopic approach is not yet standard of care and should be reserved for low-stage, low-grade tumours. Endourologic nephron-sparing treatments are still experimental in elective indications due to high local recurrence rates. For prognosis, no parameters in addition to stage and grade have been standardised.