Impact of ureteroscopy before radical nephroureterectomy for upper tract urothelial carcinomas on oncological outcomes: a meta-analysis.

OBJECTIVES: To investigate whether ureteroscopy (URS) before radical nephroureterectomy (RNU) for upper tract urothelial carcinomas (UTUCs) has an impact on oncological outcomes. PATIENTS AND METHODS: We performed a systematic literature search of PubMed, Web of Science, and EMBASE for citations published prior to September 2017 that described URS performed on patients with UTUC and conducted a standard meta-analysis on survival outcomes. RESULTS: Our meta-analysis included eight eligible studies containing 3975 patients. The results were as follows: cancer-specific survival (CSS; hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59-0.99; P = 0.04), overall survival (OS; HR 0.76, 95% CI 0.48-1.21; P = 0.24), recurrence-free survival (RFS; HR 0.89, 95% CI 0.69-1.14; P = 0.37), metastasis-free survival (MFS; HR 1.06, 95% CI 0.82-1.36; P = 0.66), and intravesical recurrence-free survival (IRFS; HR 1.51, 95% CI 1.29-1.77; P < 0.001). When excluding previous bladder tumour history, the result for IRFS was a HR of 1.81 (95% CI 1.53-2.13; P < 0.001). CONCLUSIONS: This meta-analysis indicated that URS before RNU did not have a negative impact on CSS, OS, RFS, or MFS in patients with UTUC. However, patients were at higher risk of intravesical recurrence after RNU when they had undergone URS before RNU. Further studies are needed to assess the effects of post-URS intravesical chemotherapy on intravesical recurrence.

Diagnostic Ureteroscopy for Upper Tract Urothelial Carcinoma is Independently Associated with Intravesical Recurrence after Radical Nephroureterectomy.

PURPOSE: To determine the effect of diagnostic ureteroscopy on intravesical recurrence in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterec¬tomy (RNU). MATERIALS AND METHODS: We conducted a retrospective analysis of 664 patients who were treated with RNU for UTUC from June 2000 to December 2011, excluding those who had concomitant/prior bladder tumors. Of the 664 patients, 81 underwent di¬agnostic ureteroscopy (URS). We analyzed the impact of diagnostic ureteroscopy on intravesical recurrence (IVR) using the Kaplan-Meier method. Univariate and multi¬variate analyses were used to determine the independent risk factors. RESULTS: The median follow-up time was 48 months (interquartile range (IQR): 31- 77 months). Patients who underwent ureteroscopy were more likely to have a small (p<0.01), early-staged (p=0.019), multifocality (p=0.035) and ureteral tumor (p<0.001). IVR occurred in 223 patients during follow-up within a median of 17 months (IQR: 7-33). Patients without preoperative ureteroscopy have a statistically significant better 2-year (79.3%±0.02 versus 71.4%±0.02, p<0.001) and 5-year intravesical recurrence-free survival rates (64.9%±0.05 versus 44.3%±0.06, p<0.001) than patients who un¬derwent ureteroscopy. In multivariate analysis, the diagnostic ureteroscopy (p=0.006), multiple tumors (p=0.001), tumor size <3cm (p=0.008), low-grade (p=0.022) and pN0 stage tumor (p=0.045) were independent predictors of IVR. CONCLUSIONS: Diagnostic ureteroscopy is independently associated with intravesical re¬currence after radical nephroureterectomy.

Prevalence of baseline chronic kidney disease in 2,769 Chinese patients with renal cancer: nephron-sparing treatment is still underutilized.

PURPOSE: To evaluate the prevalence of baseline chronic kidney disease (CKD) in a large cohort of patients with renal masses in a single Chinese institution. Estimated glomerular filtration rate (eGFR) and CKD stage are more clinically relevant to predict the risk of morbidity and mortality in patients after nephrectomy. But, sCr reflects renal function poorly. METHODS: We retrospectively identified patients undergoing kidney surgery between January 2002 and June 2012. eGFR was calculated using the modification of diet in renal disease formulas modified based on Chinese people. CKD stages I­V were defined using the National Kidney Foundation definitions. RESULTS: A total of 2769 patients had adequate data available to calculate a preoperative eGFR (mL/min/1.73m2) with renal cancer confirmed by pathology. Of all patients, 97.7 % awaiting surgery at our institution had a "normal" baseline sCr (≤1.4 mg/dL), and 3.2 % of patients had CKD stage III or worse. Of the 401 patients ≥70 years old, 16.7 % (67/401) had CKD stage III. CONCLUSION: Many patients with a seemingly normal sCr have CKD stage III or worse, especially in patients over 70 years old. Given the high prevalence of baseline CKD in patients with renal cancer, it is important to preserve renal parenchyma when treating them surgically.

Pattern and risk factors of intravesical recurrence after nephroureterectomy for upper tract urothelial carcinoma: a large Chinese center experience.

BACKGROUND/PURPOSE: There is currently no consensus about the pattern and risk factors of bladder recurrence after nephroureterectomy, especially in the Chinese population. We evaluated the pattern and risk factors based on data from a large Chinese center. METHODS: The clinical and pathological data of 438 patients with upper tract urothelial carcinoma (UTUC), who underwent nephroureterectomy at Peking University First Hospital, Beijing, China between 2000 and 2010, was retrospectively analyzed. Univariate analysis by log-rank test and multivariate analysis by Cox proportional hazards regression model were used to determine the independent risk factors. RESULTS: A total of 135 patients (30.8%) developed intravesical recurrence within a median follow-up of 45 months (range: 12-144 months). The median interval of bladder recurrence was 15 months (range: 2.0-98.0 months), and the two peaks for recurrence were 4-6 months and 17-19 months. Lower tumor grade, tumor multifocality, concomitant carcinoma in situ (CIS) and tumors located in the lower ureter were significant risk factors by univariate and multivariate analysis. A risk-scoring system was developed and a significant difference was found between different risk evaluations. Patients with concomitant CIS tended to develop a late bladder recurrence. One hundred and eighteen patients (87.4%) received transurethral resection after bladder tumor recurrence. CONCLUSION: Lower tumor grade, tumor multifocality, concomitant CIS and tumors located in the lower ureter tend to be predictive for bladder recurrence after nephroureterectomy, although the underlying mechanism is not fully elucidated, and the scoring system could help risk stratification. Most recurrent tumors could be treated by transurethral resection and there were two peaks for recurrence, which is probably related to the mechanisms and may be unique to the Chinese population.

Predictive factors for worse pathological outcomes of upper tract urothelial carcinoma: experience from a nationwide high-volume centre in China.

OBJECTIVES: To analyse the predictive factors for worse pathological outcome (muscle invasive pT2+, non-organ-confined pT3+ or N+ and histological Grade 3) of upper tract urothelial carcinoma (UTUC) in a Chinese population from a nationwide high-volume centre in China. PATIENTS AND METHODS: Predictors were studied by retrospectively reviewing the clinicopathological data of 729 consecutive patients with UTUC treated in our centre from January 2002 to December 2010. Univariate and multivariate logistic regression analyses were used. RESULTS: There were more female patients (56.4%) than males and more tumours were located in the ureter (52.7%) than in the pelvis. In multivariate analysis, male gender (hazard ratio [HR] 1.898, P = 0.001), sessile architecture (HR 3.249, P < 0.001), high grade (HR 5.007, P < 0.001), ipsilateral hydronephrosis (HR 4.768, P < 0.001), renal pelvis location (HR 2.620, P < 0.001) and tumour without multifocality (HR 1.639, P = 0.028) were predictive factors for muscle-invasive UTUC. Male gender (HR 2.132, P < 0.001), renal pelvis location (HR 3.466, P < 0.001), tumour without multifocality (HR 2.532, P = 0.001), sessile tumour architecture (HR 3.274, P < 0.001), and high grade (HR 3.019, P < 0.001) were predictive factors for non-organ-confined disease. Chronological old age (HR 1.047, P < 0.001), sessile tumour architecture (HR 25.192, P < 0.001), ipsilateral hydronephrosis (HR 1.689, P = 0.024), and positive urinary cytology (HR 1.997, P = 0.006) were predictive factors for histological Grade 3 UTUC. CONCLUSIONS: There was a predominance of female patients and ureteric tumours in UTUCs of this Chinese population. Male gender, sessile architecture, tumour location, tumour without multifocality, high histological grade and preoperative ipsilateral hydronephrosis were independent predictive factors for worse pathological outcome of UTUCs.

Prophylactic intravesical chemotherapy to prevent bladder tumors after nephroureterectomy for primary upper urinary tract urothelial carcinomas: a systematic review and meta-analysis.

INTRODUCTION: Intravesical recurrence after treatment of primary upper urinary tract urothelial carcinomas (UUT-UCs) is common. While intravesical instillation is widely used to prevent recurrence after transurethral resection for primary bladder tumors, there is still no consensus on the prophylactic capability of intravesical chemotherapy in preventing bladder tumor recurrence after surgery for UUT-UCs. METHODS: A meta-analysis of the published results of clinical trials was performed to compare radical surgery alone or surgery plus postoperative intravesical chemotherapy. The primary end point was to determine the percentage of patients with recurrence in the different groups. RESULTS: Our study includes five trials with recurrence information on 614 patients. During follow-up, 55 of 268 (20.5%) patients who received postoperative instillation had bladder recurrence compared to 127 of 346 (36.7%) patients who had no adjuvant treatment--a decrease of 41% in the odds of recurrence with chemotherapy (odds ratio 0.48, 95% confidence interval 0.33-0.69, p = 0.0001). No serious adverse events were reported. Subgroup analyses were temporarily unavailable. CONCLUSIONS: Postoperative intravesical chemotherapy significantly decreases the risk of bladder recurrence after nephroureterectomy for primary UUT-UCs. Postoperative intravesical instillation is considered the treatment of choice after nephroureterectomy.

Segmental ureterectomy can be performed safely in patients with urothelial carcinoma of distal ureter.

INTRODUCTION: We aimed to compare oncological outcomes by surgery type (segmental ureterectomy [SU] vs. radical nephroureterectomy [RNU]) in a large cohort of patients with upper tract urothelial carcinoma (UTUC) of the distal ureter. METHODS: We performed a retrospective analysis of 219 patients with UTUC of the distal ureter among 931 patients with UTUC who underwent SU and RNU. Clinicopathological outcomes were evaluated. Cancer-specific survival (CSS), overall survival (OS), local recurrence-free survival (RFS), intravesical recurrence-free survival (IVRFS), contralateral recurrence-free survival, and distal metastasis-free survival were assessed by the Kaplan-Meier method and Cox regression, estimating hazard ratios (HR) and 95% confidence intervals (CIs). RESULTS: A total of 179 (81.7%) patients underwent RNU and 40 (18.3%) underwent SU: 85 males (47.5%) with RNU and 17 (42.5%) with SU (p=0.568). The median age with RNU and SU was 71 years (range 31-86) and 70 years (range 46-90), respectively (p=0.499). The T stage of the two groups did not differ (p=0.122), nor did mean tumour length (3.35±2.62 vs. 3.25±2.14; p=0.953), grade (p=0.075), tumour necrosis (p=0.634), or followup time (months) (58.1±8.1 vs. 63.7±3.4; p=0.462). The two groups did not differ in CSS (p=0.358) or OS (p=0.206), and surgery type did not predict CSS (HR 0.862; 95% CI 0.469-1.585; p=0.633) or OS (HR 0.764; 95% CI 0.419-1.392; p=0.379). Local RFS was higher with RNU than SU (96.2% vs. 86.0%; p=0.02), but the groups did not differ in IVRFS (p=0.661), contralateral RFS (p=0.183), or distant metastasis-free survival (p=0.078). On multivariate analysis, SU was associated with local RFS (HR 5.069; 95% CI 1.029-24.968; p=0.046) and distant metastasis-free survival (HR 6.497; 95% CI 1.196-35.283; p=0.03). Local RFS was lower with SU than RNU for patients with pT3-4 stage (p=0.006). CONCLUSIONS: Long-term oncological outcomes were equivalent with SU and RNU in patients with UTUC of the distal ureter. SU affected local recurrence survival, especially with advanced tumour stage, and distant metastasis survival.

The role of tumor size, ultrasonographic findings, and serum tumor markers in predicting the likelihood of malignant testicular histology.

The clinical predictive factors for malignant testicular histology remain unclear because of the low prevalence. Therefore, the aim of this study was to investigate predictors of malignant histology for testicular masses and decide more testis-sparing surgeries before surgery. This retrospective study enrolled 325 consecutive testicular mass patients who underwent radical orchiectomy (310/325) or testicular preserving surgery (15/325) from January 2001 to June 2016. The clinicopathological factors, including tumor diameter, cryptorchidism history, ultrasound findings, serum alpha-fetoprotein, and human chorionic gonadotropin (HCG) levels, were collected retrospectively for statistical analysis. A predictive nomogram was also generated to evaluate the quantitative probability. Among all patients, 247 (76.0%) were diagnosed with a malignant testicular tumor and 78 (24.0%) with benign histology. Larger tumor diameter (per cm increased, hazard ratio [HR] = 1.284, P = 0.036), lower ultrasound echo (HR = 3.191, P = 0.001), higher ultrasound blood flow (HR = 3.320, P < 0.001), and abnormal blood HCG (HR = 10.550, P < 0.001) were significant predictive factors for malignant disease in all testicular mass patients. The nomogram generated was well calibrated for all predictions of malignant probability, and the accuracy of the model nomogram measured by Harrell's C statistic (C-index) was 0.92. According to our data, the proportion of patients who underwent radical orchiectomy for benign tumors (24.0%) was much larger than generally believed (10.0%). Our results indicated that the diameter, ultrasonic echo, ultrasonic blood flow, and serum HCG levels could predict the malignancy in testicular mass patients.

The significance of the initial symptom in Chinese patients with upper tract urothelial carcinoma: Regular health examination is still underutilized.

This paper is to elucidate the correlation between different symptoms of UTUC and the clinicopathological characteristics and prognosis. The clinicopathological data of 700 consecutive patients with UTUC who were treated with radical nephroureterectomy were reviewed, and symptoms were categorized into three groups: S1-no direct symptoms, S2-local symptoms (including hematuria and flank pain) and S3-systemic symptoms. We found that the distributions of patients in the S1, S2 and S3 groups were 96 (13.7%), 601 (85.9%) and 3 (0.4%), respectively, and most patients in S1 were incidentally found to have abnormal findings on ultrasound during regular health examination. Altogether, 534 patients (76.3%) presented with gross hematuria, and 111 (15.9%) presented with flank pain. Patients in S1 had a higher rate of hydronephrosis (p < 0.001), ureteral tumors (p < 0.001), worse pre-operative renal function (p = 0.020) and lower tumor stage (p = 0.038). The presence of hematuria was significantly related with renal pelvic tumors (p < 0.001), higher pre-operative eGFR (p = 0.047), papillary tumor architecture (p = 0.005) and less hydronephrosis (p < 0.001); and the presentation of flank pain was correlated with older age (p = 0.008), ureteral location (p < 0.001), hydronephrosis (p < 0.001), sessile architecture (p < 0.001) and higher tumor grade (p = 0.003). The presence of hematuria or flank pain also failed to reach significance as an independent prognostic factor. In conclusion, asymptomatic UTUC patients are featured for more hydronephrosis and lower tumor stage, while patients who presented with flank pain had a higher risk of sessile architecture and higher tumor grade. Regular health examinations might play a useful role in the early detection of UTUC patients with no symptoms.

Detection of urothelial carcinoma, upper tract urothelial carcinoma, bladder carcinoma, and urothelial carcinoma with gross hematuria using selected urine-DNA methylation biomarkers: A prospective, single-center study.

INTRODUCTION: Hematuria is the most common symptom of urothelial carcinomas (UC) but is often idiopathic. Cystoscopy is expensive which involves considerable patient discomfort, and conventional urine cytology for noninvasive UC detection and disease monitoring suffers from poor sensitivity. We aim to evaluate the performance of genes selected from a previous study in detecting UC, especially among patients with gross hematuria, as well as upper tract urothelial carcinoma (UTUC) and bladder carcinoma separately, in voided urine samples. METHODS: Using methylation-specific polymerase chain reaction, we examined the promoter methylation status of 10 genes in voided urine samples among 473 patients at our institution, including 217 UC patients and 256 control subjects. RESULTS: The final combination of VIM, CDH1, SALL3, TMEFF2, RASSF1A, BRCA1, GDF15, and ABCC6 identified UC with a sensitivity of 0.83 and a specificity of 0.60. Additionally, a panel of selected genes (CDH1, HSPA2, RASSF1A, TMEFF2, VIM, and GDF15) identified UTUC with a sensitivity of 0.82 and a specificity of 0.68, while a panel of selected genes (VIM, RASSF1A, GDF15, and TMEFF2) identified bladder carcinoma with a sensitivity of 0.82 and a specificity of 0.53. Remarkably, a different panel (CDH1, SALL3, THBS1, TMEFF2, VIM, and GDF15) identified UC in patients with gross hematuria with 0.89 sensitivity and 0.74 specificity, and sensitivity (0.91) and specificity (0.92) could be achieved when cytology was included. CONCLUSIONS: The selected urine-DNA methylation biomarkers are reliable, noninvasive, and cost-effective diagnostic tools for bladder carcinoma and UTUC, especially among patients with gross hematuria.

Validation of the Pretreatment Neutrophil-to-Lymphocyte Ratio as a Prognostic Factor in a Large Cohort of Chinese Patients with Upper Tract Urothelial Carcinoma.

BACKGROUND: The pretreatment neutrophil-to-lymphocyte ratio (NLR) has been reported to be a prognostic factor in various types of carcinomas. The aim of this study was to investigate the prognostic value of pretreatment NLR in a large cohort of Chinese patients with upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively analyzed the medical data of 656 UTUC patients who underwent radical nephroureterectomy (RNU) from 2001 to 2011 at Peking University First Hospital. Receiver operating characteristic (ROC) curve analysis was performed to calculate the optimal cutoff point of pretreatment NLR. Uni- and multi-variate analyses were used to identify the prognostic factors for cancer-specific survival (CSS) and intravesical recurrence-free survival (IVRFS). RESULTS: The optimal cutoff point of pretreatment NLR was 2.40 by ROC curves, by which patients with high NLR (NLR ≥2.40) and low NLR (NLR <2.40) accounted for 314 (47.9%) and 342 (52.1%) patients, respectively. Patients with a high pretreatment NLR tended to have high tumor grades (χ2 = 15.725, P< 0.001), high tumor stages (χ2 = 25.416, P< 0.001), tumor sizes >5 cm (χ2 = 8.213, P= 0.005), ipsilateral hydronephrosis (χ2 = 4.624, P= 0.033), and concomitant carcinoma in situ(CIS) (χ2 = 9.517, P= 0.003). A high pretreatment NLR (hazard ratio [HR] = 1.820, P= 0.001), main tumor diameter >5 cm (HR = 1.789, P= 0.009), lymph node metastasis (HR = 1.863, P= 0.024), and high tumor stage (HR = 1.745, P< 0.001) independently predicted poor CSS after surgery, while only concomitant carcinoma in situ(CIS) (HR = 2.164, P= 0.034), ureteroscopy before surgery (HR = 1.701, P= 0.015), and high tumor grade (HR = 1.645, P= 0.018) were independent predictors of IVRFS after RNU. CONCLUSIONS: The pretreatment NLR was related to some adverse clinicopathological features and was an independent predictor of CSS, although not IVRFS, in Chinese UTUC patients.

Diagnostic Ureteroscopy for Upper Tract Urothelial Carcinoma is Independently Associated with Intravesical Recurrence after Radical Nephroureterectomy

ABSTRACT Purpose: To determine the effect of diagnostic ureteroscopy on intravesical recurrence in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). Materials and Methods: We conducted a retrospective analysis of 664 patients who were treated with RNU for UTUC from June 2000 to December 2011, excluding those who had concomitant/prior bladder tumors. Of the 664 patients, 81 underwent diagnostic ureteroscopy (URS). We analyzed the impact of diagnostic ureteroscopy on intravesical recurrence (IVR) using the Kaplan-Meier method. Univariate and multivariate analyses were used to determine the independent risk factors. Results: The median follow-up time was 48 months (interquartile range (IQR): 31-77 months). Patients who underwent ureteroscopy were more likely to have a small (p<0.01), early-staged (p=0.019), multifocality (p=0.035) and ureteral tumor (p<0.001). IVR occurred in 223 patients during follow-up within a median of 17 months (IQR: 7-33). Patients without preoperative ureteroscopy have a statistically significant better 2-year (79.3%±0.02 versus 71.4%±0.02, p<0.001) and 5-year intravesical recurrence-free survival rates (64.9%±0.05 versus 44.3%±0.06, p<0.001) than patients who underwent ureteroscopy. In multivariate analysis, the diagnostic ureteroscopy (p=0.006), multiple tumors (p=0.001), tumor size <3cm (p=0.008), low-grade (p=0.022) and pN0 stage tumor (p=0.045) were independent predictors of IVR. Conclusions: Diagnostic ureteroscopy is independently associated with intravesical recurrence after radical nephroureterectomy.