• chemotherapy;
  • urinary tract cancer;
  • prognosis;
  • recurrence;
  • urothelial carcinoma;
  • renal pelvis;
  • ureter


  1. Top of page
  2. Abstract


Urothelial carcinoma of the upper urinary tract (UUT-UC) was a rare, aggressive urologic cancer with a propensity for multifocality, local recurrence, and metastasis. High-risk patients had poor outcomes. Because of the rarity of these tumors, randomized clinical trials and data regarding adjuvant chemotherapy in locally advanced tumors are currently unavailable. Our objective was to assess the effect of adjuvant chemotherapy and the impact of potential prognostic factors on survival in high-risk, postsurgical UUT-UC patients.


Using a multi-institutional, international retrospective database, identified were 627 patients with high risk UUT-UCs (pT3N0, pT4N0 and/or N+ and/or M+) who underwent surgical removal. Only patients who received adjuvant chemotherapy were included.


Overall, 140 patients (22.6%) with a median age of 67 years were included. The median follow-up was 22.5 months. The 5-year, overall survival for the entire cohort was 43%, the 5-year recurrence-free survival was 54%, and metastasis-free survival was 53% at 5 years. Positive surgical margins were an independent prognostic factor for recurrence (P = .06), cancer-specific mortality (P = .05), and overall mortality (P = .02) of any cause. Adjuvant chemotherapy was not linked with overall or cancer-specific survival in patients with high risk disease (adjuvant chemotherapy [n = 140] vs no treatment [n = 487]) (P >.5).


Adjuvant postoperative chemotherapy did not offer any significant benefit to overall survival in our population. Additional data were necessary, and studies enrolling patients at high risk in clinical trials investigating neoadjuvant chemotherapy in conjunction with chemotherapy should have been highly encouraged. Cancer 2011;. © 2011 American Cancer Society.

Urothelial carcinomas of the upper urinary tract (UUT-UCs) are rare tumors that account for 5% to 10% of all urothelial carcinomas.1-3 Invasive UUT-UCs have a poor prognosis. Patients' survival is mainly influenced by stage, and 5-year survival rates range from 90% in early pathologic stages (pTa/pT1) to less than 5% in stages with lymph node involvement or metastatic disease. Consequently, almost half of the patients with stage ≥T3 or lymph node involvement die from their disease, mainly as a result of distant metastases developing.1, 4, 5 Radical nephroureterectomy is the standard of care in UUT-UCs.2, 3, 6 Stage and grade are considered to be major prognostic factors of outcome after surgery.1, 3, 4 There are several difficulties involved with the treatment of these tumors, such as diagnosis at a late stage, multifocality, poor differentiation, and poor prognosis.3, 7, 8 Nevertheless, the high recurrence and mortality rates in high-risk patients indicate the essential role of effective additional adjuvant treatment.

Because of the rarity of these tumors, randomized clinical trials comparing different treatment modalities are not available and data regarding adjuvant chemotherapy in locally advanced UUT-UCs are currently sparse.9-12 In 2009, Hellenthal et al retrospectively identified, from a multicenter database, 542 patients who underwent nephroureterectomy for T3, T4, and/or node-positive clinically nonmetastatic UUT-UCs.13 In the current study, our aim was to report available data regarding the role of adjuvant chemotherapy in the treatment of UUT-UC after radical surgery.


  1. Top of page
  2. Abstract


A multi-institutional, international retrospective study was conducted that included patients from our French national database on UUT-UCs* and from 1 center in Greece. Overall, 627 patients with locally advanced/high-risk UUT-UCs (pT3N0, pT4N0, and/or lymph node positive, and/or metastasis) who underwent surgical resection were selected from our multicentric database. Their medical files were reviewed to collect the following data: localization of the primary tumor, tumor stage at diagnosis (TNM 2009),14 tumor grade (WHO classification),15 surgical margins status and vascular invasion, Eastern Cooperative Oncology Group (ECOG) performance status, surgical procedure (nephroureterectomy with open bladder cuff or other conservative procedures), chemotherapy regimen administered, adjuvant radiotherapy administered, date of diagnosis, date of relapse or disease progression, date of last visit or death, and cause of death.

Chemotherapy Regimens

Only patients who underwent adjuvant chemotherapy within 6 months of surgery were included in the current study. Cisplatin-based chemotherapy in various combinations was the most common regimen, depending on the patients' eligibility and renal function. Cisplatin was administered intravenously in a 1-hour infusion, at a median dose of 75 mg/m2 of body surface area (calculated using appropriate formulas from the height and weight of the patient) every 3 weeks, if renal function and circulating blood elements were at acceptable levels (creatinine clearance ≥ 60 mL/min, platelets ≥ 100,000/mm2, and polymorphonuclear leukocytes ≥ 1,000/mm2). Mannitol and pretreatment hydration with 1 to 2 liters of fluid infused for 8 to 12 hours before the cisplatin dose were used to reduce nephrotoxicity. A prophylactic regimen of cortisone in combination with antiemetics (including setrones) was administered to reduce the severity of cisplatin-induced delayed emesis. Additional administration of magnesium and potassium was used to avoid electrolyte disturbances related to cisplatin-induced renal tubular damage. Adequate hydration was maintained and urinary output was monitored over the following 24 hours. Whenever it was used in combination with paclitaxel, cisplatin was administered after paclitaxel to avoid increased hematologic toxicity due to decreased clearance. Patients unfit for cisplatin (eg, those with impaired renal function or poor performance status) were treated with carboplatin-based or single-agent regimens. Carboplatin was given in a dose of 5 AUC, which was calculated using the Calvert formula, carboplatin dose (mg) = AUC × [CrCl (mL/min)+25] (AUC = area under the curve), or using appropriate carboplatin dose formulas dependent on the renal function of the patient.

Statistical Analysis

All patients were followed from diagnosis until death or until the data were censored (with the patient still considered to be alive). Overall survival was evaluated from the date of surgery to the last follow-up visit or death. Recurrence-free survival was defined as the period between surgery and the subsequent appearance of recurrence or metastasis. Kaplan-Meier survival curves were calculated using censured data and compared using the log-rank test. Univariate analyses were used to assess associations between potential prognostic factors (ie, age, gender, tumor stage, grade, type of surgery, and adjuvant chemotherapy regimen) and survival. A chi-squared test was used for categorical variables and an unpaired Student's t test for age. Significant variables in the univariate analyses were entered into a multivariate analysis (Cox stepwise-regression). A P value of less than .05 was considered significant. All tests were conducted with SPSS© (version 17.0).


  1. Top of page
  2. Abstract

Patients' Characteristics

Table 1 compares the characteristics and clinical features of the patients who received adjuvant chemotherapy (n = 140) and of the population of high risk tumors who did not receive adjuvant treatment (n = 487). Considering the group of patients who received adjuvant chemotherapy, 140 patients were retrieved (22.6%), with a median age of 67 years. The male-to-female ratio was 2.8. Most of these patients presented with a high-grade tumor (grade 3 for 122 patients and grade 2 for 13). The majority of the patients had a low performance status (0-1), whereas 12 of them presented with a higher 1 due to comorbidities. Follow-up consisted of surveillance cystoscopy every 3 to 6 months after surgery and imaging studies of the urinary tract and the whole body every 6 months to 1 year.

Table 1. Demographics and Pathological Characteristics of Patients With High Risk UUT--UCs
VariableAdjuvant chemotherapy (n=140)No adjuvant chemotherapy (n=487)pa
  • UUT-UC indicates urothelial carcinoma of the upper urinary tract; ECOG, Eastern Cooperative Oncology Group.

  • *

    Not available for 9 patients.

  • **

    Not available for 5 patients.

    Not available for 29 patients.

  • ***

    aOnly significant values are shown.

Age, yr, median (range)67 (61-73)71 (66-85) 
Age group (%)   
 Less than 6031 (22)105 (21) 
 60-6953 (38)200 (41) 
 70-7951 (36)145 (30) 
 80 or greater5 (4)37 (8).02
Gender (%)   
 Male103 (74)328 (67)-
 Female37 (26)159 (33) 
Performance status (ECOG) (%)* -
 092 (66)358 (73) 
 127(19)98 (20) 
 28 (6)24 (5) 
 34 (3)7 (2) 
Pathologic stage (%)  .001
 T3/T4N0M071 (51)325 (67) 
 N+M038 (27)86 (17) 
 M+31 (22)76 (16) 
Grade (%)**  
 G213 (9)301 (62) 
 G3122 (87)186 (38) 
Lymphovascular invasion (%)*** -
 ILV-59 (42)241 (49) 
 ILV+52 (37)246 (51) 
Surgical margin  -
 R0115 (82)401 (82) 
 R112 (9)62 (13) 
 R26 (4)24 (5) 
Adjuvant chemotherapy based   
 Platinum + vs. -135 (82) vs. 5 (4)- 
 Gemcitabine +vs. -70 (50) vs. 70 (50)- 
Adjuvant radiotherapy   
 Yes9 (6)- 
 No131 (94)- 


In the group of patients who received adjuvant chemotherapy, the most common treatment was radical nephroureterectomy with bladder cuff removal, which was performed in 110 patients; 23 patients underwent nephrectomy with incomplete ureterectomy, 6 patients underwent segmental ureterectomy, and 1 patient underwent endoscopic resection of the tumor. In the second group, the most common treatment was also radical nephroureterectomy with bladder cuff removal, which was performed in 428 patients; 49 patients underwent nephrectomy with incomplete ureterectomy, and 10 patients underwent segmental ureterectomy.

Adjuvant Chemotherapy

The mean number of cycles was 4.4. cisplatin-based chemotherapy in various combinations was the most commonly administered therapy: 35 patients received cisplatin+gemcitabine; 31 received carboplatin-paclitaxel; 23 received carboplatin-gemcitabine; 19 received methotrexate, vinblastine, doxorubicin, cisplatin (MVAC); and 17 received cisplatin, methotrexate, and vinblastine (CMV). Table 2 reports the most commonly used chemotherapy regimens, and Table 3 depicts the adjuvant chemotherapy regimens administered.

Table 2. Chemotherapy Protocols Used in the Current Study (n=140)
Methotrexate30 mg/m2i.v.(bolus)d 1, 15, 22
Vinblastine3 mg/m2i.v.(bolus)d 1 or 2, 15, 22
Doxorubicin30 mg/m2i.v.(bolus)d 1 or 2
Cisplatin70 mg/m2i.v.(1-2 h inf)d 1 or 2
To be repeated every 4-5 weeks (with or without G-CSF).
Cisplatin70-100 mg/m2i.v.(1 h inf)d 1 or 2
Vinblastine4 mg/m2i.v.(bolus)d 1+8
Methotrexate30 mg/m2i.v.(bolus)d 1+8
Folinic acid15 mg/m2p.o. or i.v.d 2+9(24 h after MTX)
To be repeated every 3 weeks.
Gemcitabine1000 mg/m2i.v.(30 min-1 h inf)d 1, 8, 15
Cisplatin70 mg/m2i.v.(1 h inf)d 2
To be repeated every 4 weeks.
Paclitaxel + cisplatin
Paclitaxel175 mg/m2i.v.(3 h inf)d 1
Cisplatin75 mg/m2i.v.(1-2 h inf)d 1
To be repeated every 3 weeks.
Gemcitabine + carboplatin
  1. MVAC indicates methotrexate, vinblastine, doxorubicin, cisplatin; G-CSF, granulocyte colony-stimulating factor; CMV, cisplatin, methotrexate, and vinblastine; MTX, methotrexate; GC, gemcitabine, cisplatin; AUC indicates area under the curve; inf, infusion.

Gemcitabine1000-1250 mg/m2i.v. (30 min-1 h inf)d 1, 8
CarboplatinAUC=5i.v. (1 h inf)d 1 or d 2
To be repeated every 3 weeks (max 6 cycles).
Table 3. Adjuvant Chemotherapy Regimens Administered (n=140)
ChemotherapyNo. Pts patients (%)a
  • a

    Including one 1 patient treated with alternative doublet chemotherapy (ifosfamide/doxorubicin).

Gemcitabine + cisplatin35 (25)
Carboplatin + taxol31 (22.1)
Gemcitabine + carboplatin23 (16.4)
MVAC19 (13.6)
Cisplatin + methotrexate + vinblastine17 (12.1)
Gemcitabine + oxaloplatin6 (4.3)
Gemcitabine4 (2.8)
Gemcitabine + carboplatin + taxol + bevacizumab1 (0.7)
Cisplatin1 (0.7)
Cisplatin + 5-fluorouracil1 (0.7)
Cisplatin + 5-fluorouracil + doxorubicin1 (0.7)
Gemcitabine + taxol1 (0.7)

Survival and Recurrence

First, adjuvant chemotherapy after nephroureterectomy did not significantly correlate with overall or cancer-specific survival in patients with high-risk disease (ie, adjuvant chemotherapy [n = 140] versus no adjuvant treatment [n = 487]) (P >.5)).

In our population who received adjuvant chemotherapy, the median follow-up was 22.5 months (range, 10-50 months), and the mean follow-up was 37.4 months (range, 1-158 months). At the end of the study, 78 patients had died and 32 patients were still available. Among these patients, 49 died from the evolution of UUT-UCs and 29 from other causes. The 5-year overall survival and specific survival for the entire cohort who received adjuvant chemotherapy were 43% and 60% respectively (Fig. 1).

thumbnail image

Figure 1. Survival curves after adjuvant chemotherapy for patients with high-risk urothelial carcinoma of the upper urinary tract (UUT-UC) (N = 140): (A) cancer-specific survival for the whole population; (B) cancer-specific survival stratified according to TNM status; (C) recurrence-free survival curve; (D) metastasis-free survival curve.

Download figure to PowerPoint

By univariate analysis, positive surgical margins and the presence of metastatic sites at the time of surgery were significantly associated with cancer-specific mortality (P = .01, .006, and .02 for R1, R2, and metastatic sites, respectively), whereas age, gender, tumor stage, grade, performance status, lymphovascular invasion, and chemotherapy regimen were not (Table 4). On multivariate analysis, positive surgical margins were the sole independent prognostic factor for cancer-specific mortality (P = .03).

Table 4. Univariate and Multivariate Cox Regression Models Predicting Cancer?Specific Mortality, Free Recurrence Survival, and Free Metastasis Survival of Upper Tract Urothelial Carcinoma After Adjuvant Chemotherapya
CovariateRisk of cancer-specific mortalityRisk of tumor recurrenceRisk of metastasis
Univariate analysisMultivariate analysisUnivariate analysisMultivariate analysisUnivariate analysisMultivariable analysis
HR (95% CI);PHR (95% CI);PHR (95% CI);PHR (95% CI);PHR (95% CI);PHR (95% CI);P
  • HR indicates hazards ratio; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group.

  • a

    Values in boldface indicate statistically significant values.

 Female vs. male0.86 (0.42-1.74);0.68-0.88 (0.64-1.22);0.47-0.82 (0.59-1.14);0.23-
Age (continuous)0.99 (0.96-1.02);0.83-1.00 (0.97-1.03);0.78-1.00 (0.98-1.03);0.57-
 ECOG status 0.43- 0.55- 0.08-
 ECOG 1 vs. ECOG 00.46 (0.16-1.30);0.14-0.93 (0.45-1.95);0.86-1.35 (0.70-2.62);0.36-
 ECOG 2 vs. ECOG 01.95 (0.58-6.48);0.27-0.48 (0.06-3.55);0.47-3.15 (1.316-7.57);0.01-
 ECOG 3 vs. ECOG 01.15 (0.15-8.44);0.88-3.04 (0.27-2.87);0.83-2.08 (0.49-8.73);0.31-
Stage 0.06 0.17 0.54 0.88 0.002 0.007
 N+M0 vs. T3/T4N0M01.23 (0.58-2.63);0.580.79 (0.34-1.80);0.581.41 (0.75-2.63);0.281.14 (0.57-2.27);0.701.46 (0.75-2.84);0.251.14 (0.57-2.29);0.7
 M+ vs. T3/T4N0M02.24 (1.13-4.43);0.021.72 (0.84-3.51);0.131.22 (0.59-2.48);0.580.94 (0.44-1.99);0.873.04 (1.65-5.60);<0.0012.87 (1.45-5.70);0.002
Grade   0.09        
 G3 vs. G26.6 (0.91-48.5);0.065.40 (0.72-40.09);0.092.41 (0.75-7.75);0.142.05 (0.62-6.82);0.232.71 (0.84-8.69);0.092.11 (0.63-7.07);0.22
Lymphovascular invasion            
 Yes vs. no1.06 (0.71-1.57);0.77-0.46 (0.59-1.26);0.46-0.91 (0.63-1.31);0.61- 
Surgical margin status 0.03 0.03 0.009 0.18 0.07 0.22
 R1 vs. R02.45 (1.16-5.21);0.012.23 (0.99-4.94);0.051.61 (0.77-3.34);0.21.28 (0.59-2.79);0.522.15 (1.1-4.20);0.021.82 (0.89-3.70);0.09
 R2 vs. R05.72 (1.66-19.74);0.0064.93 (1.19-20.36);0.024.81 (1.68-13.71);0.0033.06 (0.92-10.11);0.0240.79 (0.10-581);0.820.75 (0.09-5.82);0.78
Platinum-based chemotherapy            
 No vs. yes0.88 (0.32-2.38);0.8-0.71 (0.26-1.92);0.5-0.80 (0.29-2.16);0.66-
Gemcitabine-based chemotherapy            
 No vs. yes0.94 (0.69-1.27);0.69-0.91 (0.68-1.20);0.5-0.77 (0.58-1.01);0.060.99 (0.72-0.98);0.97
Adjuvant radiotherapy            
 No vs. yes4.63 (0.16; 128.69);0.36-0.87 (0.48; 1.56);0.64-0.58 (0.38; 0.89);0.010.60 (0.36-0.98);0.04

The 5-year recurrence-free survival was 54%. By univariate analysis, positive surgical margins were significantly associated with recurrence-free survival (P = .009) (Table 4). The presence of positive surgical margins was an independent prognostic factor for recurrence in the multivariate analysis (P = .009). By multivariate analysis, macroscopic surgical margins was an independent prognostic factor (P = .02).

Metastasis-free survival was 53% at 5 years. Univariate analysis showed a statistically significant association between metastasis-free survival and the presence of metastatic sites at the time of surgery (P <.001), microscopic positive surgical margins (P = .02), and adjuvant radiotherapy (P = .01). By multivariate analysis, the presence of metastatic sites and adjuvant radiotherapy were the sole independent prognostic factors for metastasis-free survival (P = .002 and .04, respectively).


  1. Top of page
  2. Abstract

Urothelial carcinoma, of the upper (UUT-UC) and lower (bladder) urinary tract, are considered to be relatively chemosensitive.9, 13, 16, 17 In fact, most of the data regarding the clinical efficacy of chemotherapy in the neoadjuvant and adjuvant settings are based on outcomes from the treatment of bladder UC.17, 18 Contrary to what has been demonstrated for bladder cancer, there have been no reported effects of neoadjuvant chemotherapy for UUT-UCs. Adjuvant chemotherapy achieves a remission rate of up to 50% but has minimal impact on survival. However, because of the low frequency of UUT-UCs, there are few reported series that have included more than 50 patients.3, 9, 16

To date, however, radical surgery represents the only potentially curable therapeutic intervention for patients with UUT-UCs.2, 3 Although the role of lymphadenectomy in these tumors has not yet been clarified, recent evidence has shown that, in patients with locally advanced tumors, it improves staging and consequently could help in selecting patients for adjuvant chemotherapy.19, 20 Systemic recurrences are common in this disease; however, and it is, therefore, reasonable to consider perioperative chemotherapy in an effort to decrease a patient's risk of recurrence.21

In our study, the median survival was 22.5 months, the median recurrence-free survival was 16 months and the median metastasis-free survival was 19 months. The median survival in our study is consistent with those reported in previous studies;9, 10, 13 therefore, our study suggests that adjuvant postoperative chemotherapy does not add any significant benefit with respect to overall survival in this group of high-risk patients. A possible explanation for the findings of this study may be that this subgroup of patients presented with a more advanced disease that had high-risk features that would have limited survival expectancy anyway. Adding a certain chemotherapy-related toxicity, particularly nephrotoxicity from platinum derivatives, to a population with an already impaired postsurgical renal function may also be related to the reduced survival in these patients. The impact and possible benefit of adjuvant chemotherapy for progression-free survival and metastasis-free survival are uncertain, as clinical studies evaluating these parameters are lacking. According to the recently updated European guidelines on UUT-UCs, there are no benefits from radical nephroureterectomy in metastatic (M+) disease, although it can be considered as a palliative option.3 Additionally one would also consider certain crucial points before prescribing chemotherapy such as local response rate, pain relief, or quality of life improvement, which remain unexplored so far in these patients.

Given that UUT-UCs are urothelial tumors, one would expect results similar to those seen in bladder cancer from platinum-based chemotherapy. In fact, several platinum-based chemotherapy regimens have been proposed. From Hellenthal et al, out of 121 high risk patients, 22% received adjuvant chemotherapy.13 The patients received an average of 3.1 cycles of chemotherapy. The median follow-up was 26 months. Median survival in the group with chemotherapy was 24 months; in the group without chemotherapy, it was 26 months. Adjuvant chemotherapy was more commonly administered in the context of increased tumor grade and stage. Chemotherapy was platinum based in 97% of the patients and consisted of MVAC in most cases.

Our study identified positive surgical margins as the only independent prognostic factor for overall survival and recurrence-free survival in patients with high risk UUT-UCs. Recently, Novara et al. showed that positive margins status after radical cystectomy was a powerful independent prognostic factor of disease recurrence and cancer-specific mortality; therefore, they advocated reporting it systematically in pathologic reports.22 The authors underlined the necessity of considering it in further studies on adjuvant local and/or systemic therapy. For UUT-UCs, there is an association between overall survival and positive surgical margins and local recurrence at the anastomotic site,23 and they have been implicated in a greater risk of secondary metachronous UUT-UCs.24 Thus, our data suggest that the presence of positive surgical margins can markedly affect the patients' prognosis; therefore, accurate diagnosis and effective treatment are of substantial significance.

Although tumor grade, stage, and lymph node involvement are considered by most authors as major prognostic factors for identification of high-risk patients and predicting outcomes after surgery,1, 5 several other clinicopathologic characteristics are considered to have a prognostic significance for invasive UUT-UCs. Among them, the presence of vascular invasion has consistently been associated with a poor prognosis.5, 25 It has been reported that lymphovascular status in patients without clinically evident metastasis can identify patients with occult metastases, such as micrometastases or false-negative lymph nodes26; therefore, it can help identify patients who are candidates for adjuvant chemotherapy.

In the present study, adjuvant radiotherapy was shown to be an independent prognostic factor (P = .04) for MFS. In our series, 9 patients received adjuvant radiotherapy after the resection of their primary tumor. In general, radiotherapy is believed to act by destroying residual carcinoma cells in the surgical wound bed; therefore, this therapy is considered to be particularly effective in patients with positive surgical margins. Few data support the routine use of adjuvant radiotherapy in UUT-UC tumors.27, 28 Collectively, these data argue that it would be reasonable to consider adding systemic chemotherapy along with postoperative radiotherapy in patients with locally advanced, positive surgical margins or lymph node metastases. However, it is uncertain to what extent the increase in UUT-UC–specific MFS in this subset of patients was influenced by the adjuvant radiotherapy, the adjuvant chemotherapy, or their combination.

Finally, we believe that neo-adjuvant chemotherapy is an approach that should be evaluated more thoroughly for UUT-UCs (as it has been for bladder cancer17, 29). An important consideration is the major loss of renal reserve these patients experience after radical nephroureterectomy.30 Therefore, delivering effective doses of cytotoxic agents, particularly nephrotoxic platinum-based chemotherapy, is precluded.31 In addition, the morbidity of chemotherapy itself is far from being negligible and one should consider it carefully before deciding to launch it in these patients. Lastly, we found, as previously shown,13 that at least 1 of 4 to 5 patients received indeed chemotherapy in daily practice, although there is no recommendation advocating this prescription.3 In the absence of strong data from the evidence-based medicine, it seems that chemotherapy is often prescribed on a subjective assessment without any solid scientific rationale in these patients.


  1. Top of page
  2. Abstract

Our retrospective study showed that postoperative chemotherapy did not have any significant effect on survival in high-risk patients with UUT-UCs. To date, this is the second large study that has clearly demonstrated that there is no point in doing adjuvant chemotherapy in patients with UUT-UCs at least for a survival purpose. Only additional data from clinical trials investigating postoperative chemotherapy in these patients would be in a position to properly address this question. Obviously, such data will not be available quickly, as UUT-UCs are rare. Therefore, this type of treatment should be prohibited outside of randomized clinical trials.


  1. Top of page
  2. Abstract
  • 1
    Hall MC, Womack S, Sagalowsky AI, Carmody T, Erickstad MD, Roehrborn CG. Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30-year experience in 252 patients. Urology. 1998; 52: 594-601.
  • 2
    Margulis V, Shariat SF, Matin SF, et al. Outcomes of radical nephroureterectomy: a series from the Upper Tract Urothelial Carcinoma Collaboration. Cancer. 2009; 115: 1224-1233.
  • 3
    Roupret M, Zigeuner R, Palou J, et al. European guidelines for the diagnosis and management of upper urinary tract urothelial cell carcinomas (UUT-UCCs): 2011 update. Eur Urol. 2011; 59: 584-594.
  • 4
    Olgac S, Mazumdar M, Dalbagni G, Reuter VE. Urothelial carcinoma of the renal pelvis: a clinicopathologic study of 130 cases. Am J Surg Pathol. 2004; 28: 1545-1552.
  • 5
    Langner C, Hutterer G, Chromecki T, Winkelmayer I, Rehak P, Zigeuner R. pT classification, grade, and vascular invasion as prognostic indicators in urothelial carcinoma of the upper urinary tract. Mod Pathol. 2006; 19: 272-279.
  • 6
    Lughezzani G, Sun M, Perrotte P, et al. Should bladder cuff excision remain the standard of care at nephroureterectomy in patients with urothelial carcinoma of the renal pelvis? A population-based study. Eur Urol. 2010; 57: 956-962.
  • 7
    Catto JW, Yates DR, Rehman I, et al. Behavior of urothelial carcinoma with respect to anatomical location. J Urol. 2007; 177: 1715-1720.
  • 8
    Inman BA, Tran VT, Fradet Y, Lacombe L. Carcinoma of the upper urinary tract: predictors of survival and competing causes of mortality. Cancer. 2009; 115: 2853-2862.
  • 9
    Audenet F, Yates D, Cussenot O, Roupret M. The role of chemotherapy in the treatment of urothelial cell carcinoma of the upper urinary tract (UUT-UCC). Urol Oncol. 2010. [Epub ahead of print] doi:10.1016/j.urolonc.2010.07.016
  • 10
    Lee SE, Byun SS, Park YH, Chang IH, Kim YJ, Hong SK. Adjuvant chemotherapy in the management of pT3N0M0 transitional cell carcinoma of the upper urinary tract. Urol Int. 2006; 77: 22-26.
  • 11
    Michael M, Tannock IF, Czaykowski PM, Moore MJ. Adjuvant chemotherapy for high-risk urothelial transitional cell carcinoma: the Princess Margaret Hospital experience. Br J Urol. 1998; 82: 366-372.
  • 12
    Soga N, Arima K, Sugimura Y. Adjuvant methotrexate, vinblastine, adriamycin, and cisplatin chemotherapy has potential to prevent recurrence of bladder tumors after surgical removal of upper urinary tract transitional cell carcinoma. Int J Urol. 2008; 15: 800-803.
  • 13
    Hellenthal NJ, Shariat SF, Margulis V, et al. Adjuvant chemotherapy for high risk upper tract urothelial carcinoma: results from the Upper Tract Urothelial Carcinoma Collaboration. J Urol. 2009; 182: 900-906.
  • 14
    Sobin L, Gospodarowicz M, Wittekind C. TNM Classification of Malignant Tumours. Urological Tumours. Renal Pelvis and Ureter. 7th revised ed. New York: Wiley-Blackwell; 2009: 258-261.
  • 15
    Lopez-Beltran A, Bassi P, Pavone-Macaluso M, Montironi R. Handling and pathology reporting of specimens with carcinoma of the urinary bladder, ureter, and renal pelvis. Eur Urol. 2004; 45: 257-266.
  • 16
    O'Donnell PH, Stadler WM. The role of chemotherapy in upper tract urothelial carcinoma. Adv Urol. 2009: 419028.
  • 17
    Stenzl A, Cowan NC, De Santis M, et al. The updated EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol. 2009; 55: 815-825.
  • 18
    von der Maase H, Hansen SW, Roberts JT, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000; 18: 3068-3077.
  • 19
    Roscigno M, Shariat SF, Margulis V, et al. Impact of lymph node dissection on cancer specific survival in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. J Urol. 2009; 181: 2482-2489.
  • 20
    Roscigno M, Shariat SF, Margulis V, et al. The extent of lymphadenectomy seems to be associated with better survival in patients with nonmetastatic upper-tract urothelial carcinoma: how many lymph nodes should be removed? Eur Urol. 2009; 56: 512-518.
  • 21
    Bamias A, Deliveliotis C, Fountzilas G, et al. Adjuvant chemotherapy with paclitaxel and carboplatin in patients with advanced carcinoma of the upper urinary tract: a study by the Hellenic Cooperative Oncology Group. J Clin Oncol. 2004; 22: 2150-2154.
  • 22
    Novara G, Svatek RS, Karakiewicz PI, et al. Soft tissue surgical margin status is a powerful predictor of outcomes after radical cystectomy: a multicenter study of more than 4,400 patients. J Urol. 2010; 183: 2165-2170.
  • 23
    Abouassaly R, Alibhai SM, Shah N, Timilshina N, Fleshner N, Finelli A. Troubling outcomes from population-level analysis of surgery for upper tract urothelial carcinoma. Urology. 2010; 76: 895-901.
  • 24
    Sanderson KM, Roupret M. Upper urinary tract tumour after radical cystectomy for transitional cell carcinoma of the bladder: an update on the risk factors, surveillance regimens and treatments. BJU Int. 2007; 100: 11-16.
  • 25
    Novara G, Matsumoto K, Kassouf W, et al. Prognostic role of lymphovascular invasion in patients with urothelial carcinoma of the upper urinary tract: an international validation study. Eur Urol. 2010; 57: 1064-1071.
  • 26
    Kikuchi E, Margulis V, Karakiewicz PI, et al. Lymphovascular invasion predicts clinical outcomes in patients with node-negative upper tract urothelial carcinoma. J Clin Oncol. 2009; 27: 612-618.
  • 27
    Czito B, Zietman A, Kaufman D, Skowronski U, Shipley W. Adjuvant radiotherapy with and without concurrent chemotherapy for locally advanced transitional cell carcinoma of the renal pelvis and ureter. J Urol. 2004; 172: 1271-1275.
  • 28
    Hall MC, Womack JS, Roehrborn CG, Carmody T, Sagalowsky AI. Advanced transitional cell carcinoma of the upper urinary tract: patterns of failure, survival and impact of postoperative adjuvant radiotherapy. J Urol. 1998; 160: 703-706.
  • 29
    Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003; 349: 859-866.
  • 30
    Kaag MG, O'Malley RL, O'Malley P, et al. Changes in renal function following nephroureterectomy may affect the use of perioperative chemotherapy. Eur Urol. 2010; 58: 581-587.
  • 31
    Lerner SE, Blute ML, Richardson RL, Zincke H. Platinum-based chemotherapy for advanced transitional cell carcinoma of the upper urinary tract. Mayo Clin Proc. 1996; 71: 945-950.