Significant Predictive Factors for Prognosis of Primary Upper Urinary Tract Cancer after Radical Nephroureterectomy in Taiwanese Patients

doi:10.1016/j.eururo.2008.01.054

European Urology

Volume 54, Issue 5, November 2008, Pages 1127-1135

https://doi.org/10.1016/j.eururo.2008.01.054 Get rights and content

Abstract

Objectives

To follow up the long-term prognosis of patients who underwent nephroureterectomy for primary upper urinary tract (UUT) cancer and to evaluate the predictive factors of tumour recurrence and survival.

Methods

Between January 1990 and June 2005, 260 patients with primary UUT transitional cell carcinoma (TCC) underwent radical nephroureterectomy at our institution. The medical records of these patients were retrospectively reviewed. The clinical and histopathological data were analyzed to evaluate predictive factors.

Results

The median follow-up time was 52 mo. In total, 89 patients (34.1%) developed subsequent bladder tumours. Predictive factors of bladder tumour recurrence were being male and having renal insufficiency. Local recurrence developed in 16 patients (6.2%); only the tumour stage was significantly associated with local recurrence. Metachronous contralateral UUT tumour was diagnosed in 12 patients (4.6%), with gender being the only predictive factor. Of the 260 patients, 167 (63.9%) were disease-free and alive at a median follow-up of 56.5 mo, and 45 (17.2%) died of urothelial cancer at a median period of 20 mo. Only the tumour stage was a prognostic factor to predict cancer-specific survival.

Conclusions

In patients with UUT-TCC after radical nephroureterectomy, tumour stage is the only prognostic factor for both local recurrence and cancer-specific survival. Male patients with renal insufficiency should be alerted to the possibility of bladder tumour recurrence. Because female patients were more likely to develop contralateral recurrences, renal ultrasonography, intravenous pyelography, or retrograde pyelography should be performed more frequently for female patients who live in the high-prevalence area.

Introduction

Transitional epithelium lines the inner surface of the upper urinary tract and urinary bladder. Transitional cell carcinoma (TCC) is a malignant tumour arising from the transitional epithelium. Most TCC grows in the urinary bladder. TCC in the upper urinary tract (UUT) occurs in only about 5% of all urothelial carcinomas [1]. Nephroureterectomy with bladder cuff excision is the standard treatment for UUT-TCC, due to high recurrence rate in the remaining ureter. Despite patients undergoing this standard surgery, tumour recurrence is still common. The major hypotheses to explain recurring tumours were field cancerization, seeding, and intraepithelial migration [2]. Recurrence may develop in the urinary bladder, local retroperitoneal space, and contralateral UUT. To date, the definite risk factors of recurrence and survival for patients after radical nephroureterectomy are still unclear.

Previous studies have shown that the tumour stage is an important prognostic factor for tumour recurrence and survival of patients who undergo surgery for UUT tumours [3]. Most studies combined these three types of recurrence (bladder, local, and contralateral UUT) for prognostic analysis. However, these three types of recurrence might be generated by different mechanisms. For example, local recurrence might due to incomplete tumour resection, bladder recurrence might arise from microscopic tumour seeding or chronic carcinogen stimulation, and contralateral recurrence might develop by urine reflux. We believe that it is necessary to analyze these three types of recurrence separately. It is also important to note that most articles that analyzed risk factors included patients receiving segmental ureterectomy and patients with previous or concomitant bladder cancer. Of course, studies with different inclusion criteria for collecting patient data will result in different predictor factors.

In Taiwan, the incidence rate of UUT-TCC is much higher than the worldwide incidence rate [4], [5]. Thus, in this study we analyzed predictive factors for prognosis by using a large cohort of Taiwanese patients. We report the long-term results of primary UUT-TCC after radical nephroureterectomy. Furthermore, we used strict patient-collection criteria to clarify the possible predictive factors of bladder recurrence, local recurrence, contralateral UUT recurrence, and tumour-specific survival in patients who underwent radical nephroureterectomy for primary UUT-TCC.

Section snippets

Patients and methods

From January 1990 to June 2005, 512 patients were diagnosed with renal calyx, renal pelvic, or ureteral tumours at our institute. We reviewed those patients’ clinical and histopathological records retrospectively. Nephroureterectomy with bladder cuff excision was performed in 409 patients. Histology confirmed TCC in 386 patients (94.4%), squamous cell carcinoma in seven (1.7%), small cell carcinoma in one (0.2%), adenocarcinoma in one (0.2%), renal cell carcinoma in six (1.5%), Wilms tumour in

Results

In this study we observed 125 male and 135 female patients whose median age was 65 yr (range: 23–87), with a median follow-up of 56 mo (range: 12–181). The demographic information of these patients is summarized in Table 1. Of the 260 patients, 102 (39.2%) were renal insufficient (serum creatinine >1.4 mg%), including 20 patients with end-stage renal disease under preoperative haemodialysis. Pathologic stages and grades were distributed as follows: 101 patients had pTa, pT1, or carcinoma in

Discussion

The standard procedure for treating UUT-TCC is nephroureterectomy with bladder cuff removal. Even when patients undergo this standard surgery, however, TCC often recurs in the bladder and sometimes recurs in the previous surgical area or contralateral UUT.

Previous studies have demonstrated that 25–69% of patients after nephroureterectomy for UUT-TCC will have subsequent bladder tumour recurrence [6], [7], [8], [9], [10], [11]. Matsui et al. showed that tumour size, tumour stage, and surgical

Conclusions

Based on our 15-yr experience in treating 260 patients with primary UUT-TCC, we conclude that tumour stage is the only prognostic factors for both local recurrence and cancer-specific survival. The etiology of UUT-TCC in female patients may be different from that of bladder cancers. Gender is a very important predictive factor for Taiwanese patients with UUT-TCC after radical nephroureterectomy. We suggest that male primary UUT-TCC patients with renal insufficiency should be alert of the

Conflicts of interest

None declared.

Acknowledgements

This study was supported by a grant from the Kaohsiung Medical University Hospital (93-KMUH-044). The authors thank Dr. Susan Olmstead for English revision.

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All procedures were completed successfully and one patient needed an additional port. The mean operative time was 196.8 ± 45.8 min and the mean estimated blood loss was 58.9 ± 32.0 ml. The days required for the surgical drain removal and the hospital stay were 4.6 ± 4.6 and 11.1 ± 6.4 days, respectively. One patient developed a fever following surgery but there were no major complications. During the average follow-up period, which lasted 25.5 months, one patient developed spinal cord metastasis and died 8 months after surgery. No obvious abnormalities were found in any of the other patients.
The tansurethral approach of the distal ureter for LESS-NU is deemed safe and efficient. The technique used offers accurate control of the distal ureter and good exposure of LESS.
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Citation Excerpt :
The worldwide incidence of UTUC is less common in women.3–7 However, an epidemiological study in Taiwan showed a higher prevalence of UTUC in women than in men.9,11,12,14,15 The Taiwan Cancer Registry Annual Report15 in 2018 also revealed that the crude incidence rate was higher in women (male-to-female ratio = 1:1.3).
Upper tract urothelial carcinoma (UTUC) is a relatively rare type of urothelial carcinoma. Additionally, only few reports have examined the sex differences in patients with UTUC. Therefore, the present study aimed to identify the sex factors affecting renal function in patients with UTUC who underwent radical nephroureterectomy (RNU).
Patients who underwent RNU for non-metastatic UTUC between 2000 and 2013 were retrospectively reviewed and divided into two groups by sex. The Kaplan–Meier method was applied to evaluate the effects of sex on survival, whereas for the other clinicopathological parameters, hazard ratios were evaluated using the Cox regression model. The analyses were also performed in patients with different chronic kidney disease (CKD) stages.
A total of 368 patients were included, 147 men and 221 women. Female patients had a higher rate of anemia, advanced CKD stage, and dialysis. Male patients predominantly had a higher rate of smoking. The Kaplan–Meier analysis revealed no differences between sexes on recurrence-free survival (RFS) and cancer-specific survival (CSS). Multivariate analysis confirmed that ureteral tumors, advanced pathological tumor stage, and adjuvant chemotherapy indicated significantly worse survival outcomes in both sexes. However, only female patients with advanced CKD showed poorer RFS. After adjusting for renal function, the analysis found men had worse RFS.
The female sex is significantly associated with a higher prevalence of advanced CKD stage, and dialysis among patients with UTUC who underwent RNU in our institute. Sex differences in renal function needs to be considered when evaluating survival.
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The pandemic of COVID-19 has disrupted the clinical pathway for patients with suspected upper tract urothelial carcinoma (UTUC). This aims to investigate the optimal management of UTUC during the pandemic by determining 1) Whether a three-month delay of RNU leads to worsened overall survival, 2) Whether radical nephroureterectomy (RNU) can be performed without prior diagnostic ureteroscopy (URS).
Consecutive patients with RNU performed for suspected UTUC in four hospitals in Hong Kong and Taiwan were included. Patients with histologically proven UTUC and with RNU performed within one year were dichotomized into early (≤3 months) and delayed (>3 months) RNU groups. Diagnostic performances of predictive models based on pre-URS factors (gross haematuria, suspicious or malignant urine cytology, and filling defect or contrast-enhancing mass on computed tomography), with or without URS, were analysed using receiver operating characteristics and area under curve (AUC). Overall survival was analysed using Kaplan-Meier method and multivariate Cox regression analysis.
Between 2000 and 2019, 665 patients underwent RNU, and 491 of them had prior diagnostic URS. The early RNU group had a better overall survival (P = 0.015). Early RNU was associated with a better overall survival upon multivariate analysis (HR 1.55, 95% CI 1.03–2.33, P = 0.035). Large tumour size, multi-focal tumour, T2 or above disease, and positive nodal status were associated with a poorer overall survival. A combination of any 2 out of the 3 pre-URS factors achieved a positive predictive value of 99.5 to 100%. Presence of all 3 pre-URS factors achieved an AUC of 0.851 with URS, and AUC of 0.809 without URS.
A delay of RNU for over 3 months was associated with poorer overall survival and has to be avoided despite the current COVID-19. We can also consider direct RNU based on clinical factors alone. This also avoids URS hospitalization and expedites the clinical pathway of UTUC.
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Urothelial CancerSignificant Predictive Factors for Prognosis of Primary Upper Urinary Tract Cancer after Radical Nephroureterectomy in Taiwanese Patients

Abstract

Objectives

Methods

Results

Conclusions

Introduction

Section snippets

Patients and methods

Results

Discussion

Conclusions

Conflicts of interest

Acknowledgements

Urology

Urology

Eur Urol

Eur Urol

Urology

Urology

J Urol

Am J Kidney Dis

Urology

Eur Urol

Environ Res

Campbell's urology

Clonality of multifocal urothelial carcinomas: 10 years of molecular genetic studies

Int J Cancer

Unusual clinical presentation of upper urothelial carcinoma in Taiwan

Cancer

Time-related recurrence rates in patients with upper tract transitional cell carcinoma

Urology

Urothelial Cancer
Significant Predictive Factors for Prognosis of Primary Upper Urinary Tract Cancer after Radical Nephroureterectomy in Taiwanese Patients