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ORIGINAL ARTICLE
Year : 2023 | Volume
: 34
| Issue : 2 | Page : 80-85
Oncologic and renal function outcomes of segmental ureterectomy versus radical nephroureterectomy for urothelial carcinoma of the ureter
Sih-Han Chen1, Chun-Hsien Wu2, Richard Chen-Yu Wu1, Hsing-Chia Mai3, Victor C Lin4
1 Department of Urology, E-Da Hospital; School of Medicine, College of Medicine, I-Shou University; Department of Nursing, I-Shou University, Kaohsiung, Taiwan
2 Department of Urology, E-Da Hospital; School of Medicine, College of Medicine, I-Shou University; Department of Nursing, I-Shou University; Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan
3 Department of Nursing, I-Shou University; Department of Urology, E-Da Cancer Hospital, Kaohsiung, Taiwan
4 Department of Urology, E-Da Hospital; School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
Correspondence Address:
Victor C Lin
No. 1, Yida Road, Jiaosu Li, Yanchao District, Kaohsiung City 82445
Taiwan
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/UROS.UROS_54_22
Purpose: The gold standard for treatment of urothelial carcinoma (UC) of the ureter is radical nephroureterectomy (RNU) with bladder cuff excision. However, segmental ureterectomy (SU) can be considered in specific cases, such as serious renal insufficiency or solitary kidney. This study evaluated oncologic and renal function outcomes of SU compared with RNU for treatment of UC of the ureter. Materials and Methods: This single-center retrospective study assessed 99 patients who underwent SU or RNU for UC of the ureter from October 2005 to May 2021. Exclusion criteria were end-stage renal disease managed with regular hemodialysis (10 patients) and previous or concurrent radical cystectomy due to muscle-invasive bladder cancer (20 patients). The study enrolled 69 patients, with 39 in the RNU group and 30 in the SU group, to compare perioperative outcomes and renal function outcomes between the groups. Kaplan–Meier analysis and the log-rank test were performed to compare overall survival (OS), cancer-specific survival (CSS), intravesical recurrence-free survival (IVRFS), and disease-free survival (DFS) between the groups. Results: The mean age was 67.5 years in the RNU group and 68.3 years in the SU group. The median tumor length was 3.2 cm in the RNU group and 2.4 cm in the SU group. Patients who underwent RNU had a significantly decreased estimated glomerular filtration rate at 3 months postoperatively (−6.4 vs. 3.5 mL/min/1.73 m2; P = 0.001). No significant differences were found for OS, CSS, and IVRFS between the groups. However, the SU group had shorter DFS (P = 0.029). Conclusion: Results showed that SU may preserve better renal function. The OS and CSS were comparable between the groups; however, the SU group had shorter DFS. When preservation of renal function is warranted, SU may be considered for patients with UC of the ureter.
Keywords: Carcinoma, radical nephroureterectomy, renal function, segmental ureterectomy, ureter
Urothelial carcinoma (UC) of the ureter is an uncommon disease accounting for only 5% of UC cases, with an estimated incidence of 0.91 cases per 100,000 individuals per year.[1],[2],[3] In 17% of patients with UC of the ureter, bladder cancer coexists with the condition.[4] Radical nephroureterectomy (RNU) with bladder cuff excision is the gold standard for treatment of UC of the ureter and provides durable local control and cancer-specific survival (CSS).[5] However, a decrease in the estimated glomerular filtration rate (eGFR) after RNU may increase the risks of mortality and cardiovascular disease.[6],[7]
Kidney-sparing surgery (KSS) for low-grade and noninvasive UC of the ureter can reduce the morbidities associated with RNU, while not compromising the oncologic outcomes.[8] Ureteroscopy, percutaneous access, segmental ureterectomy (SU), and application of topical medications to the upper urinary system are all methods that can be used for KSS.[2] Current guidelines suggest that any KSS should be based on shared decision-making with the patient.[2] For patients who cannot tolerate RNU or have compelling indications such as solitary kidney, renal insufficiency, or bilateral UC of the ureter, SU should be considered a treatment for UC of the ureter.[9] The application of SU can provide valid pathologic specimens for tumor staging and guide adjuvant therapies.[8] Furthermore, SU can be safely performed for selected patients with high-grade and/or invasive UC when preservation of renal function is desired, although the remaining ureter is at risk of recurrence, and regular follow-up is necessary.[2],[8],[10] Although SU may be beneficial to preserve renal function, this approach may result in worse oncologic outcomes. To our knowledge, only limited data are available that compare oncologic and renal functional outcomes between SU and RNU as treatments for UC of the ureter, with conflicting results.[10],[11],[12],[13] Thus, the purpose of this study was to compare the oncologic and renal function outcomes between SU and RNU for UC of the ureter.
Materials and MethodsIn this single-center study, 99 patients who underwent SU or RNU for UC of the ureter at our institution between October 2005 and May 2021 were retrospectively evaluated. Patients with end-stage renal disease handled with regular hemodialysis (10 patients) and who had prior or concurrent radical cystectomy due to muscle-invasive bladder (20 patients) cancer were excluded from the study. The study enrolled the remaining 69 patients into two groups for comparison, with 39 patients in the RNU group and 30 patients in the SU group. On November 23, 2021, the E-Da Hospital's Institutional Review Board approved this study (EMRP-110-148) and exempted the participants' informed consent.
Variables
The clinicopathologic characteristics, kidney function, and oncologic outcomes were reviewed. The risk stratification of UC of the ureter in our study was based on the European Association of Urology guidelines.[2] Preoperative eGFR and postoperative follow-up data at 3 months were collected. According to the Clavien–Dindo grading system, the perioperative complications were evaluated. Intravesical recurrence-free survival (IVRFS) was defined as the length of time from surgery to the date of tumor recurrence in the bladder. Disease-free survival (DFS) was defined as the length of time from surgery to either local recurrence, intravesical recurrence, or regional lymph node or distant metastasis occurrence. Overall survival (OS) and CSS were defined as the length of time between surgery and death from any cause and from UC of the ureter, respectively.
Follow-up
Patients were followed up every 3 months for the first 2 years after surgery, every 6 months for the 3rd to 5th year after surgery, and once annually thereafter. The follow-up assessments included the measurement of serum creatinine, cystoscopy, renal ultrasound, abdominal/pelvic computed tomography, or magnetic resonance imaging. For patients who underwent SU, ureteroscopy of the index lesion side was performed every 3 months for the 1st year postoperatively.
Statistical methods
Continuous variables were expressed as mean ± standard deviation and compared using the Student's t-test, and categorical variables were analyzed using the Chi-square test. The Kaplan–Meier analysis was used to estimate OS, CSS, DFS, and IVRFS for patients treated with RNU and SU, and the log-rank test was used to assess the differences between the groups. Statistical analyses were performed using SPSS version 22 (IBM, New York, NY, USA). P < 0.05 was considered to indicate statistical significance.
ResultsOf the 69 enrolled patients, 39 were in the RNU group, and 30 were in the SU group. [Table 1] shows the demographics and characteristics of both the groups. The mean ages for the RNU and SU groups were 67.5 and 68.3 years, respectively (P = 0.54). The Charlson Comorbidity Index score was 2.8 ± 1.3 for the RNU group and 3.4 ± 1.8 for the SU group (P = 0.09). Most of the tumors in the SU group were located in the distal ureter (19 patients, 63.3%), whereas most of the ureter tumors in the RNU group were located in the upper (16 patients, 41%) and middle ureter (12 patients, 30.8%), revealing significant differences between the two groups (P = 0.007). All patients in both the groups had preoperative hydronephrosis, and all were classified as high risk according to the European Association of Urology risk stratification for upper urinary tract UC. Only one patient in the SU group underwent neoadjuvant chemotherapy.
Table 1: Demographics and characteristics of patients who underwent radical nephroureterectomy or segmental ureterectomyThe surgical and postoperative results are summarized in [Table 2]. Lymph node dissection was performed for 26 patients (66.7%) in the RNU group and for 16 patients (53.4%) in the SU group (P = 0.139). The estimated blood loss was lower in the SU versus that in the RNU patients (76.3 ± 19.5 mL vs. 147.2 ± 25.3 mL; P = 0.01). The mean length of hospital stay was comparable in both the groups (RNU: 11.6 ± 0.7 days vs. SU: 9.8 ± 0.6 days; P = 0.31). The blood transfusion rate between the groups was similar. The recorded 30-day postoperative complications ranged from Clavien–Dindo Grade II in four RNU patients to Grade IIIb in one SU patient who had ureter anastomosis site leakage, which required another ureteral catheterization under general anesthesia. The 30-day postoperative complication rate did not significantly differ between the groups (RNU: 10.3% vs. SU: 3.3%; P = 0.22).
The pathogenic features are shown in [Table 3]. The mean tumor length was 3.2 ± 2.5 cm and 2.4 ± 2.5 cm in the RNU and SU groups, respectively (P = 0.008). For patients who received lymph node dissection, the mean number of lymph nodes removed was 5.5 and 11.2 nodes in the RNU and SU groups, respectively (P = 0.323). Positive lymph nodes were found in three patients (7.7%) in the RNU group and four patients (13.3%) in the SU group (P = 0.03). Patients who underwent RNU had similar pathologic stage (P = 0.109), pathologic grade (P = 0.144), and multifocal tumors rate (P = 0.051) compared with those who underwent SU. The positive surgical margin rate was 5.1% and 10% in the RNU and SU groups, respectively (P = 0.268). Adjuvant chemotherapy was administered to 13 patients (33%) in the RNU group and to 12 patients (40%) in the SU group (P = 0.288).
The preoperative and 3-month postoperative renal function characteristics for both the groups are shown in [Table 4]. The preoperative renal function for both the groups was similar (eGFR: 43.7 vs. 45.3 mL/min/1.73 m2 for the RNU and SU groups, respectively; P = 0.61). Patients treated with SU experienced significant improvement in eGFR compared with those treated with RNU (3.5 vs. −6.4 mL/min/1.73 m2; P = 0.001). Meanwhile, 94.9% of the RNU group had postoperative eGFR <60 mL/min/1.73 m2 compared with 76.9% preoperatively; however, 70% of the SU group had postoperative eGFR <60 mL/min/1.73 m2 compared with 83.3% preoperatively.
Table 4: Renal function characteristics preoperatively and 3 months postoperativelyThe mean follow-up was 68 months and 33 months in the RNU and SU groups, respectively. In the SU group, ten patients experienced ipsilateral ureteral recurrence after surgery. Of these ten patients, seven underwent nephroureterectomy and bladder cuff excision, one patient was treated with palliative radiation therapy, one patient was treated with adjuvant chemotherapy, and one patient underwent conservative treatment due to multiple comorbidities.
Recurrent lesions over the bladder occurred in seven patients in the SU group and eight patients in the RNU group. As shown in [Figure 1]a, [Figure 1]b, [Figure 1]c, no significant differences were found between the RNU and SU groups with regard to OS (P = 0.162), CSS (P = 0.379), and IVRFS (P = 0.17). However, the DFS was shorter for the SU group compared with that of the RNU group (P = 0.029) [Figure 1]d.
Figure 1: Kaplan–Meier curves of overall survival (a), cancer-specific survival (b), intravesical recurrence-free survival (c), and disease-free survival (d) for patients who underwent RNU or SU. RNU: Radical nephroureterectomy, SU: Segmental ureterectomy Discussion The standard course of treatment for UC of the ureter is nephroureterectomy with bladder cuff excision.[2] However, decreases in eGFR after nephrectomy may increase the risk of cardiac-related death.[6] Huang et al.[14] reported that nephrectomy may increase the risk of cardiovascular events and OS compared with KSS. For patients unable to tolerate RNU or those with a solitary kidney, severe renal failure, or bilateral ureteral tumors, KSS should be considered a treatment option for UC of the ureter.[9]
Currently, SU has a role in the treatment of nonmetastatic low-risk UC of the ureter and selected high-risk UC of the ureter in patients desiring to preserve renal function.[2] The benefit of SU is that it may preserve renal function, has lower morbidity, and may reduce noncancer-related mortality.[15] Several studies have revealed that renal function is preserved for patients who underwent treatment with SU compared with those who underwent RNU.[11],[13],[16] In our study, we also found that patients treated with SU experienced renal function preservation in the eGFR compared with those treated with RNU (3.5 vs. −6.4 mL/min/1.73 m2; P = 0.001), which was concordant with the findings in previous studies.[12]
As stated in the National Comprehensive Cancer Network (NCCN) guidelines, distal ureterectomy and reimplantation of the ureter were suitable for distal ureteral tumor.[17] Nevertheless, Abrate et al.[18] concluded that patients treated with ureteroureterostomy or ureteral reimplantation for distal ureteral tumors had comparable OS, CSS, recurrence-free survival (RFS), and postoperative renal function.[18] Ureteroneocystostomy showed a higher incidence of Grade I vesicoureteral reflux than that in ureteroureterostomy (17.6% vs. 0%, P = 0.031).[19] In summary, both ureteroureterostomy and ureteral reimplantation could be safely performed for patients with distal ureteral tumors.
According to the NCCN treatment guidelines for UC of the ureter, adjuvant platinum-based chemotherapy should be considered if the pathology report showed pT3, pT4, or pN+ and no platinum neoadjuvant chemotherapy was given.[17] However, for patients who undergo RNU, delivery of cisplatin-based adjuvant chemotherapy may not be feasible because RNU might affect renal function.[20] In contrast, patients who underwent SU may have preservation of renal function and would be more likely to tolerate adjuvant chemotherapy. The renal function improvement postoperatively in the SU group may be attributed to relief of partial or complete obstruction of the ureter, which could preserve ipsilateral renal function. In our study, 94.9% of the RNU group patients had postoperative eGFR <60 mL/min/1.73 m2, and 13 patients (33%) received adjuvant chemotherapy. In contrast, 70% of the SU group patients had postoperative eGFR <60 mL/min/1.73 m2, and 12 patients (40%) underwent adjuvant chemotherapy.
In this study, the OS, CSS, and IVRFS did not differ significantly between the SU and RNU groups. However, patients in the SU group had a significantly shorter DFS than that of the RNU group. A systematic review in 2016 reported that the 5-year CSS, 5-year RFS, and 5-year IVRFS did not differ significantly between the SU and RNU groups.[21] However, another systematic review in 2020 showed that patients who underwent SU had lower 5-year RFS compared with that of the RNU group (odds ratio: 0.64; P = 0.03).[22] Xylinas et al.[23] reported that patients with a distal ureteral tumor location and previous history of bladder cancer had shorter RFS.[23] In our study, the SU group had a higher percentage of distal ureteral tumor than that of the RNU group, and this finding may explain the shorter DFS in the SU group.
Our study had several limitations. First, this was a retrospective study with relatively small sample size. Second, there might be a selection bias regarding the treatment modalities, as discussed previously. Patients who had lower ureteral UC and/or poor renal function may prefer SU rather than RNU. Finally, the RNU group had a longer mean follow-up time compared with that of the SU group, which could have an impact on the significance of our results. Regardless of these limitations, this study provides evidence that patients with UC of the ureter could choose SU when preservation of renal function is warranted.
ConclusionOur data showed that SU may better preserve the renal function of patients with UC of the ureter. The OS and CSS were comparable between the groups; however, the SU group had a shorter DFS than that of the RNU group. Based on these results, SU may be considered for patients with UC of the ureter when preservation of renal function is warranted. Further prospective randomized studies are required for the validation of these results.
Data availability statement
All data generated or analyzed during this study are included in this published article.
Financial support and sponsorship
Nil.
Conflicts of interest
Dr. Victor C. Lin, an editorial board member at Urological Science, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.
References
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