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Radical nephroureterectomy (RNU) with bladder cuff excision is considered the gold standard treatment for patients with TCC of the upper urinary tract (UUT). According to the high reported recurrence rate in the ipsilateral urothelium, tumours are frequently multifocal. Moreover, the incidence of contralateral synchronous and metachronous disease is low [1–3]. By eliminating the risk of ipsilateral recurrence, radical surgery requires less frequent follow-up examinations, thereby reducing costs .
Kidney-sparing surgery (KSS) has been used for UUT TCC in patients with severely impaired renal function, solitary kidneys, bilateral synchronous tumours or the necessity of platinum-based chemotherapy for future treatment [4,5]. In view of the encouraging oncological results in these patients, a kidney-sparing approach has also been proposed for patients with no imperative indications [6,7]. Whether KSS represents a valid alternative to standard RNU for elective indications remains a matter of debate, as long-term survival data from the few reported series are limited [8–15].
The aim of the present study was to evaluate the long-term oncological outcome in patients with primary TCC of the ureter electively treated with KSS, comparing our data with those in the current literature.
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In our series, tumours were pTa in 42.5% of patients, pT1 in 31.5%, pT2 in 17.8% and pT3 in 8.2% of patients. Ipsilateral pelvic lymph node dissection was performed in 11 patients (15.1%), five of whom were pT1, four pT2 and two pT3. Just one dissection resulted in nodal disease (9%) in a patient that turned out to be pT2 and died because of the disease 37 months after surgery. The grading was distributed as follows: 20.5% G1, 38.4% G2 and 41.1% G3. Four patients (5.5%) had associated pTis (Table 3).
Table 3. Five-year cancer-specific survival in patients with primary UUT TCC treated with segmental ureterectomy from the major series published in the literature
|Authors/year||Patients (no.)||Median/mean follow-up (months)||Stage (no. of patients)||Five-year cancer-specific survival|
|Maier et al. (1990) ||52||41.4||Ta (15), T1 (21), T2 (11), T3 (4), T4 (1)||69.2% (41.4 months)|
|Das et al. (1990) ||10||Long term*||A (5), B (3), D (2)|| * |
|Bukurov et al. (1992) ||101†||1–14 years|| * ||73%|
|Bouffioux et al. (1994) ||20‡||41||Ta (7), T1 (9), T2 (2), T3 (2)||90%|
|Racioppi et al. (1997) ||47||75|| * ||25% (15 years)|
|Hall et al. (1998) ||36||64|| * ||23%|
|Fujimoto et al. (1999) ||10||83.5||Tis (1), Ta (1), T1 (4), T2 (1), T3 (2)||91.7%|
|Chen et al. (2005) ||12||49.3§||Ta (1), T1 (11)||46.4%§|
|van der Poel et al. (2005) ||36||81|| * || * |
|Rouprêt et al. (2007) ||6||32||Ta (5), T2 (1)||100%|
|Raman et al. (2007) ||18||44.1§|| * || * |
|Giannarini et al. (2007) ||19||58||Ta (13), T2 (4), T3 (2)||64%|
|Lehman et al. (2007) ||51||96||Ta (17), T1 (14), T2 (9), T3 (3), T4 (5)||80% (10 years)|
|Dragicevic et al. (2009) ||21||67||T1 (7), T2 (10), T3 (4)||55%§|
|Eandi et al. (2010) ||4||30.5||Tis (1), T1 (2), T2 (1)||100%|
|Jeldres et al. (2010) ||569||30||T1 (231), T2 (192), T3 (124), T4 (22)||86.6%|
|Colin et al. (2012) ||52||26||Ta (22), T1 (12), T2 (12), T3 (5), T4 (1)||87.9%|
|Our results||73||87||Ta (31), T1 (23), T2 (13), T3 (26)||94.1%|
Adjuvant chemotherapy based on gemcitabine and cisplatin was administered to the pN+ patient. The median follow-up was 87 months. Recurrence of bladder urothelial carcinoma was found in 10 patients (13.7%) after a median time of 28 months (Fig. 1).
The overall survival at 5 years was 85.3%. The bladder recurrence-free survival at 5 years was 82.2%. Except for one patient, bladder cancer recurrences were all multifocal and localized in the perimeter area of previous ureteric cancers. Urothelial recurrence in the ipsilateral ureter was diagnosed in two patients (2.7%), one of whom was initially treated for a cancer pTaG2 and the other for a pT1G3. In the first patient the recurrence was endoscopically treated 56 months after the first operation with a laser resection of a pTaG2 tumour located distally to the previous TCC. In the second one the recurrence was treated after 98 months with a nephroureterectomy for a multifocal pT1G3 TCC of the ureter and a pT2G3 of the renal pelvis. Ten of the 73 patients (13.7%) died, six of them due to the disease. All the patients who underwent reimplantation on Boari flap were living and free of disease at the time of follow-up; they had undergone previous transurethral resections for bladder TCC with the following histological results: one pTaG1, one pTaG2 and one pT1G3. The cancer-specific survival at 5 years was 94.1%. Survival was also stratified by the stage of malignancy (Fig. 2) and no patient with pTa tumour died from the disease.
Regarding cancer stage, pTa and pT1 patients were also stratified by histological grade of malignancy. In this case, the survival curves were not significant for pTa (log-rank P= 0.29; Fig. 3) and significant for pT1 tumours (log-rank P= 0.04; Fig. 4) where the survival decreases with increasing grade of the disease. PT2 stage tumours occurred in 13 of 73 patients in whom we found a cancer-specific survival of 77.8% at 77.2 months of follow-up (range 24–120). Patients in whom the tumour occurred in stage pT3 were only six of the 73 total and we observed a cancer-specific survival of 75% at 70 months (range 24–85).
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In this paper we try to elucidate doubts about long-term oncological outcome in patients with UUT TCC treated with an elective open conservative approach. Analysing our series of patients we focused on the lack of data in the current literature regarding the most appropriate management; it is important to consider that the strength of the present study may probably be seen in the combination of a considerable number of patients and a quite long median follow-up. As we wanted to highlight in Table 3, these two aspects are not easy to find in the literature; in fact most studies enrolling a large number of patients usually have a shorter median follow-up and poorer information about tumour stage and bladder recurrence-free survival. There is also commonly a lack of data about the correlation between the conservative surgical approach with follow-up and tumour stage, as shown in the table.
Upper tract TCC is an uncommon disease. Primary upper tract TCC represents approximately 5% of all urothelial carcinomas and 10% of all primary renal tumours. Like TCC of the bladder, upper tract urothelial carcinoma may occur, recur and progress in any location in the urinary tract. The most common location for ureteric TCC is the distal ureter (70%), followed by the middle (25%) and proximal (5%) ureter . Recurrence in the ipsilateral kidney is common and may be as high as 84%. Upper tract TCC is frequently multifocal (up to 44%).
Recurrence rates in the contralateral ureter are less common. The incidence of contralateral synchronous and metachronous recurrence ranges from 1.8% to 5% [19,20]. The risk for contralateral recurrence persists even at 5 and 10 years. Surveillance for contralateral recurrence should continue for up to 10 years .
The treatment of choice for TCC of the distal ureter still remains controversial. According to the updated European Association of Urology guidelines , it is still considered to be RNU. For distal ureteric TCC the option of KSS is mentioned, but no clear recommendations are made. The National Comprehensive Cancer Network guidelines support the use of segmental ureterectomy in properly selected patients with low grade mid-ureteric lesions and in individuals with distal ureteric tumours . Nonetheless RNU remains an equally important option for these two categories of ureteric TCC.
The concept of KSS might be supported by the fact that, in patients with UUT TCC, tumour stage, grade and location within the ureter are the most important prognostic factors, irrespective of the treatment. Tumours of the distal ureter are more common than those of the mid-ureter and proximal ureter and are more frequently solitary, smaller and of lower stage and grade than their renal pelvic or upper ureteric counterparts [2,13]. Furthermore, they are less often associated with recurrent disease within the UUT. Recurrences, if any, occur almost exclusively distal to the primary tumour site and are frequently also of lower stage and grade [8,15,23].
Gathering these data, tumours of the distal ureter should be the most amenable in the UUT for elective KSS [2,23]. The benefit of segmental ureterectomy may reside in lesser morbidity and in renal preservation, which may protect patients from non-cancer-related mortality . Recently Jeldres et al.  illustrated the lack of inferiority when segmental ureterectomy is compared with RNU, with or without bladder cuff removal, for TCC of the ureter. The present study has several limitations related to the use of a population-based tumour registry. In particular there is no information about the localization of ureteric TCC lesions and about chemotherapy or radiotherapy administered to patients. Furthermore there is no information about recurrence-free survival and bladder recurrence-free survival.
In our series the cancer-specific survival after segmental ureterectomy is comparable with other studies (Table 3) which consider KSS and RNU so it would seem that segmental ureterectomy may offer a good oncological outcome in patients with TCC of the ureter, also in a long-term follow-up. Regarding recurrence-free survival, our series illustrates that urothelial recurrence in the ipsilateral ureter was diagnosed only in 2.7% of patients. These patients were subsequently subjected to other treatments, the first undergoing endoscopic treatment and the other a nephroureterectomy. They are now alive and free from the disease. Regarding recurrence of bladder urothelial carcinoma, our data show that the bladder recurrence-free survival at 5 years is 82.2% and this value is comparable with that obtained with RNU as described in the literature .
The sample size of patients with locally advanced disease (pT2–3 TCC) was small. Therefore, the findings regarding patients with pT2–3 disease should be interpreted with caution. However, our data seem to show that these patients should not be excluded from consideration for segmental ureterectomy. In these individuals, KSS may allow the administration of adjuvant or salvage chemotherapy, which may not be an option when RNU is performed and the glomerular filtration rate becomes unacceptably low.
This is a retrospective non-randomized study, which is clearly a limitation. However, this feature was also shared with all other studies about UUT TCC [14,15,23,25,26]. We also did not have a central pathological review. Randomized controlled trials should be encouraged but such studies are difficult to complete due to the relative rarity of the disease.
In conclusion, segmental ureterectomy represents an interesting alternative for the treatment of UUT tumours because it allows a less invasive procedure and guarantees the preservation of renal units. Furthermore, our data seem to show that this procedure does not result in worse cancer control compared with data in the literature regarding nephroureterectomy. When technically possible, segmental ureterectomy may be a valuable option in patients with carcinoma of the ureter.