Ureteral stump in the treatment of upper urothelial tumors, is it so important?

Vukotić V., Lazić M., Kojić D., Savić S., Babić U.

Department of Urology,  KBC “Dr Dragiša Mišović- Dedinje ”, Belgrade, Serbia

The most  common tumors of the urinary tract are Transitional Cell Carcinomas (TCC), one of their  important feature being the  tendency  of  formation tumors  either  synchronously and/or metachronously  in multiple foci throughout the urinary tract .  Urothelial tumors of the upper urinary tract  (renal pelvis and ureters- UUT) are rare, accounting for about 5% of all urothelial tumors. The natural history of these tumors shows that 60% of UUT-UCCs are found to be invasive at the time of diagnosis compared with only 15% of bladder tumors ; 60% of UUT-UCCs are invasive at diagnosis compared with only 15% of bladder tumors There are almost no tumors of low malignant potential in the upper urinary tract.  Transitional cell carcinoma of the renal collecting system is traditionally managed by open nephroureterectomy with en bloc resection of a bladder cuff. Since lapaparoscopic nephroureterectomy (NUT) has recently emerged as a safe, minimally invasive approach to upper tract urothelial cancers, the most controversial and challenging feature is the oncologically correct management of the distal ureter and ureterl stump.

OWN RESULTS: We have performed our own study in order  to find  out risk factors influencing prognosis in term of survival  in our patients treated with different types of  open surgery for UUT TCC . In the 9 year period  124 patient were surgically treated for suspicious UUT TCC, which was histologically confirmed  in 113 patients. 87 patient were followed , while 26 pts were lost for control.  Statistical analysis was performed using SPSS  for descriptive statists, life table and  log rank tests for analysis of  prognostic factors. Mean age of our  patients was 67.32 years ( 42- 82), both sexes were equally distributed, left side being mostly affected ( 63:50). Bilateral tumors were present in 9 patients. Tumor was located  only in pyelon in 31 pts, in ureter  in 56, while pyelon and ureter were involved in 26 pts. The localisation of the tumor in ureter was lumbal (25 pts),  illiac (15),  pelvic (21), intramural (19). The most frequent grade of the tumor was Gr 2 (63 pts), Gr 1 was found  in  27 pts, while  gr 3 was found in 23 pts. The pT stage of the disease was 1 in  21 pts, 2 in 45,  3 in  37  and  4 in 10 pts. Open nefroureterectomy (ONU) was performed in  54 pts,through two incisions while only one pararectal incision was used in  30 pts. Subtotal nephrectomy  was done in 33 pts, with later ureterectomy  in 3. Tumor ablation was performed in 12 pts. In 6  pts partial cystectomy was performed along  with NUT for intramural ureteral tumor.  Lymophadenectomy was nor routinely performed. Of  87 patients  who were evaluable for further  assesment  43 died , 38 related to the UUT.  Mean survival was  2.63 godine, 11  patients died  in the first postoperative  year.  Grade was not associated with survival, while stage of the disease significantly influnced  survival ( p<0.05).  The type of  any surgical procedure did not influence the survival . Diferent types of ONU ( one or two incisions) also  did not made a difference  in prognosis and survival, mean expected survival for two incisions being  4.99 years, for one  incision 6.4  years.

DISCUSSION:  Although the golden standard for the treatment  of UUT  is nephroureterctomy with bladder cuff excision, the result from diffferent  studies are conflicting.   Kwak  et al  did not  found bladder cuff  reccurences in patients who underwent nephroureterectomy without bladder cuff excision[i]. Ku concluded that most cancers that subsequently developed in the bladder were not muscle invasive, and, thus, the association of bladder cancer was not a poor prognostic factor [ii] . Lughezzani after the analysis analyses of  2299 patients treated with nephroureterectomy (NU) or segmental ureterectomy (SU) for UUT TCC  within  Surveillance, Epidemiology and End Results registries found that the surgery type (NU with bladder cuff removal versus NU without bladder cuff removal ) did not affect the CSM -free rate[iii]. Quite contrary to previous findings , Lughezzani analyzing 4210 patient with UUT from SEER database stress the importance of bladder cuff  removal,  unexpectadly especialy in patients  with pT3/4 stage[iv]. In a Canadian study involving 680 surgicaly treated patients about 25 % of them had incomplete ureteral resection,  complete ureteral resection defined as pathologically measured ureteral length of  10 cm. According to their results  patients with incomplete resection of ureter had worse survival[v]. Different approaches  to the bladder cuff  had comparable oncologic outcomes, with transurethral incision giving the same results as  intra or extravesical incision in patients with primary UUT-UC without coexistent bladder tumors[vi]

CONCLUSION: Since  UUT TCC   is  rare but  aggressive urologic cancer with a propensity for multifocality, it is questionable  why just the ureteral stump should be of special interest. According to our results, as well as those of some other authors, complete NUT is not always necessary. Since it is clear that any kind of  surgery alone  is not curable for patients with advanced stage of disease effective adjuvant systemic therapy would be beneficial in order to improve the outcome of some patients. The major drawback is the small number of patients, so more  multicentric studies or meta analysis should performed in order to bypass this limitation.

[i] Kwak  C., Lee SE., Jeong  IG. ,  .  KU JH.,  Adjuvant systemis chemotherapy in the treatment of patients with invasive transitional cell carcinoma of the upper urinary tract. Urol 2006:  68: 53–57,

[ii] Ku JH, M.D., Choi WS,  Kwak C Kim HH.  Bladder cancer after nephroureterectomy in patients with urothelial carcinoma of the upper urinary trac tUrol Oncol: Seminars and Original Investigations 29 (2011) 383–387

 [iii] Lughezzani G., Jeldres C, Isbarn H , Sun M.,. Shariat S, Alasker A, Pharand D., , Widmer H., , Arjane P, Graefen M., c, Montorsi F , Perrotte P., Karakiewicz .  Nephroureterectomy and segmental ureterectomy in the treatment of invasive upper tract urothelial carcinoma: Apopulation-based study of 2299 patients. EJC  , 4 5 , 2 0 0 9 ; 3 2 9 1 –3 2 9 7

[iv] Lughezzani  G.,  Sun M.,   Perrotte P.,  Shariat  S, Jeldres  C., Budaus L., Alasker A.,  Duclos A., Widmer H.,  Latour M.  Guazzoni G.,  Montorsi F., Karakiewicz  P. ,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   2 0 1 0; 5 :  9 5 6 – 9 6 2

[v] Abouassaly R, Shabbir M,. Alibhai H., 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.

[vi] Li  WM, Shen JT , Li CC , Ke HK a, Wei YC , Wua WJ, et al  . Oncologic  outcomes Following Three Different Approaches to the Distal Ureter and Bladder Cuff in Nephroureterectomy for Primary Upper Urinary Tract Urothelial Carcinoma. Eur  Urol  5 7 ( 2 0 1 0 ) 9 6 3 – 9 6 9