Lymphadenectomy in urothelial carcinoma in the renal pelvis and ureter - A randomized international clinical trial on lymphadenectomy in urothelial carcinoma in the renal pelvis and ureter

Two out of three tumors in the upper urinary tract are located in the renal
pelvis [1]. Muscle-invasive urothelial carcinoma is probably more common among
tumors in the upper urinary tract compared to tumors in the urinary bladder.
Thus, muscle-invasive tumors represent approximately 45 % of renal pelvic
tumors [2,3] compared to 25 % of tumors within the uri-nary bladder. As in the
bladder, lymph node metastases are rare in non-muscle invasive disease.
Information regarding indications, extent and possible curative potential is
currently lacking for lymphadenectomy in conjunction with nephroureterectomy
for urothelial carcinoma in the upper urinary tract (UUTUC). There are,
however, retrospective series with survival data for patients with lymph node
metastasis that report long term survival after surgery as monotherapy [4] with
similar survival proportions as in bladder cancer with lymph node metastases
after radical cystectomy. A retrospective study from Tokyo [5] was expanded to
the only available prospective study, where 68 patients with UUTUC were
submitted to template-based lymphadenectomy [6]. Another retrospective study by
the same Japanese group showed that 5-year cancer-specific and recurrence-free
survival was significantly higher in the complete lymphadenectomy group than in
the incomplete lymphadenectomy or without lymphadenectomy groups [7]. Tanaka N
et al. reported recurrence rate after nephroureterectomy without
lymphadenectomy at 1 and 3 years were 18.9 and 29.8 %, respectively [8].


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cancer. Jpn J Clin Oncol 2014: 44(12):1233-1238.
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Hypothesis:
Complete lymphadenectomy during nephroureterectomy because of invasive
urothelial carcinoma may reduce the incidence of lymph nodes metastasis, local
recurrence, and distant metastasis and improve the cancer survival rate.

Purpose:
To evaluate the influence of complete lymphadenectomy on recurrence and cancer
specific survival rate compared to limited or no lymphadenectomy.

Prospectively randomized to template based lymphadenectomy or not, in patients
with clinically muscle-invasive UUTUC in the renal pelvis or upper 2/3 of the
ureter, that will undergo nephro-ureterectomy. One to one, controlled clinical
trial. Patients will be randomly allocated into two groups, 183 patients in
each group.
Group A will be scheduled to receive routine standard open or robot assisted
nephroureterectomy without lymphadenectomy except for clinically enlarged.
Group B will be scheduled to receive mapped lymphadenectomy in conjugation with
nephroureterectomy.

Surgery:
Open or robot-assisted radical nephroureterectomy according to department
standard.

Procedure:
Robot /laparoscopic - assisted nephroureterectomy:
A 12-mm camera port is placed at the level of the umbilicus and lateral; this
port is moved farther laterally in morbidly obese patients to allow for the
instruments to reach the target organs. Three 8-mm robotic trocars are placed
under direct vision and a 12-mm assistant port is placed in the midline a 5-8
cm above the umbilicus. If needed, another 5-mm assistant port is similarly
placed below the umbilicus. The assistant ports might be moved to the other
side of the midline, especially in thin patients, to allow minimum distance
between the trocars. For right-sided tumors, an additional 5-mm port is placed
in the midline just below the xiphoid process for liver retraction. Placement
of the trocars can be changed according to surgeon preference. The same
placement of the trocars recommended for laparoscopic technique.

Nephrectomy:
After reflecting the colon medially, the ureter is identified off of the lower
pole of the kidney. Careful attention is paid to keeping the peri-ureteric
tissue with the ureter in order to allow an adequate margin in the event of
urethral invasion by the malignancy. Once the ureter is identified, a 10mm
Hem-o-lok clip (Teleflex Medical; Research Triangle Park, NC) is placed around
the ureter to prevent tumor from traveling down the ureter during manipulation.
The ureter is swept upward off of the psoas muscle and followed superiorly to
the renal hilum. The renal artery and vein dissect free and ligate individually
with a 10mm Hem-o-lok clip, two pieces central. Once the perinephric
attachments are free, dissection carries on along the ureter as distal as
possible toward the iliac vessels.

Lymphadenectomy (intervention group only):
Lymphadenectomy performs in four fractions on the right side (1, 2, 4, 5) and
two fractions on the left side (3, 6) according to Dissection template
(Appendix 1). Renal hilar nodes are included in fraction 1 and 3, respectively.
Lymph nodes located posterior to the aorta and vena cava are not included in
the template.

Excision of distal ureter with bladder cuff:
After completion of nephrectomy with or without lymphadenectomy, the ureter is
dissected down to the ureterovesical junction. Retrograde filling of the
bladder may be performed at this stage in order to better identify the
ureterovesical junction. A 1-cm cuff of bladder is carefully excised around the
ureteric orifice, and the specimen is then placed in the Endocatch bag. The
specimen removed through 7 - 10 cm incision in the inguinal region.

Open nephroureterectomy:
Radical nephroureterectomy may be performed through a long midline incision or
through a subcostal plus Gibson, lower midline, or Pfannenstiel incision.
Alternatively, through a single thoracoabdominal incision. Then the same
surgical technique as performed in robot - assisted nephroureterectomy.

Risks and complications:
Lymph edema in the form of swelling of the legs in 23%, lympho-cystic in the
form of accumulation of lymph liquid in operation*s region, thrombosis (blood
clotting) and neighbor-ing organ injury.