Therapeutic role of template-based lymphadenectomy in urothelial carcinoma of the upper urinary tract

Table 1 The incidence of primary nodal involvement in each lymph node sites according to the location of the tumor in urothelial carcinomas of the upper urinary tract

Location of the primary tumor (No. of patients with nodal metastasis)		Ipsilateral						Ipsilateral
		Suprahilar	Ipsilateral renal hilar	Para-caval	Retro-caval	Interaorto-caval	Para-aortic	Common iliac	External iliac	Obturator	Internal iliac	Presacral
Right	RP (22)	-	14 (84%)	8 (36%)	9 (41%)	3 (14%)	-	-	-	-	-
	UU (3)	-	1 (33%)	-	1 (33%)	2 (66%)	-	-	-	-	-
	MU (5)	-	-	-	1 (20%)	4 (80%)	-	-	-	-	-
	LU (7)	-	-	-	-	-	-	4 (57%)	1 (14%)	5 (71%)	2 (29%)	1 (14%)
Left	RP (25)	-	20 (80%)	-	-	1 (4%)	11 (44%)	-	-	-	-
	UU (0)	-	-	-	-	-	-	-	-	-	-
	MU (5)	-	-	-	-	-	5 (100%)	-	-	-	-
	LU (8)	-	-	-	-	-	-	4 (50%)	2 (25%)	3 (38%)	1 (13%)

R-RP: Right renal pelvis; R-UU: Right upper ureter; R-MU: Right middle ureter; R-LU: Right lower ureter; L-RP: Left renal pelvis; L-UU: Left upper ureter; L-MU: Left middle ureter; L-LU: Left lower ureter.

Table 2 Reports on staging benefit of lymphadenectomy in urothelial carcinoma of the upper urinary tract

Authors	Year	Institute	Template of LND	Subject	No. of patients	Results	Staging benefits	Ref.
Roscigno	2009	Multi	Not well described	≥ pT1	1130	5 yr-CSS: pN0 77% > pNx 69% (P = 0.032) > pN+ 35% (P < 0.001)	Yes	[29]
				≥ pT2	813	5 yr-CSS: pN0 70% > pNx 58% (P = 0.017) > pN+ 33% (P < 0.001)
Abe	2010	Multi	Not well described	pT1	66	RFS: pN0 = pNx (P = 0.702)	Yes	[30]
				≥ pT2	227	RFS: pN0 > pNx (P < 0.001) = pN+ (P = 0.134)	in ≥ pT2
Burger	2011	Multi	Not well described	Organ-confined	519	CSS: pN0 = pNx = pN+	Yes	[32]
							In locally advanced disease
				Locally advanced	266	CSS: pN0 = pNx (P = 0.633) > pN+ (P < 0.001)
Lughezzani	2010	Multi	Not described	pT1, pT2	1324	CSS: T1 pN0 = pNx (P = 0.4) = pN+ (P = 0.1)	Yes	[31]
						T2 pN0 = pNx (P = 0.8) = pN+ (P = 0.1)	In ≥ pT3
				pT3, pT4	1382	CSS: T3 pN0 = pNx (P = 0.9) > pN+ (P < 0.001)
						T4 pN0 = pNx (P = 0.3) > pNx (P < 0.001)
Mason	2012	Multi	Not described	All patients	1029	OS: pN0 66.1% = pNx 66.0% (P = 0.617)	Yes	[33]
						> pN+ 22.3% (P < 0.01)
Ouzzane	2013	Multi	Not described	All patients	714	5 yr-CSS: pN0 81% = pNx 85% (P = 0.6)	Yes	[34]
						> pN+ 47% (P < 0.001)	but in T1
				≥ pT2	337	CSS: pN0 = pNx (P = 0.44) = pN+ (P < 0.15)
TWMU	2015	Single	Well described	All patients	314	5 yr-CSS: pN0 84% > pNx 70% (P = 0.02)	Yes	-
						> pN+ 31% (P < 0.001)
				≥ pT2	212	5 yr-CSS: pN0 79% > pNx 59% (P < 0.007)
						> pN+ 31% (P < 0.004)

LND: Lymphadenectomy; CSS: Cancer-specific survival; RFS: Recurrence-free survival; LNs: Lymph nodes; CompLND: Complete lymphadenectomy; DFS: Disease free survival; OS: Overall survival.

Table 3 Reports on therapeutic benefit of lymphadenectomy in urothelial carcinoma of the upper urinary tract

Authors	Year	Institute	Property	Template of LND	Subject	No. of patients	Survival results	Independent factors in Multivariate analysis?	Therapeutic benefit?	Ref.
Kondo	2007	Single	Retrospective	Clearly described	All patients	169	CSS: CompLND = IncompLND = No-LND (P = 0.06)	Yes: CompLND for CSS	Yes	[35]
					≥ pT3	88	CSS: CompLND > No-LND (P = 0.01)		In ≥ pT3
Kondo	2012	Single	Retrospective	Clearly described	≥ pT2	191	5 yr-CSS: CompLND 77.9% > IncompLND 54.0% = No-LND 59.0% (P = 0.03)	Not determined	Yes	[23]
					≥ pT3	140	5 yr-CSS: CompLND 73.2% > IncompLND 43.7% = No-LND 47.3% (P = 0.01)		In ≥ pT2
Brausi	2007	Single	Retrospective	Described	≥ pT2	82	DFS: RPLN 81.6% > No-LND 44.8% (P = 0.007)	Yes: RPLD for OS	Yes	[36]
									in ≥ pT2
Roscigno	2008	Single	Retrospective	Described	≥ pT2	132	5 yr-CSS: LND 57% > No-LND 40%	Yes: LND and pN0 for CSS	Yes	[28]
							(P = 0.01)		in ≥ pT2
							pN0 72% > pNx 39% (P < 0.001)
					≥ pT2pN0	95	7 LNs > less than 7 (P < 0.001)	Yes: No. of LNs for CSS	Yes
									In ≥ 7 LNs removed
Roscigno	2009	Multi	Retrospective	Not well described	≥ pT2	1130	5 yr-CSS: LND 66% = No-LND 69% (P = 0.23)	Yes: pN0 for CSS	No	[29]
Roscigno	2009	Multi	Retrospective	Not well described	≥ pT1pN0	412	5y-CSS: 8 LNs or more 84% > less than 8 73% (P = 0.038)	Yes: No. of LNs for CSS	Yes in ≥ 8 LNs removed	[37]
Abe	2010	Multi	Retrospective	Not well described	All patients	293	RFS: pN0 > pNx (P < 0.001) > pN+ (P = 0.004)	Yes: pNx of RFS	Yes	[30]
Burger	2011	Multi	Retrospective	Not well described	Organ-confined	519	CSS: pN0 = pNx	No	Yes but limited only in locally advanced disease	[32]
					Locally advanced	266	CSS: pN0 = pNx (P = 0.633)	Yes: pN0 for CSS in locally advanced
Lughezzani	2010	Multi	Retrospective	Not described	All patients	2824	No; CSS is pN0 = pNx	No	No	[31]
Mason	2012	Multi	Retrospective	Not described	All patients	1029	OS: pN0 66.1% = pNx 66.0% (P = 0.617)	No	No	[33]
Ouzzane	2013	Multi	Retrospective	Not described	All patients	714	5y-CSS: pN0 81% = pNx 85% (P = 0.6) > pN+ 47% (P < 0.001)	No	No	[34]
					≥ pT2	337	CSS: pN0 = pNx (P = 0.44) = pN+ (P < 0.15)
Kondo	2014	Multi	Prospective	Clearly described	Renal pelvis	90	≥ pT2	Yes in CSS in > pT2	Yes in renal pelvic cancer in ≥ pT2	[23]
							3 yr-OS: LND 86% > No-LND 48% (P = 0.01)
							3 yr-CSS: LND 89% > No-LND 51% (P = 0.01)
							3 yr-DFS: LND 77% > No-LND50% (P = 0.06)
					Ureter	76	≥ pT2	No
							3 yr-OS: LND 46% = No-LND 71% (P = 0.57)
							3 yr-CSS: LND 54% = No-LND 71% (P = 0.99)
							3 yr-DFS: LND 54% = No-LND 59% (P = 0.79)

LND: Lymphadenectomy; LNs: Lymph nodes; CompLND: Complete lymphadenectomy; IncompLND: Incomplete lymphadenectomy; DFS: Disease-free survival; RPLD: Retroperitoneal lymph node dissection; RFS: Recurrence free survival; OS: Overall survival.

Table 4 Perioperative complications of the template-based lymphadenectomy and the no lymphadenectomy group

	Template-based lymphadenectomy (77 patients)		No lymphadenectomy (89 patients )
	Morbidity	n	Morbidity	n
	Grade 1		Grade 1
	Numbness of thigh	2	Atelectasis	1
	lymphorrhea	1	Delirium	2
	Wound infection	1	Wound infection	2
	Grade 2		Lymphorrhea	1
	Chylous leakage	1	Subcutaneous hematoma	1
	Retroperitoneal abscess	1	Grade 2
	Lymphorrhea	1	Anemia	1
	Gastric ulcer	1	Grade 4
	Grade 3a		Intraoperative massive bleeding	1
	Lymphorrhea	1
	Grade 3b
	Rectal injury	1
	Ureteral injury	1
Incidence (all grades)		11		9
		14.20%		10.10%
Incidence (≥ grade 3)		3		1
		3.90%		1.10%