Incidences and oncological outcomes of urothelial carcinoma in kidney transplant recipients

Figures & data

Table 1 Demographic characteristics of KT patients with UC

Patient no.	Gender	BMI (kg/m^2)	Risk factor	Age at KT (years)	KT type	Etiology of ESRD	Immunosuppressants	F/U duration after KT (months)
A	M	30.2		62	LDKT	HN	Steroid, CsA, AZA	135.8
B	F	22.5		65	LDKT	DMCKD	FK, MMF	72.2
C	F	23.5		54	LDKT	Unknown	Steroid, CsA, MMF	151.6
Da	M	23.9		37	DDKT	ADPKD	unknown	35.0
Ea	M	30.6	Smoking	45	LDKT	Unknown	Steroid, CsA	226.6
F	F	31.1	Smoking	41	DDKT	CGN	Steroid, CsA, AZA, MMF	233.7
G	F	22.6		49	DDKT	Unknown	Steroid, CsA, FK, MMF	139.3
H	F	23.0		46	LDKT	CGN	Steroid, CsA, MMF	217.6
I	F	26.6		42	DDKT	Medication	Steroid, CsA, MMF	213.7
J	F	24.0	Family history of bladder cancer	53	LDKT	HN	CsA, MMF	198.5
K	F	25.6		45	LDKT	Unknown	Steroid, CsA, MMF	162.1
La	F	21.9		33	DDKT	Medication	Steroid, CsA, MMF	315.9
Ma	F	33.8		50	LDKT	CGN	Steroid, FK, MMF	257.6
Na	M	21.3		54	DDKT	DMCKD	CsA	178.6
Mean (SD)		25.7 (4.0)		48.3 (8.9)				181.3 (73.3)

Notes:

a Patients who underwent KT at other hospitals and had UC treatment at our hospital.

Abbreviations: ADPKD, autosomal dominant polycystic kidney disease; AZA, azathioprine; BMI, body mass index; CGN, chronic glomerulonephritis; CsA, cyclosporine A; DDKT, deceased-donor kidney transplantation; DMCKD, diabetes mellitus chronic kidney disease; ESRD, end-stage renal disease; F, female; F/U, follow-up; FK, tacrolimus; HN, hypertensive nephropathy; KT, kidney transplantation; LDKT, living donor kidney transplantation; M, male; MMF, mycophenolate mofetil.

Table 2 Characteristics of UC and treatment strategy

Patient no.	Age at UC diagnosis (years)	First presentation	Initial UC type	pT stage	Grade	N stage	Treatment (regimen)	Interval from KT to diagnosis (months)	Alive/death (survival after diagnosis (months))
A	73	Bowel perforation	Bladder cancer	T4	High	cN2	No treatment	135.8	UC-related death (0.1)
B	70	Gross hematuria	Bladder cancer	T2	High	cN1a	TURB + Palliative CTx. (G/Cb)	65.7	UC-related death (7.1)
C	66	Gross hematuria	Bladder cancer	T2	High	cN0	TURB + CCRTx (G/C)	146.2	Alive (5.4)
Db	39	Gross hematuria	Bladder cancer	T1	High	cN0	TURB + Epirubicin instillation	16.0	UC-related death (21.0)
Eb	48	Others	Bladder cancer	T1	High	cN0	TURB	36.0	UC-related death (195.7)
F	53	Others	Transplanted renal pelvis/ureter	T3	High	pNx	Transplanted NUx	146.6	Alive (88.1)
G	54	Incidental CT finding	Bilateral renal pelvis	T4	High	pN1	Bilateral NUx + CCRTx (G/Cb)	60.0	Other-cause death (79.1)
H	52	Gross hematuria	Right distal ureter	T1	High	pNx	Right NUx	81.8	Alive (136.1)
I	55	Flank pain	Right renal pelvis	T3	High	pNx	Right NUx	156.2	Alive (57.4)
J	60	Gross hematuria	Left renal pelvis	T1	High	pNx	Left NUx	79.6	Alive (118.9)
K	58	Flank pain	Right renal pelvis/ureter	T3	High	pN1	Rt NUx + CCRTx (G/Cb)	157.0	Alive (4.8)
Lb	57	Others	Left renal pelvis	T2	High	pN0	Left NUx	286.1	Alive (29.9)
Mb	61	Gross hematuria	Right ureter	T3	High	pNx	Right NUx	122.9	Alive (136.0)
Nb	65	Gross hematuria	Left renal pelvis	T2	High	pNx	Left NUx	129.0	UC-related death (51.2)
Mean (SD)	57.9 (9.0)							115.6 (67.5)

Notes:

a Pre-operative CT urography finding: large bladder tumor with abdominopelvic lymph node metastases.

b Patients who underwent KT at other hospitals and had UC treatment at our hospital.

Abbreviations: CCRTx, concurrent chemoradiotherapy; CTx, chemotherapy; G/C/Cb, gemcitabine/cisplatin/carboplatin; KT, kidney transplantation; NUx, nephroureterectomy; TURB, transurethral resection of bladder tumor; UC, urothelial carcinoma.

Figure 1 Treatment courses of UC in KT recipients.

Abbreviations: CCRTx, concurrent chemoradiotherapy; CTx, chemotherapy; G/C/Cb, gemcitabine/cisplatin/carboplatin; G-mono, gemcitabine mono-regimen chemotherapy; NUx, nephroureterectomy; TURB, transurethral resection of bladder tumor; re-TUR, repeat-TURB.

Table 3 Clinicopathologic characteristics of bladder cancer cases of KT recipients and matched non-KT patients

		KT patients (N=7)a	Non-KT patients (N=14)	P-value
Age at diagnosis (years), mean (SD)		59.0 (11.8)	58.8 (13.1)	0.971
Gender, n (%)	Male	3 (42.9%)	6 (42.9%)	1
Prior UTUC history, n (%)		3 (42.9%)	5 (35.7%)	1
T stage, n (%)	Ta	1 (14.3%)	2 (14.3%)	0.943
	T1	4 (57.1%)	7 (50%)
	T2	2 (28.6%)	5 (35.7%)
Grade, n (%)	High grade	7 (100%)	14 (100%)	1
TURB (# of times), n (%)	1	1 (14.3%)	11 (78.6%)	0.012
	2	2 (28.6%)	2 (14.3%)
	≥3	4 (57.1%)	1 (7.1%)
Intravesical instillation (NMIBC), n (%)	None	1 (20.0%)	6 (66.7%)	0.006
(KT patients, n=5; matched patients, n=9)	BCG	0	3 (33.3%)
	Chemotherapy	4 (80.0%)	0
Treatment (MIBC), n (%)	Radical cystectomy	0	4 (80%)	0.103
(KT patients, n=2; matched patients, n=5)	Bladder preservation CCRTx	1 (50%)	1 (20%)
Bladder cancer progression (+), n (%)		4 (57.1%)	1 (7.1%)	0.025
Interval from diagnosis to bladder cancer progression (m), mean (SD)		42.2 (67.3)	55.6 (76.9)	0.701
Cancer-related death, n (%)		4 (57.1%)	2 (15.4%)	0.122
Follow-up duration (months), mean (SD)		47.7 (67.3)	58.0 (75.9)	0.765

Note:

a Including patients with initial occurrence of bladder cancer and those with bladder cancer after UTUC occurrence.

Abbreviations: BCG, Bacille Calmette-Guérin; CCRTx concurrent chemoradiotherapy; KT, kidney transplantation; MIBC, muscle invasive bladder cancer; NMIBC, non-muscle invasive bladder cancer; TURB, transurethral resection of bladder tumor; UTUC, upper urinary tract urothelial carcinoma.

Table 4 Clinicopathologic characteristics of UTUC cases of KT recipients and matched non-KT patients

		KT patients (N=10)a	Non-KT patients (N=34)	P-value
Age at diagnosis (years), mean (SD)		55.5 (6.75)	57.4 (7.10)	0.445
Gender, n (%)	Male	2 (20%)	11 (32.4%)	0.697
Prior bladder cancer history, n (%)		1 (10%)	3 (8.8%)	1
pT stage, n (%)	Ta	1 (10%)	3 (8.8%)	0.985
	T1–T2	4 (40%)	13 (38.2%)
	T3–T4	5 (50%)	18 (52.9%)
Grade, n (%)	High grade	10 (100%)	34 (100%)	1
N stage, n (%)	pNx	8 (80%)	31 (91.2%)	0.317
	cN1 or pN1	2 (20%)	3 (8.8%)
Radical nephroureterectomy, n (%)		10 (100%)	34 (100%)	1
Adjuvant treatment, n (%)	None	8 (80%)	24 (70.6%)	0.007
	CTx	0	10 (29.4%)
	CCRTx	2 (20%)	0
Adjuvant treatment, n (%)	No	8 (80%)	24 (70.6%)	0.702
	Yes	2 (20%)	10 (29.4%)
UTUC recurrence (+), n (%)		5 (50%)	13 (38.2%)	0.716
Interval from diagnosis to UTUC		57.7 (51.90)	40.8 (36.40)	0.25
recurrence (months), mean (SD)
UTUC progression (+), n (%)		3 (30.0%)	11 (32.4%)	1
Interval from diagnosis to UTUC		64.0 (52.38)	61.8 (44.50)	0.897
progression (months), mean (SD)
Cancer-related death, m (%)		2 (20%)	6 (17.6%)	1
Follow-up duration (months), mean (SD)		71.8 (47.9)	71.1 (38.4)	0.96

Notes:

a Including patients with initial occurrence of UTUC and those with UTUC after bladder cancer occurrence.

Abbreviations: CTx, chemotherapy; CCRTx, concurrent chemoradiotherapy; KT, kidney transplantation; UTUC, upper urinary tract urothelial carcinoma.

Table 5 Comparison of bladder cancer progression and bladder cancer-specific survival rate using GEE

		KT patients	Non-KT patients	P-value
Bladder cancer progression rate	Per 100,000 person-years	112.8	10.71	0.0481
	Relative risk	10.53	1
Bladder cancer-specific survival rate	Per 100,000 person year	99.74	22.15	0.1186
	Relative risk	4.5	1

Abbreviations: GEE, generalized estimating equation; KT, kidney transplantation.

Table 6 Comparison of UTUC recurrence, UTUC progression, and UTUC-specific survival rate using GEE

		KT patients	Non-KT patients	P-value
UTUC recurrence rate	Per 100,000 person year	72.21	78.04	0.8915
	Relative risk	0.93	1
UTUC progression rate	Per 100,000 person year	39.06	43.61	0.8806
	Relative risk	0.8958	1
UTUC-specific survival rate	Per 100,000 person year	23.2	18.93	0.8116
	Relative risk	1.23	1

Abbreviations: GEE, generalized estimating equation; KT, kidney transplantation; UTUC, upper urinary tract urothelial carcinoma.