Predictive characteristics for disease recurrence and overall survival in non-metastatic clinical T1 renal cell carcinoma – results from the National Swedish Kidney Cancer Register

Figures & data

Table 1. The distribution of patient’s characteristics in relation to renal cell carcinoma (RCC) type, of 4,965 patients with cT1 RCC extracted from the National Swedish Kidney Cancer Register, years 2005–2014.

Variable		ccRCC (n = 3,781)	pRCC (n = 697)	chRCC (n = 304)	Other (n = 90)	Unknown (n = 93)^a	All (n = 4,965)
Age (years)	Mean	65.0^b	66.0	63.9	66.3	74.8	65.2
	Median (range)	66 (19–92)	67 (14–87)	65 (30–90)	68 (39–87)	78 (33–91)	67 (14–92)
Gender	Men	2,238	516^c	168	54	64	3,040
	Women	1,543 (40.8%)	181 (26.0%)	136 (44.7%)	36 (40.0%)	29 (31.2%)	1,925 (38.8%)
T-stage	pT1a	1,925 (50.9%)	438 (62.8%)	171 (56.3%)	51 (56.7%)	54 (58.1%)	2,639 (59.2%)
	pT1b	1,394 (36.9%)	208 (29.8%)	99 (32.6%)	28 (31.1%)	36 (38.7%)	1,765 (35.5%)
	pT3a	462 (12.2%)	51 (7.3%)	34 (11.2%)	11 (12.2%)	3 (3.2%)	561 (11.3%)
Upstage cT1 to pT3, n (%)	Size ≤ 40 mm	91 (4.1)	20 (4.1)	10 (5.1)	1 (2.9)	0 (0.0)	122 (4.1)
	Size > 40 mm	371 (20.4)	31 (14.7)	24 (18.9)	10 (26.9)	3 (7.9)	439 (19.7)
N-stage	N0/NX	3,749	682	302	83	89	4,905
	N1	32 (0.8%)	15 (2.2%)^d	2 (0.7%)	7 (7.8%)	4 (4.5%)	60 (1.2%)
Treatments	Radical nephrectomy	2,459	324	171	47	5	3,006
	Partial nephrectomy	1,059	308^e	106	26	1	1,500
	Ablation	205	55^e	23	9	12	304
	Other surgical methods	17	1	1	1	1	21
	Surveillance	41	9	3	7	74	134

Percentage is counted as the number of patients with upstaging to pT3 upstage, N-stage, disease recurrence, and survival status in relation to total number of comparable patients, respectively.

Note: Ablation included radiofrequency ablation (n = 267), cryoablation (n = 35), and HIFU (n = 2). ^aPatients with unknown histology was significantly older than the other RCC types (p < 0.001). ^bPatients with ccRCC were significantly older than those with chRCC (p = 0.027). ^cSignificantly different from the ccRCC and chRCC groups (p < 0.001 for both). ^dpRCC had significantly more frequently N1 than ccRCC and chRCC (p < 0.001). ^eSignificantly different proportion of partial nephrectomy in pRCC (p < 0.001) and Ablation versus the other treatments (p = 0.010).

Table 2. Recurrent disease in relation to tumor size and to the performed treatment shown in 4,965 patients with cT1M0 renal cell carcinoma.

Tumor size (mm)	Radical nephrectomy		Partial nephrectomy		Ablation^a		Other^b		Surveillance or, unknown		All
	n	Recurrence, n (%)	n	Recurrence, n (%)	n	Recurrence, n (%)	n	Recurrence, n (%)	n	Recurrence, n (%)	n	Recurrence, n (%)
0− ≤ 10	15	—	15	—	2	1 (50.0)	1	—	2	—	35	1 (2.8)
10− ≤ 20	120	3 (2.5)	327	11 (3.4)	92	13 (14.1)	4	—	16	1 (6.3)	559	28 (5.0)
20− ≤ 30	412	20 (4.9)	508	27 (5.3)	152	25 (16.4)	7	—	30	2 (6.7)	1,109	74 (6.8)
30− ≤ 40	616	55 (8.9)	344	28 (8.1)	48	8 (16.7)	5	1 (20.0)	31	4 (12.9)	1,044	96 (9.2)
40− ≤ 50	747	105 (14.1)	186	20 (10.7)	8	5 (62.5)	1	—	33	5 (15.2)	975	135 (13.8)
50− ≤ 60	601	102 (17.0)	88	10 (11.4))	2	1 (50.0)	1	1 (100.0)	15	—	707	114 (16.1)
60− ≤ 70	495	121 (24.0)	32	7 (21.9)	0	—	2	1 (50.0)	7	1 (14.3)	536	130 (24.3)
Total	3,006	406 (13.5)	1,500	103 (6.9)	304	53 (17.4)	21	3 (14.3)	134	13 (9.7)	4,965	578 (11.6)

Percentage is counted as number of patients with recurrent disease in relation to number out of patients who underwent the same treatment.

^aIncludes radiofrequency ablation (n = 267), cryoablation (n = 35), and HIFU (n = 2). ^bIncludes other surgical procedures.

Table 3. Distribution of sites of disease recurrence in relation to histological tumor type in 578 patients among the 4,965 patients with cT1M0 renal cell carcinoma at primary diagnosis.

Site of recurrence	ccRCC (n = 3,781)	pRCC (n = 697)	chRCC (n = 304)	Other (n = 90)	Unknown (n = 93)	All (n = 4,965)
All	635	86	16	20	10	767
-Lung	224^a	20^a	3	5	4	256
-Skeletal	92	10	2	3	1	108
-Lymph nodes	56	8	2	4	3	57
-Treated kidney	74	17	2	2	2	96
-Local groin	35	6	1	2	0	44
-Adrenal	36	6	0	1	0	43
-Contralateral kidney	18	4	2	1	0	25
-Liver	44	10	3	1	1	59
-Brain	19	1	0	0	0	20
-Other	37	4	0	2	0	43
Patients with recurrences	480^b,c	64^b,d	12^c,d	14	8	578

ccRCC: clear cell renal cell carcinoma; chRCC: chromophobe renal cell carcinoma; pRCC: papillary renal cell carcinoma.

Notes: Patients may have more than one site of recurrence: 145 patients had two sites of recurrences, 44 patients had three sites, and four patients had four sites registered. ^ap = 0.009 comparing recurrences in the lung between ccRCC and pRCC. ^bp = 0.001 comparing recurrent disease between ccRCC and pRCC. ^cp < 0.001 comparing ccRCC and chRCC. ^dp = 0.004 comparing recurrences between pRCC and chRCC.

Table 4. Distribution of survival status in relation to RCC type, pT stage, occurrence of recurrent disease and survival in 4,965 patients with cT1 renal cell carcinoma.

		ccRCC		pRCC		chRCC		Other		Unknown
pT stage		No rec.	Rec.	No rec.	Rec.	No rec.	Rec.	No rec.	Rec.	No rec.	Rec.
	Status	(n = 3,301)	(n = 480)	(n = 633)	(n = 64)	(n = 292)	(n = 12)	(n = 76)	(n = 14)	(n = 85)	(n = 8)
pT1a	Dead, n (%)	390 (21.3)	66 (49.6)	83 (20.3)	13 (44.8)	17 (10.2)	0 (0.0)	15 (39.1)	2 (50.0)	27 (55.1)	4 (80.0)
	Censored, n (%)	1,402	67	326	16	149	5	32	2	22	1
pT1b	Dead, n (%)	329 (27.8)	149 (69.6)	63 (33.9)	17 (77.3)	17 (18.1)	3 (60.0)	10 (43.5)	5 (100.0)	27 (79.4)	2 (100.0)
	Censored, n (%)	851	65	123	5	77	2	13	0	7	0
pT3	Dead, n (%)	134 (40.7)	95 (71.4)	16 (42.1)	24 (82.7)	8 (25.0)	2 (100.0)	3 (50.0)	5 (100.0)	2 (100.0)	1 (100.0)
	Censored, n (%)	195	38	22	5	24	0	3	0	0	0

Percentage of patient’s dead of any cause without (No rec.) or with (Rec.) recurrent disease is shown in brackets.

ccRCC: clear cell RCC; chRCC: chromophobe RCC; pRCC: papillary RCC; RCC: renal cell carcinoma; Rec.: recurrent disease.

Table 5. Results for Cox regression analysis of factors important for time to recurrent disease in 4,965 patients with non-metastatic cT1 renal cell carcinoma.

	Unadjusted				Adjusted
		95.0% CI for HR				95.0% CI for HR
	HR	Lower	Upper	p-value	HR	Lower	Upper	p-value
Age (years, continuous)	1.03	1.02	1.04	<0.001	1.02	1.01	1.02	<0.001
Gender
Male	Ref.
Female	0.86	0.72	1.02	0.08	0.83	0.70	0.99	0.033
Tumor size (mm, continuous)	1.04	1.03	1.04	<0.001	1.03	1.02	1.04	<0.001
N-stage (N0/NX vs N1)	9.08	6.28	13.14	<0.001	4.77	3.24	7.02	<0.001
pT stage
pT1a	Ref.				Ref.
pT1b	2.24	1.85	2.72	<0.001	1.32	0.97	1.80	0.076
pT3a	5.10	4.10	6.33	<0.001	2.83	2.04	3.93	<0.001
Treatment
Radical nephrectomy	Ref.				Ref.
Partial nephrectomy	0.48	0.38	0.59	<0.001	1.03	0.81	1.32	0.79
Ablation	1.30	0.98	1.73	0.07	3.78	2.69	5.32	<0.001
Other surgeries	1.18	0.38	3.67	0.78	2.28	0.73	7.14	0.158
Surveillance	0.93	0.53	1.61	0.785	1.55	0.76	3.18	0.231
RCC type
ccRCC	Ref.				Ref.
pRCC	0.72	0.55	0.93	0.012	0.75	0.57	0.98	0.036
chRCC	0.29	0.17	0.52	<0.001	0.33	0.19	0.59	<0.001
Other RCC types	1.39	0.81	2.36	0.229	1.09	0.64	1.88	0.748
Unknown RCC type	0.81	0.40	1.63	0.551	0.59	0.24	1.44	0.246

CI: confidence interval; HR: hazard ratio; Ref.: reference.

Figure 1. Kaplan-Meier curves of univariate overall survival probability in relation to (a) T stage, pT1a, versus pT1b versus pT3a, (p < 0.001 for all pair-wise differences), (b) patients with recurrent disease versus no recurrence (p < 0.001), (c) RCC types (p < 0.001 for chromophobe RCC versus papillary RCC versus clear cell RCC), and (d) treatment with partial nephrectomy, ablative treatment, and radical nephrectomy (p < 0.001 for partial nephrectomy versus ablation, and versus radical nephrectomy, respectively). Number of patients at risk are shown below corresponding time points.

Table 6. Results from Cox regression analysis of factors important for overall survival in 4,965 patients with non-metastatic cT1 renal cell carcinoma, adjusted for age, gender, tumor size, RCC type, pT-stage, given treatment, recurrence status and N-stage.

	Unadjusted				Adjusted
		95.0% CI for HR				95.0% CI for HR
	HR	Lower	Upper	p-value	HR	Lower	Upper	p-value
Age (years, continuous)	1.08	1.07	1.08	<0.001	1.07	1.06	1.07	<0.001
Gender
Male	Ref.				Ref.
Female	0.94	0.85	1.04	0.240	0.86	0.77	0.95	0.004
Tumor size (mm, continuous)	1.02	1.02	1.02	<0.001	1.01	1.01	1.02	<0.001
RCC type
ccRCC	Ref.				Ref.
pRCC	0.96	0.82	1.11	0.555	1.04	0.89	1.21	0.635
chRCC	0.48	0.36	0.65	<0.001	0.59	0.44	0.78	<0.001
Other	1.81	1.32	2.49	<0.001	1.55	1.12	2.16	0.008
Unknown	2.97	2.31	3.83	<0.001	0.95	0.65	1.39	0.800
pT stage
pT1a	Ref.				Ref.
pT1b	1.55	1.39	1.73	<0.001	0.85	0.71	1.02	0.075
pT3	2.50	2.17	2.89	<0.001	1.12	0.91	1.37	0.280
Treatment
Radical nephrectomy	Ref.				Ref.
Partial nephrectomy	0.50	0.44	0.58	<0.001	0.82	0.71	0.95	0.010
Ablation	0.83	0.66	1.04	0.104	0.95	0.74	1.22	0.691
Other surgeries	1.94	1.07	3.51	0.029	2.09	1.13	3.89	0.019
Surveillance	3.31	2.70	4.07	<0.001	2.57	1.88	3.50	<0.001
Recurrence (yes vs no)	3.65	3.24	4.11	<0.001	2.86	2.53	3.24	<0.001
N-stage (N0/NX vs N1)	5.12	3.81	6.86	<0.001	2.20	1.62	2.99	<0.001

CI: confidence interval; HR: hazard ratio; Ref.: reference; other: other RCC types.