External validation of EORTC risk scores to predict recurrence after transurethral resection of brazilian patients with non-muscle invasive bladder cancer stages Ta and T1

205 patients were analyzed. The 6 parameters analyzed were: histologic grading, pathologic stage, size and number of tumors, previous recurrence rate and concomitant CIS. The time for first recurrence (TFR), risk score and probability of recurrence were calculated and compared to the probabilities obtained from EORTC risk tables. C-index was calculated and accuracy of EORTC tables was analyzed. Results: pTa was presented in 91 (44.4%) patients and pT1 in 114 (55.6%). Ninety-seven (47.3%) patients had solitary tumor, and 108 (52.7%) multiple tumors. One hundred and three (50.2%) patients had tumors smaller than 3 cm and 102 (40.8%) had bigger than 3 cm. Concomitant CIS was observed in 21 (10.2%) patients. Low grade was presented in 95 (46.3%) patients, and high grade in 110 (53.7%). Intravesical therapy was utilized in 105 (56.1%) patients. Recurrence was observed in 117 (57.1%) patients and the mean TFR was 14,2 ± 7,3 months. C-index was 0,72 for 1 year and 0,7 for 5 years. The recurrence risk was 28,8% in 1 year and 57,1% in 5 years, independently of the scoring risk. In our population, the EORTC risk tables overestimated the risk of recurrence in 1 year and underestimated in 5 years.

Conclusion:

The validation of the EORTC risk tables in Brazilian patients with NMIBC was satisfactory and should be stimulated to predict recurrence, although these may overestimated the risk of recurrence in 1 year and underestimated in 5 years.

Keywords:
Urinary Bladder; Carcinoma; Recurrence; Transurethral Resection of Prostate

Factor		Recurrence
Number of tumors
	Single	0
	2 to 7	3
	>or=8	6
Tumor diameter
	<3.0cm	0
	>or=3.0cm	3
Primary previous recurrence
	<or=1 recurrence/year	2
	>1 recurrence/year	4
Cathegory
	pTa	0
	pT1	1
Concomitant CIS
	No	0
	Yes	1
Histologic grade (OMS 1973)
	G1	0
	G2	1
	G3	2
Total score		0–17

Recurrence score	Recurrence probability in 1 year		Recurrence probability in 5 years		Recurrent risk group
	%	(95% 1A)	%	(95% 1A)
0	15	(10–19)	31	(24–37)	Low risk
1–4	24	(21–26)	46	(42–49)	Intermediate risk
5–9	38	(35–41)	62	(58–65)	Intermediate risk
10–17	61	(55–67)	78	(73–84)	High risk

Characteriscs		Our population n (%)	EORTC n (%)
Total number of patients		205	2596
Age (years)
	≤60	55 (26.8)	859 (33.1)
	61–70	86 (42)	890 (34.3)
	71–80	55 (26.8)	690 (26.6)
	>80	9 (4.4)	118 (4.5)
	unknown	0	39 (1.5)
Gender
	male	144 (70.2)	2044 (78.7)
	female	61 (29.8)	515 (19.8)
	unknown		37 (1.4)
T stage
	pTa	91 (44.4)	1451 (55.9)
	pT1	114 (55.6)	1108 (42.7)
Number of tumors
	Single	97 (47.3)	1465 (56.4)
	2 to 5	64 (31.2)	836 (32.2)
	>5	44 (21.5)	255 (9.8)
	unknown	-	45 (1.7)
Tumor size
	<3cm	103 (50.2)	2087 (80.4)
	≥3cm	102 (49.8)	464 (17.9)
	unknown	0	45 (1.7)
CIS presence
	Yes	21 (10.2)	113 (4.4)
	No	184 (89.8)	2440 (94.0)
Recurrence
	Primary	137 (66.8)	1405 (54.1)
	≤1/year	35 (17.1)	505 (19.5)
	>1/year	33 (16.1)	645 (24.8)
Histologic grade
	Low grade(G1/G2)	95 (46.3)	2260 (87.1)
	High grade (G3)	110 (53.7)	271 (10.4)
Intravesical therapy
	None	90 (43.9)	561 (21.6)
	Chemotherapy	24 (11.7)	2035 (78.4)
	BCG	46 (22.4)	-
	Chemotherapy + BCG	45 (22)	361 (13.9)
Follow-up (months)
	Medium	63.6	46.8
	Minimum	6	-
	Maximum	144	177.6
Recurrence
	Yes	117 (57.1)	1240 (47.8)
	No	88 (42.9)	1356 (52.2)
End-point
	Free of disease	127 (62)	1743 (67.1)
	Progression	25 (12.2)	279 (10.7)
	Death by disease	21 (10.2)	262 (10.1)
	Death	15 (7.3)	461 (17.8)
	Noncompliance with treatment	17 (8.3)	130 (5)
Survival
	Alive	152 (74.2)	1743 (67.1)
	Dead	36 (17.5)	279 (32.9)
	Unknown	17 (8.3)	-

Recurrence score	number of patients^* * number of patients in the presente study in each risk group of EORTC	Probability of recurrence in 1 year (IC 95%)		Probability of recurrence in 5 years (IC 95%)
Recurrence score		EORTC	Present study	EORTC	Present study
0	30	15 (10 - 19)	6.7 (0.8 - 22.1)	31 (24 - 37)	10.0 (2.1 - 26.5)
1 - 4	54	24 (21 - 26)	14.8 (6.6 - 27.1)	46 (42 - 49)	46.3 (32.6 - 60.4)
5 - 9	78	38 (35 - 41)	29.5 (19.7 - 40.9)	62 (58 - 65)	66.7 (55.1 - 76.9)
10 - 17	43	61 (55 - 67)	60.5 (44.4 - 75.0)	78 (73 - 84)	86.0 (72.1 - 94.7)
	205		28.8 (22.7 - 35.5)		57.1 (50.0 - 63.9)

	Number of patients	Sample studied	Studied variables	Endpoints	Accuracy calibration	C-index	External validation
Fernandez-Gomez et al. ( ⁸8. Fernandez-Gomez J, Madero R, Solsona E, Unda M, Martinez-Piñeiro L, Ojea A, et al. The EORTC tables overestimate the risk of recurrence and progression in patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guérin: external validation of the EORTC risk tables. Eur Urol. 2011;60:423–30. )	1062	Spain	Number of tumors, size, previous recurrence rate, T stage, tumor grade, concurrent CIS	RR 1 and 5 years stratified according to risk groups	Overestimated RR	0,63 for 1 and 5 anos	YES
Pillai et al. ( ⁹9. Pillai R, Wang D, Mayer EK, Abel P. Do standardised prognostic algorithms reflect local practice? Application of EORTC risk tables for non-muscle invasive (pTa/pT1) bladder cancer recurrence and progression in a local cohort. ScientificWorldJournal. 2011;11:751–9. )	109	United Kingdom	=	RR 1 and 5 years stratified according to risk groups	Underestimated RR in all risk groups	0,62 for 1 year 0,63 for 5 years	NO
Xylinas et al. ( ²³23. Xylinas E, Kent M, Kluth L, Pycha A, Comploj E, Svatek RS, et al. Accuracy of the EORTC risk tables and of the CUETO scoring model to predict outcomes in non-muscle-invasive urothelial carcinoma of the bladder. Br J Cancer. 2013;109:1460–6. )	4689	Spain	=	RR in 57 months	Overestimated RR mainly in high risk patients	0.597	NO
Ding et al. ( ¹⁵15. Ding W, Chen Z, Gou Y, Sun C, Xu K, Tan J, et al. Are EORTC risk tables suitable for Chinese patients with non-muscle-invasive bladder cancer? Cancer Epidemiol. 2014;38:157–61. )	301	China	-	RP in 1 and 5 years	Overlapped CI	NR	YES
Sakano et al. ( ²⁴24. Sakano S, Matsuyama H, Takai K, Yoshihiro S, Kamiryo Y, Shirataki S, et al. Risk group stratification to predict recurrence after transurethral resection in Japanese patients with stage Ta and T1 bladder tumours: validation study on the European Association of Urology guidelines. BJU Int. 2011;107:1598–604. )	592	Japan	-	recurrence-free survival	NR	NR	NO
Borkowska et al. ( ²⁵25. Borkowska EM, Jedrzejczyk A, Marks P, Catto JW, Kału ewski B. EORTC risk tables - their usefulness in the assessment of recurrence and progression risk in non-muscle-invasive bladder cancer in Polish patients. Cent European J Urol. 2013;66:14–20. )	91	Poland	=	RR in 1 year stratified according to risk groups	Overestimated RR	NR	NO
Xu et al. ( ¹⁷17. Xu C, Jiang XZ, Zhang NZ, Ma L, Xu ZS. [Efficacy of European Organization for Research and Treatment of Cancer (EORTC) risk tables for the prediction of recurrence and progression of non-muscle invasive bladder cancer after intravesical pirarubicin instillation]. Zhonghua Zhong Liu Za Zhi. 2012;34:609–12. )	389	Taiwan	-	RR 1 and 5 years stratified according to risk groups	Overestimated RR	NR	YES
Seo et al. ( ¹⁸18. Seo KW, Kim BH, Park CH, Kim CI, Chang HS. The efficacy of the EORTC scoring system and risk tables for the prediction of recurrence and progression of non-muscle-invasive bladder cancer after intravesical bacillus calmette-guerin instillation. Korean J Urol. 2010;51:165–70. )	251	South Korea	=	RR 1 and 5 years stratified according to risk groups	Overestimated RR	NR	YES
Ather and Zaidi ( ²⁰20. Ather MH, Zaidi M. Predicting recurrence and progression in non-muscle-invasive bladder cancer using European organization of research and treatment of cancer risk tables. Urol J. 2009;6:189–93. )	92	Pakistan	=	RR in 1 year	Underestimated RR	NR	YES
Altieri et al. ( ²¹21. Altieri VM, Castellucci R, Palumbo P, Verratti V, Sut M, Olivieri R, et al. Recurrence and progression in non-muscle-invasive bladder cancer using EORTC risk tables. Urol Int. 2012;89:61–6. )	259	Italy	=	RR in 1, 3 qnd 5 years	Overestimated RR in high and intermediate risk groups	NR	YES
Ajili et al. ( ¹⁹19. Ajili F, Darouiche A, Chebil M, Boubaker S. The efficiency of the EORTC scoring system for the prediction of recurrence and progression of non-muscle-invasive bladder cancer treated by bacillus Calmette-Guerin immunotherapy. Ultrastruct Pathol. 2013;37:249–53. )	112	Tunis	=	RR in 1 year stratified according to risk groups	Overestimated RR except in high risk patients	NR	YES
Hernández et al. ( ¹⁶16. Hernández V, De La Peña E, Martin MD, Blázquez C, Diaz FJ, Llorente C. External validation and applicability of the EORTC risk tables for non-muscle-invasive bladder cancer. World J Urol. 2011;29:409–14. )	417	Spain	=	RR 1 and 5 years stratified according to risk groups	Overlapped CI	NR	YES
Lammers et al. ( ²⁶26. Lammers RJ, Palou J, Witjes WP, Janzing-Pastors MH, Caris CT, Witjes JA. Comparison of expected treatment outcomes, obtained using risk models and international guidelines, with observed treatment outcomes in a Dutch cohort of patients with non-muscle-invasive bladder cancer treated with intravesical chemotherapy. BJU Int. 2014;114:193–201. )	728	Holand	-	RP in 1 and 5 years	Overlapped ci	NR	YES
van Rijin et al. ( ²²22. van Rhijn BW, Zuiverloon TC, Vis AN, Radvanyi F, van Leenders GJ, Ooms BC, et al. Molecular grade (FGFR3/MIB-1) and EORTC risk scores are predictive in primary non-muscle-invasive bladder cancer. Eur Urol. 2010;58:433–41. )	230	Multicenter	=	RR 1 and 5 years stratified according to risk groups	-	NR	YES
Almeida et al.	205	Brazil	=	RR 1 and 5 years stratified according to risk groups		0,72 for 1 year 0,7 for 5 years	YES

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[1] Correspondence address: Gilberto Laurino Almeida, MD, Avenida Marcos Konder 1120,, Itajaí, Santa Catarina, Brasil, Fax: + 55 47 3346-6700, E-mail: glalmeida@ibest.com.br