The Impact of Non-Compliance to a Standardized Risk-Adjusted Protocol on Recurrence, Progression, and Mortality in Non-Muscle Invasive Bladder Cancer

Figures & data

Table 1 Scoring System for High-Risk Group

Variables	Yes = 0 or No = 1
(3 year follow-up)
Number of missed cystoscopies:	0: No missing or 1
	1: 2 missing
	2: 3 missing
IV-MMC	0 or 1
Re-resection at (4–6 weeks)	0 or 1
BCG (Induction and at least M1)	0 or 1
Total	<3 or ≥3

Abbreviations: BCG, Bacille Calmette-Guérin; IV-MMC, intravesical mitomycin.

Table 2 Sociodemographic and Clinical Characteristics of Participants (n = 88)

Variables	Number of Participants (%)
A: Demographic and clinical presentation
Age
<60	23(26.1)
≥60	65(73.9)
Gender
Male	78(88.6)
Female	10(11.4)
Smoking
Yes	73(83.0)
No	15(17.0)
Family history
Yes	17(19.3)
No	71(80.7)
Co-morbidities (HTN, DM, or IHD)
Yes	65(73.9)
No	23(26.1)
Presentation of disease
Haematuria	63(71.6)
Scans (Ultrasound, CT scan, etc)	16(18.2)
LUTS (mainly dysuria)	5(5.7)
Others	4(4.5)
B: Risk stratification, staging and grading
Stage of tumour
pTa	12(13.6)
pT1	7(8.0)
CIS	3(3.4)
General terminology (Superficial bladder cancer)	66(75.0)
Grade of tumour
Low/PUNLMP	22(25.0)
High	66(75.0)
Risk group
Low	14(15.9)
Intermediate	11(12.5)
High	63(71.6)
Delay of diagnosis
Yes	44(50.0)
No	44(50.0)
Muscles found in the first resection
Yes	41(46.6)
No	47(53.4)
IV-MMC was given at 1^st resection
Yes	9(10.2)
No	79(89.8)
C: Compliance, RR, PR, MsR and MR Follow over 3 years
Compliance for all groups
Yes	20(22.7)
No	68(77.3)
Compliance Rate for each risk
Low	6(42.9)
Intermediate	5(45.5)
High	9(14.3)
RR
Yes	74(84.1)
No	14(15.9)
PR
Yes	34(38.6)
No	46(52.3)
Missing	8(9.1)
MetsR
Yes	24(27.3)
No	56(63.6)
Missing	8(9.1)
MR	16(18.2)

Abbreviations: LUTS, lower urinary tract symptoms; CT, computed tomography scan; BCG, Bacillus Calmette–Guérin; IV-MMC, intravesical mitomycin; DM, diabetes mellitus; HTN, hypertension; IHD, ischemic heart disease; RR, recurrence rate; PR, progression rate; MetsR, metastatic rate; MR, mortality rate; CIS, carcinoma in situ; PUNLMP, papillary urothelial neoplasm of low malignant potential.

Table 3 Sociodemographic and Clinical Aspects in Correlation with Compliance

Variables	Compliant N=20 (%)	Non-Compliant N=68	Total	P value ^a
Gender
Male	19 (95%)	59 (86.8%)	78 (88.6%)	0.270^b
Female	1 (5%)	9 (13.2%)	10 (11.4%)
Age
<60	11 (55%)	12 (17.6%)	23 (26.1%)	0.001^c
>60	9 (45%)	56 (82.0%)	65 (73.9%)
Smoking
Yes	18 (90%)	55 (80.9%)	73 (83.0%)	0.317^b
No	2 (20%)	13 (19.1%)	15 (17.0%)
Family history
Yes	20 (100%)	52 (76.5%)	72 (81.8%)	0.002^b
No	0 (0.0%)	16 (23.5%)	16 (18.2%)
Co-morbidities
	12 (60.0%)	53 (77.9%)	65 (73.9%)	0.108^c
Delay of diagnosis
(Within 2 weeks of presentation)	16 (80.0%)	47 (69.1%)	63 (71.6%)	0.002^c
	4 (20.0%)	21 (30.9%)	25 (28.4%)
RR
Yes	11 (55.0%)	63 (92.6%)	74 (84.1%)	< 0.001^c
No	9 (45.0%)	5 (7.4%)	14 (15.9%)
PR
Yes	1(5.3%)	33 (54.1%)	34(42.5)	< 0.001^b
No	18 (94.7%)	28 (45.9%)	46(57.5)
MetsR
Yes	1(5.3%)	23(37.7%)	24(30.0%)	0.003^b
No	18 (94.7%)	38 (62.3%)	56(70.0%)
MR
	0 (0.0%)	16 (23.5%)	16 (18.2%)	0.002^b

Notes: ^aP values in bold are below the significance level of 0.05. ^bStatistical significance values calculated using Fisher’s Exact Test. ^cStatistical significance values calculated using the Pearson Chi-Square.

Abbreviations: RR, recurrence rate; PR, progression rate; MR, mortality rate.

Table 4 The Correlation Between Compliance in Each Risk Group and RR, PR, and MR

Risk Compliance	Low Risk			Intermediate Risk			High Risk
	RR (%)	PR (%)	MR (%)	RR (%)	PR (%)	MR (%)	RR (%)	PR (%)	MR (%)
Compliant	33.3	16.7	0.0	40.0	0.0	0.0	77.8	0.0	0.0
Non-compliant	100.0	83.3	28.6	100.0	100.0	16.7	93.2	56.4	25.0
P value^a	0.004^b	0.016^b	0.095	0.013^b	<0.001^b	0.255	0.195	0.001^b	0.030^b

Notes: ^aP values in bold are below the significance level of 0.05. ^bStatistical significance values calculated using Fisher’s Exact Test.

Abbreviations: RR, recurrence rate; PR, progression rate; MR, mortality rate.

Table 5 The Correlation Between Compliance to Both Cystoscopy and BCG to RR, PR, MetsR and MR in High-Risk Group

	RR	PR	MetsR	MR	Total
Compliant to cystoscopy and BCG	6 (75%)	0 (0%)	1 (12.5%)	0 (0%)	8
Non-compliant to either cystoscopy or BCG	20 (95.2%)	8 (42.1%)	8 (42.1%)	6 (28.6%)	21
Total	26	8	9	6
P value^a	0.133^b	0.008^b	0.115^b	0.035^b

Notes: ^aP values in bold are below the significance level of 0.05. ^bStatistical significance values calculated using Fisher’s Exact Test.

Abbreviations: BCG, Bacille Calmette-Guérin; RR, recurrence rate; PR, progression rate; MetsR, metastatic rate; MR, mortality rate.

Table 6 The Correlation Between BCG Compliance to RR, PR, MetsR and MR in Non-Compliant Patients in High-Risk Group

	RR	PR	MetsR	MR	Total
Compliant to cystoscopy and BCG	6 (75%)	0 (0%)	1 (12.5%)	0 (0%)	8
Compliant to BCG	29 (87.9%)	14 (46.7%)	12 (40%)	7 (21.2%)	33
Non-compliant to BCG	20 (95.2%)	8 (42.1%)	8 (42.1%)	6 (28.6%)	21
Total	49	22	20	13
P value	0.363^a	0.754^b	0.884^b	0.537^b

Notes: ^aStatistical significance values calculated using the Pearson Chi-Square. ^bStatistical significance values calculated using Fisher’s Exact Test.

Abbreviations: BCG, Bacille Calmette-Guérin; RR, recurrence rate; PR, progression rate; MetsR, metastatic rate; MR, mortality rate.

Figure 1 Comparison of the estimated probability of mortality among compliant versus non-compliant patients in the follow-up of NMIBC based on the Kaplan–Meier method for 5 years post-diagnosis.

Table 7 Novel Scoring System to Predict Recurrence, Progression and Mortality in the High-Risk Group

Outcome	Number of <3	Number of ≥3	P value^a
	n=12(%)	n=52(%)
Recurrence	8 (67.0)	48 (94.1)	0.016^b
Progression	0 (0.0)	25 (49)	<0.0001^b
Mortality	0 (0.0)	13 (25.5)	0.012^b

Notes: ^aP values in bold are below the significance level of 0.05. ^bStatistical significance values calculated using Fisher’s Exact Test.