Efficacy analysis of a novel thermochemotherapy scheme with pirarubicin for intermediate- and high-risk nonmuscle-invasive bladder cancer: a single-institution nonrandomized concurrent controlled trial

Figures & data

Figure 1. (A) Appearance of BR-TRG-I urinary bladder hyperthermia treatment system. (B) The schematic diagram of the pipeline system of BR-TRG-I urinary bladder hyperthermia treatment system. Figures adapted with permission from Qifei Li, Guangzhou Bright Medical Technology Co., Ltd.

Figure 2. The schematic diagram of treatment of CTHC and THP groups. Above the dotted line is the induction treatments, maintenance treatments are below the dotted line. CTHC: three consecutive hyperthermia treatments combined with single instillations; HT: hyperthermia; THP: pirarubicin.

Figure 3. Diagram of this study. BCG: Bacillus Calmette-Guérin; Cis: carcinoma in situ; CTHC: three consecutive hyperthermia treatments combined with single instillations; MIBC: muscle invasive bladder cancer; NMIBC: nonmuscle invasive bladder cancer; MMC: mitomycin C; ITT: intention to treat; RC: radical cystectomy; TURBT: transurethral resection of bladder tumors; THP: pirarubicin.

Table 1. Demographics and baseline characteristics (n = 161).

Characteristic	CTHC (n = 76)		THP (n = 85)		p-value
	n	%	n	%
Gender					.322
Male	64	84.2	66	77.6
Female	12	16.8	19	23.4
Age, years, median, range	63 (39–87)		66 (40–88)		.066
Whether with hypertension or diabetes					.92
Hypertension	17	22.4	20	23.5
Diabetes	2	2.6	4	4.7
Hypertension and diabetes	3	3.9	3	3,.5
None	54	71.1	58	68.3
Tumor size (cm)					1
<3	48	63.1	53	62.4
≥3	28	36.4	32	37.6
Tumor number					.184
<3	68	89.5	69	81.2
≥3	8	10.5	16	18.8
Pathology type					.656
Papillary tumor only	64	84.2	74	87.1
Cis-only or concurrent Cis	12	15.8	11	12.9
T stage and grade					.693
Ta G1	5	6.6	3	3.5
Ta G2	21	27.6	23	27.1
Ta G3	5	6.6	4	4.1
T1 G2	18	23.7	25	29.4
T1 G3	15	19.7	19	22.4
Ta G1 Cis	3	3.9	1	1.2
Ta G2 Cis	1	1.3	3	3.5
Ta G3 Cis	1	1.3	0	0
T1 G2 Cis	0	0	2	2.4
T1 G3 Cis	1	1.3	2	2.4
Cis only	6	8	3	3.5
Risk category					1
Intermediate-risk tumor	26	34.2	30	35.3
High-risk tumor	50	65.8	55	64.7
Treatment					1
Induction only	4	5.3	5	5.9
Induction plus maintenance  treatments	72	94.7	80	94.1
Primary or recurrent tumor					.68
Recurrent tumor	12	15.8	16	18.8
Primary tumor	64	84.2	69	81.2

Cis: carcinoma in situ; CI: confidence intervals; CTHC: three consecutive hyperthermia treatments combined with single instillations; HR: hazard ratio; THP: pirarubicin.

Figure 4. Bladder recurrence-free survival rates (A) and progression-free survival rates (B) of CTHC group and THP group estimated using the Kaplan–Meier method. The log-rank test was used for comparing recurrence-free survival rates and progression-free survival rates between the two groups. CTHC: three consecutive hyperthermia treatments combined with single instillations; THP: pirarubicin; TURBT: transurethral resection of bladder tumors.

Table 2. Univariate and multivariate analysis of associated with recurrence.

Variable	Univariate			Multivariate
	HR	95% CI	p-value	HR	95% CI	p-value
Treatment (CTHT versus THP alone)	0.414	0.217–0.792	.008	0.422	0.214 to 0.835	.013
Gender (male versus female)	1.974	0.778–5.010	.152	/	/	/
Age	1.003	0.979–1.027	.821	/	/	/
Whether with hypertension or diabetes (ref = None)			.434	/	/	/
Hypertension	1.659	0.856–3.216	.134	/	/	/
Diabetes	1.686	0.401–7.091	.476	/	/	/
Hypertension and diabetes	1.717	0.408–7.223	.461	/	/	/
Tumor size (≥3 cm versus <3 cm)	1.050	0.572–1.927	.874	1.041	0.536 to 2.021	.906
Tumor number (≥3 versus <3)	2.468	1.271–4.794	.008	2.247	1.079 to 4.679	.031
T stage and grade (ref = Ta G1)			.452			.336
Ta G2	1.538	0.192–12.295	.685	1.147	0.134 to 9.846	.900
Ta G3	5.050	0.564–45.207	.148	5.650	0.619 to 51.544	.125
T1 G2	2.348	0.303–18.192	.414	2.044	0.254 to 16.273	.502
T1 G3	3.936	0.517–29.942	.186	3.134	0.403 to 24.508	.274
Ta G1 Cis	0.000	0.000	.978	0.000	0.000	.979
Ta G2 Cis	2.314	0.145–37.001	.553	1.892	0.105 to 34.044	.665
Ta G3 Cis	8.016	0.501–128.223	.141	11.480	0.588 to 224.310	.108
T1 G2 Cis	4.376	0.274–69.997	.297	3.581	0.216 to 59.494	.374
T1 G3 Cis	0.000	0.000	.981	2.522	0.155 to 41.120	.516
Cis Only	0.912	0.057–14.585	.948	3.707	0.372 to 36.950	.264
Pathology type (ref = papillary tumor only)
Cis only or concurrent Cis	1.112	0.496–2.493	.798	/	/	/
Treatment (ref = induction treatments only)
Induction plus maintenance treatments	1.282	0.397–4.141	.615	1.520	0.411 to 5.619	.530
Primary or recurrenttumor (ref = primary tumor)
Recurrent tumor	1.566	0.792–3.100	.197	1.380	0.608 to 3.131	.441

CI: confidence intervals; Cis: carcinoma in situ; CTHC: three consecutive hyperthermia treatments combined with single instillations; HR: hazard ratio; THP: pirarubicin; ref: reference.

Table 3. Comparison of adverse events between the two groups.

	Acute cystitis	Hematuria	Fever	Gastrointestinal reactions	Total
CTHC group	25% (19/76)	9.21% (7/76)	6.57% (5/76)	2.63% (2/76)	43.4% (33/76)
THP group	20% (17/85)	7.05% (6/85)	4.71% (4/85)	3.53% (3/85)	35.3% (30/85)
P-value	0.456	1	0.741	1	0.65

CTHC: three consecutive hyperthermia treatments combined with single instillations; THP: pirarubicin.