Evaluation of thermal dose effect in radiofrequency-induced hyperthermia with intravesical chemotherapy for nonmuscle invasive bladder cancer

Figures & data

Figure 1. Transurethral urinary catheter with incorporated radiofrequency applicator and three distended thermocouples.

Figure 2. Flow-chart of the retrospective study.

Table 1. Baseline characteristics of the study population.

Description	Subgroup
Total, n		108
Sex, n (%)	Female	18 (16.7)
	Male	90 (83.3)
Age, median (IQR)		67 (60.3-75.0)
Baseline histology, n (%)	CIS	63 (58.3)
	CIS only	48 (44.4)
	CIS + Ta	8 (7.4)
	CIS + T1	7 (6.5)
	Papillary	45 (41.7)
	Ta LG	9 (8.3)
	Ta HG	31 (28.7)
	T1 HG	5 (4.6)
Recurrence frequency, n (%)	≥1/year	72 (66.7)
	<1/year	36 (33.3)
BCG exposed, n (%)	Yes	99 (91.7)
	Failure	83 (76.9)
	Intolerance	14 (13.0)
	Unknown reason for discontinuation	2 (1.9)
	No	9 (8.3)
Risk stratification (EAU), n (%)	Intermediate	23 (21.3)
	High	85 (78.7)
Type chemotherapeutic agent, n (%)	MMC	90 (83.3)
	Epirubicin	18 (16.7)
Dose chemotherapeutic agent, n (%)	Ablative	75 (69.4)
	Adjuvant	33 (30.6)

Table 2. Descriptions of thermal dose parameters.

	Median	IQR
RF power (W)	16.65	15.03–18.08
Temperature (°C)	40.93	40.80–41.10
Intra-patient variability of temperature (°C)	0.38	0.29–0.52
CEM43T50 (min)	3.05	2.38–3.56
Intra-patient variability of CEM43T50 (min)	1.44	0.88–2.41
Duration of temperature >40.5 °C (min)	40.00	39.00–40.00
Duration of temperature >41.5 °C (min)	10.25	7.50–17.37

Table 3. Descriptions of fraction of thermal dose ‘goals’ achieved of multiple sessions per patient.

	Median	IQR
Fraction of sessions with mean temperature >41.0 °C (%)	47.73	25.00–68.36
Fraction of sessions with CEM43T50 > 2 min (%)	83.33	68.06–93.21
Fraction of sessions with duration of T > 40.5 °C for >40 min (%)	66.67	43.15–82.53
Fraction of sessions with duration of T > 41.5 °C for >10 min (%)	50.11	31.17–68.40

Table 4. Unadjusted odds ratios (OR) and hazard ratios (HR) with corresponding p-values for complete response at six months (6-mo CR; for CIS patients [CIS] and for papillary patients [papillary]), recurrence-free survival (RFS), progression-free survival (PFS) and overall survival (OS).

	Outcome	OR	HR	95% CI	p Value
RF power	6-mo CR CIS	0.86		0.68–1.09	0.22
	6-mo CR papillary	1.19		0.57–2.51	0.64
	Durable response		1.09	0.75–1.60	0.64
	RFS		1.03	0.72–1.46	0.89
	PFS		1.05	0.77–1.44	0.75
	OS		1.01	0.78–1.30	0.97
Tmedian	6-mo CR CIS	0.58		0.06–5.84	0.64
	6-mo CR papillary	17.72		0.07–1709.07	0.21
	Durable response		1.40	0.10–20.03	0.81
	RFS		2.41	0.28–21.15	0.43
	PFS		1.36	0.10–18.63	0.82
	OS		0.15	0.02–1.16	0.17
Intra-patient variability of temperature	6-mo CR CIS	2.01		0.15–26.87	0.60
	6-mo CR papillary	1.40		0.01–402.48	0.91
	Durable response		1.34	0.07–25.96	0.85
	RFS		1.59	0.03–84.39	0.82
	PFS		1.07	0.04–27.85	0.97
	OS		2.37	0.22–25.97	0.48
CEM43T50	6-mo CR CIS	0.88		0.52–1.51	0.64
	6-mo CR papillary	3.14		0.50–19.96	0.22
	Durable response		1.18	0.65–2.14	0.59
	RFS		1.13	0.68–1.87	0.65
	PFS		1.13	0.62–2.04	0.70
	OS		0.67	0.38–1.17	0.16
Intra-patient variability of CEM43T50	6-mo CR CIS	0.98		0.61–1.55	0.92
	6-mo CR papillary	2.83		0.67–11.99	0.16
	Durable response		1.61	0.90–2.88	0.11
	RFS		0.70	0.34–1.45	0.34
	PFS		1.09	0.63–1.91	0.76
	OS		0.78	0.47–1.28	0.32
Duration of temperature >40.5 °C	6-mo CR CIS	0.91		0.69–1.22	0.53
	6-mo CR papillary	1.27		0.44–3.67	0.66
	Durable response		0.96	0.89–1.04	0.34
	RFS		2.08	0.44–9.78	0.35
	PFS		1.03	0.97–1.09	0.38
	OS		1.16	0.60–2.24	0.66
Duration of temperature >41.5 °C	6-mo CR CIS	0.97		0.90–1.04	0.32
	6-mo CR papillary	1.19		0.90–1.59	0.23
	Durable response		1.02	0.93–1.11	0.68
	RFS		1.04	0.96–1.13	0.39
	PFS		1.06	0.96–1.15	0.23
	OS		0.93	0.86–1.02	0.11

Figure 3. Distribution of patients in whom bladder spasms occurred by A. T_median and B. median CEM43T50 groups.

Table 5. Association between thermal dose parameters and the occurrence of bladder spasms, presented as odds ratio (OR) with corresponding p-value.

Thermal dose parameter	Unadjusted OR	95% CI	p Value	Adjusted OR	95% CI	p Value
RF power	0.99	0.81–1.21	0.94	1.01	0.82–1.23	0.95
Temperature	0.05	0.00–0.52	<0.001	0.01	0.00–0.05	<0.001
Intra-patient variability of temperature	2.71	0.30–24.28	0.37	2.09	0.22–20.00	0.52
CEM43T50	0.34	0.21–0.56	<0.001	0.34	0.20–0.56	<0.001
Intra-patient variability of CEM43T50	0.70	0.48–1.03	0.07	0.69	0.45–1.02	0.07
Duration of temperature >40.5 °C	0.49	0.26–0.90	0.02	0.49	0.26–0.93	0.03
Duration of temperature >41.5 °C	0.83	0.77–0.90	<0.001	0.83	0.77–0.90	<0.001

Bold values are statistically significant.