A systematic review of regional hyperthermia therapy in bladder cancer

Figures & data

Figure 1. Flow diagram of evidence acquisition.

Table 1. Overview of all trials concerning regional hyperthermia therapy for bladder cancer.

Reference	Study type (retro vs pro)	Patients N	Patient population (NMIBC, MIBC)	Study description	Type	Device	Temperature °C	Complete response	Partial response
Geijsen et al. [27]	Prospective	18	NMIBC	Pilot: phase I/II	HT + intravesical MMC	AMC	40.6-42.1
Hisazumi et al. [34]	Retrospective	39	MIBC, NMIBC	Case series		8-MHz RF		9 (23%)	6 (15%)
			13 NMIBC		HT	Thermotron		0	0
					Radiohyperthermia			2 (15%)	0
					Chemohyperthermia			4 (31%)	0
			26 MIBC		HT	Thermotron		0	0
					Radiohyperthermia			3 (12%)	5 (19%)
					Chemohyperthermia			0	1 (4%)
Inman et al. [21]	Prospective	15	NMIBC	pilot	HT + intravesical MMC	BSD 2000	Goal 42 ± 2
Masunaga et al. [37]	Prospective	28	MIBC, NMIBC	Phase I and II trial	Radiohyperthermia vs radiation	Thermotron	39.4-44.0
Naito et al. [36]	Retrospective	21	MIBC	Case series	Chemohyperthermia, radiohyperthermia			0	10 (48%)
Nishimura et al. [39]	Retrospective	4	MIBC	Case series	Radiohyperthermia	Thermotron	Average 38-43	2 (50%)	1 (25%)
Noguchi et al. [33]	Prospective	35	MIBC, NMIBC	Pilot	Quadrimodal vs radiohyperthermia	RF apparatus	Goal 42	8 (23%)	12 (34%)
			18 MIBC, NMIBC		Radiohyperthermia			4 (22%)	7 (39%)
			17 MIBC, NMIBC		Chemoradiohyperthermia			4 (23%)	5 (29%)
Ohguri et al. [40]	Retrospective	3	MIBC	Case series	Chemoradiohyperthermia	Thermotron	Average/patient 43.7-45.5	3 (100%)	0
Petrovich et al. [22]	Prospective	20		Phase I	Hyperthermia + radiation	BSD 1000	Goal 42.5	0	2 (10%)
Rietbroek et al. [28]	Prospective	4	MIBC	Pilot	Chemohyperthermia	AMC	Goal 41.0	0	2 (50%)
Sapozink et al. [23]	Prospective	5	MIBC	Pilot	Radiohyperthermia	BSD 1000	Goal ≥42.0	2 (40%)	0
Uchibayashi et al. [38]	Prospective	46	MIBC	Cohort	Chemohyperthermia or radiohyperthermia	RF apparatus	Goal 42.5	5 (11%)	15 (33%)
			27 MIBC		Chemohyperthermia			3 (11%)	8 (30%)
			19 MIBC		Radiohyperthermia			2 (11%)	7 (37%)
Ueda et al. [32]	Prospective	11	NMIBC	Cohort	HT + intravesical doxorubicin	Thermotron	Goal ≥42.0	6 (54%)	3 (27%)
Van der Zee et al. [17]	Prospective	52	MIBC	Randomized	Radiohyperthermia vs radiation	BSD, and others	Goal ≥42.0	38 (73%)
Wittlinger et al. [20]	Prospective	45	MIBC, NMIBC	Phase II	Quadrimodal	BSD 2000	Goal 41.5	36 (80%)	45 (96%

AMC, Amsterdam Medical Centre; HT, hyperthermia; MIBC, muscle-invasive bladder cander, NMIBC, non-muscle-invasive; RF, radiofrequency.

Table 2. Overview of toxicity associated with regional hyperthermia therapy.

	Geijsen et al.[27]	Hisazumi et al. [34]	Inman et al. [21]	Masunaga et al. [37]	Nishimura et al. [39]*	Noguchi et al. [33]	Ohguri et al. [40]	Petrovich et al [22]*	Rietbroek et al. [28]	Sapozink et al. [23]	Uchibayashi et al. [38]	Ueda et al. [32]	van der Zee et al. [17]*	Wittlinger et al. [20]
General
Fatigue			2 (13%)							11 (26%)
Myalgia			1 (7%)
Anxiety			1 (7%)							6 (14%)
Genitourinary
Urethral pain			6 (40%)
Cystitis			4 (27%)				3 (100%)
Dysuria												3 (27%)
Haematuria			3 (20%)
Bladder spasm	10 (7%)		2 (13%)							11 (26%)
Weak urinary stream			1 (7%)
Vaginitis
Frequency						24 (69%)
Contracted bladder					1 (3%)									7 (16%)
Incontinence														1 (2%)
Dermatological
Burns/blister		21/39 (54%)						4 (8%)	2 (14%)		15 (33%)		5 (3%)
Induration/swelling		10/39 (26%)	4 (27%)								9 (20%)		20 (11%)
Pruritis			3 (20%)		3 (10%)					2 (5%)
Rash			2 (13%)
Bruising			1 (7%)
Flushing			1 (7%)
Fat necrosis					2 (6%)				5 (36%)
Neurologic
Dizziness			2 (13%)
Confusion			1 (7%)
Extrapyramidal  symptoms			1 (7%)
Infectious
Urinary tract infection			2 (13%)
Cardiovascular
Hypertension			3 (20%)	0 (0%)				4 (8%)
Gastrointestinal
Nausea or vomiting			2 (13%)			17 (49%)				8 (19%)
Anorexia										11 (24%)
Constipation			1 (7%)
Ileus														1 (2%)
Diarrhoea				1 (4%)		4 (11%)								1 (2%)
Abdominal pain			5 (33%)				1 (33%)
Procedure-related
Positional discomfort	22 (16%)
Heat intolerance/pain  with applicator	29 (20%)		1 (7%)	12 (43%)	18 (55%)			25 (47%)	31% of treatments	32 (74%)

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