Overview of bladder heating technology: matching capabilities with clinical requirements

Figures & data

Table 1. Comparison chart of clinical studies of bladder hyperthermia.

Equipment	Reference	Frequency (MHz)	Study size	Prescribed Tx	Treatment schedule	Average power (W) or temperature (°C)	Goal/achieved temperature	HT duration	Goal treatment completed	Maximum toxicity (CTCAE score)	Most common toxicity
External Deep Regional RF
BSD-2000 RF phased array system	Inman 2014 [6]  Juang 2014 [18]	80–120	14	10	6 × 1/wk + 4 × 1/month	740 ± 162 W	96% > 40 min at Tmin > 40 °C	Average time > 40 °C < 53.1 ± 8.8 min	73%	Grade 2	40% Foley catheter pain 33% abdominal discomfort
BSD-2000 RF phased array system	Fatehi 2007 [19]	75–80	5	NR	1/wk	NR	40.9 °C tumour 40.7 °C lumen	60–90 min	NR	NR	NR
AMC-4, AMC-8 Waveguide phased array	Geijsen 2015 [3]	70	18	10	6 × 1/wk + 4 × 1/month	553 W	T50 = 41.6 °C	60–90 min	83% induction 50% full	Grade 2	38% local pain and bladder spasms
Capacitive Plate Electrodes
Yamamoto Vinita RF-8 capacitive heating system	Masunaga 1994 [40]	8	28	4	2/week + RT	578 ± 86 W	42.1 + 8.0 °C	35–60 min			43% local pain and bladder spasms
Yamamoto Vinita RF-8 capacitive heating system	Uchibayashi 1995 [41]	8	46	6–10	2/week + RT		42.5 °C	60 min		Grade 2	28% burn, 24% anorexia, 20% subcutaneous induration
Intravesical Microwave Antenna
Synergo SB-TS 101 transurethral MW system	Colombo 1995 [49]	915	44	8	2/wk in <6 wks	<80 W	42.5–44.5 °C	Goal 60 min > 40 °C  minimum	97%	NR	Mild urge and urethral burning
Synergo SB-TS 101 transurethral MW system	Columbo 1996 [50]	915	29	6.8	1–2/wk in <6 wks	NR	42.5–46 °C		93%	Grade 3	Mild urgency
Synergo SB-TS 101 transurethral MW system	Columbo 1998 [51]	915	44	8	2/wk in <6 wks	<60 W	42.5–44.5 °C	Goal 60 min > 40 °C minimum	96%	NR	Moderate/severe urgency, mild urethral burning
Synergo SB-TS 101 transurethral MW system	Columbo 2003 [2]	915	29	6–8	1–2/wk in <6 wks	NR	42.5–46 °C	60 min (2 × 30 min to refresh drug)	88%	NR	Pelvic pain and posterior wall thermal reaction
Synergo SB-TS 101 transurethral MW system	Kiss 2015 [52]	915	19	8		NR	42.5–46 °C	60 min (2 × 30 min to refresh drug)	62%	Grade 4 CTC score - NCIC	57% pain and bladder spasms
Synergo SB-TS 101 transurethral MW system	Malfezzini 2014 [53]	915	42	14	4 × 1/wk +  6 × 2/mon +  4 × 1/mon	NR	42.5 ± 1.5 °C	Goal 60 min > 40 °C minimum	76%	Grade 2	100% thermal reaction posterior bladder wall
Synergo SB-TS 101 transurethral MW system	van der Heijden 2004 [54]	915	90	10–14	6–8 × 1/wk +  4–6 × 1/month	NR	41–4 °C	60 min (2 × 30 min to refresh drug)	10 ± 2	Toxicity all local healed spontaneously	72% ≥1 toxicity 100% thermal reaction posterior bladder wall
Synergo SB-TS 101 transurethral MW system	Nativ 2009 [55]	915	111	12	6 × 1/week + 6 ×  every 4–6 wks	NR	42 ± 2 °C	60 min (2 × 30 min to refresh drug)	95%	Grade 3	31% pain and bladder spasms
Intravesical Thermal Conduction
Combat BRS system, Combat Medical	Sousa 2014 [59]	–	15	8	8 × 1/wk	43 ± 1 °C	Bladder temp not measured	Goal 60 min > 40 °C minimum	99%	Grade 2	33% irritative lower urinary tract
UniThermia system, Elemedical	Ekin 2015 [60]	–	43	12	6 × 1/wk +  3 × 1/wk in months 3 and 6	NR	Bladder temp not measured	60 min	93%	Grade 5 institutional CTC score	37% non-infective cystitis
UniThermia system, Elemedical	Soria 2015 [61]	–	34	6	6× 1/wk	42.5 ± 1 °C 44.5 °C Peak	Bladder temp not measured	45 min	88%	Grade 3	24% bladder spasms

Table 2. Relative heating characteristics of clinical bladder hyperthermia systems.

	External			Intravesical
Heating criterion	Deep regional electromagnetic	Deep focused ultrasound	Capacitive current	Microwave	Circulating heated fluid
Homogeneity of heating around interior bladder wall	+	– –	−	− −	+ +
Depth of penetration of heating through tissue	+ +	+ +	+ +	−	− −
Control of maximum temperature	− −	–	− −	–	+ +
Circulation/mixing of drug in contact with bladder wall	–	–	–	+	+ +
Heating of tumour tissue outside the bladder	++	+	+	–	− −
Heating of normal tissue outside the bladder	− −	–	− −	+	+ +
Ease of heating	–	− −	–	–	+ +
Patient tolerance	–	–	–	–	+

+ + major advantage; + moderate advantage; − moderate shortcoming; − − major shortcoming.

Figure 1. Pictorial cross-section of bladder cancer staging classification as regards penetration of disease into the bladder wall. Reprinted with permission from Katelaris Urology, http://www.katelarisurology.com.au/about-bladder-cancer/.

Inman BA, Stauffer PR, Craciunescu OA, Maccarini PF, Dewhirst MW, Vujaskovic Z. A pilot clinical trial of intravesical mitomycin-C and external deep pelvic hyperthermia for non-muscle-invasive bladder cancer. Int J Hyperthermia 2014;30:171–5

 PubMed Web of Science ®Google Scholar

Juang T, Stauffer PR, Craciunescu OA, Maccarini PF, Yuan Y, Das SK, et al. Thermal dosimetry characteristics of deep regional heating of non-muscle invasive bladder cancer. Int J Hyperthermia 2014;30:176–83

 PubMed Web of Science ®Google Scholar

Fatehi D, van der Zee J, Notenboom A, van Rhoon GC. Comparison of intratumor and intraluminal temperatures during locoregional deep hyperthermia of pelvic tumors. Strahlenther Onkol 2007;183:479–86

 PubMed Web of Science ®Google Scholar

Geijsen ED, de Reijke TM, Koning CC, Zum Vorde Sive Vording PJ, de la Rosette JJ, Rasch CR, et al. Combining mitomycin C and regional 70 MHz hyperthermia in patients with nonmuscle invasive bladder cancer: A pilot study. J Urol 2015;194:1202–8

 PubMed Web of Science ®Google Scholar

Masunaga SI, Hiraoka M, Akuta K, Nishimura Y, Nagata Y, Jo S, et al. Phase I/II trial of preoperative thermoradiotherapy in the treatment of urinary bladder cancer. Int J Hyperthermia 1994;10:31–40

 PubMed Web of Science ®Google Scholar

Uchibayashi T, Yamamoto H, Kunimi K, Koshida K, Nakajima K. Radiofrequency capacitive hyperthermia combined with irradiation or chemotherapy for patients with invasive bladder cancers. Int Urol Nephrol 1995;27:735–41

 PubMedGoogle Scholar

Colombo R, Lev A, Da Pozzo LF, Freschi M, Gallus G, Rigatti P. A new approach using local combined microwave hyperthermia and chemotherapy in superficial transitional bladder carcinoma treatment. J Urol 1995;153:959–63

 PubMed Web of Science ®Google Scholar

Colombo R, Da Pozzo LF, Lev A, Freschi M, Gallus G, Rigatti P. Neoadjuvant combined microwave induced local hyperthermia and topical chemotherapy versus chemotherapy alone for superficial bladder cancer. J Urol 1996;155:1227–32

 PubMed Web of Science ®Google Scholar

Colombo R, Da Pozzo LF, Lev A, Salonia A, Rigatti P, Leib Z, et al. Local microwave hyperthermia and intravesical chemotherapy as bladder sparing treatment for select multifocal and unresectable superficial bladder tumors. J Urol 1998;159:783–7

 PubMed Web of Science ®Google Scholar

Colombo R, Da Pozzo LF, Salonia A, Rigatti P, Leib Z, Baniel J, et al. Multicentric study comparing intravesical chemotherapy alone and with local microwave hyperthermia for prophylaxis of recurrence of superficial transitional cell carcinoma [see comment]. J Clin Oncol 2003;21:4270–6

 PubMed Web of Science ®Google Scholar

Kiss B, Schneider S, Thalmann GN, Roth B. Is thermochemotherapy with the Synergo system a viable treatment option in patients with recurrent non-muscle-invasive bladder cancer? Int J Urol 2015;22:158–62

 PubMed Web of Science ®Google Scholar

Maffezzini M, Campodonico F, Canepa G, Manuputty EE, Tamagno S, Puntoni M. Intravesical mitomycin C combined with local microwave hyperthermia in non-muscle-invasive bladder cancer with increased European Organization for Research and Treatment of Cancer (EORTC) score risk of recurrence and progression. Cancer Chemother Pharmacol 2014;73:925–30

 PubMed Web of Science ®Google Scholar

van der Heijden AG, Kiemeney LA, Gofrit ON, Nativ O, Sidi A, Leib Z, et al. Preliminary European results of local microwave hyperthermia and chemotherapy treatment in intermediate or high risk superficial transitional cell carcinoma of the bladder. Eur Urol 2004;46:65–71; discussion 72

 PubMed Web of Science ®Google Scholar

Nativ O, Witjes JA, Hendricksen K, Cohen M, Kedar D, Sidi A, et al. Combined thermo-chemotherapy for recurrent bladder cancer after bacillus Calmette-Guerin. J Urol 2009;182:1313–17

 PubMed Web of Science ®Google Scholar

Sousa A, Inman BA, Pineiro I, Monserrat V, Perez A, Aparici V, et al. A clinical trial of neoadjuvant hyperthermic intravesical chemotherapy (HIVEC) for treating intermediate and high-risk non-muscle invasive bladder cancer. Int J Hyperthermia 2014;30:166–70

 PubMed Web of Science ®Google Scholar

Ekin RG, Akarken I, Cakmak O, Tarhan H, Celik O, Ilbey YO, et al. Results of intravesical chemo-hyperthermia in high-risk non-muscle invasive bladder cancer. Asian Pac J Cancer Prev 2015;16:3241–5

 PubMedGoogle Scholar

Soria F, Milla P, Fiorito C, Pisano F, Sogni F, Di Marco M, et al. Efficacy and safety of a new device for intravesical thermochemotherapy in non-grade 3 BCG recurrent NMIBC: A phase I-II study. World J Urol 2015;34:189–95. PMID 26026818

 PubMed Web of Science ®Google Scholar