A Pilot Study of Radiotherapy and Local Hyperthermia in Elderly Patients With Muscle-Invasive Bladder Cancers Unfit for Definitive Surgery or Chemoradiotherapy

Abstract

Purpose: To present the outcomes of a pilot study with hyperthermia (HT) and radiotherapy (RT) in elderly patients of muscle-invasive bladder cancers (MIBC) unfit for surgery or chemoradiotherapy (CTRT).Methods: Sixteen elderly patients with unifocal or multifocal MIBCs received a total dose of 48 Gy/16 fractions/4 weeks or 50 Gy/20 fractions/4 weeks, respectively. HT with a radiofrequency HT unit was delivered once weekly for 60 min before RT and a mean temperature of 41.3°C was attained (maximum temperature 41.1–43.5°C). Local control was assessed using RECIST criteria at 3-monthly intervals by cystoscopy with or without biopsy.Results: The median age, KPS and age-adjusted Charlson comorbidity index were 81 years, 70 and 5, respectively. At median follow-up of 18.5 months (range: 4–65), bladder preservation was 100% with satisfactory function. 11/16 patients (68.7%) had no local and/or distant failure, while isolated local, distant and combined local and distant failures were evident in 2, 2, and 1 patient, respectively. Two local failures were salvaged by TUR-BT resulting in a local control rate of 93.7%. The 5-year cause-specific (CS) local disease free survival (LDFS), disease free survival (DFS), and overall survival (OS) were 64.3, 51.6, and 67.5%, respectively while 5-year non-cause-specific (NCS)-LDFS, NCS-DFS, and NCS-OS were 26.5, 23.2, and 38%, respectively. None of the patients had acute or late grade 3/4 gastrointestinal or genitourinary toxicities.Conclusions: The outcomes from this pilot study indicate that thermoradiotherapy is a feasible therapeutic modality in elderly MIBC patients unfit for surgery or CTRT. HTRT is well-tolerated, allows bladder preservation and function, achieves long-term satisfactory locoregional control and is devoid of significant treatment-related morbidity. This therapeutic approach deserves further evaluation in randomized studies.

A Narrative Review of Regional Hyperthermia: Updates From 2010 to 2019

“…Their data, nevertheless, confirm the positive effects of HT associated with intravesical mitomycin C in terms of CR and PFS in bladder cancer. [57][58][59] As concerning STS, the association of HT with RT or CHT improves local PFS and DFS after radical surgery. 61 The same benefits are observed when HT is used in the neoadjuvant setting, resulting also in higher response rates.…”

“…Their data, nevertheless, confirm the positive effects of HT associated with intravesical mitomycin C in terms of CR and PFS in bladder cancer. 57 - 59 …”

“…The beneficial effects of HT associated with CHT or RT have been shown also for bladder cancer ( Table 6 ). 53 , 55 - 57 The induction of regional HT in bladder cancer can be attained with 3 different techniques: 70 to 120 MHz antennas, intracavitary radiofrequency HT using a 916 MHz antenna, and intravesical conductive therapy using a heated perfusate. 56 The use of 70 MHz had higher recurrence-free survival rate than the use of heated perfusate (78% vs 33%).…”

Hyperthermia with photon radiotherapy is thermoradiobiologically analogous to neutrons for tumors without enhanced normal tissue toxicity

“…Clinical delivery of HT usually involves a gradual step-wise increase in temperature before or after RT for around 60-90 min to achieve a tumor temperature of around 41-42 C, respecting the patient's tolerance of heat during the entire procedure [19,20,[37][38][39]. In view of the differential vascular configuration between tumors and normal tissues, during the heating process tumors preferentially would be retaining heat compared to the normal structures.…”

Quantification of thermal dose in moderate clinical hyperthermia with radiotherapy: a relook using temperature–time area under the curve (AUC)

“…T90, T50, T10 are the index temperatures chosen at which 90%, 50% and 10% of the measured temperature points would exceed and denoted as CEM43T90, CEM43T50, CEM43T10, respectively [2,6]. Clinical outcomes are thus reported variably using maximum (T max ), minimum (T min ) and mean (T mean ) temperatures, HT duration with or without CEM43 [3,4,[7][8][9][10][11][12][13][14][15][16][17][18].…”