36 © 2 0 0 4 B J U I N T E R N A T I O N A L | 9 3 , 3 6 – 4 1 | doi:10.1046/j.1464-410X.2004.04551.x Original Article RADIOTHERAPY AND HYPERTHERMIA IN FOR LOCALLY ADVANCED PROSTATE CANCER M. VAN VULPEN et al. Radiotherapy and hyperthermia in the treatment of patients with locally advanced prostate cancer: preliminary results M. VAN VULPEN, A.A.C. DE LEEUW, B.W. RAAYMAKERS, R.J.A. VAN MOORSELAAR*, P. HOFMAN, J.J.W. LAGENDIJK and J.J. BATTERMANN Departments of Radiation Oncology and *Urology, University Medical Centre Utrecht, Utrecht, the Netherlands Accepted for publication 15 August 2003 was delivered using a conformal three-field technique, administering 70 Gy in 2-Gy fractions in 7 weeks. RESULTS The mean initial prostate-specific antigen level was 26 ng/mL. Three patients had a T4 and 23 a T3 tumour; the tumours were classified as well (four), moderately (16) and poorly (six) differentiated. The mean follow- up was 36 months. In the combined treatments there was no toxicity of more than grade 2. In regional hyperthermia the mean index temperature (T 90 and T 50 , i.e. exceeded by 90% and 50% of the measurements) was 40.2 ∞C and 40.8 ∞C, and for interstitial hyperthermia 39.4 ∞C and 41.8 ∞C, respectively. All patients survived; seven patients had a biochemical relapse (27%), three in the regional and four in the interstitial group. The actuarial probability of freedom from biochemical relapse was 70% at 36 months for all patients together, 79% for regional and 57% for interstitial. No factors were found that could be used to predict relapse. CONCLUSIONS The clinical outcome in these patients with advanced localized prostate cancer seems to compare favourably with most series using irradiation alone, and the treatment caused no severe complications. KEYWORDS prostate carcinoma, hyperthermia, regional interstitial, radiotherapy, follow-up, hyperthermia dose OBJECTIVE To report an interim clinical evaluation of combined external beam irradiation (EBRT) and interstitial or regional hyperthermia in the treatment of locally advanced prostate cancer. PATIENTS AND METHODS From 1997 to 2001, 26 patients with T3-4/NX/ 0M0 prostate carcinoma were treated with a combination of conformal EBRT and hyperthermia. Fourteen patients received five weekly regional hyperthermia treatments within an optimization (phase II) study, using the coaxial transverse electrical magnetic system. Twelve patients received one interstitial hyperthermia treatment within a feasibility study (phase I), using the multi- electrode current source system. Irradiation INTRODUCTION The outcome of treatment for locally advanced prostate carcinoma (T3,4 NX/0 M0) using conventional radiotherapy alone is insufficient. Zagars et al. [1] described a 10- year biochemical relapse rate of 76% after conventional external beam irradiation (EBRT). An improvement in local control may result in a better disease-specific survival [2]. Local control can be enhanced by androgen suppression with local irradiation [3] or by increasing the radiation dose [4], e.g. by using intensity-modulated radiotherapy. Adding hyperthermia to conventional radiotherapy may also improve local control in prostate carcinoma. Hyperthermia is known to enhance the radiation effect in prostate cancer cells in vitro [5]. One study suggested a gain from hyperthermia in newly diagnosed patients [6], and Kalapurakal et al. [7] reported a benefit for relapsed hormone-refractory patients. Furthermore, additional hyperthermia does not seem to decrease the quality of life of patients with prostate carcinoma [8]. Different hyperthermia techniques can be used to treat prostate carcinoma; promising methods include both interstitial [9] and regional hyperthermia [6,10]. Transurethral and/or transrectal hyperthermia produces a highly variable heat distribution, because of the limited heat penetration depth [11]. Algan et al. [12] used transrectal hyperthermia and reported no improvement in treatment outcome. The feasibility of interstitial and regional hyperthermia for locally advanced prostate carcinoma was reported earlier by us [13,14]. Because added hyperthermia for treating locally advanced prostate cancer seems promising, the possibilities were evaluated for future randomized trials (20th European Society for Hyperthermic Oncology conference, Bergen, Norway, 23–25 May, 2002). Only a few studies have described the clinical results after prostate hyperthermia [6,12]. Although we realise that data on the clinical outcome of phase I/II studies are inconclusive and that the results remain preliminary, they might serve to support future discussions. PATIENTS AND METHODS From December 1997 to October 2001, 26 men with locally advanced prostate cancer (T3,4 NX/0 M0) received EBRT combined with regional or interstitial hyperthermia. The toxicity in all patients was measured using the Common Toxicity Criteria (CTC, version 2.0). All patients were irradiated using CT-planned