External beam radiotherapy and hyperthermia in the treatment of patients with locally advanced prostate carcinoma

Abstract

BACKGROUND The current study was conducted to evaluate the combination of external beam radiation therapy and hyperthermia in the treatment of patients with locally advanced prostate carcinoma. METHODS Twenty‐six patients were treated on a Phase I/II protocol between June 1990 and April 1993. The median age of the patients was 69 years. Nine patients had well differentiated adenocarcinoma, ten patients had moderately differentiated adenocarcinoma, and six patients had poorly differentiated adenocarcinoma. All patients had American Urologic Society Stage C2‐D1 adenocarcinoma. The median pretreatment prostate specific antigen (PSA) level was 29 ng/mL (range, 6–104 ng/mL). All patients received external beam radiation therapy using a four‐field technique. The median radiation dose was 6800 centigrays (cGy) given in 200‐cGy fractions. Hyperthermia was administered concurrently with radiation therapy to temperatures of 42.5 °C for 30 minutes using a transrectal ultrasound applicator with 3 thermometry probes, given as either a single treatment (9 patients) or as two treatments (17 patients). Overall survival (OS) and biochemical no evidence of disease (bNED) status were calculated using Kaplan–Meier analysis. A consensus conference definition of PSA failure was used. The Cox proportional hazards model was used for multivariate analysis. The median follow‐up for all patients was 71 months. RESULTS The median time to PSA nadir was 15 months with a median PSA nadir value of 1.0 ng/mL. The median and 5‐year OS was 88 months and 73%, respectively, and the median and 5‐year bNED survival was 36 months and 35%, respectively. Multivariate analysis revealed only the pretreatment PSA level (P = 0.03) and the PSA nadir reached (P < 0.01) to be significant predictors of bNED survival. The duration of hyperthermia therapy showed a trend toward significance for OS (P = 0.06). CONCLUSIONS The current Phase I/II protocol evaluating the combination of prostate hyperthermia and external beam radiation therapy for the treatment of patients with locally advanced prostate carcinoma suggests prostate hyperthermia to be feasible with no apparent significant increased toxicity, although there was no significant improvement in treatment outcome when compared with other studies reported in the literature evaluating external beam radiation therapy with or without androgen suppression. However, further investigation into the duration as well as the temperature of the hyperthermia with a greater number of patients is warranted. Cancer 2000;89:399–403. © 2000 American Cancer Society.

Conformal radiotherapy plus local hyperthermia in patients affected by locally advanced high risk prostate cancer: Preliminary results of a prospective phase II study

“…Temperature changes within a hyperthermia session in invasive and urethral border sensor measurements corresponded well [20] even if intraluminal data, such as urethral border, may exhibit higher values than the invasive measurement. Local hyperthermia is feasible and well tolerated with no apparent significant toxicity and without severe complications [14,20,21]. The duration of hyperthermia shows a trend toward the significance for overall survival and seems to compare favourably with most series using irradiation alone [14,20].…”

“…The consensus conference held in Osaka in 2004 (Kadota Forum), having evaluated the role of hyperthermia according to the criteria of Evidence Based Medicine (EBM), did not consider prostate cancer as a tumour which can be treated with a level 1-2 of EBM. In spite of the lack of evidence, in many centres patients affected by advanced prostate cancer have been treated with hyperthermia combined with radiotherapy, achieving positive results in terms of feasibility and very low toxicity [11,13,14]. In human prostatic cancer cells, the combination of fractionated irradiation with continuous heating at 40 C or a single acute dose radiation following heat treatment at 41 C, achieves a thermal enhancement ratio (TER) in the range of 1.4 to 2.0 even if a mild hyperthermia is given [15].…”

Clinical hyperthermia of prostate cancer using magnetic nanoparticles: Presentation of a new interstitial technique

“…Several techniques have been used for regional hyperthermia of prostate cancer, including radiofrequency, microwave or ultrasound applicators [10][11][12][13][14][15][16]. Intra-tumoural temperatures obtained with these methods have mostly been between 40-41 C. In only a few of these studies, maximum intra-prostatic temperatures of 42.5 C were reached or the critical temperature of 43.0 C, where a measurable cytotoxic effect is documented for various cell lines, was exceeded [11,14]. Most of the studies related to the treatment of prostate cancer, however, evaluated hyperthermia in the context of combined thermoradiotherapy, where temperatures in this range are thought to be sufficient for radiosensitization.…”

Hyperthermia-Induced Proteasome Inhibition and Loss of Androgen Receptor Expression in Human Prostate Cancer Cells

“…Although the molecular basis of hyperthermia is poorly understood, it is frequently used alone or in combination with radiotherapy in the treatment of prostate cancer (27)(28)(29)(30). In this study, we investigated the effect of hyperthermia on NF-nB activity, proteasome function, and cell death as well as AR expression in human prostate cancer cell lines.…”