By: Dan Sperling, MD

Hyperthermia, or extreme heat, is being done in different forms as a way to treat prostate cancer. The theory is to generate a very high (lethal) temperature uniformly throughout the gland as a way to destroy the tissue and any cancer it contains. It is used in one of two ways:

a)      As thermal ablation, meaning a single primary cancer treatment for low risk, localized tumors

b)      As a combination with other therapies, such as radiation therapy, in an effort to increase the effectiveness of the treatment.

In all cases, especially prostate cancer where the urethra passes through the gland and the prostate itself is surrounded by the bladder, rectum, and nerve bundles that control erection, the heat must be carefully controlled so as to spare healthy tissue.

The most common ways to generate hyperthermia in the prostate are microwave ablation (MA), interstitial hyperthermia (IH), radiofrequency ablation (RFA), high intensity focused ultrasound (HIFU) and locoregional hyperthermia. There are various advantages and disadvantages to each method that have to do with how evenly the heat is distributed, how well the treatment is tolerated, and the risk of side effects such as incontinence.

Hyperthermia is more common outside the U.S., especially in Europe, where it is used both as a primary treatment and as a boost for radiation. An article by a group of Italian researchers published a literature review of studies that were conducted on the second use of hyperthermia, in conjunction with conformal beam radiation (conformal radiotherapy or CFRT).[i] The patients involved in the study had stage T3-T4 prostate cancer, meaning the disease was locally advanced but had not yet spread to the lymph nodes or other parts of the body. Locally advanced prostate cancer is not treated with surgery because the cancer has already left the prostate. Thus, radiation is considered the only potentially curative local (pelvic) therapy for such cases. However, recurrence rates range from 10-60% so hyperthermia has been clinically tested in hopes of boosting the effect of CFRT.

The article’s authors examined five such studies in particular that involved hyperthermia combined with CFRT with the intent of effecting a radical (whole gland) treatment. Earlier studies of hyperthermia combined with traditional external beam radiation (EBRT) were few, but more recent efforts involved CFRT at a radiation dose of > 70 Gy because recurrence is thought to be lower with this modality. In addition, androgen deprivation therapy (ADT) to reduce testosterone was also administered to the patients, again in an effort to increase the effect of the radiation.

In reviewing the five studies, the authors compare overall survival rates, biochemical disease recurrence (rising PSA after treatment) and quality of life reported by patients. It appears from all studies that the hyperthermia itself does not add side effects beyond what the radiation itself creates, or the radiation plus ADT. On the other hand, there did not appear to be a clear benefit in terms of increased survival or decreased rates of recurrence.

One rather alarming effect occurred among patients whose prostate cancer was not yet hormone resistant (refractory, meaning the cancer no longer responds to ADT). The addition of hyperthermia in these patients actually seemed to reduce the amount of time before the cancer became refractory. Therefore, the authors suggest that the combination of hyperthermia and CFRT only be used for locally advanced cancer that has already become hormone-resistant prior to the hyperthermia treatment. They caution, though, that skilled doctors and nurses are required to administer hyperthermia: “Structurally, the prostate is a nonuniform structure; heat deposition is not uniform and the PSA level is temperature sensitive…”1

In summary, it appears that the benefits of hyperthermia as an additional therapy to enhance CFRT are inconclusive, and further study needs to occur to explore how well it might enhance the effectiveness of chemotherapy in metastatic prostate cancer.


 

[i] Baronzio G, Gramaglia A, Fiorentini G.  Current role and future perspectives of hyperthermia for prostate cancer treatment. In vivo. 2009;23:143-46.

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