Oligometastatic Prostate Cancer Part I

Man at Doctor's Visit. Credit: LilliDay / Getty Images

Over the last 15 years or so, modern thinking about how to treat the early stages of prostate metastases has been changing. Various studies are showing that a minority of patients with early stage metastases do not have widespread microscopic metastases as previously believed. Therefore, a minority of men with less than five metastases can still be cured with aggressive therapy using radiation or surgery to eradicate the metastases.

The possibility that some patients with early metastatic disease are still curable is termed oligometastases. The curability of oligometastases has been proven with different cancer types, including cancers of the lung, colon, melanoma, and prostate. Some individuals whose metastases were treated with surgery or radiation have gone into long-term remissions (Part II of this series). 

It is actually rather easy to administer treatment to a small number of nodal or bone metastases. Radiation is generally easier than surgery, but cancerous lymph nodes are potentially removable by doing an operation. The limiting factor is the discouraging fact that the treatment may prove futile if undetected micro-metastases are indeed in existence. If the latter scenario occurs the cancer will relapse down the line when the micro-metastases grow large enough to be detected.

The other concern is that there is a risk of treatment-induced side effects.

However, when radiation is used skillfully and only a few spots are treated, side effects are usually slight. At most, 4 or 5 spots should be treated. With greater numbers of metastases, the likelihood of having micro-metastases is high. Another concern is that treating bone metastases can impair the function of bone marrow, which is where the immune system resides.

Extensive radiation to the bone is, therefore, a very bad idea. However, if the area of bone marrow being treated is small, long-term effects on the immune system should be negligible.

Oligometastases are potentially curable but we are unable to determine in advance which oligometastatic patients will be cured with aggressive therapy. Even though the majority of men with oligometastatic disease go into a complete remission, only a minority of them remain in remission permanently. Therefore, with the present state of available technology, the only way to cure men who have curable oligometastases is to administer treatment to everyone who is a potential candidate.

Protocols for treating oligometastases rely on radiation or surgery to eradicate all visible sites of disease. Both intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) can be considered. IMRT has commonly been employed to treat oligometastases that are located in the lymph nodes, while SBRT is a more practical (and possibly more effective) option for the treatment of bone metastases.

IMRT is given in small doses over 6-8 weeks, whereas SBRT employs a higher dose administered in fewer sessions and is usually completed in 2 weeks or less. The increased efficacy of SBRT may be due to the fact that the high doses of radiation administered over a short period of time induce an inflammatory reaction that stimulates the patient’s immune system. 

SBRT has been demonstrated to activate both the innate and adaptive immune responses. Studies have demonstrated that even with a single ablative dose of radiation to the tumor, there is a T-cell priming effect in the draining lymphatics. This T-cell response may create an immune-mediated antitumor benefit in which the patient’s immune system can then attack the cancer in other parts of the body. Using radiation at one site that results in shrinkage of the cancer at another area in the body is termed the “Abscopal Effect.”

Hormone therapy using Lupron is often added to the radiation to improve the anticancer effect. Lupron potentially accomplishes two things: First, it enhances the killing effect of radiation. Second, it circulates through the blood where it may eradicate early-stage micro-metastatic disease (adjuvant chemotherapy with Taxotere, which also circulates through the blood to attack micro-metastatic disease, is a possible consideration as well). In Part II of this series, a clinical trial reporting favorable results using SBRT is reviewed.

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