Oligometastatic Prostate Cancer

Doctor's visit
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.

Oligometastases

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. 

Abscopal Effect

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).

Results Using SBRT 

I have reviewed some of the background theories on how treating metastatic disease, when only a limited number of metastatic sites exist, might be beneficial, and in some cases, even curative. At the meeting of the American Society of Clinical Oncology in 2015, Dr. Daniel Henderson from Royal Marsden Hospital in London reported on his experience treating 21 oligometastatic prostate cancer patients with radiation.

Dr. Henderson defined oligometastatic prostate cancer as 1-3 sites of metastasis, typically occurring some years after radical treatment for primary disease with surgery or radiation directed at the prostate gland. He pointed out in his presentation that standard treatment is long-term androgen deprivation therapy (ADT), which is effective at controlling cancer but has a negative impact on quality of life, as it causes fatigue, weight gain, osteoporosis, muscle loss, hot flashes and loss of libido.

In the study, Dr. Henderson’s group evaluated how long they could delay starting ADT by treating the metastatic site with stereotactic beam radiation therapy (SBRT), in the hopes that the SBRT would delay disease progression and forestall the need for using ADT.

The patients who had rising PSA levels after previous surgery or radiation underwent scanning with F-choline PET/CT. None of the patients received previous hormone therapy.

When the SBRT was administered, a dose of 30 Gy in 3 fractions was given with a Cyberknife system. The time delay before there was a need to start ADT was calculated starting from the time of the SBRT. PSA was checked every three months and additional scanning with F-choline PET/CT was performed as needed.

Palliative ADT for Metastatic Disease

Out of the 21 patients, 6 were given 3 to 6 months of ADT along with the SBRT. Most of the men had only one oligometastatic site, and the majority of the metastatic sites were in the lymph nodes rather than the bones. Overall, there were a total of 8 bone lesions and 20 treated lymph node sites. At a median follow up of 16.7 months, 81 percent (17 patients) have not required any therapy with ADT. Median ADT-free survival is 28 months for the whole group. Twenty of the patients had a decline in PSA after treatment. The median percent reduction in PSA was 84 percent. No serious radiation toxicity above grade 2 was noted. The incidence of grade 1 and 2 CTCAE toxicity (see below*) was 29 percent (6 patients) and 5 percent (1 patient), respectively. No toxicity of grade 3 or above was observed. Overall, Dr. Henderson and his group felt that the SBRT was well-tolerated and advantageous in delaying initiation of hormone therapy. 

This study illustrates how brand new treatment opportunities are resulting from the advent of two new types of improved technology: First, better scanning technology that can detect small metastases at an early stage, before the disease spreads to multiple areas in the body.

And secondly, how more powerful radiation that is capable of “sterilizing” the cancer, while also being accurate enough to spare the closely surrounding healthy organs from any damage from the radiation therapy. This aggressive approach of detecting metastatic disease at the earliest possible stage and then initiating an aggressive treatment protocol by administering curative doses of radiation is likely to become more popular as people become aware that this treatment option exists.

Source:

Chajon, E., Castelli, J., Marsiglia, H., & De Crevoisier, R. (2017). The Synergistic Effect of Radiotherapy and Immunotherapy: a Promising but Not Simple Partnership. Critical Reviews in Oncology/Hematology111, 124-132.

Continue Reading