SABR to oligometastases slows progression via immune response

Stereotactic ablative body radiation (SABR, or sometimes, SBRT) significantly slowed metastatic progression in men with three or fewer metastases (oligometastatic disease). SABR is a form of concentrated radiation accomplished in up to five treatments.

The trial (known as the ORIOLE trial) has been previously described in detail here. To recap, it was a small (Phase II) randomized trial with 36 men treated with SABR to bone scan/CT-detected oligometastases. There were 18 men in the untreated control group. The men were followed for 6 months to see if there was any progression of their cancer. Progression was defined as either PSA progression or new metastases detected on bone scan/CT or physical symptoms of decline (e.g., pain). Of course, with only 6 months of follow-up, most of the detected progression was PSA progression.

Phuoc Tran, the lead investigator of the ORIOLE trial, reported the 6-month results here:

  • Progression-free survival (PFS) was 81 percent in the SABR group vs 39 percent in the control group.
  • Median PFS was not yet reached in the SABR group vs 5.8 months in the control group.
  • The time to progression was reduced by 70 percent by the treatment.
  • Progression has not been reached among those treated patients followed for over a year.

Although patients were only treated for metastases discovered on a bone scan/CT, they were also given a PSMA-based PET scan (DCFPyL). Those in whom no additional metastases were discovered by the PET scan fared better:

  • PFS was 84 percent in the fully treated group vs 36 percent in those with undiscoveredmetastases.
  • Median PFS was not reached in the fully-treated group vs 11.8 months in those with undiscovered metastases.
  • Distant metastasis-free survival (i.e., metastases distant from the ones that were treated) was 29 months in the fully-treated group vs 6 months in those with undiscovered metastases.

PFS in men in whom there were any untreated metastases was not improved compared to untreated men. This seems to be an all-or-nothing sort of thing.

SBRT has been found in laboratory studies to elicit a strong immune response. It releases cancer antigens into the bloodstream that are detected by T-cells, which become activated to find more cancer. That T cell response to radiation is thought to contribute to its effectiveness (called “the abscopal effect”). The investigators tracked the T cell response and found a significant response in the SABR-treated men.

Progression-free survival when most of the progression is PSA progression is not, however, the endpoint we need to evaluate this therapy. SABR “treats” PSA. “Treating PSA” would occur if the radiation only provides excellent local control, while not necessarily delaying progression elsewhere. PSA is secreted in proportion to the size of the tumors, so treating only the tumors will do nothing to stop the micrometastases that are elsewhere. However, the strong T-cell response found by this study suggests that there may be a true delay in progression and not only a delay in PSA. Also, the fact that distant metastases were delayed by almost 2 years among those who had all of their PSMA-detected metastases irradiated, suggests a true response.

This is an important first step toward discovering whether oligometastasis-directed therapy provides a benefit, and how it works. It does not yet provide the answer to whether there is a survival benefit to such therapy. It also does not answer the question of whether ADT can be delayed when radiation has been given. There are several, larger clinical trials that will answer those questions more definitively. Meanwhile, the patient with rising PSA after prostate therapy should consider:

  • A PSMA-based PET scan (available in some clinical trials, and probably
    widely available within a year)
  • Talking to a radiation oncologist about SABR treatment of metastases if all
    discovered metastases are in places where it is entirely safe to treat them
  • Not forgoing ADT adjuvant to SABR treatment until there is more proof

Editorial note: This commentary was written by Allen Edel for The “New” Prostate Cancer InfoLink.

5 Responses

  1. I was treated last August with three sessions of SABR. My PSA began to increase from 0.02 to 0.5. PET scan with choline-11 showed activity in only one lumbar vertebra. My latest PSA result is 0.13. Next visit to the oncologist on Thursday.

    I have read somewhere that some medical teams are asking for more deep trials but they don’t have the support.

  2. The role of SABR / SBRT in treatment of is evolving. This is going to take time and money, and it won’t happen overnight.

  3. The important point to make here is what our Sitemaster points out — oligometastatic radiation as a management tool is a burgeoning and developing area of research.

    I recall the late LupronJim, who some may recall from the Inspire UsTOO forum, touting the abscopal effect many years ago. While this research supports that concept, it is a very small sample and it certainly does not reference “cure” that certain RAD/ONCs do hold out.

  4. Dear Rick:

    In defense of the RAD/ONCs who claim the possibility of a “cure”, I would point out the Jim Waldenfels has been claiming that such radiation has “cured” him of oligometastatic disease for quite some time now. It isn’t just some RAD/ONCs who are claiming this possibility, but some patients too. Whether the terminology is correct or not without at least 10 years of follow-up is, of course, debatable.

  5. I would defer to Snuffy, and at best call it a durable and continuous remission!

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this: