Baseball fans are familiar with the Baltimore Orioles, a team named for the state bird of Maryland. Since 1954, the bird has brought them luck: 7 pennants and 3 World Series. Now there’s a new ORIOLE that’s having a winning season in the fight against metastatic prostate cancer. ORIOLE stands for a study called the Observation Versus Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer, and if its clinical results are any indication, it may well be about to knock one out of the park.
Oligometastatic prostate cancer
The clinical term for prostate cancer (PCa) spread to 1-3 distant sites in the body is oligometastatic PCa. This results when aggressive tumor cells have successfully overcome the multitude of challenges posed by the body’s defenses, and managed to “colonize” another site; once established, even microscopically, cancer typically uses its own bioengineering to a) disguise itself so the immune system doesn’t recognize it as an enemy, and b) sabotage healthy cells in order to use their resources for its own development.
Oligometastatic PCa is considered incurable, though there are individual reports of treatments that appear to have put the cancer in remission.[i] There are also promising immunotherapeutic vaccine therapies, but they have not yet been widely shown to add many years to a patient’s life.
Stereotactic Ablative Radiation Therapy (SABR)
Radiation therapy, or radiotherapy, has been a valuable modality in the cancer treatment toolkit. A relative newcomer is stereotactic ablative radiotherapy (SABR), which delivers a targeted high dose to small tumors over a short period of time (3-5 sessions over 5 days). According to one author, “SABR is guided by a special imaging system such as computerized tomography or computed tomography (CT). The CT is built into the radiation treatment machine. Because CT scanning can accurately pinpoint a tumor, SABR is able to give higher doses of radiation directly to the tumor without damaging nearby critical normal structures.”[ii] SABR has shown promise for treating primary and recurrent tumors in the lung, liver, prostate and other organs. A multinational Phase II clinical study compared SABR vs. standard palliative treatments for various oligometastatic cancers. The authors found improved survival for SABR patients (41 months vs. 28 months) though 3 of the 66 SABR patients had treatment-related deaths.[iii]
The ORIOLE study: phase 2 report
Let’s take a closer look at the ORIOLE study. In September, 2019 at the Chicago meeting of the American Society for Radiation Oncology (ASTRO), ORIOLE study phase 2 results were presented by lead author Dr. Ryan Phillips, PhD (Johns Hopkins University, Baltimore MD). 54 participants with oligometastatic PCa and no hormone therapy for the previous 6 months were randomly assigned (2:1 ratio) to either SABR (36 men) or observation (18 men). All had blood tests and PSMA-PET scans at baseline and 6 months. The primary outcome was the proportion in each group with disease progression at 6 months.
The authors found that SABR patients were less likely to have PSA increases, and were more likely to go longer without PCa progression than those in the control group (median progression-free duration of 12+ months for SABR vs. 5.8 months for controls). Of great interest, the SABR group had higher T-cell levels (a key component of the immune system), perhaps in response to radiation-induced cell death.[iv]
On March 26, 2020 these results were published in the online Journal of the American Medical Association (JAMA).[v] The authors wrote that “…progression of disease at 6 months occurred in 7 of 36 participants (19%) treated with [SABR] and in 11 of 18 participants (61%) undergoing observation, a statistically significant difference.” Clearly, those who received SABR had better cancer control.
In discussing the early success of using SABR as a metastasis-directed therapy, the authors point out that more research is needed to determine which oligometastatic PCa patients will benefit from targeted radiation therapy using SABR, the nature of the apparent immunity-boosting response, and how reliable that response would be for all patients. Meanwhile, “…SABR is a safe and effective way to forestall progression of treated metastases and improves oncologic outcomes in certain patients.” Of special importance to PCa patients newly diagnosed with oligometastatic PCa, undergoing SABR may not only increase their years of survival, but forestall going on hormone therapy (androgen deprivation) with its potentially devastating side effects on lifestyle and masculinity. The authors go so far as to suggest that repeat rounds of the SABR strategy against individual early metastatic lesions might maintain cancer control without hormones for an indefinite period of time. It’s even conceivable that combining repeat SABR with a systemic therapy such as androgen deprivation may ultimately prove curable.
Is it just coincidence that the ORIOLE’s study team includes researchers from Johns Hopkins University, also located in Baltimore? We hope that Maryland’s state bird proves as fortuitous for PCa patients as it has been over the years for Baltimore’s baseball fans.
NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.
[i] “Metacure Trial: Can We Cure More Oligometastatic Prostate Cancer?” Jan. 13, 2020. https://consultqd.clevelandclinic.org/metacure-trial-can-we-cure-more-oligometastatic-prostate-cancer/
[ii] Chang, JY. Stereotactic ablative radiotherapy: aim for a cure of cancer. Ann Transl Med. 2015 Jan; 3(1): 12.
[iii] Palma DA, Olson R, Harrow S, Gaede S et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet. 2019 May 18;393(10185):2051-2058.
[iv] Casey, Brian. “ASTRO: SABR generates immune response to prostate cancer.” Aunt Minnie. Sep. 16, 2019. https://www.auntminnie.com/index.aspx?sec=sup&sub=roc&pag=dis&ItemID=126541
[v] Phillips R, Shi WY, Deek M, Radwan N et al. Outcomes of observation vs stereotactic ablative radiation for oligometastatic prostate cancer: the ORIOLE phase 2 randomized clinical trial. Jama Oncol. 2020 Mar 26. Pub online https://jamanetwork.com/journals/jamaoncology/fullarticle/2763312