Oligometastatic Disease Radiation Therapy
Few is the word that matters. When a cancer has spread to one to five places and each can be reached safely, focused radiation to every deposit has lengthened survival in randomized trials, and those same trials counted the deaths it caused. This guide gives the definition, the four trials, who qualifies, and what a treatment stay involves.
About This Department
A cancer that has spread to one, two or three places is not the same disease as a cancer that has spread everywhere. Treating each spot with focused radiation added 13 months of median survival in the first randomized test.
That trial, SABR-COMET, was small. Its results are promising and not final. Two others have since shown the same pattern in lung and prostate cancer. The trial reports also record the harm. Oligometastatic disease radiation therapy means finding every visible deposit on a high-resolution scan and destroying each one in one to five sessions, alongside the drug treatment that controls the rest. Send us your scans, your pathology and your treatment history, and a radiation oncologist will tell you whether your disease fits the definition and what the trials say about your situation.
Oligometastatic disease can be defined as one to five metastatic lesions, with a controlled primary tumor optional, where every metastatic site can be treated safely with radiotherapy of curative intent.ESTRO and ASTRO consensus, Radiotherapy and Oncology, 2020
The idea, and where it came from
For most of the twentieth century a cancer that had spread was treated as a cancer that had spread everywhere. Drugs went to the whole body. Radiotherapy was reserved for pain. The word oligometastatic, from the Greek for few, was proposed in 1995 by two radiation oncologists in Chicago to describe an intermediate state between a tumor confined to its organ and one scattered through the body, and the argument that followed from it was simple. If the deposits on the scan are the only ones there, destroying all of them might cure, or at least buy years. If they are the visible tip of many more, it would achieve nothing. For twenty years nobody could tell which patient was which.
Two things changed that.
Better scans, and stereotactic radiotherapy. PSMA PET for prostate cancer, PET-CT for most others and MRI of the brain and liver now find deposits of a few millimeters, and SBRT can destroy a deposit in one to five sessions without an operation. The randomized trials followed.
What the trials found
Four randomized trials have tested the idea, in four different populations, and the table gives each one at a glance. They are phase 2 trials, meaning they were designed to show whether an effect exists and not to settle the question, and the consensus document above lists the phase 3 trials still running.
This table scrolls sideways on a narrow screen. Swipe or drag to see every column.
| Trial | Patients | Compared | Main result | Harm recorded |
|---|---|---|---|---|
| SABR-COMET, The Lancet 2019 | 99 patients, mixed cancers, 1 to 5 metastases, primary controlled | Standard palliative care with or without SBRT to every deposit | Median survival 41 months with SBRT, 28 without | Grade 2 or worse side effects 29 percent against 9 percent. Three of 66 SBRT patients, 4.5 percent, died of treatment |
| Gomez and colleagues, Journal of Clinical Oncology 2019 | 49 patients, lung cancer, 3 or fewer metastases, no progression after first-line drugs | Maintenance drugs or observation, with or without local treatment of every site | Median survival 41.2 months with local treatment, 17.0 without. Trial stopped early for benefit | No additional grade 3 or worse side effects |
| STOMP, Journal of Clinical Oncology 2018 | 62 men, prostate cancer recurring after treatment, 3 or fewer deposits on PET | Surveillance or treatment of every deposit by SBRT or surgery | Median time before hormone therapy was needed, 21 months against 13 | Grade 1 effects in six men, nothing worse |
| ORIOLE, JAMA Oncology 2020 | 54 men, prostate cancer, 1 to 3 metastases | Observation or SBRT to every deposit | Progression at six months 19 percent with SBRT, 61 percent without. New lesions at six months 16 percent when every PSMA-avid spot was treated, 63 percent when one was missed | No grade 3 or worse side effects |
What they did not settle
Read the SABR-COMET row twice. Thirteen months of extra median survival in a mixed group of cancers is the largest effect ever reported for a radiotherapy trial in metastatic disease, and it came with three treatment deaths in 66 patients, from lung bleeding, a perforated stomach ulcer and a lung abscess after treatment of deposits near the airways, the stomach and the chest wall.
The two prostate trials measured time before hormone therapy and progression at six months, which matter to a man who wants to postpone injections, and neither has so far shown that lives are longer. The lung trial had 49 patients. Forty-nine. None of the four settles how many deposits is too many, whether four or five behave like one, or which cancers gain most, and the phase 3 trials that will answer those questions have enrolled their patients and are still to report. A clinic that quotes the 41-month figure without the 4.5 percent beside it is quoting half the trial.
This table scrolls sideways on a narrow screen. Swipe or drag to see every column.
| Likely to qualify | Unlikely to qualify |
|---|---|
| One to five deposits on a high-resolution scan, and every one of them can be treated safely | More than five deposits, or deposits that keep appearing on each scan |
| The original tumor controlled, or treatable in the same plan | The original tumor growing and untreatable |
| Up and about most of the day, with a life expectancy of more than six months | Confined to bed or chair, or with organ failure |
| Disease that has stayed stable or shrunk on drug treatment | Disease growing through drug treatment at many sites |
| Drug treatment available to continue afterward | No drug options left, which changes the aim to comfort |
| Deposits in bone, lung, liver, adrenal gland, lymph nodes or brain, away from hollow organs | Deposits in the bowel wall, the peritoneum, or fluid in the abdomen or chest |
The last row explains a great deal. It accounts for most of the harm and most of the refusals. Spread across the lining of the abdomen, or fluid around the lungs, means innumerable deposits whatever the count on the scan, and radiotherapy has no target.
Which cancers and which sites?
Prostate cancer
Lung cancer
Bowel cancer
Breast, kidney, melanoma and others
Brain metastases
How is treatment planned?
The plan begins with the scan, because the definition depends on it. The consensus document calls high-resolution imaging crucial and asks for brain imaging where the cancer can spread there. For prostate cancer that means PSMA PET, for most other cancers PET-CT, and for the liver and brain MRI. A scan older than six to eight weeks is repeated. Then the tumor board asks three questions in order. Whether every deposit can be treated safely, which decides whether the disease is oligometastatic at all. Whether surgery, ablation or radiotherapy serves each site best. And what drug treatment continues alongside and afterward, since radiotherapy to the deposits treats what is visible and the drugs treat what is not. Each deposit is then contoured and planned separately, with its own dose, chosen by what lies next to it. Bone and lymph node deposits take one to three sessions, lung and liver deposits three to five. Anything against a hollow organ takes more sessions at a lower dose or is left to another method, and a deposit that cannot be treated safely by any method takes the patient out of the definition, no matter how few the others are.
What are the risks?
During treatment there is little to notice. The effects that matter arrive weeks or months afterward in the organ that sat closest to a deposit, and the list below follows the sites.
By site
The lung comes first. Deposits there can leave an inflamed patch that causes cough and breathlessness one to six months later and answers to steroids, and a deposit against the ribs can leave chest wall pain or a fractured rib. Liver deposits bring nausea and tiredness. In a liver already damaged by disease or chemotherapy they can bring a fall in function. Spinal deposits can flare with pain for a day or two, and months later the treated vertebra can fracture if it was already weakened. Adrenal and upper abdominal deposits carry the risk of an ulcer in the stomach or bowel where these lie close, and that single mechanism, a high dose landing on a hollow organ that cannot repair itself, produced two of the three deaths in SABR-COMET and shapes every planning rule in this field.
Brain radiosurgery can cause swelling that needs steroids. A minority develop a dead patch of tissue months later. It mimics regrowth on MRI. Numbers differ by trial. Side effects of grade 2 or worse affected 29 percent of SBRT patients in SABR-COMET, and nobody reached grade 3 in the three later trials, which treated fewer deposits per patient in less dangerous places.
How many weeks will I need in Istanbul?
- Before travel. The remote review states whether your disease fits the definition, which deposits would be treated and by what method, and whether any scan needs repeating. Allow a week.
- Days one to three. Consultation with the radiation oncologist and the medical oncologist, tumor board, any repeat imaging, and the planning CT in the treatment position, in four dimensions for deposits that move with breathing.
- Days four to ten. Contouring, planning and physics checks for each deposit. You are free during these days.
- Days ten to twenty. The sessions, one to five per deposit, on alternate days, with deposits treated together where their plans allow.
- The last day. Review with the oncologist and a treatment summary listing the dose to every deposit and every nearby organ. You can fly the next day.
Count the deposits. Then count the weeks.
Two to three weeks covers one to three deposits. Five deposits, or deposits in several organs, can take four, because each plan is checked on its own and the sessions for deposits that cannot be treated together are spread over more days. Drug treatment continues at home under your own oncologist from a written plan, and a pause in chemotherapy around the sessions is agreed with that oncologist before you travel.
What decides the cost, and what about the trip?
Four things belong in any quote.
- The number of deposits the figure covers, and what each additional one adds.
- The scan that will define the disease, and whether it sits inside the figure.
- The deposits that will be treated at a reduced dose because of what lies next to them.
- A treatment summary that lists the dose to each organ, in English.
No hospital in Istanbul publishes a package for this treatment, because the count and the sites vary too much for one. Your figure follows the free review of your scans.
Language and companions
Follow-up at home
Oligometastatic disease radiation therapy FAQ
What does oligometastatic mean?
Can oligometastatic cancer be cured?
How many sessions does each metastasis need?
Will I still need chemotherapy or hormone therapy?
How long will I need to stay in Istanbul?
Can my family come with me?
References
- Lievens Y, Guckenberger M, Gomez D, et al. Defining oligometastatic disease from a radiation oncology perspective: An ESTRO-ASTRO consensus document. Radiotherapy and Oncology. 2020;148:157-166.
- Palma DA, Olson R, Harrow 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;393(10185):2051-2058.
- Gomez DR, Tang C, Zhang J, et al. Local Consolidative Therapy Vs. Maintenance Therapy or Observation for Patients With Oligometastatic Non-Small-Cell Lung Cancer: Long-Term Results of a Multi-Institutional, Phase II, Randomized Study. Journal of Clinical Oncology. 2019;37(18):1558-1565.
- Ost P, Reynders D, Decaestecker K, et al. Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial. Journal of Clinical Oncology. 2018;36(5):446-453.
- Phillips R, Shi WY, Deek M, et al. Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer: The ORIOLE Phase 2 Randomized Clinical Trial. JAMA Oncology. 2020;6(5):650-659.
Editor's note
Written by the Biruni Hospital medical editorial team. Reviewed by Prof. Dr. Mustafa Teoman YANMAZ, Medical Oncology.
Medically reviewed by
Prof. Dr. Mustafa Teoman YANMAZ
Medical Oncology
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