Dr. Piet Ost is a radiation oncologist at Ghent University in Belgium. His work focuses on post-surgery radiation therapy and metastasis-directed therapy for oligometastatic prostate cancer, or a cancer recurrence with three or fewer metastases.
Prostatepedia spoke with him about treating men with so few metastases after treatment.
Can you define oligometastatic prostate cancer?
Dr. Ost: First of all, if your doctor talks about oligometastatic disease, I think it’s very important to ask them what they mean by that? When we look through literature, there are several definitions used.
Some people use oligometastatic while others use oligorecurrence, synchronous metastases, or low volume metastases. Many of these probably mean the same, but there is no uniform definition.
In 1995, Hellman and Weichselbaum first defined oligometastases as metastases limited in number and location. These tumors have not developed the full capacity for metastatic growth. It could be an issue with the metastases—or the seed—or it could be an issue with the soil—the environment in which the metastases started to grow. That’s the biological definition.
This is not very useful as a clinician. What is limited? Is that a certain number? If you look through literature, many clinicians define it as up to three metastatic lesions with no more than two different organs involved. That is probably the most used definition, but there are alternatives. Some say that it’s only one metastasis while others say it’s as many as five or even 10 in case of brain metastases. Some say there has to be a certain amount of time between primary diagnosis and the occurrence of metastasis.
There’s a lot of confusion throughout the literature. If you read an article, you have to look at their definition. When doctors talk to each other, and when patients talk to each other, they all use the word oligometastatic, but it might be that they’re talking about a different disease.
Is there any sort of restriction on where those metastases are located—for example, in only the pelvic area?
Dr. Ost: At this time, I don’t think so. It’s a biological phenotype. We care less where the metastasis occurs. For example, we have had patients with unique lung mets at the time of recurrence where we remove those lung mets, and then these patients remain disease-free for many months or even years.
Normally, when you have a patient with lung mets, those are visceral mets, and their prognosis is supposed to be very poor no matter what. There appears to be a subset of patients with a limited number of metastases, even visceral metastases, who still benefit from removing or irradiating the metastases. We have several of those cases documented already. It’s not about the location. It’s something about the biology, and that is the big problem at this time.
Currently, when we propose a certain oligometastatic or metastasis directed therapy to a patient, we don’t know if the metastases we see and treat are the only ones there, or if three months after we remove or eradiate them, there will be 20 new metastases. We don’t know that at the start. This shows us that imaging is still far from perfect and sometimes we only see the tip of the iceberg.
When we look at the distribution or pattern of metastases in recurrent prostate cancer with Choline PET/CT and PSMA PET/CT imaging, we see that, after receiving prior prostate cancer treatment, the majority of patients relapse first in the lymph nodes.
That is mainly in the pelvic lymph nodes. If we look at all the patients that we screen for now, 70% have nodal recurrences, 25% have bone metastases, and 5% have visceral mets. If we look at all of those recurrences, two thirds of those relapses are what we call oligometastatic, meaning up to three metastatic spots. We don’t believe that there is a true limitation on the organs. How it evolves is actually a fingerprint of the disease.
When you start, you don’t know whether it’s a true oligomet. We cannot predict at this time how the disease will evolve.
How do you normally treat oligomets? With radiation or surgery? How do you decide which is most appropriate?
Dr. Ost: We still counsel our patients on the standard options. For patients with upfront metastatic disease, the landscape has changed dramatically where we now introduce Androgen Deprivation Therapy (ADT) plus Taxotere (docetaxel) or ADT plus Zytiga (abiraterone) as a standard of care.
We still do not know if these options are helpful in treating the primary tumor and its mets with metastatic-directed therapy. In situations with upfront oligometastatic disease, we counsel our patients that the standard of care is systemic drugs while the addition of any metastatic-directed therapy is one big question mark. We do not advise it outside clinical trial.
The situation is a bit different in the recurrent setting. In the recurrent setting, there’s a gray zone. For example, the older data said that starting ADT for a PSA relapse following primary therapies—just starting ADT—is not advised; it’s better to wait and see and do a delayed ADT at the time of symptomatic progression.
Now with the very sensitive imaging, we see mets earlier at PSA relapse. What should we do with these? Do we still say the standard of care is wait and see, ADT, or something else? Because new imaging created this gray zone, all of a sudden we saw a boom in these oligometastatic patients, so we decided to do a clinical trial in this setting.
In our paper published in The Journal of Clinical Oncology (JCO), we randomized our patients to wait and see. One group had surveillance while starting ADT, and the other group had surgery or radiotherapy to the mets followed by surveillance. In that study, we found that surgery or radiotherapy is better at postponing further progression to polymetastatic disease rather than just observing patients.
We have an alternative now in counseling patients: metastaticdirected therapy with either surgery or radiotherapy. We know that it’s very safe, because we did not see any grade 2 or higher toxicity, which is a positive thing to tell men with prostate cancer. We can offer you something without a whole lot of toxicity. We still have to tell you this was a Phase II trial. The endpoint was time to progression.
I’m still not sure that giving metastatic-directed therapy will change your disease in the long run, that it will make you live any longer compared with immediate ADT or surveillance. It’s still too early to tell. We try to counsel our patients with these different options.