David J. Einstein, MD
Several novel imaging modalities have emerged in nonmetastatic hormone-sensitive prostate cancer over the past few years, providing higher sensitivity and allowing for better detection of lower levels of disease compared with traditional strategies.
Now, investigators are trying to determine how these techniques improve patient outcomes and in which settings they will provide the most benefit, said David J. Einstein, MD, a genitourinary medical oncologist at Beth Israel Deaconess Medical Center.
“Typically, when we're imaging prostate cancer, we're using either CT scan or MRI plus bone scan. The problem with these imaging modalities is that they're pretty insensitive at low prostate-specific antigens (PSAs),” said Einstein. “For the patients who are just starting to recur, [when we do] these scans, we're pretty much guaranteed to not see anything. The other problem is that bone scan in particular is an indirect way of looking for cancer; it actually looks at the healing reaction to cancer rather than the cancer itself.”
These newer techniques could be particularly helpful in patients who have already received all available standard local therapies and still have a rising PSA, with no metastases found on a conventional scan. These strategies might allow for oncologists to better detect early oligometastatic recurrences and perform metastasis-directed therapy (MDT) to select areas of recurrent disease.
This idea was explored further in the phase II STOMP trial, which included patients with oligorecurrent, hormone-sensitive prostate cancer, which comprised up to 3 asymptomatic metastases identified on choline PET-CT scan.
For the trial, patients were randomized to either surveillance or MDT via surgery or stereotactic body radiotherapy. Those who received MDT were found to have a longer androgen deprivation therapy (ADT)–free survival compared with the surveillance group at 21 months versus 13 months, respectively (HR, 0.60; 80% CI, 0.40-0.90) at a median follow-up of 3 years.1
Biochemical relapse-free survival was also more favorable in the MDT arm (HR, 0.52; 80% CI, 0.36-0.76).2
In an interview during the 2019 OncLive®
State of the Science Summit™ on Genitourinary Cancers, Einstein discussed newer imaging techniques and overall progress in the treatment of patients with nonmetastatic hormone-sensitive disease.
OncLive: What are some of the novel imaging tools that have emerged in this space?
: [Many investigators] have come up with different imaging strategies to try and improve on [sensitivity]. These approaches range from choline [C-11] PET scan, to the [18F] sodium fluoride PET/CT scan, to the newly FDA-approved fluciclovine PET/CT scan, to prostate-specific membrane antigen scans, which are the way to the future. Many of these [tools] are various PET modalities that [differ from] the conventional PET scan that we think about. The idea is to pick up disease at lower levels than we were previously able to detect [with traditional methods]. The real question though is, “Does that help patients?”
The way that we think it could help patients is if we're actually able to detect small amounts of disease. For example, [if we are] just after a surgery, and we're thinking about planning salvage radiation to the prostate area, we might use sensitive imaging to guide that beam rather than radiating blindly. We also might include a little bit broader area than we would otherwise.
Another area that [these tools] could be helpful in would be in patients who have already been through all of the standard local therapies, have rising PSA, and don't have anything on a conventional scan. There’s a question of whether we can pick out early oligometastatic recurrences and do metastasis-directed therapy, meaning that we do some radiation or surgery to selected areas of recurrent cancer. That [approach] was tested in the STOMP trial and it seemed to delay the need for systemic ADT, which, of course, most patients hate as it has a lot of toxicities and it doesn't cure the disease.
Another related strategy, but one with a little bit different school of thought, is to use metastasis-directed therapy plus intensified systemic therapy in an effort to eradicate the disease at its earliest recurrence. We'll see which of these strategies wins out, but they are both up-and-coming approaches that are being tested in trials.
Could you expand on the STOMP trial?
The STOMP trial was published [in 2018], and tested this idea of going after and trying to pick off metastases as they show up. That trial seemed to demonstrate that you could delay the need for ADT in these patients through that kind of a strategy, but that clearly needs validation in a bigger trial with endpoints that are more objective. There are 2 other trials being done in this area as well—the ORIOLE trial and the METACURE trial—which are testing different methods to approach the early oligometastatic recurrent setting.
What strategies are under investigation in the management of disease?
There have clearly been many different attempts to optimize therapy for these patients. Some of them have been on the topic of metastasis-directed therapy—so using local salvage therapies. Hormonal therapies are also out there, which we know are effective in more advanced disease, but are now being moved up in the treatment course.
We also had a talk on the role of intensified ADT in the M0 castration-resistant prostate cancer space. It's very controversial because some might argue that you should delay all of that until they actually have metastatic disease, but that's a bigger question in the literature that hasn't been resolved yet.
Finally, one really exciting thing is that everyone is interested in immune therapies, particularly in this area of micrometastatic disease. There are a couple of reasons why we think that might be the optimal place to use these types of therapies. We're in the process of testing vaccines and checkpoint inhibitors in the setting of biochemical recurrent premetastatic prostate cancer.
Could you expand on some of this work?
We're currently undergoing a trial with PROSTVAC, which is a prostate vaccine out of the National Cancer Institute. I have my own patients on [that trial] and we've been working with Dana-Farber Cancer Institute to put a lot of patients on this trial. We’ve been seeing some PSA stabilization and sometimes a decline.
I'm also testing the role of checkpoint inhibitors in this setting, with the rationale that all the old checkpoint inhibitor trials were done in a much more advanced population in which the immune context is a bit different. We’re testing that right now, and we've got several patients enrolled. We're seeing some exciting results from the first few patients.
Where do you see future research headed?
The key questions here are, “Does novel imaging actually help us? If so, in which settings? Does intervening on the prostate and or the metastases help more with delaying the need for systemic therapy or more with an eye toward disease eradication?” Basically, are we going for cure or are we trying to kick the can down the road? These are some of the big questions that we'll be asking in this setting. For years to come, even as we test all of these new ways of treating prostate cancer, these vaccines and checkpoint inhibitors could act in yet a different way from the “tried and true” hormonal agents and radiation.
- 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. J Clin Oncol. 2017;36(5):446-453. doi: 10.1200/JCO.2017.75.4853.
- Zilli T and Ost P. Metastasis-directed therapy: a new standard for oligorecurrent prostate cancer? Oncotarget. 2018;9(76):34196-34197. doi: 10.18632/oncotarget.26152.