Prostate cancer treatment is on the brink of a major advance, thanks to new imaging technology that can pinpoint the location of prostate cancer cells. This new diagnostic tool allows doctors to see whether the cancer cells are still in the prostate or have spread elsewhere — crucial information for determining the best treatment for patients.
Memorial Sloan Kettering medical oncologist Michael Morris explains how the new tool will dramatically change the outlook for men with prostate cancer.
How does this new imaging technology work?
This form of imaging uses a radiotracer, a radioactive targeting molecule that selectively seeks out and attaches to a protein on the surface of cancer cells. That protein, called prostate-specific membrane antigen (PSMA), is not found on most normal cells. When the radiotracer binds to the prostate cancer cells, they can be detected using a PET scanner. On the PET scan, the cancer cells appear as bright spots.
PSMA was discovered several decades ago, and the gene for it was first cloned at MSK in 1993. MSK’s involvement with this target has been extensive. Researchers here have been very active in developing agents using PSMA as a target for both imaging and therapy. In recent years, we have collaborated with Johns Hopkins and the pharmaceutical company Lantheus to design and conduct two clinical trials testing one such imaging agent, called 18F-DCFPyL, in men with prostate cancer.
A new drug application has been submitted to the US Food and Drug Administration for this agent based on results from two clinical trials that we published in February 2021, and we anticipate that the FDA will approve the tracer this year.
What did the clinical trials show?
One trial, called CONDOR, evaluated 18F-DCFPyL in men who had undergone radiation or surgery, but who subsequently had a detectable prostate specific antigen (PSA) in their blood. PSA can suggest there are still prostate cancer cells in the body. The key question for these men is where is the residual disease that is generating the PSA? If we can find the site of disease, we can treat them with the appropriate therapy.
Standard imaging techniques are unfortunately very poor at identifying those sites that occur early, at low PSA levels, when there may be a very small amount of cancer cells. The new imaging technology works very well in this situation. The CONDOR trial involved 208 men who had a rising PSA after surgery or radiation but whose standard imaging scans detected nothing. The purpose of the study was to correctly identify and pinpoint the location of the prostate cancer. The median PSA of these patients was 0.85, which is low, but the radiotracer correctly identified the location of the cancer in 85% of patients. We reported these results in Clinical Cancer Research.
The other trial, called OSPREY, looked at the use of this agent in 385 men in two different groups. One group included newly diagnosed men who were preparing to undergo surgical removal of the prostate for high-risk disease, meaning these men were at high risk of having cancer that had already spread outside of the prostate. The other group were men who had already had their cancer relapse, meaning it came back after treatment. The point of the study was to define how well the PSMA PET scan identified disease outside of the prostate itself. In more than 80% of cases, a detection on the PET scan outside of the prostate turned out to be prostate cancer. These data were published in the Journal of Urology.
How will this new technology change the care of prostate cancer patients?
This is a major advance in diagnostics for prostate cancer, which is a very common disease. It is the biggest advance in prostate cancer detection since the PSA test was developed in the 1980s, and it will benefit people across the spectrum of the disease. In fact, PSMA-based imaging has already been approved in other countries, and they have already migrated to this new approach.
Imaging has been the Achilles heel of prostate cancer because the disease is hard to detect after it has spread. For example, the disease often spreads first to the lymph nodes in the pelvis, but the only way to tell is when the node increases in size, after the cancer has been there a while. Prostate cancer also commonly spreads to bones, but you cannot see the actual cancer cells with conventional imaging methods. Before, the only way to tell it was there was indirectly — by seeing the bone react to damage from the cancer cells by growing new layers of bone. With PSMA PET, we can now detect the cancer cells directly, and much earlier than we could with standard imaging.
Given the previous limitations of standard imaging, doctors have had to make treatment decisions based largely on assumptions and guesswork. For a man with high-risk disease preparing to undergo surgery or radiation, we had to wonder whether there was disease outside of the prostate that we couldn’t identify. Our treatments have been designed around incomplete information. For men whose prostate cancer relapsed, we often did not know where the cancer was and had to decide on a treatment plan without this knowledge. With PSMA PET, we have more accurate information to make treatment decisions. In the CONDOR study, for example, findings from the imaging led to a change in the treatment plan in 64% of the men.
There is an entire generation of clinical trials designed around this new type of imaging, including at MSK. The benefit this will bring to patients cannot be overstated, and we are very excited about the possibilities for the field.