Prostate cancer can be highly treatable when it remains confined to the prostate. But once it spreads to bones, lymph nodes, and other organs, it becomes much harder to manage as doctors work to detect and eliminate cancer cells throughout the body.

At the MCW Cancer Center, Michael Holt, MD, Assistant Professor of Radiology, and colleagues are using theranostics to find and treat disease with greater precision. This innovative approach combines diagnosis and treatment, two sides of cancer care that have traditionally been separate. Using radioactive drugs designed to seek out cancer cells, doctors can first see where the disease has spread and whether it can be targeted. They can then use that same biological target to deliver radiation directly to the cancer.

For Dr. Holt, what is happening in prostate cancer is part of a much larger shift toward treatments designed around the biology of an individual cancer. “Targeted therapy is the future of cancer therapy. Theranostic agents for nearly every cancer are being evaluated in clinical trials, and we expect tremendous growth over the next five to 10 years.”

That growth is already opening new lines of research across MCW. Clinical trials are moving theranostics earlier in prostate cancer treatment, while investigators are studying how to better measure the radiation that reaches each patient’s tumors and use that information to refine treatment. And while prostate cancer is driving much of that progress today, researchers see an opportunity for theranostics to reach much further.

A Beacon and a Bullseye

Theranostics has found a particularly strong foothold in prostate cancer because of PSMA, or prostate-specific membrane antigen, a protein found in high levels on the surface of most prostate cancer cells. More than 90% of prostate cancers overexpress PSMA, and levels often rise as the disease becomes more aggressive. That gives researchers a reliable marker to look for and, importantly, something they can target.

PSMA can act as both a beacon and a bullseye. To find the cancer, doctors give a patient a drug that seeks out PSMA and carries a small amount of radioactive material with it. Wherever the drug finds cells with high levels of PSMA, it creates a signal that can be seen on a PET/CT scan. The scan maps where the disease has spread and confirms whether there is enough PSMA present for targeted treatment.

Then the same idea is turned against the cancer. A second PSMA-seeking drug travels through the body looking for that same protein, but this time it carries radiation intended to damage the cells it reaches. The marker that helps doctors see the cancer also gives them a way to attack it. As Dr. Holt puts it, “Treat what you see and see what you treat.”

Research has shown how powerful that connection can be. In the landmark VISION trial, adding PSMA-targeted radioligand therapy to standard care for patients with advanced prostate cancer more than doubled the time their cancer was kept from progressing on imaging and helped them live longer. The results helped establish PSMA-targeted theranostics as an effective treatment for advanced disease and set the stage for researchers to test whether it could benefit patients earlier.

Those results pushed the field to explore whether theranostics could help patients sooner. The PSMAfore trial moved the treatment ahead of chemotherapy and found that patients receiving it went longer without their disease progressing than those who switched to another hormone-targeting treatment. The PSMAddition study moved it earlier still, showing benefit in patients whose disease remained sensitive to hormone therapy and helping expand its FDA approval into this earlier stage of metastatic disease.

Why Stop at One?

Theranostics is already precise. MCW researchers want to know how much more precise it can become. The Theranostics Program, co-directed by Dr. Holt and William Hall, MD, Chair of Radiation Oncology, brings together experts in Nuclear Medicine, Radiation Oncology, and Medical Oncology to study the treatment from multiple angles, including how much radiation reaches a tumor, how effectively it destroys cancer cells, and how much is absorbed by healthy tissue.

One important focus is dosimetry, which uses imaging after treatment to measure where the radiation actually went and how much was absorbed by tumors and healthy organs. Two patients can receive the same treatment but absorb different amounts of radiation in their tumors and healthy tissue. By measuring those differences, researchers hope to eventually use that information to better personalize treatment, delivering the amount needed to attack the cancer while limiting unnecessary exposure elsewhere.

Perhaps the bigger opportunity is taking what researchers have learned from PSMA and applying it to other cancers. Scientists are studying other molecules, including FAPI and GRPR, that appear in or around cancer cells and could potentially serve the same critical purpose: giving theranostics something to find and something to target.

For Dr. Holt, seeing what one target can do raises a bigger question. Why stop at one?

“The goal is to find unique targets for every cancer,” he said.