How Targeting PSMA is Changing Prostate Cancer Care

6 min read

How Targeting PSMA is Changing Prostate Cancer Care

Prostate cancer is notoriously difficult to find and treat when it spreads beyond the prostate gland to the lymph nodes and other parts of the body. Recent imaging and treatment advances, however, are chipping away at advanced prostate cancer’s ability to evade detection. Molecular imaging and radiopharmaceuticals targeting prostate-specific membrane antigen, or PSMA – a protein dwelling on prostate cancer cells – are important new tools in the campaign against advanced prostate cancer. Rocky Mountain Cancer Centers (RMCC) is at the forefront of these innovations, thanks to our participation in PSMA treatment clinical trials and the establishment of a leading-edge Theranostics Suite for specialized imaging and radiopharmaceutical therapies.

The Challenge of Identifying Advanced Prostate Cancer

The standard method of identifying prostate cancer metastases is with a CT scan and a bone scan, but these modalities can overlook standalone cells and minute tumors, according to the National Cancer Institute. A PET/CT scan using a radioactive tracer that binds to PSMA can help bring more difficult-to-detect advanced prostate cancers to light, even when prostate-specific antigen levels are low. When the tracer attaches to PSMA on the surface of prostate cancer cells, the cells are visible in PET/CT imaging.

Radiologist Monitors Results While Patient Undergoes CT Scan ProcedureOne such radioactive agent is piflufolastat F 18, also known as Pylarify®. In 2021, the Food and Drug Administration (FDA) approved Pylarify for patients with suspected metastatic or recurrent prostate cancer. At RMCC, Pylarify can identify targets for treatment with the radiopharmaceutical 177Lu-PSMA-617, the brand name of which is Pluvicto™.

Glenn Balasky, Executive Director of RMCC, believes PSMA targeting is a key advancement in prostate cancer care that may prove even more significant in the future.

“I think, right now, this is a substantive shift that could become more seismic as it plays out,” Glenn said. “What PSMA starts to represent on the imaging side is the ability to image advanced prostate cancer that couldn’t be seen well before.”

PSMA treatment holds equally exciting potential for men with advanced prostate cancer.

“Currently, if you have stage 4 prostate cancer, and you’ve been treated with surgery or radiation therapy, the next step is to go on androgen deprivation therapy or some form of chemotherapy,” Glenn said. “However, those therapies are really intended to slow the disease, whereas PSMA treatment provides an opportunity to reduce the disease burden. It may not be fully curative, but it can reduce the disease burden versus trying to maintain the disease burden with other therapies.”

Targeting PSMA: Seek and Destroy

Pylarify and Pluvicto are complementary – the former determines whether cancer has spread to other parts of the body and illuminates the metastases in imaging, and the latter delivers precision radiotherapy to the newly-identified targets.

“Pluvicto has the same sort of biological attachment as Pylarify in that it looks for the same PSMA proteins,” Glenn said. “The difference is that, instead of bringing a light to show that the cell is there, Pluvicto brings a tiny radioactive bomb to the cell to treat it with incredibly localized radiation.”

Candidates for treatment with Pluvicto include men with PSMA-positive metastatic castrate-resistant prostate cancer who have tried androgen receptor pathway inhibitors and taxane-based chemotherapy. In 2022, the FDA approved Pluvicto for certain adults with metastatic prostate cancer in the wake of the VISION trial. This phase 3 clinical trial found that patients who received Pluvicto plus standard therapy had a median overall survival of 15.3 months compared with 11.3 months for patients who received standard therapy alone. Patients who received Pluvicto plus standard treatment also experienced a median imaging-based progression-free survival of more than five months longer than patients on standard therapy (8.7 months vs. 3.4).

State-of-the-Art Home for Theranostics

Saline drip for chemotherapyPSMA imaging and treatment wasn’t RMCC’s first foray into theranostics. In 2021, we opened the Theranostics Suite at our Denver – Midtown location to provide a specialized PET/CT scan and treatment with the radioactive agent Lutathera for patients with neuroendocrine tumors.

“We knew PSMA imaging and treatment because the initial clinical trials were completed,” Glenn said. “With our experience, it was easy to discern that future molecules were going to receive approval and be available for treatment. Seeing that future coming, we made the commitment to build a larger suite.”

Patients visit the Theranostics Suite to receive six infusions of Pluvicto, with each treatment spaced six weeks apart. We prioritize patient safety, which is why the suite features lead-lined walls and stainless steel, easy-to-clean bathrooms. Our team meticulously follows best practices for storing and handling radioactive isotopes and cleaning the suite, in accordance with our radioactive materials license from the State of Colorado.

Pushing PSMA Targeting Forward

Studies are underway exploring Pluvicto’s potential to treat a larger population of patients with advanced prostate cancer. RMCC participates in these efforts.

“We feel our No. 1 job is to provide the most appropriate treatments for our patients, and one of the hallmarks of RMCC is we are very active in clinical research,” Glenn said. “Participating in clinical research allows our physicians to see and be involved in the future of medicine so when new treatments are approved, we already have experience with them. That puts us in a good position to implement these treatments quickly because we’ve participated in the clinical trials.”

One of these clinical trials is PSMAfore. This phase 3 trial involving patients with PSMA-positive metastatic castrate-resistant prostate cancer who have not received taxane-based chemotherapy compares Pluvicto to a change in androgen receptor pathway inhibitors. In late 2022, Pluvicto maker Novartis announced PSMAfore showed “Pluvicto demonstrated a statistically significant and clinically meaningful improvement in radiographic progression-free survival.”

RMCC is also participating in a phase 3 clinical trial called PSMAddition. This ongoing trial involves patients with metastatic hormone-sensitive prostate cancer. PSMAddition compares Pluvicto plus standard of care with standard of care alone.


A Hopeful Vision for the Future of PSMA Treatment

As studies of Pluvicto continue, Glenn is hopeful the therapy may one day help patients with prostate cancer earlier in the disease’s course.

“New clinical trials are in the works in which patients will receive Pluvicto before they’ve tried other forms of treatment,” he said. “The hope would be, as those clinical trial results come through, they’ll be treating healthier patients sooner. As we know in most instances in medicine, if you treat a disease sooner, you should improve survivability or even get more curative results because you’re detecting the disease earlier.”

Glenn believes Pluvicto has the potential to limit the burden of prostate cancer in healthier patients so they might be able to receive a second course of treatment two or three years after the first. Clinical trial results will provide definitive answers as to the full extent of Pluvicto’s utility. In the meantime, RMCC will continue bringing promising new therapies to our patients.

“PSMA represents a newer area of treatment that I think will continue to evolve because researchers will figure out other targets for other cancers that, in many cases, are still difficult to treat,” Glenn said. “If we can provide a better treatment that solves a problem, that’s what we want to bring to our patients.”

At RMCC, a prostate cancer specialist will partner with you and your patients to create individualized treatment plans that fit their needs. Refer a patient to the organization that treats the most adults with cancer in Colorado.