Clinicians in radiation and nuclear medicine at Northwell Health Cancer Institute (NHCI) are offering a new radiopharmaceutical therapy designed to treat patients with metastatic prostate cancer. American Cancer Society (ACS) statistics project that about one in eight men will be diagnosed with prostate cancer in his lifetime, with more than 268,000 new cases being diagnosed in 2022. More than 34,000 men will die of prostate cancer in 2022, according to the ACS.
Approved by the FDA, the new therapy in use at NHCI is designed to "offer hope for prolonged survival and reduced complications from cancer for those who have limited treatment options," according to the organization.
Known as prostate-specific membrane antigen (PSMA) therapy, the treatment is intended to target cancer cells throughout the body and destroy them. PSMA therapy is a radiopharmaceutical consisting of a small molecule carrying a therapeutic radionuclide, explained Michael R. Folkert, MD, PhD, Vice Chair and Chief of Brachytherapy at NHCI Radiation Medicine in the Center for Advanced Medicine. This carrier binds to the outside of a prostate cancer cell and is then internalized, which results in high amounts of radiation being delivered inside the target cancer cells, "damaging their DNA and killing them," he noted.
"Treatment with this radiopharmaceutical has been tested in a randomized clinical trial that showed improved survival for the treated patients over standard-of-care treatment, with reduced rates of complications such as bone fractures or cord compression caused by their metastatic cancer," Folkert continued. "It has also been shown to have a greater impact on reducing PSA values, the tumor marker for prostate cancer, than standard-of-care treatments or cabazitaxel, a second-line cytotoxic therapy."
The drug, known as lutetium-177 or Lu-PSMA, zeroes in on the PSMA protein, which is found in higher amounts in most prostate cancer cells. The drug acts like a magnet to lock on to the PSMA protein in the cancer cell membrane, delivering radiation that damages DNA and destroys cancer cells, according to NHCI, adding that the drug is administered via injection into a vein in the arm.
Typically administered in an outpatient setting, the PSMA therapy takes "only a few minutes for the drug to infuse into the bloodstream," with the excess drug excreted through the bladder. Before treatment, patients receive blood tests and positron emission tomography and computed tomography (PET/CT) diagnostic scans, and they will undergo follow-up laboratory testing and possibly imaging scans to assess the treatments.
In an NHCI statement, the organization's deputy physician-in-chief describes PSMA as a therapeutic as "a game changer for men with metastatic prostate cancer."
"For patients that fit the criteria for this treatment, it is a big opportunity for them, because we are able to offer personalized prostate cancer care when chemotherapy and hormone therapy are not working," noted Louis Potters, MD, Chair of Radiation Medicine at Northwell Health.
Looking ahead at the potential impact this therapy option could have on the way care teams approach the treatment and management of male patients with metastatic prostate cancer, the key question "is when to administer this therapy in the patient's treatment course to maximize benefit," Folkert noted.
Currently, patients receive this therapy after they have developed resistance to androgen deprivation therapy and progressed through multiple lines of systemic treatment, including cytotoxic therapy, he said, adding that trials are in progress to explore the use of PSMA therapy at earlier stages in treatment, including in patients who are still sensitive to androgen deprivation.
In the meantime, complexities in the administration and management of the radiation safety issues around this treatment mean that close collaboration between radiation oncology, nuclear medicine, and medical oncology is needed to best identify patients who will benefit most from this approach.
"Mobility, continence, hematologic reserve, and even social factors play a role due to the need to isolate immediately after treatment, as high amounts of radioactive material are present in patients' bodily fluids that can expose others," Folkert stated. "Investigators are looking into different drug formulations that may make it safer to deliver this treatment, and ways to understand the distribution of the radiation dose delivered by the radiopharmaceutical."
Mark McGraw is a contributing writer.