Metastatic hormone-sensitive prostate cancer could eventually be managed as a chronic condition rather than a terminal diagnosis, according to findings from the PSMAddition clinical trial published in The Lancet.
Researchers found that adding radioligand therapy to standard hormonal treatment reduced the relative risk of radiological progression or death by nearly one-third, La Presse Canadienne reported. The study, which involved approximately 1,150 patients across 20 countries, marks the first phase 3 trial to demonstrate the benefits of this combined approach at this specific stage of the disease.
"New-generation hormone therapy is the best treatment worldwide for someone with newly diagnosed metastases," said Dr. Fred Saad, a prostate cancer specialist at the University of Montreal Hospital Centre, as reported by La Presse Canadienne. "Patients do well with it. We’ve shown that it prolongs life and delays progression. We wanted to see if we could do even better by adding this radioligand treatment."
The therapy uses ligands and radio-isotopes to target and destroy cancer cells throughout the body. In this trial, Dr. Saad and his colleagues utilized lutetium-177 to deliver radiation specifically to cancer cells expressing the PSMA protein on their surface.
While radioligand therapy is currently used as a last resort for patients who have exhausted other options—achieving a death reduction of approximately 40% in that setting—the study aimed to determine the impact of earlier intervention. "We exceeded expectations in terms of delaying the progression of metastases or all-cause mortality," Dr. Saad told La Presse Canadienne. "It indicates to us in part that sooner is better than later, before we start having resistance, because unfortunately, the cancer develops mechanisms that resist almost everything we can give."
Initial results indicate a 28% reduction in the relative risk of radiological progression or death, though unpublished data from the study suggests that figure may reach 40%, according to La Presse Canadienne. Beyond slowing disease progression, the treatment showed high efficacy in lowering PSA levels, with nearly 90% of treated patients seeing these proteins drop to undetectable levels.
The most frequently reported side effect, occurring in approximately 5% of participants, was dry mouth. Looking ahead, Dr. Saad said that the primary challenge will be to identify which patients are most likely to benefit from this strategy through personalized medicine.
"I hope that one day we will be able to say that we can cure patients who have metastases, which would have been unthinkable not long ago," Dr. Saad told La Presse Canadienne. "We are starting to see glimmers of hope to prolong life and transform a deadly disease into a chronic disease."
How does radioligand therapy work for prostate cancer?
The treatment uses specific molecules called ligands labeled with radio-isotopes, such as lutetium-177, to locate and bind to the PSMA protein found on the surface of prostate cancer cells. Once attached, the radio-isotope delivers targeted radiation to destroy the cancer cells wherever they are located in the body.
What is the significance of the PSMAddition trial?
The trial is the first phase 3 study to evaluate the effectiveness of combining radioligand therapy with standard hormone treatment for patients with newly diagnosed metastatic hormone-sensitive prostate cancer. The study aimed to see what impact the treatment would have if introduced earlier in the progression of the disease, as soon as metastases are detected.
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