Prostate cancer is the second most common cancer in men worldwide, and one of the leading causes of cancer-related mortality in developed countries.

Advanced prostate cancer, which has metastasized to other parts of the body, is particularly challenging to treat, and patients often have a poor prognosis.

However, there is new hope for men with advanced prostate cancer. A promising therapy, called Lu-PSMA, has been shown to extend the lifespan of patients with the disease.

In this article, we will discuss what Lu-PSMA is and how it works, as well as the results of recent clinical trials and its potential as a new treatment option for advanced prostate cancer.

What is Lu-PSMA?

Lu-PSMA is a new type of targeted cancer therapy that uses a radioactive molecule to selectively destroy cancer cells.

The molecule, called Lutetium-177-PSMA (Lu-PSMA), binds to prostate-specific membrane antigen (PSMA), a protein that is overexpressed in most prostate cancer cells. Once attached to the cancer cells, the radioactive particles emitted by the molecule damage their DNA, leading to cell death.

Unlike traditional chemotherapy, which destroys both cancer and healthy cells, Lu-PSMA targets only cancer cells, minimizing side effects and improving treatment tolerability.

Moreover, Lu-PSMA can be delivered repeatedly over time without cumulative toxicity, making it suitable for patients who require long-term treatment.

How does Lu-PSMA work?

The Lu-PSMA therapy is administered intravenously, usually over a period of one or two hours. The treatment is well-tolerated, with low rates of adverse events reported in clinical trials.

After the infusion, the Lu-PSMA molecules circulate in the bloodstream, searching for cancer cells with PSMA receptors.

Once they find their target, they attach to the cell membrane and release their radioactive payload of Lutetium-177 particles, which penetrate the cell and damage its DNA. The damaged cells then either die or stop dividing, reducing the size of the tumor and slowing its growth.

Lu-PSMA has a short half-life, meaning that the radioactivity dissipates rapidly after the infusion, minimizing radiation exposure to healthy tissues.

However, patients still need to be monitored closely for potential side effects, such as low blood cell counts or kidney damage, which can occur in rare cases.

Lu-PSMA clinical trials

Lu-PSMA has shown promising results in several clinical trials, both as a stand-alone therapy and in combination with other cancer treatments.

One of the most significant studies was the TheraP trial, a randomized, open-label, multi-center Phase 2 trial that evaluated the efficacy and safety of Lu-PSMA in men with advanced prostate cancer who had previously received chemotherapy and/or androgen receptor-targeted therapy.

The TheraP trial enrolled 200 patients who were randomized to receive either Lu-PSMA plus best supportive care (BSC) or BSC alone.

The primary endpoint of the study was radiographic progression-free survival (rPFS), which measures the time from treatment initiation to the first radiographic progression or death. Secondary endpoints included overall survival (OS), prostate-specific antigen (PSA) response rate, and safety.

The results of the TheraP trial showed that Lu-PSMA significantly improved rPFS compared to BSC alone, with a median rPFS of 8.7 months in the Lu-PSMA arm versus 3.4 months in the BSC arm.

The Lu-PSMA treatment was also associated with a higher PSA response rate, indicating tumor shrinkage or stabilization, and a lower risk of death (HR=0.69, p=0.031).

Moreover, the Lu-PSMA therapy was well-tolerated, with low rates of severe adverse events reported in both arms.

The most common side effects were dry mouth, fatigue, nausea, and vomiting, which were generally mild or moderate in intensity and resolved within a few days after the infusion.

Potential as a new treatment option for advanced prostate cancer

The positive results of the TheraP trial and other studies suggest that Lu-PSMA has the potential to become a new standard of care for men with advanced prostate cancer who have exhausted other treatment options.

The therapy has several advantages over conventional chemotherapy and hormonal therapies, including:.

Targeted action – Lu-PSMA targets only cancer cells, sparing healthy cells and minimizing side effects.
Repeatable – Lu-PSMA can be delivered multiple times without cumulative toxicity, which could extend the lifespan of patients with advanced prostate cancer.
Personalized – Lu-PSMA is based on the individual PSMA expression pattern of each patient’s tumor, making it a personalized treatment option for prostate cancer.

However, Lu-PSMA is still considered an investigational therapy, and more research is needed to confirm its safety and efficacy in larger patient populations.

Ongoing clinical trials, such as the VISION trial, will evaluate the use of Lu-PSMA in various patient populations, including those with newly diagnosed and metastatic prostate cancer.

In conclusion, Lu-PSMA is a promising new therapy for men with advanced prostate cancer that has shown significant benefits in extending lifespan and reducing tumor burden.

Further research is needed to confirm its place in the treatment landscape for prostate cancer, but it provides renewed hope for men with this challenging disease.