The Rise of Radiopharmaceuticals in Prostate Cancer – New Atomic Treatments

Atomic therapy or molecular therapy, as radiopharmaceutical treatment is also known, has attracted growing interest in prostate cancer treatment in recent years. This renewed interest has substantially improved outcomes, and research is breaking new ground. Although radiopharmaceuticals have long been used in prostate cancer, much remains to be learned. Recent developments suggest that we may only be beginning to discover their potential.

What Is a Radiopharmaceutical?

Radiopharmaceuticals contain radioactive substances and are used for medical imaging or treatment. They target particular cells or tissues, delivering radiation to those locations. In cancer, they deliver radiation directly to tumor cells to control disease or relieve symptoms.

They are called atomic or molecular treatments because radioactive substances are used in a targeted way at the atomic level. By targeting particular molecules, such as PSMA on prostate cancer cells, or particular cells, radiopharmaceuticals deliver radiation to tumors. These molecular interactions directly damage tumors, hence the names atomic or molecular therapy.

The History of Radiopharmaceuticals: Early Steps

Radiopharmaceuticals have a long history in prostate cancer. Strontium-89 chloride (Metastron) and samarium-153 (Quadramet) have been used for pain relief for many years. Both were FDA-approved in the 1990s, although samarium-153 was later withdrawn from the market.

2 FDA Approvals:

• In 2013, FDA approval was granted for metastatic castration-resistant prostate cancer (mCRPC) with symptomatic bone metastases but no visceral metastases, using radium-223 (Xofigo).
• In 2022, lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617, Pluvicto) was approved for PSMA-positive mCRPC following an androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy.

How Targeted Molecular Radionuclide Therapies Work

Lutetium Lu 177 vipivotide tetraxetan binds prostate-specific membrane antigen (PSMA) on prostate cancer cells to both image and destroy tumor cells.

Radioactive peptides given intravenously (lutetium Lu 177 vipivotide tetraxetan) attach to targeted cancer cells, emit substantial radiation, and can destroy them. Patients may need to remain in hospital for several days afterward. Treatment generally requires 4-6 cycles.

PSMA-Targeted Therapies: Efficacy and Safety

Interest has revived particularly following approval of PSMA-617 (Lu 177) in recent years. PSMA-targeted radioligand therapy improved overall survival in patients whose cancer progressed despite advanced treatments such as hormone therapy and docetaxel. It is also better tolerated than chemotherapy. Main adverse effects include dry mouth and bone marrow toxicity, while nausea, vomiting, and neuropathy common with chemotherapy are generally not observed.

Hematologic toxicity (reduced blood counts) is generally mild, allowing patients to maintain quality of life and spend time with family despite often receiving late-line treatment. Some develop resistance or mixed responses to 177Lu-PSMA-617, however. Caution is also needed, particularly in patients at risk of kidney injury.

A Multidisciplinary Approach and Treatment Safety

Safe use requires a multidisciplinary approach. Contact with other people must be limited after treatment, especially once infusion is complete, because agents such as 177Lu-PSMA-617 contain radioactive components covered by detailed FDA safety instructions. Collaboration between medical oncology, nuclear medicine, and interventional radiology can sometimes complicate care coordination. Planning involving every team is therefore essential for radiation safety and a smooth treatment process.

New Agents and Combinations: Promising Research

Researchers continue intensive work on new radionuclides and ligands to improve on agents such as PSMA-617. Actinium-225 and lead-212 are being tested with more effective ligands to improve tumor targeting. At ESMO 2024, a study showed that the new radiopharmaceutical 177Lu-PNT2002 delayed progression in mCRPC. Such combination treatments have the potential to prolong survival.

PEACE-3, evaluating radium-223 with enzalutamide and bone-protective agents in mCRPC with bone metastases, also produced promising radiographic progression-free and overall survival findings. These results suggest that new, effective options may be approaching, particularly for patients with bone metastases.

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The Importance of Earlier Use: New Trials

Interest is growing in earlier use of radiopharmaceuticals. UpFrontPSMA showed improved outcomes with 177Lu-PSMA-617 plus docetaxel and androgen deprivation therapy in newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC). Significant reductions in prostate-specific antigen (PSA) were also observed, demonstrating the potential of earlier use.

The Future of Radiopharmaceuticals: Much Remains to Be Learned

Data on long-term kidney injury risks remain insufficient, and further research is clearly needed. Better understanding microscopic absorbed doses is critical to improving efficacy. I believe that advances in PSMA-targeted treatment are only beginning and that greater discoveries lie ahead.

One thing is clear: radiopharmaceuticals are transforming prostate cancer treatment. They can offer hope to more patients in the years ahead. I believe that new agents, earlier use, and multidisciplinary approaches will help this treatment modality succeed.