Radioligand Therapy After Resistance: What To Expect With Pluvicto

Hormone therapy, also known as androgen deprivation therapy (ADT), is the cornerstone of treatment for advanced prostate cancer. It works by reducing testosterone levels, a hormone that fuels the growth of prostate cancer cells. This approach can be remarkably effective, often slowing or halting the progression of the disease for months or even years.

However, most patients eventually experience what’s known as castration-resistant prostate cancer (CRPC) — a form of the disease that continues to grow despite low testosterone levels.

“Eventually, the prostate cancer cells figure out a way to grow despite not having access to testosterone or androgens. When they start to grow, even though a patient has zero testosterone, that patient progresses into a state of disease that we call castration-resistant prostate cancer,” Dr. Janaki Sharma, a medical oncologist at Sylvester Comprehensive Cancer Center-University of Miami Health System, tells SurvivorNet.

Typically, resistance to hormone therapy develops within 2 to 3 years. At this point, the cancer becomes more aggressive and requires alternative treatment strategies. Fortunately, research and pharmaceutical innovation have expanded the options available to patients—that’s where options like Pluvicto (lutetium-177 vipivotide tetraxetan) come in.

Radioligand therapy is a targeted treatment that delivers radiation directly to prostate cancer cells.

Radioligand Therapy: How It Works

Radioligand therapy (RLT) is a form of targeted radiation treatment that delivers radioactive particles directly to cancer cells while sparing most healthy tissue. This method combines two components:

• A ligand: A molecule that binds specifically to a target on the surface of cancer cells (in this case, the Prostate-Specific Membrane Antigen or PSMA)
• A radioactive isotope: This emits energy that destroys the targeted cancer cells once the ligand has guided it to its destination

This dual-action approach allows radioligand therapy to attack cancer with a high degree of precision, minimizing damage to surrounding healthy tissue and reducing many of the side effects typically associated with traditional radiation therapy.

In prostate cancer, radioligand therapy targets a protein called PSMA, which is found in large amounts on the surface of prostate cancer cells, particularly in metastatic or treatment-resistant disease.

The treatment works as follows:

• The ligand binds specifically to PSMA on the surface of cancer cells
• Once bound, the radioactive isotope (lutetium-177) emits beta particles that destroy the cancer cell from the inside
• Over time, repeated treatments can significantly reduce tumor burden and slow disease progression

Because PSMA is highly expressed on prostate cancer cells but present in low levels elsewhere in the body, this therapy allows for highly selective targeting of tumors with limited collateral damage.

“Patients can get access to this therapy from different doctors,” Dr. Sharma explains. “At some institutions, radiation oncologists are the ones administering this treatment. In other places, it may be administered in an infusion center by a medical oncologist or it may be administered by a nuclear medicine provider.”

Who Can Get Radioligand Therapy?

Pluvicto (lutetium-177 vipivotide tetraxetan) is an FDA-approved radioligand therapy designed for men with advanced prostate cancer that no longer responds to hormone therapy and has spread to other parts of the body. Specifically, Pluvicto is indicated for patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have already received other treatments, including androgen receptor pathway inhibitors and chemotherapy.

Pluvicto represents a new era in prostate cancer therapy, offering personalized and targeted treatment based on the molecular features of an individual’s tumor.

Pluvicto is generally considered for patients who meet the following criteria:

• Confirmed diagnosis of metastatic castration-resistant prostate cancer (mCRPC)
• Disease progression despite previous treatment with hormone therapy (Androgen Receptor Pathway Inhibitor)
• PSMA-positive disease, confirmed through specialized imaging such as PSMA PET scan

The PSMA PET scan is crucial, as it ensures that the cancer cells express enough PSMA for the drug to bind effectively. If a patient’s cancer is not PSMA-positive, Pluvicto is unlikely to be effective.

In March 2025, Pluvicto was approved for the treatment of metastatic castration resistant prostate cancer before starting chemotherapy based on the results of the recent PSMAfore Trial.

The benefits of this treatment approach include improved survival, tumor shrinkage, and better quality of life (based on factors like fewer side effects and less time spent in the hospital).

What Are The Side Effects?

Like all cancer treatments, radioligand therapy carries potential side effects, though they tend to be milder than those of conventional chemotherapy.

Common side effects include:

• Fatigue
• Nausea
• Dry mouth (xerostomia) – due to PSMA expression in the salivary glands
• Loss of appetite
• Decreases in blood counts – such as anemia or low white blood cell count
• Mild diarrhea or constipation

In some cases, more serious side effects such as bone marrow suppression or kidney problems may occur, particularly in patients with preexisting conditions. Regular monitoring of blood work, kidney function, and overall health is essential during treatment.

Precautions For Radioligand Therapy

Because Pluvicto (lutetium-177 vipivotide tetraxetan) contains a radioactive isotope, radiation safety precautions must be followed to protect others, especially family members and caregivers.

These may include:

• Maintaining physical distance from others (especially children and pregnant women) for several days after each dose
• Flushing the toilet twice after each use and practicing good hygiene
• Limiting close contact for a few days post-treatment to avoid exposing others to residual radioactivity
• Hydration – Patients are advised to stay well-hydrated to help flush the radioisotope from the body
• Monitoring for side effects – Routine follow-up appointments and lab work are essential to monitor for potential complications, including bone marrow suppression or kidney function changes

Patients are typically treated every six weeks for up to six cycles, depending on how well they tolerate the drug and how their disease responds.

Questions To Ask Your Doctor

• Am I eligible for treatment with Pluvicto (lutetium-177 vipivotide tetraxetan)?
• Can I undergo a PSMA PET scan to test my eligibility?
• What are the risks and benefits of this treatment approach?
• What precautions should I take before and after treatment?

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