Targeted Radiation For Advanced Prostate Cancer
- Radioligand therapy, such as Pluvicto, delivers targeted radiation to prostate cancer cells by binding to PSMA, a protein commonly found on these cells, while minimizing damage to healthy tissue.
- It is approved for men with metastatic castration-resistant prostate cancer who have already undergone other hormone-based treatments and have PSMA-positive disease confirmed by a PET scan.
- Pluvicto has been shown to improve survival and reduce symptoms, although it can cause side effects such as dry mouth, fatigue, and low blood counts.
“Radioligand therapy is the use of IV treatments that contain a molecule that seeks out a particular target, somewhere in your body, and then once it latches onto that target, releases a dose of radiation,” Dr. Janaki Sharma, a medical oncologist at Sylvester Comprehensive Cancer Center-University of Miami Health System, tells SurvivorNet.
Read MoreWhat Is Radioligand Therapy?
Radioligand therapy is a cutting-edge cancer treatment that merges two powerful concepts: the targeting accuracy of drug therapy and the cell-killing ability of radiation. This innovative approach uses a molecule (called a ligand) that specifically seeks out and binds to cancer cells. This ligand is chemically linked to a radioactive isotope, forming a “radioligand.”Once injected into the body, the radioligand travels through the bloodstream and binds to receptors found mostly on cancer cells — delivering radiation directly to the tumor site. This allows high doses of radiation to be delivered with precision, limiting damage to surrounding healthy tissue.
This approach is particularly effective in cancers like prostate cancer, where certain surface proteins such as PSMA are heavily expressed. By combining molecular targeting with internal radiation, radioligand therapy offers a promising treatment for advanced cancers that have spread beyond the prostate and are resistant to other treatments.
What Is Pluvicto?
Pluvicto (also known as lutetium Lu 177 vipivotide tetraxetan) is a form of radioligand therapy approved by the FDA for treating certain types of advanced prostate cancer. It is specifically indicated for patients with metastatic castration-resistant prostate cancer (mCRPC) who have already received other treatments like chemotherapy and androgen receptor pathway inhibitors but whose disease has continued to progress.
It can also be used for patients who have been treated with an ARPI as a way to delay chemotherapy.
Pluvicto consists of two parts: a ligand that targets PSMA, and a radioactive isotope called lutetium-177. When injected, this compound hones in on PSMA-expressing cancer cells, delivering localized radiation. Because it works systemically, it can treat not only the main tumor but also metastases — cancerous lesions that have spread throughout the body.
How Does Pluvicto Target Prostate Cancer Cells?
Pluvicto uses the PSMA molecule as a target because the protein is often found on the surface of prostate cells. While normal prostate cells have some PSMA, prostate cancer cells — especially those in advanced or aggressive stages — have a significantly higher concentration of it.
The ligand component of Pluvicto binds tightly to PSMA. Once attached, the radiolabeled component, lutetium-177, emits beta radiation over a short distance — typically a few millimeters. This radiation damages the DNA of the nearby cancer cells, causing them to die. The proximity effect of this therapy is crucial; it ensures that healthy tissues, which either don’t express PSMA or express very little of it, are exposed to far less radiation than the cancer cells.
Who Is Eligible for Pluvicto?
Pluvicto is not intended for all patients with prostate cancer. It is approved for use in men with metastatic castration-resistant prostate cancer (mCRPC) — a form of prostate cancer that no longer responds to traditional hormone therapy and has spread to other parts of the body. Based on the results of the PSMAfore Trial, the FDA recently approved Pluvicto for use after treatment failure with an androgen receptor pathway inhibitor.
To be eligible, patients generally must have:
- Confirmed mCRPC
- Progressed after at least one androgen receptor pathway inhibitor
- Evidence of PSMA-positive disease, confirmed via imaging
Importantly, eligibility hinges on whether the cancer expresses PSMA. That’s where an imaging test known as a PSMA PET scan comes in.
What Is A PSMA PET Scan & Why Does It Matter?
A PSMA PET scan is a specialized imaging test that can detect prostate cancer cells based on their expression of the PSMA protein. During this scan, a radioactive tracer that binds to PSMA is injected into the body. Areas that light up on the scan indicate PSMA-positive disease, helping doctors determine whether Pluvicto is likely to be effective.
This scan is critical because Pluvicto only works if PSMA is present on the cancer cells. If a patient has PSMA-negative or low-expressing tumors, the radioligand may not bind effectively, and the treatment may be less beneficial.
How Often Will I Be Treated?
Pluvicto is typically administered once every six weeks, with up to six treatment cycles, depending on how well the patient responds and whether side effects are manageable. Each treatment is done via intravenous (IV) infusion in a clinic or hospital, and the process usually takes a few hours from start to finish.
Before each treatment cycle, patients may undergo lab tests and imaging to monitor how the cancer is responding and to check for any side effects or toxicity, particularly to bone marrow and kidneys.
Pluvicto Risks vs. Benefits
For eligible patients, Pluvicto offers several potential benefits, including:
- Improved survival: Clinical trials have shown that Pluvicto can extend overall survival in patients with advanced, treatment-resistant prostate cancer.
- Symptom relief: Many patients experience reduced pain and improved quality of life, particularly if their disease has spread to the bones.
- Targeted action: Compared to traditional chemotherapy, radioligand therapy causes less damage to healthy tissues, which may result in fewer severe side effects.
- Systemic reach: Because it circulates throughout the body, Pluvicto can treat cancer in multiple locations at once, including hard-to-reach metastases.
While it is not a cure, it offers a meaningful option for patients with otherwise limited therapeutic choices.
However, like any cancer treatment, Pluvicto can cause side effects. Most are related to the way the radioactive compound behaves in the body.
“Unfortunately, there are some normal parts of your body that also express PSMA — places like the salivary gland or the liver — and so the side effects that we see from Lu-177 PSMA therapy typically come from getting radioactivity to places in the body where we don’t intend it,” Dr. Sharma explains.
“That may mean dry mouth, it may mean skin changes, it may mean fatigue overall from radiation therapy,” she adds.
Common side effects include:
- Fatigue
- Nausea or vomiting
- Dry mouth (xerostomia) due to salivary gland uptake of radiation
- Loss of appetite
- Mild bone marrow suppression, which can lead to decreased blood counts (anemia, low white blood cells, or platelets)
Rare but serious side effects may include kidney issues, especially in patients with pre-existing renal disease, or more severe bone marrow suppression. For this reason, patients are closely monitored with blood tests before each dose.
Questions To Ask Your Doctor
- Am I eligible for radioligand therapy?
- Have I or can I undergo a PSMA PET scan?
- How often will I be monitored while undergoing this therapy?
- What side effects should I expect?
- What sort of steps can I take to manage side effects?
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