Understanding Radiation Therapy’s Role In Treating Advanced Prostate Cancer

Your doctor will determine if your disease has progressed based on bloodwork, symptoms, and imaging.

Once it is confirmed that your disease in castration-resistant, you doctor may recommend a range of different radiation techniques, including:

• External beam radiation (EBRT) to treat localized symptoms or small metastases
• Radioligand therapy, such as Pluvicto, for widespread disease that is positive for something known as the PSMA protein
• Stereotactic body radiation therapy (SBRT) to treat a small number of metastases in patients with oligometastatic disease (which means the disease has only spread to a few select areas)

Radiation remains a valuable tool even in advanced stages, offering not only symptom control, but in many cases, extended survival and improved quality of life.

Understanding Radiation Options After Hormone Resistance in Metastatic Prostate Cancer

Prostate cancer that has spread beyond the prostate gland — known as metastatic prostate cancer — is often treated initially with hormone therapy. This approach, sometimes called androgen deprivation therapy (ADT), reduces the body’s levels of testosterone, a hormone that fuels the growth of prostate cancer cells.

While this strategy can be highly effective for a time, many patients eventually develop resistance. This means that the cancer continues to grow even when testosterone levels in the body are very low or undetectable. At this point, the disease is referred to as metastatic castration-resistant prostate cancer (mCRPC). Fortunately, even after hormone therapy stops working, several additional treatment options — including different forms of radiation — can still help.

How Will My Doctor Know If I Have Developed Castration-Resistant Disease?

Your doctor will monitor several factors to determine whether your prostate cancer has become castration-resistant. The most common signs include:

• Rising PSA levels despite low testosterone levels
• Progression of symptoms, such as new or worsening bone pain
• Radiographic progression, meaning new or growing tumors are detected on imaging studies (CT, MRI, or bone scans)

A formal diagnosis of castration resistance typically requires documentation of a testosterone level in the castrate range (usually <50 ng/dL) and evidence of disease progression (biochemical, radiologic, or clinical).

Once mCRPC is confirmed, your care team will consider additional treatments tailored to the extent of the disease and your prior therapies.

What Radiation Options Are Available?

Radiation is not just for early-stage prostate cancer. In advanced or metastatic disease, radiation can still play a key role — either as targeted external beam therapy, or systemic radiopharmaceutical therapy. Here’s a look at the primary radiation-based options:

External Beam Radiation Therapy (EBRT)

This approach uses high-energy X-rays to treat specific tumor sites.

EBRT can be used for:

• Treating painful bone metastases
• Controlling local progression in the prostate
• Managing oligometastatic disease (a limited number of metastatic sites)
• Enhancing outcomes when used with systemic treatments

EBRT is non-invasive and typically well-tolerated. It’s especially effective for palliative purposes, such as alleviating pain or preventing fractures in bones affected by cancer.

Radiopharmaceuticals (Systemic Radiation Therapy)

Unlike EBRT, radiopharmaceuticals are radioactive substances that are injected into the bloodstream and travel throughout the body to target cancer cells. These agents deliver internal radiation directly to tumor sites.

A notable example is Pluvicto™ (lutetium-177 PSMA), a radioligand therapy recently approved for patients with PSMA-positive mCRPC. Another is Radium-223 (Xofigo®), which specifically targets bone metastases and is used to relieve symptoms and potentially prolong life.

What is Radioligand Therapy?

Radioligand therapy (RLT) is an innovative treatment that combines a radioactive particle with a molecule that specifically seeks out cancer cells. In prostate cancer, these therapies often target PSMA (prostate-specific membrane antigen), a protein commonly found on prostate cancer cells, especially in advanced disease.

“The radioligand basically is kind of a targeted missile that we connect a radio-particle to the PSMA and this is able to generate a very accurate treatment to the cancer cells, sparing more of the normal tissues, the healthy tissues around the tumor,” Dr. Dal Pra explains.

In Pluvicto (Lu-177 PSMA-617), the ligand binds to PSMA, and the lutetium-177 delivers radiation directly to the cancer cells. Because this approach allows for precise targeting of tumors while sparing healthy tissues, it minimizes side effects. Radioligand therapy is a form of systemic therapy, meaning it can treat multiple metastatic sites throughout the body at once.

Radioligand therapy is typically considered in patients with:

• mCRPC
• Evidence of PSMA-positive disease on a specialized PET scan
• Prior treatment with standard hormone therapies and chemotherapy

Benefits include pain relief, PSA reduction, improved quality of life, and — in many cases — extended survival.

What Are Oligometastases And How Is Radiation Used To Treat Them?

The term oligometastasis refers to a state where cancer has spread, but only to a limited number of sites, often defined as five or fewer. This is an important concept because patients with oligometastatic disease may benefit from aggressive treatment of each individual tumor site.

In this setting, stereotactic body radiation therapy (SBRT) is often used. SBRT delivers very high doses of radiation with pinpoint accuracy, usually over just a few sessions.

It can be used to:

• Delay progression to widespread metastatic disease
• Postpone the need for systemic therapy
• Potentially improve survival outcomes

For prostate cancer patients with limited bone or lymph node metastases, SBRT to these specific areas has shown promising results. In clinical trials, it has helped delay disease progression and maintain quality of life.

This targeted approach is sometimes referred to as metastasis-directed therapy (MDT). Your oncologist may consider MDT in carefully selected cases — especially if the disease appears slow-growing and is confined to just a few sites.

Questions To Ask Your Doctor

• Is radiation therapy an option for me?
• Can we compare the side effects of the different types of radiation?
• How will I be monitored after radiation therapy?
• What can I do to help with side effects?

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