Side Effects of PSMA Therapy

How well is PSMA therapy tolerated overall?

PSMA therapy is generally described in clinical studies and in real-world practice as well to moderately tolerated. Compared to conventional chemotherapy, the side effect profile is often more targeted and less non-specific, as the radiation predominantly binds to PSMA-expressing tumor cells.

In the large VISION trial (Sartor et al., NEJM 2021), which investigated men with metastatic castration-resistant prostate cancer, treatment-related side effects were observed; however, severe complications occurred only in a subset of patients. As with any systemic therapy, an individualized risk–benefit assessment is essential.

It is important to note: the treatment is not carried out without control. Between individual cycles, blood values and the clinical condition are regularly monitored. A detailed description of this monitoring can be found under Procedure of PSMA Therapy.

Tolerability depends on several factors—including overall health status, bone marrow function, and prior treatments. For this reason, therapy planning is always carried out individually and in a structured manner.

Common Side Effects of PSMA Therapy

Most side effects of PSMA therapy are mild to moderate in severity and temporary. Their extent can vary from patient to patient.

Fatigue

Increased tiredness or reduced physical resilience is among the most common accompanying effects. Patients often report a mild decrease in physical performance in the days or weeks following a treatment cycle.

In most cases, these symptoms improve again between treatment cycles. Adequate rest and an appropriately adjusted daily routine can help manage this phase effectively.

Dry Mouth (Xerostomia)

Since PSMA is also present in small amounts in the salivary glands, temporary dry mouth may occur. This is usually described as mild to moderate.

In most cases, these symptoms are temporary. If they persist, supportive measures—such as adequate fluid intake or saliva substitutes—can be helpful.

Changes in Blood Counts

As this is a systemic radioligand therapy, the bone marrow may also be temporarily affected. Possible changes include:

• Red blood cells (anemia)
• White blood cells (leukopenia)
• Platelets (thrombocytopenia)

These changes are detected early through regular laboratory monitoring.

In most cases, these alterations are temporary and well manageable. Severe changes in blood counts occur comparatively rarely.

Less Common Side Effects

In addition to the more frequent, generally mild side effects, less common adverse effects may also occur during PSMA therapy. Overall, these are rare but should be assessed in a medical context.

Nausea or Reduced Appetite

In individual cases, patients report temporary nausea or a reduced food intake. Preventive medication administered on the day of treatment can help reduce this risk.

Temporary Changes in Kidney Function

As the radiolabeled therapeutic agent is primarily excreted via the kidneys, changes in laboratory values may occur in patients with pre-existing renal impairment. For this reason, kidney function is monitored regularly.

More Pronounced Changes in Blood Counts

In rare cases, more significant changes in blood counts may occur. This primarily affects patients with a high tumor burden or with bone marrow already compromised by prior therapies.

In such situations, it may be necessary to adjust treatment intervals or temporarily pause therapy. These decisions are made on an individual basis and under close medical supervision.

Severe or life-threatening complications are overall rare. A structured evaluation of the indication - as described under Indication for PSMA Therapy - helps to realistically assess the individual risk.

Does PSMA Therapy Affect the Bone Marrow?

PSMA therapy is a systemic radioligand therapy. This means that the therapeutic agent is distributed throughout the body via the bloodstream. In addition to tumor cells, the bone marrow may also be affected to some extent.

The bone marrow is responsible for the production of:

• Red blood cells (oxygen transport)
• White blood cells (immune system)
• Platelets (blood clotting)

During therapy, a temporary decrease in these cell lines may occur. In most cases, these changes are mild to moderate and recover between treatment cycles.

For this reason, regular laboratory monitoring is performed between treatments. This allows potential changes to be detected early and adjustments to be made if necessary.

An increased risk of more pronounced bone marrow changes exists particularly in:

• Advanced disease with a high tumor burden
• Multiple prior treatments (e.g., chemotherapy)
• Pre-existing abnormalities in blood counts

These factors are carefully considered as part of the evaluation of the indication for PSMA therapy.

Overall, it can be stated: Bone marrow involvement is possible, but it is systematically monitored and individually assessed.

Radiation Exposure and Long-Term Risks

PSMA therapy uses a radiolabeled therapeutic agent, most commonly Lutetium-177. This isotope emits so-called beta radiation, which has a very short range in tissue. The radiation acts predominantly where the agent has bound to PSMA-positive tumor cells.

The range of this radiation is only a few millimeters. As a result, primarily the immediate tumor tissue is affected, while more distant healthy tissue is largely spared.

The radioactivity remaining in the body decreases continuously and is largely excreted via the kidneys. No permanent or long-term radioactivity remains in the body.

According to current scientific evidence, severe long-term radiation damage is rare. Nevertheless, the therapy is only recommended when the expected medical benefit outweighs the potential risks.

The treatment is carried out under strict legal radiation protection regulations and standardized nuclear medicine protocols, ensuring that exposure is limited to what is medically necessary.

How Common Are Severe Side Effects?

Severe side effects during PSMA therapy are overall significantly less common than mild or moderate adverse effects, but they can occur.

In the VISION trial (Sartor et al., NEJM 2021), which investigated men with metastatic castration-resistant prostate cancer, higher-grade adverse events (grade 3 or 4) were observed in a subset of treated patients. These most commonly involved changes in blood counts.

However, proper interpretation is important:

• Severe complications were not the norm
• Most side effects were manageable
• Treatment discontinuation due to side effects occurred in only a very small proportion of patients

The severity of side effects is assessed according to internationally standardized criteria (CTCAE classification). Grade 3 or 4 adverse events do not automatically indicate life-threatening conditions, but rather describe a medically significant level that may require closer monitoring or more intensive management.

Close monitoring between treatment cycles is essential. Through regular laboratory testing and clinical assessment, potential changes can be detected early and appropriate measures can be taken.

Individual tolerability depends strongly on pre-existing conditions, bone marrow function, and tumor burden. These factors are already taken into account during the evaluation of the indication for PSMA therapy.

What Happens If Side Effects Occur?

If side effects occur during PSMA therapy, an individual medical evaluation is carried out. The goal is to relieve symptoms and, if possible, to safely continue the therapy.

Depending on the type and severity of side effects, several measures are available:

• Adjustment of treatment intervals – The time between cycles can be extended to allow the body more time to recover
• Dose adjustment – In certain cases, the administered activity can be modified
• Supportive medication – For example, for nausea or pronounced fatigue
• Temporary treatment pause – If laboratory values or overall condition require it
• Discontinuation of therapy – In rare cases, if the risk–benefit ratio is no longer favorable

Regular monitoring between treatment cycles serves precisely to detect changes at an early stage.

It is important to understand: side effects usually do not develop suddenly or go unnoticed. Through structured monitoring, medical adjustments can be made in a timely manner.

Decisions regarding further management are always made on an individual basis and in close coordination with our experienced medical team.

Who Is at Increased Risk for Side Effects?

PSMA therapy is generally well manageable; however, certain factors may increase the risk of more pronounced side effects.

An increased risk may be present in:

• Pre-existing bone marrow impairment, for example after multiple courses of chemotherapy
• High tumor burden, particularly with skeletal involvement
• Existing abnormalities in blood counts prior to treatment
• Impaired kidney function
• Advanced age in combination with multiple comorbidities

These factors do not automatically mean that treatment is not possible. However, they require particularly careful monitoring.

Through regular laboratory testing and structured follow-up, potential complications can be detected early and managed accordingly.

Individual Risk–Benefit Assessment

The decision to proceed with PSMA therapy is based not only on its potential effectiveness, but always also on a careful assessment of benefits and risks.

In advanced prostate cancer, the primary goal is often disease control. The aim of therapy is to slow progression and gain additional survival time. At the same time, it must be evaluated whether potential side effects are acceptable in the individual case.

Several factors play a role in this assessment:

• Overall health status
• Bone marrow function
• Previous treatments
• Current tumor burden
• Individual physical resilience

The structured evaluation of these factors is carried out as part of the Indication for PSMA Therapy.

Frequently Asked Questions About Side Effects of PSMA Therapy

Is PSMA Therapy Dangerous?

PSMA therapy is generally considered a well-controlled and targeted treatment. Like any effective therapy, it can cause side effects. Severe complications are overall rare and are detected early through regular monitoring.

Does PSMA Therapy Cause Hair Loss?

Complete hair loss, as seen with some chemotherapy regimens, is highly atypical with PSMA therapy. The treatment specifically targets PSMA-expressing tumor cells and does not non-selectively affect all rapidly dividing cells.

Are Side Effects Permanent?

Most side effects are temporary and resolve between treatment cycles. According to current scientific evidence, permanent severe long-term effects are extremely rare.

Should I Expect Significant Immune Suppression?

The therapy can affect blood counts, particularly red blood cells. In most cases, these changes are mild to moderate. Regular laboratory monitoring helps detect clinically relevant deviations at an early stage.

How Long Does Fatigue Last?

Fatigue may occur after a treatment cycle and can last for several days to weeks. Its severity varies individually and depends, among other factors, on overall health status and prior treatments.

Can Severe Complications Occur?

Severe side effects are possible but occur relatively rarely. In clinical studies, they most commonly involved changes in blood counts. Through structured monitoring and individualized treatment adjustments, the risk can be reduced.