What are the safety considerations for Prostate-Specific Membrane Antigen (PSMA) Lutetium-177 therapy in patients with cardiac conditions?

Safety of PSMA Lutetium-177 Therapy in Cardiac Patients

Lutetium-177 PSMA therapy appears safe in cardiac patients, with no significant cardiotoxicity demonstrated in clinical studies, though baseline cardiac assessment and monitoring following standard cardio-oncology protocols is prudent given the lack of long-term cardiac-specific data. 1

Evidence for Cardiac Safety

The most direct evidence comes from a dedicated cardiotoxicity study evaluating both Lu-177-DOTATATE and Lu-177-PSMA therapy:

• No cardiovascular events occurred during follow-up periods of 4-31 months in patients receiving Lu-177-PSMA therapy 1
• Troponin I levels remained normal before and after treatment (median 0.26 vs 0.30 ng/ml, p>0.05), indicating no myocardial injury 1
• No significant elevation in cardiac biomarkers was detected 48 hours post-treatment across 39 treatment cycles 1

This contrasts sharply with traditional chemotherapy agents like anthracyclines, which show well-documented cardiotoxicity requiring intensive monitoring 2.

Pre-Treatment Cardiac Assessment

While Lu-177-PSMA lacks specific cardiac toxicity, applying established cardio-oncology principles is reasonable:

Baseline evaluation should include:

• Clinical history focusing on prior cardiac disease, hypertension, diabetes, and previous cardiotoxic therapies 2
• ECG to establish baseline rhythm and detect pre-existing abnormalities 2
• Echocardiography with LVEF assessment in patients >60 years or with cardiovascular risk factors 2
• Lipid profile and blood pressure documentation 2

Monitoring During Treatment

Standard Lu-177-PSMA protocols involve 4-6 cycles at 6-week intervals with 7.4 GBq per cycle 3, 4. During this period:

• Hematologic monitoring before each cycle is mandatory, as myelosuppression is the primary toxicity concern 3, 4
• Renal and hepatic function assessment before each treatment cycle 4
• Cardiac-specific monitoring can follow general oncology surveillance rather than intensive protocols required for anthracyclines 2

The absence of direct cardiac toxicity means that intensive cardiac monitoring protocols used for anthracyclines (every 12 weeks, serial LVEF measurements) are not necessary for Lu-177-PSMA 2.

Clinical Context and Risk Stratification

Grade 3-4 adverse events occur in only 33% of Lu-177 patients compared to 53% with alternative treatments like cabazitaxel, with toxicity primarily hematologic rather than cardiac 3, 4. This favorable safety profile extends to cardiac patients.

Patients with pre-existing cardiac disease can proceed with Lu-177-PSMA therapy provided:

• Cardiac status is stable and optimized 2
• Standard cardiovascular risk reduction measures are implemented (blood pressure control, lipid management, smoking cessation) 2
• No contraindications exist for the required hydration protocols 4

Important Caveats

Long-term cardiac surveillance data beyond 31 months is limited 1. While radiotherapy to the chest can cause late cardiac complications (coronary disease, pericarditis, valvular disease), these typically manifest years after treatment and are dose-dependent 2. The systemic nature and lower radiation doses to the heart with Lu-177-PSMA make such complications unlikely, but very late cardiac toxicities cannot be definitively ruled out 2.

Radiation-induced cardiac injury from external beam radiotherapy requires decades to manifest and involves direct cardiac irradiation 2. Lu-177-PSMA delivers targeted beta radiation to PSMA-expressing tissues, with minimal cardiac uptake in the absence of cardiac metastases 1.

Practical Algorithm

1. Screen for cardiac risk factors (age >60, hypertension, diabetes, prior cardiac disease, previous cardiotoxic therapy) 2
2. Obtain baseline ECG and clinical assessment in all patients 2
3. Add baseline echocardiography only if risk factors present 2
4. Proceed with standard Lu-177-PSMA protocol (4-6 cycles at 6-week intervals) 3, 4
5. Monitor hematologic, renal, and hepatic function before each cycle 4
6. Reserve cardiac imaging for patients developing cardiac symptoms, not routine surveillance 2
7. Maintain cardiovascular risk reduction throughout treatment 2

The key distinction is that Lu-177-PSMA does not require the intensive cardiac monitoring protocols mandated for anthracyclines or trastuzumab, as it lacks their direct cardiotoxic mechanisms 2, 1.