Pluvicto and Hypertension: Unlikely Direct Causation
While Pluvicto (lutetium-177 PSMA-617) can cause various side effects, hypertension occurring specifically one week after infusion is not a recognized or commonly reported adverse effect of this radioligand therapy.
Understanding Pluvicto's Side Effect Profile
The available evidence from major clinical trials does not identify hypertension as a characteristic toxicity of lutetium-177 PSMA therapy:
In the pivotal VISION trial of 831 patients, the most common grade 3+ adverse events were hematologic (anemia, thrombocytopenia, neutropenia) and constitutional (fatigue), with no specific mention of hypertension as a treatment-related adverse event 1.
The safety profile across multiple studies consistently shows bone marrow suppression, fatigue, dry mouth, and nausea as the predominant toxicities, without hypertension being highlighted as a concern 2, 3.
In the AlphaBet trial combining lutetium-177 with radium-223, grade 3+ treatment-related adverse events included anemia (11%) and neutropenia (8%), but hypertension was not reported among the toxicities 4.
Why This Differs from Other Cancer Therapies
It's important to distinguish Pluvicto from other cancer treatments that DO cause hypertension:
VEGF inhibitors (bevacizumab, sunitinib, sorafenib) cause hypertension in 80-90% of patients through mechanisms involving vascular rarefaction and altered nitric oxide balance 5.
Tyrosine kinase inhibitors and proteasome inhibitors also increase blood pressure, as do adjuvant therapies like corticosteroids and anti-androgen hormone therapy 5.
However, lutetium-177 PSMA-617 is a radioligand therapy with a completely different mechanism of action—delivering targeted beta-particle radiation to PSMA-expressing cells—and does not share the vascular mechanisms that cause hypertension with anti-angiogenic agents 1.
Alternative Explanations to Consider
Given that Pluvicto is unlikely the cause, evaluate these possibilities:
Pre-existing hypertension that was previously undiagnosed or inadequately controlled—prostate cancer patients often have cardiovascular comorbidities 5.
Concurrent medications: Many prostate cancer patients receive corticosteroids (for symptom management), which can elevate blood pressure 5.
Androgen deprivation therapy (ADT): The patient is likely on ongoing ADT for castration-resistant disease, which can contribute to metabolic syndrome and hypertension over time 5.
Pain or anxiety related to cancer progression or treatment, which can transiently elevate blood pressure 5.
Unrelated causes: Essential hypertension, dietary factors, medication non-adherence, or other medical conditions 5.
Clinical Management Approach
If hypertension is confirmed (≥140/90 mmHg on repeated measurements), manage according to standard hypertension guidelines rather than attributing it to Pluvicto 5:
Confirm the diagnosis with home blood pressure monitoring or 24-hour ambulatory monitoring (target <135/85 mmHg for home readings) 5.
Initiate or optimize antihypertensive therapy with ACE inhibitors/ARBs, calcium channel blockers, or thiazide diuretics as first-line agents 5.
Do not discontinue or delay Pluvicto therapy for hypertension alone, as this is unlikely to be the causative agent and the cancer treatment benefit outweighs this manageable cardiovascular risk 5.
Screen for other contributing factors including medication review (especially corticosteroids, NSAIDs), lifestyle factors, and secondary causes if hypertension is severe or resistant 5.
Key Takeaway
The temporal association of hypertension one week after Pluvicto infusion is most likely coincidental rather than causal. Focus on standard hypertension evaluation and management while continuing cancer-directed therapy, as radioligand therapy with lutetium-177 PSMA-617 has demonstrated significant survival benefits in metastatic castration-resistant prostate cancer 1.