Discussion
Treatment with [¹⁷⁷Lu]PSMA-RL is based on the ligand binding to PSMA cell membrane receptors. A prerequisite for the treatment is therefore a high number of PSMA receptors in the prostate cancer cells, and this is assessed beforehand with [⁶⁸Ga]PSMA-11 PET/CT (1, 2). After binding to a PSMA receptor on the cell surface, the antigen-ligand complex is internalised in the cell, and this is followed by internal radiation with the beta particles emitted from Lutetium-177. The concentration of energy deposition is high enough to cause considerable radiation damage to DNA and subsequent death of the cancer cells, with low-degree damage to normal surrounding tissue. Renal excretion and physiologically high uptake in salivary glands expose the kidneys and salivary glands to risk, but the standard treatment our patient received is reported to be well tolerated with seldom severe adverse effects (1).
To evaluate response, p-PSA is measured, and CT and/or [⁶⁸Ga]PSMA-11 PET/CT are/is repeated. A randomised phase 3 trial (VISION) showed that treatment with [¹⁷⁷Lu]PSMA-617 (Pluvicto) in addition to standard treatment prolonged overall survival (median 15.3 months) compared to standard treatment alone (median 11.3 months) (1).
Both [⁶⁸Ga]PSMA-11 and [¹⁷⁷Lu]PSMA-RL target PSMA cell membrane receptors, thus forming what is called a theranostic pair. Theranostics is a portmanteau of therapeutics and diagnostics, and describes the coupling of a diagnostic biomarker and a therapeutic agent that have a common target, as seen here with PSMA.
Expectations are high for ongoing trials investigating treatment efficacy in combination with specific pharmaceuticals and treatments administered at an earlier stage of the disease than in the VISION trial (3, 4).
Our patient was not, however, treated with [¹⁷⁷Lu]PSMA-617, but [¹⁷⁷Lu]PSMA-I&T. The moiety that binds to the PSMA receptor is identical, and the only difference lies in the moiety that binds together the receptor substrate and the moiety that binds Lutetium-177. Trials have shown equal treatment efficacy for the two medications (5).
This case report describes one of the two patients we are aware of who have been treated with [¹⁷⁷Lu]PSMA-RL in Norway under the compassionate use programme. Selected patients have received the treatment abroad (primarily in Germany and Finland), where costs have been covered by the Norwegian Health Economics Administration (HELFO) (upon approval by the Office for Treatment Abroad), or they have been privately funded.
Treatments with [¹⁷⁷Lu]PSMA-RL have been introduced in the United States, Australia and several countries in Europe. The pharmaceutical was approved by the European Medicines Agency in December 2022. The Norwegian Institute of Public Health published a health technology assessment in June 2023 (6). In January 2024, Norway's Decision Forum decided against its introduction in the country as 'there is no evidence that clinical benefit justifies the cost' (7). However, the Norwegian Hospital Procurement Trust is called on to resume price negotiations with the supplier, and if new information and results emerge, this decision can be reconsidered (7).