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The following text has been machine translated from the German with no human editing.
Prostate cancer, when detected early, is generally treatable. Many patients whose tumour is detected at an early stage have a good prognosis. However, the situation becomes more difficult if the cancer is detected at a late stage. It can then spread to other parts of the body, where it forms metastases. Such metastatic prostate cancers are significantly more difficult to treat, and in some cases there is little chance of defeating the cancer, particularly if the cancer cells are also ‘castration-resistant’. This means that they continue to grow and multiply, even though levels of the male sex hormone testosterone – which is essential for tumour growth – have been significantly reduced by hormone therapy.
In recent years, PSMA radioligand therapy has emerged as one of the most important innovations in the treatment of these metastatic castration-resistant prostate cancers (mCRPC). Over the past decade, the Department of Nuclear Medicine at Saarland University Hospital, led by Professor Samer Ezziddin, has become an international pioneer in this form of therapy. In this therapy, a radioactive substance – in this case the isotope lutetium-177 – is targeted specifically to tumour cells and irradiates them from within, after being taken up into the cells via the prostate-specific membrane antigen (PSMA).
“However, the treatments established to date largely involve fixed dosages. Many patients with impaired organ function or in a poorer general condition therefore do not meet the criteria for large clinical trials and are consequently often unable to benefit from this therapy,” says Samer Ezziddin, explaining a fundamental problem. Many patients are “too ill” to be eligible for the therapy.
The Homburg-based researchers, led by the Professor of Nuclear Medicine at Saarland University, are therefore pursuing a different approach: in the study now presented, they treated patients who are particularly difficult to treat with individualised dosages, even though existing guidelines stipulate only a standard dosage. Factors such as kidney function, blood count, tumour burden, disease progression and clinical condition were taken into account in determining the dosage.
This study, the largest single-centre study of its kind worldwide to date, is based on data from the REALITY registry of the Department of Nuclear Medicine. The patients studied belonged to a particularly challenging group: all had already received chemotherapy, almost all suffered from bone metastases, and one in three patients also had metastases in internal organs. “A significant proportion would not have met the inclusion criteria for international approval trials,” says Samer Ezziddin. Yet there are many affected patients who do not meet the requirements for one criterion or another, meaning they are not eligible for radioligand therapy. “Our patient group therefore reflects everyday clinical practice much more closely than many controlled trials,” explains the scientist.
Despite the unfavourable baseline situation, many of the 227 patients responded to the treatment. In just under two-thirds of cases, the PSA level – the tumour marker – fell after the first cycle of therapy. More than half of the patients achieved a reduction in PSA of at least 50 per cent over the course of treatment. The median overall survival was 14.5 months, which is comparable to the results of large international studies.
“Our findings show that, when tailored to the individual, PSMA radioligand therapy can be successfully used even in patients who are often considered particularly challenging in everyday clinical practice. This opens up an additional therapeutic option, particularly for these patients,” says Professor Ezziddin. “In cases of higher tumour burden, a much higher dose is therefore possible than that stipulated by previous guidelines. This allows us to keep the tumour more effectively in check and reduce the dose later on, thereby avoiding side effects.” It was a strategy that paid off: the treatment proved to be well tolerated, with serious side effects being rare.
“The future of radioligand therapy lies in tailoring it as precisely as possible to the individual situation of each patient. Our data suggest that this enables us to push the boundaries of previous standard approaches without compromising on safety,” concludes Samer Ezziddin.
The authors emphasise that further studies are needed to demonstrate the benefits of individualised dosing strategies in direct comparison with standard dosages. However, the data now published show that such an approach already has the potential to expand treatment options for patients with advanced prostate cancer.
Original publication
Misirci M, Rosar F, Khreish F et al., Real-world evaluation of [177Lu]Lu-PSMA-617 RLT in post-taxane mCRPC: feasibility and safety of individualised treatment in a challenging cohort. European Journal of Nuclear Medicine and Molecular Imaging (2026). DOI: 10.1007/s00259-026-08037-4.
Web: https://pubmed.ncbi.nlm.nih.gov/42412178/
Further information:
Prof. Dr Samer Ezziddin
Tel.: (06841) 16-22201
Email: samer.ezziddin(at)uks.eu
