ESMO Guidelines Endorse Lutetium Therapy; New Data on PSMA Prediction, DOAC Safety

New European guidelines for advanced and metastatic prostate cancer now recommend lutetium-177 PSMA-617 radioligand therapy for some patients, marking the first time this treatment is endorsed in official guidance. The guidelines, published in the Annals of Oncology, also expand recommendations on precision medicine and introduce advice on supportive care.

The European Society for Medical Oncology (ESMO) guidelines cover metastatic castration-sensitive prostate cancer (mCSPC), non-metastatic castration-resistant prostate cancer (nmCRPC), and metastatic castration-resistant prostate cancer (mCRPC). They recommend germline testing for all mCSPC patients for BRCA1, BRCA2, mismatch repair genes, HOXB13, ATM, CHEK2, and PALB2. Treatment for mCSPC includes androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPI) for all patients, with six cycles of docetaxel advised for de novo high-volume disease. Radiotherapy of the primary tumor is also advised.

For mCRPC, the guidelines stratify treatment by genetic mutation, advising genomic testing for BRCA1, BRCA2, CDK12, and PALB2, and MMR deficiency testing after ARPI treatment. All mCRPC patients should receive a bone-protecting agent such as denosumab or zoledronic acid. Treatment options for mCRPC without homologous recombination repair alterations include docetaxel, abiraterone, enzalutamide, cabazitaxel, and 177Lu-PSMA-617, depending on prior therapies. For patients with prior ARPI treatment, docetaxel and 177Lu-PSMA-617 are recommended. PARP inhibitors are backed for mCRPC patients with BRCA mutations.

The guidelines also recommend exercise therapy for patients undergoing ADT, alongside monitoring of bone mineral density and cardiovascular health. Follow-up for mCSPC and mCRPC patients includes clinical assessment, PSA tests, blood counts, and potentially imaging every 3–6 months. A single fraction of external beam radiotherapy is advised for painful, uncomplicated bone metastases.

Separately, a new machine-learning approach for prostate-specific membrane antigen (PSMA) treatment of mCRPC could estimate radiation dose to tumors and healthy organs before therapy begins. Presented at the Society of Nuclear Medicine and Molecular Imaging 2026 Annual Meeting, the model uses data from pre-therapy PET/CT scans to personalize treatment plans, improve patient selection, and reduce toxicity risk. In a proof-of-concept study involving nine patients with mCRPC, the model showed promising ability to predict tumor and organ absorbed dose by combining uptake features, radiomics, and clinical biomarkers. The research is part of a planned five-year program aimed at collecting more data and developing a robust, validated model.

Additionally, a study found that direct-acting oral anticoagulants (DOACs) do not appear to interact with prostate cancer drugs to increase bleeding or clotting risks. The largest study of its kind involved 2,997 patients with advanced prostate cancer who were prescribed a DOAC or a non-DOAC and a potentially interacting ARPI between 2012 and 2023. Among those on enzalutamide or apalutamide, there was no increased risk of thrombosis in the DOAC versus non-DOAC groups (pooled hazard ratio, 0.83). Similarly, there were no significant differences in any bleeding events between the DOAC and non-DOAC arms in patients taking abiraterone (pooled hazard ratio, 1.16). The findings suggest that pharmacokinetic drug-drug interaction concerns may not translate into adverse clinical outcomes.

These updates reflect ongoing advances in prostate cancer management, from genomic-guided therapies to innovative drug safety data.