New European guidelines for advanced and metastatic prostate cancer include expanded recommendations on precision medicine and, for the first time, advice on supportive care.

The guidelines broadly back both genomic and germline testing, providing treatment guidance for specific mutations, and newly recommend lutetium-177 PSMA-617 (¹⁷⁷Lu-PSMA-617) radioligand therapy for some patients.

The European Society for Medical Oncology (ESMO) guidelines, published in the Annals of Oncology, cover metastatic castration-sensitive prostate cancer (mCSPC), non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic castration-resistant prostate cancer (mCRPC), and replace the previous iteration from 2020.

They recommend that all patients with mCSPC undergo germline testing for cancer susceptibility genes, including BRCA1, BRCA2, mismatch repair (MMR) genes and HOXB13, as well as moderate-risk genes, such as ATM, CHEK2 and PALB2.

Dr Alison Tree, Source: The ICR, London

The guidelines, co-authored by UK specialists including Dr Alison Tree, clinical oncologist at The Royal Marsden NHS Foundation Trust, advise that prognosis classifications can be used, but stress that they are imperfect tools for treatment selection.

They now also recommend androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPI) for all mCSPC patients, with six cycles of docetaxel also advised, particularly in de novo, high-volume disease.

Radiotherapy of the primary tumour is also advised for these patients, but the guidelines highlight that systemic treatment for mCSPC after local therapy is “complex”, “as many patients have oligometastatic or ‘low-volume’ disease and, thus, a good prognosis”.

“It is not currently clear when systemic treatment, local treatment of metastases, both systemic and local approaches or none of these should be used,” they stress.

Metastasis-directed therapy can be used for oligometastatic mCSPC, especially in the oligorecurrent setting, although it was described by the authors as “investigational”.

nmCRPC should be treated with ADT-ARPI combination therapy, with next-generation imaging optional.

Recommendations for mCRPC are now stratified by genetic mutation, with genomic testing for BRCA1, BRCA2, CDK12 and PALB2 advised for all patients, and MMR deficiency testing advised for patients after ARPI treatment.

All mCRPC patients should be treated with a bone-protecting agent (denosumab or zoledronic acid) alongside their anticancer treatment.

The guidelines also offer advice on sequencing treatments for mCRPC, but note that “the most effective treatment strategy remains a topic of ongoing investigation”.

For mCRPC patients without an HRR alteration, treatment with docetaxel, abiraterone, enzalutamide, cabazitaxel and ¹⁷⁷Lu-PSMA-617 are all recommended treatment options depending on prior therapies.

²²³Radium therapy is recommended in mCRPC with bone-predominant metastases if patients have not received a prior ARPI.

The guidelines highlight that mCRPC patients who have undergone prior ARPI treatment are becoming more common, with docetaxel and ¹⁷⁷Lu -PSMA-617 the recommended treatment options.

PARP inhibitors are backed for mCRPC patients with BRCA mutations, with an ARPI if they have not received one previously.

They also advise using metastasis-directed therapy with ARPI to delay disease progression in selected oligometastatic mCRPC patients.

Supportive care and follow-up

For the first time, the guidelines contain specific recommendations for supportive care in mCSPC.

Exercise therapy is advised for patients undergoing ADT, alongside monitoring of bone mineral density and cardiovascular health.

There is also advice on follow-up of mCSPC patients, with clinical assessment, PSA tests, blood counts and potentially imaging every 3–6 months recommended.

In addition, a single fraction of external beam radiotherapy should be used in the case of painful, uncomplicated bone metastases, they advise.

In mCRPC, PSA measurements and imaging every 3–6 months were also recommended for follow-up.

Read the new guidelines in full here.