How is metastatic prostate cancer treated?

2026-09-15

The treatment strategy for metastatic prostate cancer depends on the disease's hormone sensitivity (metastatic hormone-sensitive [mHSPC] or castration-resistant prostate cancer [mCRPC]), the extent of metastases (low- or high-volume disease), and its molecular/genetic characteristics.

1. Metastatic hormone-sensitive prostate cancer (mHSPC): - The cornerstone of therapy is continuous androgen deprivation therapy (ADT; GnRH agonists or antagonists, or surgical castration). - According to current clinical guidelines, intensified combination therapy is the standard of care: combining ADT with a novel androgen receptor pathway inhibitor (ARPI: e.g., abiraterone, enzalutamide, apalutamide, darolutamide) or docetaxel chemotherapy (doublet therapy). - In the case of high tumour volume (high-volume), triplet therapy is also frequently used (ADT + docetaxel chemotherapy + an ARPI, such as darolutamide or abiraterone). - In low-volume, de novo metastatic disease, radiotherapy to the primary prostate tumour (PDT) improves progression-free and overall survival as an adjunct to systemic therapy.

2. Metastatic castration-resistant prostate cancer (mCRPC): - Alongside the continuation of ADT, additional targeted ARPI therapy (abiraterone, enzalutamide) or taxane-based chemotherapy (docetaxel, or cabazitaxel in case of progression) can be administered. - Molecular profiling (genomic testing): in tumours with homologous recombination deficiency (HRR gene mutations, particularly BRCA1/BRCA2), PARP inhibitors (e.g., olaparib, talazoparib as monotherapy or combined with an ARPI) are effective. - Radioligand therapy: in PSMA-positive tumours that have previously received chemotherapy and ARPI therapy, radiopharmaceutical-based treatment (e.g., 177Lu-PSMA-617) may be used; in exclusively bone-metastatic, symptomatic cases, radium-223 is also an option.

3. Local and supportive treatments: - In oligometastatic disease, stereotactic body radiotherapy directed to metastases (MDT) can be considered, as well as the use of bone-protective agents (bisphosphonates, denosumab) to prevent skeletal-related events.

References

  1. PARP and Androgen-Signaling Inhibition plus ADT in Metastatic Prostate Cancer. PMID 42223064
  2. Radiotherapy in Men with De Novo Metastatic Prostate Cancer. PMID 41986024
  3. Systemic Treatments in Men with De Novo Metastatic Prostate Cancer. PMID 41986022
  4. Primary site- and metastasis-directed therapies in patients with metastatic prostate cancer: A narrative review. PMID 42218356
  5. Management of Metastatic Prostate Cancer. PMID 40784337
  6. PARP Inhibitors in Metastatic Prostate Cancer: Bridging Biomarker Complexity and Clinical Decision-Making Through a Pragmatic Treatment Framework. PMID 42352483
  7. EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer. Part II-2026 Update: Treatment of Relapsing and Metastatic Prostate Cancer. PMID 42457456
  8. Advances in Targeted Therapy for Metastatic Prostate Cancer. PMID 40299225
  9. Therapeutic Advances in Metastatic Prostate Cancer: A Journey from Standard of Care to New Emerging Treatment. PMID 41373813

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