Systemic therapy in metastatic hormone-sensitive prostate cancer

The landscape of metastatic hormone sensitive prostate cancer (mHSPC) has evolved rapidly in recent years with new data from landmark trials supporting upfront treatment intensification. The developments come not only on the fronts of systemic agents but also in area of therapy to primary tumour and metastases.

More recently, the ARASENS and PEACE trials have taken the concept of treatment intensification further by demonstrating survival benefit from combination of chemotherapy (docetaxel) and androgen receptor pathway inhibitors (abiraterone and darolutamide) in addition to backbone therapy of androgen deprivation therapy (ADT). Intensification of treatment has also seen evidence supporting local therapy to the primary tumour with overall survival and biochemical recurrence-free survival although only evident in low volume synchronous metastases. There is emerging evidence for metastases-directed therapy as well with pooled data suggesting improved biochemical-free and ADT-free survival.

Robust clinical data has demonstrated survival benefits with treatment intensification and this should be the new standard of care. Subgroup analysis has highlighted the importance of tailoring mHSPC treatment for patients with high- and low-volume metastatic disease. However, defining the volume of disease is becoming increasingly controversial due to heterogeneity of trial patient populations and next generation molecular imaging.