“Hit the primary”: A paradigm shift in the treatment of metastatic prostate cancer?

• We focused on the irradiation of primary tumor in metastatic prostate cancer.
• We analyzed preclinical data underlining the intrinsic capability of radiation therapy to act as a more general immune response modifier data.
• We reported on clinical data mainly from retrospective surgical series, which consistently show survival benefits in metastatic prostate cancer patients following definitive therapy to the prostate.
• We concluded that the potential and beneficial impact of local treatment of the primary tumor in metastatic prostate cancer patients is supported by a strong rationale, but requires further validation in future studies.

Patients with metastatic prostate cancer (PC) represent a heterogeneous group with survival rates varying between 13 and 75 months. The current standard treatment in this setting is hormonal therapy, with or without docetaxel-based chemotherapy. In the era of individualized medicine, however, maximizing treatment options, especially in long-term surviving patients with limited disease burden, is of capital importance. Emerging data, mainly from retrospective surgical series, show survival benefits in men diagnosed with metastatic PC following definitive therapy for the prostate. Whether the irradiation of primary tumor in a metastatic disease might improve the therapeutic ratio in association with systemic treatments remains investigational. In this scenario, modern radiation therapy (RT) can play a significant role owing to its intrinsic capability to act as a more general immune response modifier, as well as to the potentially better toxicity profile compared to surgery. Preclinical data, clinical experience, and challenges in local treatment in de novo metastatic PC are reviewed and discussed.