Oligometastatic Prostate Cancer

Prostate cancer is the commonest cancer and the most frequent cause of cancer death in Western men [ 1 ]. The median survival for men presenting with metastatic disease is 42.1 months [ 2 •]. Currently accepted treatment consists of androgen deprivation therapy (ADT) followed by chemotherapy and novel agents once the ADT is no longer effective. Treating metastatic disease is estimated to cost healthcare systems US$20,000 per man [ 3 ]. Oligometastatic disease can be defined as the development of three or fewer non-castrate lesions outside of the primary tumour [ 4 ••]. These can be bone metastases or in the soft tissue. The concept of oligometastatic disease for all cancers is based around a stepwise progression whereby a cancer initially metastasises in a limited way, before acquiring widespread metastatic behaviour [ 5 ]. In a range of solid tumours [ 6 – 8 ], it is hypothesised that this intermediate step represents a different biology compared to extensive metastatic disease, and therefore, it represents an opportunity to influence the rate of progression, and possibly even cure the patient. It is thought that in oligometastatic states, the true metastatic growth potential is limited. This may be secondary to tumour microenvironments in the primary lesion remaining sufficiently hospitable that evolutionary clonal pressure is low; therefore, cancer cells that slough off the primary do not have the properties necessary to survive the circulation and invade target organ sites effectively [ 9 •]. This is contrasted with systemic metastatic disease where the primary tumour has created many undifferentiated aggressive clones that actively migrate out of the primary tumour and have the characteristics to survive and invade target organ sites. The clinical implication of oligometastatic disease is that treatment of metastases alongside the primary tumour (if not already treated) could result in long-term survival or cure [ 10 , 11 ]. Treatment of oligometastatic disease may also decrease disease-related morbidity and reduce overall tumour burden. However, without randomised controlled trials, it is very difficult to know if the treatment of oligometastatic disease helps the patient. The current literature in all cancer types is limited by using varying definitions of oligometastasis, with a variety of endpoints and at different levels of evidence [ 9 •]. With regard to prostate cancer, while standard treatment remains long-term palliative androgen deprivation treatment, there is emerging data that treatment of the primary with stereotactic body radiotherapy (SBRT) or even radical prostatectomy may impact survival, slow symptomatic disease progression, and reduce the need for palliative surgical intervention [ 12 – 15 ]. In this review, we evaluate the three main treatment approaches for oligometastatic prostate cancer—systemic therapy, treatment of the primary tumour and metastasis-directed therapy.