Brain Metastases From Prostate Cancer

An Emerging Clinical Problem With Implications for the Future Therapeutic Scenario

Orazio Caffo; Antonello Veccia; Lucianna Russo; Enzo Galligioni


Future Oncol. 2012;8(12):1585-1595. 

In This Article

Abstract and Introduction


Brain metastases from prostate cancer (PC) seem to be more frequent than in the past, possibly because advances in the treatment of patients with castration-resistant PC have prolonged their survival. Furthermore, docetaxel (the drug of choice for the first-line treatment of castration-resistant PC) cannot cross the blood–brain barrier and control metastatic foci. However, this problem may be overcome by new active drugs such as cabazitaxel.


Prostate cancer (PC) is the most common non-skin cancer among men and the second leading cause of cancer death in the USA, where 240,890 affected men were newly diagnosed and 33,730 died in 2011.[1] The incidence and mortality rates in Europe in 2008 were similar.[2] Radical treatment of localized disease (prostatectomy, external radiotherapy and brachytherapy) can lead to the long-term survival of many patients and, even in the presence of nonlocalized disease, androgen deprivation therapy allows the disease to be controlled as long as it remains sensitive to hormonal treatment. Unfortunately, although the response to hormonal manipulation is quite favorable, this usually lasts no more than 2–3 years, and the patients eventually progress despite castration.

The unfavorable evolution of PC is related to various molecular mechanisms that allow cancer cells to escape hormonal control[3] and lead to the transition from hormone-sensitive to castration-resistant disease. Little has changed in the treatment of hormone-sensitive PC, which is still limited to androgen deprivation alone or combined with androgen receptor blockers, but the treatment of castration-resistant PC (CRPC) has undergone revolutionary changes over the last decade. Until a few years ago, nonhormonal strategies (chemotherapy with mitoxantrone) were only palliative[4,5] but this changed in 2004 when it was discovered that docetaxel significantly improved symptom control and survival,[6,7] although post-docetaxel disease management remained an unmet medical need. However, over the last 2 years, a number of drugs with different mechanisms of action have been found to improve survival in the post-docetaxel setting: cabazitaxel (a new chemotherapeutic agent),[8] abiraterone (a new androgen-deprivation agent),[9] Sipuleucel-T (a vaccine)[10] and enzalutamide (a new androgen receptor blocker).[11] As a whole, these approaches have changed (and are still changing) the natural history of PC, and have considerably improved the survival of patients with CRPC.

Brain metastases (BMs) are the most frequent intracranial neoplasms in adults. Their estimated incidence in the USA is 200,000 cases per year[12] with 8–10% of patients developing symptomatic BMs.[13,14] BMs are common during the course of various types of cancer, mainly lung (40–50%) and breast cancer (15–25%) and melanoma (5–20%).[13,14] Patients with BMs have a poor prognosis, and most live for only 4–6 months after diagnosis owing to the very limited survival benefit of the available treatments.[15]

BMs should be distinguished from other CNS metastases. The term BM should be limited to the focal seeding of the brain parenchyma (parenchymal BMs) and not used in the case of secondary lesions involving the leptomeningeal and pachymeningeal (dural) compartments; dural metastases can be further divided into epidural and subdural lesions.

The symptoms of BMs are usually related to intracranial hypertension and frontal lobe syndrome (headache, paresis and seizures), but many patients present confusion, weakness, aphasia, visual disturbances or ataxia, which may be confused with symptoms of ischemic or hemorrhagic events. However, a correct differential diagnosis can be made using improved radiological techniques.