Overview of first-line treatments for advanced prostate cancer

This review evaluated first-line treatments for metastatic castration-resistant prostate cancer (mCRPC). Authors recommend chemotherapy with docetaxel (Taxotere) for mCRPC with high tumor burden or at high risk of rapid progression. Alternative hormonal therapy or chemotherapy may be effective in other cases. 

Metastatic prostate cancer refers to cancer that has spread to distant organs. Treatment for metastatic prostate cancer usually involves hormone therapy. The most commonly used hormone therapy is androgen deprivation therapy (ADT). ADT targets the production of male hormones (such as testosterone) and reduces their effect on cancer cell growth. In some patients, cancer can continue to spread despite ADT. This is called metastatic castration-resistant prostate cancer (mCRPC). Secondary hormone therapy or chemotherapy are often recommended for mCRPC.

The aim of this review was to review first-line treatments for mCRPC in keeping with recent evidence.

Men with mCRPC often receive chemotherapy with docetaxel (Taxotere) if they are eligible. This treatment is generally not suitable for men with poor general health or serious additional medical conditions. Docetaxel remains the first-line treatment for men with moderate to severe symptoms due to mCRPC. This includes cancer with high tumor burden (the amount of cancer in the body) and cancer at high risk of rapid progression. One trial noted a significant survival benefit of docetaxel over placebo (control substance with no effect on the body) in mCRPC spread to organs such as the lungs or liver.

Cabazitaxel (Jevtana) is the most common chemotherapy used to treat patients no longer responding to docetaxel. Cabazitaxel may be used in cases of low risk of rapid progression. Sipuleucel-T (Provenge) is another type of chemotherapy. Sipuleucel-T has been found to increase overall survival in men with milder symptoms.

Radium-233 is a type of radiation therapy used to treat mCRPC with metastases of the bone. Radium-233 is reserved for patients that do not tolerate, or no longer respond to, docetaxel. One trial found average survival to be significantly longer with radium-233 (average 14.9 months) than with placebo (average 11.3 months).

Two types of newly approved secondary hormone therapies include enzalutamide (Xtandi) and abiraterone (Zytiga). These secondary hormone therapies are usually used in patients with milder mCRPC symptoms or when the risk of rapid progression is low. They have been found to significantly enhance survival both before and after chemotherapy with docetaxel. Enzalutamide was superior to placebo in prolonging survival in mCRPC spread to other organs. Recent evidence suggested that these treatments are most effective when used exclusively. Enzalutamide after abiraterone or vice versa reduced treatment effectiveness.

There are certain risk factors that have previously been associated with poorer clinical outcomes. The survival benefit with docetaxel treatment is usually greater if cancer cells are deemed less aggressive (Gleason score of 7 or lower). One trial noted an increased survival benefit of 31% compared to higher Gleason scores (of 8 or higher). Alternative chemotherapy should be considered for Gleason scores ranging from 8 to 10.

Results from routine blood tests can also help determine prognoses. Elevated PSA (prostate specific antigen, an indicator of prostate growth) levels are often associated with faster disease progression. If PSA levels rise quickly, alternative chemotherapy should be considered over secondary hormone therapy. 

The time until ADT resistance developed may help determine whether a patient will respond to further hormonal therapies. Duration of prior ADT predicted survival with abiraterone treatment in one trial. If the response to ADT was shorter than 12 months, alternative chemotherapy should be considered over secondary hormone therapy. Overall, there is not one single factor predictive of response either to hormonal therapy or chemotherapy.

Researchers concluded that docetaxel remains the first-line treatment for mCRPC at high risk of rapid progression. A number of prognostic factors should be assessed when considering alternative hormonal therapy or chemotherapy.