Combined androgen blockade before surgery for local cancers

This study examined the potential benefit of early intensive hormonal therapy (combined androgen blockade) in men with high-risk local prostate cancer, given before surgery.

Researchers concluded that intensive hormone therapy may be more effective than standard treatment in reducing androgen levels, but seldom results in complete tumor response. 

Men with high-risk local prostate cancer are at increased risk of cancer progression, or recurrence, after treatment. Therefore, aggressive interventions are often needed early on. Typically, treatment of local prostate cancer involves a combination of either surgery or radiation, followed by androgen deprivation therapy (ADT). ADT targets the production of androgens (male sex hormones such as testosterone) and reduces their effect on cancer cell growth.

In cases of advanced cancer that has spread beyond the prostate, or cancer that has progressed despite standard treatment, newly developed hormonal treatments, such as abiraterone (Zytiga), are added to standard ADT (referred to as combined androgen blockade or dual-hormonal therapy).

The aim of this study was to examine the effectivity of intensive ADT (combined androgen blockade) given early in the course of local disease, before surgery to remove the tumor.

The study included 58 men with intermediate- or high-risk prostate cancer. Men were randomly assigned to receive treatment with either standard ADT (using leuprorelin) or intensive ADT (using leuprorelin plus abiraterone). After 12 weeks of assigned treatment, all men underwent an additional 12-weeks of intensive ADT, followed by a radical prostatectomy (surgery to remove the entire prostate gland).

After the first 12 weeks of treatment, androgen levels were significantly lower in the prostates of men receiving intensive ADT, compared to men receiving standard ADT. At the end of ADT, however, most men still showed significant tumor burden, regardless of the type of hormonal treatment received. Tumors were found to remain locally advanced in 48% of men that underwent 24-weeks of intensive ADT, and in 59% of men that underwent only 12-weeks of intensive ADT. In addition, lymph node involvement (lymph nodes containing cancer cells) was noted in 24% of men that underwent 24-weeks of intensive ADT, and in 11% of men that underwent 12-weeks of intensive ADT. Overall, only few men showed complete or near-complete tumor response to ADT before surgery.

The rate of side effects was similar between standard and intensive ADT. Hot flushes, fatigue, and liver dysfunction were the most commonly reported side-effects associated with hormonal treatment.

Researchers concluded that intensive combined ADT reduces prostatic androgen levels to a greater degree than standard treatment. However, local tumors seem to develop resistance to treatment early, and combined hormonal treatment before surgery does not result in complete response in most men.

Larger randomized clinical trials are needed to investigate the potential benefits of early intensive hormonal therapy on long-term outcomes and overall survival.