Neo-adjuvant, concurrent and adjuvant hormonal therapy and EBRT
Three RCTs (37), (38), (39) have demonstrated that combined hormonal therapy treatment plus EBRT significantly improves PSA levels and biochemical free survival when compared to EBRT alone.
Two of these trials also compared combination hormonal therapy plus EBRT to neo-adjuvant hormonal therapy and EBRT only. One trial found a benefit of combined hormonal therapy at 12 months, but no significant difference at 24 months (37). The second found no significant difference between the two treatment arms at a median follow-up of 5 years (39).
There may be differences in benefit depending upon the prognostic risk group. A meta-analysis of over 2000 men with early prostate cancer, pooling data from five RCTs, highlights that men in low-risk groups do not benefit from adjuvant hormonal therapy while men in high-risk groups do (40).
It would appear that adding hormonal therapy to radiotherapy can help to improve outcomes for men with intermediate-risk and high-risk early prostate cancer, but not those with low-risk disease. There is some controversy about the optimal length of hormonal therapy (41), but men with intermediate-risk disease may benefit from having neo-adjuvant and concurrent hormonal therapy (4–6 months of treatment), while men with high-risk disease (Gleason 8-10) should probably have neo-adjuvant, concurrent and two years of adjuvant therapy (42).
Hormone therapy alone
Some men may choose to have hormone therapy as their primary treatment, as an alternative to the more conventional options of active surveillance, surgery or radiotherapy. However, there is no good evidence to support this option among men with early prostate cancer. Indeed, it might have an adverse effect on survival (the EPC trial) as well as quality of life.
Neo-adjuvant hormonal therapy and surgery
There have been several prospective randomised controlled trials which have used 3–6 months of androgen ablation before radical prostatectomy (31), (32), (33) in the hope that neo-adjuvant androgen ablation (also known as hormonal down-staging) would result in a reduction in tumour size and a decrease in positive margins.
With more than 1000 patients incorporated into trials of neo-adjuvant hormonal therapy, there is little doubt that it reduces the incidence of tumour in the margins of the operated specimens, but there is no known survival advantage (31),(34),(35).
Neo-adjuvant hormonal therapy, surgery and adjuvant hormonal therapy
There has been one RCT that looked at adding neo-adjuvant hormonal therapy to surgery with adjuvant hormonal therapy. The study found no difference in overall survival; clinical relapse free survival and PSA relapse free survival between the two groups (36).
Neo-adjuvant hormonal therapy and EBRT
Neo-adjuvant hormonal therapy has been shown to improve overall survival in men with high-risk localised prostate cancer. An RCT involving 206 men with intermediate- or high-risk disease, who were randomised to receive radiotherapy with or without six months of hormonal therapy, showed a significantly improved five year survival for those receiving the combined treatment (37).
Androgen ablation and brachytherapy
There have been no randomised controlled trials looking at adding hormonal therapy to brachytherapy.
Adjuvant hormone therapy following radiotherapy this has already been covered above
Results from RCTs looking at the role of adjuvant hormone therapy following radiotherapy are demonstrating an advantage of the combined treatment for men with high-risk, locally advanced prostate cancer. However, further studies are required to assess the value of hormone therapy as adjuvant treatment for early prostate cancer. In the mean time patients should be counselled regarding the potential unwanted effects of adjuvant hormone treatment.
Oestrogens
Giving female hormones stops the release of testosterone. Although used less commonly these days, stilboestrol tablets are sometimes used when other hormone therapies have begun to fail.