| THE EFFECT OF
COMBINING ANDROGEN SUPPRESSION WITH RADIOTHERAPY FOR HIGH-GRADE
CLINICALLY LOCALISED PROSTATE CANCER
Mr Majid Shabbir BSc(Hons) MBBS (Hons) MRCS(Eng) Urology Research Fellow, Royal Free Hospital, London |
High-grade clinically localised prostate cancer is associated with an increased rate of complications and poor survival. Patients with high-grade localised disease (defined as a PSA of >10ng/ml, a Gleason score of at least 7, or radiographic evidence of cancer spread to the seminal vesicles) are often treated with external beam radiotherapy (EBRT). Previous trials have shown that the addition of androgen suppression therapy (AST), such as zoladex, to radiotherapy improves survival among patients with locally advanced prostate cancer (Bolla et al, NJEM 1997). However, this trial used combinations of radiotherapy with 3 years of androgen suppression. Such long term androgen suppression is not without its own troubles; complications of AST include osteopenia (reduced bone density), anaemia, hot flushes, impotence, muscle loss and memory loss, and these lead to a reduced quality of life.
The aim of a recent study by D'Amico et al (JAMA 2004;292:821-27) was to assess whether androgen suppression could achieve a survival benefit in combination with radiotherapy if used for a shorter period of time. Patients were divided into 2 groups and received either 3-D conformal radiotherapy (3-D CRT) alone or in combination with 6 months of AST. Hormone therapy consisted of an LHRH analogue, such as zoladex, and an anti-androgen (flutamide). Treatment was started 2 months before, given concurrently with, and continued for 2 months after radiotherapy. Patients were followed up for on average 4.5 years. The combination of AST with radiotherapy significantly improved overall survival, survival without disease progression, and reduced the number of deaths due to prostate cancer compared to radiotherapy alone. Patients treated with combination therapy had a high rate of gynaecomastia (increase in breast tissue) and impotence compared to those treated with radiotherapy alone. No other significant differences were noted between the treatments in terms of side effects.
In conclusion, this study found that the combination of 6 months AST with 3-D CRT increased the overall survival in patients with high-grade clinically localised prostate cancer. This survival advantage was similar to that previously reported with 3 years hormone therapy, therefore advocating the use of combination therapy for shorter periods of time to improve outcome while reducing the chance of significant side-effects from hormone therapy. Further trials may help better define how short a course of AST is needed to be effective, as well as the best method and timing of combination therapy.