Prostate news article, November 2005
SHORT-TERM ANDROGEN DEPRIVATION AND RADIOTHERAPY FOR LOCALLY ADVANCED PROSTATE CANCER: RESULTS FROM THE TRANS-TASMAN RADIATION ONCOLOGY GROUP 96.01 RANDOMISED CONTROLLED TRIAL Article in Lancet Oncology, November 2005 Reviewed by: Mr Amit Patel, BSc, MBBS, MRCS |
Androgen deprivation is an established treatment in patients with disseminated prostate cancer. However its role in patients with localized cancer is less clear. There is some evidence from surgical trials that androgen deprivation given several months before prostatectomy leads to the down staging of tumours allowing complete histopathological clearance at the time of surgery; whether this translates into improved clinical outcomes is yet to be established.
Denham and colleagues performed a randomised controlled clinical trial recruiting 802 patients over a 10 year period to look at the effect of short term adjuvant androgen deprivation therapy to patients undergoing radiotherapy for locally advanced prostate cancer. Inclusion criteria included locally advanced prostate cancer (T2b, T2c, T3, T4), without lymph node involvement or metastatic spread and no significant co morbidity. There were three main arms to the study, with patients randomly assigned to a control group (radiotherapy alone - no androgen deprivation), a 3 month androgen deprivation group (treatment commenced 2 months prior to radiotherapy) and a 6 month androgen deprivation group (treatment commenced 5 months prior to radiotherapy). Patients assigned intervention received the same radiotherapy regimen as the control group. Androgen deprivation involved monthly Zoladex injections as well as 250mg of flutamide three times a day orally.
Follow up was for a minimum of 5 years and the end points studied were local failure (defined as failure of the primary tumour to disappear after treatment protocol or re-emergence following period of remission), distant failure (metastasis to sites outside the prostate region), disease-free survival (time to first evidence of clinical failure), time to salvage treatment for any type of recurrence and prostate-cancer-specific-survival.
Their results showed that 3 months’ androgen deprivation significantly increased disease-free survival and led to less need for salvage treatment, and 6 months’ androgen deprivation augmented these effects and also improved prostate-cancer-specific-survival. This was reflected in the finding that whilst 3 months’ androgen deprivation reduced the risk of local failure, it did not decrease distant failure - compared with 6 months’ treatment which did.
However, a major area of criticism with this paper and which is acknowledged
by the authors is that relatively low dose radiotherapy was used in the
treatment protocol due to limitations in the radiotherapy equipment available
at the time of the trial. Whether higher doses of radiation
with modern day equipment would obviate the need for adjuvant treatment
in patients regarded as low risk is yet to be seen. This study
has shown that 6 months’ androgen deprivation given before and during
radiotherapy improves the outcome of patients with locally advanced prostate
cancer. Further follow up is needed to estimate the precise
magnitude of this survival benefit and indeed whether this benefit is still
seen with the delivery of modern day radiation doses.
Denham J et al.
Lancet Oncol. 2005 Nov;6(11):841-50.