Phase III Trial of Conformal Radiotherapy Following Neoadjuvant Hormone Treatment in Early Prostate Cancer

Reviewer: Roberto Santiago, MD
Last Modified: October 11, 2002

Presenter: Alan Horwich
Presenter's Affiliation: The Royal Marsden Hospital & Institute of Cancer Research, Sutton & London, UK
Type of Session: Scientific


    There is evidence that a short course of neoadjuvant hormone therapy (NHT) prior to standard dose radiotherapy (RT) can increase local control in patients with clinically localized prostate cancer. There is also data supporting escalating doses of RT in patients with localized prostate cancer with an intermediate risk of failure. The benefit of dose escalation in low risk (PSA < 10 ng/ml) patients is not clear. NHT can cause a rapid decrease in tumor bulk, PSA, and proliferation of cancer cells as well as an increase in apoptosis. This study attempts to determine if there is a need for dose escalation in early, low-risk prostate cancer patients given the mentioned effects of NHT. The study estimates the efficacy and safety of radiation dose escalation and determines the appropriate margin around the prostate for the planning target volume (PTV) in patients treated with NHT for 3?6 months prior to 3-D conformal RT.

Materials and Methods

  • One hundred and twenty six men with localized prostate cancer were randomized in a phase III trial using a 2 × 2 factorial design.
  • The dose groups were either standard dose RT (SD) to 64 Gy in 32 fractions in 6.5 weeks or higher dose (HD) in which the standard dose treatment was supplemented by a boost of 10 Gy to a total dose of 74 Gy in 37 fractions over 7.5 weeks.
  • The PTV randomization compared a margin of 1cm (M1) around the tumor volume compared to a margin of 1.5cm (M1.5). In the HD group the boost was delivered to the prostate only with no margin.
  • Patients were stratified according to risk of seminal vesicle involvement based on Roach?s formula and when the seminal vesicle needed coverage the tumor volumes were modified accordingly.
  • The patient population in the trial had a median age of 67 years, median presenting PSA of 14 ng/ml and estimated risk of seminal vesicle involvement was low in 29% and moderate in 71%.
  • The study endpoints included acute toxicity (RTOG defined), late side effects, (RTOG/LENT-SOM), biochemical failure (defined as the first date of 2 consecutive rises in PSA above 2 ng/ml), clinical disease control and overall survival.


  • median follow up after RT of 4.25 years
  • 36 of the 126 patients have biochemical PSA failure, 23 after SD and 13 after HD (Fishers exact test, 1 sided P = 0.048). There was no difference in the failure rate by PTV randomization, 18 in each arm.
  • Late bowel complications were more common after HD (p = 0.03) and with larger margins M1.5 (p = 0.008).
  • All grade 3 complications occurred in the HD M1.5 subgroup.
  • No significant differences were seen in the incidence of late bladder toxicity (grade 2?10%, grade 3?5%). A similar incidence of impotence (66% at 1 year) was seen in all subgroups (38% at baseline pre treatment).

Author's Conclusions

  • After 3?6 months of NHT, early prostate cancer patients treated with conformal RT experienced an improvement in biochemical control with increased radiation dose.
  • Although there were relatively low levels of acute and late toxicity, these were more common in the high dose group as well as the larger PTV group.
  • No benefit was detected for the larger PTV margin.
  • A large ongoing Medical Research Council trial (MRC RTO1) will determine the most effective of these two dose levels.

Clinical/Scientific Implications

    Radiation dose escalation appears to play a significant role in controlling prostate cancer despite neoadjuvant hormonal treatment. However, the dose used in the "standard dose" arm of this study is no longer considered optimal. Prospective randomized trials are needed to answer this question of dose escalation in combination with hormonal therapy.

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