Prostate Cancer Radiation Dose Response: Final Planned Analysis Of A Phase III Randomized Trial

Reviewer: Roberto Santiago, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 18, 2002

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Presenter: Alan Pollack
Presenter's Affiliation: Fox Chase Cancer Center
Type of Session: Scientific


  • Between 1993 and 1998, a randomized trial at MDACC was conducted to assess the effectiveness of two radiotherapy doses, 70 Gy versus 78 Gy, in preventing biochemical and/or clinical relapse of prostate cancer.

Materials and Methods

  • Of 301 evaluable patients, 150 were randomized to receive 70 Gy and 151 to 78 Gy
  • Treatment arms were evenly balanced in terms of stage, Gleason score, pretreatment PSA, and previous TURP
  • The median follow-up was 60 months
  • Freedom from biochemical and/or clinical failure (FFF) from the completion of radiotherapy was estimated using the Kaplan-Meier Method
  • The log-rank test was used to compare groups


  • 6-year FFF rates for the 70 and 78 Gy arms were 64% and 70%, respectively (p=0.03)
  • The benefit in FFF with dose escalation to 78 Gy was more prominent in patients with pretreatment PSA >10 ng/ml, achieving a FFF rate of 62% vs. 43% for those who received 70 Gy (p=0.01)
  • There was no significant dose response for patients with a pretreatment PSA < 10 ng/ml in terms of FFF, with an average 6-year FFF rate of approximately 75%
  • There was no difference in overall survival
  • In patients with pretreatment PSA >10 ng/ml, there was a nearly significant improvement in freedom from distant metastasis at 6 years for those treated to 78 Gy (98% vs 88%, p = 0.056)
  • Grade 2 or higher rectal toxicity rates at 6 years for the 70 Gy and 78 Gy arms were 12% and 26%, respectively (p = 0.001)
  • Grade 2 or higher bladder toxicity rates were similar at 10%
  • In the 78 Gy arm, grade 2 or higher rectal toxicity highly correlated with the percentage of the rectal volume treated above 70 Gy

Author's Conclusions

  • A significant improvement in FFF was achieved by delivering an additional 8 Gy of radiotherapy in patients considered at intermediate-to-high risk of recurrence
  • Rectal side effects were significantly more frequent in those receiving the additional 8 Gy
  • Newer radiotherapy techniques that facilitate minimizing the rectal volume that receives > 70 Gy to less than 25% should help reducing the rectal complications

Clinical/Scientific Implications

    Dose escalation with radiation therapy has become extremely popular in the prostate cancer area despite limited long-term data. This study shows some benefit in regards to FFF in patients with a PSA > 10 ng/ml. There was no overall survival benefit. The authors used the FFF endpoint as opposed to strictly a PSA biochemical failure endpoint. It was not clear how many failed clinically but not biochemically. The current trend is to treat all early stage prostate cancer patients with higher doses then were traditionally delivered a few years ago, but this study does not support that practice for patients with a PSA < 10 ng/ml. There are some important technical issues in this study. The doses mentioned in this study are calculated at the isocenter of the radiation field. Doses at the periphery of the gland were ~5% lower. The group receiving 70 Gy was treated entirely with a 4-field technique while the group receiving 78 Gy was treated with a 4-field technique up to 46 Gy and then with a 3D-conformal technique with tight posterior/superior margins for the remainder 32 Gy. It is unknown how the outcome achieved by new technologies that use tighter margins (like IMRT) to reduce rectal complications will be affected by factors like organ motion, beam penumbra, and daily set-up variations

Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.

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