ORLANDO—Dose-escalated three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) do not improve overall survival (OS) compared with lower-dose radiotherapy regimens for localized prostate cancer, according to a randomized phase 3 clinical trial (Abstract 4) reported during the 2015 Genitourinary Cancers Symposium.1
“Dose escalation to 79.2 Gy for intermediate risk prostate cancer did not improve overall or disease-specific survival,” reported lead study author Jeff M. Michalski, MD, of Washington University in St. Louis in St. Louis, MO. “Dose escalation did improve local control, distant metastasis-free, and biochemical disease-free survivals.”
The study was the largest randomized trial to date, Dr. Michalski noted.
“Patients receiving high dose radiation experience more late toxicity,” Dr. Michalski noted. However, dose escalation was also associated with fewer salvage therapies.
A total of 1,499 men with localized prostate cancer were deemed eligible and were randomly assigned to receive 79.2 Gy in 44 fractions (751 patients) or 70.2 Gy in 39 fractions (748 patients) radiotherapy. Median age was 69 years; 70% of participants had PSA less than 10 ng/mL. Sixty-six percent of participants received 3DCRT.
At a median follow-up of 7.0 years, the 5-year and 10-year OS rates were 88% and 67%, respectively, for men in the 79.2 Gy arm and 89% and 66%, respectively, in the 70.2 Gy arm (P=0.87, not significant).
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“There was, however, a striking improvement in biochemical outcomes,” noted Dr. Michalski. ASTRO biochemical failure rates at 5 and 10 years in the 79.2 Gy arm were 25% (Phoenix: 16%) and 30% (Phoenix: 26%), respectively. In the 70.2 Gy arm the ASTRO biochemical failure rates at 5 and 10 years were 40% (Phoenix: 21%) and 45% (Phoenix: 43%), respectively (Ps<0.0001).
The 5-year and 10-year local progression and distant metastasis rates were also statistically significantly different between the 79.2 Gy arm and the 70.2 Gy arm (Ps=0.0059 and 0.026, respectively).
“The high dose arm had lower rate of salvage therapy, 13.5% versus 20.6% (P=0.0002),” Dr. Michalski said. “Time to late grade 3 or higher GI [toxicity] was higher for the 79.2Gy arm (P=0.035) but time to late grade 3 or higher GU toxicity was not (P=0.14).”
Grate 3 or higher gastrointestinal late toxicities (RTOG/EORTC criteria) were significantly elevated in the 79.2 Gy study arm participants compared to the 70.2 Gy study arm (5% vs. 3% at 5 years and 5% vs 4% at 10 years; P=0.036).
- Michalski JM, Moughan J, Purdy J, et al. A randomized trial of 79.2Gy versus 70.2Gy radiation therapy (RT) for localized prostate cancer. 2015 Genitourinary Cancers Symposium. Abstract 4.