Phase I/II trial of combined hormonal therapy and hypofractionated accelerated radiotherapy with concomitant intensity-modulated boost for high-risk prostate cancer: Toxicity analysis.

Abstract

4634 Background: Combined external beam radiotherapy (RT) and 2-3 years of hormonal therapy (HT) is a standard treatment option for high risk localized prostate cancer. Dose escalated RT alone has been shown to improve disease-free survival. Increased sensitivity of prostate cancer to high dose per fraction has led to hypofractionation as a method to radiobiologically escalate dose. We report on the acute and late toxicities of combining hypofractionated RT and HT. Methods: A prospective phase I/II study enrolling patients with any of: clinical T3, PSA ≥20, or Gleason ≥8. Forty-five Gy (1.8 Gy/fraction) was delivered to the pelvic nodes (4-field technique for the first 67 patients and intensity-modulated radiotherapy (IMRT) for the next 30 patients) with a concomitant 22.5 Gy boost to the prostate using IMRT, for a total of 67.5 Gy (2.7 Gy/fraction), in 25 fractions over 5 weeks. Image-guidance was performed using 3 gold seed fiducials. Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group late morbidity scores were used to assess acute and late toxicities, respectively. Biochemical failure was determined by Phoenix definition. Results: Ninety-seven patients were treated and followed for a median of 39 months, with 88% of patients having a minimum 24 months follow-up. Maximum toxicity scores are reported. Acute gastrointestinal (GI) toxicities were Grade 0 in 7%, 1 in 55%, and 2 in 38%. Acute urinary toxicities were Grade 0 in 3%, 1 in 52%, 2 in 40%, and 3+ in 5%. Late GI toxicities were Grade 0 in 55%, 1 in 39%, and 2 in 6%. There were no Grade 3+ late GI toxicities. Late urinary toxicities were Grade 0 in 81%, 1 in 10%, 2 in 5%, and 3+ in 4%. Most severe (Grade 3+) toxicities resolved at last follow-up with only 1 patient with Grade 3 late urinary toxicity. To date, 3 patients have failed biochemically. Conclusions: Pelvic RT with concomitant hypofractionated IMRT boost to the prostate combined with HT is well tolerated with low rates of severe late GI and urinary toxicity. Additional follow-up is necessary to evaluate biochemical control and 5 year prostate biopsy results. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca AstraZeneca, sanofi-aventis