The first study was Randomized Trial of a Hypofractionated Radiation Regimen for the Treatment of Localized Prostate Cancer, published in Journal of Clinical Oncology. Three non-inferiority trials have been published to date on this topic – RTOG 0145, PROFIT, and CHHiP. PROFIT randomized 1204 men with intermediate risk prostate cancer to standard versus hypofractionated radiotherapy protocol. The primary endpoint of biochemical free survival demonstrated no differences between treatment arms (HR 0.96, 90% CI 0.77-1.20). Other endpoints such as PSA failure, clinical failure, start of ADT and prostate cancer death were not different in the protocols utilized. However, in this analysis, as well as a separate meta-analysis, there was a higher risk of acute GI toxicity in the hypofractionated group compared to standard protocols. Some caveats of this study include a relatively short follow up, the inability to apply these findings to patients with high risk disease, or lack of support for extreme hypofractionation regimens.
A second study analyzed was Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Compared a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer, published in International Journal of Radiation Oncology, Biology, and Physics. This study randomized 398 patients with intermediate and high-risk prostate cancer to a standard arm of 12 months of ADT and pelvic radiation to 46 Gy followed by a dose escalated EBRT to 78 Gy versus an experimental arm of low dose rate brachytherapy boost. Median follow up was 6.5 years and the primary endpoint was biochemical progression free survival. Data demonstrated a statistically significant improvement in biochemical progression in patients who received low dose rate brachytherapy (p=0.001). However, there was no difference in overall survival between the two groups. Additionally, the quality of life endpoints was worse for patients treated in the experimental group.
Finally, Dr. Bossi discussed Radiation with or without Antiandrogen Therapy in Recurrent Prostate Cancer, published in the New England Journal of Medicine. Previous publications had demonstrated a 5-year biochemical relapse free survival of approximately 55% in men with surgically treated high risk prostate cancers. Additionally, a quicker time from surgery to biochemical recurrence (<36 months vs >36 months) has been associated with worse 5 and 10-year cancer specific mortality. RTOG 96-01 randomized patients with pT3N0 or pT2N0 with positive margins to 64.8 Gy EBRT with antiandrogen therapy (bicalutamide 150mg daily) versus placebo. Patients treated with bicalutamide had a 12-year OS of 76.3% compared to 71.3% in the placebo group (HR 0.77, 95% CI 0.59-0.99, p=0.04). Additionally, patients with higher PSA (>1.5 ng/ml) had greater benefit in overall survival with bicalutamide therapy compared to placebo (HR 0.45, 95% CI 0.25-0.81, p=0.007). In conclusion, the addition of 24 months of 150mg/day of bicalutamide to salvage radiotherapy resulted in greater overall survival with a lower rate of death from prostate cancer and lower rate of distant metastasis without higher toxicity.
Presented by: Alberto Bossi, MD Department of Radiation Oncology Institut Gustave Roussy, Villejuif
Written by: David B. Cahn, DO, MBS @dbcahn, Fox Chase Cancer Center, Philadelphia, PA at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA