In a two-institute phase III trial reported in the Journal of Clinical Oncology, Malone et al found no difference in biochemical relapse–free survival with androgen-deprivation therapy (ADT) initiated prior to or concurrently with dose-escalated external-beam radiotherapy in patients with localized prostate cancer.

Study Details

In the open-label trial, 432 men with newly diagnosed localized prostate cancer with Gleason score < 7, clinical stage T1b to T3a disease, and prostate-specific antigen < 30 ng/mL were randomly assigned between July 2002 and March 2012 to receive neoadjuvant (n = 215) or concurrently initiated (n = 217) ADT with dose-escalated radiotherapy. ADT was given for 6 months, starting 4 months before radiotherapy in the neoadjuvant group and simultaneously with radiotherapy in the concurrent group.

ADT consisted of 50 mg of oral bicalutamide once daily plus 10.8 mg of subcutaneous goserelin starting 7 days after bicalutamide, with a second injection 3 months thereafter. All patients received a total radiotherapy dose of 76 Gy in 38 fractions over 7.5 weeks. The primary endpoint was biochemical relapse–free survival.

Biochemical Recurrence–Free Survival

The median follow-up of surviving patients was 146 months. At 10 years, rates of biochemical progression-free survival were 80.5% in the neoadjuvant group vs 87.4% in the concurrent group (hazard ratio [HR] for concurrent vs neoadjuvant group = 0.66, 95% confidence interval [CI] = 0.41–1.07, P = .10). At 10 years, overall survival rates were 76.4% vs 73.7% (HR = 0.94, 95% CI = 0.68–1.30, P = .70).

Toxicity

For the concurrent vs neoadjuvant groups, there were no differences in risk for grade ≥ 2 radiotherapy-related gastrointestinal (odds ratio [OR] = 0.79, P = .82) or genitourinary toxicity (OR = 1.11, P = .83). No significant differences were observed between the concurrent vs neoadjuvant groups in 3-year incidence of late radiotherapy-related grade ≥ 3 gastrointestinal (3.9% vs 2.5%) or genitourinary toxicity (2.9% vs 2.9%).

The investigators concluded, “In our study, there was no statistically significant difference in [biochemical relapse–free survival] between the two treatment groups. Similarly, no difference was seen in [overall survival] or late radiotherapy-related toxicities. On the basis of these results, both neoadjuvant and concurrent initiations of short-term ADT with dose-escalated [prostate] radiotherapy are reasonable standards of care for [localized prostate cancer].”

Shawn Malone, MD, of the Division of Radiation Oncology, The Ottawa Hospital Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by AstraZeneca. For full disclosures of the study authors, visit ascopubs.org.