Neoadjuvant and Adjuvant ADT With Dose-Escalated PRT Show Similar Outcomes in Prostate Cancer

Shawn Malone, MD

Neoadjuvant and concurrent androgen-deprivation therapy (ADT) with dose-escalated prostate radiotherapy (PRT) and concurrent and adjuvant ADT plus dose-escalated PRT were found to have no statistically significant differences in biochemical relapse-free survival (bRFS) in patients with localized prostate cancer, according to results of a phase III trial.

The 2 approaches also showed no difference in overall survival (OS) or PRT-related toxicities.

“On the basis of these results, both neoadjuvant and concurrent initiations of short-term ADT with dose-escalated PRT are reasonable standards of care for [localized prostate cancer],” first author Shawn Malone, MD, The Ottawa Hospital Regional Cancer Center, and coinvestigators wrote.

In the phase III trial, 432 patients with newly diagnosed localized prostate cancer were randomized between July 2002 and March 2012 to receive either neoadjuvant and concurrent ADT followed by dose-escalated PRT (n = 215) or concurrent and adjuvant ADT with PRT (n = 217).

Patients enrolled in the study had newly diagnosed localized prostate cancer with a Gleason score of ≤7 and clinical stage of T1b to T3a, and a prostate-specific antigen level of 30 ng/mL. Patients were randomly distributed to both arms for 6 months, 4 months prior to PRT (neoadjuvant group) or concurrent and adjuvant ADT for 6 months simultaneously with PRT (adjuvant group).

The primary endpoint was bRFS, and a stratified log-rank test was used to compare bRFS and OS. Incidence of grade ≥3 late PRT-related toxicities was compared by log-rank test.

The median duration of PRT in the neoadjuvant/concurrent and concurrent/adjuvant arms was 56 days and 57 days, respectively. PRT dose was reduced in 3 patients in the neoadjuvant arm and 1 patient in the adjuvant arm, and the median duration of ADT was 5.6 months in both arms. One patient in each arm did not receive ADT.

Moreover, the median follow-up of surviving patients across both arms was 146 months. A total of 40 and 28 patients experienced relapse in the neoadjuvant and adjuvant arms, respectively.

Across, both cohorts, 10-year bRFS rate was 83.6% (95% CI, 79.8%-87.6%). Five- and 10-year bRFS rates were 88.3% (95% CI, 84.0%-92.8%) and 80.5% (95% CI, 74.8%-86.6%), respectively, in the neoadjuvant/concurrent ADT arm. These rates were 91.8% (95% CI, 88.1%-95.6%) and 87.4% (95% CI, 82.7%-92.3%), respectively, in the concurrent/adjuvant ADT arm.

No significant difference in bRFS (P = .10) or OS (P = .70) were found between both groups. The 10-year OS rates were 76.4% and 73.7%, respectively. Relative to the neoadjuvant group, the hazard ratio for the adjuvant arm for bRFS was 0.66 (95% CI, 0.41-1.07) and was 0.94 for OS (95% CI, 0.68-1.30).

Regarding safety, researchers recorded a total of 147 deaths; 75 deaths occurred in the neoadjuvant arm and 72 in the concurrent arm. There was also no significant difference in the 3-year incidence of PRT-related grade ≥3 gastrointestinal (GI; 2.5% vs 3.9%) or genitourinary (GU; 2.9% vs 2.9%) adverse events (AEs).

Patients developed acute toxicity within a median of 41 days from the first treatment of PRT. The collective rates of late PRT-related grade ≥3 GI, GU, and other toxicities, over the course of 3-years were 2.5%, 2.9%, and 4.8%, in the neoadjuvant arm, and 3.9%, 2.9%, and 6.2%, in the adjuvant arm.

“Our study raises the possibility of a modest improvement in biochemical or clinical relapse with concomitant and adjuvant ADT rather than neoadjuvant and concurrent ADT combined with dose-escalated PRT in [localized prostate cancer],” Malone and coinvestigators wrote. “This difference, however, did not reach statistical significance, possibly because of a lower-than-anticipated event rate with a corresponding loss of statistical power…these results demonstrate encouraging long-term oncologic outcomes with the combination of short-term ADT and dose-escalated RT in intermediate-risk [prostate cancer]. The results of our study support flexibility in tailoring the sequence of ADT and RT to optimize treatment adherence and convenience for patients with [localized prostate cancer].”

Malone S, Roy S, Eapen L, et al. Sequencing of androgen-deprivation therapy with external-beam radiotherapy in localized prostate cancer: a phase III randomized controlled trial. J Clin Oncol. 2019;38(6):593-610. doi: 10.1200/JCO.19.01904.