In a phase III trial (NRG Oncology/RTOG 0534 SPPORT) reported in The Lancet, Alan Pollack, MD, PhD, and colleagues found that both the addition of short-term androgen-deprivation therapy (ADT) and the addition of ADT and pelvic lymph node radiotherapy (PLNRT) to salvage prostate bed radiotherapy (PBRT) improved freedom from disease progression among patients with persistent prostate-specific antigen (PSA) levels after prostatectomy for adenocarcinoma of the prostate.

Alan Pollack, MD, PhD

Study Details

In the open-label trial, 1,716 eligible patients from sites in the United States, Canada, and Israel were randomly assigned 1:1:1 between March 2008 and March 2015 to receive PBRT alone (n = 564), PBRT plus 4 to 6 months of ADT (n = 578), or PBRT plus short-term ADT plus PLNRT (n = 574). PBRT consisted of 64.8 to 70.2 Gy at 1.8 Gy per fraction daily. PLNRT consisted of 45 Gy at 1.8 Gy per fraction, and then a volume reduction to the planning target volume for the remaining 19.8 to 25.2 Gy. ADT was started 2 months before radiotherapy, and consisted of 250 mg of flutamide three times daily or 50 mg of oral bicalutamide once daily and injections of long-acting luteinizing hormone-releasing hormone agonists.

The primary endpoint was freedom from progression, with progression defined as biochemical failure (PSA ≥ 2 ng/mL over the nadir PSA), clinical failure (local, regional, or distant), or death from any cause. A planned interim analysis was performed in 1,191 patients, including 399 in the PBRT group, 398 in the PBRT/ADT group, and 394 in the PBRT/ADT/PLNRT group. Significance of comparisons between groups was set at P < .001.

Freedom From Progression Rates

In the interim analysis among 1,191 patients, 5-year freedom from progression rates were 71.1% (95% confidence interval [CI] = 66.4%–75.9%) in the PBRT group, 82.7% (95% CI = 78.8%–86.6%) in the PBRT/ADT group (difference vs PBRT = 11.5%, P = .00011), and 89.1% (95% CI = 85.9%–92.2%) in the PBRT/ADT/PLNRT group (difference vs PBRT = 17.9%, P <.0001; difference vs PBRT/ADT= 6.4%, P = .0063).

At the final planned analysis among all 1,716 patients, with additional follow-up after interim analysis (median follow-up among survivors of 8.2 years, interquartile range = 6.6–9.4 years), 5-year freedom from progression rates were 70.9% (95% CI = 67.0%–74.9%) in the PBRT group, 81.3% (95% CI = 78.0%–84.6%) in the PBRT/ADT group (difference vs PBRT = 16.5%, P < .0001), and 87.4% (95% CI = 84.7%–90.2%) in the PBRT/ADT/PLNRT group (difference vs PBRT = 10.4%, P < .0001; difference vs PBRT/ADT = 6.1%, P = .0027).

Toxicity

Acute grade ≥ 2 adverse events were significantly more common in the PBRT/ADT/PLNRT group vs the PBRT/ADT group (44% vs 36%, P = .0034) and in the PBRT/ADT group vs the PBRT group (18%, P < .0001). Grade ≥ 3 acute adverse events occurred in 11%, 7%, and 3% of patients, respectively (overall P < .0001). Late toxicity did not differ significantly between the groups, except for more late grade ≥ 2 blood or bone marrow events in the PBRT/ADT/PLNRT group vs the PBRT/ADT group (4% vs 2%, P = .0060).  

The investigators concluded, “The results of this randomized trial establish the benefit of adding short-term ADT to PBRT to prevent progression in prostate cancer. To our knowledge, these are the first such findings to show that extending salvage radiotherapy to treat the pelvic lymph nodes when combined with short-term ADT results in meaningful reductions in progression after prostatectomy in patients with prostate cancer.”

Dr. Pollack, of the Department of Radiation Oncology, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, is the corresponding author for The Lancet article.

Disclosure: The study was funded by the National Cancer Institute. For full disclosures of the study authors, visit thelancet.com.