Addition of androgen deprivation therapy to PBRT halts progression of prostate cancer: Lancet

A new study published in The Lancet shows the advantage of combining short-term androgen deprivation treatment (ADT) with prostate bed radiation (PBRT) to prevent prostate cancer development.

Salvage prostate bed radiation leads to around 70% of patients being free of progression at 5 years in males with detectable prostate-specific antigen (PSA) levels following prostatectomy for prostate cancer. A three-group randomized experiment was planned and conducted by Alan Pollack and team to see if adding 4–6 months of short-term androgen deprivation treatment to PBRT, or both short-term ADT and pelvic lymph node radiation (PLNRT) to PBRT, may result in incremental increases in patient outcomes.

The SPPORT experiment was conducted at 283 radiation oncology cancer treatment centers in the United States, Canada, and Israel. It was an international, randomized, multicenter, controlled trial. Eligible patients (aged 18 years) had a consistently detectable or originally undetected and growing PSA of between 01 and 20 ng/mL following prostatectomy for prostate cancer. If there was no clinical or pathological indication of lymph node involvement, patients with and without lymphadenectomy (N0/Nx) were eligible. Other qualifying criteria were pT2 or pT3 disease, a Gleason score of 9 or less after prostatectomy, and a Zubrod performance status of 0–1. Eligible patients were randomly randomized to one of three groups: PBRT alone (group 1), PBRT plus short-term ADT (group 2), or PLNRT plus PBRT plus short-term ADT (group 3). The primary outcome was independence from progression, which was defined as biochemical failure using the Phoenix criteria, clinical failure, or death from any cause. A proposed interim analysis of 1191 patents with a minimum prospective follow-up duration of 5 years used a Haybittle-Peto threshold of p0001 (one-sided) to compare 5-year freedom from progression rates across treatment groups.

The key findings of this study were as follow:

1. 1792 eligible patients were enrolled and randomly allocated to one of three therapy groups between March 31, 2008 and March 30, 2015.

2. 76 individuals who were later discovered to be ineligible were eliminated from the analysis, leaving 1716 patients in the evaluable patient sample.

3. When group 1 was compared to group 3, the Haybittle-Peto barrier for 5-year independence from progression was exceeded at the interim analysis.

4. The disparity between groups 2 and 3 did not go above the limit.

5. With extended follow-up beyond the interim analysis, the 5-year freedom from progression rates across all 1716 eligible patients were 70.9% in group 1, 81.3% in group 2, and 87.4% in group 3.

6. According to protocol criteria, group 3's independence from advancement was superior to groups 1 and 2.

7. Acute grade 2 or greater adverse events were substantially more likely in group 3 than in group 2, which was more common than in group 1.

8. Similar outcomes were seen for adverse events of grade 3 or above.

9. Late toxicity, however, did not differ substantially between groups, with the exception of more late grade 2 or worse blood or bone marrow events in group 3 compared to group 2 due to the inclusion of PLNRT in this group.

In conclusion, these are the first studies to indicate that combining short-term ADT with salvage radiation to treat pelvic lymph nodes leads to considerable decreases in progression following prostatectomy in patients with prostate cancer.

Reference:

Pollack, A., Karrison, T. G., Balogh, A. G., Gomella, L. G., Low, D. A., Bruner, D. W., Wefel, J. S., Martin, A.-G., Michalski, J. M., Angyalfi, … Sandler, H. M. (2022). The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial. In The Lancet (Vol. 399, Issue 10338, pp. 1886–1901). Elsevier BV. https://doi.org/10.1016/s0140-6736(21)01790-6