Large phase III study showing short-term ADT + EBRT did not show an improvement in OS compared to EBRT alone. There was an improvement in PSA failure, metastasis rates and prostate cancer-related deaths. If used, SADT+EBRT should be highly individualized, preferably in patients with longer life expectancies and higher SE risk tolerance.
It remains unknown whether or not short-term androgen deprivation (STAD) improves survival among men with intermediate-risk prostate cancer (IRPC) treated with dose-escalated radiotherapy (RT).
The NRG Oncology/Radiation Therapy Oncology Group 0815 study randomly assigned 1,492 patients with stage T2b-T2c, Gleason score 7, or prostate-specific antigen (PSA) value >10 and ≤20 ng/mL to dose-escalated RT alone (arm 1) or with STAD (arm 2). STAD was 6 months of luteinizing hormone–releasing hormone agonist/antagonist therapy plus antiandrogen. RT modalities were external-beam RT alone to 79.2 Gy or external beam (45 Gy) with brachytherapy boost. The primary end point was overall survival (OS). Secondary end points included prostate cancer–specific mortality (PCSM), non-PCSM, distant metastases (DMs), PSA failure, and rates of salvage therapy.
Median follow-up was 6.3 years. Two hundred nineteen deaths occurred, 119 in arm 1 and 100 in arm 2. Five-year OS estimates were 90% versus 91%, respectively (hazard ratio [HR], 0.85; 95% CI, 0.65 to 1.11]; P = .22). STAD resulted in reduced PSA failure (HR, 0.52; P <.001), DM (HR, 0.25; P <.001), PCSM (HR, 0.10; P = .007), and salvage therapy use (HR, 0.62; P = .025). Other-cause deaths were not significantly different (P = .56). Acute grade ≥3 adverse events (AEs) occurred in 2% of patients in arm 1 and in 12% for arm 2 (P <.001). Cumulative incidence of late grade ≥3 AEs was 14% in arm 1 and 15% in arm 2 (P = .29).
STAD did not improve OS rates for men with IRPC treated with dose-escalated RT. Improvements in metastases rates, prostate cancer deaths, and PSA failures should be weighed against the risk of adverse events and the impact of STAD on quality of life.
10-year metastasis-free survival was 71.9% in the short-course ADT group (6 months) and 78% in the long-course ADT group (24 months). So, it seems the longer the duration, the better the outcome. 93% had a Gleason score of 7 or higher.
We know that combination PARP and antiandrogen is better than antiandrogen alone. I have wondered if we need antiancrogen on those patients. This shows that, YES, we do. The combination also was better than PARP inhibitor monotherapy in those patients carrying HRRm.
It might be costly to get the PET scans but helps with prognosis and directing patients to palliative care since positive lesions in all predicts shorter overall survival.
The role for immunotherapy in combination with multitargeted therapy in prostate cancer, for patients who had previous docetaxol, or had visceral disease (liver) showed more benefit from the combination vs. second novel hormonal therapy. Recall that patients who had exposure to docetaxol can be treated with pluvicto. Genomic and genetic testing is encouraged for those patients as PARP targeted mutations can be found (homologous recombination-repair mutations).
SBRT improves PFS in addition to antiandrogen therapy. The question is, with oligomets, do we need systemic therapy in all patients? Or will SBRT be sufficient?
I encourage our FCS radiation oncologists to provide their input on this study, as well.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
