TOPLINE:

A recent meta-analysis suggests there may be no meaningful overall survival benefit from adding hormone therapy to early salvage postoperative radiotherapy (PORT) in patients with prostate cancer who had low prostate-specific antigen (PSA) levels (≤ 0.5 ng/mL) at baseline. However, subgroup analyses revealed that adding hormone therapy was associated with improved overall survival among patients who have higher PSA levels, with the greatest benefit likely among those with PSA levels of ≥ 1.6 ng/mL. 

METHODOLOGY:

• Adding hormonal therapy to definitive radiotherapy for intact prostate cancer has been shown to improve overall survival, but the overall survival benefit of adding hormonal therapy to PORT for prostate cancer remains unclear.
• Researchers conducted an individual patient data meta-analysis of 6 randomized phase 3 trials comparing PORT with or without hormone therapy. The analysis included 6057 patients with a median follow-up of 9.0 years.
• The primary outcome was overall survival, with analyses evaluating the effect of adding hormone therapy, short-term hormone therapy (4-6 months), or long-term hormone therapy (24 months) to PORT.
• Most patients in the analysis (86%) received androgen deprivation therapy (ADT) with gonadotropin releasing hormone agonist medications.

TAKEAWAY:

• Overall, adding hormone therapy to PORT was not associated with a significant improvement in overall survival (hazard ratio [HR], 0.87; P = .06), with 10-year overall survival rates of 83.6% with PORT alone vs 84.3% with PORT plus hormone therapy.
• When looking at survival outcomes by PSA level before PORT, the associations varied. Among patients with PSA ≤ 0.5 ng/mL at baseline, adding hormone therapy to PORT was not associated with an overall survival benefit. However, subgroup analyses revealed that adding hormone therapy was associated with improved overall survival among patient with PSA levels between 0.51-1.00 ng/mL (HR, 0.72; P = .02) and PSA greater than 1.00 ng/mL (HR, 0.69; P = .03) with the most notable benefit among those with PSA ≥ 1.6 ng/mL, according to an exploratory analysis.
• Adding hormone therapy was associated with improvements in metastasis-free survival (HR, 0.79; P < .001), with 10-year rates of 74.1% with PORT alone vs 77.9% with the addition of hormone therapy, though the magnitude of benefit was small.
• No significant interaction was found between hormone therapy duration and overall survival effect (P for interaction = .17), with similar outcomes for short-term and long-term hormone therapy.

IN PRACTICE:

“Our findings, we believe, provide the strongest level of evidence to date suggesting there might be no meaningful overall survival benefit to adding hormone therapy, either short-term or long-term hormone therapy, to PORT for PSA [of] 0.5 ng/mL or less,” the authors concluded.

SOURCE:

The study, led by Amar U Kishan, MD, University of California, Los Angeles, was published online in Lancet.

LIMITATIONS:

The analysis included patients enrolled over a 17-year period (1998-2015) during which biochemical recurrence definitions varied and both stage and Gleason grade migration occurred; however, trial-stratified models ensured comparisons against concurrent controls. Most patients received gonadotropin releasing hormone agonist-based hormone therapy, with a notable exception being androgen receptor antagonist monotherapy in NRG/RTOG 9601, which contributed 70% of patients in the long-term hormone therapy subgroup and may have diluted results. Detailed information on baseline comorbidities, PSA doubling times, and testosterone recovery was not available. A larger impact on overall survival with longer follow-up cannot be ruled out.

DISCLOSURES:

The National Institutes of Health (NIH) provided funding for this study. Kishan disclosed receiving grant support from the NIH and the Department of Defense; contracts from Novartis, Janssen, Lantheus, Varian Medical Systems, and ViewRay Systems; consulting fees from Lantheus, Varian Medical Systems, Novartis, and Janssen; honoraria from Janssen, Boston Scientific, Varian Medical Systems, and Lantheus; and holding stock in MiraDx and Alethian AI. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.