TOPLINE

Although adverse pathologic features after radical prostatectomy are prognostic for worse outcomes in patients with prostate cancer, their cumulative burden does not predict the benefit of adding hormonal therapy to postoperative radiotherapy (PORT), a meta-analysis suggests. Even patients with multiple high-risk features, including grade group (GG) 4-5 disease and seminal vesicle invasion, did not experience differential overall survival or metastasis-free survival benefit when treated at prostate-specific antigen (PSA) levels < 0.5 ng/mL.

METHODOLOGY

• Pre-PORT PSA demonstrated a significant interaction effect with the benefit of hormone therapy in the POSEIDON analysis, and for patients with a PSA level > 0.5 ng/mL, outcomes with adding hormone therapy indicated a clinically meaningful benefit. In the new meta-analysis, researchers obtained individual patient data from five randomized phase 3 trials (RTOG 9601, GETUG-16, RADICALS-HD 2-way, RADICALS-HD 3-way, and RTOG 0534/SPPORT) comparing PORT alone with PORT plus hormone therapy in patients with recurrent prostate cancer, with a total of 4781 patients included.
• An adverse feature count (AFC) was prospectively defined as a simple integer score ranging from 0 to 4, summing four binary pathologic findings: GG 4-5 disease, seminal vesicle invasion, positive surgical margins, and extracapsular extension, with pre-PORT PSA excluded from the AFC.
• Intention-to-treat one-stage meta-analytical models stratified by trial were used to assess whether AFC modified the overall survival and/or metastasis-free survival treatment effect of adding hormone therapy to PORT, with adjustments for age group and log-transformed PSA, and AFC modeled both as a continuous integer and as categorical groups (AFC 0-1, low; AFC 2-3, intermediate; and AFC 4, high).
• A restricted AFC score (AFC2) ranging from 0 to 2, comprising only GG 4-5 and seminal vesicle invasion, was also evaluated as a prespecified sensitivity analysis, with a median follow-up of 9.14 years across all trials conducted in the United States, the United Kingdom, and France.

TAKEAWAY

• AFC was independently prognostic for both overall survival (hazard ratio [HR], 1.25; P < .001) and metastasis-free survival (HR, 1.29; P < .001) when analyzed as a continuous variable.
• AFC did not significantly modify the overall survival benefit of hormone therapy (interaction HR, 0.93) or metastasis-free survival benefit (interaction HR, 0.88) when adjusted for age and pre-PORT PSA.
• When restricting interaction analyses to a restricted AFC that included only presence of seminal vesicle invasion and/or GG 4-5 disease in 869 patients with a PSA level < 0.5 ng/mL, no significant interactions were found with the overall benefit of hormone therapy (interaction HR, 0.76) or metastasis-free survival benefit (interaction HR, 0.74).
• Results were similar when AFC was analyzed categorically and in two-stage analyses that yielded quantitatively similar results, suggesting no aggregation bias.

IN PRACTICE

“Overall, the data suggest that although adverse pathological features are prognostic, they do not appear predictive of [hormone therapy] benefit after [PORT], which is relevant for patients with a PSA ≤ 0.5 ng/mL before radiation,” the authors of the study wrote.

SOURCE

The study was led by Amar U. Kishan, MD, University of California, Los Angeles. It was published online on July 28 in European Urology.

LIMITATIONS

The analysis specifically evaluated the interaction between AFC and the impact of hormone therapy on metastasis-free survival and overall survival. While these interactions were not significant, this does not mean the absolute benefit of adding hormone therapy cannot be meaningfully different in patients with no AFC vs a high AFC because a given patient with a very high AFC could derive a quantitatively greater absolute benefit than a patient with a lower AFC even if the AFC does not directly modify this benefit. The study included patients enrolled in trials over a 17-year period from 1998 to 2015, with varying definitions of biochemical recurrence and heterogeneous approaches to surveillance and management. Because AFC is prognostic for metastasis-free survival and the trials were conducted before the advent of advanced molecular imaging, it is possible that patients with increasing AFC have occult metastatic disease that could obfuscate any impact of hormone therapy. Certain specific subgroups were limited in size, and the median follow-up of 9.1 years might still be limited with respect to a long-term benefit, particularly in younger patients and those with higher grade cancers.

DISCLOSURES

Kishan disclosed receiving grant support from the National Institutes of Health and the Department of Defense, as well as receiving contracts from Novartis, Janssen, Lantheus, Varian Medical Systems, and ViewRay Systems. He also reported receiving consulting fees from Lantheus, Varian Medical Systems, Novartis, and Janssen, along with receiving honoraria from Janssen, Boston Scientific, Varian Medical Systems, and Lantheus and holding low-value 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.