TOPLINE:

In patients with oligometastatic prostate cancer, metastasis-directed therapy plus standard of care was associated with significant improvements in progression-free survival (PFS), radiographic PFS, and castration resistance-free survival compared to standard of care alone. Researchers reported a near-significant trend toward improved overall survival and found adverse event rates were similar between groups.

METHODOLOGY:

• Metastasis-directed therapy is increasingly being incorporated into the management of oligometastatic prostate cancer, though most prior randomized prospective evidence has come from phase 2 trials.
• In the current study, researchers conducted a systematic review and individual patient-level meta-analysis to evaluate the efficacy of metastasis-directed therapy in oligometastatic prostate cancer.
• The researchers identified seven randomized phase 2 trials that included 574 men with oligometastatic prostate cancer (up to five metastases). Six of these trials randomly assigned patients to metastasis-directed therapy plus standard of care (n = 248) vs standard of care alone (n = 224); the seventh randomly assigned patients to metastasis-directed therapy plus observation or plus intermittent hormone therapy.
• Primary endpoints were PFS and overall survival, with secondary endpoints of radiographic PFS and castration resistance-free survival. Median follow-up time was 40.7 months.

TAKEAWAY:

• Adding metastasis-directed therapy to standard of care was associated with a significant improvement in PFS (trial-level hazard ratio [HR], 0.44; P < .0001; patient-level HR, 0.45; P < .0001) compared with standard of care alone. In the pooled analysis, this translated to an estimated median PFS improvement of approximately 7.6 months.
• Metastasis-directed therapy was associated with a significant improvement in radiographic PFS (trial-level HR, 0.60; P = .0039; patient-level HR, 0.59; P < .0001), with an estimated median improvement of approximately 4.9 months. Metastasis-directed therapy was also associated with a significant improvement in castration resistance-free survival (trial-level HR, 0.58; P = .019), with an estimated median improvement of about 2.5 months.
• Overall survival outcomes favored the metastasis-directed therapy group, but the benefit was not statistically significant (trial-level HR, 0.63; 95% CI, 0.39-1.00; P = .051; patient-level HR, 0.64; 95% CI, 0.40-1.01; P = .057).
• Adverse event rates were similar between groups both in individual trials and the pooled analysis.

IN PRACTICE:

“In lieu of phase 3 randomized trials, to the best of [our] knowledge, these data provide the most compelling evidence to date of benefit from [metastasis-directed therapy] across endpoints,” the study authors concluded.

“We commend the authors for this important and timely meta-analysis, which provides evidence supporting [metastasis-directed therapy] in oligometastatic prostate cancer,” according to the authors of an accompanying editorial.

SOURCE:

The study, led by Chad Tang, MD, The University of Texas MD Anderson Cancer Center in Houston, and an accompanying editorial were published online in The Lancet Oncology.

LIMITATIONS:

The study had several limitations including inconsistent definitions of PFS across trials. The widespread availability of salvage therapies and relatively favorable prognosis of metastatic prostate cancer made signals for later endpoints like overall survival difficult to interpret. Standard of care regimens were heterogeneous, reflecting different trial eras, with observation and single-agent androgen deprivation therapy not reflecting current practice. Additionally, caution should be taken in extrapolating results from patients staged with conventional imaging to those using PSMA-PET, which represents the most sensitive current imaging approach.

DISCLOSURES:

The study was supported by the Cancer Center Support Grant to MD Anderson Cancer Center from the National Cancer Institute and philanthropic support. Tang disclosed serving on scientific advisory boards for Bayer, Lantheus, Telix Pharmaceuticals, and Molli Surgical and receiving honoraria from Elekta, support for attending meetings from Vision RT, consulting fees from Boston Scientific, royalties from Wolters Kluwer, and research support from Myriad Genetics, Merck, and Guardant Health. 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.