Metastasis-Directed Therapy Improves Survival in Oligometastatic Prostate Cancer
Meta-analysis of seven phase 2 trials shows metastasis-directed therapy plus standard care significantly improves progression-free survival and other endpoints in oligometastatic prostate cancer patients, with a near-significant trend toward improved overall survival.
Adding metastasis-directed therapy to standard of care was associated with significant improvements in several survival endpoints in oligometastatic prostate cancer, according to research published in the February issue of The Lancet Oncology. The systematic review and individual patient data meta-analysis examined 574 men with oligometastatic prostate cancer across seven randomized phase 2 trials.
Six trials randomly assigned 472 patients to metastasis-directed therapy plus standard of care versus standard of care alone (248 and 224, respectively), with a median follow-up of 40.7 months. Patients had up to five metastases at enrollment.
Metastasis-directed therapy was associated with improved progression-free survival, with a trial-level hazard ratio of 0.44 and patient-level hazard ratio of 0.45. In the pooled analysis, this translated to an estimated median progression-free survival improvement of approximately 7.6 months.
The therapy also showed significant improvement in radiographic progression-free survival, with a trial-level hazard ratio of 0.60 and patient-level hazard ratio of 0.59. The estimated median improvement was approximately 4.9 months. Castration resistance-free survival also improved significantly, with a trial-level hazard ratio of 0.58 and 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. The trial-level hazard ratio was 0.63 (95% CI, 0.39-1.00; P = .051) and patient-level hazard ratio was 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. The research team noted that metastasis-directed therapy significantly benefits patients without adding any notable safety risks.
The study had several limitations including inconsistent definitions of progression-free survival 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.
The study was supported by the Cancer Center Support Grant to MD Anderson Cancer Center from the National Cancer Institute and philanthropic support.