Intensified systemic therapy with ADT improves outcomes in high-risk prostate cancer

In patients with high-risk or unfavourable nonmetastatic prostate cancer (nmPC) receiving local definite therapy, the intensification of systemic therapy using chemotherapy or an androgen receptor signaling inhibitor (ARSI), in combination with androgen deprivation therapy (ADT), leads to better oncologic survival measures, reports a recent meta-analysis.

Drawing from the online databases of Scopus, Web of Science, and PubMed, researchers synthesized evidence from 15 randomized studies, nine of which looked at chemo-hormonal treatments and six assessed ARSI-based strategies. Primary outcomes included overall survival (OS), cancer-specific survival (CSS), metastasis-free survival (MFS), and failure-free survival (FFS). Adverse events and pathologic outcomes were also assessed as secondary endpoints.

In patients treated with radiation therapy alone, the combination of docetaxel and ADT led to a significantly improved FFS (hazard ratio [HR], 0.72, 95 percent confidence interval [CI], 0.63–0.84; p<0.001), but not OS (p=0.3), CSS (p=0.072), or MFS (p=0.079).

In contrast, the ARSI-ADT combination significantly improved OS (HR, 0.60, 95 percent CI, 0.48–0.73), CSS (HR, 0.49, 95 percent CI, 0.37–0.65), MFS (HR, 0.54, 95 percent CI, 0.45–0.65), and FFS (HR, 0.39, 95 percent CI, 0.33–0.47; p<0.001 for all).

Network meta-analysis confirmed that ARSI+ADT outperformed docetaxel+ADT in terms of survival endpoints, while also conferring a more favourable safety profile.

“The highest efficacy was achieved with ARSI plus ADT, specifically in patients treated with radiation therapy, providing a new standard-of-care in high-risk disease,” the researchers said.

“Nonetheless, we currently lack strong evidence regarding the benefits of routine administration of combination therapies in the radical prostatectomy setting to justify their toxicity,” they added.

“There is a need for future studies to identify the patients with nmPC who will benefit the most from specific drug combinations,” the researchers said.