Therapy Intensification Improves Oncologic Endpoints in High-Risk Nonmetastatic Prostate Cancer

Intensification of systemic therapy beyond hormonal treatment can benefit selected patients with high-risk nonmetastatic prostate cancer, according to study findings published in European Urology.

Researchers conducted a systematic review and meta-analysis of 15 studies to assess outcomes in patients with high-risk and/or unfavorable nonmetastatic prostate cancer (nmPC) after adding combination systemic treatment to primary definitive local therapy. Nine of the studies evaluated chemohormonal treatment and 6 looked at androgen receptor signaling inhibitor (ARSI) treatment strategies.

The investigation revealed several findings. In both radical prostatectomy and radiation therapy settings, adding docetaxel to androgen deprivation therapy was associated with significantly better cancer-specific survival (researchers reported a .68 pooled hazard ratio), metastasis-free survival (.82 pooled hazard ratio), and failure-free survival (.70 pooled hazard ratio). The pooled hazard ratio for overall survival was .86, which did not meet the conventional level of statistical significance.

For patients treated with radiation therapy alone, docetaxel-based combination treatment met the significance threshold for failure-free survival (.72 pooled hazard ratio) but not for overall survival, cancer-specific survival, or metastasis-free survival.

The investigation also revealed that compared with androgen deprivation therapy alone, adding docetaxel to androgen deprivation therapy resulted in a more than threefold higher likelihood of grade 3 or higher adverse events among patients with nmPC.

Finally, network meta-analysis of radiation therapy studies showed that androgen receptor signaling inhibitor plus androgen deprivation therapy outperformed docetaxel plus androgen deprivation therapy for survival endpoints with an adverse event profile that was more favorable.

“Intensification of systemic therapy with docetaxel or an androgen receptor signaling inhibitor in addition to androgen deprivation therapy improves oncologic endpoints in high-risk and/or unfavorable nmPC treated with local definitive therapy,” concluded researchers. “The highest efficacy was achieved with androgen receptor signaling inhibitor plus androgen deprivation therapy, specifically in patients treated with radiation therapy.”

Reference:
Rajwa P, Pradere B, Gandaglia G, et al. Intensification of systemic therapy in addition to definitive local treatment in nonmetastatic unfavourable prostate cancer: a systematic review and meta-analysis. Eur Urol. Published online April 21, 2022. S0302-2838(22)01802-4. doi:10.1016/j.eururo.2022.03.031