JU INSIGHT Neoadjuvant Novel Hormonal Therapy Followed by Prostatectomy versus Up-Front Prostatectomy for High-Risk Prostate Cancer: A Comparative Analysis

By: Praful Ravi, MB, BChir; Lucia Kwak, MS; Wanling Xie, MS; Kaitlin Kelleher, MD; Andres M. Acosta, MD; Rana R. McKay, MD; Adam S. Kibel, MD; Mary-Ellen Taplin, MD | Posted on: 01 Oct 2022

Ravi P, Kwak L, Xie W, et al. Neoadjuvant novel hormonal therapy followed by prostatectomy versus up-front prostatectomy for high-risk prostate cancer: a comparative analysis. J Urol. 2022;208(4)838-845.

Study Need and Importance

Neoadjuvant therapy has been proposed as a means to improve outcomes in men with high-risk prostate cancer (HRPC). Though trials evaluating neoadjuvant androgen deprivation therapy did not show improved survival compared to radical prostatectomy (RP) alone, encouraging rates of pathological response have been seen in recent phase 2 trials evaluating novel hormonal agents (NHAs). These have led to the ongoing phase 3 PROTEUS trial where men with HRPC are randomized to neoadjuvant (and adjuvant) androgen deprivation therapy with or without apalutamide. However, this study will not directly compare outcomes between neoadjuvant therapy and up-front RP. We therefore assessed oncologic outcomes in a cohort of patients with HRPC treated on a clinical trial at our institution with a neoadjuvant NHA (neo-RP, 112) and a comparator cohort of patients who received up-front RP (259), and used the inverse probability of treatment weighting (IPTW) method to minimize confounding between the 2 cohorts.

What We Found

Median followup after RP was 4 years in both cohorts. After IPTW, time to biochemical recurrence was significantly longer in the neo-RP group compared to the RP group (HR=0.25, p <0.01). The neo-RP group had significantly improved metastasis-free survival (MFS; HR=0.26, p <0.01), with a 3-year MFS of 96% compared to 68% in the RP group (see Figure).

Figure. MFS in the neo-RP and RP cohorts after IPTW. The number of participants at risk is based on unweighted population.

Limitations

This was a comparative analysis between a clinical trial cohort (neo-RP) and an observational, retrospective cohort (RP) and there are likely unmeasured confounders beyond those addressed by IPTW. There was selection bias in that the RP group met eligibility criteria for the neoadjuvant trials but underwent up-front RP.

Interpretation for Patient Care

Neoadjuvant therapy with an NHA significantly improved oncologic outcomes compared to up-front RP for men with HRPC. These are hypothesis-generating findings and need validation in a randomized trial before neoadjuvant therapy can become a standard-of-care in the treatment of HRPC.

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