# Treatment Intensification Prior to Radical Prostatectomy for Clinically Localized Prostate Cancer

## TL;DR

This review discusses the potential benefits and ongoing research on using hormone therapy before surgery for high-risk prostate cancer.

## Contribution

The paper provides a comprehensive overview of recent studies and ongoing trials on neoadjuvant therapy for localized prostate cancer.

## Key findings

- Neoadjuvant ADT may reduce surgical complexity and improve pathologic outcomes.
- Current trials are exploring second-generation androgen blockers and PARP inhibitors for long-term survival benefits.
- Despite some benefits, neoadjuvant ADT has not yet shown improvements in cancer progression or survival.

## Abstract

For unfavorable intermediate- or high-risk prostate cancer, current guidelines primarily recommend radical prostatectomy (RP) or radiation with androgen deprivation therapy (ADT). While emerging interest exists in neoadjuvant ADT prior to RP for this population, previous trials, despite suggesting benefits like reduced surgical complexity, pathologic downstaging, decreased positive margins, and lower nodal positivity, have not demonstrated improvements in cancer progression or survival, thereby precluding its routine recommendation for surgical patients. Conversely, as ADT remains a cornerstone for metastatic disease, there is ongoing exploration of its expanded neoadjuvant use for clinically localized disease, with several ongoing trials investigating second-generation androgen blockers, radiopharmaceuticals, and PARP inhibitors to assess potential long-term cancer-specific survival benefits. This review will comprehensively overview the recent literature and ongoing efforts to integrate neoadjuvant therapy for clinically localized prostate cancer patients at high risk of recurrence post-prostatectomy.

Current guidelines recommend either radical prostatectomy (RP) or radiation with androgen deprivation therapy (ADT) for unfavorable intermediate- or high-risk prostate cancer. There has been emerging interest in the potential benefits of neoadjuvant ADT prior to RP for this population. Past trials indicate neoadjuvant ADT may be associated with reduced surgical complexity, pathologic downstaging, decreased positive margins, and decreased rates of nodal positivity, although they have not shown benefits for cancer progression and survival. Accordingly, neoadjuvant ADT is currently not recommended for surgical patients. Conversely, ADT is a mainstay of treatment in metastatic disease, and interest remains in expanding its use towards patients with clinically localized disease. There are several ongoing trials of second-generation androgen blockers such as enzalutamide, darolutamide, radiopharmaceuticals, and poly (ADP-ribose) polymerase (PARP) inhibitors to explore long-term cancer-specific survival benefits with neoadjuvant use. In this narrative review, we provide a comprehensive overview of the recent literature and ongoing efforts to incorporate neoadjuvant therapy for clinically localized prostate cancer patients who are at high-risk of recurrence after prostatectomy.