Dr Ravi on Neoadjuvant ARPIs Prior to Radical Prostatectomy in Prostate Cancer

Praful K. Ravi, MB, BChir, MRCP, medical oncologist, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, instructor, medicine, Harvard Medical School, discusses findings from a pooled analysis of 5 phase 2 trials conducted between 2006 to 2018 that evaluated the use of neoadjuvant androgen receptor pathway inhibitors (ARPIs) prior to radical prostatectomy in patients with high-risk, localized prostate cancer.

Ravi and colleagues presented findings from this pooled analysis at the 2024 ASCO Annual Meeting. Metastasis-free survival (MFS) and residual cancer burden (RCB), which was defined as tumor volume multiplied by tumor cellularity, were both evaluated in the study. Investigators showed that RCB was highly prognostic for MFS with this treatment approach, Ravi begins. The 5-year MFS rate for patients treated with ARPIs prior to surgery was 83% (95% CI, 77%-88%). This rate compares favorably with 5-year MFS rates observed in similar high-risk patient populations treated with radiotherapy and androgen deprivation therapy. The study also highlighted the prognostic significance of RCB, showing that the extent of residual disease following neoadjuvant therapy and surgery had a strong correlation with patient outcomes, he reports.

One key finding was that 11% of the patients achieved a pathologic complete response (pCR), defined as RCB-0, and an additional 11% had minimal residual disease, defined as up to 5 mm of residual cancer (RCB-1), Ravi continues. Patients who achieved pCR had a 5-year MFS rate of 100%, meaning none of these patients experienced metastasis or death within the 5-year period, he notes.

Patients with minimal residual disease (RCB-1) also had favorable outcomes, with a 5-year MFS rate of 90%. However, the majority of patients had more extensive residual disease categorized as RCB-2 or RCB-3. These patients demonstrated poorer outcomes, with 5-year MFS rates ranging from 82% to 63%, he explains. The findings suggest that patients with higher residual disease burden after neoadjuvant therapy and surgery are more likely to experience metastasis and poorer long-term outcomes.

This study underscores the importance of RCB as a prognostic marker in high-risk, localized prostate cancer, and it highlights the potential benefit of neoadjuvant ARPIs in improving MFS in this patient population, Ravi concludes.