Long-term Outcomes and Prognostic Impact of Residual Cancer Burden After Intensified Neoadjuvant Therapy in High-risk Prostate Cancer

Abstract

Background and objective

Long-term outcomes and the prognostic impact of the extent of residual disease after neoadjuvant therapy (NAT) with androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI) before radical prostatectomy (RP) for high-risk localized prostate cancer (HRLPC) are not known.

Methods

We analyzed data for patients treated in five trials evaluating 6 mo of ARPI NAT for HRLPC at our institution between 2006 and 2018. Residual cancer burden (RCB) was quantitated as the calculated tumor volume adjusted for cellularity in the primary tumor. The primary outcome was metastasis-free survival (MFS) according to conventional imaging. We explored RCB categories using the Contal-O’Quigley method to distinguish high- and low-risk groups for MFS.

Key findings and limitations

Among 218 eligible patients, median prostate-specific antigen at diagnosis was 8 ng/ml, 42 (20%) had cT3–4 disease, and 154 (71%) had a biopsy Gleason score of 8–10. At RP, 24 (11%) had a pathologic complete response and median RCB was 0.05 cm³ (interquartile range 0.00–0.32). By median follow-up of 5 yr, 45 patients had developed metastases and 11 died; the 5-yr MFS rate was 83% (95% confidence interval [CI] 77–88%). On multivariable analysis, higher RCB was associated with poorer MFS (hazard ratio 1.21, 95% CI 1.01–1.47). The 5-yr MFS rates were 100%, 90% (95% CI 72–97%), 82% (95% CI 73–88%), and 63% (95% CI 40–79%) for patients with RCB-0 (a pathologic complete response or no residual disease), RCB-1 (<0.003 cm³), RCB-2 (0.003–0.672 cm³), and RCB-3 (≥0.672 cm³), respectively. The key limitation is lack of a validation cohort.

Conclusions and clinical implications

The 5-yr MFS rate for patients treated with ARPI NAT before RP for HRLPC was 83%. The depth of pathologic response, evaluated as the RCB, was highly prognostic for MFS. RCB could be used to guide NAT and post-NAT adjuvant trials in HRLPC.