A Pooled Analysis of Phase 2 Trials

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on prostate cancer, and a presentation by Dr. Praful Ravi discussing the prognostic impact of residual cancer burden on long-term outcomes after neoadjuvant androgen receptor pathway inhibitor and radical prostatectomy for high-risk localized prostate cancer.

Previously, six months of neo-androgen receptor pathway inhibitor prior to radical prostatectomy for high-risk localized prostate cancer has shown promising results in a series of phase 2 trials, with 15-20% of patients experiencing pathologic complete response or minimal residual disease (≤5 mm residual tumor). However, longer-term outcomes and the prognostic impact of residual cancer burden at radical prostatectomy has not been evaluated.

 Data from patients treated on 5 neoadjuvant trials evaluating 6 months of neo-androgen receptor pathway inhibitor (abiraterone, enzalutamide, abiraterone + apalutamide) + ADT at Dana-Farber Cancer Institute between 2006 to 2018 were pooled. All patients had central pathology review performed to evaluate pathologic complete response/minimal androgen receptor pathway inhibitor and residual cancer burden on the radical prostatectomy specimen. Residual cancer burden was quantified as the calculated tumor volume adjusted for tumor cellularity. Metastasis-free survival was defined as the time from radical prostatectomy to development of metastasis outside of the pelvis on CT, bone scan, or MRI, or death from any cause, or censored at the date of last follow-up.

Utilizing the Contal & O’Quigley method, the optimal cut-off value for residual cancer burden, distinguishing high- and low-risk groups for metastasis-free survival, was determined based on the log-rank statistic. A dichotomous residual cancer burden cut-off was chosen between 5% and the 95% percentiles of the residual cancer burden distribution for patients with residual disease (residual cancer burden > 0). Multivariable Cox proportional hazards model was used to quantify the association of residual cancer burden with metastasis-free survival after adjusting for age, biopsy Gleason score, and clinical T stage.

There were 218 patients evaluable, with a median age of 61 years (IQR 57-66). There were 154 (71%) patients that had Gleason 8-10 at biopsy, 42 (19%) had cT3-4 disease, and 40 (18%) had a baseline PSA > 20ng/mL. Overall, 170 (78%) were classified as NCCN high/very-high risk and 48 (22%) as unfavorable intermediate-risk. At radical prostatectomy, 117 patients (54%) had ypT3 and 23 (11%) had pN1 disease, while 24 patients (11%) had pathologic complete response and 24 (11%) had androgen receptor pathway inhibitor. The median residual cancer burden was 0.05 cm³ (IQR 0.00-0.32). During a median follow-up of 5 years, 45 patients (21%) developed metastases and 11 (5%) died:

The 5-year metastases-free survival rate was 83% (95% CI 74-86). On multivariable analysis, a higher residual cancer burden was associated with poorer metastasis-free survival (HR 1.26, 95% CI 1.03-1.54), along with cT3-4 disease (HR 3.86, 95% CI 1.59-9.41). Residual cancer burden index categories were defined as:

• Residual cancer burden-0 (no residual disease [ie. pathologic complete response]; n = 24)
• Residual cancer burden-1 (3; n = 35)
• Residual cancer burden-2 (0.003-0.672 cm³; n = 114)
• Residual cancer burden-3 (>= 0.672 cm³; n = 25)

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, May 31 – Tues, June 4, 2024.