3229 - A Prospective Cohort Study Evaluating the Efficacy and Safety of Adjuvant Chemotherapy in High-Risk Non-Metastatic Prostate Cancer Patients with High Gleason Scores

M. W. Ma¹, X. S. Gao¹, H. Z. Li¹, W. Yu², X. Ren¹, and J. Chen¹; ¹Department of Radiation Oncology, Peking University First Hospital, Beijing, China, ²Department of Urology, Peking Universtiy First Hospital, Beijing, China

Purpose/Objective(s): Gleason grade group 5 prostate cancers (Pca) are aggressive, have high metastasis rates, and are not sensitive to androgen deprivation therapy (ADT). Even those with a limited (i.e., tertiary) Gleason pattern 5 component may exhibit highly aggressive biological behavior. Selecting an appropriate intensified systemic therapy strategy for the high-malignant population is the focus of intensified treatment. This study aims to conduct a prospective, interventional cohort study by selectively enrolling high Gleason Score Pca patients, in order to validate the efficacy and patient tolerability of adjuvant chemotherapy strategies. Materials/

Methods: A prospective cohort study was conducted to compare the efficacy and safety of adjuvant chemotherapy versus no adjuvant chemotherapy following standard radical treatment (i.e post-operative radiotherapy or definitive radiotherapy) in patients with non-metastatic, high-risk Pca. Enrollment criteria include patients diagnosed with Pca by biopsy or surgical pathology, with a Gleason Grade Group 5 or containing a Gleason pattern 5 component, and no evidence of distant metastasis on systemic evaluation. The primary study endpoint is Failure-Free Survival (FFS). Secondary endpoints include Biochemical Relapse-Free Survival (BRFS), Metastasis-Free Survival (MFS), Overall Survival (OS), and adverse events. Additionally, we explored the mutation status of homologous recombination repair (HRR) genes in these patients.
Results: 1) A total of 362 patients meeting the inclusion and exclusion criteria were consecutively enrolled, including 84 patients in the chemotherapy group and 278 patients in the standard treatment group. 2) In terms of efficacy, with a median follow-up of 23 (1~53) months, the 4-year FFS was 89.4% and 71.36% in the chemotherapy group and the standard treatment group, respectively (p = 0.035). After propensity score matching based on baseline characteristics, the FFS was 89.4% and 70.4% (p = 0.024), and the BRFS was 89.4% and 69.2% (p = 0.050) in the two groups, respectively. The other endpoints did not reach statistical significance before and after matching. Subgroup analysis showed that the postoperative radiotherapy subgroup benefited more from the addition of adjuvant chemotherapy compared to the radical radiotherapy subgroup. 3) In terms of safety, the overall tolerability was acceptable. Grade 3 or higher adverse events in the chemotherapy group were mainly hematological toxicity, fatigue, and alopecia. 4) Furthermore, we found a higher prevalence of HRR gene mutations in patients with high Gleason scores, with 13.6% harboring mutations in the HRR pathway. BRCA2 was the most common mutation, with a mutation rate of 4.5% in the overall population, followed by ATM mutations (3.3%).
Conclusion: The interim analysis results suggest that adjuvant chemotherapy may reduce the overall risk of relapse and metastasis in patients with high Gleason score Pca. However, further follow-up is needed.