120 - 5-Year Results of a Prospective, Non-Randomized Controlled Study: Comparison of the Efficacy and Safety of ADT + Docetaxel vs. ADT + Novel Hormone Therapy in High Gleason Score Non-Metastatic Prostate Cancer Patients Receiving Radiotherapy

Purpose/Objective(s):

The NCCN guidelines recommend intensified systemic treatment for very high-risk prostate cancer, with a focus on novel hormone therapies (NHT) and the inclusion of docetaxel (Doc) as an option. Those with Grade Group 5 (GG5) prostate cancer, characterized by the highest biological malignancy and resistance to endocrine therapy, may require even more intensive treatments that go beyond anti-androgen mechanisms. This study aimed to compare the efficacy and safety of combining NHT or Doc with radical treatment in GG5 non-metastatic prostate cancer patients.

Materials/Methods:

A prospective cohort study was conducted to consecutively enroll patients diagnosed with non-metastatic prostate adenocarcinoma (GG5) between 2019 and 2024. Following standard radical treatment, which included radical radiotherapy or postoperative radiotherapy, patients were assigned to the ADT + NHT group or the ADT + Doc group. Patients in the ADT + Doc group received 4-6 cycles of Doc after completing standard treatment. The primary observational endpoint was Failure-Free Survival (FFS). Secondary endpoints included Biochemical Relapse-Free Survival (BRFS), Metastasis-Free Survival (MFS), Overall Survival (OS), and adverse Events. Statistical analyses were performed using a log-rank test and multifactorial Cox regression analysis.

Results:

110 patients were enrolled in the study, with 51 in the ADT+NHT group and 59 in the ADT+Doc group. All patients received standard radical treatment. The median age was 67 years (48-86), and the median follow-up period was 22.4 months (2.6-60.3). The 5-year outcomes demonstrated significant differences between the two groups. The ADT+Doc group showed superior FFS (98.0% vs. 57.1%, p=0.001), BRFS (98.0% vs. 71.3%, p=0.008), MFS (97.9% vs. 54.4%, p=0.009), and OS (100.0% vs. 44.1%, p=0.025) compared to the ADT+NHT group. A 1:1 matching procedure was performed based on 6 baselines, including age, PSA, and others, resulting in 88 matched patients (44 in each group). Survival analysis post-matching further confirmed the superiority of the ADT+Doc group over the ADT+NHT group, with 5-year FFS (97.3% vs. 58.0%, p=0.0028), BRFS (97.3% vs. 73.2%, p=0.028), and MFS (97.2% vs. 69.9%, p=0.026) being significantly better. Subgroup analysis showed that the FFS and MFS benefits were most pronounced in patients aged =65 years and those with N0 status (p < 0.05). BRFS was most improved in N0 patients and those receiving postoperative radiotherapy (p < 0.05). Regarding adverse events, the overall tolerability was acceptable. However, the incidence of grade 3 and above leukopenia or neutropenia was significantly higher in the ADT+Doc group compared to the ADT+NHT group (p < 0.05).

Conclusion:

The addition of Doc to standard radiotherapy and ADT significantly improves survival outcomes in patients with GG5 non-metastatic prostate cancer compared to NHT with well-toleration, indicating that Doc may be a promising option for intensifying treatment in this high-risk population.