3320 - Real-World Comparison of Initial Local Treatment Strategies for Gleason Grade 5 Prostate Cancer: Radiotherapy vs. Surgery Cohort Study

Purpose/Objective(s): Gleason Grade 5 (GG5) prostate cancer is highly aggressive, and optimal initial treatment remains unclear. This study compared real-world outcomes of radical radiotherapy (RT) versus surgery in GG5 patients to inform clinical decision-making.

Materials/Methods:

This study consecutively enrolled patients diagnosed with GG5 prostate cancer between 2019 and 2024, all of whom had no evidence of distant metastasis at the time of initial local treatment. Patients were stratified into radiotherapy (RT) group and surgery group based on the initial local treatment. All patients in the radiotherapy group received radical radiotherapy encompassing the prostate and pelvic lymphatic drainage regions, combined with long-term androgen deprivation therapy (LT-ADT) with or without chemotherapy. The treatment strategy in the surgery group consisted of radical prostatectomy (RP) ± adjuvant/salvage radiotherapy ± postoperative ADT ± neoadjuvant ADT ± chemotherapy, as clinically indicated. The primary endpoint was distant metastasis–free survival (DMFS). Secondary endpoints included biochemical failure–free survival (BFS), clinical progression–free survival (cPFS), and chronic genitourinary (GU) toxicity. Statistical analyses were performed using the Kaplan-Meier method, log-rank test, and Cox regression analysis.

Results:

A total of 514 patients were included, with 145 in the RT group and 369 in the surgery group. The median age was 73 years (IQR 68–77) in the RT group and 66 years (IQR 62–71) in the surgery group. IPTW was performed based on baseline characteristics.The median follow-up duration was 36.8 months (IQR 25.3–50.4). After weighting, there was no significant difference in 4-year DMFS between the radiotherapy and surgery groups (93.9% vs. 90.7%, HR = 0.596, p = 0.269). This finding remained consistent in the standard-treatment subgroup analysis (RT + LT-ADT vs RP ± adjuvant/salvage RT ± postoperative ADT; p = 0.776). At 4 years, radiotherapy was associated with significantly improved BFS (p < 0.001) and superior cPFS (p = 0.012) compared with surgery. 8.4% patients in the surgery group developed local recurrence or pelvic lymph node metastasis, whereas no such events were observed in the RT group (p < 0.001). Notably, 72.1% of surgical patients received postoperative RT, of whom 62.8% underwent salvage RT. After adjustment for age, the RT group had significantly lower risks of urinary incontinence (p < 0.001) and using urine pad (p < 0.001) compared with the surgery group.

Conclusion:

Among patients with GG5 prostate cancer, RT and RP had comparable distant metastasis risk, but RT reduced biochemical recurrence and clinical progression. Majority of patients in the surgery group required postoperative RT, suggesting that upfront RT-based strategy may avoid multimodality treatment and reduce the risk of GU toxicity. Nevertheless, given the relatively limited follow-up duration of 4 years, longer-term follow-up is warranted to validate these findings.