Trends in local therapy utilization and survival of patients with de-novo metastatic prostate cancer treated by hormone therapy with or without systemic therapy intensification with chemotherapy.
Authors: Hu Siqi , Melchiode Zachary , Xu Jiaqiong , Riveros Carlos , Huang Emily , Kaushik Dharam , Farach Andrew M. , Miles Brian , Sonpavde Guru P. , Efstathiou Eleni , Wallis Christopher J.D. , Satkunasivam Raj 
Published: January 2024

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Background: Guideline-recommended treatment for de novo metastatic prostate cancer (mPCa) includes hormone therapy (HT) and androgen receptor axis-targeted (ARAT) therapy with or without chemotherapy. While retrospective data have implicated the potential survival benefit of treating the primary tumor with radical prostatectomy, prospective clinical trials have demonstrated a benefit of definitive local radiotherapy in the context of low-volume mPCa. Given this emerging data, we sought to assess population-based treatment trends in the utilization of local therapy (LT) for mPCa and the association between the receipt of contemporary LT and overall survival in patients with mPCa. Methods: Using the National Cancer Database from 2004 to 2020, we identified men aged 18-90+ who were diagnosed with de-novo mPCa. To mitigate potential confounding, propensity score matching (PSM) was employed to balance patient characteristics between the two groups, including metastatic volume. High-volume mPCa was defined as the presence of any visceral metastases or bone metastases with at least 1 distant invasion. Cox proportional hazard models with clustering were utilized to estimate hazard ratios (HRs) for the risk of all-cause mortality to account for the inherent correlation created by PSM. Results: Among 30,713 patients, 2,569 (8.36%) received both LT and systemic therapy, while 26,038 (84.78%) received systemic therapy alone. Of these, 5,453 (19.06%) had high-volume PCa, and 23,154 (80.94%) had low-volume PCa. No upward trend in LT utilization was observed from 2004 to 2020, with fluctuations in rates observed over time. After PSM, LT was associated with lower all-cause mortality risk (HR=0.87, 95% CI: 0.81-0.93, p<0.001). In patients without chemotherapy intensification, LT was correlated with an 18% lower all-cause mortality risk (HR=0.82, 95% CI: 0.26-0.70, p<0.001), specifically, radical prostatectomy with a 72% lower risk (HR=0.28, 95% CI: 0.20-0.38, p<0.001). For patients receiving chemotherapy intensification, definitive radiotherapy was related to an 18% increased all-cause mortality risk (HR=1.18, 95% CI: 1.01-1.39, p=0.04), while radical prostatectomy showed a 54% decreased risk (HR=0.46, 95% CI: 0.29-0.74, p=0.001). Conclusions: We did not observe an increasing population-based utilization of LT. This contemporary analysis showed that LT was associated with a 13% reduction in the risk of all-cause mortality. Importantly, this observation was also seen in patients receiving systemic therapy intensification with chemotherapy. The retrospective nature of this data, as well as residual confounding despite PSM (including metastatic volume), remain important limitations in this study. Ongoing Phase 3 trials (S1802) will be critical for informing future widespread uptake of LT in mPCa.