Treatment Patterns and Survival Among Veterans With De Novo Metastatic Hormone-Sensitive Prostate Cancer

Abstract

Importance: Combination therapy for metastatic hormone-sensitive prostate cancer (mHSPC) has been widely adopted, yet clinical use and outcomes are unknown. Furthermore, optimal therapy is uncertain due to lack of direct comparison of androgen receptor pathway inhibitors (ARPIs) and docetaxel in high-volume disease.

Objective: To evaluate the use of combination therapy and its association with overall survival among patients with mHSPC and to compare ARPIs vs docetaxel doublet therapy by volume of disease.

Design, setting, and participants: This retrospective cross-sectional study was conducted in the US Veterans Health Administration among 6216 US veterans with de novo mHSPC from January 1, 2013, to December 31, 2022, treated with androgen deprivation therapy (ADT) within 3 months of diagnosis. Treatments for mHSPC were collected within 4 months of ADT. Volume of disease was assessed from radiology report review. Data were analyzed from July 2023 to October 2024.

Main outcomes and measures: Overall survival (OS) and clinical progression-free survival (PFS), indicated by time to castration resistance or death.

Results: Among 6216 male veterans with mHSPC (mean [SD] age, 73.9 [9.7] years), use of combination therapy increased from 344 of 637 veterans (54.0%) in 2020 to 465 of 737 veterans (63.1%) in 2022. Among 4106 veterans treated from 2017 to 2022, combination therapy was associated with longer OS (40.3 [95% CI, 38.0-42.1] months vs 33.0 [95% CI, 31.2-35.1] months; hazard ratio [HR], 0.80 [95% CI, 0.74-0.87]) and was used more frequently among younger veterans with fewer comorbidities. Among 1174 veterans with high-volume mHSPC, there was no difference in OS between ARPIs and docetaxel (32.3 [95% CI, 29.5-35.3] months vs 34.7 [95% CI, 31.7-37.1] months; HR, 1.06 [95% CI, 0.91-1.23]); however, ARPIs were associated with longer PFS (18.7 [95% CI, 17.1-20.9] months vs 16.0 [95% CI, 14.0-17.7] months; HR, 0.80 [95% CI, 0.70-0.91]; P = .001). In a multivariable model of high-volume mHSPC, there was no difference in OS between ARPIs and docetaxel (adjusted HR, 0.89 [95% CI, 0.76-1.05]). Among 366 veterans with low-volume mHSPC, there was no difference in OS between ARPIs and docetaxel (68.4 [95% CI, 52.6 months to not reached] months vs 55.3 [95% CI, 41.7-78.9] months; HR, 0.81 [95% CI, 0.58-1.13]), but ARPIs were associated with longer PFS (39.7 [95% CI, 34.3-52.9] months vs 24.0 [95% CI, 20.3-32.9] months; HR, 0.57 [95% CI, 0.43-0.76]).

Conclusions and relevance: In this cross-sectional study of veterans with de novo mHSPC, use of combination therapies increased over time and were associated with longer survival compared with ADT monotherapy. In both high- and low-volume mHSPC, no differences in OS were observed between ARPI and docetaxel combinations; however, ARPIs had longer PFS. Future research into the role of docetaxel is needed to elucidate the benefit of chemotherapy in mHSPC.

Figure 1.. Trends in Use of Therapy for De Novo Metastatic Hormone-Sensitive Prostate Cancer From 2013 to 2022

Use of androgen deprivation therapy (ADT) monotherapy decreased from 97.1% in 2013 to 36.9% in 2022. Docetaxel combinations increased from less than 1% in 2013 to a maximum of 18.7% in 2016 to 9.4% in 2022. Androgen receptor pathway inhibitor (ARPI) combinations increased from 2.2% in 2013 to 53.7% in 2022. Overall, combination therapy increased from 2.9% to 63.1% in 2022.

Figure 2.. Overall Survival (OS) Among Veterans Treated for De Novo Metastatic Hormone-Sensitive Prostate Cancer From 2017 to 2022

Overall survival by treatment among 4106 patients treated from 2017 to 2022 for de novo metastatic hormone-sensitive prostate cancer who survived at least 4 months. Overall survival in combination therapy (docetaxel and androgen receptor pathway inhibitor combinations) compared with androgen deprivation therapy (ADT) monotherapy had a hazard ratio of 0.80 (95% CI, 0.74-0.87).

Figure 3.. Overall Survival (OS) and Clinical Progression-Free Survival (PFS) of Veterans Treated With Combination Therapy for De Novo Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) Based on Volume of Disease

A, Overall survival in patients with high-volume mHSPC: hazard ratio (HR), 1.06 (95% CI, 0.91-1.23). B, Overall survival in patients with low-volume mHSPC: HR, 0.81 (95% CI, 0.58-1.13). C, PFS in high-volume mHSPC: HR, 0.80 (95% CI, 0.70-0.91). D, PFS in low-volume mHSPC: HR, 0.57 (95% CI, 0.43-0.76). ARPI indicates androgen receptor pathway inhibitor.

Figure 4.. Initial and Subsequent Therapy for De Novo Metastatic Hormone-Sensitive Prostate Cancer Based on Castration Resistance

Sankey diagram of initial and subsequent therapy in 6216 patients with metastatic hormone-sensitive prostate cancer in the Veterans Health Administration. There were 3873 of 6216 veterans (62.3%) who did not develop castration resistance and 3020 of 3873 (78.0%) received no further therapy. Castration resistance developed in 2343 of 6216 veterans (37.7%) and 591 of 2343 (25.2%) received no additional therapy. ADT indicates androgen deprivation therapy; and ARPI, androgen receptor pathway inhibitor.