ABSTRACT
Background
The introduction of novel androgen receptor signaling inhibitors (ARSIs) has substantially transformed the systemic treatment landscape for non‐metastatic castration‐resistant prostate cancer (nmCRPC). Unfortunately, ARSI therapy is associated with considerable adverse events (AEs) and high medical costs. Dose reduction has been proposed as a potential strategy to improve tolerability and reduce costs; however, the efficacy, safety, and cost‐effectiveness of reduced‐dose ARSIs in patients with nmCRPC remain unclear.
Methods
This multicenter retrospective study included 251 patients with nmCRPC who underwent ARSI therapy. Patients were categorized into reduced‐dose (n = 46) and full‐dose (n = 205) groups according to the initial ARSI dose. The prostate‐specific antigen progression‐free survival (PSA‐PFS), metastasis‐free survival (MFS), and overall survival (OS) were compared between the groups. AEs and monthly medical costs for the first ARSI treatment were also evaluated.
Results
No significant differences in PSA‐PFS, MFS, or OS were observed between the two groups (p = 0.307, p = 0.199, and p = 0.287, respectively). Multivariable analysis showed that the initial ARSI dose was not significantly associated with MFS (p = 0.984). The incidence rates of any‐grade and grade ≥ 3 AEs did not significantly differ between the two groups (p = 0.171 and P = 1.000, respectively). In contrast, the median monthly cost of the first ARSI treatment was significantly lower in the reduced‐dose group than in the full‐dose group ($998 vs. $1644, p < 0.001).
Conclusions
Reduced‐dose ARSI therapy was associated with comparable oncological outcomes to full‐dose therapy in patients with nmCRPC, while suggesting potential cost savings. Dose reduction may be considered a treatment option in selected populations, such as elderly patients, who were predominant in our cohort.
Keywords: cost‐effectiveness, nmCRPC, novel ARSI, oncological outcomes, reduced dose, safety
1. Introduction
Prostate cancer (PC) is one of the most common malignancies in men worldwide [1]. Androgen deprivation therapy (ADT) is the gold standard primary treatment for patients who develop recurrence after radical therapy, as well as for those with unresectable or metastatic PC [2, 3]. Although many patients initially respond to ADT, a substantial proportion eventually develop castration‐resistant PC (CRPC) [4, 5].
Non‐metastatic CRPC (nmCRPC) frequently progresses to metastatic CRPC (mCRPC), an incurable condition with a poor prognosis [6]. The introduction of novel androgen receptor signaling inhibitors (ARSIs) has dramatically changed the landscape of systemic treatment for nmCRPC [7, 8, 9, 10]. However, ARSI therapy causes significant adverse events (AEs) and is associated with increased medical costs [11, 12]. Dose reduction of ARSIs may help mitigate AEs and reduce treatment costs. In real‐world clinical practice, 27–39% of patients receive reduced initial ARSI doses based on age, comorbidities, and performance status (PS) [13, 14, 15]. Nevertheless, the efficacy and safety of reduced‐dose ARSIs in nmCRPC remain unclear. Furthermore, the effect of dose‐reduction strategies on cost‐effectiveness in this setting has not been evaluated.
Thus, in this study, we aimed to evaluate the efficacy, safety, and cost‐effectiveness of reduced versus full initial doses of ARSIs in patients with nmCRPC.
2. Patients and Methods
2.1. Ethics Statement
This study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the ethics committees of the Hirosaki University Graduate School of Medicine (Authorization Numbers: 2019‐099‐2 and 2021‐158‐1) and those of all participating hospitals. Written informed consent was waived because the study information was publicly disclosed (opt‐out approach).
2.2. Patient Selection
This multicenter retrospective study assessed 355 consecutive patients with nmCRPC treated at 12 participating hospitals between June 2001 and May 2025. Among these patients, 104 were excluded based on the following criteria: (1) insufficient information regarding the initial ARSI dose (n = 2) and (2) lack of treatment with any novel ARSIs, including abiraterone acetate, enzalutamide, apalutamide, or darolutamide, during nmCRPC treatment (n = 102). Ultimately, 251 patients were included in the final analysis (Figure 1). nmCRPC was defined as PSA > 1 ng/mL, castrate testosterone levels < 50 ng/dL, and the absence of metastatic lesions on conventional imaging (computed tomography or bone scintigraphy) [16].
Figure 1.
Selection of study patients. Flowchart showing the numbers of included and excluded patients. ARSI, androgen receptor signaling inhibitor; nmCRPC, non‐metastatic castration‐resistant prostate cancer. [Color figure can be viewed at wileyonlinelibrary.com]
2.3. Evaluation of Variables
The following variables were analyzed: age and Eastern Cooperative Oncology Group PS (ECOG PS) at nmCRPC diagnosis; PSA concentration at initial diagnosis; biopsy Gleason score; clinical tumor and node stages at initial diagnosis; history of radical treatment; clinical node stage at nmCRPC diagnosis; and PSA doubling time (PSADT). The PSADT was calculated using the Sloan Kettering method, which requires at least three PSA measurements of ≥ 0.2 ng/mL obtained at intervals of at least 1 month within the 12 months preceding the diagnosis of nmCRPC [17]. AEs associated with novel ARSI treatment were evaluated using the Common Terminology Criteria for Adverse Events version 5.0.
2.4. Treatment
All patients included in this study received ADT, including bilateral orchiectomy or luteinizing hormone‐releasing hormone agonists or antagonists, throughout the course of their PC treatment. In Japan, enzalutamide, abiraterone acetate, apalutamide, and darolutamide became clinically available for nmCRPC in May 2014, September 2014, March 2019, and January 2020, respectively. The choice of ARSI and its initial dose for nmCRPC treatment was left to the discretion of the treating clinician. Patients were categorized into two groups: those who received reduced initial ARSI doses at the start of the first ARSI treatment (reduced‐dose group) and those who received full initial ARSI doses at the start of the first ARSI treatment (full‐dose group).
2.5. Evaluation of Medical Cost for ARSI Treatment
Medical costs for the first ARSI treatment were estimated using the 2025 National Health Insurance drug prices in Japan (Table S1). Because our database did not have the information on costs related to ADT, examinations, and physician fees, these components were not incorporated into the cost analysis. The monthly medical cost of the first ARSI treatment was compared between the reduced‐dose and full‐dose groups. We also compared the actual costs incurred in the reduced‑dose group with the estimated costs that would have been incurred if these patients had received full‑dose ARSI therapy throughout their first ARSI treatment.
2.6. Statistical Analysis
SPSS version 29.0 (IBM Corp., Armonk, NY, USA) and GraphPad Prism 9 (GraphPad Software, San Diego, CA, USA) were used for statistical analyses. The quantitative variables are presented as medians with interquartile ranges. Differences in quantitative variables between the two groups were assessed using the Mann–Whitney U test. Categorical variables were compared using Fisher's exact test or the χ 2 test. The rates of any‐grade and grade ≥ 3 AEs, treatment discontinuation due to AEs, any PSA response, PSA decline ≥ 50%, and PSA decline ≥ 90% during the first ARSI treatment were compared between the reduced‐dose and full‐dose groups. The optimal PSADT cutoff value for metastasis‐free survival (MFS) was determined using a receiver operating characteristic curve. PSA progression‐free survival (PSA‐PFS) was defined as the time from the initiation of the first ARSI treatment to PSA progression. PSA progression was defined as an increase in PSA of > 25% and > 2 ng/mL above the nadir, confirmed by progression at two timepoints at least 3 weeks apart [16]. The PSA‐PFS, MFS, and overall survival (OS) were estimated using the Kaplan–Meier method and compared using the log‐rank test. Univariable and multivariable Cox proportional hazards regression analyses were performed to evaluate the effects of reduced versus full initial ARSI doses on MFS. The MFS and OS were calculated from the date of nmCRPC diagnosis to the date of the first event or last follow‐up. Statistical significance was defined as p < 0.05.
3. Results
3.1. Patients' Characteristics
The median age of the patients at nmCRPC diagnosis was 77 years, and the median follow‐up duration after nmCRPC diagnosis was 50 months. Among the 251 patients, 46 (18%) and 205 (82%) were categorized into the reduced‐dose and full‐dose groups, respectively. In the reduced‐dose group, the most frequently used first ARSIs were enzalutamide and darolutamide (both n = 17, 37%), followed by apalutamide (n = 7, 15%) and abiraterone acetate (n = 5, 11%). In the full‐dose group, the most frequently used first ARSI was darolutamide (n = 84, 41%), followed by enzalutamide (n = 75, 37%), abiraterone acetate (n = 28, 14%), and apalutamide (n = 18, 8.8%). The distribution of the starting doses for each ARSI is shown in Figure 2A. Apalutamide was administered at reduced doses more frequently than the other ARSIs. In the reduced‐dose and full‐dose groups, 25 (54%) and 73 (36%) patients, respectively, had received docetaxel and/or vintage hormone therapies, such as bicalutamide, flutamide, estramustine phosphate, or ethinylestradiol, for nmCRPC prior to the first ARSI treatment; the median number of prior treatments was 1.0 in both groups (Table 1). Significant differences in age, clinical T stage at initial diagnosis, history of radical treatment, and prior therapy before the first ARSI treatment were observed between the two groups (Table 1). The median PSADT was 3.6 months. The optimal PSADT cutoff for MFS was 5.5 months (Figure S1).
Figure 2.
ARSI dose and sequential changes during treatment. The distribution of initial ARSI doses by ARSI agent is shown in Figure 2A. Reasons for initiating ARSI therapy at reduced doses are shown in Figure 2B. Sequential changes in ARSI dosing during the first ARSI treatment are illustrated using a Sankey diagram (C). Abi: abiraterone acetate, AE, adverse event; Apa, apalutamide; ARSI, androgen receptor signaling inhibitor; Dar, darolutamide; Enz, enzalutamide. [Color figure can be viewed at wileyonlinelibrary.com]
Table 1.
Patients' backgrounds.
| All n = 251 | Full‐dose group n = 205 | Reduced‐dose group n = 46 | P value | |
|---|---|---|---|---|
| Age, years | 77 (72–82) | 75 (71–81) | 80 (74–87) | 0.003 |
| ECOG PS ≥ 1 | 77 (31%) | 58 (28%) | 19 (41%) | 0.084 |
| Initial PSA, ng/mL | 27 (11–100) | 24 (11–100) | 39 (14–108) | 0.177 |
| Biopsy Gleason score ≥ 8 | 176 (70%) | 146 (71%) | 30 (65%) | 0.422 |
| Clinical stage at initial diagnosis | ||||
| cT4 | 44 (18%) | 30 (15%) | 14 (30%) | 0.011 |
| cN1 | 63 (25%) | 50 (24%) | 13 (28%) | 0.584 |
| cT4 or cN1 | 79 (32%) | 60 (29%) | 19 (41%) | 0.112 |
| History of radical treatment | 128 (51%) | 115 (56%) | 13 (28%) | < 0.001 |
| Prostatectomy | 82 (33%) | 74 (36%) | 8 (17%) | |
| Radiation therapy | 46 (18%) | 41 (20%) | 5 (11%) | |
| Clinical N stage at nmCRPC diagnosis | ||||
| cN1 | 60 (24%) | 48 (23%) | 12 (26%) | 0.701 |
| Therapy prior to ARSI treatment | ||||
| None | 153 (61%) | 132 (64%) | 21 (46%) | 0.019 |
| Docetaxel | 20 (8.0%) | 16 (7.8%) | 4 (8.7%) | 0.769 |
| Vintage hormone therapy | 91 (36%) | 68 (33%) | 23 (50%) | 0.032 |
| Number of therapies prior to ARSI treatment | 1.0 (1.0–2.0) | 1.0 (1.0–2.0) | 1.0 (1.0–2.0) | 0.968 |
| PSADT, months | 3.6 (2.3–6.2) | 3.5 (2.2–5.9) | 5.5 (2.7–7.8) | 0.080 |
| Follow‐up period, months | 46 (27–71) | 42 (28–70) | 46 (27–71) |
Note: All data are presented as n (%) or median (interquartile range).
Abbreviations: ARSI, androgen receptor signaling inhibitor; ECOGPS, Eastern Cooperative Oncology Group Performance Status; nmCRPC, non‐metastatic castration‐resistant prostate cancer; PSA, prostate‐specific antigen; PSADT, prostate‐specific antigen doubling time.
3.2. ARSI Treatment
The most common reason for initiating ARSIs at a reduced dose was advanced age, followed by comorbidities and poor ECOG PS (Figure 2B).
The changes in ARSI dosing are illustrated using a Sankey diagram (Figure 2C). In the reduced‐dose group, 13 (28%) patients escalated their ARSI dose to the full dose during the first ARSI treatment. In contrast, 19 (9.3%) patients in the full‐dose group required dose reduction during the first ARSI treatment.
3.3. Oncological Outcomes
The rates of any PSA response, PSA decline ≥ 50%, and PSA decline ≥ 90% did not differ significantly between the two groups (Figure 3A–C; p = 0.640, p = 0.785, and p = 0.171, respectively).
Figure 3.
PSA response and oncological outcomes. The rates of any PSA response (A), PSA decline ≥ 50% (B), and PSA decline ≥ 90% (C) were compared using the χ 2 test. PSA progression‐free survival (D), metastasis‐free survival (E), and overall survival (F) were evaluated using the Kaplan–Meier method and compared using the log‐rank test. ARSI, androgen receptor signaling inhibitor; nmCRPC, non‐metastatic castration‐resistant prostate cancer; PSA, prostate‐specific antigen. [Color figure can be viewed at wileyonlinelibrary.com]
The PSA‐PFS, MFS, and OS were not significantly different between the two groups (Figure 3D–F; p = 0.307, p = 0.199, and p = 0.287, respectively). Age and PSADT were significantly associated with MFS in univariable analyses (Table 2). After adjusting for confounding variables, the initial ARSI dose was not significantly associated with MFS (Table 3).
Table 2.
Univariable analyses for metastasis‐free survival.
| Factor | p value | Hazard ratio | 95% CI | |
|---|---|---|---|---|
| Age | Continuous | < 0.001 | 0.945 | 0.917–0.975 |
| Performance status | ≥ 1 | 0.118 | 0.641 | 0.367–1.120 |
| PSA at initial diagnosis | Continuous | 0.553 | 1.000 | 1.000–1.000 |
| Biopsy Gleason score | ≥ 8 | 0.272 | 1.403 | 0.766–2.570 |
| History of radical treatment | Positive | 0.058 | 1.597 | 0.984–2.592 |
| Clinical N stage at nmCRPC diagnosis | cN1 | 0.108 | 1.507 | 0.914–2.485 |
| PSA doubling time | < 5.5 months | 0.002 | 2.596 | 1.416–4.759 |
| Initial ARSI dose | Reduced dose | 0.203 | 0.634 | 0.315–1.278 |
Abbreviations: ARSI, androgen receptor signaling inhibitor; CI, confidence interval; nmCRPC, non‐metastatic castration‐resistant prostate cancer; PSA, prostate‐specific antigen.
Table 3.
Multivariable analysis for metastasis‐free survival.
| Factor | p value | Hazard ratio | 95% CI | |
|---|---|---|---|---|
| Age | Continuous | 0.110 | 0.971 | 0.937–1.007 |
| Performance status | ≥ 1 | 0.555 | 0.831 | 0.450–1.536 |
| Biopsy Gleason score | ≥ 8 | 0.488 | 1.252 | 0.663–2.364 |
| History of radical treatment | Positive | 0.280 | 1.343 | 0.786–2.295 |
| Clinical N stage at nmCRPC diagnosis | cN1 | 0.155 | 1.471 | 0.865–2.503 |
| PSA doubling time | < 5.5 months | 0.012 | 2.229 | 1.193–4.165 |
| Initial ARSI dose | Reduced dose | 0.984 | 0.992 | 0.467–2.107 |
Abbreviations: ARSI, androgen receptor signaling inhibitor; CI, confidence interval; nmCRPC, non‐metastatic castration‐resistant prostate cancer; PSA, prostate‐specific antigen.
3.4. AEs Associated With ARSI Treatment
The most common any‐grade AE associated with ARSI treatment was general malaise or fatigue (n = 25, 10%), followed by skin rash (n = 16, 6.4%) and liver dysfunction (n = 14, 5.6%). AEs associated with each ARSI in all patients are shown in Figure S2. The incidence rate of any‐grade AEs was lower in the reduced‐dose group than in the full‐dose group (Figure 4A; 24% vs. 33%, respectively), although the difference was not statistically significant (p = 0.171). The incidence rates of grade ≥ 3 AEs in the reduced‐dose and full‐dose groups were 4.3% and 3.9%, respectively (Figure 4B; P = 1.000).
Figure 4.
Adverse events associated with ARSI treatment and economic outcomes. The rates of any‐grade AEs (A) and grade ≥ 3 AEs (B) were compared using Fisher's exact test or the χ 2 test. The monthly medical costs of the first ARSI treatment were compared using the Mann–Whitney U test (C). Actual costs incurred in the reduced‑dose group were compared with the estimated costs that would have been incurred if these patients had received full‑dose ARSI therapy throughout their first ARSI treatment period (D). AE, adverse event; ARSI, androgen receptor signaling inhibitor. [Color figure can be viewed at wileyonlinelibrary.com]
In the reduced‑dose group, 2 (4.3%) patients experienced treatment interruption, and 2 (4.3%) patients discontinued treatment due to AEs associated with ARSI therapy. In contrast, in the full‑dose group, 6 (2.9%) patients experienced treatment interruption, and 20 (9.8%) patients discontinued treatment due to AEs. There were no significant differences between the two groups (P = 1.000 and p = 0.386, respectively).
3.5. Economic Outcomes
The monthly cost per patient for the first ARSI treatment was significantly lower in the reduced‐dose group than in the full‐dose group, with median monthly costs of $998 and $1644, respectively (Figure 4C). Comparison of the actual total costs incurred in the reduced‐dose group with the estimated costs that would have been incurred if these patients had received full‐dose ARSI therapy throughout the first ARSI treatment period demonstrated an absolute cost reduction of $580,828, corresponding to a 35% decrease in total ARSI‐related expenditures (Figure 4D).
4. Discussion
To the best of our knowledge, this is the first study to comprehensively evaluate the efficacy, safety, and cost‐effectiveness of reduced versus full initial doses of ARSIs in patients with nmCRPC. Our findings indicate that reduced‐dose ARSI therapy achieved oncological outcomes comparable to those of full‐dose treatment. Although dose reduction did not result in a statistically significant decrease in AE rates, reduced‐dose ARSI therapy led to a substantial reduction in ARSI‐related treatment costs, demonstrating a clear economic advantage without compromising clinical effectiveness. These results suggest that reduced‐dose ARSI therapy may represent a feasible and economically favorable treatment option for patients with nmCRPC.
In the present study, no significant differences in oncological outcomes were observed between the reduced‐dose and full‐dose groups. These findings are consistent with those of previous studies evaluating reduced‐dose ARSI strategies across different ARSI agents and disease settings. Oishi et al. reported that CRPC‐free survival in patients with metastatic castration‐sensitive PC (mHSPC) did not differ significantly between the full‐dose and reduced‐dose groups (p = 0.525) [14]. Similarly, a multicenter randomized phase III non‐inferiority trial by Shah et al. demonstrated that a reduced dose (250 mg) of abiraterone acetate achieved comparable PSA response rates, PSA‐PFS, and OS to the standard dose (1000 mg), despite significantly lower blood abiraterone acetate levels [18]. Moreover, Belabaci et al. conducted a systematic review evaluating the efficacy of reduced‐dose enzalutamide in patients with CRPC and concluded that reduced‐dose enzalutamide may maintain therapeutic efficacy in selected patients [19]. Nevertheless, several studies have reported conflicting results [20], suggesting that dose reduction may adversely affect oncological outcomes in certain patient populations or treatment contexts, thereby precluding definitive conclusions regarding the universal applicability of reduced‐dose ARSI strategies. Importantly, evidence specific to the nmCRPC setting remains limited, as most available data are derived from studies in metastatic disease. Given the unique disease biology of nmCRPC and its typically prolonged treatment duration [21], further randomized prospective studies are warranted to clarify the efficacy and optimal patient selection for reduced‐dose ARSI strategies in this population.
Contrary to initial expectations, the present study failed to demonstrate a statistically significant reduction in AEs with reduced‐dose ARSI therapy. Several previous studies support these findings. A retrospective study including 233 patients with CRPC reported that an initial reduced dose of enzalutamide did not significantly decrease the incidence of AEs [22]. Similarly, Oishi et al. demonstrated that dose reduction of apalutamide was not significantly associated with the incidence of skin‐related AEs [14]. In contrast, other studies have successfully demonstrated the benefits of reduced‐dose ARSI therapy in decreasing AEs and improving treatment tolerability [19, 23, 24]. Notably, these studies often focused on specific patient populations, such as elderly or frail patients, and incorporated more detailed assessments of treatment tolerability, including patient‐reported outcomes and symptom‐specific evaluations. Taken together, the inconsistent findings regarding AEs between reduced‐dose and full‐dose ARSI therapy may be attributable to differences in patient characteristics, definitions, and assessment of AEs, actual drug exposure during treatment, and study design.
Importantly, this study demonstrated that dose reduction of ARSIs contributed to improved cost‐effectiveness compared with full‐dose therapy. ARSI agents are well recognized as among the most expensive treatments in contemporary PC care [12, 25, 26]. Accordingly, dose reduction of ARSIs represents a rational strategy to mitigate treatment‐related financial burden. Several studies have reported that reduced‐dose ARSI strategies, particularly low‐dose abiraterone acetate, can result in substantial cost reductions while maintaining comparable clinical efficacy. A pharmacoeconomic analysis estimated that low‐dose abiraterone acetate could result in approximately $700 million in annual cost savings in the United States compared with standard full‐dose regimens [27]. While previous cost‐effectiveness studies of reduced‐dose ARSIs have largely focused on abiraterone acetate, the present study extends these findings by including a substantial proportion of patients treated with other ARSIs, such as enzalutamide, apalutamide, and darolutamide. Our results demonstrate that dose reduction across multiple ARSI agents was associated with a significant reduction in ARSI treatment costs in real‐world clinical practice. Given the current lack of evidence regarding the optimal ARSI dose that balances efficacy, safety, and cost‐effectiveness in nmCRPC, further prospective studies incorporating both clinical and economic endpoints are warranted.
This study has several limitations that warrant discussion. First, its retrospective design precludes definitive causal inferences because selection bias and unmeasured confounding factors could not be fully controlled. Confounding by indication may have occurred because reduced‐dose ARSIs were more likely to be prescribed to older or frailer patients with comorbidities. Second, the interval between nmCRPC diagnosis and initiation of the first ARSI treatment varied among patients, which may have influenced disease progression and oncological outcomes. Although this reflects real‐world clinical practice, the heterogeneity in treatment timing may have introduced bias. Third, this study focused exclusively on outcomes associated with the first ARSI treatment. Subsequent therapies administered after ARSI discontinuation were not fully accounted for and may have affected long‐term oncological outcomes, particularly OS. Fourth, patients were categorized according to their initial ARSI dose. However, ARSI dosing was not static during treatment, and dose escalation or reduction during the first ARSI therapy may have influenced both the efficacy and safety outcomes. Although we partially addressed this issue by evaluating dose changes over time, we cannot exclude residual bias related to cumulative drug exposure. Finally, this multicenter study was conducted within a single healthcare system, which may limit the generalizability of the findings to other populations with different prescribing practices, healthcare policies, or reimbursement systems.
5. Conclusions
In patients with nmCRPC, reduced‐dose novel ARSIs showed oncological outcomes comparable to those of full‐dose therapy in this retrospective cohort, while suggesting potential cost savings. However, given the inherent limitations and possible biases of this study, these findings should be interpreted with caution. Reduced‐dose ARSI therapy may be considered a treatment option in selected populations, such as elderly patients, who were predominant in our cohort, and prospective studies are warranted to validate its clinical utility and cost‐effectiveness.
Ethics Statement
The current study followed the principles of the Declaration of Helsinki and was approved by the ethics committees of the Hirosaki University Graduate School of Medicine (authorization numbers: 2019‐099‐2 and 2021‐158‐1), and all other participating hospitals included.
Consent
Written informed consent was not required because of the public disclosure of study information (opt‐out approach).
Conflicts of Interest
Shingo Hatakeyama received honoraria from Janssen Pharmaceutical K.K., Astellas Pharma Inc., AstraZeneca K.K., Ono Pharmaceutical Co. Ltd., Bayer AG, Pfizer Inc., Bristol‐Myers Squibb, Merck Biopharma Co. Ltd., Kaneka Corporation, and Nipro Corporation. The other authors declare no conflicts of interest.
Supporting information
Figure S1: Optimal cutoff point of PSADT for MFS. The optimal cutoff point of PSADT for MFS was determined using a receiver operating characteristic curve. PSADT, prostate‐specific antigen doubling time; MFS, metastasis‐free surviva.
Figure S2: Adverse events associated with each ARSI. Adverse events (AEs) associated with enzalutamide (A), abiraterone acetate (B), apalutamide C), and darolutamide (D) are presented.
Table S1: Medical costs for androgen receptor signaling inhibitor treatment.
Acknowledgments
We would like to thank Editage (www.editage.jp) for English language editing. This work was supported by a Grant‐in‐Aid for Scientific Research (No. 25K12244) from the Japan Society for the Promotion of Science.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Figure S1: Optimal cutoff point of PSADT for MFS. The optimal cutoff point of PSADT for MFS was determined using a receiver operating characteristic curve. PSADT, prostate‐specific antigen doubling time; MFS, metastasis‐free surviva.
Figure S2: Adverse events associated with each ARSI. Adverse events (AEs) associated with enzalutamide (A), abiraterone acetate (B), apalutamide C), and darolutamide (D) are presented.
Table S1: Medical costs for androgen receptor signaling inhibitor treatment.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.