New Hormone Drugs Transform Prostate Cancer Outcomes in Japan, Landmark Real-World Study Shows

Prostate cancer has quietly become one of Japan’s most pressing health challenges. In 2022 alone, roughly 96,400 Japanese men were diagnosed with the disease, and an estimated 13,300 died from it. For men whose cancer has already spread at diagnosis—a condition known as metastatic castration-sensitive prostate cancer, or mCSPC—the central clinical question has been which first-line treatment offers the best chance of controlling the disease. A large new retrospective study published in Advances in Therapy now provides some of the most detailed real-world answers yet, drawing on the medical records of more than 17,000 patients treated across Japanese hospitals between 2020 and 2024.

The research team, led by Taketo Kawai of the National Center for Global Health and Medicine together with colleagues from Astellas Pharma Inc., mined the Medical Data Vision database, one of Japan’s largest hospital-based administrative data resources covering approximately 30 percent of the nation’s Diagnosis Procedure Combination hospitals. Their goal was to move beyond the carefully selected populations of phase 3 clinical trials and measure how modern prostate cancer therapies actually perform in routine clinical practice, where patients are older, carry more comorbidities, and are managed under the constraints of a universal health insurance system.

The therapeutic landscape they examined has shifted dramatically over the past decade. For most of modern oncology history, advanced prostate cancer was treated with androgen-deprivation therapy, or ADT, which suppresses the testosterone that fuels tumor growth, often supplemented by older nonsteroidal antiandrogens such as bicalutamide and flutamide. Beginning in 2018, however, Japan approved a wave of androgen receptor signaling inhibitors—abiraterone, followed by enzalutamide and apalutamide in 2020, and darolutamide combined with docetaxel chemotherapy in 2023—that block the androgen receptor pathway more aggressively. Phase 3 trials had already shown these agents extend overall survival when added to ADT, but Japanese guidelines stop short of telling physicians which specific inhibitor to choose.

To capture treatment effects with precision, the investigators constructed two overlapping cohorts. The first, comprising 1,306 men with measurable prostate-specific antigen, or PSA, records, allowed the team to track biochemical responses to therapy. The second, encompassing all 11,737 eligible patients regardless of PSA data availability, enabled broader analyses of how long patients stayed on treatment and whether they survived. The primary endpoint was the proportion of patients achieving a 90 percent or greater reduction in PSA—a blood marker that correlates closely with tumor burden—during the first-line treatment period, with secondary measures including 50 percent PSA reductions, deep responses to 0.2 nanograms per milliliter or below, time to PSA progression, and time to treatment discontinuation.

The results were striking. At three months, cumulative PSA90 response rates reached 91.8 percent for ADT plus enzalutamide, 90.9 percent for ADT plus apalutamide, and 90.7 percent for ADT plus abiraterone, with the newer triplet regimen of darolutamide, docetaxel, and ADT achieving 81.2 percent. By contrast, only 69.3 percent of men on ADT plus older nonsteroidal antiandrogens and 63.2 percent of those on ADT alone had achieved the same threshold. After statistical adjustment for age, comorbidities, metastasis sites, hospital size, and baseline PSA, the advantages of the androgen receptor signaling inhibitors remained highly significant. The pattern held for deeper responses as well: by twelve months, nearly 80 percent of enzalutamide patients had driven PSA to 0.2 nanograms per milliliter or lower, compared with just 30.3 percent on ADT alone.

Equally important, the modern regimens delayed disease progression. Median time to PSA progression stretched to approximately 35 months for enzalutamide, 33.6 months for abiraterone, and 33.4 months for apalutamide, versus 23.8 months for ADT alone and a mere 15.2 months for ADT combined with older antiandrogens. Notably, no statistically significant differences emerged among the androgen receptor signaling inhibitors themselves on any PSA-related endpoint, suggesting that in biochemical terms the newer agents perform comparably. Sensitivity analyses that varied treatment gap definitions, follow-up windows, and baseline PSA measurements confirmed the robustness of these findings.

Treatment duration told a more nuanced story. In the full cohort, men on ADT plus enzalutamide remained on first-line therapy for a median of 32.4 months and those on abiraterone for 28.6 months, while the darolutamide triplet had not yet reached its median. ADT alone lasted a median of 12.9 months and ADT plus older antiandrogens only 10.7 months. Yet apalutamide stood out with a significantly shorter median duration of 19.5 months, despite PSA responses and progression times indistinguishable from its peers. Because the database does not record why patients stop treatment, the authors speculate that tolerability issues, patient and physician preferences, or switching behavior—apalutamide patients more often moved to another inhibitor—likely explain the gap rather than inferior efficacy.

Survival signals reinforced the case for treatment intensification. After adjustment, non-abiraterone inhibitor regimens were associated with significantly lower mortality risk than conventional therapy, with enzalutamide, apalutamide, and the darolutamide triplet each showing reduced risk of in-hospital death compared with ADT alone or ADT plus older antiandrogens. The darolutamide triplet demonstrated the lowest death risk of all, though the authors caution this result is difficult to interpret because the regimen was only approved in 2023, leaving small patient numbers and short follow-up. The analysis also revealed a striking pattern in treatment selection: patients receiving the newer inhibitors were generally younger than those on conventional therapy, hinting that age, comorbidity burden, and even Japan’s cost-sharing caps under the High-Cost Medical Expense Benefit system shape who gets intensified treatment.

The study’s authors are candid about its limitations. The database captures primarily hospital-based care, potentially overrepresenting larger specialized institutions; PSA data were available from only about 10 percent of contributing facilities; reasons for discontinuation, disease severity, imaging results, and pathology details were not recorded; and mortality was limited to in-hospital deaths. Race and ethnicity variables were absent, and retrospective claims analyses are always vulnerable to unmeasured confounding. Still, the consistency of the PSA findings across multiple sensitivity analyses, and their close alignment with prior clinical trial results, lends considerable weight to the conclusions.

For the roughly 96,000 Japanese men diagnosed with prostate cancer each year, the message is clear and consequential. Adding a modern androgen receptor signaling inhibitor to hormone deprivation produces faster, deeper PSA declines, delays progression by more than a year, extends time on effective therapy, and appears to improve survival compared with the older standard of care. But the equally important lesson may be that drug choice within this class is not merely a biochemical decision. Adverse event profiles, patient background, financial considerations, and the preferences of patients and their physicians all shape whether a treatment is sustained. As the authors conclude, these real-world factors deserve careful weight when clinicians and patients choose among therapies that, on paper, look remarkably alike.

Subject of Research: Real-world effectiveness of androgen receptor signaling inhibitors as first-line therapy for metastatic castration-sensitive prostate cancer in Japan

Article Title: Real-World Longitudinal Treatment Outcomes for Patients with Metastatic Castration-Sensitive Prostate Cancer in Japan

Article References: Kawai, T., Kiyonaga, F., Uno, S., Shibata, H., & Saito, A. (2026). Real-World Longitudinal Treatment Outcomes for Patients with Metastatic Castration-Sensitive Prostate Cancer in Japan. Advances in Therapy. https://doi.org/10.1007/s12325-026-03759-1

Image Credits: AI Generated

DOI: 10.1007/s12325-026-03759-1

Keywords: prostate cancer, metastatic castration-sensitive prostate cancer, androgen deprivation therapy, androgen receptor signaling inhibitors, enzalutamide, apalutamide, abiraterone, darolutamide, PSA response, real-world evidence, Japan, treatment outcomes