Androgen deprivation therapy, or ADT, remains the backbone of prostate cancer treatment worldwide. By suppressing testosterone, which fuels the growth of most prostate tumors, these therapies slow disease progression and extend survival. Modern treatment regimens increasingly combine ADT with androgen receptor signaling inhibitors or chemotherapy, but every one of those combination strategies depends on the hormonal foundation. In Japan, that foundation is delivered through injectable gonadotropin-releasing hormone, or GnRH, drugs: two agonists called leuprorelin and goserelin, and one antagonist called degarelix. Each agent comes in formulations with different durations of action, ranging from one month to six months per depot injection.

Because clinical trials and meta-analyses have shown no clear difference in cancer outcomes between GnRH agonists and antagonists, the choice among these drugs increasingly hinges on practical considerations: patient preference, cardiovascular safety, compatibility with radiotherapy, and increasingly, the burden of repeated clinic visits. Each injection requires a trip to a hospital or clinic, the time of a healthcare professional trained to administer the depot, and for the patient, the physical and psychological strain of regular needle procedures. A formulation that stretches the interval between shots from one month to six can eliminate most of those visits entirely.

To quantify how Japanese practice has changed, researchers at Yokohama City University Medical Center turned to the National Database Open Data published by the Ministry of Health, Labour and Welfare, a resource that aggregates nearly all health insurance claims in Japan. They extracted dispensing records for injectable GnRH drugs from fiscal year 2017 through fiscal year 2024, restricted to men aged 40 and older to exclude other indications such as breast cancer in women or precocious puberty in boys. Because the open data reports dispensed vials rather than individual patients, the team estimated patient-years by weighting each formulation by the treatment period it covers, dividing one-month depots by twelve, three-month depots by four, and six-month depots by two.

The scale of the dataset is remarkable: 2,276,025 patient-years of treatment, with a mean patient age of 79.8 years and nearly half of all patients between 80 and 89 years old. Over the eight-year window, the number of patients rose by 12.9 percent, from 269,328 patient-years in 2017 to 304,181 in 2024. The relative popularity of the three drugs shifted only modestly. Leuprorelin’s share climbed from 66.0 to 73.3 percent, goserelin’s fell from 28.2 to 20.9 percent, and degarelix held steady at about 5.8 percent. The dramatic change was not in which drug patients received, but in how long each injection lasted.

The six-month formulation of leuprorelin tells the clearest story. In 2017, it accounted for just 22 percent of leuprorelin use, while the three-month depot dominated. By 2021, the six-month formulation had overtaken the three-month version, and it eventually plateaued at around 70 percent of use before settling at 65.7 percent in 2024. Goserelin patients were already concentrated on the three-month formulation, which held a share above 93 percent throughout. Degarelix, whose three-month depot was developed and approved only in Japan, saw its long-acting share grow slowly to about a quarter of use by 2024, though most patients still receive the monthly version.

The consequences for patients and the health system were substantial. Although the patient population grew, the total number of injections fell by 21.5 percent, from 1,275,081 to just over 1,000,000 per year among originator products. Injections per patient per year dropped from 4.97 to 3.55, a 28.7 percent reduction. To understand what drove these changes, the researchers applied Shapley value decomposition, a mathematical technique borrowed from cooperative game theory that assigns each factor its average marginal contribution across all possible orderings, ensuring the factors sum exactly to the observed change. The analysis showed that the shift to long-acting formulations alone reduced the number of injections by roughly 384,000 per year, overwhelming the increase of about 109,000 injections attributable to the growing patient population.

The financial picture was equally striking. Total drug costs for originator products fell from 70.4 billion yen in 2017 to 42.1 billion yen in 2024, a decline of 28.3 billion yen. Decomposition attributed 5.4 billion yen of increase to more patients, a 26.0 billion yen reduction to government price revisions, and 7.7 billion yen to the shift toward long-acting depots. Sensitivity analyses, recalculating the formulation effect under different price and patient-volume assumptions, placed the savings between 5.5 and 10.1 billion yen per year. The per-patient economics are intuitive: at 2017 prices, a year of monthly leuprorelin cost 453,324 yen, while the six-month formulation cost 204,828 yen, less than half as much.

The researchers also probed whether the trend was merely an artifact of a well-known supply crisis. From June 2020, leuprorelin shipments were restricted while the manufacturing plant underwent re-validation, leaving the three-month formulation out of stock entirely. Their data mirror that disruption, and generic versions of the one-month formulation briefly peaked at 8.4 percent of use in 2022, suggesting generics served as substitutes during the shortage. Yet the shift to six-month depots persisted and even strengthened after supplies normalized in September 2022, and decomposition of sub-periods before and after the shortage showed injection reductions in every interval. The authors conclude the shift reflects an established practice pattern, not a temporary substitution.

The findings carry implications well beyond Japan. Fewer injections mean fewer hospital trips for elderly patients, many of whom travel significant distances for routine depots, and lighter workloads for nursing staff. Previous work by the same team, measuring 851 actual injections, found the six-month leuprorelin depot minimized both time in the hospital and patient burden, while degarelix required longer visits because the drug must be reconstituted and the injection site cooled. The study’s limitations are acknowledged: aggregated data cannot track individual patients, the analysis is descriptive rather than causal, and formulation choice may be confounded by patient characteristics, with older men more likely to receive six-month depots. The rise of the oral GnRH antagonist relugolix, which eliminates injections altogether, may further reshape the landscape. Still, the Japanese experience offers a compelling demonstration that when long-acting formulations become available, both patients and payers stand to gain.

Subject of Research: Trends in long-acting GnRH depot formulation use for androgen deprivation therapy in prostate cancer in Japan

Article Title: Fewer Injections and Lower Drug Costs With Long‐Acting GnRH Depot Formulations: A Nationwide Analysis of 2.3 Million Patient‐Years in Japan

Article References: Kawahara, T., Hashizume, A., Yamazaki, M., Takamoto, D., Takeshima, T., Uemura, H., Makiyama, K., & Teranishi, J.-I. (2026). Fewer Injections and Lower Drug Costs With Long‐Acting GnRH Depot Formulations: A Nationwide Analysis of 2.3 Million Patient‐Years in Japan. Cancer Reports, 9(9), Article e70688. https://doi.org/10.1002/cnr2.70688

Image Credits: AI Generated

DOI: 10.1002/cnr2.70688

Keywords: prostate cancer, androgen deprivation therapy, GnRH agonists, leuprorelin, degarelix, depot formulations, Japan National Database, drug costs, injection burden, health economics, Shapley decomposition, pharmacoepidemiology