Real-world evaluation of primary prophylactic use of granulocyte colony-stimulating factor in patients with metastatic castration-sensitive prostate cancer treated with triplet therapy.

BACKGROUND

Triplet therapy with androgen deprivation therapy (ADT), docetaxel, and androgen receptor signaling inhibitors improves outcomes in metastatic castration-sensitive prostate cancer (mCSPC), but hematologic toxicity remains a major concern. The role of primary prophylactic granulocyte colony-stimulating factor (G-CSF) in real-world practice remains unclear. We evaluated its impact on toxicity and treatment delivery.

METHODS

This retrospective multicenter cohort study included 121 patients with mCSPC treated with ADT, docetaxel, and darolutamide across eight institutions (February 2023-December 2025). Primary G-CSF use was at physician discretion. Adverse events were graded per CTCAE v5.0. Relative cumulative dose (RCD) of docetaxel and febrile neutropenia (FN) incidence were assessed. Logistic regression identified factors associated with severe toxicity.

RESULTS

Primary G-CSF was independently associated with reduced risk of grade ≥ 3 neutropenia (OR 0.087; 95% CI 0.030-0.25; p < 0.001) and FN (OR 0.15; 95% CI 0.030-0.78; p = 0.022). Without prophylaxis, grade ≥ 3 neutropenia and FN occurred in 64.9% and 23.4%, respectively, mostly during cycle 1. Primary G-CSF did not significantly improve overall RCD; however, patients with FN had lower RCD (80.0% vs. 93.3%, p = 0.035) and were less likely to achieve RCD > 80% (45.0% vs. 74.3%, p = 0.009). Docetaxel discontinuation was lower with primary G-CSF (p = 0.032).

CONCLUSION

Primary prophylactic G-CSF was associated with reduced hematologic toxicity, while FN was strongly linked to impaired treatment delivery. Early G-CSF use may help prevent hematologic toxicity, particularly in patients at high risk of FN.