Japanese researchers have identified frailty assessments as valuable predictive tools for determining which metastatic hormone-sensitive prostate cancer (mHSPC) patients may experience severe adverse events when treated with docetaxel-based regimens, according to findings presented at the 2025 American Urological Association Annual Meeting in Las Vegas.
The multicenter retrospective study, led by Sosuke Omizo from Hirosaki University Graduate School of Medicine, demonstrated that the G8 screening tool in particular could help clinicians identify patients who might require modified treatment approaches.
G8 Screening Tool Shows Strong Predictive Value
Of the 32 patients included in the final analysis, 18 (56%) experienced at least one severe adverse event, defined as grade 3 or higher. The study found significant differences between patients who did and did not experience severe adverse events in three key metrics:
- G8 screening tool scores (P<.001)
- Body mass index (BMI) (P=.011)
- Serum albumin levels (P=.046)
Other factors including age (P=.458), ECOG performance status (P=.238), and hemoglobin levels (P=.123) did not show statistically significant correlations with adverse event occurrence.
The receiver operating characteristic curve analysis revealed the G8 screening tool had the highest predictive value with an area under the curve (AUC) of 0.850, compared to 0.762 for BMI and 0.706 for serum albumin. When these factors were combined into a nomogram, the predictive power increased to an AUC of 0.857.
Probability Model for Severe Adverse Events
The researchers developed a probability model that could have significant clinical implications. For a patient with a BMI of 23 and serum albumin level of 4.0 g/dL, the probability of experiencing a severe adverse event varied dramatically based on G8 score:
- G8 score of 17: 10% probability
- G8 score of 14: 43% probability
- G8 score of 13: 59% probability
- G8 score of 12: 73% probability
"Patients with less tolerability for up-front docetaxel might be estimated by the frailty assessment. The G8 could be a useful tool when evaluating the safety of docetaxel," wrote Omizo and colleagues in their poster presentation.
Study Design and Patient Characteristics
The study initially examined 68 patients treated with upfront docetaxel or a triplet therapy regimen between January 2014 and April 2024. Of these, 32 patients had undergone frailty evaluation using the G8 screening tool and were included in the final analysis.
Patients who experienced severe adverse events had an average G8 score of 11.75 (range 5-75) compared to 15 (range 11.5-17) in those without severe events. The median age was similar between groups: 70.5 years for those with severe adverse events versus 71 years for those without.
Other notable differences included lower BMI (21.9 vs 24.2) and lower serum albumin levels (3.85 g/dL vs 4.2 g/dL) in patients who experienced severe adverse events.
Clinical Implications for Treatment Decisions
The study focused on patients receiving androgen deprivation therapy (ADT) plus upfront docetaxel, or ADT with darolutamide (Nubeqa) plus docetaxel—treatment combinations that have become standard of care for many mHSPC patients.
While these regimens have shown survival benefits in clinical trials, the significant rate of severe adverse events highlights the importance of patient selection. The G8 screening tool, which was originally developed to identify geriatric patients who might benefit from comprehensive geriatric assessment, appears to have valuable applications in oncology treatment planning.
"Further study is needed to evaluate whether the treatment intensity needs to be modified based on the risk classification," the authors concluded, suggesting that treatment protocols might need adjustment for patients identified as high-risk for severe adverse events.
This research represents an important step toward personalized treatment approaches for mHSPC patients, potentially allowing oncologists to better balance efficacy with tolerability based on objective frailty assessments.
