Objective: Cell-free DNA (cfDNA) is a potential biomarker of surgical invasiveness, but its relationship with postoperative outcomes remains unclear. This study evaluated whether total cfDNA levels measured immediately after robot-assisted radical prostatectomy (RARP) predict postoperative outcomes, including surgical stress markers, pain, and complications.
Methods: We retrospectively analyzed 80 patients who underwent RARP at Hirosaki University Hospital. Total cfDNA levels were measured preoperatively and immediately postoperatively. Postoperative pain intensity was assessed on postoperative days 1-3 using the numerical rating scale (NRS). Patients were categorized into mild pain (NRS < 4) and moderate-to-severe pain (NRS ≥ 4) groups. Associations between cfDNA and NRS were evaluated and compared with conventional surgical stress markers (operative time, estimated blood loss, white blood cell count, C-reactive protein, and oxidative stress).
Results: The cfDNA ratio was higher in the NRS ≥ 4 group than in the NRS < 4 group (p = 0.029). In adjusted analyses, cfDNA ≥ 2.00 was associated with greater odds of moderate-to-severe pain (odds ratio 2.90, 95% confidence interval 1.09-7.72). Conventional markers-including CRP, white blood cell count, operative time, and blood loss-were not associated with pain. Oxidative-stress indices showed only weak correlations with NRS and were not correlated with cfDNA. Limitations include the retrospective, single-center design, and modest sample size.
Conclusions: Immediate postoperative cfDNA is significantly associated with postoperative pain severity and may serve as a rapid, sensitive biomarker for early pain prediction. The cfDNA ratio could support the development of personalized perioperative pain-management strategies. A prospective validation is warranted.
Keywords: NRS; RARP; biomarker; cfDNA; postoperative pain; prostate cancer.
© 2025 The Japanese Urological Association.