Immediate Postoperative cfDNA Elevation Predicts Pain After Robot-Assisted Radical Prostatectomy

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.

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).

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.

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.