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Background <p>Failure of postoperative systemic recovery has increasingly been recognized as a determinant of long-term outcomes after major cancer surgery. While exaggerated inflammation and immune dysfunction have been linked to oncologic risk, it remains unclear how recovery dynamics during the perioperative period influence early molecular residual disease.</p> Methods <p>We conducted a prospective longitudinal cohort study of patients aged ≥ 65&#xa0;years undergoing curative-intent resection for gastric or colorectal cancer. Postoperative recovery dynamics were characterized using serial physiological, inflammatory, and immune assessments from the preoperative period through postoperative day (POD) 7. Systemic inflammatory burden and resolution were quantified using longitudinal interleukin-6 measurements, and early immune effector restoration was evaluated using postoperative immune profiling. Dynamic autonomic recovery trajectories were derived from perioperative heart rate variability measurements as an upstream marker of recovery capacity. Circulating tumor DNA-defined minimal residual disease (MRD) was assessed at 30&#xa0;d. Multivariable regression, temporally ordered mediation analyses, and survival models were performed.</p> Results <p>Among 532 patients, 30-day MRD positivity occurred in 18.0%. Impaired postoperative recovery was characterized by greater cumulative inflammatory burden, delayed inflammatory resolution, and reduced early immune effector restoration. Slower inflammatory resolution and impaired immune restoration were independently associated with higher odds of MRD positivity. Dynamic autonomic recovery trajectories were associated with MRD status, with significant indirect effects mediated through inflammatory resolution and early immune exhaustion at POD7. Unfavorable MRD dynamics were strongly associated with inferior disease-free survival during 36&#xa0;months of follow-up.</p> Conclusions <p>Delayed inflammatory resolution and impaired immune restoration represent core features of postoperative recovery failure and are associated with early ctDNA-defined minimal residual disease after curative gastric and colorectal cancer surgery. These findings position perioperative recovery biology as a critical link between systemic resilience and long-term oncologic outcomes.</p>

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Perioperative autonomic recovery and inflammatory resolution are associated with early molecular residual disease and survival after curative gastric and colorectal cancer surgery in older adults: a prospective cohort study

  • 期刊论文

  • 发表日期：

    2026年4月9日

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  • Shengjie Pan,
  • Gang Wang

摘要

Background

Failure of postoperative systemic recovery has increasingly been recognized as a determinant of long-term outcomes after major cancer surgery. While exaggerated inflammation and immune dysfunction have been linked to oncologic risk, it remains unclear how recovery dynamics during the perioperative period influence early molecular residual disease.

Methods

We conducted a prospective longitudinal cohort study of patients aged ≥ 65 years undergoing curative-intent resection for gastric or colorectal cancer. Postoperative recovery dynamics were characterized using serial physiological, inflammatory, and immune assessments from the preoperative period through postoperative day (POD) 7. Systemic inflammatory burden and resolution were quantified using longitudinal interleukin-6 measurements, and early immune effector restoration was evaluated using postoperative immune profiling. Dynamic autonomic recovery trajectories were derived from perioperative heart rate variability measurements as an upstream marker of recovery capacity. Circulating tumor DNA-defined minimal residual disease (MRD) was assessed at 30 d. Multivariable regression, temporally ordered mediation analyses, and survival models were performed.

Results

Among 532 patients, 30-day MRD positivity occurred in 18.0%. Impaired postoperative recovery was characterized by greater cumulative inflammatory burden, delayed inflammatory resolution, and reduced early immune effector restoration. Slower inflammatory resolution and impaired immune restoration were independently associated with higher odds of MRD positivity. Dynamic autonomic recovery trajectories were associated with MRD status, with significant indirect effects mediated through inflammatory resolution and early immune exhaustion at POD7. Unfavorable MRD dynamics were strongly associated with inferior disease-free survival during 36 months of follow-up.

Conclusions

Delayed inflammatory resolution and impaired immune restoration represent core features of postoperative recovery failure and are associated with early ctDNA-defined minimal residual disease after curative gastric and colorectal cancer surgery. These findings position perioperative recovery biology as a critical link between systemic resilience and long-term oncologic outcomes.