Total neoadjuvant therapy for rectal cancer: Implications for subsequent liver metastases and chemotherapy-associated...

Total neoadjuvant therapy for localized rectal cancer entails delivery of all systemic chemotherapy and pelvic radiation before proctectomy to improve pathologic response, disease-free survival, and potentially organ preservation. In patients who develop liver metastases during or after total neoadjuvant therapy, the effects of total neoadjuvant therapy on patient outcomes and chemotherapy-associated liver injury are unknown.

A single-institution prospectively maintained database was queried for patients who underwent hepatectomy for metastatic rectal cancer, with or without total neoadjuvant therapy between 2014 and 2024. Surgical pathology reports were reviewed for histologic changes in the background liver.

Among 286 patients undergoing hepatectomy for metastatic rectal cancer, 30 patients received total neoadjuvant therapy, and 256 patients did not receive total neoadjuvant therapy. Overall survival was significantly lower among patients in the total neoadjuvant therapy group (median overall survival 48.7 months, total neoadjuvant therapy vs 99.5 months, non-total neoadjuvant therapy, P = .01). On multivariable analysis, total neoadjuvant therapy remained an independent predictor of worse overall survival (hazard ratio 0.41, 95% confidence interval 0.22-0.79, P = .008). Sinusoidal injury rates were not significantly different with or without total neoadjuvant therapy (26.9% total neoadjuvant therapy vs 32.9% non-total neoadjuvant therapy, P = .69). Patients who received total neoadjuvant therapy had significantly higher rates of steatosis or steatohepatitis (30.8% total neoadjuvant therapy vs 8.7% non-total neoadjuvant therapy, P = .002).

In this preliminary analysis, patients who developed liver metastases during or after total neoadjuvant therapy for rectal cancer had significantly worse overall survival after hepatectomy than patients who did not receive total neoadjuvant therapy. Steatosis and steatohepatitis rates were higher with total neoadjuvant therapy. Further study is needed to identify factors associated with worse outcomes in patients who undergo hepatectomy after total neoadjuvant therapy.