VERY-EARLY RECURRENCE AFTER LIVER RESECTION FOR COLORECTAL LIVER METASTASES. IS THIS A BIOMARKER OF FUTILE SURGERY?
Damiano Gentile*, Luca Viganò, Jacopo Galvanin, Fabio Procopio, Cimino Matteo Maria, Matteo Donadon, Daniele Del Fabbro, Guido Torzilli
Department of Upper Gastro-Intestinal Surgery, Humanitas Research Hospital, Rozzano, Milano, Italy
Background
Liver resection (LR) with perioperative chemotherapy is the standard treatment of patients with colorectal liver metastases (CLM), even in presence of severe tumor burden. Such aggressive indications lead to non-negligible recurrence rate. Some patients even experience very-early recurrence (VER), i.e. recurrence ≤3 months after LR. VER puts in doubt the completeness of LR and its beneficial impact on prognosis. The present study aims to depict the incidence of VER after aggressive surgical indications, to analyze VER predictive factors, to elucidate its prognostic impact, and to evaluate patients’ survival benefit from LR when VER occurs.
Methods
We reviewed all consecutive patients undergoing a first LR for CLM between 2004 and 2017 at the authors institution. Patients with available data about the recurrence status at 3 months and with a follow-up >12 months were selected. The exclusion criteria were: 90-day mortality; incomplete LR (including patients who did not completed staged hepatectomies); and disease progression while on preoperative chemotherapy.
Results
A total of 484 patients were analyzed. Of those, 364 (75.2%) had recurrence, including 55 (11.4%) with VER. At multivariable analysis, independent predictive factors of VER were: number of metastases (solitary CLM 3.6%, 2-9 CLM 8.1%, 10-14 CLM 20.0%, and ≥15 CLM 42.2%; p<0.05); extra-hepatic disease (yes, 23.2% vs. no, 9.8%; p=0.007); age (≤70 years, 14.0% vs. >70 years, 5.4%; p=0.022); and adjuvant chemotherapy (yes, 8.2% vs. no 14.3%; p=0.007). RAS status and preoperative CHT data were not associated with VER risk.
VER adversely affected prognosis. After a mean follow-up of 34 months, 5-year overall survival rate was 17.3% for VER group vs. 44.5% for not-VER group (p<0.001).
One-fourth of patients with VER (14/55) underwent repeat treatment (LR or ablation) and had higher survival than patients without VER repeat treatment (3-year survival 50.8% vs. 13.1%; p=0.001). VER not amenable to repeat treatment occurred in 4% of patients with <10 CLM without extrahepatic disease, while it occurred in 57% of patients with ≥15 CLM and extrahepatic disease.
Conclusion
When aggressive indications to LR for CLM are adopted, about 10% of patients experience VER. This risk is consistently increased in patients with numerous CLM or extrahepatic disease, while is reduced in patients receiving adjuvant chemotherapy. VER is associated with poor survival. Repeat loco-regional treatment of VER may still improve survival, but it is feasible in only one-fourth of patients. Patients with VER not amenable to repeat treatment did not have a survival benefit from LR. The risk for VER should be considered whenever scheduling LR, especially in patients with numerous CLM and extrahepatic disease.
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