Liver Resection for Primarily Unresectable Colorectal Metastases Downsized by Chemotherapy

Abstract

This study was performed prospectively to assess the effect of systemic chemotherapy (FOLFIRI protocol) in patients with initially unresectable colorectal liver metastases (CRLM) and, after performing liver resection in patients with downsized metastases, to compare the postoperative and long-term results with those of patients with primarily resectable CRLM. Records from a prospective database including all consecutive admissions for CRLM between June 2000 and June 2004 were reviewed. The analysis addressed all patients who underwent hepatectomy for primarily resectable CRLM (Group A), or underwent chemotherapy for primarily unresectable CRLM and among these, particularly the patients who were finally resected after downsizing of CRLM (Group B). There were 60 primarily resected patients (Group A). Forty-two other patients underwent chemotherapy; after an average of nine courses, 18 of them (42.8%) with significantly downsized lesions were explored and 15 (35.7%, Group B) were resected, whereas three had peritoneal metastases. Group B differed from Group A for a significantly higher rate of synchronous CRLM upon diagnosis of colorectal cancer, a larger size of CRLM upon evaluation in our center, and a lower rate of major hepatectomies (20.0% vs. 51.6 %) at surgery. No patient in Group B had positive margins of resection. Operative mortality was nil and morbidity was 20.0% in both groups. In Group B vs. Group A median survival after hepatectomy was 46 vs. 47 months (n.s), 3-year survival rate was 73% vs. 71% (n.s.), disease-free survival rate was 31% vs. 58% (p = 0.04) and, at a median follow-up of 34 months, tumor recurrence rate was 53.3% vs. 28.3% (n.s.). Four out of the eight Group B patients with recurrence underwent a re-resection, and were alive at 9 to 67 months after the first resection. These results show that in about one-third of the patients with primarily unresectable CRLM, downsizing of the lesions by chemotherapy (FOLFIRI protocol) permitted a subsequent curative resection. In these patients, operative risk and survival did not differ from the figures observed in primarily resectable patients and, in spite of a lower disease-free survival with more frequent recurrence, re-resection still represented a valid option to continue treatment.

Liver Resection for Colorectal Cancer Metastases

“…The Nordlinger et al trial 45 limited preoperative chemotherapy to 6 cycles. Most of the preoperative chemotherapy studies for initially unresectable metastases [question 2(b)] performed repeat imaging during chemotherapy, with resection as soon as was technically feasible [52][53][54] .…”

“…Most studies of preoperative chemotherapy for initially unresectable metastases used repeat imaging during chemotherapy, with resection as soon as was technically feasible [52][53][54] . In patients in whom resectability is achieved, it is common to offer further adjuvant chemotherapy, but no direct evidence is available on which to base a recommendation concerning either the utility of adjuvant chemotherapy or the total duration or number of cycles of chemotherapy.…”

Erweiterte multimodale Leberresektionen bei primären und sekundären Lebertumoren

“…Kolorektale Lebermetastasen Im Gegensatz zu HCC und CCC sowie dem hilären Gallengangskarzinom liegen für die beiden wichtigsten Indikationsgruppen bei den sekundären Lebertumoren (kolorektale Lebermetastasen, neuroendokrine Lebermetastasen) vergleichsweise valide Literaturdaten vor [35][36][37][38][39][40][41][42]. So hat sich in den letzten Jahren zunehmend durchgesetzt, dass die früher für die Resektion kolorektaler Lebermetastasen geforderte tumorfreie Sicherheitszone von mindestens 1 cm allenfalls eine untergeordnete prognostische Bedeutung besitzt [35,38] [42] ein nahezu identisches 3-Jahres-Überleben von 73 versus 71% bei jedoch signifikant niedrigerem tumorfreien 3-Jahres-Überleben von 31 versus 58% (p = 0,04) bei erst sekundär resektablen Metastasen angeben.…”

“…So hat sich in den letzten Jahren zunehmend durchgesetzt, dass die früher für die Resektion kolorektaler Lebermetastasen geforderte tumorfreie Sicherheitszone von mindestens 1 cm allenfalls eine untergeordnete prognostische Bedeutung besitzt [35,38] [42] ein nahezu identisches 3-Jahres-Überleben von 73 versus 71% bei jedoch signifikant niedrigerem tumorfreien 3-Jahres-Überleben von 31 versus 58% (p = 0,04) bei erst sekundär resektablen Metastasen angeben.…”

The Assessment and Management of Chemotherapy Associated Liver Injury

“…[21] Similar results have been reported with a 5-FU/Irinotecan regimen by Nuzzo et al with 15 out of 42 patients (36%) with inoperable disease being able to undergo subsequent surgical treatment. [22] In an attempt to determine the most appropriate regimen for use as conversion chemotherapy the GERCOR trial randomised patients with inoperable metastatic colorectal cancer to receive either 5-FU/Irinotecan until disease progression or unacceptable toxicity and then 5-FU/Oxaliplatin or the reverse sequence (n=113 per arm). Those patients receiving first line Oxaliplatin demonstrated a higher resection rate (n=24; 22%) than those receiving first line Irinotecan (n=10; 9%) and as such this is the approach most commonly applied in UK practice.…”