Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy

A model to predict long-term survival

René Adam, Valérie Delvart, Gérard Pascal, Adrian Valeanu, Denis Castaing, Daniel Azoulay, Sylvie Giacchetti, Bernard Paule, Francis Kunstlinger, Odile Ghémard, Francis Levi, Henri Bismuth, Harold J. Wanebo, Robert Joseph Fitzgibbons, Steven M. Strasberg, David W. Easter

Research output: Contribution to journalArticle

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Abstract

Objective: To evaluate the long-term survival of patients resected for primarily unresectable colorectal liver metastases (CRLM) downstaged by systemic chemotherapy and to use prognostic factors of outcome for a model predictive of survival on a preoperative setting. Summary Background Data: Surgery of primarily unresectable CRLM after downstaging chemotherapy is still questioned, and prognostic factors of outcome are lacking. Methods: From a consecutive series of 1439 patients with CRLM managed in a single institution during an 11-year period (1988-1999), 1104 (77%) initially unresectable (NR) patients were treated by chemotherapy and 335 (23%) resectable were treated by primary liver resection. Chemotherapy mainly consisted of 5-fluorouracil and leucovorin combined to oxaliplatin (70%), irinotecan (7%), or both (4%) given as chronomodulated infusion (87%). NR patients were routinely reassessed every 4 courses. Surgery was reconsidered every time a documented response to chemotherapy was observed. Among 1104 NR patients, 138 "good responders" (12.5%) underwent secondary hepatic resection after an average of 10 courses of chemotherapy. At time of diagnosis, mean number of metastases was 4.4 (1-14) and mean maximum size was 5.2 cm (1-25). Extrahepatic tumor was present in 52 patients (38%). Multinodularity or extrahepatic tumor was the main cause of initial unresectability. All factors likely to be predictive of survival after liver resection were evaluated by uni- and multivariate analysis. Estimation of survival was adjusted on risk factors available preoperatively. Results: Seventy-five percent of procedures were major hepatectomies (≥3 segments) and 93% were potentially curative. Liver surgery was combined to portal embolization, to ablative treatment, or to a second-stage hepatectomy in 42 patients (30%) and to resection of extrahepatic tumor in 41 patients (30%). Operative mortality within 2 months was 0.7%, and postoperative morbidity was 28%. After a mean follow-up of 48.7 months, 111 of the 138 patients (80%) developed tumor recurrence, 40 of which were hepatic (29%), 12 extrahepatic (9%), and 59 both hepatic and extrahepatic (43%). Recurrence was treated in 52 patients by repeat hepatectomy (71 procedures) and in 42 patients by extrahepatic resection (77 procedures). Survival was 33% and 23% at 5 and 10 years with a disease-free survival of 22% and 17%, respectively. It was decreased as compared with that of patients primarily resected within the same period (48% and 30% respectively, P = 0.01). At the last follow-up, 99 patients had died (72%) and 39 (28%) were alive; 25 were disease free (18%) and 14 had recurrence (10%). At multivariate analysis, 4 preoperative factors were independently associated to decreased survival: rectal primary, ≥3 metastases, maximum tumor size >10 cm, and CA 19-9 >100 UI/L. Mean adjusted 5-year survival according to the presence of 0, 1, 2, 3, or 4 factors was 59%, 30%, 7%, 0%, and 0%. Conclusions: Modern chemotherapy allows 12.5% of patients with unresectable CRLM to be rescued by liver surgery. Despite a high rate of recurrence, 5-year survival is 33% overall, with a wide use of repeat hepatectomies and extrahepatic resections. Four preoperative risk factors could select the patients most likely to benefit from this strategy.

Original languageEnglish
Pages (from-to)644-658
Number of pages15
JournalAnnals of Surgery
Volume240
Issue number4
DOIs
StatePublished - Oct 2004

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Colorectal Surgery
Neoplasm Metastasis
Drug Therapy
Survival
Liver
Hepatectomy
Recurrence
oxaliplatin
irinotecan
Neoplasms
Multivariate Analysis
Leucovorin
Fluorouracil

All Science Journal Classification (ASJC) codes

  • Surgery

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Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy : A model to predict long-term survival. / Adam, René; Delvart, Valérie; Pascal, Gérard; Valeanu, Adrian; Castaing, Denis; Azoulay, Daniel; Giacchetti, Sylvie; Paule, Bernard; Kunstlinger, Francis; Ghémard, Odile; Levi, Francis; Bismuth, Henri; Wanebo, Harold J.; Fitzgibbons, Robert Joseph; Strasberg, Steven M.; Easter, David W.

In: Annals of Surgery, Vol. 240, No. 4, 10.2004, p. 644-658.

Research output: Contribution to journalArticle

Adam, R, Delvart, V, Pascal, G, Valeanu, A, Castaing, D, Azoulay, D, Giacchetti, S, Paule, B, Kunstlinger, F, Ghémard, O, Levi, F, Bismuth, H, Wanebo, HJ, Fitzgibbons, RJ, Strasberg, SM & Easter, DW 2004, 'Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: A model to predict long-term survival', Annals of Surgery, vol. 240, no. 4, pp. 644-658. https://doi.org/10.1097/01.sla.0000141198.92114.f6
Adam, René ; Delvart, Valérie ; Pascal, Gérard ; Valeanu, Adrian ; Castaing, Denis ; Azoulay, Daniel ; Giacchetti, Sylvie ; Paule, Bernard ; Kunstlinger, Francis ; Ghémard, Odile ; Levi, Francis ; Bismuth, Henri ; Wanebo, Harold J. ; Fitzgibbons, Robert Joseph ; Strasberg, Steven M. ; Easter, David W. / Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy : A model to predict long-term survival. In: Annals of Surgery. 2004 ; Vol. 240, No. 4. pp. 644-658.
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title = "Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: A model to predict long-term survival",
abstract = "Objective: To evaluate the long-term survival of patients resected for primarily unresectable colorectal liver metastases (CRLM) downstaged by systemic chemotherapy and to use prognostic factors of outcome for a model predictive of survival on a preoperative setting. Summary Background Data: Surgery of primarily unresectable CRLM after downstaging chemotherapy is still questioned, and prognostic factors of outcome are lacking. Methods: From a consecutive series of 1439 patients with CRLM managed in a single institution during an 11-year period (1988-1999), 1104 (77{\%}) initially unresectable (NR) patients were treated by chemotherapy and 335 (23{\%}) resectable were treated by primary liver resection. Chemotherapy mainly consisted of 5-fluorouracil and leucovorin combined to oxaliplatin (70{\%}), irinotecan (7{\%}), or both (4{\%}) given as chronomodulated infusion (87{\%}). NR patients were routinely reassessed every 4 courses. Surgery was reconsidered every time a documented response to chemotherapy was observed. Among 1104 NR patients, 138 {"}good responders{"} (12.5{\%}) underwent secondary hepatic resection after an average of 10 courses of chemotherapy. At time of diagnosis, mean number of metastases was 4.4 (1-14) and mean maximum size was 5.2 cm (1-25). Extrahepatic tumor was present in 52 patients (38{\%}). Multinodularity or extrahepatic tumor was the main cause of initial unresectability. All factors likely to be predictive of survival after liver resection were evaluated by uni- and multivariate analysis. Estimation of survival was adjusted on risk factors available preoperatively. Results: Seventy-five percent of procedures were major hepatectomies (≥3 segments) and 93{\%} were potentially curative. Liver surgery was combined to portal embolization, to ablative treatment, or to a second-stage hepatectomy in 42 patients (30{\%}) and to resection of extrahepatic tumor in 41 patients (30{\%}). Operative mortality within 2 months was 0.7{\%}, and postoperative morbidity was 28{\%}. After a mean follow-up of 48.7 months, 111 of the 138 patients (80{\%}) developed tumor recurrence, 40 of which were hepatic (29{\%}), 12 extrahepatic (9{\%}), and 59 both hepatic and extrahepatic (43{\%}). Recurrence was treated in 52 patients by repeat hepatectomy (71 procedures) and in 42 patients by extrahepatic resection (77 procedures). Survival was 33{\%} and 23{\%} at 5 and 10 years with a disease-free survival of 22{\%} and 17{\%}, respectively. It was decreased as compared with that of patients primarily resected within the same period (48{\%} and 30{\%} respectively, P = 0.01). At the last follow-up, 99 patients had died (72{\%}) and 39 (28{\%}) were alive; 25 were disease free (18{\%}) and 14 had recurrence (10{\%}). At multivariate analysis, 4 preoperative factors were independently associated to decreased survival: rectal primary, ≥3 metastases, maximum tumor size >10 cm, and CA 19-9 >100 UI/L. Mean adjusted 5-year survival according to the presence of 0, 1, 2, 3, or 4 factors was 59{\%}, 30{\%}, 7{\%}, 0{\%}, and 0{\%}. Conclusions: Modern chemotherapy allows 12.5{\%} of patients with unresectable CRLM to be rescued by liver surgery. Despite a high rate of recurrence, 5-year survival is 33{\%} overall, with a wide use of repeat hepatectomies and extrahepatic resections. Four preoperative risk factors could select the patients most likely to benefit from this strategy.",
author = "Ren{\'e} Adam and Val{\'e}rie Delvart and G{\'e}rard Pascal and Adrian Valeanu and Denis Castaing and Daniel Azoulay and Sylvie Giacchetti and Bernard Paule and Francis Kunstlinger and Odile Gh{\'e}mard and Francis Levi and Henri Bismuth and Wanebo, {Harold J.} and Fitzgibbons, {Robert Joseph} and Strasberg, {Steven M.} and Easter, {David W.}",
year = "2004",
month = "10",
doi = "10.1097/01.sla.0000141198.92114.f6",
language = "English",
volume = "240",
pages = "644--658",
journal = "Annals of Surgery",
issn = "0003-4932",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy

T2 - A model to predict long-term survival

AU - Adam, René

AU - Delvart, Valérie

AU - Pascal, Gérard

AU - Valeanu, Adrian

AU - Castaing, Denis

AU - Azoulay, Daniel

AU - Giacchetti, Sylvie

AU - Paule, Bernard

AU - Kunstlinger, Francis

AU - Ghémard, Odile

AU - Levi, Francis

AU - Bismuth, Henri

AU - Wanebo, Harold J.

AU - Fitzgibbons, Robert Joseph

AU - Strasberg, Steven M.

AU - Easter, David W.

PY - 2004/10

Y1 - 2004/10

N2 - Objective: To evaluate the long-term survival of patients resected for primarily unresectable colorectal liver metastases (CRLM) downstaged by systemic chemotherapy and to use prognostic factors of outcome for a model predictive of survival on a preoperative setting. Summary Background Data: Surgery of primarily unresectable CRLM after downstaging chemotherapy is still questioned, and prognostic factors of outcome are lacking. Methods: From a consecutive series of 1439 patients with CRLM managed in a single institution during an 11-year period (1988-1999), 1104 (77%) initially unresectable (NR) patients were treated by chemotherapy and 335 (23%) resectable were treated by primary liver resection. Chemotherapy mainly consisted of 5-fluorouracil and leucovorin combined to oxaliplatin (70%), irinotecan (7%), or both (4%) given as chronomodulated infusion (87%). NR patients were routinely reassessed every 4 courses. Surgery was reconsidered every time a documented response to chemotherapy was observed. Among 1104 NR patients, 138 "good responders" (12.5%) underwent secondary hepatic resection after an average of 10 courses of chemotherapy. At time of diagnosis, mean number of metastases was 4.4 (1-14) and mean maximum size was 5.2 cm (1-25). Extrahepatic tumor was present in 52 patients (38%). Multinodularity or extrahepatic tumor was the main cause of initial unresectability. All factors likely to be predictive of survival after liver resection were evaluated by uni- and multivariate analysis. Estimation of survival was adjusted on risk factors available preoperatively. Results: Seventy-five percent of procedures were major hepatectomies (≥3 segments) and 93% were potentially curative. Liver surgery was combined to portal embolization, to ablative treatment, or to a second-stage hepatectomy in 42 patients (30%) and to resection of extrahepatic tumor in 41 patients (30%). Operative mortality within 2 months was 0.7%, and postoperative morbidity was 28%. After a mean follow-up of 48.7 months, 111 of the 138 patients (80%) developed tumor recurrence, 40 of which were hepatic (29%), 12 extrahepatic (9%), and 59 both hepatic and extrahepatic (43%). Recurrence was treated in 52 patients by repeat hepatectomy (71 procedures) and in 42 patients by extrahepatic resection (77 procedures). Survival was 33% and 23% at 5 and 10 years with a disease-free survival of 22% and 17%, respectively. It was decreased as compared with that of patients primarily resected within the same period (48% and 30% respectively, P = 0.01). At the last follow-up, 99 patients had died (72%) and 39 (28%) were alive; 25 were disease free (18%) and 14 had recurrence (10%). At multivariate analysis, 4 preoperative factors were independently associated to decreased survival: rectal primary, ≥3 metastases, maximum tumor size >10 cm, and CA 19-9 >100 UI/L. Mean adjusted 5-year survival according to the presence of 0, 1, 2, 3, or 4 factors was 59%, 30%, 7%, 0%, and 0%. Conclusions: Modern chemotherapy allows 12.5% of patients with unresectable CRLM to be rescued by liver surgery. Despite a high rate of recurrence, 5-year survival is 33% overall, with a wide use of repeat hepatectomies and extrahepatic resections. Four preoperative risk factors could select the patients most likely to benefit from this strategy.

AB - Objective: To evaluate the long-term survival of patients resected for primarily unresectable colorectal liver metastases (CRLM) downstaged by systemic chemotherapy and to use prognostic factors of outcome for a model predictive of survival on a preoperative setting. Summary Background Data: Surgery of primarily unresectable CRLM after downstaging chemotherapy is still questioned, and prognostic factors of outcome are lacking. Methods: From a consecutive series of 1439 patients with CRLM managed in a single institution during an 11-year period (1988-1999), 1104 (77%) initially unresectable (NR) patients were treated by chemotherapy and 335 (23%) resectable were treated by primary liver resection. Chemotherapy mainly consisted of 5-fluorouracil and leucovorin combined to oxaliplatin (70%), irinotecan (7%), or both (4%) given as chronomodulated infusion (87%). NR patients were routinely reassessed every 4 courses. Surgery was reconsidered every time a documented response to chemotherapy was observed. Among 1104 NR patients, 138 "good responders" (12.5%) underwent secondary hepatic resection after an average of 10 courses of chemotherapy. At time of diagnosis, mean number of metastases was 4.4 (1-14) and mean maximum size was 5.2 cm (1-25). Extrahepatic tumor was present in 52 patients (38%). Multinodularity or extrahepatic tumor was the main cause of initial unresectability. All factors likely to be predictive of survival after liver resection were evaluated by uni- and multivariate analysis. Estimation of survival was adjusted on risk factors available preoperatively. Results: Seventy-five percent of procedures were major hepatectomies (≥3 segments) and 93% were potentially curative. Liver surgery was combined to portal embolization, to ablative treatment, or to a second-stage hepatectomy in 42 patients (30%) and to resection of extrahepatic tumor in 41 patients (30%). Operative mortality within 2 months was 0.7%, and postoperative morbidity was 28%. After a mean follow-up of 48.7 months, 111 of the 138 patients (80%) developed tumor recurrence, 40 of which were hepatic (29%), 12 extrahepatic (9%), and 59 both hepatic and extrahepatic (43%). Recurrence was treated in 52 patients by repeat hepatectomy (71 procedures) and in 42 patients by extrahepatic resection (77 procedures). Survival was 33% and 23% at 5 and 10 years with a disease-free survival of 22% and 17%, respectively. It was decreased as compared with that of patients primarily resected within the same period (48% and 30% respectively, P = 0.01). At the last follow-up, 99 patients had died (72%) and 39 (28%) were alive; 25 were disease free (18%) and 14 had recurrence (10%). At multivariate analysis, 4 preoperative factors were independently associated to decreased survival: rectal primary, ≥3 metastases, maximum tumor size >10 cm, and CA 19-9 >100 UI/L. Mean adjusted 5-year survival according to the presence of 0, 1, 2, 3, or 4 factors was 59%, 30%, 7%, 0%, and 0%. Conclusions: Modern chemotherapy allows 12.5% of patients with unresectable CRLM to be rescued by liver surgery. Despite a high rate of recurrence, 5-year survival is 33% overall, with a wide use of repeat hepatectomies and extrahepatic resections. Four preoperative risk factors could select the patients most likely to benefit from this strategy.

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