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Resection of colorectal liver metastases: only for younger patients?
Reflection and Reaction
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5
Koizumi W, Narahara H, Hara T, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol 2008; 9: 215–21. Ajani JA, Rodriquez W, Bodoky G, et al. Multicenter phase III comparison of cisplatin/S-1 (CS) with cisplatin/5-FU (CF) as first-line therapy in patients with advanced gastric cancer (FLAGS): secondary and subset analyses. Proc Soc Am Clin Oncol 2009; 27: Abstr 4511.
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Yamada Y, Yamamoto S, Ohtsu A, et al. Impact of dihydropyrimidine dehydrogenase status of biopsy specimens on efficacy of irinotecan plus cisplatin, S-1, or 5-FU as first-line treatment of advanced gastric cancer patients in JCOG9912. Proc Soc Am Clin Oncol 2009; 27: Abstr 4535.
Dr P Marazzi/Science Photo Library
Resection of colorectal liver metastases: only for younger patients?
If you would like to respond to an article published in The Lancet Oncology, please submit your correspondence online at: http://ees.elsevier. com/thelancetoncology
116
A large body of evidence supports the role of liver resection for liver-confined metastatic colorectal cancer. Although case series have calculated survival from different time points, 5-year survival approaching 60% has been reported. Some studies report patients surviving for 10 years, with these patients considered to be cured. Most patients, however, present with initially unresectable liver disease. In the past decade, conversion therapy (ie, unresectable disease becoming resectable after systemic chemotherapy) has become possible. Tandem advances in surgical technique and post-operative care have resulted in more patients becoming candidates for liver resection. The CELIM study, a randomised phase 2 trial reported in January in The Lancet Oncology,1 showed that the addition of cetuximab to modern systemic chemotherapy resulted in an increase in resectability of 28% (from 32% at baseline to 60% after chemotherapy). Our concern regarding this study is the median age of the patients in each treatment group (62·0 and 65·1 years [range 56·1–70·7]) and the message this sends to oncologists; clinicians may be forgiven for thinking that patients with an Eastern Cooperative Oncology Group performance status of 80% or higher, and younger than 70 years, are the population in whom to consider a conversion strategy. Unfortunately, many studies of chemobiological conversion therapy (chemotherapy with or without a biological agent), both prospective phase 2–3 trials and retrospective series, report a population of similar age distribution—ie, median age 59–65 years (range 20–80).2–3 In some studies, up to 82% of patients are younger than 70 years.3 Since practice guidelines are derived from peerreviewed work, it is worrying that key studies do not reflect the actual age demographic of patients being treated. In Europe and the USA, more than 60% of new cancer cases and 70% of cancer deaths occur in patients aged 65 years or older,4 and up to 75% of colorectal cancers occur in this age group. In developed countries, the mean life expectancy of a 65-year-old is 17·1–20·0 years.5 Given the substantial improvements in 5-year survival of
metastatic colorectal cancer, and the possibility for many years of good-quality life remaining, it is imperative that patients 65 years and older (who constitute the majority of cases) be considered for inclusion in clinical trials and for aggressive multimodality management. Surgical resection of liver metastases and the use of modern systemic chemobiological therapy are safe and effective in this age group.6,7 Despite increased comorbidities, decreased hepatic reserve, and an under-representation of older patients undergoing liver resection, most published data does not support a correlation between poor outcome and increasing age. A healthy aging liver is able to cope with chemobiological conversion therapy and ensuing hepatic resection. Because the 5-year survival of liver-confined metastatic colorectal cancer in the absence of liver resection is 0%, we urge medical and surgical oncologists to consider optimum treatment strategies for older patients, since published survival data are likely to apply to most of this group as well. Derek G Power*, Stuart M Lichtman Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA [email protected] The authors declared no conflicts of interest. 1
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3
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Folprecht G, Gruenberger T, Bechstein WO, et al. Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol 2010; 11: 38–47. Goldberg RM SD, Morton RF, Fuchs CS, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004; 22: 23–30. Van Cutsem E, Rivera F, Berry S, et al. Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 2009; 20: 1842–47. Papamichael D, Audisio R, Horiot JC, et al. Treatment of the elderly colorectal cancer patient: SIOG expert recommendations. Ann Oncol 2009; 20: 5–16. National Center for Health Statistics. Health, United States, 2006. http://www.cdc.gov/nchs/data/hus/hus06.pdf (accessed Dec 16, 2009). Cummings LC, Payes JD, Cooper GS. Survival after hepatic resection in metastatic colorectal cancer: a population-based study. Cancer 2007; 109: 718–26. Kabbinavar FF, Hurwitz HI, Yi J, et al. Addition of bevacizumab to fluorouracil-based first-line treatment of metastatic colorectal cancer: pooled analysis of cohorts of older patients from two randomized clinical trials. J Clin Oncol 2009; 27: 199–205.
www.thelancet.com/oncology Vol 11 February 2010
4
5
Koizumi W, Narahara H, Hara T, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol 2008; 9: 215–21. Ajani JA, Rodriquez W, Bodoky G, et al. Multicenter phase III comparison of cisplatin/S-1 (CS) with cisplatin/5-FU (CF) as first-line therapy in patients with advanced gastric cancer (FLAGS): secondary and subset analyses. Proc Soc Am Clin Oncol 2009; 27: Abstr 4511.
6
Yamada Y, Yamamoto S, Ohtsu A, et al. Impact of dihydropyrimidine dehydrogenase status of biopsy specimens on efficacy of irinotecan plus cisplatin, S-1, or 5-FU as first-line treatment of advanced gastric cancer patients in JCOG9912. Proc Soc Am Clin Oncol 2009; 27: Abstr 4535.
Dr P Marazzi/Science Photo Library
Resection of colorectal liver metastases: only for younger patients?
If you would like to respond to an article published in The Lancet Oncology, please submit your correspondence online at: http://ees.elsevier. com/thelancetoncology
116
A large body of evidence supports the role of liver resection for liver-confined metastatic colorectal cancer. Although case series have calculated survival from different time points, 5-year survival approaching 60% has been reported. Some studies report patients surviving for 10 years, with these patients considered to be cured. Most patients, however, present with initially unresectable liver disease. In the past decade, conversion therapy (ie, unresectable disease becoming resectable after systemic chemotherapy) has become possible. Tandem advances in surgical technique and post-operative care have resulted in more patients becoming candidates for liver resection. The CELIM study, a randomised phase 2 trial reported in January in The Lancet Oncology,1 showed that the addition of cetuximab to modern systemic chemotherapy resulted in an increase in resectability of 28% (from 32% at baseline to 60% after chemotherapy). Our concern regarding this study is the median age of the patients in each treatment group (62·0 and 65·1 years [range 56·1–70·7]) and the message this sends to oncologists; clinicians may be forgiven for thinking that patients with an Eastern Cooperative Oncology Group performance status of 80% or higher, and younger than 70 years, are the population in whom to consider a conversion strategy. Unfortunately, many studies of chemobiological conversion therapy (chemotherapy with or without a biological agent), both prospective phase 2–3 trials and retrospective series, report a population of similar age distribution—ie, median age 59–65 years (range 20–80).2–3 In some studies, up to 82% of patients are younger than 70 years.3 Since practice guidelines are derived from peerreviewed work, it is worrying that key studies do not reflect the actual age demographic of patients being treated. In Europe and the USA, more than 60% of new cancer cases and 70% of cancer deaths occur in patients aged 65 years or older,4 and up to 75% of colorectal cancers occur in this age group. In developed countries, the mean life expectancy of a 65-year-old is 17·1–20·0 years.5 Given the substantial improvements in 5-year survival of
metastatic colorectal cancer, and the possibility for many years of good-quality life remaining, it is imperative that patients 65 years and older (who constitute the majority of cases) be considered for inclusion in clinical trials and for aggressive multimodality management. Surgical resection of liver metastases and the use of modern systemic chemobiological therapy are safe and effective in this age group.6,7 Despite increased comorbidities, decreased hepatic reserve, and an under-representation of older patients undergoing liver resection, most published data does not support a correlation between poor outcome and increasing age. A healthy aging liver is able to cope with chemobiological conversion therapy and ensuing hepatic resection. Because the 5-year survival of liver-confined metastatic colorectal cancer in the absence of liver resection is 0%, we urge medical and surgical oncologists to consider optimum treatment strategies for older patients, since published survival data are likely to apply to most of this group as well. Derek G Power*, Stuart M Lichtman Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA [email protected] The authors declared no conflicts of interest. 1
2
3
4 5 6
7
Folprecht G, Gruenberger T, Bechstein WO, et al. Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol 2010; 11: 38–47. Goldberg RM SD, Morton RF, Fuchs CS, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004; 22: 23–30. Van Cutsem E, Rivera F, Berry S, et al. Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 2009; 20: 1842–47. Papamichael D, Audisio R, Horiot JC, et al. Treatment of the elderly colorectal cancer patient: SIOG expert recommendations. Ann Oncol 2009; 20: 5–16. National Center for Health Statistics. Health, United States, 2006. http://www.cdc.gov/nchs/data/hus/hus06.pdf (accessed Dec 16, 2009). Cummings LC, Payes JD, Cooper GS. Survival after hepatic resection in metastatic colorectal cancer: a population-based study. Cancer 2007; 109: 718–26. Kabbinavar FF, Hurwitz HI, Yi J, et al. Addition of bevacizumab to fluorouracil-based first-line treatment of metastatic colorectal cancer: pooled analysis of cohorts of older patients from two randomized clinical trials. J Clin Oncol 2009; 27: 199–205.
www.thelancet.com/oncology Vol 11 February 2010