liver metastases in stage 4 colorectal cancer: surgical treatment advances. dr. anton titov, md: hello, we are with dr. graeme poston, who is the leading liver surgeon specializing in treatment of colorectal cancer and liver metastatic disease. dr. poston is professor of surgery at university of liverpool in the uk. he is also a past president of european society of surgical oncology, and british association of surgical oncology. dr. poston is author of nine textbooks on oncological surgery, as well as more than 200 scientific articles about metastatic colorectal cancer. dr. poston's particular interest is in liver metastatic disease in colorectal cancer. dr. poston, hello and welcome. - thank you. let's outline why liver metastatic disease in colorectal cancer is just so important. because 25% of patients at the time of colorectal cancer diagnosis have already developed liver metastatic disease. and in total about 50% of patients with colorectal cancer develop liver metastatic disease at some point during colon cancer disease course. - right. - you have over 40 years of experience doing surgical treatment for liver metastatic disease in colorectal cancer. how situation improved for patients with liver metastases from colorectal cancer recently? how do you treat metastatic colon cancer in the liver? dr. graeme poston, md (leading liver cancer surgeon, uk): yes, i think you've got to look at this in the context of colorectal cancer as a public health problem.
it's the second commonest cancer now in western society after lung cancer. breast cancer in women is more common. but obviously with the men and women counted together, colorectal cancer is second most common cancer. colorectal cancer is increasing in its incidence at 5% per year. in china and india, colon cancer is increasing amongst the middle classes. so colorectal cancer is a major public health problem. if colorectal cancer spreads to the liver, and nothing is done, the prognosis is grim. when liver metastases develop in stage 4 colorectal cancer patients, survival prognosis is probably six to nine months, if no treatment's offered at all. and as we know, 25% of the patients already have colorectal cancer spread to the liver at the time of diagnosis. we operate on stage 4 colorectal cancer patients and we think that their colon cancer is confined to the bowel, the colon, the rectum. 50% of these patients will progress to the liver metastases after removal of primary colorectal cancer tumor. historically, if we go back 30 years ago, 35 years ago, the stage 4 metastatic colon cancer prognosis was probably six months, if you were lucky, once cancer spread to the liver. and at that time, there was no effective treatment for stage 4 metastatic colon cancer. there were no effective colon cancer treatment medications. nobody was offering surgery for the liver metastases in colon cancer. we started to do liver surgery in the 1970s, and people thought we were mad. the liver is a very vascular organ. at any moment in time 25% of your blood is in the liver. there's a lot of bleeding, we were lucky if patients didn't bleed to death during the operation. and people said operating on stage 4 metastatic colon cancer in the liver was insane.
we had no survival data to show why we were doing it at all. we had ineffectual cancer treatment medications, 5 fluorouracil, 5-fu, which was useless in metastatic colon cancer treatment. dr. graeme poston, md (leading liver cancer surgeon, uk): and so, very few patients were being offered any form of active treatment at all for metastatic stage 4 colorectal cancer. then everyone realized that we actually had people living five years after the liver operation for metastatic stage 4 colorectal cancer. and initially it was something like 25-30% of people who had liver cancer surgery were alive five years later without disease. then, we had new drugs coming in the 1990s: irinotecan, oxaliplatin. they were extremely effective for stage 4 metastatic colon cancer treatment. and so we had new drugs in the marketplace. most importantly, these new drugs would convert people with unresectable metastatic stage 4 colon cancer disease to resectability. and then patients could then have a liver resection operation of their metastatic tumors after the tumors had become much smaller. when liver tumors become smaller, they were technically operable. so these patients with liver metastases from stage 4 colorectal cancer had a chance of cure. so suddenly, everything changed. also, we were very conservative in the 1990s. we used to say, well, if a patient had more than three metastatic tumors in the liver, they were incurable. dr. graeme poston, md (leading liver cancer surgeon, uk): and if metastatic tumor was involving both sides of the liver, patients were incurable. and then we realized that was not true. more data emerged that the number of metastatic lesions didn't matter. what mattered most for metastatic stage 4 colon cancer surgery was basically how much liver did not have cancer.
so you could remove the cancerous liver, as long as they had about 30% of their healthy liver with a good blood supply that was free of cancer. then it was reasonable to remove the cancerous liver. dr. anton titov, md: so you could remove the 70% of essentially diseased liver (affected by colorectal cancer metastases). but the 30% of healthy liver would be sufficient to maintain metabolism and to regenerate? dr. graeme poston, md (leading liver cancer surgeon, uk): and regenerate. and we knew that their prognosis wasn't as good. and we know the factors that give metastatic stage 4 colorectal cancer patient a worse prognosis. these factors are: higher numbers of tumors, size of tumors, the differentiation degree of the primary colon cancer tumor. if the primary colon cancer tumor is poorly differentiated, the metastases are going to be poorly differentiated. important metastatic colorectal cancer prognostic factors are: the blood ca-125 level very high, lymph node status of the primary colon cancer tumor. if lymph nodes were involved as well as the liver, that affected prognosis to the worse. the last thing, the one thing the liver surgeon can control, is the size of the resection margin on the liver around the metastatic colon cancer tumor. and we used to say it had to be a centimeter of healthy liver tissue. we now know that's not necessary. we will take two or three millimeters of healthy liver tissue around the metastatic colon cancer tumor that we remove. if we can get the cancer out, even if that cancer is pushing into other anatomical structures, that helps patients a lot. so the whole philosophy of treating stage 4 metastatic colorectal cancer to the liver changed overnight about 15 years ago. and then we had some even more important developments.
in particular the egfr receptor antibodies, cetuximab (erbitux), panitumumab (vectibix). these targeted colon cancer medications have a very high response rate when added to conventional chemotherapy for colorectal cancer. and, the response rate of metastatic stage 4 colon cancer almost doubles. so double the number of patients who were previously not suitable for surgery to remove liver metastases now had resectable liver metastatic lesions. we call that "conversion" of irresectable to resectable colon cancer liver metastases. so we now think probably, for those patients with liver-limited stage 4 metastatic disease, probably up to 40% could be candidates for surgery to remove liver metastases from colon cancer. so, this has been the real change in the whole treatment of advanced colon cancer over the last 20 years. dr. anton titov, md: that is very dramatic results, clearly. and that is the primary role for the surgeon to surgically cure metastatic colon cancer disease at the metastatic level. dr. graeme poston, md (leading liver cancer surgeon, uk) - yes.
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