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Response to Chemo Before Liver Met Resection Doesn't Predict Survival

Patients who had tumors shrink in response to chemotherapy given before they had surgery for colorectal cancer that had spread to their livers had no better long-term survival than patients whose cancer remained the same or even got worse.

Doctors in New York followed 111 patients who had chemotherapy before surgery to remove liver metastases (neoadjuvant chemotherapy). After five years of follow-up, median overall survival was 62 months.  Overall survival was similar in three different groups:  those who had a complete or partial response to neoadjuvant chemotherapy, those whose tumors remained stable, and those whose cancer progressed during chemotherapy.

All patients the study had liver tumors that surgeons believed could be cured surgically.

Median overall survival after liver surgery:

  • For all patients:  62 months
  • Patients with complete or partial response to chemo: 58 months
  • Patients with stable disease after chemo: 65 months
  • Patients with progressive disease: 61 months

Factors that predicted better survival after surgery were:

  • CEA (carcinoembryonic antigen level) less than 5 ng/dL.
  • Metastatic lesions 5 centimeters or less.
  • Negative lymph nodes in the primary tumor in colon or rectum.
  • No cancer cells in margins of surgically removed tissue.

There was a trend for patients whose cancer progressed during pre-surgical chemotherapy to do better if they had chemotherapy infused directly into their livers after surgery (hepatic arterial infusion). Those who had HAI had 70 percent survival three years after surgery compared to 50 percent of those who didn’t.

David J. Gallagher and the team from Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University concluded,

Response to neoadjuvant chemotherapy did not correlate with overall survival even after controlling for margins, stage of primary tumor, and postoperative carcinoembryonic antigen level. Postoperative salvage treatment may have helped the survival of some patients.

SOURCE: Gallagher et al..Annals of Surgical Oncology, Volume 16, Number 7, July 2009.

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3 Comments

  1. j.d. said:

    This is a significant study and the result should encourage any patient who is facing the disappointment of not responding to neoadjuvant treatment.

    It is worth noting, however, that this study is already somewhat out of date because the chemotherapy being offered to stage 4 patients is now different and almost always includes a biological agent. As the authors conclude: “Because of the small numbers, we were unable to examine the effect of other factors on outcome, such as whether novel agents like bevacizumab and cetuximab improved response and survival.”

    It is quite possible that under the current regimens those who respond to neoadjuvant chemo will do better after hepatic resection than those who do not.

  2. Susan said:

    This study puzzles me, and I wish I had more information. If the patients were suitable candidates for surgery with curative intent at time of dx, why give them neo-adjuvant chemo? If they weren’t suitable candidates then, why were the ones who progressed deemed suitable later? I know I was accepted for surgery only because I got great results on neo-ad chemo. If I had progressed, surgery would have been ruled out. It is great that they did so well, but will any tumor board start advocating surgery for people who progress because of this study? As for the 4 indicators of success, do they mean low CEA after chemo and surgery or at time of dx? Ditto size of tumor, before or after? Fascinating Study! Susan

  3. Kate Murphy said:

    As I understand this study, all the patients included had surgically resectable tumors at the time of diagnosis.

    However, some doctors believe in a short (three months or less) course of pre-surgical chemotherapy to test the response to chemo or see if tumors progress.

    In my mind, this study casts some doubt on that theory since there was no difference in long-term survival whether or not tumors responded or even got worse.

    We do not have very good evidence about whether or not neo-adjuvant chemotherapy makes a difference in survival for patients who initially have resectable tumors.

    This is one piece of evidence, but more trials are needed, particularly a trial that randomly assigns patients to chemo or immediate surgery.

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