Resectable Colorectal Carcinoma

1
Resectable Colorectal Carcinoma

• Dr. Oliver Bathe
• Surgical Oncologist
• Tom Baker Cancer Centre
• Calgary AB

2
Learning Objectives

• As a result of reading the following case study,
  physicians will be able to
• Discuss some controversies in immediate
  management of metastatic colorectal carcinoma
• Review the treatment options for isolated liver
  metastases from colon cancer
• Discuss controversies about peri-operative
  chemotherapy

3
Mr. R.S.

• A 65 year old male underwent a screening
  colonoscopy which revealed a cecal cancer.
• A right hemicolectomy was performed, and 2 out of
  16 lymph nodes in the surgical specimen were
  found to be positive.
• The patient received 6 months of adjuvant
  chemotherapy with 5-FU and leucovorin, and
  tolerated this regimen without any difficulty.
• He was followed with serial serum CEAs as well as
  routine physical examination.

4
Mr. R.S.

• He was found two years after the completion of
  his chemotherapy to have an elevated CEA (ie
  10.2).
• His CT scan revealed a single mass in the lateral
  segment of the left lobe of the liver, measuring
  about 2 cm. MRI confirmed single lesion.
• No extrahepatic disease was identified.

5
Treatment

• Practice Point What are the treatment options
  available to this individual?
• treatment options for colorectal liver metastases
  include
• Best supportive care
• Palliative chemotherapy
• Resection
• Other ablative techniques (eg radiofrequency
  ablation).

6
Treatment

• Practice point What, if any, other
  investigations should be performed?
• The initial workup should be directed at fully
  evaluating the extent of the patients disease.
• A CT of the chest, abdomen and the pelvis should
  be performed.
• In some instances, an MRI of the liver might be
  considered, particularly if there are hepatic
  lesions that are equivocal.
• Colonoscopy should be performed if it has not
  been done in the last year.
• PET scan may be beneficial in ruling out other
  foci of disease (Zealley, 2001).

7
Mr. R.S.

• According to two recent large series, prognostic
  factors include
• Number of metastases
• Size of the metastases
• CEA level
• Margin status following resection
• Whether the metastases are synchronous or
  metachronous may also be important.
• Given that this patient has a single metachronous
  lesion, he has a relatively good prognosis with
  resection, with an estimated 5 year survival rate
  of 35 to 45 with resection alone.

Fong, 1999 Pawlik, 2005
8
Practice Point

• Practice Point What is the role of
  chemotherapy? Neo-adjuvant vs Adjuvant?
• The role of chemotherapy in this situation is
  unclear.
• One might argue that, because this patients
  prognosis is relatively good following resection,
  no chemotherapy would be required.
• On the other hand, one might also argue that
  metastasis to the liver signifies more extensive
  systemic disease. Therefore, systemic therapy is
  likely to be of benefit.
• Unfortunately there are few data to support
  either postulate. However, given the high
  likelihood of recurrence, serious consideration
  should be made to giving chemotherapy.

9
Neo-Adjuvant

• Potential advantages of neoadjuvant chemotherapy
  include the following
• The response to chemotherapy provides in vivo
  chemosensitivity data.
• The clinician is afforded the opportunity to
  observe the patient for any additional
  progression or appearance of extrahepatic
  disease, which portends a particularly bad
  prognosis (Allen, 2003 Adam, 2004). In such a
  situation, an unnecessary hepatectomy would be
  avoided.
• A response to chemotherapy might suggest a
  likelihood of benefit from additional
  chemotherapy following resection.
• Possible removal of less liver parenchyma

10
QUESTION Does preoperative chemotherapy reduce
the amount of liver that needs to be removed?
Dead cells on perimeter of tumor, live cells at
centre.
Model A Shrinking Ball
(Chemotherapy)
Residual live disease randomly localized
throughout area of former tumor
Model B Random Cell Death
11
Neo-Adjuvant

• There are also a number of potential drawbacks to
  neo-adjuvant chemotherapy that should be
  considered
• Toxicities related to the chemotherapy may delay
  surgery or may make resection impossible.
• Hepatic steatosis is a known effective
  chemotherapy and may increase the risk of
  postoperative liver failure (Kooby, 2003 Pocard,
  2001).
• Currently, there is very little evidence that
  neoadjuvant or adjuvant chemotherapy is better,
  but the arguments for using adjuvant chemotherapy
  alone are the converse of those discussed above.

12
Treatment

• A number of chemotherapy options have been
  described in the setting of resectable liver
  metastases, including oxaliplatin and
  irinotecan-based regimens, as well as hepatic
  artery infusion of FUDR (Allen, 2003 Lorenz
  2003 Wein, 2003 Kemeny, 1999).
• Given the paucity of data demonstrating clear
  benefit of chemotherapy in this setting, it is
  impossible to predict the superiority of any
  particular type of chemotherapy.

13
Practice Point

• Oxaliplatin vs Irinotecan?
• Does the choice of agent matter?
• Would you treat this gentleman with Irinotecan
  based therapy assuming him to be metastatic, or
  with Oxaliplatin assuming him to be neoadjuvant
  and possibly not benefiting from IFL containing
  regimes based on the CALGB, PETACC 3 and Accord
  trials?

14
Results

• After 3 months of chemotherapy using Irinotecan
  based therapy, he has a complete response to
  therapy
• He undergoes an uncomplicated resection

Pre-chemotherapy
Post chemotherapy
15
Practice Point

• In the setting of a good performance status
  patient, would you offer chemotherapy after
  resection?
• If he had NOT had chemotherapy before surgery,
  would it alter your decision?

16
Mr. R.S.

• He is currently in his 19th month of follow-up
  post 6 months of adjuvant therapy using
  Douillard (Irinotecan) with no signs of disease
  recurrence.
• Chemotherapy in this setting may cure the disease
  or at least, delay the onset of recurrence.
• Enrollment in clinical trials is needed to help
  answer this question.

17
References

• Adam R, Pascal G, Castaing D, et al. Tumor
  progression while on chemotherapy a
  contraindication to liver resection for multiple
  colorectal metastases? Ann Surg 2004 240
  1052-1064.
• Allen PJ, Kemeny N, Jarnagin W, DeMatteo R,
  Blumgart L, Fong Y. Importance of response to
  neoadjuvant chemotherapy in patients undergoing
  resection of synchronous colorectal liver
  metastases. J Gastrointest Surg 20037(1)109-15
  discussion 116-7.
• Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart
  LH. Clinical score for predicting recurrence
  after hepatic resection for metastatic colorectal
  cancer. Analysis of 1001 consecutive cases. Ann
  Surg 1999 230 309-321.
• Kemeny N, Huang Y, Cohen AM, Shi W, Conti JA,
  Brennan MF, Bertino JR, Turnbull AD, Sullivan D,
  Stockman J, et al Hepatic arterial infusion of
  chemotherapy after resection of hepatic
  metastases from colorectal cancer. N Engl J Med
  1999, 3412039-48.
• Kooby D, Fong Y, Suriawinata A, Gonen M, Allen P,
  Klimstra D, et al. Impact of steatosis on
  perioperative outcome following hepatic
  resection. J Gastrointest Surg 20037(8)1034-1044
  .
• Lorenz M, Staib-Sebler E, Gog C, Proschek D,
  Jauch KW, Ridwelski K, et al. Prospective pilot
  study of neoadjuvant chemotherapy with
  5-fluorouracil, folinic acid and oxaliplatin in
  resectable liver metastases of colorectal cancer.
  Analysis of 42 neoadjuvant chemotherapies.
  Zentralbl Chir 2003128(2)87-94.
• Pawlik TM, Scoggins CR, Zorzi D, et al. Effect of
  surgical margin status on survival and site of
  recurrence after hepatic resection for colorectal
  metastases. Ann Surg 2005 241 715-724.
• Pocard M, Vincent-Salomon A, Girodet J, Salmon
  RJ. Effects of preoperative chemotherapy on liver
  function tests after hepatectomy.
  Hepatogastroenterology 200148(41)1406-8.
• Twelves, C. et al. Capecitabine is Adjuvant
  Treatment for Stage III Colon Cancer. N Eng J
  Med 20053522696-2704.
• Wein A, Riedel C, Bruckl W, Merkel S, Ott R,
  Hanke B, et al. Neoadjuvant treatment with weekly
  high-dose 5-fluorouracil as 24-hour infusion,
  folinic acid and oxaliplatin in patients with
  primary resectable liver metastases of colorectal
  cancer. Oncology 200364131-138.