Should staging of metastatic colorectal cancer be improved?

Does the current system of staging all patients with metastatic colon or rectal cancer in one group (stage IV) still make sense?  Is it time for  a new system that defines stages that reflect the potential for surgical cure?

In the June 20, 2006 issue of the Journal of Clinical Oncology Drs. Graeme Poston, Rene Adam, and Jean-Nicolas Vauthey consider that question in an article Downstaging or Downsizing:  Time for a New Staging System in Advanced Colorectal Cancer?

Ten years ago, very few patients with metastatic colon or rectal cancer survived five years.  Less than 1% of those whose cancer had spread but could not be removed surgically lived beyond five years.  However, for about 10% of patients surgery to remove cancer that had spread to their liver was possible, and for that 10%, a surgical cure was possible.  Thirty to forty percent of that small group survived.

Time has changed that situation considerably.  Better, safer surgery for metastatic tumors is now available.  More patients are considered eligible for surgery.  And improved chemotherapy can now reduce tumor size and make patients who were initially not eligible for surgical treatment resectable.

Resection is now possible for a much wider range of patients including some who have mets outside the liver if they can also be successfully surgically removed.  According to Poston and his colleagues a broader definition of liver resectability makes surgery much more feasible:

Now the definition of resectability with curative intent is the ability of the surgeon to clear, with negative margin, all measurable disease from the liver while leaving a healthy future remnant liver of 20% of the total liver volume. …. Liver resection is now considered selectively in some subsets of patients with limited resectable extrahepatic disease. Hilar lymph node metastases; lung, ovarian,and adrenal metastases; and local or regional recurrence are no longer formal contraindications.

New criteria for selecting patients makes at least 20% of patients with liver-only metastases eligible for surgery at the beginning of their cancer treatment.  Statistical evidence is finding that up to 50% of those patients are surviving 5 years or more.  Similar results are emerging for patients with lung-only mets.

New chemotherapy, not available ten years ago, also contributes to potential resectability of liver mets.  Depending on the study, survival after surgery after such chemotherapy ranges from 6% to 60%.

Given this new situation, the authors propose a new system of staging for metastatic colorectal cancer that takes into account the potential for surgical cure.  A better system would help patients and physicians decide on the best treatment strategies from the very beginning.  It would also allow better comparison of results of clinical studies.

The proposal system would divide the current stage IV colorectal cancer into two substages, each with three categories of their own:

• IV R — Resectable disease
• IVRa — resectable liver only
• IVRb — resectable extrahepatic only (spread outside of the liver only)
• IVRc — resectable both liver and extrahepatic

• IV U — Unresectable disease

• IVUa — unresectable liver only
• IVUb — unresectable extrahepatic only
• IVUc — unresectable liver and extrahepatic

The writers warn that experienced surgeons and multi-disciplinary teams be involved in staging to prevent  misdiagnosis that might limit the choice of patients for surgery that might lead to long-term remission of their cancer.

 The proposals outlined earlier should be subjected to expert surgical review and be tested robustly in real life because there could be fears that nonexpert surgeons and nonsurgeons might be tempted to stage such patients before referral to a specialist center.

Given the considerable progress made in both surgery and chemotherapy in the past ten years, a new staging system might well improve the chance that an individual patient would be directed to the best treatment strategy — one that might save his life.

Poston, Adam, and Vauthey conclude:

Advanced colorectal cancer is rapidly evolving from an acute terminal illness into a chronic and manageable condition. The increasing evidence of chemotherapy response that is sufficient to render previously nonresectable disease now resectable with curative intent opens up the possibility that achieving resectability could become a recognized end point for future clinical trials in medical oncology. Although this new classification proposal would need to be validated prospectively, we believe that there is sufficient evidence to support its adoption since prognosis (within stage IV) is now clearly different between these two groups in relation to resectability and also to sites (single and multiple) of metastatic disease.

Poston et. al. Journal of Clinical Oncology, Vol 24, No 18 (June 20), 2006: pp. 2702-2706

WHAT THIS MEANS FOR PATIENTS

While the proposed staging system has not yet been agreed to, newly diagnosed patients can ask their surgeons and oncologists to work together to decide whether or not mets are resectable or potentially resectable. A multidisciplinary team at a major cancer center is probably the best resource for making this critically important first decision.

If mets are not resectable, ask if it is possible that chemotherapy can reduce them and make surgery possible.  Again, involving a team of oncologists, surgeons, and radiologists is important.  Get a second — or third — opinion before deciding that resection is impossible.

Posted by Kate Murphy on July 11th, 2006
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Exercise reduces recurrence after treatment for stage III colon cancer

Patients with stage III colon cancer who walked at an average pace six days a week or had equivalent exercise had a 51% reduced risk of having their cancer return compared to those who were less active.

As part of a study comparing two chemotherapy regimens, patients were enrolled in an evaluation of their exercise levels after treatment. Researchers compared exercise using a standardized unit called a MET or metabolic equivalent task.  One MET equaled the energy expended during an hour of sitting quietly  Walking at an average pace for an hour equaled 3 METS, running expended 12 METS, while swimming, bicycling, and tennis each resulted in 7 METS per hour.

To be sure that illness from cancer or chemotherapy was not effecting exercise levels, patients were questioned about their exercise activities 6 months after finishing chemotherapy for their cancer and only those who were cancer-free were included in the study.

Patients whose exercise reached 18 METS in a week had an 85 percent chance of being alive and cancer-free three years after the study questionnaire, those with less than 18 METS had a 75 percent chance of similar survival.  18 METS was equivalent to walking a mile at an average pace 6 days a week.

Both men and women benefited from exercise as did people younger and older than 60.  There was no significant difference in benefits based on body mass index, number of lymph nodes, treatment received, or overall health at the beginning of treatment.  Furthermore, exercise benefits after cancer diagnosis and treatment were independent of exercise habits before cancer.  Additional exercise above the 18 METS improved disease-free survival even more, but after about 27 METS a week improvement reached a plateau.

Younger and leaner male patients tended to have the highest activity levels.  However, the average body mass index in all activity categories was in the overweight range.  Those with the highest level of activity gained less weight during the time after treatment, but at least 75 percent of patients in each category gained weight.

The research team emphasized that their data does not include the impact of exercise during or immediately after treatment.  Patients in the study were assessed 14 months after initial diagnosis of colon cancer including time for surgery, surgical recovery, six months of chemotherapy, and six months after chemotherapy ended.  None of the patients whose cancer recurred during that time period were included in the study.

The study, appearing online ahead of print, will be published in the August 1, 2006 Journal of Clinical Oncology.

Jeffrey A. Meyerhardt and his colleagues from the Cancer and Leukemia Group B concluded:

Beyond surgical resection and postoperative adjuvant chemotherapy for stage III colon cancer, for patients who survive and are recurrence free approximately 6 months after adjuvant chemotherapy, physical activity appears to reduce the risk of cancer recurrence and mortality.

In an accompanying editorial Wendy Demark-Wahnefried from the School of Nursing at Duke University says, “It’s time to get moving!” She reviews the evidence from the two colon cancer studies in the Journal of Clinical Oncology and similar protective effects of exercise for breast cancer survivors and suggests studies of interventions to help survivors increase exercise after treatment.

An article about the study appears in EurekaAlert.

colon cancer recurrence exercise and cancer

Posted by Kate Murphy on July 7th, 2006
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Abdominal fat increases colon cancer risk in both men and women

A large European study of nearly 370,000 people has found an increased risk of colon cancer in both men and women who had large deposits of fat around their waistline. 

Researchers measured body weight, body mass index (BMI), and the ratio of waist to hip circumference (WHR).  To make comparisons, they divided individuals in the study into five groups — quintiles — from the highest numbers to the lowest.  All groups were followed for 6 years.

• Men in the highest quintile of body mass index were about one and a half times as likely to get cancer during the 6 year followup period compared to men in the lowest quintile.  There was no similar increased risk for women.
• Both men and women had an increased risk for colon cancer if they had a large waist — an additional risk of about 40% for men and 50% for women between the highest and lowest quintiles.
• Men and women also had about a 50% increased risk of colon cancer when there was a large difference between waist and hip measurements (WHR) and their waists were larger than their hips.
• Waist hip ratio didn’t appear to affect colon cancer risk for a group of post-menopausal women who also took hormone replacement therapy.
• There was no connection between obesity, abdominal fat, or waist-hip ratio for rectal cancer in this study.

Tobias Pischon MD, MPH and his colleagues reported their findings in the July 5, 2005 issue of the Journal of the National Cancer Institute.  They concluded:

Waist circumference and WHR, indicators of abdominal obesity,were strongly associated with colon cancer risk in men and women in this population. The association of abdominal obesity with colon cancer risk may vary depending on HRT use in post menopausal women; however, these findings require confirmation in future studies.

Pischon et. al. Journal of the National Cancer Institute, Vol. 98, No. 13, 920-931

An article about the study appears on Reuters Health.

Posted by Kate Murphy on July 6th, 2006
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NSAIDS don’t reduce colon cancer risk in smokers

While non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin and ibuprofen reduce risk for colon and rectal cancer, long-term smokers may not enjoy the benefit.  One group of smokers may have no benefit at all.

Researchers at the Fred Hutchinson Cancer Center in Seattle studied 3,300 area adults, half of whom had colon cancer.  They found that people who had smoked for more than 20 years and had never used NSAIDS had the highest risk for colon cancer.  But smokers who did use NSAIDS regularly had an increased risk for colon cancer that was about 1/3 higher than non-smokers.

In particular, the research team looked at colorectal cancers with microsatellite instability(MSI).  Microsatellites instability results from changes in short sequences in DNA which aren’t corrected.  Increased numbers of microsatellites can result in some types of colon cancer, often when genes that repair damage are faulty (mismatch repair genes)  About 15% to 20% of colon cancers have high levels of microsatellite instability.

Smokers whose cancers were high in microsatellite instability got no benefit at all from NSAID use.  Risk for colorectal cancer was as high in NSAID-using smokers as it was in smokers who did not use NSAIDS regularly.

Virginia Chia, who headed the study, believes that it is possible that long-term smoking provides such frequent and consistent assaults on cell DNA that it cannot be reliably repaired, particularly in people who already lack the mismatch repair gene.  She wrote,

"This accumulated damage might not be reversible. NSAIDs act to suppress inflammatory processes and may help limit the progression toward cancer. However, people who have microsatellite-unstable tumors may be even more susceptible to the effects of smoking because they already have a reduced capacity to repair DNA, even in the presence of strong anti-inflammatory agents.”

Results of the study appear in the July 1, 2006 issue of Cancer Research.

An article about the study appears on EurekaAlert.

smoking and colorectal cancer microsatellite instability non-steroidal anti-inflammatory drugs

Posted by Kate Murphy on July 2nd, 2006
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The Senate and DeWine: One Constituent’s Impact

The evening of June 6 Senate and House conferees met to discuss the Fiscal Year (FY) 2006 Supplemental Appropriations bill. There was an attempt to add to the bill a "deeming" resolution establishing the appropriations allocation for FY 2007, Senators on the conference committee introduced an amendment to this resolution which would add the $7.1 billion for health and education programs that were part of the Specter-Harkin Amendment.

In order for it to pass the amendment needed the support of two Republican Senators. One Voice Against Cancer (OVAC) assumed Senator Arlen Specter (R-PA) would support the effort and felt Senator Mike DeWine’s (R-OH) vote was a key to the amendment’s passage but was unsure of his support.

I contacted Rebecca Dague, colon cancer survivor and C3: Colorectal Cancer Coalition advocate who lives in Ohio, to ask she call Senator DeWine to urge him to support the amendment. She called his office that night to leave a message and followed up with another call the next morning.

The next day (June 7) I recieved a message from OVAC which said the Senators on the conference committee approved the amendment and that Senators Specter and DeWine were the two Republicans who supported it. Unfortunately, House members of the confernce committee did not accept its adoption into the bill.

A short while after this Nancy Roach, C3 President, attended an OVAC meeting which discussed the vote on the amendment. She said the OVAC people were "very, very surprised" that Senator DeWine voted for the amendment. At the time of the meeting Nancy did not konw of Rebecca’s contact with Senator DeWine.

Nancy’s email went on to say:

"Your personal connection makes a big impact when it comes to specific asks. Elected officials want to be re-elected, so they want to please voters — and that means YOU."

I do not claim that Rebecca’s calls to Senator DeWine were THE reason he voted for the amendment but it could very well have been the nudge needed to get his support. Most of us do not have Sneators and Representatives in position’s as key to the passage of cancer legislation but that does not matter. What does matter is that you remember you do not know what will push elected officials to decide one way or the other so it is vital for youi to start, build and maintain a relationship with them and their staffs.

The Hill is feeling the impact of the cancer community in general and C3 in particular. Members of Congress must realize that in addition to their support we want adequate funding of cancer programs. The FY 2007 Labor/HHS appropriations process is not over thus you still have opportunity to influenc the final bill Congress sends to the President. 

Posted by Dusty Weaver on June 28th, 2006
Posted in: Policy & Advocacy News | No Comments »