Research supports more aggressive treatment for colon cancer in older patients
BY KENDALL POWELL
The patient was an 86-year-old woman, and surgeon Mark Bloomston, MD, carefully considered whether to remove half her liver to treat her metastatic colon cancer. “She looked younger than 86, but I knew her liver was 86 and that older people can have unpredictable outcomes after major liver operations,” he recalls. He explained to her that there was a risk she might die as a result of surgery; she told him she wanted to “go down swinging.”
“She survived the operation, went home four days later and never looked back,” says Bloomston, a surgical oncologist and associate professor of surgery at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James). “I had weighed surgery as a viable option because of her age, but she did fine.”
Bloomston’s decision to aggressively treat his older patient is consistent with a nationwide trend among physicians treating colorectal cancer (CRC) patients. Most of these patients are 70 and older, have multiple health conditions, take numerous medications and have mobility limitations, all of which makes treating them trickier. But new techniques and technologies are enabling oncologists to offer older patients better options for fighting advanced colon cancer, and research is showing that healthy older patients reap as much benefit from aggressive treatments as younger patients.
“Colon cancer is a disease of aging,” explains Richard Goldberg, MD, medical oncologist and physician-in-chief at the OSUCCC – James. “Seventy-one is the average age of diagnosis in the U.S.” But it is one of the slowest growing, and screening has made CRC one of the most preventable of cancers (see "Colon Cancer – A Snapshot"), he says.
Forty percent of all CRC cases arise in people age 75 or older, and these patients have an average of five other medical conditions at the time of diagnosis. Common comorbidities include anemia, hypertension, other gastrointestinal (GI) problems, and heart, liver and kidney disease, complications that can affect tolerance to chemotherapy and a patient’s ability to withstand and recover from major surgery. Mobility limitations can affect treatment for patients who live alone or no longer drive.
“Managing older patients with colon cancer can be challenging,” says Goldberg, who specializes in treating older people with colorectal cancer.
Attitude Adjustments
Sometimes older patients with advanced disease will tell Goldberg: “Please don’t knock me to my knees just to give me a few extra months to live.” But others exemplify how attitudes are shifting among both patients and physicians about aggressive CRC treatments in the so-called elderly. Goldberg mentions a retired executive in his late 70s with advanced colon cancer that had metastasized to his liver and lungs. Shortness of breath brought him to the hospital.
“When I saw him in the clinic, he could barely speak,” Goldberg remembers. On first examination, the patient’s age and other indicators might have led Goldberg to advise the family to arrange hospice care. “But he had been fully functional just three month
before,” says Goldberg.
Instead, he sat down with the patient and family and suggested an aggressive treatment approach. It included a combination chemotherapy regimen, and it had a slightly higher rate of complications in older patients. But Goldberg and his colleagues had shown in a 2006 Journal of Clinical Oncology paper that the multi-drug approach benefited patients over 70 just as much as younger ones.
“He chose the aggressive therapy, and now he’s out riding his tractor mowing his lawn,” Goldberg reports. He notes that, except in cases where patients are critically ill with another ailment, older patients not only tolerate standard therapies well, but also do well on them. “We can tailor treatment to their other medical needs and their preferences.”
Research has shown that older stage IV colon-cancer patients treated with the chemotherapy agent 5-fluorouracil alone have a median survival of around 1 year. On the other hand, treating with combination therapy that includes two newer drugs, irinotecan and bevacizumab, the median survival time jumps to 28 months. “If older patients are fit and robust, we can treat them aggressively and more than double their life expectancy.”
The same seems true for aggressive and potentially curative surgery. Advances in laparoscopic and robotic surgeries are making it easier to treat patients formerly perceived as too frail to recover from major surgery.
“We are learning that older people aren’t frail based solely upon their age. A healthy 80-year-old can be as able as a healthy 50-year-old,” says Bloomston. Indeed, physicians who treat elderly CRC patients turn to performance-status measurements such as the Charlson co-morbidity index or Karnofsky performance scale to estimate frailness. Health status and performance-status – measures of daily activity and stamina – are more telling than a person’s biological age.
Tailoring Treatments
Currently, oncologists generally use six drugs to treat colorectal cancer: three chemotherapeutics (5-fluorouracil, or its oral form capecitibine; oxaliplatin; and irinotecan) and three targeted therapies (the VEGF inhibitor bevacizumab; and two EGFR inhibitors, cetuximab and panitumumab).
Goldberg mostly sees patients with advanced cancers commonly treated with combination chemotherapy. However, as drugs are combined in patients who may be on multiple agents already, the potential for side effects increases. Goldberg chooses to start with either a single drug and add more as the patient tolerates it, or to start a three-drug regimen with a reduced dose that can be escalated. “It’s not one size fits all,” he says; rather, chemotherapy should be tailored to the individual patient’s medical and lifestyle needs.
For example, bevacizumab can aggravate high blood pressure and necessitate upping a patient’s anti-hypertensive drug dosage. Oxaliplatin can cause sensory neuropathy, a numbness in the fingers and toes, which can increase the risk of an injury due to a fall for older patients. This is where the new specialty of geriatric oncology comes into play, using assessment tools like the Charlson Index to determine “who is robust and who might worry you,” says Goldberg.
These assessment tools help physicians determine whether a factor like “walks with a cane” is a true sign of frailty. Such assessments identify patients at high risk of serious chemotherapy side effects or those not able to withstand surgery.
Surgical Shifts
Bloomston notes that it’s the recovery, rather than the surgery, That concerns him when treating older patients. “Older patients can often handle an operation; what they don’t handle well are complications,” he says.
Developments such as post-operative pneumonia, infections or confusion, along with a higher risk of falling, can initiate a downward spiral for older patients. “By minimizing even small complications, we can potentially prevent the domino effect of complication upon complication,” Bloomston says. Along these lines, minimally invasive laparoscopic surgery techniques to remove colon tumors have been shown to be as effective as traditional surgery and also reduce complication rates, particularly in older patients. “Today, surgical oncologists and colorectal surgeons have so much experience with laparoscopy that any part of the colon could potentially be removed with minimally invasive techniques,” says Bloomston, although these techniques are more complicated the further downstream in the colon or rectum the tumor is located.
After such surgery, the smaller incisions mean less pain and a faster return to mobility with several potential benefits. Less pain means less need for narcotic pain relievers, and this in turn can lower the risk of respiratory complications. Reduced narcotic use also lowers the risk of confusion, which is often exacerbated in older patients and can lead them to pull out intravenous fluid lines, oxygen tubes and monitoring lines or to attempt to get out of bed prematurely.
For CRC patients who develop metastatic disease, surgery can prolong their lives. “And a handful we can actually cure with surgery – pretty extensive surgeries, that is,” Bloomston notes.
Fortunately, the liver – the organ most affected by metastatic CRC – has an exceptional ability to regenerate. In younger patients, up to 80 percent of the organ can be safely removed and will re-grow after removal, Bloomston explains. “But that’s not the case even in a very healthy 80-year-old. Aged livers do not regenerate as quickly or as robustly,” he says.
Surgical oncologists, however, have liver-sparing, minimally invasive options that enable them to treat even advanced cases of metastatic CRC in older patients.
For patients who may not tolerate surgery at all, a surgeon can use a technique called microwave ablation, in which a needle placed into a liver tumor carries an electrical current that literally cooks the tumor from the inside out. Heating the tissue to above 100 degrees Celsius kills the tumor cells and can work effectively for tumors three centimeters in diameter or smaller. A surgeon can also use a combined approach, removing some tumors and ablating others.
Another technique enables a surgeon to estimate the liver’s ability to regenerate prior to an extensive resection. “We can trick the liver into starting the regeneration process before we operate,” Bloomston says. The outpatient procedure involves closing off the liver’s right portal vein, which forces the liver’s blood supply to the left side. This releases a hormone signal that tells the liver to begin regenerating the left side.
“This litmus test can tell us if an older patient’s liver is capable of regeneration at all,” says Bloomston. If the answer is yes, the liver will have begun the process of regeneration before the major resection begins.
Certain comorbid conditions such as fatty liver disease, diabetes and cirrhosis can rule out major surgery. Liver metastases in these patients can be treated using stereotactic ablative radiation therapy, a non-invasive, nonsurgical procedure that delivers high-dose radiation to liver tumors. Terence Williams, MD, assistant professor of Radiation Oncology at the OSUCCC – James who specializes in treating GI and thoracic malignancies, notes that this method can achieve a local control rate of 70-90 percent for one to two years. “Especially for patients with liver-limited disease, this can afford better control of the growth of these tumors,” Williams says.
Williams notes that the older patients he treats, mainly for rectal cancer, are benefitting from advances in how radiation therapy is delivered. Intensity-modulated radiation therapy (IMRT) divides radiation up into “beamlets” that allow for more degrees of freedom in designing the radiation fields. A computer algorithm controlsthe intensities of the beamlets to deliver a well-controlled dose and to protect nearby structures such as the bladder, small bowel and hip joints. Chronic side effects in these areas, such as fracture of the hips, diarrhea, bowel obstruction and urinary frequency or incontinence, can be especially difficult to manage for elderly patients with limited mobility.
“For certain rectal cancer patients, IMRT allows us to carefully sculpt the radiation dose around sensitive structures that we want to avoid receiving high doses of radiation,” Williams explains.
The number of robust older CRC patients will only increase as the baby-boomer generation ages, Goldberg notes. “It’s important to have risk-benefit discussions with older patients and their families at every stage of CRC screening and treatment. It’s important to talk to each patient to establish what their goals are and to work within those goals. Then you adjust your approach so that patients get what they want out of treatment. The options available to older colorectal cancer patients today are much greater than they were in the past.”
Lynch Syndrome
Universal screening finds hereditary colon cancer in older patients
While the vast majority of colon cancers arise from spontaneous mutations, about 3 percent of cases result from inherited mutations in one of four genes for DNA-mismatch-repair protiens. Called Lynch Syndrome (LS), these inherited forms of colon cancer were thought until recently to show up at an earlier age.
But two studies led by OSUCCC – James researchers revealed several surprises, says genetic counselor Heather Hampel, associate director of the Division of Human Genetics at the OSUCCC – James.
Hampel and her colleagues tested more than 1,500 colorectal cancer patients for the inherited mutations, regardless of age or family history.
Although the average age for diagnosis of LS was thought to be around 45, the Ohio State-led team revealed it to be 54. “In addition, half the people diagnosed with LS in our study were age 50 or older,” notes Hampel. In other words, if hospitals screened only patients younger than 50, they would miss half of the cases with LS.
The finding has critical implications, Hampel says. Identifying LS patients early can save both their lives and the lives of relatives: An LS patient’s siblings and children have a 50-percent risk of carrying the same mutation. LS patients themselves are at high risk for multiple cancers – most commonly colorectal, uterine, ovarian and gastric cancers – and they are more likely to develop a second primary colon cancer after successful treatment of the first.
Since 2006 the OSUCCC – James has screened all CRC patients for LS. Hampel’s study showed that every patient with LS has three family members on average who are also affected. Relatives who learn they also carry a mutation can undergo earlier and more frequent cancer screenings.
“If you find people with LS before they get cancer, you have the potential to really save lives,” Hampel says. LS patients can prevent colon cancer by having colonoscopies earlier, starting at age 20 to 25 every one to two years for life. To prevent uterine and ovarian cancers, women with LS may choose to have a hysterectomy and oophorectomy once they are done having children.
Hampel’s team estimates that LS affects one of every 370 people in the United States, making it a bit more frequent than hereditary breast cancer. “There were some patients with colon cancer in their 80s that I never would have guessed in a million years had LS, but they did,” says Hampel, underscoring how universal screening finds surprising cases without a previous family history and saves lives.