ON THE VERGE OF UNDERSTANDING: That’s what the cover of this issue of CURE declares, and that’s exactly where science is when it comes to figuring out colorectal cancer today.

With notable recent advances accumulating, researchers are now on the brink of discovery when it comes to understanding the inner workings of this disease, and thus treating it with more precision—vitally important for a cancer that often hides silently until it becomes advanced and aggressive.

If you are reading this issue of CURE, it’s likely you have had personal experience with colorectal cancer. We’ve put this special issue together expressly for you, because we’re committed to keeping you up to date on medical advancements in the disease. In our article about treatment, we look carefully at the value and side effects of the various targeted therapies approved, in recent years, for use in combination with chemotherapy. And we look ahead at drugs in the pipeline, with a word of advice from an oncologist to patients: Help move research forward by enrolling in clinical trials.

Also in these pages, we fill you in on the latest developments in colorectal cancer prevention, diagnosis, survivorship and caregiving.

As we finished our work on this issue, national Colorectal Cancer Awareness Month was coming to a close. Rightfully, awareness activities in March focused on a very important issue — screening for the disease. Although, as you will read, colonoscopy screening is not a guaranteed preventive measure for every case of colorectal cancer, it is remarkably successful overall. In this issue of CURE, we grapple with the questions that remain about this practice: how to reach more of those eligible for screening, whether colonoscopy could be replaced with less invasive tests, and whether younger adults should be routinely screened.

We also explore several hereditary syndromes that raise the risk of colorectal cancer, looking at the often life-changing physical and emotional aftereffects of a diagnosis.

For survivors, we look not only at the difficulties of living with changes such as ostomies or preventive hysterectomies, but also at the hope inherent in evidence that a non-Western diet and regular exercise can improve outcomes and quality of life. And we highlight some important aspects of how to be a successful caregiver to a patient with colorectal cancer, as well as advising spouses in patient-caregiver roles on how to retain their intimate relationships.

Included in the mix is the perspective of one survivor of colorectal cancer, an entertainer who is grateful both to take the stage and to simply drive himself to the grocery store, and who is working hard to give something back to others undertaking similar journeys.

We hope that this special issue of CURE will enhance your own understanding of colorectal cancer, preparing you to ask good questions and make sound decisions as you navigate your experience with this disease.

Articles

From the Chairman

ON THE VERGE OF UNDERSTANDING: That's what the cover of this issue of CURE declares, and that's exactly where science is when it comes to figuring out colorectal cancer today.

Coming to an Understanding

Robin Dubin didn’t easily think of herself as her husband’s caregiver, despite having been first thrust into that role when Dave Dubin was diagnosed with stage 3b colon cancer. The year was 1997. The Dubins, both 29, had a 15-month-old baby boy, Zachary, and had recently moved into their first house.

	“We went through the standard reaction of, ‘Why me?’” Dave recalls.

	One answer: Statistically, colorectal cancer— cancer that develops in the colon or rectum&mdash;is the third most common cancer in the United States, according to the U.S. Centers for Disease Control and Prevention.

	For Dave, treatment initially consisted of a difficult surgery to remove part of his colon and six months of chemotherapy.

Robin Dubin is a caregiver to her husband, Dave, who has colon cancer. Photo by Ed Mulholland.

	“I never felt I was taking care of a patient, because he was self-sufficient. Even throughout chemo, it’s not like he spent days in bed,” Robin says. “It took its toll, but he was still working and very active.”

	Likewise, after his cancer reappeared following a 10-year hiatus, Robin credits her husband with helping to make her caregiver role manageable. Sure, she goes with him to many of his medical appointments and has helped him adjust to a drastically altered dietary lifestyle of small but frequent meals because the majority of his colon has been removed.

	But her most important role, as she sees it, is to be knowledgeable about treatment and screening options and to stay deeply engaged with his medical team.

	“As a caregiver, I feel a big part of my job is really making sure we are asking all the right questions and understanding all that’s happening and all the details,” she says. “There’s so much information that it’s overwhelming, so it’s really my job to make sure we’re doing everything that we can.”

	Each relationship between patients and their primary family caregivers is unique.

	But common challenges that could arise for the caregiver include increased financial pressures, time demands, stress related to battles with insurance companies and anxiety over the results of the next test or procedure.

	For some couples, as with the Dubins, fears of passing on an increased risk of cancer to their children may be a major source of guilt and stress.

	In cases where patients have undergone an ostomy procedure, which creates a surgical opening in the abdomen for the elimination of waste, the caregiver may have to deal with body-image worries the patient might have.

	Whatever the challenges, experts say it’s essential that family caregivers be mindful of their own well-being, even if that takes some effort.

	“Putting up a mirror and shining a light on yourself, which is not the easiest thing to do, may be important for a caregiver to do,” says Karen Y. Mechanic, director of psychiatry at Temple Health Fox Chase Cancer Center, in Philadelphia.

	To help deal with some of the stress caregivers face, Mechanic suggests talking with mental health professionals, support groups, family and friends.

	And she urges making the time to step out of the caregiver role, even for a short period, on a regular basis.

	“It actually makes you a model for good caregiving for the patient,” Mechanic says. “If the patient sees you as a person who takes care of yourself, it’s possible that they become better at taking care of themselves.”

	The Dubins say they have done as much as they felt necessary to take care of themselves and each other through Dave’s cancer experience.

	Robin says the cornerstone of that care has been open communication between the two of them.

	“We’ve been together since we were 19. We really are very close, very open. We share with each other emotionally,” Robin says. “In that respect, I think we help each other out to get through all this.”

	Sue Kidera, of New York, who has late-stage colon cancer and is cared for by her husband, Tom Kidera, agrees that the most important roles any family caregiver can play are as sounding boards and sources of comfort.

	“When I need support, I look to him to care for me. When I come back from the hospital, he cooks for me, he’s there for me to talk to me,” she says. “The most important thing is to be able to have someone to talk to.”

	Open communication should be a pillar in any patientcaregiver relationship, says Meredith Cammarata, a licensed clinical social worker at Memorial Sloan Kettering Cancer Center in Manhattan.

	“The best thing patients and caregivers can do for each other is to have open conversations and to remind each other that there’s life outside of cancer, and to take time to do enjoyable activities together,” Cammarata says.

	Even so, caregivers may be more stressed than they realize by the burden of seeing a loved one stricken with cancer.

	Depression and anxiety are common not only among cancer patients, but their family caregivers as well—sometimes even more so, Cammarata says.

	Tom, 60, knows firsthand the mental-health toll a colon cancer diagnosis can take not only on the patient, but on the caregiver, too.

	The late-stage colon cancer with which his wife was diagnosed in 2005 has since metastasized. Now 58, Sue has undergone dozens of surgeries, chemotherapy regimens and radiation treatments.

	Four or five years ago, Tom fell into a major depression without initially realizing it. Some signs were evident, he says in retrospect: he stopped caring about his work, and he drank more.

	“I just really lost myself. I believed I’d been handling (Sue’s cancer) OK through the first diagnosis,” he says. “But I became really depressed and I didn’t know it.”

	His depression, as well as anxiety, arose in part from feelings of not being adequate as a caregiver for his wife, he says.

	After turning to a psychiatrist for help, that low point is behind him with the aid of meditation and anti-anxiety and anti-depressant medications, Tom says.

	“As a spouse of someone who’s living with cancer, mental health is something you really have to be conscious of,” says Tom, a retired attorney who runs a real estate firm with his wife from their hometown of Pittsford, N.Y., just outside Rochester. He encourages others to make use of the palliative or supportive care teams at their cancer centers early in treatment because they are good conduits to connecting people with mental health professionals.

Tom Kidera experienced depression while caring for his wife, who has colon cancer. Photo by Kate Melton. 

	In the Dubins’ cancer struggle, there is some irony in the fact that a family history of colon cancer helped Dave and Robin react to their situation more positively than they otherwise might have, Dave says.

	His grandfather, who eventually wound up needing an ostomy because of his cancer, survived well into his 80s and passed away mostly from the ravages of Alzheimer’s disease, not cancer, he says. Dave’s father, who has been clear of cancer for an extended period of time, is now 83.

	Dave, too, was rid of his cancer for about 10 years.

	In that time, he and his wife, who live in northern New Jersey, went about their lives even as Dave continued to get regular screenings to make sure the cancer had not re-emerged.

	They had two more children, Corey and Maxwell. The boys’ father stayed active in soccer, a game he is passionate about, and the couple tended to the family’s medical supply business.

	Then cancer resurfaced in his colon in 2007 and new testing determined it was the result of Lynch syndrome, an inherited genetic disorder that increases the risk of many types of cancer—most commonly colorectal cancer. While Lynch syndrome doesn’t pass cancer itself from parent to child, it does pass on the risk, and so it is recommended that all direct blood relatives have genetic counseling. The U.S. National Institutes of Health estimate that Lynch syndrome accounts for 3 to 5 percent of colorectal cancer cases.

	The Dubins have since learned that their oldest, who is 19, has the Lynch syndrome mutation, although he shows no evidence of cancer.

	The Dubins had to contend with that knowledge even as Dave underwent a second colectomy that left him with about 18 inches of colon out of the normal 5 feet, and, two years later, surgery to remove part of his right kidney because a carcinoma had developed there, as well.

	They have been told it’s best to wait to screen their two younger boys until they are 18 or 19 because, even if the Lynch mutation is present, cancer likely would not develop before then.

	Robin has to balance her own feelings of guilt and distress about the future against her husband’s similar worries.

	“It’s hard not to feel guilty about passing this on to your children, but it’s also something that you have absolutely no control over,” she says.

	Cammarata suggests that caregivers talk to the mental health professionals at their cancer centers, seek out caregiver support groups those centers might provide, or turn to independent groups like the Caregiver Action Network (caregiver.org) or similar resources available through the American Cancer Society and other organizations.

	There are also colorectal cancer-specific foundations and groups that can be resources for caregivers. These include the Colon Cancer Coalition (coloncancercoalition.org), the Colon Cancer Alliance (ccalliance.org) and a colon cancer foundation that the Dubins themselves started (aliveandkickn.org).

	The Dubins started the organization because they wanted to contribute in their own way toward raising awareness about colon cancer, Robin says.

	The organization, which focuses on younger colorectal cancer survivors and the role of genetics in some forms of the disease, also ties colon cancer awareness in with soccer. That’s partly because Dave loves the sport and partly because, through a sport as international as soccer, the Dubins believe they are able to reach a broader audience.

Caregivers' Corner

Caring for a loved one means being there through treatment, side effects and worry&mdash;but also finding time for yourself.

Care Package

As Rachel Lefebvre approached a certain age, she began to take heed of the advice of a few older friends. Forty, they warned—in that half-joking way&mdash;was a tipping point after which everything went downhill. She vowed to enter the decade in fighting form, and began eating better and exercising regularly. For a while she felt great, but as she crossed the threshold of her milestone year, exhaustion set in.

	Soon she wound up at her doctor, wondering aloud about vitamin deficiency. Instead, some funky liver enzyme readings led to a precautionary ultrasound, which escalated to an MRI, which resulted finally in a biopsy and a diagnosis of metastatic colon cancer.

	There is no whiplash like discovering stage 4 cancer at 40. “It was so surreal,” she says 18 months later, recovering from an advanced radiation treatment called Y-90 (intra-arterial yttrium-90 radioembolization) that’s gaining favor in the treatment of metastatic disease to the liver. Doctors placed radioactive beads not much larger than red blood cells into tumors in her liver. Now she’s contemplating her next medical steps.

	She fired her first doctor, who told her she spent too much time on Google. “Wouldn’t you?” she countered. “You gave me two years and I have two kids. There is no way I’m not doing everything and anything I can to outlive this.”

	Empowered by the engaged stage 4 patients she found in the online forums at Colon Town (chris4life.org/colontown), she found a doctor three hours away at an academic medical center in Central Florida. Now she has options.

	Colorectal cancer is an interesting example of both how far cancer treatments have advanced, and how far they still need to go. Patients with stage 4 colorectal cancer used to survive an average of just nine months; that number now hovers around 30 months.

	But while incremental advances in treatment have nearly tripled survival time for those with advanced disease over the last two decades, colorectal cancer is still waiting for its miracle. Drugs like Herceptin (trastuzumab) for breast cancer have turned certain subtypes of cancer from lifethreatening diseases into conditions that can be managed for years.

	“We are jealous of some of the other cancers,” says oncologist John Marshall, director of the Otto J. Ruesch Center for the Cure of Gastrointestinal Cancer at Georgetown University.

	Researchers have been refining their treatments, and that’s been a key to the improving outcomes. But: “That’s different than finding what makes the cancer tick,” he says. “Right now, we are measuring one street corner and saying that we understand the traffic. We are measuring one gene when we know that there are multiple genes involved. We need to understand more.”

	But intriguing biological clues point to complexities we’re on the verge of understanding. For example, preliminary indications are that, after diagnosis, eating a non-Western diet and exercising both increase a patient’s chance of survival. More curiously, whether the cancer appears on the left or right side of someone’s body is a clue to its origin.

	Colon cancers on the right side tend to be hereditary, while those on the left side tend to be sporadic. Scientists hypothesize that it may be about how intestinal bacteria help break down food, changing its chemistry as the waste passes toward the toilet.

	Patients with colon cancer versus rectal cancer have very different experiences when the disease is caught early. Slicing out a piece of the colon and stitching it back together can be a relatively simple surgical procedure. But as you get closer to muscles of the rectum, surgery has a more radical impact. Strategic radiation to shrink tumors before surgery becomes an important tool as doctors try to preserve bodily functions.

	Despite these differences between subtypes, doctors tend to talk about colorectal cancer as one entity because, once the disease has spread and become metastatic, there does not appear to be any difference. The treatments are the same.

	Stage 1 colorectal cancer comes with the potential for an easy surgical cure. The catch: the disease tends to remain asymptomatic, and thus hidden, until later stages. The disease can be uncovered via screening tests, but people under 50 years of age are not routinely screened, and those aged 50 and older, for whom screening is recommended, don’t always comply.

	Louis Diaz, associate professor of oncology at Johns Hopkins Medical School, thinks of colorectal cancer in three groups defined by their surgical possibilities. Stage 1, 2 and 3 colorectal cancer can be operated on immediately, and can be cured. About 5 percent of stage 4 colon cancers are also immediately operable—for example, those with a single metastatic growth that can be removed along with the colon resection.

	Some stage 4 disease is borderline—two to four months of chemotherapy or radiation are used to shrink tumors. Because metastatic disease can be hidden, doctors need to know if they are looking at the whole iceberg or just the tip. If treatment indicates that the cancer is relatively contained, surgery can proceed with curative intent. “When you go in surgically, you don’t want to have to go back in,” says Diaz. “Get it all.”

	For a stage 1 diagnosis, surgery is the only treatment. For stage 3, it’s been proved that post-operative chemotherapy composed of fluorouracil (5-FU) and Eloxatin (oxaliplatin) for six months significantly improves a patient’s chance of being disease-free in five years, and significantly improves survival from cancer.

	Stage 2 is the sticking point. Current guidelines say that post-operative chemotherapy does not have an appreciable impact on the treatment outcome. Yet, says Diaz, about half of practitioners will treat patients who are higher-risk with some kind of chemotherapy. Measuring the levels of expression of multiple genes, or “gene profiling,” using tests such as Oncotype DX or MDA114, is emerging as better way to determine prognosis and decide who needs chemotherapy.

	“What we’ve got to work on is to not treat all cancers the same, but figure out their different subtypes,” explains Georgetown’s Marshall. “We’re beginning to do that now with colorectal cancer.”

For example, about 5 percent of colorectal cancer patients have one or more inherited genetic mutation in any of five specific genes, a condition called Lynch syndrome, formerly known as hereditary nonpolyposis colorectal cancer (HNPCC). Another 15 percent have similar mutations, but didn’t inherit them. The involvement of these five genes suggests a high rate of microsatellite instability (MSI), a condition that leads DNA to malfunction as it undergoes natural repair processes in the cell.

MSI-high tumors behave differently, Marshall says, whether the mutations were inherited or developed during someone’s life. New treatment guidelines support MSI testing for all patients with colorectal cancer. “Giving chemotherapy to stage 2 patients is controversial,” he says, and a high MSI score suggests that chemotherapy would in fact be harmful. “I don’t treat stage 2 patients without knowing their MSI.”

When Jennifer Walls was 55, she had her first colonoscopy—she now wishes she’d done it sooner&mdash; and was diagnosed with stage 1 colon cancer. Doctors took a foot from her colon and prescribed lab work every six months so they could follow the levels of CEA (carcinoembryonic antigen) in her blood. CEA exists while a fetus is developing, but is typically absent in the blood of a healthy adult. It reappears in some colon cancer, allowing doctors to track cancerous activity. Walls’ CEA levels were high before surgery, so they hoped to monitor the possibility of the cancer returning via CEA.

It didn’t work. After a medically complicated couple of years, Walls developed a cough that wouldn’t go away, and pain around her liver. Ultrasound picked up a spot, then a subsequent MRI cleared the liver but caught a worrisome lesion on the lung. Finally, a CT scan in spring of 2012 revealed the cancer was back in both lungs.

For patients like Walls and Lefebvre with metastatic disease, chemotherapy treatments may vary but generally follow a well-laid path. The backbone cocktail of drugs begins with 5-FU, which has been in use since 1958. Folinic acid (leucovorin), approved in 1991, helps activate the 5-FU. Combinations using Camptosar (irinotecan), Eloxatin and Xeloda (capecitabine) began to emerge in the early 2000s, and have evolved into regimens known as FOLFOX and FOLFIRI, both given intravenously. FOLFOX is 5-FU and folinic acid with Eloxatin, while FOLFIRI replaces Eloxatin with Camptosar.

Patients typically begin with FOLFOX, though this combination can cause neuropathy in the hands and feet— weakness, numbness and pain from nerve damage. Patients who are particularly dependent on their hands, such as musicians, might want to start with FOLFIRI, which is equivalent but less likely to cause neuropathy. Still, after starting one of these regimens, patients will need to switch to the other if their disease continues to progress.

	Treatment currently lasts for six months, but trials are underway to test if three months of FOLFOX will achieve the same result, with fewer side effects. In addition to neuropathy, FOLFOX side effects can include mouth sores, diarrhea and hand-foot syndrome; FOLFIRI can cause hair loss, blood disorders, gastric upset and fatigue.

	Avastin (bevacizumab), an intravenous drug designed to hamper cancer’s ability to create its own blood supply, is often part of this early mix, as well, since this has been shown to delay progression compared to chemotherapy alone. Or, instead of Avastin, first-line FOLFOX or FOLFIRI could be paired with a targeted compound like Erbitux (cetuximab, approved in 2012) or Vectibix (panitumumab, approved in 2006). A patient might start treatment with FOLFIRI plus Avastin, for instance, and then, if the regimen becomes less effective, switch to FOLFOX with Erbitux or Vectibix.

	In a phase 3 trial, Erbitux with chemotherapy—as compared with chemotherapy alone&mdash;improved survival by four months and progression-free survival by a month and a half in patients who didn’t have mutations in genes called KRAS or NRAS.

	Vectibix, originally approved for use alone as a later-line drug due its tumor-shrinking ability, was given a second FDA approval last year as a firstline drug to be used in combination with FOLFOX. In the study that led to that approval, its benefits closely matched those offered by Erbitux in patients without KRAS mutations.

	Both of these drugs interfere with the cellular signaling needed to sustain some cancers by targeting a protein on the outsides of cancer cells: the epidermal growth factor receptor, or EGFR. But because they have no benefit for patients with KRAS or NRAS mutations, they are unable to help more than half of those with colorectal cancer.

	Another option in this setting is Zaltrap (ziv-aflibercept, approved in 2012)—similar to Avastin in that it prevents blood vessel growth to tumors&mdash;which is used in combination with FOLFIRI. In a study, the drug added about a month and a half to overall survival compared with the use of FOLFIRI alone.

	Unlike the targeted-drug skin rash that can appear with Erbitux and Vectibix, the most common side effects with infused Zaltrap and Avastin include fatigue, hypertension, bleeding, headaches, a drop in the number of white blood cells, sores in the mouth, diarrhea and loss of appetite.

	If those regimens become less effective, a potential option— depending on the sequence of treatments&mdash;is Stivarga (regorafenib, approved in 2012), a pill that ratchets down a cancer’s ability to create its own blood supply by blocking several enzymes. The drug offers about six additional weeks of survival on average, and two months free of additional disease progression, when compared to best supportive care alone.

	While several of these newer targeted drugs offer modest boosts in survival, they come with steep price tags when compared with chemotherapy (5-FU costs about $30 per treatment). A study that closely followed the advent of FOLFOX estimated its monthly price at nearly $6,000.

	Erbitux costs between $8,400 and $10,600 a month. Avastin, which must be taken for many months in order to generate a benefit, costs about $5,000 a month, while patients or their health insurers are charged $11,000 per month for the similarly effective but later-line Zaltrap.

	The prices of targeted cancer therapies can mean different things to different patients, depending on whether they are insured and what level of coverage their plans provide. As one example, Medicare patients foot the bill for about 20 percent, or $2,000 per month, of the cost of Zaltrap.

	Still more novel agents are on the horizon. Cyramza (ramucirumab), which also controls blood-vessel growth to tumors, improved survival in patients with metastatic colorectal cancer when combined with FOLFIRI in a recent study.

	“We know that when patients with advanced colorectal cancer have progression of their disease on first-line chemotherapy plus (Avastin), we can either continue the (Avastin) with second-line chemotherapy or use a different angiogenesis inhibitor, Zaltrap, with chemotherapy. And now we know that (Cyramza) can be given with chemotherapy in this setting, as well,” oncologist Smitha S. Krishnamurthi told the media days before the findings were presented at the 2015 Gastrointestinal Cancers Symposium in January. “All of these approaches have had a similar increase in survival.”

	Since colorectal cancer shares a family of mutations with melanoma, the successful MEK and BRAF inhibitors developed for that condition are now being tested in metastatic colorectal cancer. Immunotherapy agents that have also proved successful in melanoma, PD-1 and PD-L1 inhibitors, are also being tested for their potential in some colorectal cancers.

	And TAS-102, a close relative of 5-FU, recently completed clinical trials and is expected to gain approval by mid-December.

	The drug was tested in the phase 3 RECOURSE study, which compared TAS-102 to placebo in patients with colorectal cancer who had taken at least two prior kinds of therapy. For patients treated with TAS- 102, median overall survival was 7.1 months compared with 5.3 months for those who took placebo; those findings included results for those with KRAS-mutated tumors, in whom the drug was less effective. Patients taking TAS-102 also saw a slight improvement in progression-free survival compared with placebo (2 months versus 1.7 months). Moderate to severe side effects consisted mainly of blood disorders, including decreases in platelets, white blood cells, red blood cells or neutrophils.

	It is not yet clear where TAS-102 will fit into the treatment sequence among the other drugs already available for metastatic colorectal cancer.

	Meanwhile, there are other investigational drugs being tested, too. As of late February, more than 100 clinical trials were open and testing a wide variety of therapies.

“Twenty years ago we had 5-FU. That was it,” says Randall F. Holcombe, chief medical officer for cancer in the Mt. Sinai Health System. “We didn’t understand that we could treat patients after surgery to prevent relapse. And we now know that it works best to give a combination of 5-FU/ oxaliplatin.”

	The proliferation of chemotherapy, targeted therapy and more advanced surgical and radiation techniques gives more choices to patients and doctors. “Because we can use many of these therapies sequentially, we can provide very significant benefit for our patients and really prolong their life expectancy even with metastatic disease,” Holcombe says.

	Take Jennifer Walls, for example. After she finished her FOLFOX regimen, the tumor was reduced enough that doctors could operate robotically, removing the diseased portion of the lung. That paved the way for participation in several clinical trials. She tried the experimental drug dovitinib, which is thought to inhibit a number of cellular pathways involved in colorectal cancer, but she became violently ill, she says, and had to quit the trial: “I had severe nausea. It felt like my head was exploding.”

	In May of last year she tried a different trial, this time of Medi-565, a vaccine that targets CEA. The side effects were minimal this time, but by September her tumor had regrown by over 20 percent. That was disappointing, except that now it was large enough to be treated with Cyberknife, a precision radiation treatment. That treatment, as do radiofrequency ablation and Y-90, allows radiologists to safely deliver radiation to liver metastases where chemotherapy has failed and surgery is impossible.

	Due to the array of medical and radiation options now available in late-stage metastatic disease, “It’s no longer a disease where we have set pathways,” says Diaz. “We now have tools to intervene in a non-toxic, non-surgical way that is apparently extending life.”

	Still, there is lots of work to be done. “The standard is better than it was, but it’s not good,” says Marshall. Improvement, as always, will come via clinical trials. “I don’t want to make patients feel guilty for not going on a clinical trial, but if there is one open to them, I would strongly encourage them. We’ve got to keep trying. We need our patients as partners.”

	As an example, he’s nervously watching some research on patients diagnosed with stage 4 rectal cancer who are electing not to have surgery. It’s a risky decision, but these patients have decided they do not want to lose rectal function. They know that in about 20 to 30 percent of patients who have chemotherapy or radiation, and then undergo surgery, the surgeon doesn’t find any visible cancer to remove. Unfortunately, those patients have to undergo the operation—and lose the muscles of the rectum&mdash;to find that out. Now, doctors are holding off on surgery in patients who have responded well to chemo and radiation, following them very closely for signs of recurring disease.

	A study at Memorial Sloan Kettering Cancer Center compared patients who were observed after chemotherapy and radiation with those who underwent surgery after those treatments. Researchers found that 75 percent of the patients in the surveillance group didn’t need surgery during the four-year follow-up period, while 25 percent did. Survival in the surveillance group nearly matched that in the surgery group (91 versus 95 percent).

Next, a phase 2 study will follow such patients at 20 institutions across the United States. Non-surgical management will be offered to participants if their tumors disappear after chemotherapy and radiation.

“Clearly, this is a case where involvement with a clinical trial is the right thing,” Marshall says. By finding out which patients are most likely to have success with this treatment, oncologists will improve their standard of care by doing less—the proverbial win-win.

	“We’re all very nervous about this, honestly,” he says. “But I completely understand the push from the patients who will risk it.”

Features

Advances in the treatment of metastatic colorectal cancer have tripled survival rates, but more profound leaps are anticipated as researchers unravel the disease's complexities.

On the Verge of Understanding

I'm not proud to admit it: Before cancer, I took life for granted. I didn’t realize how precious it was to wake up in the morning feeling healthy, to have good friends who care about me or how lucky I was to make a living doing something I love.

	After having stomach pains and digestive issues for some time, I remember waking up from the anesthesia following my colonoscopy.

	Groggy and recharged at the same time, I was relieved to have the test behind me. But when my doc entered the room, my stomach dropped. I could tell he had news, and not the good kind. “You have a tumor, Wade. It’s so large, you’ve likely had it for years.”

	I felt blindsided. How could this even happen? I was in such good shape and had no family history of cancer. In fact, I’d been talking to my doctor about my symptoms and we thought I was too young to even consider something like that.

	Apparently that wasn’t the case. At age 42, I was diagnosed with stage 4 colon cancer. And that unappreciated life of mine quickly flashed before my eyes. I had to make a choice, and I decided to fight like heck.

	I dived into surgeries, chemotherapy and anything that might help kill this cancer before it killed me.

	I tried to keep doing what made me feel like myself— writing and performing music. Through my cancer journey, I used writing as an outlet for my fears, frustrations and hopes.

	When I was diagnosed, I’d been spending much of my time on stage and on the road for gigs. When I started treatment, the traveling and shows were quickly put on hold. The chemo was tough. My body faced some side effects that I’m still overcoming today. Chemo destroys soft tissue, and as treatment progressed, it caused neuropathy and damaged my throat and nose. Singing and playing guitar became very difficult; I’m just now starting to feel like my old self again, and man, does it feel amazing.

	After my last treatment, I went to visit my doc, who’d become a good friend of mine through this whole mess.

	He looked me in the eyes and told me something I’ll never forget: that there was no evidence of disease in my body. He said, “Now it’s time to go live your life.”

	After three years of surgeries, chemo and some recurrences, today I consider myself a healthy and humbled man. “Go live your life” has a totally different meaning for me in my post-cancer world. It means getting in my truck and realizing how lucky I am to be able to drive myself to the grocery store. It means stopping in my tracks at the gym and remembering the days I barely had the energy to walk to the front door. It means taking advantage of every chance I have to give back by spreading the word about colon cancer prevention and early detection.

	After that day, I went home and wrote my newest song, “Go Live Your Life.” It’s about chasing your dreams and jumping at every opportunity that’s presented to you.

	Since then, I’ve done just that. I’ve partnered with the Colon Cancer Alliance on national initiatives that will help raise awareness about this disease. At Colon Cancer Alliance events and concerts throughout the country, I remind people about the importance of being screened for colorectal cancer. Genentech is helping me give back by donating $1 for every song download of “Go Live Your Life” to the Colon Cancer Alliance’s Blue Note Fund, which provides financial stipends for people undergoing colon cancer treatment.

	Although the road to recovery has been slower than I’ve wanted at times, I look at the big picture and am grateful that I’m still around. I’m still here and have the opportunity to help spare somebody from going through what I did, and that’s what it’s all about. In my second chance, I am truly living my life.

—Originally from Oklahoma, Wade Hayes made his country-music debut in 1994 with his gold-certified album “Old Enough to Know Better.” His soon-to-be-released latest album will feature the song “Go Live Your Life.” To learn more about Wade Hayes, visit 

Speaking Out

After treatment for stage 4 colorectal cancer, a country singer is using his talents to express his gratitude and help others.

Go Live Your Life

Halloween is supposed to be frightening, but not the way it was for Denise Cesta a few years ago. On that holiday in 2011, she started treatment for stage 2 colorectal cancer.

	Facing a harsh therapeutic regimen, Cesta worried about how she would hold up physically and emotionally, and how well radiation, surgery and chemotherapy would work against her cancer.

	“It was one of the scariest days of my life,” she recalls. Since then, Cesta has joined the ranks of long-term survivors of the disease—and that has created a new set of challenges.

	For survivors of colorectal cancer, struggles can include negative body image, persistent gastrointestinal problems and sexual dysfunction—issues that can diminish quality of life and jeopardize relationships.

	Recent research has shown that, although the overall incidence of colorectal cancer is decreasing, rates are increasing in young adults, and this group faces particular challenges, including dating and discussing life after cancer with their children, especially if they have a genetic predisposition.

	And survivors of colorectal cancer face a risk of disease recurrence, secondary cancers or comorbidities such as cardiovascular disease, musculoskeletal problems, lung or breathing problems, and depression.

	Of course, adhering to a recommended schedule of screenings and follow-up visits with health care providers can make a big difference in how patients fare after colorectal cancer. But there is more survivors can do to improve their quality of life, from joining support groups to pursuing a healthy lifestyle. Studies suggest that a diet low in red meat and fat, along with an exercise regimen, can help prevent recurrences and comorbidities among survivors of colorectal cancers, and can promote a sense of well-being.

After being treated for stage 2 colorectal cancer, Denise Cesta started a vigorous exercise regimen. Photo by Sy Bean.

	“There is increasing evidence on how lifestyle factors may impact outcomes for survivors, including being physically active, maintaining a healthy diet and maintaining healthy levels of vitamin D,” explains Jeffrey Meyerhardt, lead author of the 2013 clinical practice update to the American Society of Clinical Oncology’s (ASCO’s) guidelines on follow-up care for survivors of colorectal cancer.

	It’s a mindset Cesta has fully embraced. She’s added more whole foods to her diet, pursues holistic therapies like acupuncture, acupressure and massage, and has adopted a new fitness regimen.

	Prior to her diagnosis, Cesta recalls, “I was thinking that I have this long life to live, and I didn’t need to worry about things like processed foods and microwaves. Now, I understand—this is it. I want to put the best things into my body and be as strong as I can.”

	For people like Cesta, diagnosed at a time when earlier detection and improved treatments are making their mark, the prospects are better than ever, and the majority of patients with local or regional disease will be cured. Although colorectal cancer remains the second leading cause of cancer death in the United States, nearly two-thirds of patients remain alive five years after diagnosis, and for the 75 percent of patients whose cancer is detected at an earlier stage, the fiveyear relative survival statistics are even better: nearly 90 percent for patients with localized disease and 70 percent for those whose cancer has spread to regional lymph nodes.

	That’s good news for patients, but those statistics didn’t do much to soothe Cesta when she started her treatment, a grueling regimen involving nearly six weeks of daily chemoradiation, then resection and ileostomy surgery, followed by another round of chemotherapy. To make matters worse, the day she received her first treatment, her husband landed in the intensive care unit with pneumonia and a collapsed lung.

	How did she cope? Part denial, she says, and part just going through the motions. As a project manager for a small health care communications firm in metro Seattle, Cesta explains, “I just went into project management mode.” She adhered strictly to her treatment schedule, continuing to work on her laptop during four-hour infusion treatments. She missed work only after her resection and ileostomy reversal surgeries (for five weeks each time), and, she admits, that was the hardest time.

	“I had never really been a depressed person before, but I didn’t leave the house,” she says. “I was just so fearful of an accident and that people would see my ileostomy or smell it.”

	Colorectal cancer also took a toll on her relationship with her husband, who had lost his mother to cancer when he was 25. “It was all very raw. We weren’t connecting and communicating. Cancer can bring some couples closer together, but unfortunately for us, it drove us apart.” The two separated for eight months, but have since reconciled.

	Despite that arduous journey, Cesta now sees that chapter in the rearview mirror as a speed bump on her journey.

	She says that her relationship with her husband was ultimately enriched by the experience. She is refocused on what is important in life and has emerged proud, strong and devoted to a healthy and active lifestyle—an approach experts agree is crucial to living well as a colorectal cancer survivor, along with vigilant surveillance and regular, robust communication with health care providers.

	Prevention of recurrence is the most important consideration after treatment ends, especially during the first five years, when the risk is highest. On its Cancer.Net website for patients and caregivers, ASCO provides a five-year schedule for follow-up blood tests, screenings (including CT scans and colonoscopy), and regular physician examinations based on the patient’s cancer stage (http://tinyurl.com/numkgqd).

	This period is a critical (and worrying) time for cancer survivors, and careful adherence to the guidance of their health care teams for follow-up monitoring is important, notes Meyerhardt, clinical director of the Gastrointestinal Cancer Center at Dana-Farber Cancer Institute, in Boston.

	“Patients with colorectal cancer have surgery and, for those appropriate, chemotherapy, and they’re followed very closely in the clinic every two weeks,” continues Meyerhardt.

	“Suddenly, they’re coming in every three months. That can sometimes be an adjustment for patients.”

	Yet once active treatment ends and surveillance begins, he stresses, “it’s really important for patients to get back into their normal lives, while still being followed intermittently but closely.”

	For some survivors, that’s easier said than done. Fear of recurrence can be stirred up when aches and pains previously associated with a cancer arise; when a relative or friend receives a cancer diagnosis; when cancer is covered by the media; or upon follow-up medical appointments. It’s a fear that can be extremely intrusive.

	Experts agree it should diminish over time, especially if a patient is having a positive experience as a well person. Still, for some, it can persist with emotional and physical impact.

	To cope, survivors can try using calming self-statements, imagery and distraction, journaling, or talks with family, friends, doctors or nurses.

	“The fear of cancer recurring is part of the contract you never agreed to sign from the club you never wanted membership in. Fortunately, this is a manageable and controllable document that empowers you to take ownership of your fear and live your best life possible with and through your disease,” Matthew Zachary, founder and CEO of the nonprofit Stupid Cancer, told CURE for its 8th Annual Cancer Guide.

	Even without a recurrence, life can change quite a bit after colorectal cancer. Cesta says she has permanent neuropathy in her feet (which in some can be an aftereffect of oxaliplatin therapy, notes Meyerhardt), and the chemotherapy treatments resulted in early menopause. Individuals who have had abdominal surgery are at higher risk of bowel obstruction, she adds—something for which she has been hospitalized three times. “I don’t think my digestive tract will ever be the same as it was before,” she says.

	The bowel issues associated with colorectal cancer represent an understandably sensitive topic for patients and survivors, and Cesta says that joining a support group and participating in online forums can help.

	“It is a very personal type of cancer,” she says, “and to be in a room full of people who have been there and can all talk about it without blushing is a really nice thing to have.”

	Cesta occasionally attends a Living with Colorectal Cancer support group near her home, which meets monthly under the auspices of the Seattle Cancer Care Alliance. She also participated in “Colon Talk,” a colorectal cancer support forum of The Colon Club. “When I was going through treatments, I wasn’t a very active poster,” she says, “but I would read others’ posts, and it really helped me to know what to expect.” Recent topics and questions posted to the forum include abdominal distension following surgery, diet recommendations to address bowel issues, and anxiety over follow-up scans.

	Nurse practitioner Zana Correa, who since 2007 has been providing care to and supporting colorectal cancer survivors through Memorial Sloan Kettering Cancer Center’s Adult Survivorship Program, agrees that such interactions can be really helpful in addressing the psychosocial issues, such as depression and fear of recurrence, that may accompany a colorectal cancer diagnosis. With a social worker, she co-facilitates a Life after Colorectal Cancer support group at Sloan Kettering where such issues can be freely discussed.

	“There can be a sense of shame when discussing bowel dysfunction. Patients will ask, ‘Will I have an accident?’ ‘Where is the nearest bathroom?’ They feel more comfortable in a setting where other people can relate.”

	At Sloan Kettering, once patients have completed their treatment for colorectal cancer, they are referred to Correa, where the appointment first and foremost involves surveillance for cancer recurrence, and attention is also given to prevention, symptom management and health promotion. She encourages patients to ask: “What changes can I make in my life?”

	Correa provides advice on the management of bowel dysfunction by advising on the use of fiber or anti-diarrheal medications, dietary changes and pelvic floor strengthening as needed. In addition, she makes referrals to an onsite dietitian-nutritionist, a tobacco-cessation program if the patient is a smoker, or to other specialists who can help manage late effects of treatment.

	“Stress management is key,” says Correa. Along with recommending support groups, she refers survivors to Sloan Kettering’s Integrative Medicine Service for touch therapies, mind-body therapy or acupuncture.

	Survivors treated for cancer at smaller facilities may not have such services on their doorsteps, meaning that communication with their health care teams is especially important. Survivors should not be afraid to ask questions and take notes, so that they can learn about important lifestyle factors and identify reputable resources for information and support.

	Survivors should also encourage the members of their health care teams to communicate with one another.

	“Most oncologists will be following patients for issues related to their colorectal cancer,” Meyerhardt points out, “but a lot of these patients have other needs to attend to, whether it’s hypertension, diabetes or screening for comorbidities based on their age.”

	After her treatment ended, Cesta determined to live the healthiest lifestyle she could. She signed on to Livestrong’s “Survive & Thrive,” a 12-week program involving a personal trainer and other survivors that helped her to get back into an exercise routine. She took her fitness regimen to the next level by participating in an Athletes 4 Cancer camp, joining survivors on a trip to Maui, where she learned to surf.

	She says these activities helped her to build confidence and showed her that she could accomplish things she once never thought possible. She continues her focus on fitness today with weight training and exercise and dance classes.

	In addition, Cesta decided she wanted to help others who are facing cancer. She participates in a number of colon cancer Facebook groups and sponsored walks to raise funds for research. And she is a volunteer buddy for the Colon Cancer Alliance, which matches her with newly diagnosed patients facing issues similar to those she experienced, usually middle-aged women dealing with an ileostomy.

	“Having this cancer was a wake-up call for me,” says Cesta. “Before I had cancer, I felt I was invincible, and I was just going through the motions of life.” Now, she says, she is in a position to help other cancer survivors live their best life.

	“I just really want to focus on the future,” she says, “being healthy and helping other people like me.”

After her treatment ended, Cesta signed on to Livestrong’s “Survive & Thrive,” a 12-week program involving a personal trainer and other survivors that helped her to get back into an exercise routine. Photo by Sy Bean.

Healing Well

For survivors of colorectal cancer, struggles can include negative body image, persistent gastrointestinal problems and sexual dysfunction&mdash;issues that can diminish quality of life and jeopardize relationships.


A Healthy Change

In 1994, at age 27, Keira Berman became acutely ill with what she thought was the flu. She also had blood in her stool, an issue she had dealt with since childhood and assumed to be a reaction to certain foods. Berman’s physician sent her to a gastroenterologist, who detected thousands of polyps in her colon via colonoscopy.

Neither her gastroenterologist nor his pathologist knew what the polyps were, so they sent slides to several universities, Berman recalls. Johns Hopkins University responded that, based on her age and the number of polyps in her colon, the New Jersey resident likely had a relatively rare hereditary syndrome known as familial adenomatous polyposis (FAP).

The impact of the diagnosis was dramatic. Informed that the polyps in her colon would likely become cancerous soon, Berman underwent a total colectomy and ileoanal anastomosis surgery to construct a J pouch for waste elimination. In the years that followed, FAP affected almost every aspect of her life, from the foods she could eat to her decision to have a family.

Colorectal cancer is diagnosed in an estimated 135,000 Americans each year, and is responsible for more than 50,000 deaths, report the Centers for Disease Control and Prevention. Of that number, 5 to 10 percent of cases are the result of an inherited genetic mutation, most commonly Lynch syndrome and, less so, FAP.

While relatively uncommon, these inherited syndromes can pose significant health issues for individuals who carry the genetic mutations, and for their family members. Among the most concerning is a dramatically increased risk for colorectal cancer and other specific cancer types.

Other long-term health issues are created by treatment, which can include removal of all or most of the colon, either prophylactically or during surgery for colorectal cancer. In addition, some women with Lynch syndrome choose to have preventive hysterectomies with removal of their fallopian tubes and ovaries once they are done having children, as a means of reducing their heightened risk for gynecologic cancers. And the syndromes mean that regular screening will forever remain a part of patients’ lives.

Lynch syndrome, previously known as hereditary nonpolyposis colorectal cancer (HNPCC), affects approximately one in 2,000 people. It is responsible for a little more than 3 percent of colon cancers, notes Dennis J. Ahnen, professor of medicine at the University of Colorado Denver School of Medicine, and co-director of the school’s Hereditary Cancer Clinic.

	“Colon cancer risk is enormous in this group,” Ahnen states. “It is estimated that between 30 and 55 percent of people who have a Lynch syndrome mutation will develop colon cancer, compared to a little less than 5 percent for the general population.” In addition to having a higher risk, individuals with Lynch syndrome typically develop colon cancer at a much younger age than those in the general population.

	Colon cancer isn’t the only cancer that can occur among individuals with Lynch syndrome, Ahnen adds. Women with the condition have a much higher risk of endometrial and ovarian cancers, and both men and women face a higher risk of cancers of the small bowel, stomach and ureter.

	Classic FAP, which has an incidence at birth of 1 in 8,300 people, differs from Lynch syndrome in that it predisposes individuals to develop hundreds to thousands of polyps, known as adenomas, in the colon. Only a small percentage of adenomas progress to cancer, explains Ahnen, but because there are so many, colon cancer is almost inevitable. Without intervention, those with FAP have a 90 percent chance of developing the disease by the age of 45. As a result, the most common treatment for classic FAP is removal of the entire colon.

	Whereas mutations in any one of five different genes may cause Lynch syndrome, FAP is caused by mutations in the APC gene, reports Francis M. Giardiello, the John G. Rangos Sr. Professor of Medicine at The Johns Hopkins University School of Medicine, and director of the Johns Hopkins Colorectal Cancer Registry and Risk Assessment Clinic. “People who have FAP usually present by age 15 with multiple colon adenomatous polyps and, if nothing is done, will develop colon cancer by age 39, on average,” Giardiello says.

	Most people with FAP receive the gene mutation from their parents. But others, such as Berman, spontaneously develop the mutation, making them the first in their families to develop the syndrome. Immediately after Berman was diagnosed with FAP, her parents and sister were tested and found to be free of the syndrome.

Hereditary syndromes that can cause colorectal cancers are uncommon, but for those who have them, diagnosis and preventive measures are key.

Colorectal Cancer Special Issue | CURE

Coming to an Understanding

Care Package

On the Verge of Understanding

Go Live Your Life

A Healthy Change

Hand Me Down Genes

Tackling Testing

Taking a Detour

During Colorectal Cancer Awareness Month and All Year Round, Prevention is a Central Theme

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