Colorectal cancer survivorship has risen in recent years due to earlier detection and advances in treatment. In 2014, colorectal cancer survivors accounted for about 1.2 million of the 15 million cancer survivors in the United States, and the number is growing.1 With this increase, primary care providers (PCPs) may see more and more of these patients in their clinics and need to understand how to address the issues these patients face. Frameworks for caring for patients who have survived colorectal cancer also can be applied to survivors of other types of cancer, with the ultimate goal of maintaining long-term quality of life.
Patients who have completed active cancer therapy may face a number of issues following treatment and for the duration of their lives. These include risk of recurrence and second cancers, both in primary and nonprimary sites; long-term and late effects from treatment; and comorbid health issues as they age, such as hypertension, heart disease, and diabetes. PCPs must monitor and screen patients for cancer, manage treatment effects, and address comorbid conditions to preserve the overall health of patients who have survived cancer.
PCPs must be prepared to care for the large and growing number of cancer survivors, many of whom may live for decades after diagnosis and treatment. The impending shortage of oncologists along with an aging general population makes the issue even more critical.2 Several tools are available and others are under development to help PCPs care for these patients.
The Institute of Medicine recommends that all cancer patients completing active treatment be provided with a survivorship care plan that can be used to guide future care.3 The plan should include:
- A summary of the cancer treatment the patient received
- Information about follow-up care and surveillance recommendations
- Information on post-treatment needs, treatment effects, and other risks
- Delineation of roles for the oncologist and PCP and timing of transfer of care
- Recommendations for healthful behaviors.3
Although survivorship care plans are being implemented in oncology practices, they have not yet become available to all cancer survivors. For example, a recent national survey reported that fewer than 10% of survivors received a survivorship care plan to pass along to their PCPs.4 A survey of PCPs found that a wide majority wanted recommendations for ongoing care for patients who have survived cancer, including guidance for managing long-term effects of treatment, screening for cancer and other diseases, and information about which aspects of care should be handled by the PCP.5
If these individualized summaries are not obtainable, guidelines for various issues dealing with survivorship care are available online from the American Cancer Society (www.acs.org), American Society of Clinical Oncology (www.asco.org), and National Comprehensive Cancer Network (www.nccn.org). The American Cancer Society is coordinating with experts in oncology and primary care to develop comprehensive survivorship guidelines for 10 priority cancer sites. To date, guidelines for breast, head and neck, prostate, and colorectal cancer survivorship have been published.
SURVIVORS OF COLORECTAL CANCER
Colorectal cancer is the second most survivable cancer among men after prostate cancer and the third among women after breast and uterine cancer, respectively.1 Survivors of colorectal cancer, on average, tend to be age 60 years or older, although the age of diagnosis is decreasing. Their overall health and quality of life is influenced by the cancer stage at diagnosis and type of therapy undertaken. Studies report that about two-thirds of patients survive 5 years after diagnosis of colorectal cancer and 50% of patients survive beyond 10 years after completing treatment.6,7 For patients with stages I to III disease (nonmetastatic), the most common treatment is surgery with additional therapy, including systemic chemotherapy (for patients with high-risk stage II or stage III disease) and radiation therapy for patients with rectal cancer.8,9 These therapies are given neoadjuvantly (preoperatively) or adjuvantly (postoperatively).8,9 Treatment is individualized for patients with stage IV (metastatic) disease.8,9
Survivors of colorectal cancer face several health issues. For patients with stage I through III disease who have completed treatment and have no evidence of disease, surveillance remains the most critical issue. Despite potentially curative measures, 25% to 40% of patients will experience a recurrence.10,11 More than 90% of colorectal cancer recurrences occur within 5 years of diagnosis, with about 80% of patients having a recurrence within the first 3 years.8,12 These survivors are also at risk for developing second primary colorectal cancers and other noncolorectal primary cancers.13 Survivors also often are affected by their cancer treatment, with the potential of experiencing both physical and psychologic adverse reactions. Because most survivors are in their 60s, comorbid health conditions and lifestyle play an important role in their overall health.
Because most patients with metastatic colorectal cancer receive almost all of their cancer-related care from their oncologist, this article will focus on patients with stages I through III who have completed therapy for colorectal cancer.
GUIDELINES FOR SURVIVORS
Watching for recurrence
The goal of surveillance is to screen for recurrence of the original cancer and occurrence of new cancers. Many factors increase the risk of recurrence, such as higher stage, poorly differentiated histology, lymphovascular and/or perineural invasion of the tumor, bowel perforation or obstruction, indeterminate or close resection margins, and fewer than 12 regional lymph nodes examined postoperatively. The ACS makes the following recommendations for surveillance:
- For the first 2 years after treatment completion, patients should have a history and physical examination and serum carcinoembryonic antigen (CEA) level checked every 3 to 6 months.6 At these clinic visits, patients are assessed for any symptoms or signs of recurrence, such as new abdominal pain, change in stools, rectal bleeding, anemia, and/or rising CEA levels that may warrant further evaluation beyond these surveillance guidelines; CT scans of the chest, abdomen, and pelvis with contrast are recommended annually.6 No recommendations support positron emission tomography (PET) scans for surveillance.6
The NCCN recommends (and ACS concurs) that patients have a colonoscopy 1 year after a large bowel resection, unless a colonoscopy was not completed before resection, oftentimes because of an obstructive mass. If a colonoscopy was not done before resection, a complete colonoscopy is recommended 3 to 6 months after surgery.
If no advanced adenomas or abnormalities are found, a repeat colonoscopy is recommended at 3 years.6 If an advanced adenoma is found, the time frame for repeat colonoscopy is based on the gastroenterologist's or colorectal surgeon's recommendations.6
- In years 3 to 5 posttreatment, patients should have a history, physical examination, and CEA level every 6 months, and a CT scan of the chest, abdomen, and pelvis annually.6 A colonoscopy is recommended in year 4; if no advanced adenomas are found, repeat the colonoscopy every 5 years indefinitely.6
- After 5 years, routine serum CEA levels and CT scans are not recommended, as no specific guidelines endorse these tests after 5 years.6
Lifelong screening for second primary cancers
Studies have shown that colorectal cancer survivors are at an increased risk of developing a subsequent primary cancer, most consistently seen as a second primary colorectal cancer.14 Patients with a diagnosis of initial colorectal cancer have an increased risk (up to 1.4-fold) of a subsequent primary cancer compared with the general population.14-16 Some evidence, although less consistent, suggests an increase in the risk of cancer of the stomach, small intestine, breast, ovaries, prostate, bladder, kidney, and endometrium after colorectal cancer. This risk may be higher for organs that have developmentally related epithelia to the colon and rectum.14,16 Despite these findings, the ACS recommends that survivors of colorectal cancer receive age- and sex-appropriate screening for patients of average risk for breast, cervical, endometrial, lung, and prostate cancers.6
Although most cases of colorectal cancer are sporadic, 25% of patients have a personal or family history, which suggests a hereditary colorectal cancer syndrome. These syndromes increase the chance of early-onset colorectal cancer and risk for a second primary cancer, as well as raise the patient's lifetime cumulative risk of cancer. These hereditary colorectal cancer syndromes also may cause cancer outside of the colon and rectum. Lynch syndrome, or hereditary nonpolyposis colorectal cancer (HNPCC), accounts for 2% to 4% of all colorectal cancers.17 Survivors of colorectal cancer who are diagnosed with HNPCC are at increased risk of endometrial and ovarian cancer (up to 71% for endometrial and up to 14% for ovarian) as well as stomach, small bowel, urinary tract, kidney, and brain tumors.6 Other less-common hereditary syndromes include familial adenomatous polyposis (FAP), attenuated FAP, and MUTYH-associated polyposis (MAP); these syndromes also increase patients' risk for colorectal cancer and other cancers outside of the colon.17
Patients with hereditary colorectal cancer syndromes should follow guidelines for screening specific to their hereditary syndrome. PCPs must be aware of these conditions and refer patients for appropriate evaluation. If the PCP suspects that a patient who has survived colorectal cancer has a hereditary syndrome (for example, the patient is under age 50 years and/or has a strong family history of colorectal cancer), the PCP should refer the patient to a genetics counselor, if the patient did not see one at the time of cancer diagnosis.
EFFECTS FROM TREATMENT
Surgical resection is the cornerstone of cure for localized colorectal cancer, and involves removing the tumor and associated blood supply with adequate margins. The resection can be several inches to feet in length. Depending on the location of the tumor, patients with colon cancer may have a left or right hemicolectomy, limited transverse colectomy, or resection of the sigmoid colon. For patients with rectal cancer, a low anterior resection or an abdominoperineal resection is performed based on the distance of the tumor (and adequate margins) from the anal verge. In a low anterior resection, the colon is anastomosed to the distal rectum or anus and the anal sphincter is preserved. An abdominoperineal resection involves the sigmoid colon, rectum, and anus with construction of a permanent colostomy. These abdominal and pelvic surgeries increase the risk of adhesions, intestinal obstruction, hernia, urogenital and sexual dysfunction, incontinence, and altered bowel function.
For many survivors of colorectal cancer, bowel dysfunction is a common, long-term problem. Chronic diarrhea affects almost half of survivors.6 Patients who have had a low anterior resection or lower surgical anastomoses may have low anterior resection syndrome, characterized by bowel symptoms including increased stool frequency, fecal urgency, fecal leakage, bowel incontinence, increased gas, and incomplete evacuations.18 Patients who have had a colostomy experience issues such as leakage from the colostomy site and lack of bowel control. Treatment for some of these bowel problems includes antidiarrheal medications such as loperamide or diphenoxylate/atropine. Dietary adjustments may be recommended, such as following a low-fat diet and avoiding raw vegetables.6,19 PCPs are encouraged to ask patients about their bowel habits, as survivors of colorectal cancer may assume that abnormal bowel movements are inevitable and may not discuss their concerns at clinic visits.19
Dissection of the pelvic autonomic nerves during rectal surgery may lead to urinary dysfunction. In patients who have survived rectal cancer, stress and urgency incontinence are the most common, with prevalence after rectal cancer surgery ranging from 30% to 70%.20 However, these rates are inconclusive because incontinence rates tend to be higher in the older population in general.20
Suggested treatments for urinary dysfunction include avoiding foods that irritate the bladder, such as citrus, tomatoes, and caffeine. Patients also may follow a bladder retraining program, such as by adhering to a fixed voiding schedule and performing Kegel exercises to strengthen pelvic floor muscles. In addition, using anticholinergic or antimuscarinic agents may help patients with stress or urge/mixed incontinence. Refer patients to a urologist as appropriate.6
Survivors also may experience sexual dysfunction depending on the extent of the dissection of the pelvic nerves during surgery. Studies have shown that 30% to 40% of previously sexually active patients reported sexual dysfunction following treatment, with survivors of rectal cancer reporting more difficulties than patients with colon cancer (25% compared with 11%).6,12 Women who have survived colorectal cancer, regardless of whether the cancer was in the colon or rectum, are substantially more likely to report sexual dysfunction than women in the general population.6 Because sexual dysfunction may reduce patients' overall quality of life, PCPs must ask patients about this issue and address it. For men, oral phosphodiesterase-5 inhibitors, testosterone replacement, and intracavernous pharmacologic therapies may be used. For women, vaginal lubricants can help with vaginal dryness or dyspareunia. Referral to sexual health programs and counseling may be beneficial for both sexes.6
The standard of care for patients with stage II or III rectal cancer is radiation, given either in the pre- or postoperative setting in conjunction with chemotherapy. After radiation treatment, these patients have an increased risk for developing chronic radiation proctitis or colitis, altered bowel function, urogenital and sexual dysfunction, bone loss or fractures, and second cancers.
Because of radiation damage to the blood vessels supplying the colon, chronic radiation proctitis or colitis can present with diarrhea, rectal bleeding, and painful defecation. These patients also are at risk for fistulas and intestinal obstruction, and should be promptly referred to gastroenterology or colorectal surgery if these conditions develop.12,21 Patients also may have persistent issues with altered bowel function, such as chronic diarrhea, fecal leakage, incontinence, and anorectal dysfunction with reduced reservoir capacity.19
Radiation therapy to the pelvic area also increases the risk of urogenital dysfunction, including infertility. In men, radiotherapy has been shown to lead to erectile dysfunction and a decrease in serum testosterone levels. In women, radiotherapy can cause atrophy, fibrosis, and adhesions of the vagina. Radiotherapy can cause radiation-induced ovarian failure.20 For some of these issues, PCPs may offer hormone replacement therapy for men and women, vaginal dilators for women, and referrals to specialists as needed.
Pelvic radiation may put patients at risk for bone loss and fractures. In a large retrospective study of women diagnosed with cervical, anal, or rectal cancer, patients with rectal cancer who underwent radiation therapy were more likely to have a pelvic fracture than women who did not undergo radiation therapy, a 1.65-fold increase.22 Survivors of rectal cancer who have had postoperative radiation therapy should undergo regular bone density monitoring, be treated for osteopenia or osteoporosis, and be evaluated if they develop symptoms suggestive of a fracture.12,19
Radiation-associated secondary malignancies are rare but possible because of cellular damage in the pelvic radiation field. However, no studies are investigating the specific risk after radiation treatment for rectal cancer.12
Following surgery, patients with high-risk stage II and stage III colorectal cancer are treated with adjuvant chemotherapy to reduce the risk of disease relapse and recurrence.
Patients with high-risk stage II have T4 tumors, tumors with poorly differentiated histology, perivascular or perineural invasion of the tumor, bowel obstruction, positive surgical margins, or fewer than 12 lymph nodes examined after surgery. Stage III tumors have various depths with an identified spread to a regional lymph node.8 The most common and standard of care chemotherapy regimens for these patients are the FOLFOX or Cape OX regimen, comprising an antimetabolite agent (5-FU IV or oral capecitabine) and the platinum drug oxaliplatin, given over 6 months. Most of the toxicities related to these agents are treatment-related and are reversible after treatment ends. However, oxaliplatin can cause long-term adverse reactions, including a cumulative sensory neuropathy with loss of sensation and tingling and/or pain in the distal extremities. This sensory neuropathy can be accompanied by changes in proprioception affecting fine motor skills. Chronic oxaliplatin-induced peripheral neuropathy is thought to be caused by a dose-dependent accumulation of platinum compounds in the dorsal root ganglia, causing neuronal atrophy and apoptosis.23 Although most patients' symptoms improve over time, some patients have significant symptoms after completing therapy. In a review of three studies of patients who received oxaliplatin for colorectal cancer, neuropathy persisted in 10% to 12% of patients for 2 years or more.23 These symptoms can affect physical functioning of patients' hands, fingers, feet, and toes. Pain associated with oxaliplatin-induced peripheral neuropathy can be treated with duloxetine, gabapentin, pregabalin, tricyclic antidepressants, or topical gels or creams such as menthol, capsaicin, or a mix of baclofen, ketamine, and amitriptyline.24 If oxaliplatin-induced peripheral neuropathy symptoms are disabling, PCPs should refer patients to neurology.
Cancer survivors, in general, experience more psychosocial issues than the general population. Fear of cancer recurrence or developing a new cancer, adjustments to physical changes, adverse reactions from treatment, problems with social relationships, returning to work, and financial strains all affect the survivors' quality of life. Depression, anxiety, negative body image, cognitive dysfunction, and fatigue are some of the psychosocial issues facing survivors.6 Twenty-four percent of survivors report depression scores high enough to warrant evaluation for clinical depression.19 Survivors also may have adverse feelings related to bowel dysfunction and/or having a colostomy, leading to reduced social, emotional, sexual, and occupational functioning.12 For example, 25% of survivors with a stoma report negative feelings about their body appearance compared with 12% of survivors who do not have a stoma.19 PCPs should screen survivors for depression, anxiety, and other psychosocial stressors, prescribe antidepressants and antianxiolytics as appropriate, and/or refer patients to mental health professionals.
Like other cancer survivors who have received chemotherapy, survivors of colorectal cancer also may report a decline in cognitive function, sometimes called chemo brain, that includes memory loss, slower processing time, and/or difficulty with concentration and attention. These symptoms may occur during chemotherapy but can continue months to years after treatment ends. For example, memory loss was reported in 40% of patients receiving any chemotherapy versus those without cancer.6 Unfortunately, evidence to guide management of this condition is limited, and no brief, effective screening tool exists for cancer-associated cognitive dysfunction.25
Survivors who have no evidence of disease and have completed treatment may continue to experience long-term fatigue.6 Screen these patients for treatable conditions such as anemia, vitamin deficiency, pain, and sleep disorders. Because cognitive changes and fatigue may be compounded by physical inactivity, depression, anxiety, and other psychosocial issues, evaluating and treating these conditions may require a multifaceted approach. Use mental health questionnaires to evaluate patients, treat when appropriate, refer patients as appropriate to neurology and psychiatry/counseling services, and encourage patients to eat a balanced diet and get regular physical exercise.6
PCPs are probably the most qualified healthcare providers to ensure that the long-term needs of cancer survivors are met, especially relating to the management of comorbid disease (such as heart disease and diabetes), mental health, and acute care.26 Patients who survive cancer often lose consistent contact with PCPs while in care of their oncologists, and may place their other healthcare needs on hold. After patients complete active cancer treatment, PCPs have the important role of optimizing treatment for these comorbidities.26 PCPs also should encourage patients to take preventive measures and steps to promote overall health, as most patients who survive colorectal cancer die of other causes.27 As with all patients, survivors of colorectal cancer should be counseled on maintaining a healthful body weight, being physically active, eating a healthful diet, and smoking cessation.
Between 17% and 35% of patients with colorectal cancer who receive adjuvant chemotherapy are obese.28 Evidence indicates that being overweight or obese increases the risk of colorectal cancer recurrence and death.28 Obesity also puts these patients at risk for other obesity-related cancers such as breast, endometrial, pancreatic, esophageal, and kidney cancer.6,28
Regular physical activity has been shown to reduce colorectal cancer recurrence.13,27 The American College of Sports Medicine recommends that cancer survivors get 150 minutes of moderate-intensity aerobic activity per week and muscle strengthening 2 days a week.27 Eating a plant-based diet, limiting red meat intake, and maintaining normal vitamin D levels are all recommended for improved survival outcomes. A comprehensive review of physical and nutrition guidelines is available through the American Cancer Society.29
Smoking cessation is vital for patients who have survived colorectal cancer. Studies have indicated that patients who smoked cigarettes before and/or after diagnosis are nearly twice as likely to die as a result of their cancer and double their overall mortality risk compared with nonsmokers.6 For patients who smoke, offer counseling on the risks of smoking, provide smoking cessation treatment, and refer them to smoking cessation counseling.
With the increasing number of survivors of colorectal cancer, PCPs will play an integral role in caring for these patients after they complete cancer treatment. That role includes monitoring for cancer recurrence and new cancers, addressing patients' long-term and late effects from treatment, and evaluating and addressing patients' psychosocial issues. Because PCPs are trained to treat comorbid conditions, promote health, and help prevent disease, they will be on the front lines to improve patient quality of life and ultimately survival. Cancer survivorship may be the newest of the chronic conditions handled by PCPs.30
1. Desantis CE, Lin CC, Mariotto AB, et al Cancer treatment and survivorship
statistics, 2014. CA Cancer J Clin
2. Erikson C, Salsberg E, Forte G, et al Future supply and demand for oncologists: challenges to assuring access to oncology services. J Oncol Pract
3. Hewitt M, Greenfield S, Stoval E, eds. From Cancer Patient to Cancer Survivor: Lost in Transition
. Washington, DC: National Academies Press; 2006.
4. Blanch-Hartigan D, Forsythe LP, Alfano CM, et al Provision and Discussion of Survivorship
care plans among cancer survivors: results of a nationally representative survey of oncologists and primary care
physicians. J Clin Oncol
5. Salz T, Oeffinger KC, Lewis PR, et al Primary care
providers' needs and preferences for information about colorectal cancer survivorship
care. J Am Board Fam Med
6. El-Shami K, Oeffinger KC, Erb NL, et al American Cancer Society colorectal cancer survivorship
. CA Cancer J Clin
7. Ngune I, Jiwa M, McManus A, Hughes J. Do patients with long-term side effects of cancer treatment benefit from general practitioner support? A literature review. Int J Integr Care
10. Buie WD, Attard JA. Follow-up recommendations for colon cancer. Clin Colon Rectal Surg
11. Tjandra JJ, Chan MK. Follow-up after curative resection of colorectal cancer
: a meta-analysis. Dis Colon Rectum
12. Ho M, Winson C. After the treatment phase of colorectal cancer
and follow-up. J Cancer Ther
13. Wong-Ting EY, Chua C, Beh SY, et al Addressing the needs of colorectal cancer
survivors: current strategies and future directions. Expert Rev Anticancer Ther
14. Phipps AI, Chan AT, Ogino S. Anatomic subsite of primary colorectal cancer
and subsequent risk and distribution of second cancers. Cancer
15. Raj KP, Taylor TH, Wray C, et al Risk of second primary colorectal cancer
among colorectal cancer
cases: a population-based analysis. J Carcinog
16. Enblad P, Adami HO, Glimelius B, et al The risk of subsequent primary malignant diseases after cancers of the colon and rectum. A nationwide cohort study. Cancer
17. Kline RP. Recognizing hereditary colorectal cancer
18. Martellucci J. Low anterior resection syndrome: a treatment algorithm. Dis Colon Rectum
19. Denlinger CS, Barsevick AM. The challenges of colorectal cancer survivorship
. J Natl Compr Canc Netw
20. Lange MM, van de Velde CJ. Urinary and sexual dysfunction after rectal cancer treatment. Nat Rev Urol
21. Babb RR. Radiation proctitis: a review. Am J Gastroenterol
22. Baxter NN, Habermann EB, Tepper JE, et al Risk of pelvic fractures in older women following pelvic irradiation. JAMA
23. Weickhardt A, Wells K, Messersmith W. Oxaliplatin-induced neuropathy in colorectal cancer
. J Oncol
24. Hershman DL, Lacchetti C, Dworkin RH, et al Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol
26. Ganz PA. Survivorship
: adult cancer survivors. Prim Care
27. Jorgensen ML, Young JM, Solomon MJ. Optimal delivery of colorectal cancer
follow-up care: improving patient outcomes. Patient Relat Outcome Meas
28. Gibson TM, Park Y, Robien K, et al. Body mass index and risk of second obesity-associated cancers after colorectal cancer
: a pooled analysis of prospective cohort studies. J Clin Oncol
29. Rock CL, Doyle C, Demark-Wahnefried W, et al Nutrition and physical activity guidelines
for cancer survivors. CA Cancer J Clin
30. Westfall MY, Overholser L, Zittleman L, Westfall JM. Cancer survivorship
for primary care
annotated bibliography. J Cancer Policy
Keywords:Copyright © 2018 American Academy of Physician Assistants
colorectal cancer; survivorship; guidelines; primary care; surveillance; depression