As defined by the Institute of Medicine, surveillance in the context of the treatment of cancer survivors encompasses three elements: surveillance for cancer recurrence, surveillance for second cancers, and surveillance for medical and psychosocial late effects of cancer treatment. In the care of the elderly, the approach to surveillance should be considered in the overall context of the health of the patient. As an example, active surveillance for cancer recurrence and second cancers may not be appropriate in patients whose comorbidities (e.g., moderate to severe dementia, end-stage chronic obstructive pulmonary disease) make further cancer treatment impossible or inadvisable. For these patients, the emphasis should be on initiating timely and appropriate palliative treatment if symptoms of cancer recurrence develop.
This chapter will discuss surveillance in the context of the treatment of cancer survivors who are considered to be in remission or cured, with an emphasis on cancers commonly encountered among the elderly. The strategies discussed presume that the overall health of the patient is such that active surveillance for cancer recurrence and second cancers is of potential benefit. Specific strategies and guidelines are reviewed for survivors of common cancers among the elderly, including breast, prostate, and colon cancer.
A 66-year-old woman presents for preventive care. Her past medical history is significant for stage 1 breast cancer diagnosed by mammography 2 years previously. The tumor was estrogen and progesterone receptor-positive and HER-2/Neu negative. She was treated with lumpectomy with sentinel node evaluation and radiation therapy. Her current medications include an aromatase inhibitor. She asks the following questions: (1) What follow-up tests do I need? (2) Should I have an annual breast MRI? (3) Should I be tested for the BRCA gene?
A 72-year-old man presents for preventive care. He underwent radical prostatectomy at age 60 for prostate cancer. His PSA is now undetectable. He asks: (1) How often do I need PSA testing? (2) Do I need to see a urologist on a regular basis?
General Principles of Surveillance
Surveillance strategies should be guided by available evidence, when possible. Although randomized trials have addressed many important surveillance issues for common cancers, published surveillance strategies are based partly on expert opinion. An important element of performing surveillance in cancer patients who are free of disease is ensuring that other, unrelated medical issues or problems, as well as non–cancer-related preventive measures, are not overlooked. This is particularly relevant in the elderly, who frequently suffer from comorbidities that are unrelated to cancer.
Asymptomatic cancer survivors are often followed clinically on a regular basis for indefinite periods by medical, surgical, and/or radiation oncologists In recent years, there has been recognition that a “one size fits all” approach to selecting the appropriate clinician to perform follow-up of cancer survivors is not appropriate. Important issues to consider in determining which clinicians should provide surveillance for disease-free survivors include balancing access to appropriate expertise with overall accessibility, affordability, and coordination of care. Although more research is needed, available evidence suggests that well-trained generalists are as capable as oncologists of performing surveillance, and that nurses working with oncologists also provide high quality surveillance care.
Because all elderly patients have significant preventive health needs, elderly cancer patients who are cancer-free should have a primary care clinician as part of their health care team. For many patients, once treatment is completed, surveillance may be effectively performed by the primary care clinician, with consultation with the oncologist on an as-needed basis. Elderly patients at high risk of recurrence may be best served by co-management by an oncologist and a generalist or geriatrician. Co–management may also be indicated for elderly patients who have a high likelihood of complications from therapy, particularly early in their posttreatment course. Co–management should also be available should the patient, the generalist or geriatrician, or the oncologist feel it is in the patient’s best interest. Specialized survivorship clinics may be appropriate for some patients. Guidelines tools (described later) exist to assist physicians in performing evidence-based surveillance for patients who have been treated for common cancers.
Testing for recurrent disease should be performed proactively if recurrence can be treated for cure. Examples include serial PSA testing in prostate cancer patients, examination and mammography of preserved breasts in breast cancer patients, and computed tomography (CT) scanning to detect liver metastases in high-risk colon cancer patients. Randomized trials have not shown either survival or quality-of-life benefit for strategies that test for incurable disease before patients are symptomatic, even though such strategies may identify disease before it is clinically apparent. For this reason, performing laboratory or radiological tests to detect asymptomatic metastatic disease that is incurable is not recommended. As an example, performing “routine” bone scans and liver-associated enzyme tests in asymptomatic breast and prostate cancer survivors is not recommended.
Surveillance for second primary cancers is performed when such cancers are frequent. As an example, the absolute incidence of contralateral breast cancer in breast cancer survivors is 0.5% to 1% per year. Annual screening mammography is therefore recommended. Appropriate genetic testing is indicated to identify cancer syndromes where enhanced screening and/or other preventive measures to prevent second cancers are available. Research suggests that screening and interventions are beneficial for such patients. Because genetic testing has only recently been widely performed, it is important to ascertain the family history of all cancer survivors, including those whose treatment was remote, to identify those who may benefit from genetic testing.
Surveillance for medical and psychosocial aftereffects of treatment is often overlooked after the initial treatment is completed. All cancer survivors should have regular contact with a physician who accepts responsibility for this aspect of care. Long-term medical effects are treatment-specific; the physician responsible for identifying complications of treatment must therefore be informed of the treatment the patient received.
Patient education is an important element of surveillance. Patients should be informed of current recommendations for surveillance, as well as signs and symptoms of recurrence and late treatment effects. Physicians performing surveillance of medical and psychosocial effects should be aware of community and peer resources for their patients.
Recently, the Institute of Medicine has promoted the concept of a “survivorship care plan.” A survivorship care plan provides a comprehensive summary of care and recommended follow-up in written (and, ideally, electronic) form, is clearly and effectively explained to the patient at the completion of active therapy, and is communicated to all members of the patient’s health care team.
Surveillance Issues for Cancers where Survivors are Common among the Elderly
Breast Cancer
There are over two million breast cancer survivors in the United States. Most of these women will die of causes unrelated to their breast cancer diagnosis. The risk of breast cancer increases with age, making breast cancer a common diagnosis among elderly women. Treatment usually consists of surgical resection of the cancer by lumpectomy or mastectomy and sentinal lymph node biopsy. Patients with positive lymph node biopsy may undergo lymph node dissection. Adjuvant therapy includes radiation therapy of the affected breast for patients treated with lumpectomy, and chemotherapy and/or hormonal therapy depending on the characteristics of the tumor. Commonly used chemotherapeutic agents include cyclophosphamide, methotrexate, fluorouracil, doxorubicin, and paclitaxel in various combinations, and trastuzumab. Hormonal agents include aromatase inhibitors (anastrozole, letrozole, and exemestane), and selective estrogen receptor modulators (tamoxifen).
Surveillance for Cancer Recurrence
Recommendations for surveillance for recurrence among breast cancer survivors are mainly based on the results of large clinical trials performed in the late 1980s and early 1990s that randomized women to either intensive or conservative follow-up strategies. Both groups underwent periodic history and physical examination and mammography. The intensive follow-up groups in addition underwent periodic laboratory testing including both blood and radiological tests. Although women followed with batteries of tests had recurrences detected, on average, 3 months earlier, there was no difference in survival between groups after 10 years of follow-up, and satisfaction with care was identical in the two groups. Although additional methods of early detection of distant recurrence, such as positron emission tomography/computed tomography (PET/CT) scanning and serological tumor marker testing, have become more widely used since the 1990s, the availability of these tests has not changed expert opinion that such testing is not beneficial.
Surveillance for breast cancer recurrence focuses on the use of physical examination and mammography in preserved breasts to detect local recurrences, which are potentially curable, at an early stage. Surveillance for distant recurrence, which is incurable, is accomplished by history and physical examination, with additional testing as indicated. It is important that women be informed of the signs and symptoms of recurrence, because palliative treatment may be delayed if symptoms such as musculoskeletal pain or cough are not recognized as cancer-related. American Society of Clinical Oncology guidelines for surveillance in breast cancer are summarized in Table 23-1 .
| Type of Cancer | Organization | Summary Recommendations |
|---|---|---|
| Breast | ASCO | History and physical examination every 3-6 months for 3 years, every 6-12 months for 2 years, then annually ∗ |
| Mammography 6 months after radiation therapy (if breast preserved), then annually | ||
| Genetic (BRCA) testing when indicated ( Table 23-2 ) | ||
| Specifically NOT recommended in asymptomatic patients who lack other indications: CBC, chemistry panels, tumor markers (CEA, CA 15-3, CA 27.29), bone scans, liver ultrasounds, CXR, CT scans with or without PET, breast MRIs | ||
| Colon | ASCO | Colonoscopy 3 years after operative treatment, and then every 5 years if normal; flexible proctosigmoidoscopy every 6 months for 5 years for rectal cancer patients who have not been treated with pelvic radiation |
| History and physical examination every 3-6 months for 3 years, every 6-12 months for 2 years, then at discretion of the physician for patients diagnosed with stage II or III colorectal cancer | ||
| CEA measurement every 3 months for 3 years for patients diagnosed with stage II or III colorectal cancer | ||
| CT of the chest and abdomen annually for 3 years for patients at high risk of recurrence † | ||
| Specifically NOT recommended in asymptomatic patients who lack other indications: CXR, CBC, liver function tests | ||
| Prostate | National Comprehensive Care Network | PSA measurement every 6-12 months for 5 years, then annually |
| Digital rectal exam annually ‡ |
∗ Includes patient education regarding symptoms of recurrence and “regular gynecological follow-up”
† Not rigorously defined. Includes stage III patients, some stage II patients with adverse risk factors
‡ History and physical examination is recommended for patients at high risk of recurrence
Surveillance for Second Cancers
Compared to women who have not had breast cancer, breast cancer survivors have a two to six times greater risk of developing breast cancer in the contralateral breast. Physical examination and mammography are recommended to detect second cancers at an early stage. Unfortunately, studies have shown that many elderly breast cancer survivors do not receive appropriate mammographic screening. In one recent national study, over 30% of elderly breast cancer survivors did not receive recommended screening, despite being enrolled in integrated health care systems.
Magnetic resonance imaging (MRI) with gadolinium has been shown to have increased sensitivity compared to mammography in women at highest risk for breast cancer, including women with BRCA mutation or equivalent risk. However, screening MRI is not currently recommended for women who, like most breast cancer survivors, do not have a lifetime risk of primary or recurrent cancer of 20% or greater Lack of specificity of screening MRI continues to be a problem, with 25% or more of subjects in studies of screening MRI requiring additional imaging to further define abnormalities, the vast majority of which are benign. The role of screening MRI continues to be studied.
Recently, increasing emphasis has been placed on identifying breast cancer survivors whose family history identifies them as being at high risk for carrying a BRCA gene. American Society of Clinical Oncology recommendations for selecting breast cancer survivors for BRCA testing are summarized in Table 23-2 . Breast cancer survivors with the BRCA gene have a risk of developing ovarian cancer of 1.4% per year, which is ten times the rate observed in breast cancer survivors without the BRCA mutation. They also have a risk of developing contralateral breast cancer of over 5% per year. These risks accrue over the patient’s entire life, so otherwise healthy elderly women should be considered for testing as part of a strategy to prevent future cancers. For elderly women for whom genetic testing might not be indicated because of comorbidities, testing may still be indicated if the patient wishes to obtain genetic information to inform family members of the potential for genetic risk. In case-control cohort studies, prophylactic salpingo-oophorectomy reduces subsequent ovarian cancer risk by 90%. Many women also choose prophylactic mastectomy. For BRCA-positive women who do not elect prophylactic mastectomy, annual screening MRI of the breasts with gadolinium is recommended. The costs of genetic testing, prophylactic surgery, and screening MRI are generally included in insurance coverage for patients who meet published indications.
| Ashkenazi Jewish heritage |
| Personal history of bilateral breast cancer |
| Personal history of ovarian cancer |
| First- or second-degree relative with ovarian cancer at any age |
| First-degree relative with a history of breast cancer diagnosed before age 50 |
| Two or more first- or second-degree relatives with breast cancer diagnosed at any age |
| Relative diagnosed with bilateral breast cancer |
| Male relative diagnosed with breast cancer |
Late Medical and Psychosocial Effects in the Elderly
Fortunately, advances in surgical treatment have reduced the number of breast cancer survivors with severe lymphedema. However, a significant number of women still undergo lymph node dissection, and late presentation of lymphedema continues to occur. Patients are generally advised to avoid compression, venipuncture, and trauma to the arm ipsilateral to lymph node dissection. All patients who have undergone axillary lymph node dissection should be aware that they should report swelling to their clinician. Elevation and the use of a lymphedema sleeve are the usual treatments. Although patients have often been counseled to avoid weight lifting with the affected arm, a recent study suggests that exercise, including moderate weight lifting, may be beneficial in preventing or ameliorating lymphedema.
Elderly women who were taking estrogen prior to their breast cancer diagnosis may develop hot flashes when estrogen is stopped. Treatment with aromatase inhibitors and tamoxifen are also associated with hot flashes. Selective serotonin reuptake inhibitors (SSRIs), selective serotonin and norepinephrine reuptake inhibitors (SNRIs), and gabapentin are effective interventions to treat vasomotor symptoms. SSRIs are generally avoided in patients taking tamoxifen because SSRIs may alter tamoxifen metabolism in some women, rendering it less effective. Vaginal dryness and dyspareunia may be treated with nonhormonal vaginal moisturizers or low-dose intravaginal estradiol (some experts recommend using intravaginal estradiol with caution).
Women treated with aromatase inhibitors are at risk for treatment-associated arthralgias and musculoskeletal pain. Musculoskeletal symptoms also occur with tamoxifen treatment but less frequently. Imaging should be considered to evaluate for possible metastatic disease. Medical management with acetaminophen or other pain medications may be considered. Nonsteroidal anti-inflammatory drugs are avoided in the elderly, when possible, because of an enhanced risk of bleeding complications. Consideration of change or cessation of adjuvant treatment is sometimes unavoidable.
Breast cancer survivors are at high risk of osteoporotic fracture. All breast cancer survivors should have adequate intake of calcium (1200-1500 mg daily) and Vitamin D (1000-2000 IU daily), and have bone densitometry performed at age 65 and each 5 years thereafter, or more frequently if indicated by low bone mineral density or other risk factors. Adjuvant treatment with aromatase inhibitors places patients at very high risk of fracture. For this reason, patients treated with aromatase inhibitors should have bone densitometry performed at initiation of therapy, and annually while receiving therapy. Bisphosphonate therapy is the preferred treatment of osteoporosis in breast cancer survivors.
Patients who undergo radiation of the left chest wall are at increased risk of cardiovascular disease. The usual strategies to reduce cardiovascular risk, including screening and treatment of hypertension, diabetes, and hypercholesterolemia, as well as promotion of a healthy lifestyle including exercise, weight maintenance, and healthy diet, are recommended. Patients who receive treatment with anthracyclines or trastuzumab are at risk of congestive heart failure. No effective prophylaxis is known. Patients should be monitored and, if congestive heart failure develops, they should be treated according to the standard medical protocols.
Patients treated with tamoxifen are at increased risk of uterine cancer, venous thrombosis, and cerebrovascular disease. Vaginal bleeding should be promptly evaluated by endometrial biopsy.
Cognitive dysfunction, depression, fatigue, and weight gain are all commonly reported in breast cancer survivors and they should be diagnosed and treated as per the usual strategies. Symptoms of cognitive dysfunction and fatigue should be fully evaluated in the elderly to ensure that they do not represent unrelated comorbid processes (such as Alzheimer disease, hypothyroidism, or other systemic disease).
Prostate Cancer
Prostate cancer is the most common cancer in American men. Of the 10 million cancer survivors in the United States, 18% are survivors of prostate cancer. Treatment modalities include radical prostatectomy, external beam radiotherapy, and permanent (low-dose) brachytherapy. Active surveillance (close monitoring of men with prostate cancer with curative treatment offered only to those who fit certain criteria) and watchful waiting (management of men medically unsuitable for curative treatment consisting of initiation of palliative treatment for symptoms) are also strategies for management of prostate cancer. Patients with disease that is at very high risk of recurrence may be treated with androgen-deprivation therapy in addition to other modalities. These strategies will not be discussed further in this chapter. Recurrence (defined by elevated serum prostate-specific antigen [PSA] after initial treatment) is relatively common, ranging from 10% in those with low-risk cancers to over 60% in high-risk patients. Within 10 years of initial treatment, 10% to 20% of men with high-risk clinically localized prostate cancer die of the disease.
Surveillance for Cancer Recurrence
The cornerstone of monitoring for cancer recurrence is serial PSA measurement. There is marked variation among various guidelines groups as to the recommended frequency of PSA measurement, which reflects the lack of randomized, controlled trial data on this topic. In general, testing is advised no more frequently than every 3 months, with many groups endorsing longer intervals after patients have been disease-free for a specified length of time. The role of digital rectal examination (DRE) is controversial. Some groups recommend it only if the PSA is judged to be abnormal. Others recommend annual examination. Guidelines from the National Comprehensive Cancer Network are summarized in Table 23-1 .
Late Medical and Psychosocial Effects in the Elderly
Erectile dysfunction is reported by up to 80% of prostate cancer survivors. Erectile function may improve with time after prostate cancer surgery, but generally declines with time after radiation treatment. Phosphodiesterase inhibitors are effective in improving erectile dysfunction in up to 75% of men who have undergone nerve-sparing radical prostatectomy, as well as men who have undergone radiation therapy. Elderly men are less responsive to phosphodiesterase inhibitor treatment compared to younger men. Intraurethral and intracorporeal alpostadil is offered to men who do not respond to phosphodiesterase inhibitors, and is useful for men who have received all types of treatment, including those who had non–nerve-sparing treatment. In studies, about half of men show benefit.
Urinary incontinence is reported by 10% to 20% of prostate cancer survivors. Urinary continence improves for up to a year after surgery. Urinary incontinence is treated with pelvic floor exercises, behavioral modification, and weight loss. Electrical stimulation for bladder retraining, periurethral collagen injection, and surgery to place an artificial sphincter or bulbourethral sling are sometimes recommended.
Additional side effects in men treated with radiation therapy and brachytherapy include hematuria, cystitis, bladder contracture, urethral stricture, rectal bleeding, rectal ulceration, rectal/anal stricture, and chronic diarrhea. All are uncommon. Patients should be specifically asked about these complications, and treated or referred to specialists for treatment. Because these side effects are often associated with psychosocial distress, screening for depression is recommended by some experts.
Colon Cancer
Colorectal cancer is a disease of the elderly. Two thirds of invasive colorectal cancers are diagnosed in persons older than 65 years. In persons older than 75 years, colorectal cancer is the most common cancer diagnosis. There are over 1 million survivors of colorectal cancer in the United States. Treatment generally consists of surgical resection, followed by adjuvant 5-fluorouracil, leucovorin, capecitabine, oxaliplatin, or irinotecan in various combinations for patients with high-risk stage II or stage III disease.
Surveillance for Cancer Recurrence
According to current guidelines from the American Society for Clinical Oncology ( Table 23-1 ), surveillance should include a history and physical examination, serial colonoscopy, and, for patients with rectal cancer who have not been treated with pelvic radiation, flexible proctosigmoidoscopy at frequent intervals. Serial carcinoembryonic antigen (CEA) testing is recommended for patients who are candidates for surgery or chemotherapy. Because several studies have shown survival advantage for colorectal cancer survivors with resectable metastases in the liver and lung, computed tomography of the chest and abdomen is recommended annually for three years for patients at high risk of recurrence, usually defined as those with node-positive malignancies, if the patient would otherwise be a candidate for resection. Chest x-rays, complete blood counts, liver-associated enzyme tests, and other molecular or cellular marker tests are not recommended at present.
Surveillance for Second Cancers
In addition to serial colonoscopy as recommended for surveillance for cancer recurrence, colon cancer survivors should be assessed to determine whether testing for Lynch Syndrome (hereditary nonpolyposis colon cancer) is indicated. Experts recommend patients with Lynch Syndrome undergo colonoscopy every 1 to 2 years.
Patients with Lynch syndrome are also at risk for uterine, urological, and additional gastrointestinal malignancies. For women, prophylactic total abdominal hysterectomy and bilateral salpingo-oophorectomy may be of benefit. Enhanced surveillance for urological and upper gastrointestinal malignancies is also recommended by some experts. Criteria for Lynch Syndrome testing in patients with colon cancer are listed in Table 23-3 .
|
Late Medical and Psychosocial Effects in the Elderly
Long-term colorectal cancer survivors do not differ from healthy controls in terms of physical functioning. Advanced age and lower income are associated with lower levels of function. Long-term effects include fatigue, pain, and diarrhea. Bowel symptoms are more frequent among rectal cancer survivors. Although negative body image is more common among survivors with ostomies, as are symptoms of diarrhea and cramping, overall quality of life, social functioning, and activities of daily living do not appear to be permanently affected. Depression, however, is relatively frequently reported. Some experts recommend screening for depression in colon cancer survivors.
Over 90% of patients treated with adjuvant oxaliplatin develop peripheral neuropathy during active therapy. However, only about one in 10 patients reports persistent symptoms after completion of treatment. Such patients may benefit from pharmacological treatments for neuropathy, as well as specialty referral for pain management. Chronic diarrhea is generally managed with antidiarrheal regimens and the use of incontinence garments. Patients may not volunteer symptoms, so physicians should actively ask about bowel problems during follow-up. Patients who have undergone pelvic radiation for rectal cancer are at increased risk for pelvic fracture; thus all survivors with a history of pelvic radiation should undergo bone-mineral density testing, and medical treatment of osteopenia and osteoporosis should be considered. Survivors of pelvic radiation also commonly suffer from urinary and sexual dysfunction including urinary incontinence, erectile dysfunction in men, and vaginal dryness in women. Phosphodiesterase inhibitors have shown benefit for erectile dysfunction in men after pelvic radiation. Vaginal dilators may be of benefit for women with vaginal stenosis after pelvic radiation.
Breast Cancer
There are over two million breast cancer survivors in the United States. Most of these women will die of causes unrelated to their breast cancer diagnosis. The risk of breast cancer increases with age, making breast cancer a common diagnosis among elderly women. Treatment usually consists of surgical resection of the cancer by lumpectomy or mastectomy and sentinal lymph node biopsy. Patients with positive lymph node biopsy may undergo lymph node dissection. Adjuvant therapy includes radiation therapy of the affected breast for patients treated with lumpectomy, and chemotherapy and/or hormonal therapy depending on the characteristics of the tumor. Commonly used chemotherapeutic agents include cyclophosphamide, methotrexate, fluorouracil, doxorubicin, and paclitaxel in various combinations, and trastuzumab. Hormonal agents include aromatase inhibitors (anastrozole, letrozole, and exemestane), and selective estrogen receptor modulators (tamoxifen).
Surveillance for Cancer Recurrence
Recommendations for surveillance for recurrence among breast cancer survivors are mainly based on the results of large clinical trials performed in the late 1980s and early 1990s that randomized women to either intensive or conservative follow-up strategies. Both groups underwent periodic history and physical examination and mammography. The intensive follow-up groups in addition underwent periodic laboratory testing including both blood and radiological tests. Although women followed with batteries of tests had recurrences detected, on average, 3 months earlier, there was no difference in survival between groups after 10 years of follow-up, and satisfaction with care was identical in the two groups. Although additional methods of early detection of distant recurrence, such as positron emission tomography/computed tomography (PET/CT) scanning and serological tumor marker testing, have become more widely used since the 1990s, the availability of these tests has not changed expert opinion that such testing is not beneficial.
Surveillance for breast cancer recurrence focuses on the use of physical examination and mammography in preserved breasts to detect local recurrences, which are potentially curable, at an early stage. Surveillance for distant recurrence, which is incurable, is accomplished by history and physical examination, with additional testing as indicated. It is important that women be informed of the signs and symptoms of recurrence, because palliative treatment may be delayed if symptoms such as musculoskeletal pain or cough are not recognized as cancer-related. American Society of Clinical Oncology guidelines for surveillance in breast cancer are summarized in Table 23-1 .
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