In women, the most common cancers are breast, lung, and colorectal. In men, they are prostate, lung, and colorectal. The types of cancer that best meet the criteria for screening are breast cancer, cervical cancer, colorectal cancer, lung cancer, melanoma, and urologic cancer. Table 12-1 presents the American Cancer Society’s 2017 recommendations for early cancer detection. See also Chapter 13 in this volume.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.
Smith RA, Brooks D, Cokkinides V, Saslow D, Brawley OW. Cancer screening in the United States, 2013: a review of current American Cancer Society guidelines, current issues in cancer screening, and new guidance on cervical cancer screening and lung cancer screening. CA Cancer J Clin. 2013;63(2):88–105.
Though now surpassed by lung cancer as the most common cause of death in women older than 40 years, breast cancer remains the most common malignancy in women. The overall prevalence of breast cancer in the United States is 10%–12%. The age-adjusted incidence of breast cancer declined by 6.7% in 2003 (12% decline in women older than 50 years). This decrease was mostly due to a 50% reduction in the use of hormone replacement therapy (HRT). In the Women’s Health Initiative, a US National Institutes of Health randomized trial, HRT with estrogen and progesterone was associated with an increased risk of invasive breast cancer and abnormal mammograms. From 1989 to 2015, the breast cancer death rate in the United States decreased by 39%, although black women had a significantly higher death rate than white women. More than 75% of all breast cancers are cured with current therapy. Nevertheless, approximately 266,000 new cases of breast cancer and more than 41,000 related deaths were projected for the United States alone for 2018.
The importance of specific screening is increased by the presence of known risk factors, all of which are identifiable by patient history: (1) first-degree relative with breast, ovarian, or tubal cancer, (2) prior breast, ovarian, or tubal cancer, (3) nulliparity, (4) first pregnancy after age 30, (5) early menarche or late menopause, (6) radiotherapy to the chest between the ages 10 and 30, and (7) BRCA mutation status. Additional risk factors are high breast density, elevated serum estrogen or testosterone levels, a high-fat diet, obesity, and a sedentary lifestyle.
Table 12-1 American Cancer Society Recommendations for Early Cancer Detection in Asymptomatic Adult Patients, 2017
Approximately 42% of breast cancers detectable by mammography are not detectable by physical examination alone, and one-third of those found during mammographic screening are noninvasive or, if invasive, less than 1 cm in size. Because mammograms can yield false-negative results, the best detection strategy involves a physical examination plus mammography, followed by fine-needle aspiration or biopsy if either reveals an abnormality. Mammography has been shown to be safe as well as effective; the current low-dose radiation associated with it does not significantly increase the risk of radiation-induced cancer. False-positive results may lead to overtreatment; in the Canadian National Breast Screening study, the incidence of over-diagnosis was 22%.
Counseling alone is generally recommended for women with an average risk of breast cancer until 40 years of age. According to the recommendation by the US Preventive Services Task Force, mammographic screening should be performed every 2 years for average-risk women aged 50–75 years, and screening should be discussed with women from age 40. The American Cancer Society continues to recommend yearly mammography after age 45. In addition to general screening recommendations, assessment tools can help estimate an individual patient’s risk of breast cancer, for example, the Gail model (www.mdcalc.com/gail-model-breast-cancer-risk). Although the ideal mammographic screening interval is not clear, the American Cancer Society and US Preventive Services Task Force recommendations, as well as results from large studies done in the United Kingdom and Europe (eg, EUROSCREEN), continue to support the life-saving value of mammography.
Other modalities available for breast cancer screening include ultrasonography, digital mammography, and MRI. Because MRI of the breast is more sensitive but less specific than other methods, it should be used primarily in high-risk younger patients. Women with known mutations in the breast cancer 1 gene (BRCA1) or BRCA2 gene are at dramatically increased lifetime risk for breast and ovarian cancer and require more intensive counseling and surveillance, including yearly mammography and breast MRI.
DeSantis CE, Ma J, Goding Saur A, Newman LA, Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 2017;67(6):439–448.
Cervical cancer is the most common gynecologic cancer in patients between 15 and 34 years of age. Overall, approximately 12,000 cases of invasive cancer of the cervix (about 4000 resulting in death) and 45,000 cases of carcinoma in situ occur each year in the United States. Worldwide, approximately 86% of the 450,000 cervical cancer cases diagnosed each year occur in developing countries. Despite advances in the diagnosis and treatment of cervical cancer, approximately half the women with the disease worldwide will die. In many developed countries (including the United States), mortality has been reduced by more than 50% due to the implementation of cytologic screening. Cervical cancer is the eighth most common cause of cancer mortality in the United States. The incidence of cervical cancer in the nations of the European Union (EU) varies widely; the highest incidence is in Romania and the lowest is in Finland. As of 2017, screening for cervical cancer is recommended in 22 EU countries.
The risk factors for cervical cancer include the presence of high-risk serotypes of HPV, the number of lifetime sexual partners, low socioeconomic status, positive smoking history, use of corticosteroid contraceptive hormones, and a history of other sexually transmitted infections. More than 99% of all cervical cancers are positive for HPV. Early detection and appropriate treatment markedly reduce the morbidity and mortality from invasive cancer of the cervix. Cervical cancer is asymptomatic when it occurs in situ, and the most effective screening technique remains the Papanicolaou test (“Pap smear”). HPV can be detected with polymerase chain reaction assay techniques, and patients aged 30–65 years should consider receiving HPV testing at the time of their Papanicolaou test (“dual testing”). Vaccines to prevent HPV infection and its sequelae are discussed later in this chapter.
Curry SJ, Krist AH, Owens DK, et al; US Preventive Services Task Force. Screening for cervical cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;320(7):674–686.
Kahn JA. HPV vaccination for the prevention of cervical intraepithelial neoplasia. N Engl J Med. 2009;361(3):271–278.
Colorectal cancer is a major killer in developed countries, second only to lung cancer in incidence and mortality. In the United States, the cumulative lifetime probability of developing colon cancer is roughly 4.5%, and approximately one-third of affected individuals will die from this disease. Although the overall incidence of colorectal cancer in the United States has been declining since 1980, there has been a steady increase in the incidence of colorectal cancer in individuals under the age of 50.
Most authorities accept the theory that colorectal cancer develops from an initially benign polyp in a mitotic process that occurs over approximately 10 years. Colonoscopic removal or ablation of all polyps has become the standard of care where facilities and trained personnel are available. Factors associated with a higher risk of development of colon cancer include increased size and number of polyps, high-grade dysplasia or villous features on biomicroscopy, and sessile polyps only partially removed during a previous colonoscopy. Increased dietary fiber intake and reduced dietary fat intake have been associated with reduced risk of colorectal cancer. Also, calcium supplementation, multivitamins containing folic acid, and the use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a moderate reduction in the risk of recurrent colorectal adenomas.
It is estimated that the mortality rate of colorectal cancer could be reduced by more than 50% with widespread adoption of screening studies, for example, the guaiac-based fecal occult blood test (gFOBT), fecal immunochemical test (FIT), flexible sigmoidoscopy, and colonoscopy, with aggressive follow-up of patients with positive test results. Another stool-based screening test, fecal DNA testing, can detect molecular tumor markers associated with colorectal cancer. FIT and fecal DNA testing are easier to use and more sensitive than gFOBT, so patient adherence may be better.
Flexible sigmoidoscopy (every 5 years) and home gFOBT (annually) have been recommended in asymptomatic adults between 50 and 75 years of age. Recommendations remain controversial because of a lack of randomized trials. FIT, fecal DNA testing, and gFOBT are now accepted screening modalities by the American Cancer Society. Sigmoidoscopy offers good specificity but misses proximal cancers. Home gFOBT has been shown to decrease the mortality rate of colon cancer by up to 40%. For this test, 3 gFOBT cards are completed at home; a single gFOBT completed at the time of an annual physical examination is not sufficient.
Colonoscopy has been increasingly used as a screening test for asymptomatic patients older than 50 years. When results are negative in low-risk patients, the test is repeated every 10 years. Many of the lesions discovered with colonoscopy would not be detected with sigmoidoscopy. Yearly colonoscopy has been advocated in populations at very high risk, such as patients with familial polyposis and first-degree relatives of patients with colon cancer. The disadvantages of colonoscopy are its higher cost when compared with other screening methods, the number of trained personnel required to conduct the procedure, and the risks associated with intravenous sedation and of colonic perforation (approximately 0.2%). Colonoscopy’s advantage is its detection of suspicious polyps, which can then be removed, preventing progression to cancer.
CT colonography, another screening tool, may be able to screen out patients without neoplasia. Colonoscopy could then be reserved for only those patients with significant lesions. CT colonography may be preferable for those patients who are not healthy enough to undergo colonoscopy.
For persons older than 50 years, current American Cancer Society guidelines recommend a variety of screening tests, the exact method to be determined following discussion between the physician and the patient (see Table 12-1). In 2012, the European Council recommended only gFOBT screening for individuals between the ages of 50 and 74 years.
Lansdorp-Vogelaar I, von Karsa L; International Agency for Research on Cancer. European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition—Introduction. Endoscopy. 2012;44(Suppl 3):SE15–30.
Yang DX, Gross CP, Soulos PR, Yu JB. Estimating the magnitude of colorectal cancers prevented during the era of screening: 1976 to 2009. Cancer. 2014;120(18):2893–2901.
Accounting for 80%–90% of cases, the primary risk factors for squamous cell carcinoma of the esophagus are tobacco use and alcohol consumption. The main risk factors for adenocarcinoma of the esophagus are gastroesophageal reflux disease (GERD), obesity, and a history of Barrett esophagus (a complication resulting from long-standing GERD). Treatment for esophageal cancer has poor results; thus, prevention or elimination of the risk factors is worthwhile. The incidence of adenocarcinoma of the esophagus is increasing in developed countries, but squamous cell carcinoma remains dominant in developing areas. Currently, no effective preventive screening programs are available, and most patients present with advanced or metastatic disease.
Gastric cancer appears to be associated with certain geographic areas (Japan, China, Central and South America, Eastern Europe, and parts of the Middle East), high ingestion of nitrates, loss of gastric acidity, lower socioeconomic status, and blood type A. It remains the second most frequent and lethal malignancy worldwide. Although routine endoscopic screening is not cost-effective, widespread screening for and treatment of Helicobacter pylori infection in high-incidence populations could be an effective strategy for reducing gastric cancer in these groups. Further testing is recommended only for individuals in high-risk groups.
Pancreatic cancer is 2–3 times more common in heavy smokers than in nonsmokers, and it has also been associated with chronic pancreatitis, diabetes mellitus, and obesity. Familial pancreatic cancer represents only about 5%–10% of all cases but carries a higher mortality rate than sporadic pancreatic cancer. Several genetic mutations have been identified that are responsible for a small percentage of familial cases.
Hepatocellular cancer is more common in persons with preexisting liver disease, especially cirrhosis and hepatitis B and C.
Lung cancer is the leading cause of cancer-related deaths in men and women in the United States. Worldwide, there were 1.6 million deaths due to lung cancer in 2012. Among male patients with lung cancer in the United States, 85% are smokers. The number and percentage of cases in women have risen with the increased incidence of smoking in women. Fortunately, with the decreasing incidence of smoking, the incidence of and death rate from lung cancer in the United States have been declining. The usefulness of chest radiography and sputum cytologic screening in the general population is generally considered to be low. In high-risk patient groups, screening protocols effect a higher yield. In the US National Lung Screening Trial, lung cancer mortality in high-risk patients decreased when these patients were screened annually with low-dose helical chest CT. Positron emission tomography is a promising tool for identifying early malignant changes in the central airways; fluorescent bronchoscopy may also be useful for this purpose. New molecular markers detected in sputum and serum show promise in the future of lung cancer screening. Prevention through smoking cessation remains the most effective way to decrease lung cancer mortality.
Church TR, Black WC, Aberle DR, et al; National Lung Screening Trial Research Team. Results of initial low-dose computed tomographic screening for lung cancer. N Engl J Med. 2013;368(21):368:1980–1991.
Melanoma is the deadliest form of skin cancer, and its incidence is increasing faster than that of all other cancers. In the United States, about 1 in 75 persons will develop melanoma during his or her lifetime. According to the American Cancer Society, an estimated 91,270 new melanoma cases and 9320 related deaths were predicted in the United States in 2018.
Most melanomas probably arise from dysplastic nevi. Risk factors for melanoma include history of melanoma or atypical moles, presence of more than 50 moles, positive melanoma family history, history of previous nonmelanoma skin cancer, giant congenital nevus (>20 cm), xeroderma pigmentosum, treatment with UV-A and psoralens, frequent tanning with UV-A light, and a history of 3 or more severe (blistering) sunburns. Other, less significant risk factors are light complexion of the hair and eyes, freckles, inability to tan, indoor occupation with outdoor hobbies, and proximity to the equator.
UV damage probably causes most melanomas. Intense intermittent exposures are directly related to melanoma, whereas other skin cancers are more associated with cumulative exposure. UV radiation causes DNA damage, which is usually corrected by DNA repair enzymes; however, these DNA repair processes degrade with increasing age.
A pigmented lesion with any of the following characteristics, easily remembered by the ABCDE mnemonic, is suggestive of melanoma: asymmetrical lesions, border (irregular), color (variable), diameter (≥6 mm), and evolving (change in size, shape, or color). Other characteristics suggestive of melanoma are pruritus, bleeding, changing morphology, and new lesions or scalp lesions. Everyone should perform periodic self–skin examinations; suspicious lesions require referral to a dermatologist and possible biopsy. Avoiding the sun during peak hours and using sunblock can reduce the risk of melanoma and other skin cancers. In addition to providing simple visualization, when conducted by skilled examiners, dermoscopy (epiluminescence microscopy) can increase the specificity of clinical examination for the detection of melanomas.
In the United States, approximately 16% of new cancer cases per year are found in the prostate, bladder, kidney, and testes, with most of the common malignancies occurring in middle-aged and older men. Approximately 164,690 new cases of prostate cancer and nearly 29,430 related deaths are expected in 2018 in the United States. Although prostate cancer can sometimes be detected early by digital rectal examination (DRE) of the prostate, no effect on mortality has been demonstrated, so annual DRE is no longer recommended. Serum prostate-specific antigen (PSA) screening remains controversial, and data suggest that this screening does not affect mortality. The PSA false-negative rate varies between 15% and 38%, and only about 30% of patients with elevated PSA levels truly have prostate carcinoma. A trend of increasing PSA levels is a more sensitive indicator of prostate cancer than is an individual elevated PSA level. Because of the high rate of false-negatives, minimal disease identified by PSA screening, and the potentially significant adverse effects of treating minimal disease, routine yearly serum PSA screening is no longer recommended except for higher-risk individuals, such as African American men and those with a positive family history of prostate cancer. Instead, in 2017, the US Preventive Services Task Force recommended individualized discussion of the risks and benefits of prostate cancer screening for men between the ages of 55 and 69; this guidance is similar to that given by the European Society for Medical Oncology.
Although prostate cancer is a potentially lethal illness, many detectable prostate cancers are of little threat to life. Some studies suggest that more than 75% of men with screen-detected localized disease may not even need treatment. Some men with low-grade prostate cancer receive curative treatment, even though their disease may not require treatment. More specific screening methods are needed to allow differentiation between potentially lethal and nonlethal cancers.
Grossman DC, Curry SJ, Owens DK, et al; US Preventive Services Task Force. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;319(18):1901–1913.
Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.