Attention A T users. To access the menus on this page please perform the following steps. 1. Please switch auto forms mode to off. 2. Hit enter to expand a main menu option (Health, Benefits, etc). 3. To enter and activate the submenu links, hit the down arrow. You will now be able to tab or arrow up or down through the submenu options to access/activate the submenu links.

HIV/AIDS

Quick Links

Veterans Crisis Line Badge
My healthevet badge

Cancer Screening

for Health Care Providers

Cancer Screening

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary. Consult VA pharmacists for alternatives.

Key Points

General recommendations from the United States Preventive Services Task Force (USPSTF) regarding cancer screening include the following:

  • Men and women at average risk should be screened for colorectal carcinoma (CRC) starting at age 50, using fecal occult blood testing (FOBT), flexible sigmoidoscopy with or without FOBT, or colonoscopy. Office-based digital rectal examination (DRE) plus FOBT should not be used.
  • Women aged 50 and older at average risk should be screened every 1-2 years for breast cancer using mammography.
  • Sexually active women should be screened every 3 years for cervical cancer using the Papanicolaou ("Pap") smear.
  • There is not adequate evidence to recommend for or against screening men for prostate cancer.

These recommendations may be applied to HIV-infected patients with CD4 counts of >350 cells/µL or completely suppressed HIV RNA. For patients with lower CD4 counts, screening should be discussed in the context of the patient's prognosis, preferences, and health goals.

Background

HIV-infected persons are at higher risk than HIV-uninfected persons of developing AIDS-defining cancers as well as many non-AIDS-defining cancers (NADC), despite the effective use of antiretroviral therapy. HIV infection is particularly associated with a higher incidence of cancers attributable to an infectious etiology (eg, Hodgkin lymphoma, hepatocellular carcinoma, anal carcinoma) as well as cancers associated with cigarette smoking (lung, kidney, and laryngeal). HIV-infected individuals have a higher death rate attributable to many NADC than their HIV-uninfected counterparts.

Cancers occurring at a higher rate in the HIV-infected population include the following:

  • AIDS-Defining Cancers
    • Kaposi sarcoma
    • Cervical carcinoma
    • Non-Hodgkin lymphoma (including primary CNS lymphoma, and primary effusion lymphoma)
  • Non-AIDS-Defining Cancers
    • Anal squamous cell carcinoma (SCC)
    • Colorectal carcinoma
    • Lung cancer
    • Skin cancer, including melanoma
    • Oropharyngeal cancer
    • Vaginal cancer
    • Hodgkin lymphoma
    • Hepatocellular carcinoma

HIV-infected patients with chronic HBV or HCV infection may be at much higher risk of developing hepatocellular carcinoma than those without HIV coinfection (see Liver Disease).

  • Although the rates of many NADC are higher in HIV-infected individuals, in general, screening recommendations for most cancers are the same as for HIV-uninfected individuals, as outlined by the USPSTF. However, physicians may need to tailor their recommendations based on individual patient risk factors and in situations where no guidelines exist for screening (such as screening for anal SCC).
  • Of the cancers on this list, the USPSTF has issued screening recommendations regarding cervical and colorectal cancers, which are presented in this chapter. In addition, this chapter includes USPSTF recommendations on screening for breast cancer and prostate cancer. Additional screening recommendations can be found in other chapters (see Anal Dysplasia; Liver Disease; GERD; and Women's Health).
  • Because most cancer screening requires a 5- to 10-year life expectancy to show a favorable cost/benefit ratio, it is reasonable to screen HIV-infected persons for cancer if they have a CD4 count of >350 cells/µL or a suppressed HIV viral load. Screening patients with more advanced HIV disease is unlikely on average to extend life expectancy or be cost-effective, and should be discussed with patients in the context of their prognosis, preferences, and health goals. However, screening for cervical carcinoma is recommended for all HIV-infected women, regardless of CD4 count.
  • For cancers in which there is a hereditary component of risk, the following definitions of degree of relatedness are used:
    • 1st-degree relative: a parent, sibling, or child
    • 2nd-degree relative: a grandparent, uncle, or aunt
    • 3rd-degree relative: a great-grandparent or cousin

Colorectal Cancer

Summary

Most CRC arises from adenomatous polyps, which grow relatively slowly; polyps and colorectal tumors can be detected with varying degrees of sensitivity by any one of several screening techniques, including FOBT, endoscopic visualization and biopsy (flexible sigmoidoscopy and colonoscopy). The incidence of CRC increases with age. The USPSTF and the VA/DoD recommend that persons at average risk be screened for CRC starting at age 50. In persons at above-average risk, screening should start at an earlier age. The choice of screening procedure (see Table 1) depends on patient preferences and availability of procedures at particular facilities.

HIV-infected persons may be at slightly increased risk of CRC compared with HIV-uninfected persons.

Epidemiology/Pathogenesis

  • Most colon cancers develop from adenomatous polyps; polyps >1 cm in size carry a higher risk than smaller polyps of development of CRC.
  • Prevalence of adenomatous polyps increases with age.
  • Average lifetime risk of developing colon cancer in the United States is 6%.
  • The following confer a higher-than-average risk of developing CRC:
    • History of CRC in a 1st-degree relative
    • Family history of large polyps before age 60
    • Ulcerative colitis or Crohn disease
    • Polyps >1 cm in size
  • Patients with specific genetic predisposition to CRC such as familial adenomatous polyposis (FAP) or hereditary nonpolyposis colon cancer (HNCC) are at extremely high risk of developing CRC.

Screening Methods

  • FOBT: Detection of blood in a stool specimen, usually done by smearing a stool specimen onto absorbent paper impregnated with guaiac, followed by application of hydrogen peroxide; any blood present in the specimen will catalyze the oxidation of guaiac by peroxide, producing a rapid color reaction. Samples blood loss from any point in the GI tract. Specimens can be prepared at home using commercial test cards. High-sensitivity FOBT (Hemoccult II or SENSA) is recommended. Dietary modifications (eg, no red meat, no vitamins) prior to FOBT may not be necessary.
  • Flexible sigmoidoscopy: Examination of the colon from the rectum to the splenic flexure, a region in which the majority of malignant lesions arise, with a 60 cm flexible fiberoptic endoscope with biopsy capability.
  • Colonoscopy: Examination of the entire colon with a 100-160 cm flexible fiberoptic endoscope with biopsy capability.
  • Efficacy of screening methods is shown in Table 1.

Recommendations for CRC Screening

  • 80% of CRCs occur in people at average risk.
  • Multiple recommended screening methods for average-risk patients (see Table 1).
  • Screening recommendations for higher-risk patients are shown in Table 2.
  • Screening recommendations for persons at very high risk (individuals with, or relatives of persons with, familial colon cancer syndromes such as FAP or HNCC) are beyond the scope of this chapter; consultation with GI or Oncology is recommended.
  • FOBT on specimens obtained by DRE is not recommended.
    • DRE is not sensitive and ↓ FOBT specificity
    • If performed, a positive result should be followed up with colonoscopy
  • Fecal immunochemical test (FIT) and stool DNA test (sDNA) have not been recommended by the VA or the USPSTF.
  • Virtual colonoscopy is under investigation but is not yet recommended by the USPSTF.
  • Barium enema is no longer recommended by the USPSTF (lower sensitivity than recommended methods).
  • Screening of patients aged 76-85 is not routinely recommended.
  • Screening of patients > 85 years of age is not recommended.
Table 1. Recommended Screening Methods for Persons at Average Risk of Developing Colorectal Cancer
Screening Method Recommended by USPSTFAccuracy and EffectivenessComments/ Limitations/Risks
Colonoscopy every 10 years↓mortality >50%

Sensitivity:

  • 90% for polyps >1cm
  • 75% for polyps =1 cm
Colonoscopy has been the reference standard against which FOBT and sigmoidoscopy have been studied
Complete bowel prep required.

Colonoscopy can visualize entire colon. Suspicious lesions can be removed for biopsy and as treatment.

Greater yield of colonoscopy (most sensitive test for polyps) must be weighed against risks of perforation, bleeding, and conscious sedation, as well as inconvenience of full colonic preparation and conscious sedation.

Risk of screening colonoscopy
  • Any major complication: 0.3%
  • Perforation: 0.05%
  • Bleeding: 0.15-0.18%
Risk of colonoscopy as therapeutic procedure is higher
  • Perforation: 0.07-0.72%
  • Bleeding: 0.2-2.7%
Risks of procedure are greater in persons >70 years of age, but so are benefits, as proximal lesions are more common in this population.
Home FOBT every year↓ mortality 15-33%, depending on frequency of screening

Positive predictive value (percentage of patients with positive test result who have cancer or large polyp):

  • Rehydrated specimens: 6-8%
  • Unrehydrated specimens: 20-40%
Rehydration before adding developer:

  • ↑ sensitivity from 40% to >50%
  • ↓ specificity from 98% to 90%
  • Leads to more colonoscopies
Annual screening found 49% of cancers; 38% of patients tested required colonoscopy

Screening every 2 years found 39% of cancers; 28% of patients tested required colonoscopy
Patient submits three 2-window cards, 1 card each from 3 consecutive stools collected at home.

Do not use DRE to collect specimens.

The American Gastrointestinal Association (AGA) recommends against rehydrating specimens.

If result is positive in any card window, obtain colonoscopy.

FOBT itself is extremely low risk, but leads to many colonoscopies being performed, with associated risks of bleeding and perforation.
Flexible sigmoidoscopy every 5 years↓ mortality 59% for cancers within reach of sigmoidoscope

Sensitivity: 70-80%

Specificity difficult to define
Complete or partial bowel prep required.

Misses lesions proximal to the splenic flexure.

Proximal lesions more common in women than men.

Estimated to find 80% of patients with abnormal findings, as distal abnormalities will prompt examination of entire colon with colonoscopy.

In one study, sigmoidoscopy alone would have missed 65% of women with advanced lesions detected by colonoscopy.

In another study, 52% of patients with advanced proximal lesions (by colonoscopy) had no distal lesions.

Presence of an adenoma generally necessitates full colonoscopy. Controversy exists regarding presence of small tubular adenomas, though many providers would perform colonoscopy.

Complication rate:

  • Perforation: <0.01%
  • Bleeding: 2.5-5.5%
FOBT + flexible sigmoidoscopy every 5 years In one study, rigid sigmoidoscopy + 3-card FOBT (hydrated) detected 76% of advanced lesions vs 70% for sigmoidoscopy alone; 24% of advanced lesions were missed; incidence of death from cancer decreased by approximately 50% in sigmoidoscopy + FOBT group vs sigmoidoscopy alone

Studies of adding flexible sigmoidoscopy to FOBT show doubling of diagnostic yield
Positive FOBT result necessitates full colonoscopy, so perform FOBT before sigmoidoscopy.

Complete or partial bowel prep required before flexible sigmoidoscopy.

Print table

Table 2. Screening Recommendations for Persons at Increased Risk of Colorectal Cancer
Risk Factor*Screening Recommendations
* Not including characterized familial colon cancer syndromes
Adapted from Levin et al. See References.
Abbreviations: AP = adenomatous polyp; CD = Crohn disease; UC = ulcerative colitis
1st-degree relative with CRC or AP diagnosed ≥60 years of age

OR

Two 2nd-degree relatives with CRC or AP at any age
Screen as for person at average risk, but start at age 40.
1st-degree relative with CRC or AP diagnosed <60 years of age

OR

Two 1st-degree relatives with CRC or AP diagnosed at any age

Screening colonoscopy every 5 years, starting at age 40, or 10 years before age at which relative was diagnosed, whichever comes first.
2nd- or 3rd-degree relative(s) with CRCScreen as for person at average risk (see Table 1).
Inflammatory bowel disease (UC or CD) Colonoscopy every 1-2 years with biopsies for dysplasia.

Younger age at diagnosis of CD seems to increase risk, as does distal (colon) vs proximal (ileum) disease.
Personal history of CRC Patients with CRC should undergo high-quality perioperative colonoscopy to detect synchronous lesions. Colonoscopy should be performed 1 year after the resection (or 1 year following the colonoscopy that confirmed absence of synchronous disease). If the examination performed at 1 year is normal, then the next examination should be performed in 3 years. If that colonoscopy is normal, then the interval to the subsequent examination should be 5 years. Following the examination at 1 year, the intervals between subsequent examinations may be shortened if there is evidence of HNCC or if adenoma findings warrant earlier colonoscopy.

If an obstructing tumor prevents high-quality colonoscopy at the time of resection, examination for synchronous tumors can be performed by double-contrast barium enema or CT colonography.

After low anterior resection of rectal cancer, periodic examination of the rectum may be considered to identify local recurrence. This usually is performed at 3- to 6-month intervals for the first 2 or 3 years.

Print table

Reminders

CPRS reminder definition and resolution options for CRC screening may differ among VA Medical Centers, depending on local decisions and procedure availability. An example of a typical CPRS reminder for CRC screening is shown.

Figure

What to do with a positive result

  • A positive screening result should be followed by a full colonoscopy, unless contraindicated.
  • Patients with negative screening but with symptoms suggestive of CRC or polyps should be offered a full colonoscopy.

Breast Cancer

Summary

Breast cancer is the most common cancer diagnosed among women in the United States. There is no clear evidence that HIV infection increases the risk of breast cancer or alters treatment outcomes; a 2009 metaanalysis suggests that the risk of breast cancer since the availability of effective combination ART became widespread appears to have increased compared with the earlier years, but that may be attributable to increased survival of HIV-infected patients rather than to a true increased risk of breast cancer. Incidence of breast cancer increases with age, and there is evidence that mammographic screening reduces both incidence and disease-specific mortality. Most cases of breast cancer are detected by mammography. Current USPSTF guidelines recommend mammogram screening every 2 years for women not at elevated risk of breast cancer. Whereas the benefits of starting screening for women older than 50 are well established, there has been considerable debate about starting screening at age 40. The rate of false-positive screening results in women 40-50 years of age is high, and the benefits of screening need to be weighed against the potential for emotional distress and additional testing caused by false-positive results. In light of a 2009 study that found limited benefit of screening women under 50 years of age, the current USPSTF guidelines recommend against routine screening for breast cancer in women aged 40-49. Clinical breast examination (CBE) may be part of screening, depending on patient and provider preference. Breast self-examination (BSE) is no longer routinely recommended by the USPSTF.

Epidemiology

Lifetime risk of invasive breast cancer in U.S. women is approximately 12.5%; breast cancer is the most common cancer among women in the United States, and the second most common cause of cancer death among women in the United States (after lung cancer).

Women at increased risk of breast cancer are those with:

  • Family history of breast cancer in a 1st-degree relative
    • Risk higher if multiple 1st-degree relatives with breast cancer
    • Risk higher if affected relatives were <40 years of age when diagnosed
  • Women with a specific mutation conferring risk of breast cancer, such as BRCA1 or BRCA2
  • History of atypical hyperplasia on previous breast biopsy
  • History of first pregnancy after age 30
  • Increased estrogen exposure
    • Early menarche or late menopause
    • Hormone replacement therapy
  • Older age
    • 0.4% annual incidence at age 30-39
    • 1.5% annual incidence at age 40-49
    • 2.8% annual incidence at age 50-59
    • 3.6% annual incidence at age 60-70

Breast cancer in women <40 years of age appears to be less common but more aggressive. Thus, screening may have less of a protective effect than it does for older women. The increased density of breast tissue in younger women also may reduce the ability of mammography to detect abnormalities.

Screening methods

  • Mammography involves low-dose radiography of the breasts. It should be performed at an accredited, certified facility, with interpretation by an appropriately trained and certified radiologist.
  • CBE and BSE are no longer routinely recommended.
  • MRI may be useful for women at high risk of breast cancer, who have a need for screening at a younger age, or who have particularly dense breasts. MRI is not routinely recommended for screening women who are not at elevated risk of breast cancer.

Effectiveness of screening

  • Mammography is less reliable (lower sensitivity, specificity, and positive predictive value) in younger women than in older women.
  • Sensitivity of mammography is 77-95%.
  • Specificity of one-time mammogram is 94-97%.
  • Positive predictive value of one-time mammography:
    • 2-22% of women with an abnormal result will require further workup
    • 12-78% of women with an abnormal result will require biopsy
  • Mammography reduces breast cancer-specific mortality as much as 32%, depending on the study; metaanalysis finds a reduction in disease-specific mortality of about 15%, including among women <50 years of age.
    • Improvements in the relative risk of death due to breast cancer for women screened with mammography: age 39-49: RR=0.85; age 50-59: RR=0.86; age 60-69: RR=0.68; age 65- 74: RR=0.78. Benefits to women older than 75 years of age have not been demonstrated.
  • MRI in high-risk women without breast cancer has a sensitivity of 71-100% and a specificity of 81-97%.
  • There is no evidence at present that CBE reduces breast cancer-specific mortality.
  • Two available studies have indicated no mortality benefit from BSE and an increase in the number of biopsies and additional imaging studies required.

Recommendations for breast cancer screening

  • Providers should screen patients for an elevated risk of breast cancer and tailor screening for those at higher risk.
  • In women without an elevated risk of breast cancer, conduct screening mammography every 2 years for women 50-69 years of age.
  • Providers should discuss screening with women aged 70 and older, taking into account estimated life expectancy and presence of comorbid disease.

Reminders

CPRS reminder definition and resolution options for mammography may differ among VA Medical Centers, depending on local decisions. An example of a typical CPRS reminder for annual mammography is shown.

Figure

What to do with a positive result

  • Results should be communicated to the patient as soon as possible. Generally, a lay summary will be sent to the patient by the interpreting radiologist. However, the ordering provider should ensure that results have been communicated to the patient within a reasonable time frame.
  • Patients with an abnormal result should be referred to the appropriate service (Women's Health, Gynecology, or General Surgery, depending on the facility) as soon as possible for evaluation and possible biopsy.

Cervical Cancer

Summary

Although there are no randomized controlled trials showing the effectiveness of cervical cancer screening, numerous observational studies have found an association between screening and reductions in the incidence of cervical cancer and disease-specific mortality.

HIV-infected women are at elevated risk of cervical dysplasia and cervical cancer. Cervical cancer is highly associated with type 16 and 18 human papillomavirus (HPV) infection (high-risk subtypes). HPV prevalence is higher among HIV-infected women than among HIV-uninfected women, and HIV-infected women have increased persistence of HPV and greater likelihood of infection with high-risk types of HPV. Although the time between diagnosis of carcinoma in situ (CIS) and development of invasive disease is shorter among HIV-infected women who are not on ART than among HIV-uninfected women, ART has not been shown consistently to prevent or alter the course of cervical dysplasia in HIV-infected women. Women with advanced immunosuppression (CD4 count of <200 cells/µL) are at higher risk of cervical abnormalities than women with CD4 counts of >200 cells/µL. Vaccination against HPV has been shown to be effective in preventing cervical dysplasia in HIV-uninfected women; studies in HIV-infected women are ongoing.

The USPSTF and VA/DoD recommend cervical cancer screening using Pap smear or liquid-based cytology in sexually active women with a cervix. In sexually active women, screening should be started at age 21. For HIV-infected women, most authorities recommend more frequent screening than for HIV-uninfected women.

Epidemiology/pathogenesis

Cervical cancer is associated with genital HPV infection; cancer is preceded by identifiable neoplastic changes (cervical intraepithelial neoplasia, or CIN) in the transformation zone of the cervix. Localized cervical cancer is highly curable (5-year survival of 92%), whereas disseminated disease is not (5-year survival of 13%). HIV-infected women progress from CIS to invasive disease faster than HIV-uninfected women. Cervical cancer is an AIDS-defining condition.

Women at increased risk of cervical cancer include those with:

  • Immunosuppression (including HIV infection)
  • Tobacco use (smoking)
  • Increased risk of HPV infection, such as:
    • Earlier onset of sexual intercourse
    • Multiple sexual partners
    • Sexual partners who have had multiple sexual partners

Screening methods

  • Pap smear: Cervical epithelial cells, collected by brush and spatula, are either smeared directly on a slide and fixed, or suspended in a liquid fixative and spun onto a slide. Liquid-based cytology is preferred, if available, owing to its higher sensitivity. The smear should be examined by an experienced cytopathologist.
  • Cervical detection of HPV has higher sensitivity but lower specificity than traditional Pap smear for cervical cancer. The 2003 USPSTF recommendations do not propose HPV DNA testing as a screening method in HIV-infected women. However, recent data suggest that in women with CD4 cell counts of >500 cells/µL, the combination of a normal PAP smear and the absence of oncogenic HPV is associated with a low risk of cervical dysplasia in the subsequent 3 years.

Effectiveness of Screening and Screening Interval

  • Sensitivity of a single Pap smear for high-grade CIN is 60-80%; specificity is approximately 98%.
  • Effectiveness of cervical cancer screening on incidence and mortality of cervical cancer has not been studied prospectively. Nevertheless, data from good-quality case-control and ecological studies show a strong association between screening and reductions in cervical cancer incidence and disease-specific mortality.

Screening recommendations

  • Screen HIV-infected women at the time of diagnosis and 6 months thereafter.
  • If initial results are normal, rescreen annually if CD4 count is >200 cells/µL or every 6 months if CD4 count is <200 cells/µL.
  • HIV-infected women also should be screened annually for anal carcinoma using Pap smears (see Anal Dysplasia).
  • Because of the increased risk of vaginal cancer associated with HIV infection, HIV-infected women with a history of high-grade CIN or invasive cervical cancer should be screened with regular vaginal cuff Pap smear following hysterectomy.

Reminders

Because the frequency of recommended screening for cervical cancer differs between HIV-infected and HIV-uninfected women, the standard CPRS reminder for cervical cancer screening generally is not applicable to the former. HIV providers should work with the local Information Resource Management Service to construct HIV-specific reminders for cervical cancer screening.

What to do with a positive result

  • Most experts recommend more aggressive management of HIV-infected women than HIV-uninfected women, while some recommend the same management regardless of HIV serostatus.
  • The following recommendations are based largely on the 2006 consensus guidelines of the American College of Obstetrics and Gynecology for management of cervical abnormalities, regardless of HIV serostatus (see Table 3):
    • ASCUS, LSIL, and HSIL refer to cytologic grade of cervical abnormality.
    • CIN refers to histologic grades of cervical abnormality. CIN 2 and CIN 3 are considered high-grade precursors of cervical cancer.
Table 3. Management of Women with Abnormal Cervical Cytology on Screening
Cytology ResultNext StepComments
Refers to the management of adult women only, and not to adolescents, pregnant women, or the elderly.
Adapted from Wright TC Jr, Massad LS, Dunton CJ, et al. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol. 2007 Oct;197(4):346-55.
Atypical Squamous Cells of Undetermined Significance (ASCUS)
  • Refer for colposcopy
    Could consider:
  • HPV testing for oncogenic subtypes
    OR
  • Repeat cytology (Pap)
There is controversy about management of ASCUS in HIV-infected women:
  • Many authorities recommend that all HIV-infected women with ASCUS be referred for colposcopy.
  • In HIV-infected women, there are insufficient data to recommend HPV DNA testing for oncogenic HPV types as part of management of ASCUS.
  • If colposcopy is chosen, and no CIN is found, repeat cytology at 12 months.
  • If HPV testing is chosen, reflex HPV testing of samples collected during cytologic screening is preferred, for patient's convenience. This requires liquid-based cytology or samples collected specifically for HPV testing and held. Otherwise, HPV testing requires another Pap smear.
    • If HPV negative, repeat cytology at 12 months.
    • If HPV positive, manage as for LSIL (below).
  • If repeat cytology is chosen, repeat at 6-month intervals until 2 consecutive negative tests, then return to normal screening interval. If repeat shows ASCUS or higher, refer for colposcopy.
Atypical Squamous Cells/cannot exclude HSIL (ASC-H)
  • Refer for colposcopy
If no CIN 2 or 3 is found on colposcopy, perform cytology at 6 and 12 months, or HPV testing at 12 months. If above are negative, return to regular cytologic screening schedule.
Low-Grade Squamous Intraepithelial Lesion (LSIL)
  • Refer for colposcopy
If no CIN 2 or 3 is found on colposcopy, perform cytology at 6 and 12 months, or HPV testing at 12 months. If above results are negative, return to regular cytologic screening schedule.
High-Grade Squamous Intraepithelial Lesion (HSIL)
  • Refer for colposcopy or loop electrosurgical procedure (LEEP)
  • If no CIN 2 or 3 is found, multiple options include: colposcopy and cytology every 6 months for 1 year as long as colposcopy is adequate and cytology is negative; excisional diagnostic procedure.
  • If colposcopy is chosen, excisional procedure is indicated if repeat colposcopy shows HSIL or is unsatisfactory. If repeat colposcopies are negative, return to routine cytologic screening.

Print table

See also Women's Health

Prostate Cancer

Summary

In contrast to screening for colorectal, breast, and cervical cancer, there is controversy over whether to screen men for prostate cancer. The VA/DoD does not recommend routine screening, whereas the USPSTF recommends against routine screening. The American Cancer Society (ACS) and the American Urological Association (AUA) favor annual screening for all men at age 50, and for higher-risk men at age 45, as long as they have a life expectancy of ≥10 years, following discussion about the potential risks, benefits, and uncertainties of screening. Although screening is effective at detecting prostate cancer in its early stages, it is not clear that screening reduces disease-associated or overall mortality. Likewise, the effect of treating prostate cancer in its early stages on overall mortality is not clear, and treatment, whether by prostatectomy or radiation, carries a substantial risk of side effects such as urinary incontinence and sexual dysfunction (see below).

Epidemiology

  • Lifetime risk of developing prostate cancer is 16% among men in the United States.
  • 10-year risk of developing prostate cancer increases with age, from 0.17% at age 40 to 6.46% at age 60.
  • Lifetime risk of death caused by prostate cancer is 3% among men in the United States.
  • Most deaths resulting from prostate cancer occur at age >65.
  • Disease confined to the prostate gland at diagnosis carries a better prognosis than disease extending beyond the gland.
  • Incidence of disease and mortality are greater among African American men than among white men in the United States, and among men with a 1st degree relative with prostate cancer.

Screening methods

  • Screening for prostate cancer includes measurement of serum prostate-specific antigen (PSA) combined with DRE.
  • Prognosis is associated with degree of differentiation of tumor cells (Gleason score) on biopsy and whether disease is confined to the gland or is extraprostatic. Higher Gleason scores (indicating less-differentiated cells) and extraprostatic disease confer a worse prognosis.
  • Elevated PSA is associated with prostate cancer, and with benign prostate abnormalities such as benign prostatic hyperplasia (BPH), prostatitis, and trauma to the gland.
  • The higher the PSA, the higher the likelihood of prostate cancer, and the higher the likelihood that the cancer has spread beyond the prostate gland:
    • PSA ≤4 ng/mL is classified as "normal." Although up to 27% of men with a PSA <4 ng/mL will have cancer, most of these will have disease confined to the gland.
    • PSA >4 ng/mL is classified as "elevated." Approximately 1 in 3 men with elevated PSA will actually have cancer. For PSA 4-10 ng/mL, 1 in 4 men will have cancer. Most of these cancers will be confined to the gland, but the low positive predictive value of the test means that many men will undergo unnecessary biopsy. For PSA >10 ng/mL, up to two thirds of men will have cancer and more than half of those cancers will be extraprostatic.

Treatment for early prostate cancer: Side effects and benefits

  • Treatment consists of active surveillance (watchful waiting), prostatectomy, or radiation therapy.
  • Risk of persistent (at least 12 months in duration) side effects from radical prostatectomy:
    • Impaired sexual function: 20-70%
    • Urinary incontinence: 15-50%
  • Risk of persistent (at least 12 months in duration) side effects from external-beam radiation therapy:
    • Impaired sexual function: 20-45%
    • Urinary incontinence: 2-16%
    • Bowel problems: 6-25%
  • When compared with watchful waiting, radical prostatectomy following clinical detection of moderately to well-differentiated prostate cancer confined to the gland decreases disease-specific mortality. The effect on overall mortality is less clear. Whether this applies to cancer detected by screening is also not clear.

Effectiveness of Screening

  • When analyzed properly, the one randomized trial of screening with PSA and DRE vs no screening showed no mortality benefit from screening.
  • Additional prospective trials of screening effectiveness are ongoing.

Screening recommendations

  • Patients should be counseled annually regarding the risks and benefits of screening for prostate cancer by PSA and DRE; screening may be performed if desired by the patient.
  • Depending on Veterans Integrated Service Network (VISN), facility, and clinician decision making, prostate cancer screening may be offered to patients deemed to be at increased risk.

Reminders

CPRS reminder definition and resolution options for prostate cancer counseling and screening may differ among VA Medical Centers, depending on local decisions. An example of a typical CPRS reminder for annual prostate cancer counseling and screening is shown.

Figure

What to do with a positive result

  • Refer to urologist for transrectal ultrasound (TRUS) and biopsy for:
    • Elevation in PSA (PSA >4 ng/mL)
    • Prostatic abnormality (asymmetry, nodule, or induration of the gland) on DRE

Anal Cancer

See chapter Anal Dysplasia

References