Cancer screening Dr V.Mehrzad Hematologist&Oncologist

Cancer screening is synonymous with secondary prevention, in which earlier therapeutic intervention is possible through screening an asymptomatic population to identify cancer at an earlier stage than it would have been diagnosed in the absence of screening

The expectation is that early diagnosis and treatment lead to a reduction in mortality from the disease and/or a reduction in the severity of the disease

Principles of Screening 1-The disease should be an important public health problem in terms of its frequency and/or severity 2-The natural history of the disease presents a window of opportunity for early detection 3-An effective treatment should be available that favorably alters the natural history of the disease 4-A suitable screening test should be available, that is, one that is accurate, acceptable to the population, fairly easy to administer, safe, and relatively inexpensive

Methods of Screening for Colorectal Cancer Colorectal cancer screening is unique in that there are at least five screening methods that are recommended in existing guidelines

Fecal Occult Blood Testing Although it remains the only method to have been proven effective in replicated randomized trials against usual care, after years of increasing, the rates of screening by FOBT have been declining in general

These immunochemical tests have been studied in case-control studies, particularly in Japan, and by comparing them to the older guaiac-based tests in general have shown themselves to have lower rates of false positivity and equal or greater sensitivity for polyps

Stool DNA Testing such methods will need to be evaluated in large populations to determine efficacy relative to already accepted methods of screening

Endoscopy Rigid Proctoscopy/Sigmoidoscopy It is estimated that flexible sigmoidoscopy will find 60% to 83% of cancers and polyps found by colonoscopy Colonoscopy, which allows a complete examination of the rectum and colon to the cecum, has become the screening method for colorectal cancer preferred by gastroenterologists and many other physicians and public health experts

NCCN consensus guidelines  The National Comprehensive Cancer Network (NCCN), a multispecialty panel, issued revised screening guidelines for CRC in January 2010 These guidelines recommend colonoscopy every ten years, when available, as the preferred screening strategy Suggested alternatives are annual stool testing with guaiac or immunochemical reagent; or sigmoidoscopy every five years with or without annual stool testing The NCCN advises barium enema only when colonoscopy cannot be performed and did not come to consensus regarding CT colonography or fecal DNA as screening modalities

Screening for breast cancer  Major risk factors for breast cancer in women are age, genetic predisposition and estrogen exposure

IMAGING STUDIES Mammography remains the mainstay of screening for breast cancer Ultrasonography is commonly used for diagnostic follow-up of an abnormality seen on screening mammography, to clarify features of a potential lesion The role of magnetic resonance imaging (MRI) for breast cancer screening is emerging; currently MRI screening, in combination with mammography is targeted to high risk patients Newer tests, such as tomography, are under evaluation

Full-field digital mammography  Full-field digital mammography is similar to traditional film-screen mammography except that the image is captured by an electronic detector and stored on a computer film mammography remains an acceptable screening modality for all women Digital mammography, when available, may offer a small screening advantage in women younger than 50 years old

Frequency of mammography An observational study comparing mammogram screening annually or every two years for predominantly Caucasian women aged 50 to 69 years in Vermont, US (annual) and Norway (biennial) found no significant difference in breast cancer detection rate or prognostic stage

Screening with mammography The American Cancer Society , American College of Radiology , American Medical Association , the National Cancer Institute , the American College of Obstetrics and Gynecology and the National Comprehensive Cancer Network (NCCN)  recommend starting routine screening at age 40 The American Academy of Family Physicians recommends screening mammography every one to two years for women ages 40 and older

 The USPSTF recommends biennial mammography screening for women who are screened Most other North American groups recommending screening for women in their 40s have tended to shift towards annual examinations because of the evidence of more rapid tumor growth in younger women

The American Cancer Society recommends clinical breast examination every three years from age 20 to 39, and annually thereafter The US Preventive Services Task Force concludes that evidence is insufficient to assess additional benefits of clinical breast examination beyond mammography, and the Canadian Task Force on Preventive Health Care recommends clinical breast examination with mammography every one to two years beginning at age 40 and 50, respectively The World Health Organization does not recommend clinical breast examination No group recommends clinical breast examination alone

Guidelines from the National Comprehensive Cancer Network (NCCN) recommend annual breast MRI in addition to mammography for women with a strong family history or genetic predisposition The criteria specified include: BRCA 1 or 2 mutation carriers Untested women who have a first degree relative with a BRCA 1 or 2 mutation Lifetime risk of breast cancer of 20 to 25 percent or more, defined by models that are largely dependent on family history (eg, BRCAPRO and others) Received radiation treatment to the chest between ages 10 and 30 Genetic mutation in the TP53 or PTEN genes

Cervical cancer  Cervical cancer screening guidelines in the US are issued by three major organizations: the US Preventive Services Task Force (USPSTF) , the American Cancer Society (ACS) , and the American College of Obstetricians and Gynecologists (ACOG)

Starting age   All three organizations strongly recommend screening for cervical cancer 2009 ACOG guidelines recommend initiating screening at age 21; older guidelines from the USPSTF and ACS recommend initiating screening at age 21 or three years after the onset of sexual activity, whichever comes first

 The USPSTF recommends stopping screening at age 65, and the ACS suggests stopping at age 70 for women who have had adequate recent screening with normal Pap smears and are not otherwise at high-risk; ACOG states it is reasonable to discontinue screening in women at 65 to 70 years of age who have had three or more consecutive normal smears, and no abnormal results in the previous ten years

 The USPSTF recommends screening at least every three years; ACS advocates annual screening (biennial if using liquid-based testing) and ACOG biennial for women under age 30 and reducing the frequency to every two to three years for women aged 30 and older who have had three consecutive normal Pap tests, or no more than every three years if they also are tested for HPV DNA

 Both ACS and ACOG allow for screening using liquid based cytology or a combination of cytology plus HPV testing (the latter for women 30 and older) When screening is performed with combination of cytology and HPV test, both ACS and ACOG recommend that the screening interval be no more often than every three years The USPSTF makes no recommendation for or against liquid-based technology or HPV testing, due to insufficient evidence

prostate cancer The American Cancer Society (ACS) emphasizes the need for involving men in the decision whether to screen for prostate cancer Men need to have sufficient information regarding the risks and benefits of screening and treatment to make an informed and shared decision; providing them with a decision aid may facilitate the decision-making process For men who decide to be screened, the ACS recommends PSA testing with or without DRE for average-risk men beginning at 50 years of age Screening should not be offered to men with a life expectancy less than 10 years

Men whose initial PSA level is greater than or equal to 2 Men whose initial PSA level is greater than or equal to 2.5 ng/mL should undergo annual testing; men with a lower initial level can be tested every two years

The guidelines also recommend beginning screening discussions at age 40 to 45 in patients at high-risk of developing prostate cancer (eg, black men and men with a first-degree relative with prostate cancer diagnosed before age 65) The guideline also recommends keeping the biopsy referral threshold at 4.0 ng/mL

Screening for ovarian cancer Clinical studies of ultrasonography and the CA 125 radioimmunoassay have so far been too small to provide sufficient support to justify a policy of routine ovarian cancer screening for most women

No definitive large randomized controlled trials have been completed to show whether any screening strategy decreases mortality from ovarian cancer Nevertheless, a practical clinical approach to the issue of screening can be based upon assessment of an individual woman's risk of ovarian cancer

Women at average risk Screening for ovarian cancer with CA 125 or ultrasound is not currently recommended for premenopausal and postmenopausal women without a family history of ovarian cancer

The predictive value of either test alone (less than 3 percent) yields an unacceptably high rate of false-positive results and attendant morbidity and costs

Women at higher risk Postmenopausal women with this type of limited family history may be reasonable candidates for screening because of an elevated risk of developing ovarian cancer For women who desire screening, a strategy of annual CA 125 testing with transvaginal ultrasound in women with CA 125 levels above 30 U/mL is the approach that is best supported by existing data

Women with a suspected hereditary ovarian cancer syndrome should be referred to a genetic counselor for consideration of testing for BRCA1 and BRCA2 mutations

Women who are found to have BRCA1 and/or BRCA2 mutations should be referred to a gynecologic oncologist for follow-up Protocols in clinical use for surveillance of such women include combinations of pelvic examinations, CA 125 and other tumor marker measurements, vaginal ultrasonography, and color Doppler imaging

The optimal interval for screening has not been determined Expert groups have recommended a six-month interval , and this is a reasonable option However, the evidence indicate limited effectiveness of screening in this population, and physicians and patients should not be falsely reassured by negative screening test results

Prophylactic oophorectomy at the completion of childbearing or by age 35 has generally been recommended for women with hereditary ovarian cancer syndromes Evidence from prospective and retrospective studies of women with BRCA1 or BRCA2 mutations demonstrated a substantial reduction in subsequent ovarian and breast cancers in women who had prophylactic oophorectomy compared with those undergoing surveillance only

Screening for lung cancer Systematic screening with either CT or chest x-ray is not unequivocally recommended by any major professional organization The US Preventive Services Task Force (USPSTF) concluded that current evidence was insufficient to recommend for, or against, screening for lung cancer

Lung cancer is the leading cause of cancer-related death Prevention (promoting smoking cessation) is likely to have far greater impact on lung cancer mortality than is screening

Early trials of chest x-ray screening in males at high risk for lung cancer found no mortality benefit for x- ray alone or x-ray plus sputum cytology Screening CT scans in high risk groups identify a high prevalence of stage 1 lung cancer and greater than 50 percent prevalence of benign nodules There are no data yet available from randomized studies of CT scanning

While awaiting results from ongoing randomized control trials, we suggest not screening asymptomatic individuals for lung cancer outside of a clinical trial Plain chest X-ray has been shown to be ineffective for lung cancer screening For individuals committed to screening for lung cancer, we suggest screening with chest CT

Screening and early detection of melanoma The clinician examination for skin cancer and ascertainment of risk factors can be carried out in tandem, taking only a few minutes, with a source of bright light and a magnifying lens Melanomas can occur anywhere on the skin surface, but are frequently located on the back and other areas that may be easy to miss with self-inspection

Superfacial spreading melanoma

Nodular melanoma

Lentigo maligna melanoma

Acral lentiginous melanoma

The A, B, C, D, Es of melanoma recognition are valuable for patient education and for all clinicians : Asymmetry Border irregularities Color variegation (ie, different colors within the same region) Diameter greater than 6 mm Enlargement or evolution of color change, shape, or symptoms

A seven point checklist was designed in England and is a sensitive screening test for the early detection of melanoma. The checklist includes three major features : Change in size Change in color Change in shape There are also four minor features : Inflammation Bleeding or crusting Sensory change Lesion diameter greater than 6 mm

The American Cancer Society recommends that all adults receive at least a baseline total body skin cancer screening examination from a clinician, with subsequent skin examinations at the clinician's discretion as determined by risk status