cancer screening

Treatment Guidelines from The Medical Letter® Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication IN THIS ISSUE (starts on next page) Cancer Screening .p 87 Important Copyright Message The Medical Letter® publications are protected by US and international copyright laws Forwarding, copying or any distribution of this material is prohibited Sharing a password with a non-subscriber or otherwise making the contents of this site available to third parties is strictly prohibited By accessing and reading the attached content I agree to comply with US and international copyright laws and these terms and conditions of The Medical Letter, Inc For further information click: Subscriptions, Site Licenses, Reprints or call customer service at: 800-211-2769 FORWARDING OR COPYING IS A VIOLATION OF US AND INTERNATIONAL COPYRIGHT LAWS The Medical Letter publications are protected by US and international copyright laws Forwarding, copying or any other distribution of this material is strictly prohibited For further information call: 800-211-2769 Treatment Guidelines from The Medical Letter® Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication Volume 10 (Issue 124) December 2012 www.medicalletter.org Take CME exams Table of Contents: Breast Cervical Colorectal Lung Ovarian Prostate Page Page Page Page Page Page 88 89 89 91 92 93 Cancer Screening Table Cancer Screening Recommendations Recommended for Screening Age (yrs) Frequency Yes >402 Annual Yes Yes, combined with Pap test 21-29 30-65 30-65 Every yrs Every yrs3 Every yrs Yes See footnote See footnote See footnote >504 >504 >504 >504 Every 10 yrs5 Annual Every yrs Every yrs No — — Lung Low-dose CT scan Chest X-ray Sputum cytology See footnote No No 55-74 — — Unknown9 — — Ovarian CA-125 plus transvaginal ultrasound Carriers of BRCA1 or BRCA2 until they undergo RRSO Begin at age 30-3510,11 Every 6-12 mos Prostate Digital rectal exam PSA Yes Yes12 >40 >5013 Annual Annual or every years Breast Mammography1 Cervical Pap test HPV DNA screening Colorectal Colonoscopy Fecal occult blood6 Sigmoidoscopy Computed tomography colonography Double-contrast barium enema RRSO = risk-reducing salpingo-oophorectomy MRI and/or ultrasound may also be recommended for women at high risk or with dense breasts The US Preventive Services Task Force (USPSTF) recommends screening for women 50-74 years old If used without HPV testing In conjunction with HPV testing, the recommended interval is years For average-risk patients Positive family history: >40 yrs or 10 yrs earlier than the age at which the youngest affected relative was diagnosed African Americans: >40-45 yrs Patients with a history of colorectal cancer in a first-degree relative diagnosed before age 60 should be screened at 5-year intervals Patients with inflammatory bowel disease may be screened every year Fecal immunochemical tests are preferred over guaiac-based tests When colonoscopy is not available or the patient declines the procedure, flexible sigmoidoscopy and fecal occult blood tests are recommended alternatives Some guidelines also recommend computed tomography colonography as an option Colonoscopy should be used as a follow-up for positive results regardless of the noncolonoscopic screening test used Recommended only for former (quit in last 15 years) or present heavy smokers with >30 pack-year history Patients in the NLST trial were screened annually for years The most effective frequency or duration of screening is unknown 10 Or 5-10 years earlier than the earliest age of first diagnosis in the family 11 The National Comprehensive Cancer Network (NCCN) recommends starting at age 30 12 The USPSTF does not recommend PSA screening 13 The American Urological Association recommends starting at age 40 for all patients The American Cancer Society recommends starting at age 40 for African Americans and those with a family history of prostate cancer Federal copyright law prohibits unauthorized reproduction by any means and imposes severe fines 87 Cancer Screening Use of screening tests to identify cancers before they cause symptoms can lead to earlier therapy and may improve outcomes Screening tests for some common cancers are reviewed below BREAST Annual or biennial screening mammography can decrease breast cancer mortality in women 50-74 years old.1 WOMEN UNDER 50 — The mortality benefit of mammography screening for women in their 40s is less well established; no randomized controlled trials of screening have demonstrated statistically significant risk reductions, but most meta-analyses have found a decrease in breast cancer mortality with screening of women in this age group.2,3 Younger women have denser breasts, a higher incidence of false-positive results, a lower overall incidence of disease, and a higher incidence of fast-growing cancers WOMEN OVER 70 — Older women have the highest incidence of breast cancer The sensitivity and specificity of mammography is greatest in this population.4 POSSIBLE HARMS OF SCREENING — In one review, false-positive results occurred in 9.8% of women 40-49 years old and in 8.7% of those 50-59 years old per screening round.1 Other potential adverse consequences include unnecessary follow-up testing and surgery, anxiety, physical discomfort, and expense Over-diagnosis and over-treatment of clinically insignificant disease is possible, especially if ductal carcinoma in situ is found Theoretical concerns have been raised (though not well studied) about radiationinduced breast cancer from repeated exposure to mammography, but the potential benefits appear to outweigh the risks.5 NEW APPROACHES — Digital mammography has replaced film screen mammography in more than 70% of mammography centers in the US It is more accurate than film mammography in women 30 years old are less likely to be infected with HPV CLINICAL STUDIES — A randomized trial in 12,527 women found that women in their mid 30s who were screened with both tests had a 40% reduction in the risk of CIN or cancer at subsequent screening rounds, compared to those who were screened with a WHO/ICO information centre on HPV and cervical cancer Human papillomavirus and related cancers Summary report update November 15, 2010 Available at: http://apps.who.int/hpvcentre/statistics/dynamic/ ico/country_pdf/xwx.pdf?CFID=96657&CFTOKEN=53393793 Accessed November 12, 2012 EF Dunne et al Prevalence of HPV infection among females in the United States JAMA 2007; 297:813 M Plummer et al A 2-yr prospective study of human papillomavirus persistence among women with a cytological diagnosis of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion J Infect Dis 2007; 195:1582 AC Rodriguez et al Rapid clearance of human papillomavirus and implications for clinical focus on persistent infections J Natl Cancer Inst 2008;100:513 P Naucler et al Human papillomavirus and Papanicolaou tests to screen for cervical cancer N Engl J Med 2007; 357:1589 MH Mayrand et al Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer N Engl J Med 2007; 357:1579 ACOG ACOG Practice Bulletin No 131: Screening for cervical cancer Obstet Gynecol 2012; 120:1222 D Saslow et al American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer CA Cancer J Clin 2012; 62:147 US Preventive Services Task Force Screening for cervical cancer: current recommendation Available at http://www.uspreventiveservicestaskforce.org/uspstf/uspscerv.htm Accessed November 12, 2012 COLORECTAL Most colorectal cancers arise from adenomatous polyps in a process estimated to take about 10 years; removal of a premalignant colonic lesion can prevent cancer from developing About 80% of colon cancers detected during screening of asymptomatic patients are Treatment Guidelines from The Medical Letter • Vol 10 ( Issue 124) • December 2012 89 Cancer Screening stage I and II, and only 20% have positive lymph nodes or metastases (stage III and IV) Once symptoms have developed, 40% of colorectal cancers are stage III or IV years) of 2602 patients who had colonoscopic removal of adenomatous polyps found that mortality from colon cancer decreased by 53% compared to the expected incidence in the general population.13 FECAL OCCULT BLOOD TESTS — A randomized controlled trial in 46,551 patients 50-80 years old found that guaiac-based fecal occult blood testing of stool samples (2 samples on occasions) reduced mortality from colorectal cancer, after 18 years of followup, by 21% with biennial screening and by 33% with annual screening.1 The usefulness of guaiac-based screening is limited by its inability to detect non-bleeding polyps or cancers, the need for repeated testing, and a high rate of false-positive results Colonoscopy requires more extensive bowel cleansing than sigmoidoscopy and has a higher risk of perforation and complications related to sedation A study of colonoscopy screening in 21,375 patients found a serious complication rate within 30 days of the exam of 0.3%.14 Fecal immunochemical tests (FITs) use antibodies to human globin to detect occult blood in stool Since globin does not survive passage through the upper GI tract, FITs are more specific for colorectal bleeding than guaiac-based tests and are not affected by diet or medication.2 In an interim analysis of an ongoing trial comparing FIT to colonoscopy in asymptomatic adults 50-69 years old, the rate of detection of colorectal cancer on baseline screening examination was similar in both groups, but more adenomas were detected in the colonoscopy group.3 BARIUM ENEMA — Double-contrast barium enema (DCBE) may miss up to 22% of colon cancers.4 It has poor sensitivity in detecting flat lesions or small polyps Even for polyps >1 cm, its sensitivity is 10 mm has varied from 88-98% CT COLONOGRAPHY — Computed tomography colonography (CTC), also called virtual colonoscopy, generates a 2- or 3-dimensional colorectal image using data input from a helical (spiral) CT scan It offers a less invasive screening option, but follow-up with traditional colonoscopy is often needed to evaluate lesions detected by CTC Unlike traditional colonoscopy, CTC exposes the patient to radiation.15 A multi-center study in 2600 patients >50 years old with an average risk of colorectal cancer reported that CTC had a sensitivity of 90% for detecting polyps or cancers >10 mm in diameter and 78% for polyps >6 mm.16 In a study in patients at increased risk for colorectal cancer, the sensitivity of CTC for detecting lesions >6 mm was 85%.17 NEW APPROACHES — Tests that detect abnormal DNA in stool are under investigation in clinical trials Evidence to support their use is currently insufficient and no tests are commercially available RECOMMENDATIONS FOR AVERAGE RISK — Multiple guidelines recommend screening averagerisk patients with colonoscopy beginning at age 50 and repeated every 10 years When colonoscopy is not available or the patient declines the procedure, they recommend screening with flexible sigmoidoscopy every years and/or fecal occult blood tests annually (FITs are preferred over guaiac-based tests).18 Some guidelines now recommend CTC every years as an alternative for average-risk patients.19 The American College of Physicians (ACP) recommends not screening adults >75 years old or those with a life expectancy of 50% higher incidence and 2.5-fold higher mortality rates than white Americans, and men who have a first-degree relative with prostate cancer (two-fold increase in risk) Prostate cancer is highly heterogeneous in terms of its risk of progression Many low-risk prostate cancers are indolent and never progress to cause symptoms or mortality, whereas higher-risk prostate cancers lead to more deaths among men than any cancer except lung cancer.1 Whether radical prostatectomy for localized prostate cancer improves mortality appears to vary with the circumstances; one study in men with tumors mostly detected by palpation found that it did, while another in men with tumors detected by PSA screening found that it did not, except in a subgroup of patients with a PSA >10 ng/mL.2,3 DIGITAL RECTAL EXAM — A digital rectal exam looking for prostate nodules, induration or asymmetry has long been used for detection of prostate cancer All men with an abnormal exam should have a transrectal ultrasound (TRUS)-guided prostate biopsy PROSTATE-SPECIFIC ANTIGEN (PSA) — PSA, a serine protease secreted by prostatic epithelial cells and peri-urethral glands, is the most widely used screening test for prostate cancer A PSA of ng/mL has been considered the upper limit of normal, but prostate cancer can be present at lower levels of PSA In a study of men 62-91 years old, the prevalence of prostate cancer on biopsy was 6.6% with a PSA 10 ng/mL, 4365% PSA levels increase with age They can be elevated in benign conditions such as benign prostatic hypertrophy (BPH), prostatitis or mechanical manipulation (catheter, cystoscopy, transrectal ultrasound), and can be raised by recent ejaculation They can be lowered by drugs such as finasteride (Proscar) or dutasteride (Avodart).5,6 CLINICAL STUDIES OF PSA SCREENING — The prostate arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial randomized men age 55-74 to annual PSA screening for years or to usual care There was no significant difference in mortality between the two arms after 13 years of follow-up,7 but high rates of PSA screening were reported in the “usual care” arm In contrast, the European Randomized Study of Screening for Prostate Cancer (ERSPC) (PSA screening every years; 11 years of follow-up) and the Göteborg screening study (PSA screening every years; 14 years of follow-up) found relative risk reductions in cancer-specific mortality of 21% and 44%, respectively, in screened men compared to unscreened men; neither study found an effect on overall mortality.8,9 POSSIBLE HARMS OF PSA SCREENING — PSA testing of asymptomatic men leads to unnecessary biopsies and uncovers some cancers that would not have become clinically significant during life Overdiagnosis of prostate cancer leads to overtreatment because many men diagnosed with prostate cancer (even with low-grade, early-stage disease) choose to undergo some form of active treatment Overtreatment can cause impotence, incontinence and other complications NEW APPROACHES — Circulating PSA is found in multiple forms In patients with prostate cancer, the percentage of free PSA (fPSA) is reduced; in patients with a PSA level of 4-10 ng/mL, using a threshold of fPSA of 20-25% can identify 90-95% of cancers.10 An isoform of fPSA, [-2]proPSA, has been associated with prostate cancer; used in combination with PSA and/or fPSA, it may further increase the accuracy of screening.11 In general, combining several markers, including PSA and fPSA, appears promising.12 The rate of change in PSA over time (PSA velocity) has also been used to improve the accuracy of screening.13 RECOMMENDATIONS — The US Preventive Services Task Force recently issued a highly controversial recommendation against PSA screening for all men, based on the conclusion that the benefits of screening not outweigh the harms.14,15 The American Cancer Society recommends that men >50 years old (40-45 for African-Americans or those with a family history of prostate cancer) with a life expectancy of at least 10 years be informed of the risks and benefits of screening and be given the choice to be screened or not.16 The American Urological Association recommends beginning screening at age 40.17 R Siegel et al Cancer statistics, 2012 CA Cancer J Clin 2012; 62:10 A Bill-Axelson et al Radical prostatectomy versus watchful waiting in early prostate cancer N Engl J Med 2011; 364:1708 T Wilt et al Radical prostatectomy versus observation for localized prostate cancer N Engl J Med 2012; 367:203 IM Thompson et al Prevalence of prostate cancer among men with a prostate-specific antigen level