Pocket Oncology (Pocket Notebook Series), 1st Ed.

CANCER PREVENTION & SCREENING

Payal D. Shah and Victoria Blinder

General Principles

• Primary cancer prevention: To reduce cancer incidence & mortality; eg, smoking cessation, sun avoidance, cancer virus vaccination, chemoprevention

• Screening: Method of secondary cancer prevention; to identify asx cancers w/the goal of earlier interventions & mortality reduction

• Note various guidelines (USPSTF, NCCN, ACS, ASCO, etc.) differ

Breast Cancer

• Primary prevention:

• Surgery: See “Cancer Genetics: BRCA1/2

• Chemoprevention: For women >age 35 only; NSABP-BCPT: Tamoxifen ↓ the incidence of breast cancer in postmenopausal women & in high-risk premenopausal women, but has significant potential adverse effects including endometrial cancer, DVT, PE (J Natl Cancer Inst 2005;97:1652); tamoxifen reduces incidence of contralateral 2nd primary breast cancer; exemestane also preventive in postmenopausal women (N Engl J Med 2011;364:2381)

• Lifestyle modification: EtOH & obesity ↑ risk of breast cancer

• Recommended screening for average-risk women (for high-risk women, see “Cancer Genetics: BRCA1/2”):

• Ages 20–39, CBE q1–3y + breast awareness

• Ages 40+, annual (per ACS & NCCN, though other groups suggest q2y or individualized for ages 40–49) CBE & screening mammography + breast awareness; no reduction in mortality w/SBE; possible reduction in mortality w/CBE; mammography demonstrates mortality reduction (Lancet 2002;359:909)

• Dense breasts: Mammo has lower Sn but currently insufficient evidence to recommend supplemental imaging

• USPSTF notes insufficient evidence for screening after age 75

• Annual MRI: For BRCA mutation carriers (adjunct to annual mammogram), untested 1st degree relatives of BRCA mutation carriers, lifetime risk of ≥20% using risk assessment models; h/o chest radiation between ages 10 & 30

• U/S: Not routinely recommended for screening

Cervical Cancer

• Vaccination: Rate of vaccination ∼32% in US adolescents; HPV vaccines are directed at specific subtypes but provide some cross-protection (HPV 16 & 18 responsible for 70% of cervical cancer)

• Quadrivalent HPV vaccine (Gardasil®): Protects against certain high-risk HPV subtypes including 16, 18, 6, 11; 3-y efficacy was 98% for preventing CIN 2/3 from HPV 16 or 18 w/no prior infection, but 44% in those infected prior to vaccination (FUTURE II NEJM 2007;356:1519); duration of immunity unclear, estimated at least 5 y & up to 9.5 y; approved in females ages 9–26; best if given prior to initiation of intercourse

• Bivalent HPV vaccine: Protects against subtypes 16 & 18; approved in the United States for females 10–25; effective for at least 8 y; approved in more than 90 other countries

• Screening methods: Cytologic methods (liquid-based cytology now more common than Papanicolaou smears); HPV DNA testing for high-risk subtypes sometimes used as a component of primary screening (co-testing)

• Age at screening initiation: Begin screening at age 21 even if not sexually active, even if received HPV vaccine (other oncogenic HPV subtypes); avoid screening if younger than 21 as cervical cancer is rare & treatment can lead to complications

• Screening frequency: q3y w/cytology alone for ages 21–29, more frequently if immunocompromised (eg, HIV-infected), h/o cervical dysplasia/cancer, in utero DES exposure; for age 30–65, q5y cytology + HPV DNA co-testing (preferred) or cytology alone q3y

• Discontinue screening if: S/p total hysterectomy for benign disease & no residual cervix; intact cervix, age >65, adequate negative prior results (3 consecutive negative cytology results or 2 consecutive negative co-test results w/in past 10 y); no h/o abnl cervical cytology; comorbid or life-threatening illness

Colon Cancer

• Prevention in familial syndromes: See “Cancer Genetics: LS/FAP”

• Prevention: Polypectomy, removal of adenomatous polyps

• Screening modalities: Colonoscopy; flexible sigmoidoscopy; CT colonography: Capable of detecting cancer as well as precancerous lesions; stool-based tests: Detect cancer but not adenomatous polyps; follow abnl results w/full colonoscopy

• When to begin screening

• Average risk: Begin age 50

• 1st degree relative w/CRC <50 y or 21st degree relatives w/CRC at any age: Age 40 or 10 y before earliest diagnosis of 1st degree relative, whichever first

• 1st degree relative w/CRC aged ≥50: Age 50 or 10 y before earliest diagnosis, whichever first

• 1st degree relative w/advanced adenoma(s): Age 50 or at age of onset of relative, whichever first

• Screening intervals: Shorter than q10y if:

• + Family hx

• Suboptimal colonoscopy (poor bowel prep)

• Sx

• Adenomatous or villous polyps removed during prior colonoscopy

Prostate Cancer

• SELECT trial: Selenium & vitamin E do not prevent prostate CA

• PSA testing: Controversial; early detection may not correlate w/improved survival, as most prostate cancer low-grade; interpretation of studies limited 2/2 contamination of control groups (no screening arm gets screened), lack of stratification by risk level

• ERSPC trial: Reduction in prostate cancer specific but not all-cause mortality from screening (PSA on average q4y); 1410 men needed to be screened to prevent one death; screening 1410 men resulted in 48 prostate CA diagnoses

• PLCO trial: Screening may benefit those in good health due to lack of competing cause for mortality; no overall mortality benefit

• Utility of PSAV controversial

• No consensus regarding testing: Consider age, life expectancy, family hx, risks & benefits a/w early detection & treatment of prostate cancer

Lung Cancer

• Smoking cessation: Most effective prevention, dose-response relationship of smoking to risk of lung CA

• Screening: No benefit in mortality w/CXR, sputum cytology

• Annual low-dose helical CT: 20% lung cancer-specific mortality benefit (NEJM 2011;365:395); results not yet replicated in separate cohort

• Current recommendations: Annual LDCT for selected high-risk smokers (former smokers age 55–74 w/30py tobacco hx); when to discontinue screening unclear