Cancer Screening & Prevention
Who to screen, when to start, when to stop — and the syndromes that hide the tumor
Principles of screening
Good screening needs a treatable target. Screening looks for disease in asymptomatic people. It works only for common cancers with a detectable preclinical phase and an effective early treatment, and it is judged by a fall in disease-specific mortality. Two biases inflate apparent benefit:
- Lead-time bias: earlier diagnosis lengthens measured survival without delaying death, so there is no true survival gain.
- Length-time bias: screening over-detects slow-growing, indolent tumors; its extreme is overdiagnosis of cancers that would never have caused harm.
USPSTF grades. A and B are recommended; C means offer selectively as an individual decision; D means do not screen; I means the evidence is insufficient.
Average-risk screening schedule
| Cancer | Who | Test and interval | Stop or caveat |
|---|---|---|---|
| Breast | Women 40–74 (2024, Grade B; old start age was 50) | Mammography every 2 years | Insufficient evidence at ≥75 |
| Cervical | Ages 21–65, starting at 21 regardless of sexual history | 21–29: cytology every 3 years. 30–65: cytology every 3 years, hrHPV every 5 years, or co-testing every 5 years | Stop at 65 after adequate negative screening; none under 21 |
| Colorectal | Ages 45–75 (2021); 76–85 individualized | Colonoscopy every 10 years, annual FIT, FIT-DNA every 1–3 years, flexible sigmoidoscopy or CT colonography every 5 years | Any positive non-colonoscopy test needs colonoscopy |
| Lung | Ages 50–80, ≥20 pack-years, smoking now or quit within 15 years (2021) | Annual low-dose CT | USPSTF: stop after 15 smoke-free years (ACS 2023 does not use years since quitting) or if life expectancy or fitness for curative surgery is limited |
| Prostate | Men 55–69 (Grade C) | PSA after shared decision-making; no screening DRE | Do not screen at ≥70 (Grade D) |
Breast MRI is added only for high-risk women: BRCA carriers, prior chest radiation, or a lifetime risk of 20% or more.
Cervical nuances. HPV-vaccinated women follow the same schedule. At 30–65, primary hrHPV testing or co-testing gives the longest safe interval (5 years). Women whose cervix was removed at hysterectomy for benign disease stop screening.
Colonoscopy is the gold standard because it is also therapeutic (polypectomy).
Lung eligibility. Pack-years = packs per day × years smoked: 1 pack/day for 20 years is 20 pack-years, and 1.5 packs/day for 20 years is 30. Chest radiography and sputum cytology are not screening tests.
Prostate. PSA screening at 55–69 is an individual decision after weighing a small mortality reduction against overdiagnosis, biopsy complications, and overtreatment.
Do not screen average-risk adults for ovarian (CA-125, transvaginal ultrasound), pancreatic, or testicular cancer: harms exceed benefit. Screening is targeted, not universal, so know what not to order.
Higher-risk surveillance and hereditary syndromes
Family history of colorectal cancer. A first-degree relative diagnosed before 60 (or two first-degree relatives at any age) calls for colonoscopy every 5 years starting at 40 or 10 years before the youngest relative's diagnosis, whichever is earlier. Patients with cirrhosis get liver ultrasound (with or without AFP) every 6 months for hepatocellular carcinoma.
BRCA1/2 mutations cause autosomal dominant hereditary breast-ovarian cancer syndrome. BRCA1 confers roughly 55–72% lifetime breast and ~40% ovarian cancer risk; BRCA2 adds male breast, prostate, and pancreatic cancer. Refer high-risk family histories for genetic counseling. Risk-reducing salpingo-oophorectomy, typically by 35–40 after childbearing, markedly lowers ovarian cancer risk and reduces breast cancer risk and mortality.
Lynch syndrome (HNPCC) is an autosomal dominant mismatch-repair mutation causing microsatellite instability: right-sided colorectal cancer without prior polyposis (unlike FAP) plus a high endometrial cancer risk. Endometrial cancer is the second most common Lynch cancer and often the sentinel tumor in women. By contrast, FAP (APC mutation) carpets the colon with hundreds of adenomas, requiring endoscopic surveillance from early adolescence and prophylactic colectomy.
| Feature | BRCA1/2 | Lynch syndrome |
|---|---|---|
| Defect | DNA repair by homologous recombination | Mismatch repair (MLH1, MSH2, MSH6, PMS2); microsatellite instability |
| Main cancers | Breast and ovarian | Colorectal (right-sided) and endometrial |
| Other cancers | Male breast, prostate, pancreas | Ovarian, gastric, urothelial |
| Management | Annual MRI plus mammography; risk-reducing mastectomy and salpingo-oophorectomy | Colonoscopy every 1–2 years from age 20–25 |
| Red flags | Ashkenazi Jewish ancestry; early-onset or bilateral breast or ovarian cancer | Amsterdam 3-2-1: 3 relatives, 2 generations, 1 under age 50 |
Paraneoplastic clues to occult cancer
Signals from a distance. Paraneoplastic syndromes are caused by tumor-secreted hormones or antibodies acting far from the tumor, and they can be its first sign. Small cell lung cancer is the great endocrine mimic.
| Clue | Mechanism | Classic tumor |
|---|---|---|
| Euvolemic hyponatremia | SIADH | Small cell lung |
| Cushing syndrome | Ectopic ACTH | Small cell lung |
| Proximal weakness that improves with use | Lambert-Eaton: anti-voltage-gated calcium channel antibodies | Small cell lung |
| Hypercalcemia with suppressed PTH | PTHrP: bone resorption plus renal calcium retention | Squamous cell lung, head and neck |
| Acanthosis nigricans; sign of Leser-Trélat (eruptive seborrheic keratoses) | Cutaneous paraneoplastic sign | Gastric adenocarcinoma |
| Migratory superficial thrombophlebitis | Trousseau syndrome | Pancreatic adenocarcinoma |
| Heliotrope rash, Gottron papules | Dermatomyositis | Raises adult malignancy risk (e.g., ovarian, lung, GI) |
| Polycythemia | Ectopic erythropoietin | Renal cell, hepatocellular carcinoma |
Prevention
Smoking cessation is the single highest-yield cancer prevention step. Counsel every smoker with the 5 A's: Ask, Advise, Assess, Assist, Arrange. Varenicline, a partial nicotinic receptor agonist, is the most effective single drug; combination nicotine replacement or bupropion follow. Avoid bupropion in seizure or eating disorders. Pairing medication with behavioral support gives the best quit rates.
- Vaccines: HPV vaccination (routinely at 11–12, catch-up through 26) prevents cervical, anal, and oropharyngeal cancers; hepatitis B vaccination prevents hepatocellular carcinoma. Vaccination does not replace cervical screening.
- Chemoprevention: women at increased breast cancer risk and low risk of adverse effects can be offered tamoxifen, raloxifene, or an aromatase inhibitor.