# Cancer Screening: Evidence, Benefits, and Harms

## Introduction

Cancer screening aims to detect malignancy at a pre-symptomatic stage when treatment is more effective and survival is improved. However, screening is not without harm. Overdiagnosis, false positives, procedural complications, and psychological burden must be weighed against potential benefits. Internal medicine residents must understand the evidence behind major screening recommendations and engage patients in informed, shared decision-making.

## Principles of Screening

- **Lead-time bias**: screening detects cancer earlier, making survival appear longer even if death occurs at the same time
- **Length-time bias**: screening preferentially detects slow-growing tumors (better prognosis), inflating apparent benefit
- **Overdiagnosis**: detection of cancers that would never have caused symptoms or death during the patient's lifetime
- **Number needed to screen (NNS)**: the number of individuals who must be screened to prevent one cancer death
- The only definitive measure of screening benefit is **reduction in disease-specific or all-cause mortality** in randomized controlled trials

## Colorectal Cancer Screening

| Cancer | Population | Modality | Interval | Grade |
|--------|-----------|----------|----------|-------|
| Colorectal | Age 45-75 | Colonoscopy | Every 10 years | A/B |
| | | FIT (stool) | Annual | A/B |
| | | FIT-DNA (Cologuard) | Every 1-3 years | A/B |
| | | CT colonography | Every 5 years | A/B |
| Lung | Age 50-80, ≥20 pack-years | Low-dose CT | Annual | B |
| Breast | Women 40-74 | Mammography | Biennial | B |
| Cervical | Age 21-65 | Cytology or HPV testing | Every 3-5 years | A |
| Prostate | Men 55-69 | PSA (shared decision) | Individualized | C |

### Recommendations (USPSTF 2021)

- **Age 45-75**: screen all average-risk adults (Grade A for 50-75; Grade B for 45-49)
- **Age 76-85**: individualize (Grade C)
- **Preferred modalities**: colonoscopy every 10 years, annual FIT (fecal immunochemical test), FIT-DNA (Cologuard) every 1-3 years, or CT colonography every 5 years
- Colonoscopy remains the only modality that is both diagnostic and therapeutic (polypectomy)

### High-Risk Populations

- **First-degree relative with CRC before age 60**: colonoscopy starting at age 40 or 10 years before earliest diagnosis, every 5 years
- **Lynch syndrome**: colonoscopy every 1-2 years starting at age 20-25
- **Inflammatory bowel disease**: colonoscopy with chromoendoscopy 8 years after diagnosis, then every 1-3 years

![Colorectal cancer screening algorithm by risk category](images/crc-screening-algorithm.png)

## Lung Cancer Screening

- **USPSTF 2021**: annual low-dose CT (LDCT) for adults aged 50-80 with >= 20 pack-year smoking history who currently smoke or quit within 15 years
- **NLST**: LDCT reduced lung cancer mortality by 20% compared to chest X-ray
- **NELSON trial**: 24% mortality reduction at 10 years with LDCT vs. no screening
- **Harms**: 25% false-positive rate leading to additional imaging, invasive procedures, anxiety
- **Lung-RADS** classification standardizes management of screen-detected nodules
- Smoking cessation counseling must accompany every screening visit

## Breast Cancer Screening

- **USPSTF 2024**: biennial mammography for women aged 40-74 (Grade B)
- **ACS**: annual mammography starting at age 45 (biennial at 55)
- **Overdiagnosis rate**: estimated at 10-20% of screen-detected cancers
- **Dense breasts**: supplemental screening with MRI or ultrasound may be considered; state notification laws vary
- **High-risk women** (BRCA1/2, >= 20% lifetime risk): annual mammography + breast MRI starting at age 25-30
- Digital breast tomosynthesis (3D mammography) improves cancer detection and reduces recall rates

## Cervical Cancer Screening

- **USPSTF 2018**: cytology (Pap) every 3 years (age 21-65), HPV testing every 5 years (age 30-65), or co-testing every 5 years (age 30-65)
- **ACS 2020**: primary HPV testing every 5 years starting at age 25 is preferred
- **Stop screening**: age 65 if adequate prior negative results; after total hysterectomy for benign indications
- HPV vaccination has dramatically reduced HPV 16/18 prevalence and is expected to further reduce screening needs

## Prostate Cancer Screening

- **USPSTF 2018**: individualized decision for men aged 55-69 (Grade C); recommend against screening in men >= 70 (Grade D)
- **PSA screening** reduces prostate cancer mortality modestly (ERSPC: 1 death prevented per 781 men screened over 13 years)
- **Harms**: high overdiagnosis rate (20-50%); biopsy complications (infection, bleeding); treatment side effects (incontinence, erectile dysfunction)
- **Active surveillance** has reduced overtreatment for low-risk cancers (Gleason 3+3)
- MRI-targeted biopsy improves detection of clinically significant cancer while reducing detection of insignificant disease

![Summary of USPSTF cancer screening recommendations](images/cancer-screening-summary.png)

## Other Screening Considerations

### Hepatocellular Carcinoma

- **At-risk populations**: cirrhosis (any etiology), chronic hepatitis B (even without cirrhosis in certain groups)
- **Modality**: abdominal ultrasound with or without AFP every 6 months
- Surveillance improves early detection and is associated with survival benefit in observational studies

### Skin Cancer

- **USPSTF**: insufficient evidence for population-based skin cancer screening (Grade I)
- High-risk patients (prior melanoma, dysplastic nevi, strong family history) warrant dermatologic surveillance

### Ovarian Cancer

- **USPSTF**: recommends AGAINST screening in average-risk women (Grade D)
- CA-125 and transvaginal ultrasound have not reduced ovarian cancer mortality (UKCTOCS, PLCO trials)

## Shared Decision-Making Framework

- Present **absolute risk reduction**, not just relative risk reduction
- Use **decision aids** to clarify benefits and harms in patient-centered terms
- Incorporate **life expectancy and competing comorbidities**: screening is unlikely to benefit patients with < 10-year life expectancy
- Respect patient values and preferences regarding downstream testing and treatment

![Shared decision-making framework for cancer screening](images/sdm-cancer-screening.png)

## Key Clinical Pearls

- Screening saves lives only when the cancer has an effective treatment at early stage and the test reliably detects it before clinical presentation
- Overdiagnosis is the most underappreciated harm of screening; it leads to unnecessary treatment with real physical and psychological consequences
- FIT is the preferred stool-based test for colorectal cancer screening due to superior specificity and lower cost compared to guaiac-based tests
- Always pair lung cancer screening with smoking cessation; the mortality benefit of quitting far exceeds that of screening alone

## References

1. US Preventive Services Task Force. Screening for Colorectal Cancer: USPSTF Recommendation Statement. *JAMA*. 2021;325(19):1965-1977.
2. de Koning HJ, van der Aalst CM, de Jong PA, et al. Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial (NELSON). *N Engl J Med*. 2020;382(6):503-513.
3. US Preventive Services Task Force. Screening for Breast Cancer: USPSTF Recommendation Statement. *JAMA*. 2024;331(22):1918-1930.
4. Fenton JJ, Weyrich MS, Durbin S, et al. Prostate-Specific Antigen-Based Screening for Prostate Cancer: Evidence Report and Systematic Review. *JAMA*. 2018;319(18):1914-1931.