PLCO Screening Trial: What It Found

In brief

The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial was designed by the National Cancer Institute to settle a question observation cannot: does screening healthy people for these four cancers mean fewer of them die from those cancers? It enrolled about 155,000 people. For three of the four, the answer was no.

Trial at a glance

Field	Detail
Trial	PLCO Cancer Screening Trial
Identifier	NCT00002540
Design	Randomized, screening versus usual care, 10 US centers
Enrollment	About 155,000 adults aged 55 to 74
Enrolled	November 1993 to July 2001
Primary endpoint	Death from the screened cancer

Who took part

Adults aged 55 to 74 from the general US population, recruited at ten centers and not selected for high risk. Half were offered a set screening schedule; half received usual care, which at the time often included some screening.

What the trial found

Prostate. 76,685 men were offered annual PSA testing for six years and digital rectal exams for four. After 13 years, screening found more cancers — 108.4 versus 97.1 cases per 10,000 person-years, a 12% relative increase (RR 1.12; 95% CI, 1.07 to 1.17) — but did not reduce deaths. Prostate cancer mortality was 3.7 versus 3.4 per 10,000 person-years (RR 1.09; 95% CI, 0.87 to 1.36).

Ovarian. 78,216 women were offered annual CA-125 blood tests for six years and transvaginal ultrasound for four. Over a median 12.4 years, 118 screened women died of ovarian cancer (3.1 per 10,000 person-years) against 100 in usual care (2.6); the mortality rate ratio was 1.18 (95% CI, 0.82 to 1.71). The harms were not theoretical: 3,285 women had false-positive results, 1,080 went on to surgery, and 163 of those — 15% — had at least one serious complication.

Lung. Annual chest X-rays for four years produced 1,213 lung cancer deaths in the screened group versus 1,230 in usual care over 13 years (RR 0.99; 95% CI, 0.87 to 1.22).

Colorectal. This is the exception. Flexible sigmoidoscopy, repeated at three or five years, cut colorectal cancer incidence by 21% (RR 0.79; 95% CI, 0.72 to 0.85) and deaths by 26% (2.9 versus 3.9 per 10,000 person-years; RR 0.74; 95% CI, 0.63 to 0.87). Deaths from cancers in the lower colon fell by half; those higher up did not change.

What changed in practice

PLCO helped move guidance away from the assumption that more testing is better. The US Preventive Services Task Force recommends against ovarian cancer screening in asymptomatic women, and treats PSA testing at ages 55 to 69 as an individual decision, advising against it from age 70. NCI states plainly that CA-125 and ultrasound together "does not decrease the number of deaths from ovarian cancer." Lung screening changed tools rather than disappearing: the National Lung Screening Trial found low-dose CT cut lung cancer deaths by 20% in high-risk people.

What this story cannot tell you

• It does not say screening never works: within the same trial, sigmoidoscopy reduced colorectal cancer deaths. Each test has to be proven on its own.
• It does not apply to people at high inherited risk, such as those with BRCA1 or BRCA2 variants or Lynch syndrome. PLCO enrolled a general population aged 55 to 74.
• The prostate comparison had a flaw: many usual-care men were screened anyway — PSA use there rose from 40% in year one to 52% by year six — so it tested organized versus opportunistic screening, not versus none.
• It tested the technology of its time, and cannot tell you how MRI before biopsy, active surveillance or newer blood tests change the balance of benefit and harm today.
• A null result is not proof of no effect; it means any effect was too small to detect in a trial this large.

Questions worth asking

• For this test, has screening been shown to reduce deaths, or only to find more cancers?
• What happens if my result is abnormal, and what are the risks of the follow-up?
• Does my family or personal history put me outside the group these trials studied?

Sources

This article was written from the sources below, which were checked on the source-check date shown above.

• NCI: The PLCO Cancer Screening Trial (reference)
• NEJM 2009: PLCO prostate mortality (primary)
• JNCI 2012: PLCO prostate, 13 years (primary)
• JAMA 2011: PLCO ovarian mortality (primary)
• JAMA 2011: PLCO chest radiograph (primary)
• NEJM 2012: PLCO sigmoidoscopy (primary)
• ClinicalTrials.gov: NCT00002540 (registry)
• NCI: Ovarian Cancer Screening (PDQ) (reference)
• USPSTF: prostate and ovarian screening (reference)
• NEJM 2011: NLST low-dose CT screening (supporting)

Related: benefits and harms of screening, prostate cancer screening.

How this article was prepared

Prepared by Cancer Explained's AI-assisted editorial system and checked against the sources listed above. This article has not been reviewed by a healthcare professional unless a named reviewer is specifically shown.

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