Nearly forty years ago, President Richard Nixon famously declared a "War on Cancer" by signing the National Cancer Act of 1971. Like the Manhattan Project, the Apollo program that was then landing men on the Moon, and the ongoing (and eventually successful) World Health Organization-led initiative to eradicate smallpox from the face of the Earth, the "War on Cancer" was envisioned as a massive, all-out research and treatment effort. We would bomb cancer in submission with powerful regimens of chemotherapy, experts promised, or, failing that, we would invest in early detection of cancers so that they could be more easily cured at earlier stages.
It was in the spirit of the latter that the National Cancer Institute launched the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening trial in 1992. This massive study, which eventually enrolled more than 150,000 men and women between age 55 and 74, was designed to test the widespread belief that screening and early detection of the most common cancers could improve morbidity and mortality in the long term. Not a few influential voices suggested that the many millions of dollars invested in running the trial might be better spent on programs to increase the use of these obviously-effective tests in clinical practice.
They were wrong. As of this week, the PLCO study is 0-for-2.
Miss #1 occurred in March of 2009 when the PLCO study first reported no mortality benefit from annual PSA testing, a test that a majority of men over 50 undergo routinely. Miss #2 occurred over the weekend, when the Journal of the American Medical Association published a landmark paper that ended with the following paragraph:
We conclude that annual screening for ovarian cancer as performed in the PLCO trial with simultaneous CA-125 and transvaginal ultrasound does not reduce disease-specific mortality in women at average risk for ovarian cancer but does increase invasive medical procedures and associated harms.
The lung and colorectal screening components of PLCO have not yet reported mortality data, and there is reason to believe that at least the latter will likely yield some positive results. Although it has largely been supplanted by colonoscopy and CT colonography (aka "virtual colonoscopy") in the U.S., flexible sigmoidoscopy was already shown to reduce deaths from colorectal cancer in a randomized trial published in the Lancet last year. And PLCO's screening chest x-rays are probably a loser, but a preliminary report from NCI's National Lung Screening Trial suggest that screening CT scans can reduce lung cancer mortality in heavy smokers. (Even after this report is confirmed in a peer-reviewed scientific journal, there will still be plenty of reasons not to rush into lung cancer screening, as I outlined in a previous blog post.)
Still, these are hardly the magic bullets or the resounding victories that many expected from the "War on Cancer." The same can be said for chemoprevention, or the strategy of prescribing medications for healthy adults to prevent cancers from developing at all. The vast majority of "high risk" women have avoided breast cancer chemoprevention with tamoxifen and raloxifene due to their unpleasant side effects (which include hot flashes and life-threatening blood clots), despite a 2002 recommendation from the U.S. Preventive Services Task Force for clinicians to discuss these drugs with their patients. (This recommendation has not been updated since, largely due to politics, not science.) A new study published in the New England Journal of Medicine has reported that the drug exemestane reduces the risk of invasive breast cancer without the other drugs' side effects. But here's the rub: we can't be sure how many of those breast cancers are the ones that inevitably lead to symptoms and death, rather than the 1 in 3 that are thought to be overdiagnosed.
The bottom line from recent research is that there are no easy victories in cancer screening and prevention - just slow, incremental progress. Companies that have a profitable product to push would like you to believe otherwise, but when it comes to cancer prevention, there is no substitute for a healthy lifestyle: Don't Smoke. Drink in Moderation. Exercise. And Eat a Well-Balanced Plate.