New approaches to cancer screening and diagnosis

I see five major themes in cancer care advances: new approaches to screening and diagnosis, better understanding of the role of viruses as causative agents, targeted therapies, new technologies and improved approaches to ensuring better quality of life.

Screening for the most common major cancers has been straight forward for years – women should get an annual mammogram and Pap smear, men should get a PSA test annually, both should get colonoscopies and there was no accepted screening for lung cancer. Now these standards have been turned on their heads – and controversy reigns.

The US Preventive Services Task Force in October, 2011 came out in Annals of Internal Medicine with the new recommendation that prostate specific antigen (PSA) should no longer be a routine test for detecting the possibility of prostate cancer. Their conclusion was that “prostate-specific antigen–based screening results in small or no reduction in prostate cancer–specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary.” The Task Force had previously recommended against routine PSA screening in men older than 75 years. With this new recommendation it suggests that all men not have this screening test preformed. It gives the test a “D” score meaning “there is moderate or high certainty that the service has no benefit or that the harms outweigh the benefits.” They looked at the available data from randomized controlled trials and other studies to reach their conclusions.

PSA is a very widely used test and most physicians recommend that their adult male patients have the test done so this comes as a major course correction. There is already and will continue to be substantial controversy with many arguing against the Task Force recommendation. However it should be remembered that the Task Force is made up of individuals without any apparent bias and who based their recommendations’ on the best available evidence.

The chair of the Task Force, Virginia Moyer MD, expressed her opinion in USA Today that PSA has definite limitations and that if it was of benefit it should be apparent by now “and it is not.” She points out that about one third of men aged 40-60 years have cancer cells in their prostate yet very few are aggressive and need treatment. Yet when found, most men are treated – with the risk of surgery or radiation and the development of side effects such as incontinence or impotence which develop in 20 to 30 percent of these treated men. She urged further research to find ways to detect the aggressive prostate cancers that are a risk to life yet to also identify the indolent ones that are best left to watchful waiting. The paper however editorialized that it is better to have extra biopsies and some stress than not knowing you have cancer. That opinion has been expressed by many in recent days so the controversy will persist for some time.

In another highly controversial statement, The US Preventive Services Task Force recommended in 2009 that women between the ages of 40 and 49 probably did not need to get routine mammograms, assuming they had no specific risk factors such as a family history. The rationale was that the number of patients screened to detect one cancer was high; the chance for a false positive was also high and the resultant biopsies and anxiety all weighed together. The Task Force suggested that the data for women over 70 is unclear as to whether routine mammograms are useful. Finally they said that women ages 50 to 69 should continue to get mammograms but could switch to every other year from every year following a normal mammogram.

At about the same time the Task Force recommended that women who had multiple negative Pap smears and a monogamous sexual relationship could switch to every other year screening for cervical cancer. Further, women over the age of 70 with multiple negative smears could skip further exams.

And now there is evidence that low dose CT scanning of high risk individuals can detect early lung cancer, meaning that it can be detected before it advances and is no longer treatable by surgery alone. There had been suggestive evidence of this before but the new data used lower dose CT screening and followed high risk individuals for a prolonged time period. This was compared to annual chest X-rays as a control.

The gold standard for colon cancer screening is colonoscopy. Colonoscopy allows visualization of the entire colon from cecum to anus and, since most cancers arise from polyps, they can be removed either before cancer develops or at a very early state. But not everyone is willing, able or can afford colonoscopy so alternatives would be desirable. Virtual colonoscopy using CT scanning is effective although it too requires a colon purge, a dissuader for some, and is not covered at this time by Medicare. Flexible sigmoidoscopy has generally been discouraged because it cannot visualize the entire colon. But new data shows that its use will decrease the incidence of colon cancer by about one half. Since the prep is less intense it might be more acceptable to some individuals and therefore, although certainly not as effective as colonoscopy, has utility as a screening tool.

So the approach to screening is changing — dramatically.

As to diagnosis, it has now been demonstrated with a large scale clinical trial of patients with breast cancer that for those with no palpable axillary lymph nodes, the finding of a biopsy positive sentinel node can adequately inform therapy and that the long held practice of doing an axillary node dissection for women with breast cancer is not necessary (the 5 years survival with axillary dissection was 91.9% versus 92.5% for those with out dissection.) In another study, it was found that if the sentinel node was negative, there was no need to do the further step of axillary dissection to look for positive nodes. Here again, in a randomized trial, there was no difference in long term survival or recurrence. This is useful information because absent this procedure, patients will have less discomfort and much less lymphedema of the arm.

It is also now clear that genomic subtyping of breast cancer has a predictive prognostic effect. Patients can be categorized into a number of progressively adverse groups for which adjustments in therapy may be prudent. It can be expected that this approach will be used for many cancers in the coming years where genetic and epigenetic signatures will be increasingly used to define prognosis and direct therapy.

New approaches to cancer screening and diagnosisStephen C. Schimpff is an internist, professor of medicine and public policy, and former CEO of the University of Maryland Medical Center.  He is the author of The Future of Medicine — Megatrends in Healthcare and blogs at Medical Megatrends and the Future of Medicine.

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