A study conducted by researchers at Stanford University School of Medicine provides strong new evidence that malignant tumors may grow undetected in the body for a decade or more before they can be sniffed out by the most sophisticated blood tests currently available. The findings, which were published in the journal Science Translational Medicine, emphasize the urgent need to identify and clinically validate more sensitive biological markers (biomarkers) that can detect tiny cancers in the body before they grow large enough to become dangerous. 

Most types of cancer, aside from skin cancer, are discovered either when tumors start causing symptoms or grow large enough to become visible on X-ray or MRI. By the time cancer gets to this point, it is much more difficult to treat and is likely to have spread (metastasized) beyond the site of origin. Ovarian cancer, for example, has a 5-year survival rate of 90% if caught early (stage I). Unfortunately, most cases of ovarian cancer are diagnosed when the patient experiences symptoms—usually stages III or IV)—at which point the 5-year survival rate drops to less than 30%. 

For this reason, cancer researchers are urgently searching for biomarkers that can indicate the presence of tiny, early stage tumors growing somewhere in the body. As they grow, malignant tumors shed numerous proteins, DNA fragments and other substances into the bloodstream. Detecting these substances using simple blood tests would be an inexpensive, non-invasive method for diagnosing cancer, monitoring response to treatment, and even screening healthy individuals. For example, growing tumors secrete large amounts of growth factors that stimulate new blood vessel growth (angiogenesis). Oncologists are looking for blood-based markers of tumor angiogenesis that could be used to monitor response to antiangiogenic cancer therapies, and possibly to also detect microscopic cancers in the body in otherwise healthy individuals. 

Only a few cancer biomarkers are currently used in the clinic, and most are not very specific, meaning that tests for them yield a high number of false positive results, which can lead to unnecessary tests and treatments. Current cancer biomarker tests are also not particularly sensitive—i.e., they are only able to detect larger tumors. The Stanford researchers used sophisticated mathematical models to determine the smallest size of ovarian and prostate cancers likely to be detectable using currently available blood tests for these tumor types. For ovarian cancer, the scientists used a widely available blood test for CA125, a protein secreted by ovarian cancer cells, which is mainly used to monitor for disease recurrence. 

Based on their modeling, an ovarian tumor could grow unnoticed for at least 10 years to a size of 25.36 millimeters, or about the size of a large grape, before being detectable by a blood test for CA125. This is because healthy women have small amounts of CA125 in their blood circulation, so that cancerous ovarian tumors need to grow quite large before the amount of CA125 produced by the tumor exceeds the normal cutoff limit. Other studies have indicated that the non-detectable growth times of pancreatic and colorectal cancers could range up to 50 years. 

Many clinical trials of cancer drugs now include panels of investigational biomarkers to help to predict treatment response based on patient and tumor characteristics. While some of these show promise, significant challenges remain. One problem is that cancer does not tend to grow in a steady, linear fashion; tumors can remain dormant for long periods of time followed by a period of rapid growth, such as occurs after angiogenesis is initiated. Therefore the levels of any particular biomarker in the blood can fluctuate dramatically.

Cancer is also an exceedingly complex disease, with many different processes occurring at once and interacting with each other. Despite these hurdles, most cancer physicians are optimistic that sensitive blood tests can be developed to find microscopic cancers in the body and allow for intervention at the earliest stages, whether through dietary ‘chemoprevention’, lifestyle modification or other routes.