Detect Cancer Early Using Blood Biopsy
Innovative blood biopsy tests are revolutionizing cancer screening by detecting tiny traces of tumor DNA in the bloodstream, allowing for earlier diagnosis
In his wonderful book, "The Emperor of All Maladies: A Biography of Cancer", Siddhartha Mukherjee presents cancer as a formidable, timeless, and pervasive adversary that humanity has been battling for centuries. Despite centuries of efforts, cancer has remained an elusive and deadly disease, earning it the moniker of the "emperor of all maladies".
Thanks to the human genome project and advances in understanding cancer biology, there has been a welcome development of targeted therapies that specifically inhibit cancer-driving mutations. For example, in lung cancer, targeted therapies against EGFR and HER2 mutations have significantly improved 1-year survival rates from around 10% without treatment, to 60-80% with targeted therapy. In addition, immunotherapies such as checkpoint inhibitors have extended lifespans for patients with advanced cancers that were previously very difficult to treat. For example, checkpoint inhibitors like pembrolizumab (Keytruda), nivolumab (Opdivo), and ipilimumab (Yervoy) have led to durable, long-term remissions in patients with advanced melanoma, lung cancer, kidney cancer, and other solid tumors. In some cases, checkpoint inhibitors have resulted in complete responses and cures, especially when used in combination.
The challenge lies in detecting the presence of cancerous cells at an early stage when interventions can result in positive outcomes for the patient. For instance, some 40% of lung cancers are not discovered until the cancer reaches the most serious stage (IV), when the survival rates are extremely poor. The patient does not notice any symptoms early on, while the cancer cells multiply exponentially. Unfortunately, only 5 types of cancer—colorectal, lung (for those at risk), breast, cervical, and prostate—have recommended screening tests that can identify cancer earlier. Most other cancers, like pancreatic and ovarian, do not show symptoms early and are often diagnosed at a later stage.
As shown in the chart, the 5-year survival rate is strongly dependent on the stage when cancer is detected in the patient: localized (Stage I) versus metastasized (Stage IV). For instance, when lung cancer is diagnosed early before it has time to spread (Stage IA1), the overall 5-year cancer-specific survival rate is almost 9 times higher than when cancer is diagnosed late (Stage IVA).
What are Liquid (Blood) Biopsies?
Fortunately, there is a promising new approach for detecting various types of cancer early and monitoring cancer progression and treatment response through a simple blood draw. These so-called liquid biopsies analyze cell-free circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) that are shed by tumor cells into the bloodstream. The presence and amount of these tumor components (either their DNA or entire tumor cells) in the blood can indicate the presence of cancer. Given that each tumor has its distinct set of genetic mutations, the ctDNA in the blood can be analyzed to look for the telltale mutational patterns that are associated with lung cancer, or any other type of tumor for that matter. In addition to early detection, liquid biopsies can also be performed repeatedly to monitor how well a patient is responding to treatment by tracking changes in ctDNA levels over time, helping guide adjustments to therapy. After treatment, liquid biopsies also allow for earlier detection of cancer recurrence by identifying rising ctDNA levels much before the tumor shows up on radio-graphic images or clinical symptoms manifest. A key advantage of liquid biopsies is that they only require a simple blood draw, avoiding the risks and discomfort associated with invasive surgical tumor biopsies such as brain biopsies, a subject I will cover in a later blog post.
Galleri - An Cancer "Early Detection" Test from Grail
The good news is that there is an early detection blood test for cancer that is commercially available. The Galleri test, developed by GRAIL, can detect signals of over 50 types of cancers before symptoms appear. If a cancer signal is detected, the test can also predict the likely place of origin in the body. While the test has shown promising results in clinical studies, it is important to note that it is not yet FDA-approved and can produce false positives and false negatives. Currently, the test is not covered by either Medicare or any of the private insurance payers. While the list price is $949, Grail does run promotions, so watch out.
As shown by the accompanying chart, the sensitivity (ability to detect cancer when present) of the Galleri test is significantly lower for Stage I and Stage II cancers. For Stage I and II cancers combined, the sensitivity is only 27.5%, meaning it misses over 70% of early stage cancers. Clearly, the science needs a lot more work before Galleri can call itself a true early detection test for cancer. In the near future, I will highlight other disruptive startups that are employing innovative approaches to addressing this difficult challenge.
Having said that, here are some actual patient examples that hint at its potential moving forward.
Valerie's story: Valerie was healthy and active, with no suspicion of cancer, when she took the Galleri test. The test detected a cancer signal and predicted the origin as the pancreas and gallbladder. Further testing confirmed this unexpected diagnosis, allowing for earlier intervention.
Mary's story: Mary's doctor, Robert Korolevich, MD, ordered the Galleri test for her. The test detected a cancer signal, which led to additional testing that diagnosed Mary with cancer.