Will I get bowel cancer like my mother, or will it be breast cancer like my sister, or something else? After decades working in cancer and witnessing its devastating impact on people close to me, I can’t help but ask myself this from time to time.
Half of all cancer diagnoses are one of the four most common types—bowel, breast, lung or prostate—while the rest fall among the 200-plus less common types. But well over half of all cancer deaths are not in one of the most common types. And no one gets to choose which cancer they’ll get.
If we had a choice, we’d opt for a cancer with a high survival rate where the treatments don’t have too many side effects. Typically this means cancers that have a fair chance of being detected early. Cancers detected at an earlier stage (especially before stage IV) are usually easier to treat, with more available options, fewer side effects and better outcomes.
For most cancer types, poor outcomes for late stage disease are driven by the strikingly low survival at stage IV. For example, only about one in 20 people diagnosed with stage IV oesophageal cancer survive five years, compared with one in five people diagnosed at stage III. In the past few years there have been significant advances in curative treatments for many stage III cancers, such as using new immunotherapy drugs after surgery, with further treatments coming through clinical trials.
Screening is a key pillar of early detection, with programmes in England for bowel, breast, cervical and (for those at high risk) lung cancers. Patient outcomes are also better when cancer is detected through screening compared to other routes, such as emergency presentation. One quarter of people with rare and less common cancers are diagnosed following an emergency admission to hospital, compared with one in five for people with the four most common cancers.
But our current approach to screening is ignoring the vast majority of cancer types. Among the unscreened cancers are some of the most aggressive types that are usually detected at harder-to-treat stages, such as pancreatic, ovarian, oesophageal and liver.
Despite this disparity, having a screening programme for every less common cancer is not the solution. Each single-cancer screening programme has its own individual false-positive rate, and these can add up for people participating in multiple screening programmes. This increases the chance of people being told they might have cancer when they don’t, leading to unnecessary procedures and, often, anxiety.
In addition, the low prevalence of each less common cancer means that the trials required to prove any new single-cancer screening test would need to be unfeasibly large, because so few people have the disease at any given time. It’s also highly unlikely that adding progressively more single-cancer screening tests for cancers with low incidence would be cost-effective, because in a potential screening programme, only a modest number of new cases would be detected each year relative to the population being screened.
A new generation of blood tests that can detect many types of cancer from a single blood sample provides hope for early detection for people with rare and less common cancers
A new generation of blood tests that can detect many types of cancer from a single blood sample provides hope for early detection for people with rare and less common cancers. These multi-cancer early detection (MCED) tests screen simultaneously for many cancer types to detect a signal of cancer even before symptoms appear. Ideally the test should also predict the most likely origin of the cancer signal, to help determine the diagnostic investigations needed to confirm a cancer diagnosis. GRAIL has taken this approach with its Galleri® test, the only clinically validated MCED test with demonstrated performance in individuals being screened for cancer.
A crucial feature of the Galleri test is that a cancer signal detected (positive) result strongly indicates the presence of cancer, considerably more so than an abnormal result from a single-cancer screening modality. This is known as the positive predictive value (PPV). For Galleri, this value is driven by the high combined cancer prevalence when screening for multiple cancers and the test’s single low false-positive rate. This advantage is especially important for the many rare and less common cancer types for which current screening capability is effectively zero.
If the less common cancers are ever to benefit from screening and the possibility of earlier detection, we need to shift our thinking away from one screening programme per cancer type. Multi-cancer screening offers a tantalising prospect that could be realised in the not too distant future, given that the results from the world’s first randomised controlled trial of an MCED test, the NHS-Galleri trial, are anticipated this year.
The multi-cancer approach would improve equity of opportunity for screening across cancer types, providing a chance to stem the tide of late diagnosis and poor outcomes experienced by many people with rare and less common cancers. Soon, the opportunity for early detection won’t be determined by what cancer you get.
Sara Hiom is vice president of external affairs at GRAIL Bio UK
