Cancer — 5

Listing cancer types by organ—which has been the only classification used for over one hundred years—exemplifies our unwillingness to acknowledge progress in the science. Cancers can now much more usefully be defined by their molecular characteristics, often agnostic to the organ in which they first showed up. Having sequenced the genomes of tens of thousands of tumors to identify driver mutations, and tagged these to treatment response, we have new ways to categorize cancer that are not yet part of routine medical practice. This is causing unnecessary delays for treatment in millions of people. Patients with breast or gynecologic cancer had to wait seven to ten years before they could receive nivolumab (Opdivo), an immunotherapy monoclonal antibody that targets the PD-L1 protein, expressed at high levels by many cancers across organ types. Similarly, PARP inhibitors, such as olaparib (Lynparza) were shown to kill cells with BRCA1 or BRCA2 mutations in 2005. In 2014, olaparib was approved for ovarian cancer, but it took up to six years before it got approval for breast, pancreatic, and prostate cancers. With that delay, about two hundred thousand people who might have benefited lost their lives. We now have so many mutation-specific treatments, as I’ll review, but the potential to apply these for people with cancer is too often lost, because they don’t match up by the habitual organ classification. We frequently miss out because patients do not have full molecular characterization of their tumor. This is tragic at a time when sequencing costs have been dramatically reduced and when AI can often determine driver mutations alongside response to immunotherapy.

Figure 6.3. New cancers by type and sex in the United States, 2024 cancer types. Adapted from Brianna Abbott, “Many cancers are on the rise in the U.S., even as overall deaths fall,” Wall Street Journal, January 17, 2024, https://www.wsj.com/health/healthcare/cancer-deaths-rates-prevention-f73c82a4.

The one-size-fits-all approach is based on age, and it isn’t working well. For five organ cancers—breast, colon, lung, cervical, and prostate—age is the singular criterion used for who should have screening. But only 14 percent of cancers diagnosed each year in the United States for the first four organ types are detected via screening. This comes at a cost of over $40 billion per year, a high rate of false positives, and marked controversy as to what should be the appropriate age for initiation, frequency, and cutoff. The data show how low a yield we see from our current approach of mass screening: only one person out of one thousand screened over ten years avoids death from that particular cancer.