Early Detection

CATCHING CANCER WHEN IT'S CURABLE


BRUCE RATNER and ADAM BONISLAWSKI


“Drawing on success stories with cervical, lung, prostate, and colon cancer, [Ratner and Bonislawski] provide clear examples of effective screening programs . . . that have reduced not only overall cancer mortality but also healthcare disparities. A wonderful voice of optimism, balanced caution, and a path forward.” —Jose G. Guillem, MD



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About the Book

Catching cancer early remains the single best way to combat a disease that is the second-leading killer in both the US and worldwide. But the vast majority of resources in the fight against cancer are devoted to relatively ineffective late stage treatments. Early Detection examines this important anomaly in an accessible and expertly researched survey.

In a co-authorship that brings together the passion and urgency of someone touched deeply by the experience of cancer with the knowledge of a skilled science writer, Ratner and Bonislawski narrate compelling case studies across a range of screening programs and different forms of cancer. They look at the science underpinning early detection and discuss the organizational and social challenges of widespread screening, a dimension that has been shown to be especially important in the COVID-19 pandemic. And they call for the government and the medical establishment to provide resources for expanding screening, especially in economically disadvantaged communities that have traditionally been underserved.

320 pages • Paperback ISBN 978-1-68219-420-1 • E-book ISBN 978-1-68219-352-5

About the Authors

ratner and bonislawski author photo

Photo by Colin Robinson

Bruce Ratner (right) has led an eclectic life. After focusing much of his undergraduate coursework on math, biology, and physics, he started his career in law and public service as an assistant professor at New York University Law School and Commissioner of Consumer Affairs under Mayor Ed Koch. In his late 30s, he moved into real estate, becoming one of the city’s largest developers. In 2016, Ratner’s brother, Michael, died of metastatic cancer. Through this tragedy, Ratner came to realize that early detection was the key to reducing cancer mortality. Following his brother’s death, he founded a non-profit, the Michael D. Ratner Center for Early Detection of Cancer, to research and promote better cancer screening. He is on the boards of Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, and the Cold Spring Harbor Laboratory.

Adam Bonislawski is a science writer with more than 10 years of experience covering genomic and proteomic research and diagnostics development with a focus on cancer and early detection. His writing ranges widely over academic research, companies and technologies. The publications he writes for, GenomeWeb and 360Dx, are read by thousands of cancer researchers and doctors as well as a wide range of healthcare entrepreneurs and investors, and he has scientific and media contacts at many of the major cancer and academic research centers in the United States and Europe. In addition to his work as a science writer, Adam writes about business and real estate for the Wall Street Journal, New York Post, and Commercial Observer.

Read an Excerpt

From Chapter 1: No Way to Fight a War

On December 23, 1971, flanked by Christmas greenery and a set of gaudy yellow curtains, Richard Nixon stepped before some 130 scientists and legislators gathered in the White House dining room and announced the enactment of the National Cancer Act.

Neither the text of the bill nor the President’s remarks made any reference to a “war” on cancer, but that’s how the effort Nixon inaugurated that afternoon became known, and today we’re nearly six decades into the longest, albeit metaphorical, military engagement in United States history.

Which raises the question—how are we doing?

To be blunt, not so great. We’re fifty years in with no end in sight.

There are many reasons our battle against cancer has proceeded so haltingly, not the least of which is the basic fact that cancer is a devastating disease and exceedingly challenging to treat. It hasn’t helped, though, that from the very beginning we’ve fundamentally misplaced our priorities in fighting it.

Each year, the American Cancer Society publishes a report detailing cancer incidence and mortality trends. According to the organization’s most recent figures, the US cancer death rate peaked in 1991 and has declined since then by around 1.5 percent a year. All told, that amounts to a 32 percent drop, from 215 deaths per 100,000 people in 1991 to 146 deaths per 100,000 in 2019 [i](the last year for which data is available).

That’s respectable, if hardly stunning, progress. It’s been largely driven, however, by two things: a drop in smoking rates and the earlier detection of breast, prostate, and colorectal cancers. Take away those developments, and the cancer landscape looks very much like it did five decades ago.

A quick survey of survival statistics makes this clear. For example, from 1974 to 1985, 14 percent of patients diagnosed with late-stage colon cancer survived for five years or more[ii]. Three decades and billions of research dollars later, that figure hadn’t budged. Patients diagnosed between 2011 and 2017 (the most recent years for which data is available) still had a five-year survival of 14 percent[iii].

Just 1 percent of late-stage lung cancer patients diagnosed during the 1974 to 1985 window lived five years or more. By 2011 to 2017, that number had risen, but only to 8 percent.

For breast cancer, the figures are 19 percent and 29 percent[iv], respectively. The story is the same for prostate cancer. Five-year survival for late-stage patients was 30 percent between 1974 and 1985. It was 31 percent during the 2011 to 2017 span[v].

The converse is also true. Patients diagnosed with early-stage cancer had, and continue to have, relatively good five-year survival rates. Between 1974 and 1985, 84 percent of patients with localized colon cancer survived for five years or more. Between 2011 and 2017, 91 percent did. For breast cancer, the corresponding figures were 91 percent and 99 percent, respectively. For prostate they were 84 percent and 99 percent. For lung cancer they were 37 percent and 64 percent.

With a few exceptions like testicular cancer and certain leukemias and lymphomas, this pattern holds across the board and has for half a century. If you catch and treat your cancer early, your odds of survival are fairly good. If you find your cancer only after it has spread, you are probably going to die fairly soon.

The European Society for Medical Oncology (ESMO), a professional organization for cancer doctors, maintains what it calls its Magnitude of Clinical Benefit Scale[vi], a compilation of approved cancer drugs scored according to their effectiveness. The database is divided into two sections—one for drug-cancer combinations that are potentially curative and the other for those that aren’t expected to be curative but that could possibly extend a patient’s life. Of the 318 treatments regimes currently detailed in the database, just thirty-eight fit the first category. That means the other 280, roughly 90 percent of the list, offer not the possibility of a cure but only of somewhat longer survival.

Probably not for very much longer, though. Even for the most effective agents, survival gains are almost always measured in months, not years.

Take, for instance, the ESMO scale’s scoring of Merck’s immune checkpoint inhibitor Keytruda as a treatment for patients with advanced lung cancer. Checkpoint inhibitors work by inactivating proteins on the surface of cancer cells that let them hide from a patient’s immune system. By attacking these proteins, the drugs clear the way for the body’s own defenses to fight off the cancer.

Heavily hyped, these immunotherapies have on occasion actually lived up to expectations, with some late-stage patients experiencing miraculous responses. Perhaps the most famous case is that of President Jimmy Carter, who received Keytruda for metastatic melanoma and is alive and essentially cancer-free five years after his diagnosis. In 2018, MD Anderson Cancer Center researcher James P. Allison and Kyoto University’s Tasuku Honjo were jointly awarded the Nobel Prize in Physiology or Medicine for their work illuminating the science underpinning these drugs.

All of which is to say it’s perhaps unsurprising that the ESMO guide rates Keytruda a 5, the top score available, indicating a “very high benefit.” But what does that score actually mean? Another five years of life? Four years? Three?

Not even. According to the studies upon which the ESMO score is based, Keytruda offered the median patient an extra 11.7 months of overall survival compared with the previous standard of care, the chemotherapy docetaxel. Docetaxel by itself provided 14.2 months of overall survival. Add them together and you’re at almost thirty months total. That’s what the war on cancer’s most cutting edge weaponry gets you—about two and a half years[vii].

Most people, though, are in the dark about this situation. In 2012, a team led by doctors at Boston’s Dana-Farber Cancer Institute set out to learn how realistic late-stage cancer patients were about the effectiveness of chemotherapy. They surveyed 1,193 patients, 710 with stage IV lung cancer and 483 with stage IV colorectal cancer, asking them whether they thought chemotherapy might cure them. Like the majority of stage IV cancers, both diseases are almost invariably fatal, and yet 69 percent of lung cancer patients and 81 percent of colorectal cancer patients said they believed that chemotherapy offered them a chance of being cured[viii].

This sort of false hope is a shame, but it’s understandable. Most patients aren’t cancer experts, after all. Vastly more troublesome is the fact that a similar misapprehension has underpinned our entire cancer fighting strategy. Our successes have come overwhelmingly from improved prevention and early detection, but if you were to look at how we spend research dollars, you’d almost certainly come to the opposite conclusion.

Bert Vogelstein is one of the preeminent cancer biologists of our time. An oncologist at Johns Hopkins University in Baltimore, he was one of the first to characterize the role of certain genetic mutations in cancer development. Our fight against the disease has been “too focused on the idea of retaliation,” he said. “Cancers are only incurable once they have spread… and in the future we need to focus on detecting them before they have spread.”

Most common cancers take decades to develop, Vogelstein noted. “We have this huge window of opportunity… to intervene in that process, to detect those tumors early, and to cure them. But the amount of research that is devoted to these sorts of preventions is essentially trivial compared to that devoted to curing advanced cancers.”[ix]

Importantly, early detection and cancer drug development need not be seen as antagonists. On the contrary, earlier detection of cancer improves the outcomes of drug treatments. The lower a cancer patient’s disease burden, the better, on average, they respond to therapy. That’s true even for metastatic disease, where chemotherapy cure rates for individuals with micro-metastases (growths too small to be detected on a CT scan) are many-fold higher than for those with larger metastases. Earlier detection, in other words, can help some of our so-called “miracle drugs” come closer to fulfilling their promise. The idea isn’t to pit cancer screening against drug development; rather, it’s to more sensibly balance our support for the two so that each can work more effectively.

The bill President Nixon signed in the winter of 1971 called for $400 million to fund the National Cancer Institute (NCI) in 1972, $500 million in 1973, and $600 million in 1974. An additional $20 million was set aside in 1972 for cancer early detection and prevention efforts. That figure rose to $30 million in 1973 and $40 million in 1974.

Prevention and early detection, then, received less than 7 percent of the funds initially directed to the “War on Cancer.” Since then that number has climbed to around 10 percent of the NCI’s annual budget. In 2020[x], the institute spent just 13 percent of its $4 billion research budget studying cancer detection and diagnosis. That compares to 23 percent spent on investigations of basic cancer biology, 34 percent spent on research into treatments, and 29 percent on studies of cancer causation. As of April 2022, NCI had 94 ongoing clinical trials evaluating different cancer screening methods (a number of which are not actually focused on early detection but instead on areas like detection of recurrence in cancer patients following treatment). It had 4,830 looking into cancer therapies.

Footnotes:

[i] American Cancer Society (2022) Cancer Facts & Figures 2022.

[ii] Boring CC, Squires TS, Tong T. Cancer statistics, 1991. Bol Asoc Med P R. 1991 Jun;83(6):225-42. PMID: 1930475.

[iii] American Cancer Society (2022, March 1) Survival Rates for Colorectal Cancer.

[iv] American Cancer Society (2022, March 1) Survival Rates for Breast Cancer.

[v] American Cancer Society (2022, March 1) Survival Rates for Prostate Cancer.

[vi] ESMO (2020, January) ESMO-Magnitude of Clinical Benefit Scale Scorecards.

[vii] Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016 Apr 9;387(10027):1540-1550. doi: 10.1016/S0140-6736(15)01281-7. Epub 2015 Dec 19. PMID: 26712084.

[viii] Weeks JC, Catalano PJ, Cronin A, Finkelman MD, Mack JW, Keating NL, Schrag D. Patients’ expectations about effects of chemotherapy for advanced cancer. N Engl J Med. 2012 Oct 25;367(17):1616-25. doi: 10.1056/NEJMoa1204410. PMID: 23094723; PMCID: PMC3613151.

[ix] “Can we prevent cancer? Yes, says Bert Vogelstein, if we try harder.” YouTube, uploaded by Breakthrough, 22 August 2016

[x] National Cancer Institute (2022, January 26) Funding Allocated to Major NCI Program Areas.

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