Friday, March 25, 2016

Progress against cancer? Let's think about it.

It is difficult to pick up a newspaper these days without reading an article proclaiming progress in the field of cancer research. Here is an example, taken from an article posted on the MedicineNet site (1). The lead-off text is: "Statistics (released in 1997) show that cancer patients are living longer and even "beating" the disease. Information released at an AMA sponsored conference for science writers, showed that the death rate from the dreaded disease has decreased by three percent in the last few years. In the 1940s only one patient in four survived on the average. By the 1960s, that figure was up to one in three, and now has reached 50% survival."

Optimism is not confined to the lay press. In 2003, then NCI Director Andrew von Eschenbach, announced that the NCI intended to "eliminate death and suffering" from cancer by 2015 (2), (3). Update: it's 2016 and still no cancer cure.

Bullish assessments for progress against cancer are a bit misleading. There is ample historical data showing that the death rate from cancer has been rising throughout the twentieth century, and that the burden of new cancer cases will rise throughout the first half of the twenty-first century (4). If you confine your attention to the advanced common cancers (the cancers that cause the greatest number of deaths in humans), we find that the same common cancers that were responsible for the greatest numbers of deaths in 1950 are the same cancers killing us today, and at about the same rates (5), (6). Furthermore, the age-adjusted cancer death rate, the only valid measurement of progress against cancer, is about the same today as it was in 1950 (7). According the the U.S. National Center for Health Statistics, the age-adjusted cancer death rate in 1950 was 194 deaths per 100,000 population (8). In 2004, the death rate was the same, 194 per 100,000 population (8). Hardly an occasion for celebration.

In 1971, President Richard M. Nixon signed the National Cancer Act into law, marking the year that the United States launched its War on Cancer. For the next two decades, the U. S. cancer death rate rose steadily. Then in 1991, the U. S. cancer death rate began to decline, incrementally. It is tempting to conclude that 1991 marked the beginning of victory in our war against cancer, and that the steady, incremental declines in U. S. cancer death rates will continue in future decades, until cancer is fully eradicated. The decline in the cancer rate since 1991 is counter-balanced by the rise in the rate of cancer deaths between 1975 and 1991. What accounts for the rise in cancer deaths after 1975 and the restoration of the 1975 rates following 1991? There's no mystery here. The rise was due to smoking; the fall was due to smoking cessation (4). The post-1991 drop in the U.S. cancer death rate has only served to bring us full circle to our 1950 cancer death rate.

You may be thinking that cancer is a difficult problem, but at least the U.S. is working on the leading edge of cancer care. If cancer is a problem for us, it must be must worse for all the underdeveloped countries in the world. Nope. The U.S. has a high cancer death rate when compared to other countries (9). Kuwait, Panama, Ecuador, Mexico and Thailand have a much lower cancer death rate than the United States. American citizens intent on lowering their cancer death rate would be better off immigrating across the border, to Mexico, than waiting for the U.S. win its war against cancer.

Despite the many billions of dollars spent on research and treatment for cancer, we have made negligible progress toward reducing the number of people who die each year from cancer. The reason that cancer organizations can announce major gains against cancer and can promise to eliminate cancer deaths by 2015 is due entirely to the magic of data misinterpretation!

To see how the deception works in the cancer field, you need to start with the definition of "survival." To a layperson, the term "survival" indicates avoidance of death. For example, the survivors of a plane crash are the people who did not die in the crash. To an oncologist, survival is the time interval between diagnosis and death. Suppose that oncologists announce that a new treatment of pancreatic cancer produces a 1% increase in survival. Layman will interpret this to mean that a person with pancreatic cancer will have a 1 in 100 chance of being cured of his cancer above and beyond his chances for cure with the older treatment. To most people with cancer, that 1 in 100 improvement, though small, is worth any price. Unfortunately, this is not the case at all. To the oncologists who made the announcement, a 1% increase in survival indicates that if the life expectancy following diagnosis of pancreatic cancer is 100 days, then the life expectancy following diagnosis with the new treatment is 101 days. In either case, most patients with advanced pancreatic cancer will die. The patients receiving the new treatment may reasonably expect to survive a bit longer (in this hypothetical case, an average of one day longer).

You may be asking yourself about the validity of claims that we can now cure many childhood cancers that could not be cured in prior generations. Thankfully, these claims are true and accurate. Many children with cancer can now be cured. However, the overall incidence of childhood cancers has risen 36% since 1976 (10). This rise in childhood cancer incidence has erased about half of the overall benefits from the rising cure rates.

Real progress has been made towards curing rare cancers, such as gastrointestinal stromal tumors (GISTs), chronic myelocytic leukemia, and Hodgkin Disease. There is a biological reason why the rare cancers are easier to cure than the common cancers, and this fascinating topic is discussed in detail in my book, Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases. In a nutshell, research into the genetics of tumors has shown us that some cancers are characterized by simple genetic errors. It turns out that the tumors with simple genetic errors coincide with the rare tumors of childhood and certain rare tumors of adults. The small number of gene alterations in these rare tumors permits us to effectively target chemotherapeutic agents against a single vulnerable metabolic pathway. Complex common cancers may share key metabolic pathways with simple rare cancers, but it will take a while before we can effectively use this knowledge to develop effective treatments for the common cancers.

Cancer projections provided by the NCI's SEER program (the National Cancer Institute's Surveillance, Epidemiology, and End Results), indicate that between the years 2000 and 2050, the number of new cancer cases per year will more than double, from 1.3 million new cases in 2000 to 2.8 million new cases in 2050 (11). The projected yearly increase in cancer cases, if unchecked, will put additional strain on the wobbly American healthcare system.

After hundreds of billions of dollars were spent on cancer research and cancer treatment, with little to show for the effort, why did any of us believe that the dying would end by 2015? Humans live in hope; we would rather believe a hopeful lie than a hopeless truth.

- Jules Berman (copyrighted material)

key words: cancer, rare diseases, orphan diseases, cancer cure, cancer treatments, progress in cancer research, cancer statistics, jules j berman


[1] MedicineNet. Better and Longer Survival for Cancer Patients. Available from:

[2] Kaiser J. NCI Goal Aims for Cancer Victory by 2015. Science 299:1297-1298, 2003.

[3] Eschenbach AC. NCI sets goal of eliminating suffering and death due to cancer by 2015. Journal of the National Medical Association 95:637-639, 2003.

[4] Berman JJ. Precancer: The Beginning and the End of Cancer. Jones and Bartlett, Sudbury, 2010.

[5] Bailar JC, Gornik HL. Cancer undefeated. N Engl J Med 336:1569-1574, 1997.

[6] Leaf C. Why We're Losing The War On Cancer: And How To Win It. Fortune Magazine, March 22, 2004.

[7] Hoyert DL, Heron MP, Murphy SL, Kung H-C. Final Data for 2003. National Vital Statistics Report. 54:(13), April 19, 2006.

[8] Health, United States, 2004. National Center for Health Statistics, Hyattsville, Maryland, 2004.

[9] Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. Lyon, France: International Agency for Research on Cancer, 2013.

[10] Ries LAG, Smith MA, Gurney JG, Linet M, Tamra T, Young JL, et al. Cancer Incidence and Survival among Children and Adolescents: United States SEER Program 1975-1995, National Cancer Institute, SEER Program. NIH Pub. No. 99-4649. Bethesda, MD, 1999.

[11] Hayat MJ, Howlader N, Reichman ME, Edwards BK. Cancer Statistics, Trends, and Multiple Primary Cancer Analyses from the Surveillance, Epidemiology, and End Results (SEER) Program. The Oncologist 12:20-37, 2007.

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