Highlights of the VA’s Contributions to Cancer Research

WASHINGTON — In the more than 90 years since the VA established its first tumor research laboratory at the Hines, Ill., VA hospital, the agency has published some of the most instrumental studies in cancer in the U.S.

Lung cancer

Click to Enlarge: The VA has remained at the forefront of smoking cessation efforts, especially since most veterans report smoking at some point in their lives. In 1999, 33% of veterans enrolled in VA health care identified as smokers, but by 2020 that number had dropped to 13.3%. Poster from VA

In the 1950s, VA researcher Robert Schrek, MD, a pathologist at the Hines facility, published a stunning study showing tobacco smoking as a cause of cancer of the lungs, larynx and pharynx.¹ Until that point, environmental pollutants were thought to be the leading cause of the rising number of lung cases, in part, because smoking was so ubiquitous.

Shrek’s results remained controversial until another VA researcher, Oscar Auerbach, MD, of the VA’s East Orange hospital, proved the connection by causing lung cancer and other pathological changes in the lungs of animals who were taught to smoke and inhale cigarettes over a three-year period. Further, Auerbach demonstrated the risk of lung cancer in individuals exposed to second-hand smoke.^{2, 3}

VA teams also tackled cancer care, with researchers at the Greater Los Angeles Healthcare System developing the nicotine patch for smoking cessation in the 1980s.⁴

In another cancer often caused by smoking, VA research in the 1990s provided a less radical option for a treatment of laryngeal cancer. Total laryngectomy, removal of the vocal cords, was standard of care until the VA Laryngeal Cancer Study Group showed that patients with advanced laryngeal cancer who received chemotherapy and radiation had the same survival rate as those who had surgery and radiation.⁵

Viral cancers

The 1950s also saw a breakthrough in the work by Ludwik Gross, MD, who served as chief of cancer research at the Bronx VA. Gross demonstrated that leukemia could be virally transmitted in mammals, and that the host’s immune system could also block development of the disease. In the process, he discovered retroviruses, which cause a range of mammalian leukemias, lymphomas and sarcomas as well as autoimmune deficiency syndrome (AIDS). He published his reference work, Oncogenic Viruses, in 1970 and received the Albert Lasker Basic Medical Research Award in 1974 for his contribution to medicine in 1974.⁶

Prostate cancer

Research on prostate cancer ramped up in the 1960s, and in 1962, Donald Gleason, MD, and his colleagues at the Minneapolis VA developed the Gleason score still used today for classification and prognosis of prostate cancer.⁷

In 2017, the groundbreaking PIVOT study by the VA demonstrated that most men with prostate cancer do not achieve a mortality benefit from surgery, leading to further research to better define those that could benefit and refine the best approach to “watchful waiting” for others.⁸

Men who experience recurrence of prostate cancer following initial treatment typically receive androgen receptor-targeted therapy. In time, however, many of them will relapse and develop castration-resistant prostate cancer. Stephen Plymate, MD, of the VA Puget Sound Health Care System, received Middleton prize, the highest honor bestowed by the VA Biomedical laboratory Research and Development Service, for his decades of work increasing understanding of the biological mechanisms underlying the development of resistance to androgen deprivation, how to predict patient response to therapies, and development of drugs to that target androgen resistance.⁹

A study published in 2020 found that while in the U.S. as a whole, Black men are more likely to be diagnosed with prostate cancer and are twice as likely to die from it, in the VA they do not, calling into question whether the cancers are actually more aggressive or if lack of access to health care is the primary factor in disparities in outcomes. In fact, the research conducted by Paul Riviere, MD, and colleagues at the VA San Diego Health Care System determined that Black men did not have more aggressive disease at diagnosis, and that, in the VA, they were slightly less likely than non-Hispanic white men to die of prostate cancer within 10 years of diagnosis.¹⁰

Colorectal cancer

Researchers from 13 VAMCs published a study in 2000 showed that colonoscopy, which can evaluate the entire colon, outperforms sigmoidoscopy, which examines only the lower part of the organ, in detection of neoplasms in asymptomatic individuals. The study led to recommendations for use of colonoscopy for screening of average-risk adults and supported coverage of the procedure by Medicare and other payers.¹¹

Like the San Diego VA-led study on prostate cancer, research led by a team at the Richard Roudebush VAMC in Indianapolis explored whether genetic differences existed that drove higher rates of colorectal cancer in Black individuals than in non-Hispanic whites. Analyzing results from 90,000 veterans screened by colonoscopy at 18 VA facilities, the team determined that, overall, Black veterans did have a higher risk of the cancer. Among those who were routinely screened, however, there was no difference in risk, indicating that non-biological factors played the determining factor in cancer progression and outcomes.¹²

1. Schrek R, Baker LA, et al. Tobacco smoking as an etiologic factor in disease; cancer. Cancer Res. 1950 Jan;10(1):49-58. PMID: 15398042.
2. Auerbach O, Petrick TG, Stout AP, Statsomger AL, Muehsam GE, Forman JB, Gere JB. The anatomical approach to the study of smoking and bronchogenic carcinoma; a preliminary report of forty-one cases. Cancer. 1956 Jan-Feb;9(1):76-83. doi: 10.1002/1097-0142(195601/02)9:1<76::aid-cncr2820090106>3.0.co;2-d. PMID: 13284702.
3. Auerbach O, Stout AP, Hammond EC, Garfinkel L. Changes in bronchial epithelium in relation to cigarette smoking and in relation to lung cancer. N Engl J Med. 1961 Aug 10;265:253-67. doi: 10.1056/NEJM196108102650601. PMID: 13685078.
4. Rose JE, Jarvik ME, Rose KD. Transdermal administration of nicotine. Drug Alcohol Depend. 1984 May;13(3):209-13. doi: 10.1016/0376-8716(84)90061-9. PMID: 6734425.
5. Department of Veterans Affairs Laryngeal Cancer Study Group; Wolf GT, Fisher SG, Hong WK, Hillman R, Spaulding M, Laramore GE, Endicott JW, McClatchey K, Henderson WG. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med. 1991 Jun 13;324(24):1685-90. doi: 10.1056/NEJM199106133242402. PMID: 2034244.
6. Gross L. Oncogenic Viruses. Second Ed. Pergamon Press, Oxford: 1970.
7. Gleason DF. Classification of prostatic carcinoma. Cancer Chemother Rep. 1966 Mar;50:125-128.
8. Wilt TJ, Jones KM, Barry MJ, Andriole GL, Culkin D, Wheeler T, Aronson WJ, Brawer MK. Follow-up of Prostatectomy versus Observation for Early Prostate Cancer. N Engl J Med. 2017 Jul 13;377(2):132-142. doi: 10.1056/NEJMoa1615869. PMID: 28700844.
9. Plymate SR, Haugk K, Coleman I, Woodke L, Vessella R, Nelson P, Montgomery RB, Ludwig DL, Wu JD. An antibody targeting the type I insulin-like growth factor receptor enhances the castration-induced response in androgen-dependent prostate cancer. Clin Cancer Res. 2007 Nov 1;13(21):6429-39. doi: 10.1158/1078-0432.CCR-07-0648. PubMed PMID: 17975155.
10. Riviere P, Luterstein E, Kumar A, Vitzthum LK, Deka R, Sarkar RR, Bryant AK, Bruggeman A, Einck JP, Murphy JD, Martínez ME, Rose BS. Survival of African American and non-Hispanic white men with prostate cancer in an equal-access health care system. Cancer. 2020 Apr 15;126(8):1683-1690. doi: 10.1002/cncr.32666. Epub 2020 Jan 27. PMID: 31984482.
11. Lieberman DA, Weiss DG, Bond JH, Ahnen DJ, Garewal H, Chejfec G. Use of colonoscopy to screen asymptomatic adults for colorectal cancer. Veterans Affairs Cooperative Study Group 380. N Engl J Med. 2000 Jul 20;343(3):162-8. doi: 10.1056/NEJM200007203430301. Erratum in: N Engl J Med 2000 Oct 19;343(16):1204. PMID: 10900274.
12. Imperiale TF, Daggy JK, Imler TD, Sherer EA, Kahi CJ, Larson J, Cardwell J, Johnson CS, Ahnen DJ, Antaki F, Ashley C, Baffy G, Dominitz JA, Hou J, Korsten MA, Nagar A, Promrat K, Robertson DJ, Saini S, Shergill A, Smalley WE. Prevalence of Advanced Colorectal Neoplasia in Veterans: Effects of Age, Sex, and Race/Ethnicity. J Clin Gastroenterol. 2021 Nov-Dec 01;55(10):876-883. doi: 10.1097/MCG.0000000000001402. PMID: 34049372.