In its 2012 annual plan titled “Cancer: changing the conversation”, NCI seems to advocate continuation of the status quo that justifies its ongoing broad-based initiatives, rather than to re-directing its activities. For instance, under “Prevention and Screening”, it states,

Cancer prevention includes efforts to forestall the process that leads to cancer, along with the detection and treatment of precancerous conditions at their earliest, most treatable stages, and the prevention of new, or second primary, cancers in survivors [713].

Perhaps NCI’s future direction in cancer prevention and screening will be better focused than outlined in the report. Indeed, while an in-depth knowledge of the specific molecular events that promote the development and progression of each type of cancer is lacking, we do know that approximately 53 % of all new cases of cancer are attributable to smoking, obesity [714], and alcoholism (Table 4.​1). Another 10 % can be traced back to exposure to carcinogenic viruses, 1.5 % to alcoholism, and 1.0 % to exposure to ultraviolet radiation [715]. These five, mostly behavior-associated cancers account for more than one third of all cancer deaths in the US [716]. Their control calls for behavioral changes supported by appropriate motivational and even compulsory legislation when needed. Although human behavior cannot be legislated successfully, the usefulness of anti-smoking campaigns has been validated by a 54 % decline in the smoking US population since 1965 (Table 3.​6), saving hundreds of thousands of lives each year. Altering other cancer-associated behaviors would generate similar results.

Except for immunization against cancer-causing viruses, any efficacious cancer prevention policy entails a long-term commitment to lifestyle changes of difficult implementation, reluctant participation by all parties involved, and deferred benefits. The success of such a policy hinges on being goal-oriented, realistic, and participatory, involving all stakeholders at the national, community, and caregiver levels. Hence, it must meet the following basic criteria:
In the US, targeting smoking, obesity, alcoholism, and over-exposure to ultraviolet light and carcinogenic viruses would meet the first criteria. Focusing on lung cancer within this category would, in part, meet the second. For instance, re-invigorating anti-smoking campaigns would further encourage smoking cessation and reduce the incidence rate of all types of cancers linked to cigarette smoking, including lung, oral cavity, esophagus, stomach, bladder, kidney, pancreas, larynx, cervix, and acute myelogenous leukemia. A concomitant early detection program focused on lung cancer would have a greater impact on overall cancer deaths than all other smoking-related cancers combined. Indeed, with its 7,000-plus chemical components, including at least 70 carcinogens, a cancer risk well-known by the tobacco industry as early as 1961 [717], tobacco is the most lethal of human carcinogens, a distinction underlined in the 1982 Surgeon General report that branded tobacco “the major single cause of cancer mortality in the United States.” However, despite successful national and local efforts to curb smoking, it retains its dominant position as the most hazardous cancer-promoting behavior, being responsible for approximately 28 % of cancer deaths in the United States [718]. Successful smoking cessation reduces disability and premature deaths by 50 % within 10 years of cessation. This is due to a 50 % reduction of coronary heart disease within 1 year, and a 50 % decreased incidence of strokes and of cancers of the lung, the oral cavity, and the esophagus after 10–15 years of abstinence [719]. After 15 years of tobacco abstinence, death rates fall to levels recorded in persons who never smoked.

Although obesity in itself does not cause cancer, unlike smoking, the strong correlation between obesity and several types of cancer is an indication that the obese individual has been exposed for many years to yet unknown cancer promoters contained in or mediated by certain types of diets. Diets deficient in cancer-protecting agents also have been postulated, leading to exploratory clinical trials designed to assess the potential cancer-preventive effect of selenium, retinoids,¹ vitamins, lycopenes,² and green tea, among others, with mixed results, at best. For instance, the Selenium and Vitamin E Cancer Prevention Trial (SELECT), launched to assess the long-term effect of vitamin E and/or selenium on risk of prostate cancer, enrolled 35,533 men. After 7–12 years follow-up, vitamin E was shown significantly to increase the risk of prostate cancer [720]. Instead, obesity prevention should rely primarily on national state, local, and caregiver-based educational campaigns modeled after smoking-cessation, aimed primarily at the general population but also at those who, for reasons of their own (e.g., ideological or financial), subscribe to the misguided and counterproductive hypothesis that obesity is a disease.

Likewise, vaccination against carcinogenic viruses such as HPV and HBV should be pursued aggressively, as should the development of new vaccines funded by the public purse, for the pharmaceutical industry is more interested in developing blockbuster drugs than revenue-poor vaccines. In fact, vaccination against HPV-16 and HPV-18 infections that cause 70 % of all cervical cancers [721], coupled with the safe and reliable Pap smear for detecting surgically curable early stage cervical cancer, provide the tools and the opportunity sharply to reduce the onset of the disease and progression to advanced stages and deaths, respectively. Regrettably, opposition to teenage vaccination and other factors have limited vaccine penetration to only 70 % of the eligible population and is responsible for a stagnant 5-year survival from cervical cancer between 1975 and 2008. In this context, it is ironic that recent research in cancer vaccines has focused not on developing vaccines against known carcinogenic viruses, but on vaccines designed to enhance the ability of the immune system to recognize alleged tumor antigens (e.g., MAGE, MART, CEA, HER-2, MUC-1, PSA) in attempts to mediate tumor rejection. Yet, after 20 years of attempts to coax the immune system into rejecting cancers using various forms of immunotherapy, only anecdotal successes have been reported. How then to explain researchers’ enduring fascination with the concept of immunotherapy? The answer is multifaceted but includes three major factors. First, the intellectual attractiveness of extending the concept of immune rejection of non-self (e.g., bacteria, viruses, transplanted organs) to cancer cells, even after the latter have been shown to be part of the self, albeit harboring genetic alterations. Second, the complexity of the immune system is challenging to immunologists, molecular biologists, and geneticists interested in probing its multifaceted dimensions. Third, the anticipation of academic and financial rewards and media acclaim that are sure to accompany any breakthrough in this domain, especially when compared to what is perceived as the lackluster endeavor of prophylactic anti-viral vaccine development.

Given the unassailing logic and safety of adopting the outlined cancer prevention approach as a national policy, the current practice of cancer chemoprevention is a misguided and often harmful concept emanating from our drug culture. There are several reasons for this. First, chemoprevention consists of administering agents expected to reduce the incidence or recurrence of cancer, especially in high-risk individuals, rather than to curbing the five unhealthy behaviors responsible for over 50 % of all cancers in the entire population. Second, the mechanism of action of chemoprevention is ill-defined and long-term side effects often offset cancer-preventing benefits. Moreover, because benefits are expected to accrue to a subpopulation of participants and long-term harmful effects and the size of the affected participants are unpredictable, very large studies and years of follow-up are necessary to establish their safety, efficacy, and risk-benefit ratio, at a very high cost, as demonstrated by the SELECT study and the Tamoxifen for Prevention of Breast Cancer trial [722]. Chemoprevention is another facet of the hit-and-miss approach that is the foundation of the search for anti-cancer drugs and has met the same fate: decades of stagnation. On the other hand, the outlined evidence-based prevention initiative focused on curbing smoking, obesity, and alcoholism that together account for more than 50 % of all cancers, year after year, constitutes the first step of a highly focused, evidence-based, three-prong approach to cancer control that offers the best prospects of achieving incremental reductions in national cancer incidence and mortality rates that should validate its well-grounded foundation, promote stakeholders’ cooperation and support, and ensure its long term success.

At present, most cancers are diagnosed in relatively advanced stages or reach that level when treatment fails or as disease progresses after partially successful therapy. Because not all cancers can be prevented and the outcome of patients with advanced cancer is largely unaffected by current therapies, a change in direction also must include a greater emphasis on detection of cancer in surgically excisable stages. In order to achieve the latter goal and ensure stakeholders’ continued support, cancer screening must target cancers responsible for most cancer deaths. Cancers concerned include lung and bronchus in men and women, female breast, prostate, and colorectal in men and women. Together, these cancers are expected to cause 472,370 deaths or 81.4 % of the total (580,350) expected in 2013 (Table 4.​2). Ideally, cancer-screening tests should be low-tech, dependable, reproducible, noninvasive, inexpensive, harmless, and simple to perform in the physician’s office or at the local laboratory. Yet, except for the reliable Pap smear, there is a tendency towards high-tech tools, such as CT scans, MRIs, flow cytometry, and molecular techniques, that are more useful for assessing the tissue of origin, stage, presence of metastases, and growth potential of cancer and predicting treatment responses or relapses, than for screening purposes. Because of their non-specificity, current screening tools, sophisticated or not, often lead to false positive and false negative results that negatively impact patients’ subsequent management, QOL, and survival. This has led to controversial changes in screening guidelines, as illustrated by PSA and mammography for prostate and breast cancer, respectively.