Quantifying the economic burden of cancer in Chile
In developed countries the economic impact of a disease is a major public policy issue. In Chile, where 23.8% of national mortality is due to cancer (Figure 2), we have calculated that Chile currently spends US2.100 million (1% GDP) on cancer care and treatment. Calculating the chronic disease burden in Chile we see that cancer accounts for notable proportions of Years Lost due to Disability (YLD) and Years of Life Lost due to premature death (YLL). Disability-Adjusted Life Years (DALYs) corresponds to the sum of YLD + YLL (Figure 2). Whilst no formal economic studies of the burden of cancer have been conducted in Chile, the authors of this paper have estimated that the national income lost to cancer per year DALYs is US$ 3.5 billion. This value was achieved by multiplying the calculated VLL (175,711) by an estimated per capita income of US$20,000. This suggests that cancer has a major economic impact in Chile. However, along with cancer, an aging population also brings an increase in neuropsychiatric problems that will only place further burden on the Chilean economy. The absence of integrated health economic studies is notable in Chile and in public policy terms this is a major deficit that needs to be urgently rectified.
Stomach and gallbladder cancer: the Chilean phenomenon
Based on world statistics, the Chilean population presents notoriously higher than average mortality and incidence rates for both stomach and gallbladder cancers [27, 28]. Stomach cancer has historically been one of the principal causes of cancer related death worldwide. However, while rates have declined in westernized populations of North America, Northern and Western Europe, regions such as South America still post high mortality rates [29].
While stomach cancer is currently the most common malignancy in Chile, in the United Kingdom (UK), stomach cancer no longer figures as one of the ten most common cancers, with the incidence rate having fallen by over 60% since the mid-70s [30]. In 2009, Chile registered 3,350 deaths from stomach cancer giving a rate of 19.8 per 100,000 inhabitants [12].
As has been reported globally there is also a strong correlation between stomach cancer and the indigenous population [31]. This is also true in Chile, where between 1998 and 2002, a crude incidence rate of 29.2 per 100,000 inhabitants was reported in the city of Valdivia in the mid-southern region of the country [27]. Most stomach cancer patients are male, with urban residence and a low level of schooling [27, 32]. Along with social determinants and advanced clinical stage at consultation, infection with the bacteria Helicobacter pylori is also recognized as a principal risk factor for stomach cancer in the Chilean population [27, 32]. In addition, Helicobacter infection has been associated to lower socioeconomic structure. This observation is in line with statistics implicating the involvement of infection in 22.9% of cancers in lower income countries, as opposed to 16% globally [14, 33].
Another factor in the Chilean stomach cancer story is salt. In Chile, it is estimated that the average salt (NaCl) consumption is around 10.4 g per day in adults [34, 35].This value is significantly higher than in British adults who consume on average 8.1 g per day [36]. The interaction between salt, Helicobacter and genetic predisposition in the Chilean population are likely to underlie this high incidence. However, genetic factors aside, these above mentioned risk factors suggest that prevention, through health education and eradication of Helicobacter pylori, together with better screening procedures for precancerous lesions may well deliver a notable improvement in incidence and prognosis to the Chilean population.
While stomach pattern follows a worldwide trend in reducing as socioeconomic status increases, a statistic that is uniquely Chilean is the incidence of gallbladder cancer [37]. In the UK, gallbladder is considered a rare cancer, with 700 new cases and 438 deaths recorded in 2008 [38]. Chile recorded 1819 deaths from gallbladder and bile duct related cancer in the same year. Further emphasizing the gallbladder problem, in Chile the estimated incidence and mortality rates for this cancer are 13.4 and 11.5 per 100,000 female habitants, while in Latin-American these rate are 3.7 and 3.0, and in the USA 1.6 and 0.6 respectively [39]. The highest risk group for gallbladder cancer is among Amerindians, Mapuche and Hispanic women with less than four years of schooling [28]. On the other hand, the lowest standardized incidence rates were among Hispanic men and women with more than eight years of schooling. Thus, ethnic origin, low schooling, the female sex and urban residence were deemed independent risk factors. In the Mapuche population, the incidence of gallbladder cancer has reached 269.2 per 100,000 women in specific age groups [28]. Interestingly, cholelithiasis is always a precursor to gallbladder cancer, suggesting that screening programs and cholecistectomy could significantly decrease gallbladder cancer death. A pilot study of gallbladder cancer lead by the US-National Institute of Health (NIH) (Government trial identifier NCT01520259) in conjunction with Chilean Universities intends to recruit 120 cases to assess the feasibility of a full-scale population based multidisciplinary gallbladder cancer study [40]. Another recognized risk factor is the chronic carriage of Salmonella typhi, which would be the long-term effect of the hyperendemic of Typhoid Fever that occurred in Chile during the 1970s and 80s [41]. As Chile moves towards a more westernized lifestyle, the risk factors and incidence are likely to fall, however, the sheer numbers of gallbladder cancer cases in Chile suggests a genetic or environmental factor that is not being fully addressed by the nation’s scientific and medical community [42].
Another malignancy that demonstrates peculiar statistics in Chile is lung cancer. The majority of Chile presents slower than developed country incidence rates. However, the occurrence of high arsenic exposure in drinking water (>200 ug/L as opposed to now recommended <10 ug/L) from 1930 to 1977 in the Antofagasta Region in the north of the country and in particular levels of 860 ug/L in the City of Antofagasta between 1958 to 1970 has resulted in high lung cancer incidence and mortality [43]. Despite water filters and regulations being introduced in the 1970s, a significantly high odds ratio to develop lung and bladder cancer in this region still exists up until today [44]. However, not all cancers increased in mortality. A recent publication has speculated a rapid reduction in breast cancer mortality in the years during and directly following exposure to arsenic-contaminated drinking water in Antofagasta [45].
Obesity and cancer in the Chilean population
In the National Health Survey of 2009, it was reported that over 67% of the surveyed population was overweight with 25% obese. Over 88% of the population was estimated to lead a sedentary lifestyle and an alarming statistic was the appearance of a significant number (3.3%) of morbidly obese females within the population [46, 47]. In neighboring areas within Chile’s capital Santiago, girls at private school underwent menarche six months later that girls at a state run school. Obesity in this case appears to be the smoking gun, with age of menarche correlating almost perfectly with body mass index [48]. Unsurprisingly, increased obesity numbers also correlated well with an increase in type-2 diabetes from 6.3% in 2003 to 9.4% in 2010 [48]. Interestingly and again demonstrating inequality, diabetes was three times more prevalent in members of the society with lower schooling [48].
Chile is now part of the Latin American Consortium of Studies in Obesity (LASO) [49] and it has also joined with the United Nations sponsored schemes on obesity control. The government statistics demonstrate that 24.5% of the men and 33.6% of women are obese, placing Chile together with Venezuela and Argentina in leading South America in this category. A recent publication suggests that 20% of Chilean cancers are directly related to obesity, with most affected being endometrial (47%) in women, and esophageal (35%) and pancreatic (31%) in men [39]. The authors of this publication conclude, again demonstrating Chile’s rapid incorporation of a westernized lifestyle, that the incidence of obesity-related cancers resembled the distribution of the USA and the UK more than developing countries [39]. Obesity-related health problems maybe confounded in coming years by the observation of increased gallstone incidence in obese and overweight children [50]. This, coupled to the observation that all gallbladder cancer patients first present gallstones, may further increase Chile´s notorious burden of gallbladder cancer.
Analysis to allow the development of a cancer healthcare system in an emerging economy
Despite persistent inequalities in cancer distribution, the Chilean population now has greater access to a public and private health system than a decade ago. Provision of services is mainly delivered by public sector services with an overlay of private providers under contract with public insurance system. The Ministry of Health is responsible for setting public policy in health including cancer prevention and mandatory strategies for infections, and chronic disease including cancer and mental conditions [51]. The 2005 Health Reform established a set of guarantees for access, care and quality for a significant number of health conditions including some cancers [52, 53]. This reform has impacted positively in coverage and equity in healthcare across the Chilean population, including cancer. On the delivery side, the public system runs a network of Primary Health care, with around 1500 points of service managed by municipalities in a decentralized mode. Regional Health care services administer 60 hospitals tasked with complex case management (tertiary), 100 less complex hospitals (equivalent to secondary or district level care) and a small number of highly specialized institutes (e.g. Neurosurgery, Cardio-respiratory, and Cancer) [54]. Currently, Chile only offers first line therapy within the public system, and there is also a need to re-consider the overall quality and delivery of radiotherapy, surgery and pathology to assess what Chile’s essential cancer guidelines should or should not include.
Chile currently possesses 60 oncologists (data kindly supplied by the Chilean Society of Medical Oncology), a number clearly inadequate to meet the pending cancer burden. To achieve the same coverage of oncologists per capita currently present in the USA, Chile would have to increase their number of oncologists to over 500. This statistic mirrors the overall observation that Chile possesses only 1.6 medical doctors per 1000 inhabitants as opposed to the OECD average of 3.2 medics per 1000 inhabitants.
Clinical trials
In the clinical trial registry at the Chilean National Institute of Health (ISP Chile), 65 cancer clinical trials were active or in progress in 2014 [55]. Most of them (76.9%) are phase II/III or III and only 4.6% are in early phases (IB or I/II). The majority support comes from outside the country with Roche accounting for 10% of trials, Pfizer 7.6%, Bristol-Myers Squibb 7.6%, Merck Sharp and Dohme 6.6% and Amgen 6.6%. Through GOCCHI (Grupo Oncológico Cooperativo Chileno de Investigación) [56], a Breast International Group member, Chile is involved in multicenter trials such as the US-LA-CRN (United States-Latin-American- Cancer research Network) trial looking into the molecular profiling of stage I and II breast cancers in Latin-America and the worldwide ATLAS trial (Adjuvant Tamoxifen: Longer Against Shorter) [57, 58].
Cancer registries, tumor banks and legislation
Chile is in the initial stages of establishing and implementing a regulatory legal framework in biomedical scientific research. Chile is in transition from technical standards, focused exclusively on clinical trials (Technical Standard No. 57 of 2001), to specific legislation encompassing all biomedical research (Law No. 20120 of 2006 [59] and its Regulatory Decree No. 114 of 2010 [60], as amended in 2013 [61]). However, there are imperfections in this legal framework that require urgent clarification to permit biobanking, biomedical research and the participation of Chilean subjects in clinical trials.
Chile currently possesses a national registry of pediatric cancers [62] and three established regional cancer registries. The established registries, two of which are IACR (International Association of Cancer Registries) registered [63], provide incidence data from populations in the North (Registro de cancer de Antofagasta) [64] and South (Registro de cancer de Valdivia and Bio-Bio) of the country [65, 66]. Together with the established registries, there are three registries in development (Región de Arica-Parinacota, Región del Maule, Provincia de Concepción), which when fully operational should give vigilance of 18.5% of the country. Despite persistent underfunding, often only having one part-time worker, these six databases have provided key information about the most frequent cancers in the country. However, approximately 40% of the Chilean population is centralized in the capital Santiago, and there are no immediate plans to monitor cancer incidence in this region.
Through involvement in clinical trials such as the above mentioned US-LA-CRN, Chile created its first centralized biobank for breast tumor samples. The concept and requirement for tumor banking in Chile is gathering momentum, however, while public universities and several private universities and clinics have started to implement banking systems, there is no collective consensus on methodology and little interaction between the players. This is principally due to a lack government priority, regulatory confusion on the legal aspects of sample taking and a scarcity of funding.