SEOM guide to primary and secondary prevention of cancer: 2014

Purpose The current incidence of cancer in the world is 14 million cases in 2012, with a mortality rate of 8.2 million in that year. The incidence of cancer in Spain exceeds 215,000 cases a year, and survival rates are the highest when compared to those of our neighbouring countries. Among the reasons for the steady decrease in cancer mortality rates in Spain, two causes must be highlighted: the increasing efficacy of treatment and prevention measures. It is important evaluate the opportunity of early detection and prevention in these tumors. Methods We have reviewed the evidence published in the most prevalent tumors. The evidence levels described in this paper are based on the GRADE system. Results We show the recommendations about primary and secondary prevention in breast cancer, cervical cancer, colorectal cancer, prostate cancer and lung cancer.ConclusionThe diffusion of these preventive tools can reduce the incidence of cancer and increase the number of early diagnostics in the most prevalent tumors.

# Introduction
The current incidence of cancer in the world is 14 million cases in 2012, with a mortality rate of 8.2 million in that year. The incidence of cancer in Spain exceeds 215,000 cases a year, and survival rates are the highest when compared to those of our neighbouring countries. Among the reasons for the steady decrease in cancer mortality rates in Spain, two causes must be highlighted: the increasing efficacy of treatment and prevention measures.
The present study analyses tumours in which prevention has shown to be of use, or is at least being debated as a useful possibility. Both primary and secondary prevention measures have been assessed.
The evidence levels described in this paper are based on the GRADE system [fig_ref] Table 1: GRADE system classification of the quality and strength of evidence [/fig_ref].

## Breast cancer
Breast cancer (BC) is the most frequent cancer among women and the first cause of death among European women. In 2012, the estimated age-adjusted annual incidence in the European Union was 82.1/100,000 and the mortality 15.5/100,000 (GLOBOCAN). The incidence has increased after the introduction of mammography screening and the ageing of the population and the mortality has The focus of this guideline is summarising the current evidence on prevention of BC in women at average risk of developing BC. In this subgroup, women must have no symptoms, no history of invasive BC, ductal or lobular carcinoma in situ or atypical hyperplasia, no family history in a first-degree relative, no suggestion/evidence of a hereditary syndrome and no history of chest wall radiation. For women at increased risk, please consult the SEOM clinical guideline for hereditary cancer.

## Primary prevention
The main risk factors for BC (personal, familiar and reproductive factors and age) cannot be changed. Regular physical activity beginning in the early childhood, weight control and alcohol intake reduction are strategies that can decrease the probability to develop this disease. The use of pharmacologic interventions for BC reduction is not recommended for women at average risk.

## Secondary prevention
Early detection through screening remains the primary tool available to healthy women in preventing the development of BC, and thus reducing BC mortality.

## Mammography
Screening mammography is currently the best available method to detect BC at an early stage and the only that is associated with significant reduction in mortality [bib_ref] The benefits and harms of breast cancer screening: an independent review, Marmot [/bib_ref]. Expert groups and medical societies recommend routine screening with mammography for women aged 50 and older [bib_ref] Canadian Task Force on Preventive Health Care, Recommendations on screening for breast..., Tonelli [/bib_ref] [bib_ref] Screening for breast cancer: an update for the US, preventive services task..., Nelson [/bib_ref]. However, there is controversy about women in their 40s, due to lower risk of BC, smaller reduction in mortality compared with older women and higher impact of harms related to screening mammography (false-positive and overdiagnosis rates) [bib_ref] Screening for Breast Cancer with mammography Cochrane, Gtzsche [/bib_ref]. The decision to start screening before age 50 years should be an individual one and should take into account patient context, including the patient's values regarding specific benefits and harms. There is insufficient current evidence to assess the additional benefits and harms of screening mammography in women aged 75 years or older. The appropriate interval for screening mammography is 2 years [fig_ref] Table 2: Screening recommendations for BC in women at average risk [/fig_ref].

## Magnetic resonance imaging (mri)
There are no data evaluating whether screening women at average risk of breast cancer using MRI scans reduce mortality as compared with mammography or no screening.

## Breast examinations
No evidence is found to show that clinical breast examination (CBE) or breast self-examination (BSE) reduces the risk of mortality.
BC screening remains a subject of intense debate. Although mammography remains the gold standard, it also has limitations and recent studies raise questions of potential harms [bib_ref] The benefits and harms of breast cancer screening: an independent review, Marmot [/bib_ref]. Besides, as treatment of clinically detected disease improves, the benefit of the screening probably diminishes. Optimal BC screening will probably require a personalised approach, with application of technologies best suited to the individual's age and risk.

## Cervical cancer

## Primary prevention
The most important cause of cervical cancer is persistent human papillomavirus (HPV) infection, in particular the oncogenic subtypes such as HPV 16 and 18. Randomised clinical trials have shown that HPV 16 and 18 vaccination is highly effective in preventing moderate-grade cervical dysplasia or worse pathology (CIN2?) among women not previously exposed to these types of HPV [bib_ref] Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer..., Paavonen [/bib_ref] [bib_ref] Impact of human papillomavirus (HPV)-6/11/16/18 vaccine on all HPV-associated genital diseases in..., Munoz [/bib_ref]. There currently are 2 HPV vaccines available: a quadrivalent vaccine that protects against infection by HPV types 6, 11, 16 and 18 and a bivalent vaccine that protects against HPV types 16 and 18. These vaccines will be more cost-effective if given prior to initiating sexual activity, and the priority target population is young adolescent females [fig_ref] Table 3: Recommendations for the screening of cervical and prostate cancer [/fig_ref].

## Prostate cancer

## Primary prevention
There is strong evidence indicating an association between androgens and the risk of prostate cancer. The 5a-reductase inhibitors that are used to treat benign prostatic hyperplasia block the conversion of testosterone to dihydrotestosterone and have shown to reduce the risk of prostate cancer [bib_ref] Effect of dutasteride on the risk of prostate cancer, Andriole [/bib_ref]. Moreover, several randomised trials using antioxidants such as selenium and vitamin E have failed to demonstrate benefit.

## Secondary prevention
Currently, best evidence supports the use of serum prostate-specific antigen (PSA) for the early detection of prostate cancer. However, many experts continue to recommend digital rectal examination (DRE) for screening, as some clinically significant cancers may potentially be missed using a serum PSA cut point alone. The true benefits of prostate cancer screening are unclear despite the results from two large randomised trials [bib_ref] Prostate-cancer mortality at 11 years of follow-up, Schroder [/bib_ref] [bib_ref] Prostate cancer screening in the randomized prostate, lung, colorectal, and ovarian cancer..., Andriole [/bib_ref] investigating whether PSA testing reduces prostate cancer mortality. In addition, early detection results in identification of many men with indolent disease that could not benefit from immediate treatment. False positive results of PSA and DRE can contribute to patient anxiety, increased costs and potential complications associated with unnecessary biopsies. For these reasons, the patient and the physician should discuss the risks and potential benefits prior to testing. [fig_ref] Table 3: Recommendations for the screening of cervical and prostate cancer [/fig_ref].

## Colorectal cancer
Colorectal cancer (CRC) is the most frequent type of cancer among the population. Mortality rates have decreased in past years, mainly as a result of the implementation of CRC screening programmes in many industrialised countries. The different known aspects of primary and secondary prevention, as well as the evidence levels described in the scientific literature, are discussed in the following paragraphs.
Primary prevention [bib_ref] GRADE working group. rating quality of evidence and strength of recommendations GRADE:..., Guyatt [/bib_ref] - Consumption of red meat, processed meat and cooked meat that is very well done or has been prepared in direct contact with the source of heat should be moderate (Grade B recommendation). - A low-fat diet that is high in fibre, fruit and vegetables is advisable (Grade B), although published results are not conclusive. A diet that is high in milk and dairy products is also recommended (Grade B). - Folate, calcium and vitamin D intake must be adequate (Grade B), but not provided in the form of dietary supplements. - Antioxidant supplements should not be taken.
- Physical exercise and avoidance of excess weight and obesity must be encouraged to prevent CRC (Grade B). - NSAIDs and aspirin should not be taken systematically to prevent CRC (Grade B), nor should hormone treatment be administered (Grade A).
CRC screening recommendations in the average risk population [fig_ref] Table 4: CRC screening recommendations in average risk populations [/fig_ref] Individuals of 50 years of age and over, with no additional risk factors, are considered to be at average risk for CRC. Individuals of under 50 years of age, with no specific risk factors, are considered to be at low risk for CRC, and do not require screening. However, individuals with personal and/or familial CRC risk factors should be considered for screening or observation, based on their personal background and medical history (colonic polyposis, Lynch syndrome, family history of CRC, ulcerative colitis, etc.).
- Tests for the detection of hidden blood in faeces (SOH) are a useful tool, and must be considered in CRC screening programmes (Grade A). Recommendations for population-wide CRC [bib_ref] GRADE working group. rating quality of evidence and strength of recommendations GRADE:..., Guyatt [/bib_ref] screening programmes [fig_ref] Table 5: Recommendations for population-wide CRC screening programmes Recommendation Evidence CRC screening should be... [/fig_ref] - CRC screening should be offered to all individuals with no risk factors as from the age of 50. In accordance with guidelines established in our milieu (European Union, Spain and its regions), SOH detection tests should be performed every two years in men and women of 50-74 years of age (Grade A). - Screening tests in population programmes should be based on a quantitative SOHi analysis with a positive cutoff point that guarantees an optimal balance between sensitivity and specificity, depending on the availability of colonoscopies. The choice of other screening tests (annual or biennial SOHg determination, sigmoidoscopy every 5 years or colonoscopy every 10 years) might be warranted if resources are available (Grade B).
- Individuals included in higher-risk groups (polyposis, etc.) must be identified, that they may benefit from specific screening and supervision measures (Grade A).

## Lung cancer
According to the latest update of the GLOBOCAN 2012 study, lung cancer in Spain is the second most frequent cancer in men and the fourth most frequent cancer in women. Lung cancer is the third most frequent carcinoma if we combine the data for both sexes (26,700 cases in 2012, with a mortality rate of [bib_ref] Benefits and harms of CT screening for lung cancer: a systematic review, Bach [/bib_ref]. This accounts for 20 % of all cancer deaths in Spain. Data for the US indicate that lung cancer is the main cause of early death from cancer in that country, with an estimated cost of 2.37 million years of life in 2010. These data reveal the importance of lung cancer prevention. If we bear in mind that the most important factor involved in the development of the disease-cigarette smoking-is clearly identified, neglect of preventive measures is inexcusable.
In recent years, different randomised studies [bib_ref] International association for the study of lung cancer computed tomography screening workshop, Field [/bib_ref] have examined the potential value of low-dose computerised tomography in the prevention of lung cancer. These studies have revealed that the yearly performance of CT scans in high-risk groups (that is, individuals of 55-74 years of age who are active smokers or gave up the habit \15 years previously, with a history of at least 30 pack years) can decrease lung cancer mortality rates by 20 %, as compared to annual chest X-rays, with no added collateral damages resulting from radiological exposure [bib_ref] Benefits and harms of CT screening for lung cancer: a systematic review, Bach [/bib_ref].
Apart from the recommendation of yearly TC scans in high-risk groups [bib_ref] On behalf of the US preventive services task force. Screening for lung..., Moyer [/bib_ref] , it is crucial to insist that smokers give up their habit, and to make sure that people who do not smoke do not begin to do so. Lung cancer screening should not be regarded as an alternative to giving up smoking [fig_ref] Table 6: Recommendations for lung cancer prevention Recommendation Evidence Giving up smoking or not... [/fig_ref]. Finally, it is essential that screening tests for lung cancer are personally discussed with all potential candidates, and carried out by multidisciplinary teams made up of experts in the management and treatment of the disease.

# Conclusions
Improved rates of cure for cancer are due in recent years to improvements in treatment and to the implementation of prevention programmes.
In some types of cancer, primary and secondary prevention measures can have a very significant effect on the reduction of incidence rates, and on the increase of survival as a result of earlier detection and diagnosis.
It is indispensable to encourage research into further prevention measures, especially in tumours whose rates of survival are the lowest.
[table] Table 1: GRADE system classification of the quality and strength of evidence [/table]
[table] Table 2: Screening recommendations for BC in women at average risk [/table]
[table] Table 3: Recommendations for the screening of cervical and prostate cancer [/table]
[table] Table 4: CRC screening recommendations in average risk populations [/table]
[table] Table 5: Recommendations for population-wide CRC screening programmes Recommendation Evidence CRC screening should be offered to all individuals with no risk factors as from the age of 50. In accordance with guidelines established in our milieu (European Union, Spain and its regions), SOH detection tests should be performed every 2 years in men and women of 50-74 years of age AScreening tests in population programmes should be based on a quantitative SOHi analysis with a positive cutoff point that guarantees an optimal balance between sensitivity and specificity, depending on the availability of colonoscopies. The choice of other screening tests (annual or biennial SOHg determination, sigmoidoscopy every 5 years or colonoscopy every 10 years) might be warranted if resources are available B Individuals included in higher-risk groups (polyposis, etc.) must be identified, that they may benefit from specific screening and supervision measures [/table]
[table] Table 6: Recommendations for lung cancer prevention Recommendation Evidence Giving up smoking or not taking up the habit A Annual, low-dose CT scans in high-risk groups (individuals of 55-74 years of age who are active smokers or gave up the habit \15 years previously, with a history of at least 30 pack years) [/table]