Best Practice & Research Clinical Anaesthesiology 27 (2013) 399–408

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The global burden of cancer Keyuri Popat, MD, Associate Professor of Anesthesiology a, *, Kelly McQueen, MD, MPH, Associate Professor of Anesthesiology b, 2, Thomas W. Feeley, MD, Division Head of Anesthesiology and Critical Care a,1 a

Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA b Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, USA

Keywords: cancer aging anaesthesiology health care delivery global burden of cancer

The global burden of cancer is increasing. By 2020, the global cancer burden is expected to rise by 50% owing to the increasingly elderly population. The delivery of cancer care is likely to increase the need for perioperative physicians for both operative procedures and pain management, offering new professional challenges. Specifically, these challenges will include volume and financial management, as well coordination of cancer treatment and pain management. Coordinated, team-based cancer care will be essential to ensure value-based care. Short and long-term outcome measurement is an integral part of the process. Ó 2013 Elsevier Ltd. All rights reserved.

Introduction Cancer is the fastest growing disease worldwide. Each year, about 12 million people are diagnosed with cancer across the globe. Seven million patients die of cancer annually, and 25 million people are currently living with a diagnosis of cancer. In developed countries, cancer has become the leading cause of death, and in developing countries, it is second only to heart disease [1]. Furthermore, the * Corresponding author. Department of Anesthesiology and Perioperative Medicine, Unit 409, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Tel.: þ1 (713) 792 6902; Fax: þ1 (713) 745 2956. E-mail addresses: [email protected] (K. Popat), [email protected] (K. McQueen), tfeeley@mdanderson. org (T.W. Feeley). 1 Department of Anesthesiology and Perioperative Medicine, Unit 409, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Tel.: þ1 (713) 792 7115; Fax: þ1 (713) 745 2956. 2 Department of Anesthesiology, Vanderbilt University Medical Center, 1301 Medical Center Drive, #4648 TVC, Nashville, TN 37232, USA. Tel.: þ1 (615) 835 5892. 1521-6896/$ – see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.bpa.2013.10.010

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global burden of cancer is increasing rapidly as the average age of the general population increases. The average life spans of the male and female populations worldwide increased from 56.4 to 61.2 years, respectively, in 1970 to 67.5 and 73.3 years, respectively, in 2010 [2]. Researchers project that by 2030, the annual number of new cancer diagnoses will be 21 million worldwide, with 17 million patients dying of cancer every year and 75 million people living with cancer diagnoses. After the age of 55 years, the risk of cancer increases to 78% in developed countries as opposed to 58% in developing countries. In the United States alone, 1.6 million individuals received new cancer diagnoses in 2012. Furthermore, cancer was responsible for one in four deaths in the United States in 2012. The increasing incidence and prevalence of cancer will place new demands on health care systems, including and especially for perioperative and pain services. This chapter highlights the impact of cancer on anaesthesiologists, critical care and pain management providers for the foreseeable future. Geographical and gender differences in cancer incidence Investigators have observed marked geographic differences in the types of cancer diagnosed worldwide. These differences owe to variation in the prevalence of major risk factors, average age of the population, and type and sophistication of medical care and cancer screening. In 2008, two of the four most common cancers in men (stomach and liver cancer) and women (cervical and stomach cancer) in developing countries were related to infection. Fifteen percent of all cancers worldwide are attributable to infection. The prevalence of infection-related cancer is more common in developing countries (26%) than in developed countries (8%). The greatest variation in cancer type among male patients is in Africa, where the most common cancers included prostate, lung, liver, oesophageal, and bladder cancer; Kaposi sarcoma; and non-Hodgkin lymphoma. In female patients, the most common cancers are breast and cervical cancer except for in China (lung cancer), South Korea (thyroid cancer), and Mongolia and Vietnam (liver cancer). Hereditary and environmental factors influence the development of cancer. Environmental factors, which are amenable to behavioural change include tobacco use, poor nutrition, physical inactivity, obesity, exposure infectious agents, certain medical treatments, excessive exposure to sunlight, and exposure to environmental carcinogens. In the United States, occupational exposure to carcinogens results in 6% of all cancer deaths each year (about 34,320 deaths/year) [3,4]. Cancer and the aging population Worldwide, increased life expectancy has resulted the expansion of the population at and over the age of 60 years [5] Fig. 1. The population over 60 years of age was 605 million in 2000, and it is projected

Fig. 1. Estimates of global population by gender and age 2000 and 2030 (Reproduced with permission WHO World Cancer Report).

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to increase to 1.2 billion in 2025 [6]. In developed countries 78% of the new cancer diagnosis occurs in patients above the age of 55, compared to 56% in developing countries. In the United States, individuals over the age of 85 years make up the fastest growing segment of the elderly population and will account for 5% of the overall population by 2050. Aging weakens natural defences against unchecked cell growth and is associated with greater genomic instability, resulting in increased cancer risk [7]. Cardiovascular disease is the leading cause of death worldwide. Cancer however is now the leading cause of death in the developed world. In white men, the risk of cancer is higher than that of cardiovascular disease up to the ninth decade of life [8] Fig. 2. The increased incidence of cancer in the elderly poses an ethical dilemma for treatment. Appropriate treatment for age and co-morbidities must be considered. Geriatricians offer expertise in the physiology of the elderly, including common issues such as incontinence, impaired cognition, delirium, dementia, impaired balance, and impaired hearing and vision. The Comprehensive Geriatric Assessment, as well as traditional tools such as the Karnofsky score and Eastern Cooperative Oncology Group performance status will offer additional guidance for physicians treating the elderly. Elderly individuals are a heterogeneous group, many are very healthy with few co-morbidities, while others are extremely frail. With this in mind, cancer treatment for the elderly must be holistic and individualized. The complexity of cancer care, may offer greater challenges in low resources settings than in the developed world.

Implications of increasing cancer burden for perioperative clinicians: anaesthesiology, critical care, and pain management Implications for anaesthesiology Surgical intervention plays an important role in the diagnosis and treatment of cancer. Therefore, surgical volume can be expected to increase as the incidence and prevalence of cancer also grow. Perioperative physicians are essential to the delivery of surgical care and patient safety. Understanding cancer interventions and the consequent alterations in physiology, as well as the effects of related radiation and chemotherapy are necessary for the safe perioperative management of the cancer patient. Considerations for postoperative monitoring and pain management must also be part of the surgical plan, and the perioperative physician is best poised to provide this expertise. Ambulatory surgery sites are often selected for cancer surgery, and may improve the experience of the patient and family. Co-morbidities and risks of surgery must be evaluated prior to the selection of an ambulatory setting, and when same day surgery is appropriate short-acting anaesthetic agents,

Fig. 2. Crude incidence of overall cancer and major cardiovascular disease by age. Driver JA et al. BMJ 2008; 337 (Reproduced with permission from BMJ publishing group ltd).

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aggressive pain management, including adjuvant nerve blocks, and prevention of nausea, vomiting and other side effects are crucial. Interventions for the diagnosis and treatment of cancer are also common outside the operating room, and many of these procedures require the remote administration of anaesthesia. Interventions for the diagnosis and treatment of cancer are also common outside the operating room, and many of these procedures require the administration of anaesthesia in remote locations. Cancer interventions are often unique, and may be complicated by multiple surgical teams and lengthy anaesthetics. Communication and teamwork among and between the surgical team, anaesthesiologist and operating room personnel is required for enhanced patient safety, including planning for appropriate postoperative disposition. Evidence supports that the careful choice of anaesthesia and pain management allows for the best patient outcomes. The current controversy is if perioperative use of opioids affect cancer recurrence .For example, several retrospective studies of prostate cancer patients have suggested that intraoperative use of opioids compared to and use of epidural local anaesthetic along with general anaesthesia are associated with increased risk of cancer relapse [9,10]. Similar observations have been made in retrospective studies of breast cancer patients who undergo surgery [11]. Randomized, multi institutional prospective studies are currently underway to evaluate the effects of anaesthetic techniques on oncological outcomes. These are retrospective studies, but researchers are performing several prospective studies at different sites in attempts to support that intraoperative opioid use is associated with increased cancer recurrence. One explanation for the possible link between this opioid use and recurrence is that the effect of opioids on the body is complex, as small doses given for pain are helpful but larger doses are immunosuppressive. This facilitates cell growth owing to suppression of cell-mediated immunity. The role of the anaesthesiologist in cancer surgery is specialized and critical for best outcomes. Adequate analgesia must be geared toward improving return to functionality and return to next cancer treatment step may it be radiation or chemotherapy. Implications for critical care Mortality rates in cancer patients admitted to intensive care units (ICUs) are high, but have improved in recent years. Intensive care providers face a unique challenge in managing the aging cancer patient population with co-morbidities undergoing intensive medical and surgical treatments. The average 30-day mortality rate in cancer patients in the ICU is close to 50% [12]. Researchers have also attempted to identify the key predictors of increased mortality in the cancer ICU population, such as 7-day organ dysfunction and viral infection. In addition, the cancer physician in the ICU must be aware of the toxicity of cancer therapies. Critical care for cancer patients is frequently complicated by infections, especially in neutropenic patients. In patients with worsening respiratory status, attempting non-invasive ventilation prior to committing to mechanical ventilation with tracheal intubation is recommended, especially in those with haematological malignancies. Implications for pain management Pain secondary to cancer is common due to the pathophysiology as well as to the related intervention and treatment for cancer. Results of several surveys have suggested that two thirds of patients with advanced cancer receiving treatment require pain management, and this management is critical for quality of life and the maintenance of function [13]. The World Health Organization estimates that up to 5.5 million people around the world receive minimal to no treatment of their cancer pain [14]. The morphine consumption and pain management indices are used to assess the adequacy of pain control. Opioid consumption is sometimes limited owing to availability and regulation. Specifically, less than 10% of the world’s morphine supply is available in developing countries, where up to 70% of cancer deaths occur, whereas 68% of world’s morphine supply is available in developed countries, which have only 6% of all cancer deaths [15].

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Barriers to pain management are specific to country and culture. Political barriers include regulations initiated by local and national governments, which in many cases limit the prescription or distribution of narcotics. Western institutions like the University of Wisconsin have helped influence the policy makers with their collaborative work to modify these regulations and make opioids more available to patients who need them [16]. Individual barriers to pain management include sex, race, low education level, age (both the elderly and paediatric populations), discrepancies between patient and physician estimation of pain severity, patient reluctance to report pain, and lack of staff time dedicated to managing pain. A recent pan-European survey demonstrated that 56% of cancer patients experience moderate pain, showing inadequate pain management even in developed countries [17]. Thus, under treatment of cancer pain is a global problem and not confined to developing countries. Furthermore, this problem is not getting better as shown in a Canadian study, which demonstrated that the rate of under treatment of bony metastasis increased from 40% in 1999 to 48% in 2006 [18]. Challenges of the increasing cancer burden in developing countries Cancer is an important contributor to mortality, disability, and chronic pain worldwide. In particular, by 2030, stomach, colon, rectal, and liver cancer will rank among the 20 leading causes of mortality globally [19]. Importantly, these are not the only cancers contributing to disability and premature death in low- and middle-income countries (LMICs), where untreated cancer is a growing concern. For example, the incidence of breast and cervical cancer is increasing in the poorest countries, where women routinely receive diagnoses very late in their disease courses and cost-effective cancer treatments are rarely available even if disease is diagnosed early. Also, lung cancer is an important contributor to mortality in these countries owing to unchecked cigarette smoking, which has been an epidemic over the past several decades. The contribution of pain to disability in cancer patients is large and growing and must be considered important to the global cancer burden. Treatment of human immunodeficiency virus infection/acquired immunodeficiency syndrome with antiretroviral medications in LMICs has impacted mortality and longevity rates in those countries and contributed to a global shift from communicable disease to non-communicable diseases (NCDs) Fig. 3 and accidents as common causes of death. The Global Burden of Disease Project confirmed the impact of NCDs on disability and premature death in its December 2012 report [20], which revealed the increasing cancer burden, especially in LMICs Fig. 4. The increasing cancer burden affirms the need for surgical cure, treatment, and palliation and for safe anaesthesia for cancer patients. Not unexpectedly, in countries where the prevalence of advanced

Fig. 3. The shift toward non-communicable disease and accidents as cause of death. The World Health Organization. World Health Report 2008: Primary Health Care (Reproduced with permission from WHO).

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Fig. 4. Cancer deaths in men. The World Health Organization. World Health Report 2008: Primary Health Care (Reproduced with permission from WHO).

cancer and numbers of new cases are the greatest, access to surgery and safe anaesthesia is lowest. Advocates for both these resources have been working diligently to impact the global surgical and anaesthesia crises [21,22] and increase the availability of surgery for cancer and other NCDs. Lack of infrastructure, including trained providers and basic equipment, means that the surgical expense is exaggerated and the time to surgical access is lengthy. Therefore, cancer will continue to lead to disability, pain, and premature death in the poorest countries for the foreseeable future. A methodical approach to improving access to surgery and safe anaesthesia must be embraced by ministries of health, national health care systems, and international donors to impact the burden of cancer. Although some physicians may argue that surgery is not the only approach to cancer treatment and palliation, it is often needed for diagnosis and is required for the cure offered by successful excision of a single non-invasive tumour. Furthermore, most of the surgical interventions that would be applied in LMICs are cost-effective and radiation therapy and chemotherapy are unlikely to be available soon in these settings. Experts in surgery have considered a practical approach to cancer surgery in LMICs. Prioritization of surgical interventions [23] as well as classification of non-emergent surgical interventions as “essential” [24] have provided a framework for discussions at the policy level. The global health community has always supported “emergency surgery” for appropriate population-based interventions for cancer [25], but only recently have essential surgical interventions become part of the discussion. Most physicians agree that surgical interventions in LMICs must be appropriately and responsibly planned, facilitating the most needed and easiest interventions at the district hospital level and reserving rare and complicated interventions for either provincial level facilities or regional centres. The rate-limiting step in surgery for cancer in LMICs is access to safe anaesthesia. The anaesthesia crisis in LMICs is far worse than the surgical crisis [26]. Fewer trained providers, unpredictable oxygen and medicine supplies, and a lack of safety monitoring have resulted in high rates of preventable anaesthesia-related mortality [27,28]. Acute and chronic pain are consequences of untreated cancer

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and may be managed with medication and interventions provided by primary care and anaesthesia providers. Treatments of both acute and chronic pain, including narcotics and non-steroidal anti-inflammatory drugs (NSAIDS), are not routinely available in LMICs. Therefore, pain treatment and access to safe anaesthesia must be addressed in advance of planning surgical intervention for cancer given the growing cancer burden. The present decade is an important period in the history of global health. The contribution of NCDs to the global disease burden in LMICs has never been higher. The role of surgery and safe anaesthesia in the treatment of many NCDs cannot be challenged. Therefore, old misconceptions and myths regarding the cost-effectiveness of appropriate surgical intervention can finally be dispelled. Access to surgery and safe anaesthesia would benefit the populations in LMICs without previous access to emergency and essential surgery, including that for cancer. The addition of pain management to the spectrum of care for patients with NCDs must be considered. Surgical intervention, safe anaesthesia, and pain management are important contributors to the health of populations at all economic levels. The emergence of cancer and related pain as major causes of disability and premature death worldwide affirms the need for surgery for diagnosis, treatment, palliation, and cure in cancer patients and the role of safe anaesthesia in ensuring the best possible outcome of cancer treatment. Challenges of effective value-based cancer care delivery With increasing cancer incidence and increasingly limited resources in all countries, providing value-based, cost-effective care is a worthy goal. In the United States, Medicare is the largest payer of health care expenses for the elderly, spending $124 billion in 2010. Furthermore, it is estimated that Medicare will spend $178 billion annually by 2020. More than 50% of bankruptcies in the United States can be attributed to health care costs. In 2007, the National Institutes of Health estimated the overall cost of cancer care to be $227 billion, with $104 billion going to direct medical costs. Ballooning cancer incidence and improved survival rates have put an enormous amount of stress on the health care delivery system. Worldwide, health care payers, individuals, governments, or third parties, are demanding value-based care. Cancer care programs must therefore regularly measure, analyse and improve outcomes and the quality of care, while at the same time decreasing costs. Outcomes Outcome measurement and analysis is a routine feature of medical care. Importantly these outcomes may be benchmarked between providers and institutions, and offer a measurement of success and improvement over time. Cancer outcomes of importance include mortality, 5-year survival, and recurrence. Additional outcomes of importance are related to complications of treatment. Authors have suggested a three-tier outcome measurement process that ranges from immediate procedural outcomes to long-term functional status to outcomes related to cancer recurrence [29]. Outcome measurement for a specific disease may be different in different groups of patients. For example a 5-year cancer recurrence rate may not offer a 90 year old the same information as the overall risk of mortality of a treatment. Physicians must offer appropriate guidance for patients and help them understand their health care options. Cost of cancer care Cancer care, like all heath care costs, varies within and between countries, based on resources available and the organization of the hospital and system. Resource utilization and fixed costs contribute to the cost calculation. For cancer care, patient education and choices are essential, and the indirect costs of time away from work and other impact on support systems resources must be considered. Researchers at the Harvard Business School reported that measuring the actual cost of delivering health care and understanding the effect of a treatment/intervention on outcome can ensure effective value-based care [30]. One of these researchers developed a method for measuring the true costs of cancer care known as time-driven activity-based costing. This method identifies the units of time taken

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to perform a service and the cost per unit of time and then multiplies these two so as to quantify the cost of the service. This can used over and over depending on the quantity of the service utilized [31]. This is an accurate tool for measuring the value of care when patient-oriented outcomes are balanced against cost. Currently, health care costs are often cut across the board in most institutions to maintain fiscal health of the institution. However, using the above concept, cost of service for each step in the entire patient encounter can be derived and rational decisions made to deliver most cost-effective care. As an example, having knowledge of personnel cost of the clinic visit (clerk, nurse and doctor patient interaction time) and the processes of care for each patient encounter, physician’s time can be effectively managed for more direct patient time than performing non clinical tasks. Similar methodology can be applied to all aspects of anaesthesiology, critical care medicine and pain practices [32]. In 2012, the Institute of Medicine reported an estimated waste in the US health care system of more than $750 billion annually (one third of all US health care expenditures), which is approximately six times greater than the annual amount currently spent to treat cancer in United States. This waste results from services provided with no evidence of improved outcome, errors in treatments, preventable complications of treatments, fragmented delivery of health care services, and inefficient processes. Anaesthesia providers must participate with others in the cancer care delivery team to eliminate and modify wasteful processes in cancer care [33]. Quality of cancer care Quality is central to effective cancer care. A recent report by the Institute of Medicine has found that there is a crisis in the United States in the quality of cancer care being delivered. This is due to the rapidly rising elderly population, a shortage of trained care providers, lack of informed patient engagement and rapidly escalating costs [34]. All members of the health care team are needed to improve quality and anaesthesia providers are no exception. Internationally many hospital systems are centralized and provide a spectrum of health care from paediatric to obstetric to complex cardiac and cancer care. Cancer Centres for multidisciplinary care of cancer patients may offer improved quality and cost-containment for cancer patients. For example, a surgeon who performs only a few liver resections a month and spends the rest of his or her time performing cholecystectomies and appendectomies cannot be as effective at liver procedures as a surgeon who does only liver-related surgeries. Thus, the importance of focused practice units like cancer care centres is increasing, because of greater cancer-focused surgical volume. This has led to an increasing need for perioperative physicians to become part of disease-focused integrated care delivery units to ensure the best possible outcomes. Several studies have suggested that hospitals with high volumes of patients with certain types of disease have better outcomes of those diseases than do hospitals with lower patient volumes. The reason for this may be multifactorial, probably a combination of better infrastructure, facilities, and trained personnel geared toward the diseases in question. Special training for anaesthesiologists caring for cancer patients is under consideration. The increasing demands for and varieties of cancer care may warrant additional training for those interested. Several major cancer centres including MD Anderson and Memorial Sloan-Kettering Cancer Center have started offering training for anaesthesiology for cancer surgery. The goal is to inspire and aid future anaesthesiologists through specific education on cancer, related therapies, anaesthesia implications and pain management. Of course, these types of fellowships also encourage research and the study of outcomes. The concept of a multidisciplinary approach to improving perioperative care for patients is not new and its use for cancer care is quickly becoming a standard of care. Over the past few years, authors have reported evidence that a fast-track multidisciplinary approach to perioperative care has had positive effects such as decreased hospital stays, early mobilization, and reduced postoperative ileus durations [35]. Conclusion Efforts directed at screening for, treating, and improving survival of cancer as well as developing innovative strategies to manage the costs related to cancer are current healthcare priorities. Cancer is a

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diverse set of diseases, impacting populations across the globe. Preparing for a compassionate and appropriate cancer strategy is complicated by the reality that cancer strikes across age groups, gender and socioeconomic disparities. Healthcare strategies must include prevention and early detection of cancer, appropriate, evidence-based treatment strategies, access to effective and timely pain management, supportive care to meet patient needs and social programs that provide support and dignity in all settings. The perioperative physician is central to the management of cancer patients, in the operating theatre, for pain management and through analysing outcomes for the improvement of quality.

Practice points - Incidence of Cancer is an increasing rapidly, with geriatric population being most vulnerable. - Imbalance between the demand for cancer care and resource availability is going to burden the health care system - Attention should thus be placed on cancer prevention, proven treatments and cost efficient care - Multidisciplinary approach to patient care will be needed

Research agenda - Specialties of anaesthesiology, critical care and pain medicine will need to define appropriate outcome metrics - Different modalities of assessing true cost of effective care need to be evaluated

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The global burden of cancer.

The global burden of cancer is increasing. By 2020, the global cancer burden is expected to rise by 50% owing to the increasingly elderly population. ...
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