The above age 60 demographic is the largest growing segment of our patient population in the USA. It is projected that 20% of the US population will be over 65 years of age by 2030. In 2016, an estimated 1.7 million new cancer cases will be diagnosed with approximately 600,000 cancer -related deaths [1]. Given that age is the single most important risk factor for cancer and the median age at diagnosis is over 60 years for greater than 50% of new cases, it is expected that 70% of cancers and 85% of all cancer-related deaths will occur in this patient population [2]. In 2014, cancer was the leading cause of death in all people in the USA ages 45–64 and second leading cause of death of all people in the USA over 65 years second only to heart disease [3]. Solid tumors are common in this patient population, and surgery in appropriate patients remains the mainstay for control of tumor burden. However, an age-related higher incidence of comorbid burden in this patient population and inability to rapidly recover from postoperative complications due to decreased physiologic reserve, frailty, altered drug pharmacokinetics/pharmacodynamics, and higher incidence of postoperative delirium and cognitive abnormalities put these patients at higher risk for postoperative morbidity and mortality. Nevertheless, the current data on the operative mortality and morbidity after complex cancer surgery in older patient population is conflicting [4–6]. While some single-center studies of elderly patients undergoing major cancer surgery reported an operative mortality rate of less than 5% [7–10], a few larger observational studies reported a substantially higher risk for worse operative outcomes [11,12]. Given the conflicting data about operative outcomes in this age group, it is vital to understand the differences between the physiology of normal aging from the higher incidence of disease burden in older patients. In a recent report of major cancer surgery in the elderly, the authors report that older patients were more likely to have preoperative comorbidities and to receive intraoperative blood transfusions. Increased age was also associated with higher operative mortality (4.83% for >75 years vs. 1.09% for ages 40–55 years), a greater frequency of major complications, and more prolonged hospital stays—all of which persisted after multivariable adjustments. However, despite its strong association with 30-day operative mortality, the authors reported that the impact of older age was comparable to other preoperative risk factors predictive of short-term operative outcomes [13]. Age alone should therefore not be a reason to withhold adjuvant, neoadjuvant, curative, or palliative treatment options in this patient population.

A good understanding of preoperative, intraoperative, and postoperative factors that may contribute to outcomes in this patient population will help develop appropriate care strategies to minimize perioperative risk foradverse short-term operative outcomes . Despite its association with increased perioperative morbidity and mortality, chronological age alone is not a good gauge of the physiology of aging and its effects on perioperative outcomes in a particular patient. Due to significant interindividual variability in the biology of aging, comorbid burden, frailty, and functional status, the detailed assessment of each individual patient as well as establishing clear goals of therapy (curative intent or palliation of symptoms ) becomes critical in the elderly patient with cancer. Elderly patients are less likely to undergo surgical treatments regardless of disease stage [3]. As with any surgical patient, medical optimization ofcomorbid burden is vitally important. It is also important to identify the patient’s symptom burden prior to surgical intervention as these directly influence patient distress, quality of life (QOL), and survival [14]. Preoperative assessment of symptom burden may aid in optimizing intraoperative and postoperative management strategies aimed at returning the patient to his or her presurgical baseline. There are many tools available for the practitioner to administer in assessing a broad spectrum of symptom content. Each tool varies in psychometric validation [14].

Although the role of a geriatrician has not been established in surgical care of the cancer patient, many studies show preoperative geriatric assessment predicts postoperative mortality and morbidity as well as survival in geriatric oncology patients [15,16]. A comprehensive geriatric assessment (CGA ) is defined as “a multidimensional, interdisciplinary diagnostic process to determine the medical, psychological, and functional capabilities of an older person in order to develop a coordinated and integrated plan for treatment and long-term follow-up” [17]. In fact, some of the first studies of the relationship between CGA status and perioperative morbidity and mortality were performed in patients with cancer. Particularly telling were the assessments ofinstrumental activities of daily living (IADLs), degree of comorbidities, and polypharmacy. Recently there has been an increasing focus on actual testing of the patient rather than the use of questionnaires for functional assessment. Examples of performance-based measures of functional status are the “Timed Up and Go” test, the 6-minute walk test, and the grip strength. Despite this focus, additional studies are still needed to test the prognostic ability of performance-based measures of functional status as well as any statistical correlation between objective and subjective measures of functional status in the geriatric oncology patient. Understanding the functional capacity and fatigue level in the elderly oncologic patient may aid in determining candidacy for surgical intervention [6]. The Preoperative Assessment of Cancer in the Elderly (PACE ) is a prospective, international study designed to determine if the fitness of elderly surgical patients with malignant tumors can be assessed accurately enough to permit individualization of treatment [6]. Overall, the burden of comorbidity is associated with worse survival in patients with cancer [18–22]. It is becoming evident that concomitant diseases impact not only overall survival but also the behavior of the cancer itself. For example, diabetes decreases the 8-year disease-free survival of stage III colon cancer patients to an extent similar in magnitude to the beneficial effect of fluorouracil/levamisole adjuvant therapy [18]. Similarly, hyperinsulinemia is associated with a worse disease-specific survival in patients with prostate cancer [19], colon cancer [20], and breast cancer [21].Obesity is also associated with a worse progression-free survival and worse overall survival in patients with ovarian cancer [22]. Nagle et al. demonstrated that overweight, obese, and morbidly obese women with ovarian cancer had worsened survival when compared with women of normal range body mass index (BMI). Furthermore, risk of death increased 3% for each five unit increase in BMI above 18.5 kg/m² [23]. The effect ofobesity on cancer survival is not limited to women as it is a risk factor for prostate cancer in men and is associated with an increased risk of disease progression after confirmatory biopsy in men in low-risk prostate cancers [24–26]. IGF-1, a growth factor pathogenic in tumor development, is elevated in both obese and hyperinsulinemic patients and is implicated in part in the carcinogenesis in these patient populations [27]. When controlling for all comorbidities, obese, elderly patients have a 25% increased risk of readmission compared to nonobese, elderly patients [28]. BMI is directly proportional to the rate of readmission in elderly patients [28].

Although surgery alone may be curative forearly-stage solid tumors , many elderly patients will require neoadjuvant therapy (chemotherapy, radiation therapy, or hormone therapy as a single intervention or the combination) to shrink tumor prior to surgical resection. It is therefore extremely important to understand the potential systemic side effects of such treatments in temporal relationship to the operative procedure. In a study of over 34,000 patients with non-small cell lung cancer, Hardy et al. demonstrated significant associations with the use of chemotherapy/radiation therapy and risks of developing cardiac toxicity. The risks of treatment-associated ischemic heart disease or cardiac dysfunction were greatest among patients with left-sided lung tumors [29]. In addition, perioperative risk associated with neoadjuvant therapy increases with increasing age and increasing time from initial diagnosis. It is not clear if combination neoadjuvant therapy confers additional risk compared to a single-agent therapy [29–34]. Interestingly, radiation to the left chest carries greater risk for a patient to develop myocardial ischemia than radiation to the right chest [29]. Specificchemotherapeutic agents have known cardiac side effects regardless of single or multimodal therapy [35]. For example, anthracyclines are associated with acute heart failure, arrhythmia, and QT prolongation, whereas antibody-based TK inhibitors are known for LV dysfunction. Antimetabolites (5-fluorouracil, capecitabine) are associated with myocardial ischemia, acute myocardial infarction, and arrhythmia. Otherchemotherapeutic agents are known for pulmonary toxicity including doxorubicin, methotrexate, bleomycin, and busulfan. Reported incidence of acute pulmonary toxicity with bleomycin is up to 40% with a fatality rate of 1.5%. The toxicity patterns can range from subacute progressive pulmonary fibrosis to hypersensitivity pneumonitis, organizing pneumonia or an acute chest pain syndrome. While the symptoms and signs usually develop during treatment and regress with discontinuation of therapy, they could be delayed in manifestation up to 6 months after completion of therapy and may not ever completely resolve. Hyperoxia may potentiate acute pulmonary toxicity from bleomycin and should therefore be avoided [36,37]. One proposed mechanism is that the production of highly oxidized radicals may be increased with increased FiO2.Oxidative stress occurs when a cell cannot destroy the excess free radicals. These free radicals may exert toxicity on surfactant production increasing damage to alveoli as well as nuclear DNA which results in fibrosis as well as potentially increase risk for malignancy [36,38]. Preoperative questioning of exposure to these medications, detailed history on the tolerance and course of therapy, as well as signs and symptoms of pulmonary toxicity from exposure are important for planning perioperative care strategies. For patients with a history of pulmonary toxicity to bleomycin, intravenous fluid therapy should be guided to avoid volume overload and perioperative pulmonary edema. In the absence of a history of bleomycin-induced pulmonary toxicity, exposure to bleomycin in itself is not a reason to restrict higher FiO2.

Frailty is now widely regarded as an independent risk factor for poor outcomes in the elderly patient with cancer [39].Phenotypic frailty , the most widely studied preoperative screening tool, uses five criteria including involuntary weight loss, exhaustion, slow gait, poor grip strength, and sedentary behavior [40]. Two separate investigations have concluded that frailty is an independent predictor of discharge to a supported facility, the number of complications, and length of stay [41,42]. Both concluded that adding frailty index to either theASA physical status or other indices of risk such as either the Lee or Eagle Index would improve the area under the receiver operating characteristic (ROC) curve to about 0.86 for prediction of surgical complications and discharge to an assisted or skilled nursing facility [43]. Most recently, Chen et al. demonstrated that frail and sarcopenic geriatric patients demonstrated increased postoperative complications after total gastrectomy for gastric cancer [44]. Unfortunately, despite these risk factors, it is difficult to find afrailty assessment index that can sufficiently cull patients needing further preoperative assessment [45].

Tahiri et al. have demonstrated that elderly patients who experience a greater number of more severe complications take longer to return to their preoperative functional status following abdominal surgery. However, assessing the overall contribution of the number and the severity of postoperative complications to outcomes has been a challenge. The comprehensive complication index (CCI ), first developed by Clavien et al., is a tool which accounts for both the number and severity of complications and generates a numeric score on a scale of 0 to 100 with higher numbers indicating greater likelihood of taking longer to return to preoperative functional status [46]. Of all statistically significant predictors of recovery, the comprehensive complication index score was the only potentially modifiable factor [47]. Instituting evidence-based perioperative care pathways to minimize symptom burden with a particular focus on pain control and delirium prevention; early rescue to prevent cardiovascular, thrombotic, pulmonary, renal, and infectious complications; and improving functional recovery by early mobilization (with adequate fall precautions) are key in this vulnerable patient population. One such pathway is the enhanced recovery pathway. This is a philosophy of care, which utilizes multidisciplinary interventions in the preoperative, intraoperative, and postoperative phases of care in order to expedite recovery of the patient to his or her baseline. An important component of the perioperativecare continuum is patient preparation including advanced care planning (ACP) and optimization for surgery, with particular focus on pre-habilitation programs. Advanced care planning occurs when the patient, while able to understand and make decisions for end-of-life care, discusses and makes known those desires with the physician and family members [48]. Wright et al. demonstrated that patients who did not have end-of-life discussions receive more aggressive end-of-life care than those who did designate their wishes. Further, patients’ quality of life decreased as the number of aggressive interventions increased [49]. A discussion with the patient and his or her loved ones regarding advanced care planning is essential in the management of any oncologic patient.

Perioperative care of the elderly patient requires recognition of special considerations of the contracted intravascular volume status, higher vascular tone (sympathetic dominance), left ventricular hypertrophy, and diastolic dysfunction, all of which lead to higher risk for hypotension at induction of anesthesia. Furthermore, they are dependent on both heart rate and adequate ventricular filling pressures to maintain their cardiac output secondary to diastolic dysfunction. A large retrospective [50] as well as a case-controlled [51] study has independently reported an increased incidence of 30-day mortality and postoperative ischemic stroke, respectively, with intraoperative hypotension. While in the former study, there was a relationship between the area under threshold (AUT) for blood pressure deviations based on the population and individual patient-related baseline data, the later study demonstrated hypotension best defined as a decrease in mean blood pressure relative to a preoperative baseline value. Extension of the importance of avoiding intraoperative hypotension is perhaps the concept of “triple low.” The triple low condition consists of mean arterial pressure (MAP)<75 mm Hg, BIS<45, and an end-tidal volatile anesthetic concentrations in minimum alveolar concentration (MAC) equivalents of<0.8. Cumulative duration of triple low was shown to be associated with perioperative mortality [52]. In a subsequent study, patients enrolled in the B-Unaware, in the BAG-RECALL, and in the Michigan Awareness Control Study were evaluated for cumulative concurrent duration of MAC less than 0.8, MAP less than 75 mmHg, and BIS less than 45 (triple low) [53]. Triple low in this study was independently associated with an increased risk of 30- and 90-day postoperative mortality even after controlling for patient comorbidity through propensity matching. It could be speculated that perhaps triple low identifies patients who are sensitive to anesthesia secondary to poor cerebral reserve (age, frailty, systemic disease and illness) and possibly at risk of brain hypoperfusion.

Other intraoperative management strategies aimed at reducing postoperative complications include those within an enhanced recovery after surgery program. Enhanced recovery after surgery was first introduced by Henrik Kehlet in the early 1990s. It is a multimodal approach which utilizes strategies in all phases of the perioperative period to attenuate the surgical stress and as a result decrease length of stay and reduce postoperative complications [54–57]. Within the intraoperative phase, key components are fluid management and opioid-sparing analgesia as well as minimizing indwelling catheters, drains, and nasogastric tubes.Goal-directed fluid therapy (GDFT) and hemodynamic optimization based on regulating vascular content, tone, and integrity may have value in patients undergoing complex surgery with risk for major blood loss [58]; however, the data is conflicting [59–61]. Specific oncologic procedures coupled with disease-specific variations in the pathophysiology may show different results based on potential complications directly related to intraoperative fluid management. For example, Colantonio et al. demonstrated the use of GDFT in patients undergoing cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy improves outcomes as measured by systemic postoperative complications and length of stay as compared to standard fluid therapy [62]. Another prospective study examining malignant ascites in epithelial ovarian cancer revealed that fluid demands steadily increase in patients with high-volume malignant ascites which can be treated using GDFT coupled with cardiac output monitoring [63]. Conversely, GDFT did not improve clinical outcomes in patients undergoing major elective rectal surgery as opposed to colonic resection [64], again supporting that physiologically distinct processes coupled with individual patient characteristics [65] may be an explanation for applicability in GDFT. Nonetheless, intraoperative hemodynamic stability is a crucial piece in maintaining end-organ perfusion and reducing postoperative complications.

Perioperative blood transfusion in patients with cancer is a complicated story. Fluid therapy, hemodynamic optimization, and anemia management are to be considered together in the perioperative period to maintain optimal tissue oxygen delivery. Frequently patients with cancer are anemic, undergo complex surgical procedures with major blood loss, and are frequently administered large amounts of intravenous fluids in the perioperative period. To maintain tissue oxygen delivery, these patients often receive allogeneic erythrocyte transfusions along with fluid therapy for hemodynamic optimization. There is a concern over the possible negative effects of erythrocyte products on cancer progression and recurrence due to the immunomodulation and inflammatory consequences of blood transfusions. There are relatively few randomized trials related to transfusions and cancer recurrence. Pooled estimates of the effect of perioperative blood transfusions on recurrence in colon resections for cancer resulted in an OR of 1.42 (95% confidence interval, 1.20–1.67) against transfused patients from randomized studies in a recent Cochrane review. Although heterogeneity was detected, stratified meta-analyses confirmed these findings by site and stage of disease, timing of administration of blood products, type of products administered, and volume of transfused products. However, given the heterogeneity and the inability to assess the effect of the surgical technique , the authors were not able to attribute a definite causal relationship [66]. In a recent randomized control trial of patients admitted to the ICU after major surgery for abdominal cancer, a liberal erythrocyte transfusion strategy using a hemoglobin threshold of 9.0 g/dl was found to be superior compared to a restrictive strategy with a hemoglobin threshold of 7.0 g/dl [67]. The decision to transfuse in these patients should therefore be carefully considered balancing the acute effects of untreated anemia on immediate postoperative complications and the long-term oncologic effects of erythrocyte transfusions. In those patients who are at risk of developing significant anemia during or immediately after surgery (hemoglobin <9 g/dl), an active blood and anemia management program consisting of preoperative administration of iron supplements or blood transfusions, minimal access surgical techniques, and intraoperative strategies to conserve and minimize blood loss may prove helpful. This is particularly important in the elderly patient population given their poor physiologic reserve and inability to tolerate inadequate tissue oxygen delivery with significant impact on morbidity and mortality.

Another key component of the enhanced recovery program is opioid-sparing analgesia while providing effective dynamic analgesia. In a retrospective review of over 300,000 patients, 12% had anopioid-related adverse event (ORADE) [68]. ORADE contributed to increased length of stay and increased likelihood for readmission [68]. An additional retrospective study examining greater than 100,000 patients undergoing abdominal surgical procedures demonstrated approximately 10% ileus in the postoperative period leading to increased readmission rate, increased length of stay, and increased total cost [69]. The pharmacokinetics of most opioids have significant variability. Due to changes in gut absorption, metabolism and clearance with aging, coupled with the pharmacodynamics of aging, generally cause opioids to be more potent and have a longer duration of action than compared to younger patients [70]. Multimodal opioid-sparing analgesia can be effective in managing postoperative pain without the risk of opioid-related adverse events. Nonsteroidal anti-inflammatory medications and selective Cox-2 inhibitors consistently reduce postoperative opioid consumption [71]. Local and regional anesthesia also decreases postoperative opioid consumption when utilized as part of a multimodal strategy [72]. While minimizing ORADE contributes to improved outcomes in the elderly, it remains to be seen if wider adoption ofnonsteroidal anti-inflammatory drugs (NSAIDs) and Cox-2 inhibitors as part of the multimodal opioid-sparing regimen will result in other unexpected adverse events and morbidity. It is important to assess the patient’s history and understand the planned surgical procedure when developing the plan of care.