The elderly population is dramatically increasing in most countries, and exponential growth is expected in some countries, including South Korea [1]. As a result, most elderly diseases are on the rise. Pancreatic cancer is one of those diseases. More than 50% of pancreatic cancer patients in Korea are over the age of 70 years, and nearly 20% are over the age of 80 years [2]. Surgeons will see more and more elderly patients with pancreatic cancer. This trend stems from an extended life span.

Pancreatic cancer has dismal prognosis, demanding major surgery with high risk and life quality problems, especially in the elderly. Therefore, treatment selection, whether or not to undergo surgery, preoperative risk assessment, and perioperative management of the elderly are becoming critical issues. In this paper, the surgical treatment of elderly patients with pancreatic cancer is reviewed.

In a large population-based cohort study, early outcomes after pancreatectomy including mortality worsened with age, and the odds ratio of in-hospital mortality was remarkable in those aged 80 years or older [3]. A national study in the United States using a nationwide inpatient sample reported a higher surgical mortality rate for octogenarian patients [4]. Cancer registry data from the Netherlands also demonstrated an increasing mortality rate with advancing age after pancreatic cancer surgery; however, the long-term survival benefit was acceptable despite a slight decline in the elderly [5]. A Chinese study also showed that pancreatic cancer-specific survival by American Joint Committee on Cancer (AJCC) stage and Surveillance, Epidemiology, and End Results (SEER) stage was negatively correlated with age [6]. Studies in Japan and Korea demonstrated better outcomes after surgery than nonsurgical treatment in potentially resectable cancer in the elderly [78]. According to data from Seoul National University, once resection was performed, there was no difference in the cumulative recurrence rate in the elderly [9].

A recent systematic review summarized the outcomes of surgery for pancreatic cancer in the elderly [10]. In the enrolled studies, the age definition of the elderly was elevated from the 70s to the 80s over time. The authors compared surgical mortality, complications, and overall survival between elderly and non-elderly adults during the 2 time periods starting study enrollment before and after 2000. Mortality rate of older adults improved and became the same as in younger adults, while complications and survival rates improved but still had a worse prognosis in older adults.

An analysis of data from the United States National Cancer Database on 98 pancreatic cancer patients over the age of 90 showed high mortality and low survival rates. In addition, chemoradiation alone showed similar survival results with surgery alone [11].

In summary, morbidity and mortality are higher in the elderly, but the gap is narrowing. It would be difficult to explain how surgery has become safer over time for elderly patients with pancreatic cancer. Improvement of perioperative and operative care as well as general health status of the elderly would be the important reasons. Long-term survival in older people is generally worse, but surgical treatment offers a better chance than other treatment modalities. Surgical resection may benefit appropriately selected elderly patients with pancreatic cancer.

Surgeons must appropriately select surgical candidates and decide on neoadjuvant therapy (NAT) vs. upfront surgery. Both host and disease factors must be considered for decision-making. A United States national study found that patients older than 80 years had worse survival outcomes, particularly those with 2 or more comorbid conditions [4]. A study from the National Cancer Center, which found that the overall survival rate after surgery was significantly higher in elderly patients with resectable pancreatic cancer compared to nonsurgical treatment, also revealed that the comorbidity index was an independent factor in the overall survival rate [7]. Satoi and colleagues [8] showed that overall survival in patients with potentially resectable cancer in their 80s was better only in mentally and physically fit older patients with favorable operative risk scores. Therefore, the risk of surgery must be assessed to detect impairment not identified on routine examination and to predict short-term outcome and overall survival so that appropriate treatment can be selected. For this purpose, a comprehensive geriatric assessment is strongly recommended to develop a treatment plan [12].

Fig. 1 shows risk assessment scales, indices, or scoring systems used in practice [1314151617181920212223242526]. Fig. 2 shows some samples of general or specific risk scoring systems for predicting pancreatectomy morbidity and mortality, and there are different scoring systems for predicting specific complications [1327282930]. The International Society of Geriatric Oncology established a consensus on geriatric assessment in older patients before treatment [12]. The domains to be measured and some tools are summarized in Table 1 [12]. Winer and Dotan [31] explored relevance in geriatric domains including functional, nutritional, and psychological status, social support, comorbidity, polypharmacy, cognition, and prediction of chemotherapy toxicity for pancreatic cancer, which was mostly about tolerability and effects on treatment modalities.

As one of the disease factors, decisions should be made considering the extent of the disease and resectability. Kondo et al. [32] reported that patients older than 80 years of age had a similar prognosis for resectable pancreatic cancer, but a worse prognosis for borderline or locally advanced cancer than those younger than 80 years of age. A multicenter study in Japan showed poor long-term outcomes in the elderly, especially in borderline resectable cancer, and suggested that the poorer survival rates in the elderly were due to lower adjuvant therapy completion rates [33]. A study by the European group RESPECT reported that elderly patients treated with NAT had comparable resectability and survival rates to that of younger borderline resectable and locally advanced pancreatic cancer patients [34].

As age is a major risk factor for dropout in treatment after surgery, NAT might provide a greater chance to complete adjuvant therapy for the elderly. Recent studies by some influential groups have consistently reported that NAT is safe and effective for elderly patients with resectable pancreatic cancer [35363738]. Randomized clinical trials for NAT are recommended in elderly pancreatic cancer patients who are considered tolerable to both surgery and chemotherapy.

The next step is decision-making. Surgery in the elderly can lead to unwanted burdens and unintended consequences such as loss of function and reduced quality of life. The elderly may have different values, goals, and preferences. In addition, there is a lack of high-quality evidence to interpret the results of preoperative risk assessment in geriatric patients, not only because there is no objective cutoff in preoperative evaluation criteria, but also because geriatric patients are under-represented in clinical trials. Thus, traditional ‘informed consent’ is not sufficient. A patient-centered approach using shared decision-making has been proposed to integrate the patient’s preferences, values, and goals with underlying health conditions so that patients and physicians can make decisions together. Potential outcomes of shared decision-making include reduction of unwanted and aggressive treatment, fewer symptoms of postoperative stress, and value concordant decisions [38].

Once the decision is made to proceed with surgery, preoperative, operative, and postoperative geriatric-specific management should be considered. The purpose of prehabilitation, which is likely to be most useful for older cancer patients, is to help prepare the patient for surgery in order to reduce recovery time and postoperative complications. The core components are cardiovascular and skeletal muscle training, nutritional management, psychological support, and medical optimization. The benefits of prehabilitation have been seen in some major surgeries but have not been clear in pancreatic surgeries. However, pancreatic cancer often has modifiable risk factors associated with significant nutritional impairments such as cachexia and sarcopenia, which are potential targets for prehabilitation. Therefore, elderly patients with pancreatic cancer may benefit the most from a prehabilitation program to improve nutritional status as well as cardiorespiratory function.

According to a recent systematic review and meta-analysis on minimally invasive pancreaticoduodenectomy in the elderly, minimally invasive surgery is safe, feasible, and can be used as a potential alternative to open surgery. Although minimally invasive surgery cannot eliminate a high risk of mortality and morbidity, it is recommended because it is less painful, and early recovery is very important for the elderly [3940].

How about vascular resection? Vein resection does not appear to cause significantly higher morbidity, and survival outcomes are comparable for younger patients [4142]. However, in cases of arterial resection, there are only a few reports on successful experiences of celiac axis resection in the elderly [4344].

After surgery, postoperative care specific to geriatric patients should be performed. Fig. 3 is a list of postoperative geriatric care requiring a multidisciplinary approach. Whether enhanced recovery after surgery (ERAS) is effective for pancreatectomy and applicable in the elderly remains a question to be answered. According to the updated ERAS guidelines and meta-analysis, although there are some favorable reports on the benefits of ERAS, new randomized controlled trials with low risk of bias are needed to provide evidence of the effectiveness of ERAS in pancreatic surgery [4546]. Thus, at this point, ERAS may be particularly important for older patients and/or less physically fit patients.

Of the short-term outcome measures of ERAS, at least the length of hospital stay after pancreaticoduodenectomy decreased in elderly patients [47]. Although prehabilitation and ERAS are clearly beneficial for the elderly, a tailored multimodal prehabilitation and ERAS program for elderly patients based on evidence-based cutoff values is needed [48].

Therefore, the same operating principle can be applied to the elderly if properly selected. However, adding surgical risk through extensive surgery is not recommended, especially in very elderly patients with localized advanced disease. Tailored perioperative care may improve operative outcomes in elderly patients.

Some countries have good institutional system models for geriatric surgical care. For example, the Dukes Center for Geriatric Surgery’s Perioperative Optimization of Senior Health system seems well established. As a result of using this system, it was reported that the length of hospitalization, readmission rate, and complication rate decreased, indicating that the institutional system is working properly [49].

Only 7% of randomized controlled trials are specifically designed for the elderly. Elderly pancreatic cancer patients have been under-represented in clinical trials because the elderly group in clinical trials is much smaller than the actual cancer population. As a result, it is not possible to simply extrapolate clinical trial data to the elderly [50]. Therefore, clinical trials designed specifically for the elderly with pancreatic cancer are needed.

Among several clinical practice guidelines, only the Japan Pancreas Society guidelines raised the age-specific question of whether surgical treatment is recommended for pancreatic cancer patients aged 80 years or older. Their statement was “surgical treatment may be considered for elderly patients with pancreatic cancer 80 years or older if they wish to undergo surgery and their general condition allows it” [51]. Although it seems obscure, it describes all the important factors, the patient’s wishes, and risk assessment.

In 2019, experts in geriatric oncology and hepato-biliary-pancreatic surgery met to conduct a state-of-the-art overview of multimodality approaches and explore the latest clinical pathways for geriatric patients with hepato-biliary-pancreatic malignancies. The results of this study were published in a special issue of the European Journal of Surgical Oncology [52].

Although the elderly are expected to have higher morbidity and mortality and lower long-term survival outcomes, surgery is becoming safer over time. Appropriate surgical indication selection, patient-centered decision-making, adequate prehabilitation, and postoperative geriatric care including ERAS are expected to improve surgical outcomes in the elderly. Surgeons must have the concept of geriatric care, and efforts based on institutional systems and academic societies are required. If well selected and prepared, the same surgical principle as non-elderly patients can be applied to elderly patients.