March 29, 2021

Patients undergoing major cancer interventions such as surgical, chemotherapy, radiotherapy, and immunotherapy are prone to the adverse effects of their cancer, as well as side effects of cancer treatments. For complex surgery, such as that most often needed in the treatment of hepatobiliary and pancreatic (HPB) cancers, morbidity and mortality rates remain high, despite advancing innovations and the use of more minimal resection techniques.

The majority of patients presenting with HBP malignancies are older than 65 years.

With physiological and mental reserve decreasing with age, older patients are vulnerable to adverse health outcomes and even minor illnesses can lead to substantive declines in health. In this context, surgery represents an exceptional challenge for the frail older cancer patient.

Preoperative assessment and risk stratification of older patients with cancer should take into account not only their age, comorbidities, specific disease process and invasiveness of surgery, but also their functional capacity, malnutrition presence of depression, frailty and level of functional independence, cognitive impairment, and polypharmacy. Preoperative assessment is valuable not only to stratify surgical risk and adequately allocate medical resources (i.e., high dependency unit or intensive care unit admission) but most importantly to allow preoperative optimization to reduce the risk of post-operative complications and facilitate recovery which is directly related to improved long-term results.

With these purposes in mind, a multidisciplinary approach, including surgeons, anaesthesiologists, geriatricians, nutritionists, and whenever possible, physiotherapists, is recommended. When this approach is used, older patients with poor baseline functional capacity have shown a greater improvement, before and after surgery, compared to younger and fitter patients, when treated with multimodal pre-habilitation (prehab) programs.

The preoperative period can be an opportune time to increase the physiological reserve in anticipation of surgery with the intention to improve outcomes and accelerate recovery. The main determinants of poor functional capacity are the physical, nutritional, and psychological status, and these represent risk factors for poor surgical outcomes. However, there is sufficient evidence that these factors can be modified in anticipation of surgery. This implies that we move from restoring functional capacity after surgery to preoperative preventative strategies.

Following a cancer diagnosis, the prehab process aims to optimize a person’s physical, nutritional, and psychological health in the time period before their cancer treatment begins and throughout treatment for non-surgical interventions. The core components of a multi-faceted prehab program include cardiovascular and skeletal muscle fitness training, nutritional management, wellbeing with psychological support, and medical optimization. This optimization process supports the patient in preparing for the physiological challenges of their cancer treatments, whilst aiming to shorten recovery time, reduce peri-operative complications, and improve compliance with nonsurgical treatments.

The most effective prehab programs provide a holistic approach to promote patient

empowerment, adherence, and improved experience. This includes a graded, evidence-based exercise prescription to give the best opportunity to improve fitness in the constrained time-period before cancer treatment. High-intensity interval training (HIIT) exercise provides an effective, time-efficient approach to increasing fitness, but any exercise could be viewed as potentially beneficial for patients.

Most supporting evidence for prehab has come from surgical patients undergoing colorectal, lung, and oesphago-gastric resections. There is currently less evidence supporting the use of prehab programs in HPB surgery but preliminary results emerging from ongoing prehab studies in patients undergoing liver resection at The HPB Unit in Manchester (Manchester Royal Infirmary, University of Manchester, UK) have shown improvement in pre-operative physical fitness especially in the least fit groups.

People with cancer often present with low muscle mass/sarcopenia at diagnosis, and this can worsen throughout their treatment or disease progression. Multi-modal prehab may prove to be particularly important in the surgical treatment of pancreatic cancer, a diagnosis often associated with cachexia and malnutrition. Recent evidence from ongoing initiatives in Manchester recommends nutritional assessment and supplementation before and after major pancreas resection. Therefore, a key aim within nutritional prehab is to preserve muscle mass or promote muscle anabolism, alongside exercise therapy. When designing nutritional interventions, it is important to ensure appropriate levels of energy, helping to stimulate protein synthesis, and suppress protein breakdown. Patients with pancreatic exocrine insufficiency (PEI) often suffer from malnutrition and sarcopenia because of malabsorption. Untreated PEI has been linked to worse quality of life and survival among individuals with pancreatic cancer.

NICE guidelines recommend that enteric-coated pancreatin is offered to all patients with unresectable disease, and that it should be considered before and after pancreatic cancer resection. Pancreatic enzyme replacement has also been associated with increased survival following pancreatoduodenectomy for periampullary malignancy. Given its association with malnutrition, sarcopenia, and survival, the treatment of PEI should be seen as a vital component of nutritional prehab in this cohort of patients.

In conclusion, multidisciplinary prehabilitation programs incorporate innovative and comprehensive preoperative risk evaluation and stratification accompanied by structured and personalized interventions with particular attention for those patients at risk. The published data on prehab in older, frail patients is still insufficient to demonstrate a positive impact of the multimodal interventions on clinical outcome. Several reasons such as heterogeneity of outcome measured and different intensity of surgical stress, difficulty to distinguish frailty classifications, and inconsistency of compliance to the protocols by the patients, can explain some of the negative results. The integrated role of preoperative exercise training, adequate nutrition, and psychosocial balance within the perioperative medical and surgical care deserves to receive more attention in the future for our older, frail patients.