Nutrition Risk and Assessment Process in Patients with Bladder Cancer Undergoing Radical Cystectomy

Abstract

Malnutrition and depleted muscle stores adversely affect bladder cancer patients and contribute to poorer outcomes. These nutrition-related problems are often not addressed, in part because they are not being identified with screening and assessment tools. In this essay, we discuss validated nutrition screening and assessment tools such as the Patient-Generated Subjective Global Assessment; however, each healthcare team must decide on the one which will work best for their clinic. Patients with bladder cancer may be at risk for specific nutrient deficiencies which should be monitored and corrected to improve outcomes and overall health.

Introduction

Malnutrition, sarcopenia, sarcopenic obesity, and frailty negatively impact bladder cancer patient outcomes, particularly in patients with muscle-invasive bladder cancer (MIBC). This essay will present the problem of unidentified and untreated nutrition risk as well as provide strategies to better screen and assess nutrition status in these patients. Moreover, this commentary will discuss potential gaps that may remain and ways that healthcare teams can potentially optimize the physical health status of MIBC patients for improved outcomes.

Problem

The American Society of Clinical Oncology (ASCO) treatment guidelines for MIBC recommend neoadjuvant chemotherapy followed by radical cystectomy (RC) [1, 2]. Many MIBC patients have poor nutritional status at completion of neoadjuvant chemotherapy which is then compounded by the catabolic effects of RC [3–5]. RC impairs gut function and metabolism in part due to reconstruction, which routes urine through intestinal segments. As a result, infection, rapid skeletal muscle wasting, and other complications are common. On average, RC surgery leads to a 5% loss in body weight and 7–17% loss in muscle mass by 2 weeks post-surgery [4, 6]. Using the Nutritional Risk Screening (NRS-2002) tool, between 21–55% of patients were found to be at risk of malnutrition before RC [7–10]. However, using a more robust, validated malnutrition screening and assessment tool, the Patient-Generated Subjective Global Assessment (PG-SGA), 28% of patients were identified as moderately or severely malnourished before surgery [11]. Patients that are malnourished or sarcopenic before RC have increased cancer specific mortality as well as overall mortality [12–14]. Malnutrition may worsen after RC, leading to delays in recovery and healing as well as higher readmission rates. Data suggests that muscle lost after this surgery is not fully restored even six months after the surgery [4].

The problem lies in the issue that many urologic oncology practices do not employ a routine process to identify and assess nutritional risk of these patients [15]. Further complicating this inability to identify patients at nutritional risk are other factors that affect physical health such as sarcopenia, undereating from age-related or socioeconomic factors, or sarcopenic obesity which is often missed by many nutrition screening tools [16]. Given the catabolic nature of RC and the impact neoadjuvant chemotherapy can have on nutritional status [12], routine nutrition screening and assessments are critically needed in this population. Furthermore, many patients could be considered moderately malnourished, or at risk, but are not caught early enough to intervene. Cancer itself impacts energy expenditure, metabolism, and triggers symptoms that alter intake [13]. Smokers and frail elderly with multiple chronic comorbidities are common to the MIBC population and are particularly vulnerable to malnourishment. Chemotherapy before surgery often reduces appetite and perturbs the senses which leads to lowered intake for months prior to surgery putting patients at even higher nutritional risk [12]. Then, surgery increases energy expenditure and depletes muscle and fat stores [4]. Thus, there is a serious need for clinicians to screen and assess the nutritional status of MIBC patients throughout treatment, especially prior to RC.

Nutrition Screening and Assessment Tools

Screening is an important first step in identifying those most at risk for malnutrition and those that would benefit most from a nutrition intervention. In 1996, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) mandated that all patients be screened for nutrition risk before surgery; however, there remains low national adherence with less than half of institutions using validated screening tools with appropriate triggers for follow-up assessment and intervention [17].

The Nutritional Risk Screening (NRS-2002) and Malnutrition Universal Screening Tool (MUST) have the strongest evidence for validity and reliability in surgical oncology populations [18]. NRS-2002 measures malnutrition using four constructs: weight status (body mass index – BMI), weight change (unexpected weight loss), food intake (decreased appetite), and metabolic stress (i.e., surgery, sepsis, and multi-trauma) [19]. MUST is an instrument with three questions that measure malnutrition by weight status (current BMI), unintentional weight loss in the past 3 to 6 months, and food intake changes due to acute disease [20]. Both tools require obtaining the patient’s body weight. Neither tool detects sarcopenia which is an opportunity for new tools and processes to be developed. Regardless, every health system needs to implement a standardized process for nutrition evaluation of patients with MIBC both in the inpatient and outpatient settings. Nutrition screening performed by nursing or patient navigation may allow for earlier identification and referral of at-risk patients to nutrition services within most urologic oncology practice environments.

Patients deemed at nutrition risk are referred to dietitians to implement the nutrition care process which includes assessment, intervention, monitoring, and evaluation [21]. To address this issue of underdiagnosed malnutrition, the Academy of Nutrition and Dietetics (AND) and the American Society for Parenteral and Enteral Nutrition (ASPEN) released a consensus statement in 2012 to standardize both identification and documentation of malnutrition [17]. The consensus statement defines adult malnutrition as the diagnosis of two or more of the following six characteristics: insufficient energy intake, unintended weight loss, loss of muscle mass, loss of subcutaneous fat, fluid accumulation, or diminished muscle function [22].

An important feature of nutrition assessment is a nutrition-focused physical exam to better direct the intervention. The Subjective Global Assessment (SGA) uses weight change, dietary intake, gastrointestinal symptoms, functional status, metabolic stress, and a physical exam to assess fat and muscle stores as well as fluid balance and historically has been shown to be predictive of major postoperative complications in patients undergoing major gastrointestinal surgery [23]. The SGA tool requires a brief physical exam, patient interview, and chart review providing a gradation of diagnoses of well-nourished, moderately malnourished, or severely malnourished [24]. However, the limitation of the SGA is the inability to detect change in a short time frame such as during inpatient stays [25] and does not account for symptoms reported by the patient.

Another tool which utilizes physical assessment is the PG-SGA which was adapted from the SGA and is the gold standard for nutrition assessment [26]. This tool assesses seven constructs of malnutrition: unintentional weight change, muscle status, fat mass, fluid status, metabolic stress, mobility status or functional performance, and food intake (changes in amount, type and consistency) and symptoms that impact food intake [27, 28]. The PG component alone may also be used as a nutrition screener; the SGA component must be performed by a licensed practitioner and takes less than 5 minutes to complete. The tool categorizes the degree of malnutrition by well-nourished, moderately malnourished, or severely malnourished. In addition, the PG-SGA also provides a numerical score with higher scores indicating a greater need for a nutrition intervention to help care teams triage need.

Sarcopenia and Frailty

Nutritional assessments that include a physical assessment component help direct nutritional therapy; yet a standardized process to evaluate nutrition status does not ensure that patients with sarcopenia or frailty are clearly identified and treated. Comorbidities including sarcopenia, sarcopenic obesity and frailty are modifiable prognostic factors in the treatment of MIBC. Sarcopenia, defined as low muscle mass and function, increases the risk for frailty. Frailty increases surgical risk for longer hospital stays, complications, and higher mortality [29]. Mayr et al. found an independent association of sarcopenia and increased cancer-specific mortality in patients undergoing cystectomy [30]. Ha et al. reported that a greater loss in lean mass after cystectomy increased the probability of all-cause mortality [31]. Therefore, it is important to identify patients that are malnourished or sarcopenic before RC to provide interventions to build resiliency, optimize nutrition, and preserve lean mass.

Nearly 25% of obese patients are sarcopenic; however, these patients may not appear malnourished [32]. Excessive adiposity can mask muscle wasting and undernutrition when evaluated by nutrition screening tools. Sarcopenia is best identified by measuring lean mass. Methods to assess lean mass include computed tomography, dual-energy X-ray absorptiometry, bioelectrical impedance, or ultrasound. Since computed tomography is routinely performed as part of diagnosis and staging, it may be easiest to implement. Body composition analysis is not always available in health systems. In such cases, validated tools to assess muscle function, rather than lean mass, for sarcopenia assessment include: SARC-F (Strength, Assistance with walking, Rise from a chair, Climb stairs, and Falls) and the SPSM (the Short Portable Sarcopenia Measure) [33]. Assessing lean mass and providing interventions to maintain or increase body stores could impact patient outcomes and may be key in reducing mortality rates in this patient population. For example, data from Ritch et al. suggest that perioperative oral nutrition support may stave off sarcopenia post-cystectomy and reduce RC complication rates and readmissions [34]. Similarly, Minnella et al. found that a prehabilitation program, that included exercise and nutrition, may speed functional recovery after RC [35]. Data from our group show oral nutrition support with immune modulating arginine and fish oil components tended to preserve lean mass better than standard oral nutrition supplements [36] and will be evaluated as a secondary aim in a currently enrolling phase III clinical trial (NCT03757949). Interventions are currently underway to evaluate the amount of protein people need to eat to maintain lean mass during colon cancer treatment [37], to test the implementation of identifying frail patients and triaging interdisciplinary pre-operative care before major cancer surgery with the goal to improve physical function in elderly (NCT03857620), and to evaluate whether perioperative immunonutrition reduces 30-day postoperative complications from RC better than standard oral nutrition support (NCT03757949).

Nutrient Deficiencies

Nutrient deficiencies are another important aspect of nutritional status that needs assessed in MIBC patients. Low plasma vitamin D concentrations are associated with a higher risk of urothelial bladder cancers [38]. Vitamin D levels are depleted in cancer cachexia [39], and low vitamin D is associated with reduced muscle strength [40]. Vitamin C needs increase after major surgery in order to promote wound healing, and deficiency is often seen in the critically ill [41]. Vitamin B12 is another nutrient of concern in the MIBC population. B12 absorption often declines with age alone [42]. Since the terminal ileum exclusively absorbs vitamin B12, removal of the ileum for use in lower urinary tract reconstruction may predispose patients to vitamin B12 deficiency [43]. Deficiency of B12 could take years, as body reserves deplete over time, thus observable symptoms may not appear immediately after RC. Awareness of this risk and monitoring of the signs and symptoms of deficiency are crucial. Deficiency may cause megaloblastic anemia and result in symptoms such as fatigue, ataxia, glossitis, or can be neurological in nature [43]. Medications that inhibit gastric acid production, and may be commonly used in the aging population, can compound absorption issues of vitamin B12 [44]. B12 serum levels can confirm a suspected diagnosis.

Mineral micronutrients may also be impacted from MIBC treatment. Iron depletion can occur from blood losses during surgery or can be the result of chemotherapy agents and presents as microcytic hypochromic anemia. Supplementation of iron may not suffice. The cause of depletion should first be addressed, whether that cause be a lack of erythropoietin, a hormone that signals production of red blood cells that is impacted by platinum chemotherapy agents, or from surgical blood loss [45]. Zinc could become depleted after RC and is critical for wound healing [46]. Zinc supplementation may be helpful in addressing taste changes that arise during chemotherapy treatment [47] and, in theory, could impact overall intake and nutritional status. If taste changes occur, assessing zinc status with labs or supplementing with zinc and monitoring for taste change improvement may be warranted. Electrolyte imbalance is a common side effect of platinum-based chemotherapies which requires monitoring and treatment [48]. Symptoms of abnormal labs can vary and may include muscle cramping, arrhythmias, and even behavioral changes; however, patients may be asymptomatic. Correcting low levels of sodium, magnesium, phosphorus, and calcium is important to improve patient outcomes. Low magnesium is of particular importance as deficiency can lead to refractory depletion of the other electrolytes [48]. Micronutrient deficiencies can be insidious, with a few physical signs and symptoms that may present as tongue swelling and brittle or spoon shaped nails. Therefore, obtaining labs is the most effective way to assess and monitor. With any deficiency, food intake is first consideration, but supplementation may also be warranted.

Guidelines

The 2017 Non-Metastatic MIBC: AUA/ASCO/ASTRO/SUO Guidelines committee guideline statement 15 states: “cystectomy patients at high risk for malnutrition should undergo nutritional counseling in preparation for surgery with the goal of optimizing nutritional status prior to surgery”. The method of optimization was not discussed nor prescribed. Few nutrition intervention studies in the cystectomy population have been published. Before enhanced recovery after surgery (ERAS) pathways were widely adopted, only total parenteral nutrition (TPN) studies [10, 49] or pre-surgery oral supplements [50] had been used for nutritional support [51]. Data show that following a regular healthy diet decreased the length of stay compared to TPN post-operative feeding [52]. Similar to other surgical nutrition support literature, TPN in RC has led to higher infection rates when compared to consuming a regular diet (32% vs 11%; p = 0.001) [10]. These data are not surprising since the guidelines from the Society of Critical Care Medicine/American Society of Parenteral and Enteral Nutrition (SCCM/ASPEN) suggest that enteric feeding is best to maintain gut integrity and modulate the immune response [53].

ERAS pathways preserve gut function after RC and open opportunities for intervention: perioperative nutrition [52, 54]. Preliminary studies are promising; however, there is a critical need to identify the most effective forms of perioperative nutritional support and to determine their impact on surgical outcomes. Without this care, RC will continue to save lives, but at a high cost in terms of downstream adverse surgical complications. The ESPEN expert group recommendations for action against cancer-related malnutrition recommend screening and increasing intake by offering oral nutrition support [55]. The ESPEN guideline for clinical nutrition in surgery recommends with strong consensus that perioperative nutrition therapy is indicated in patients with malnutrition and those with nutritional risk [56]. The SCCM/ASPEN Critical Care guidelines recommend that surgical patients consume perioperative immune modulating formulas that include arginine and nutrient combinations such as fish oil along with arginine, regardless of baseline nutrition status [53]. The quality of evidence for this recommendation was determined to be moderate to low revealing that we currently do not have robust scientific evidence on this point. To date, there are only three published studies in this area. In a small (n=60), case-controlled, pilot study in the RC population, Bertrand and colleagues reported that SIM taken before surgery resulted in a reduction of post-operative complications (40% vs. 77% in the historical control) (P = 0.008) and infection rates (23% vs. 60% in the historical control) (P = 0.008) [50]. In a randomized pilot trial, our group found that giving immune modulating supplement drinks before and after cystectomy reduced post-operative complications by 33% and most notably, reduced infections by 39% compared to an identical oral nutrition support lacking the immuno-modulators [6]. However, Lyon et al. and Kukreja et al. did not find statistically significant differences in infection or complication rates with immune modulating nutrition interventions compared to standard of care [57, 58].

Conclusion

There are many quick, easy to use nutrition screening tools that can be used in the outpatient and inpatient settings. Choosing the appropriate tool will depend on each institution’s availability, time, budget, and other factors. Nutritional screening and assessments should be made throughout the patient’s bladder cancer care process including at initial diagnosis, during and after chemotherapy treatments, pre-operatively, during surgery admission and annually post RC. Obesity may mask sarcopenia; therefore, assessing weight status and body mass index is not enough. Ideally, clinical teams will be evaluating muscle and fat losses, energy needs, micronutrient deficiencies, and addressing factors related to intake such as chemotherapy agents, taste changes, and barriers to food security throughout care in the MIBC population. Appropriate nutritional assessment, intervention and monitoring may be a key opportunity for improving outcomes and reducing complications.