Abstract
Background:
Coordinated preoperative optimization programs for radical cystectomy (RC) are limited and non-comprehensive. We evaluated the feasibility and acceptability of a coordinated, multi-faceted prehabilitation program for RC patients at a high-volume bladder cancer referral center.
Methods:
We performed a narrative literature review for prehabilitation in bladder cancer management as of December 1, 2020, with specific emphasis on examining higher-level evidence sources. We selected domains with the highest level of evidence and recruited a multidisciplinary team of experts to design our program. We implemented a comprehensive prehabilitation program with a pre-defined order set as standard of care for all patients undergoing RC beginning February 1, 2021. Demographic and clinicopathologic data were collected prospectively. Rates of adherence to the prehabilitation program services were analyzed using Stata version 13.
Results:
A total of 82 patients were enrolled between February – December 2021, of which 67 (81%) had undergone RC at data cutoff. Mean age was 68 years (SD 11) and 63 (76%) identified as male. Neoadjuvant chemotherapy (NAC) was utilized in 48 (59%) patients. The mean Charlson Comorbidity Index was 3.8 (SD 2.3). 100% of patients were screened for malnutrition, with 82% consuming nutritional supplements. Fifty-two percent of patients attended physical therapy pre-op. The 30-day and 30- to 90-day rates of complications were 56% and 40%, respectively. Resource length of stay (RLOS) declined after implementation of prehabilitation.
Conclusions:
Implementation of a comprehensive prehabilitation program at a high-volume bladder cancer referral center is feasible and has a modest effect on resource consumption and complications in our early experience.
Keywords: Radical cystectomy, Prehabilitation, Outcomes, Complications, Implementation science, Quality improvement
1. Introduction
Contemporary outcomes of patients undergoing radical cystectomy (RC) for bladder cancer continue to demonstrate a high rate of perioperative complications ranging from 30% to 65%, and perioperative mortality ranging from 1.5% to 10% [1,2]. Multifactorial etiologies contribute to perioperative morbidity in this patient population, including advanced age, frailty, medical and psychiatric comorbidity, functional deficits, and high rates of present and past tobacco use [3–5]. Frailty is a multi-system syndrome owing to decreased physiologic reserve, poor adaptation to biological stressors, and increased vulnerability to adverse outcomes [6]. Prior studies have shown both a high prevalence of frailty in the RC population and worse clinical outcomes in patients with baseline frailty before RC [3,4,7]. Enhanced recovery after surgery (ERAS) has evolved to mitigate the morbidity of RC, but most efforts focus on intra- and postoperative optimization. These efforts have resulted in incremental improvements in length of stay (LOS) and postoperative complications [8]. However, these efforts often begin within a few days or on the day of surgery.
Prior literature describing multidisciplinary and multimodal prehabilitation in RC patients is extremely limited [3,9]. Previous studies describe small series and have focused on monotherapies [10,11]. Only 1 randomized trial comparing multimodal prehabilitation to usual care has been reported and demonstrated modest improvements in functional status vs. usual care [12]. Per the current American Urological Association Guidelines (AUA), many patients undergoing RC should receive neoadjuvant chemotherapy before RC [13]. This affords a timely window of opportunity for prehabilitation in this patient population. This report is aimed at aiding in implementation science for prehabilitation, with the work of Souwer et al. in colorectal cancer serving as a framework for design of our program [14]. In their paper, they hypothesized that such a program would be feasible, and might also reduce mortality rates by half and reduce the frequency of complications. Although the mortality endpoint was not met, multidisciplinary prehabilitation improved complication rates and decreased length of stay [14]. We hypothesized that implementation of a comprehensive, multi-disciplinary prehabilitation program would be both feasible and acceptable to patients preparing for RC for bladder cancer and would not delay the timely performance of cystectomy when adapted to individual patient needs.
2. Methods
We performed a narrative literature review of data for prehabilitation treatment options for patients with bladder cancer as of December 1, 2020, with specific emphasis on examining higher-level evidence sources (prospective trials). Keywords utilized for the search included: bladder cancer, radical cystectomy, prehabilitation, rehabilitation, perioperative optimization, physical therapy, ostomy, morbidity, smoking cessation, complications, malnutrition, and clinical trial. We then identified the domains with the highest level of evidence for utilization in our program. In total, 11 trials representing 5 domains with at least moderate evidence of efficacy in reducing morbidity were identified for inclusion in our program. These included: 1) referral to smoking cessation for current smokers, 2) stoma/ostomy education, 3) malnutrition screening and intervention, 4) physical therapy/ physical medicine referral and prescribed exercise, and 5) onco-psychology screening and referral.
We then implemented a comprehensive prehabilitation program for all patients undergoing RC at our institution beginning February 1, 2021. We utilized a personalized order set that was fully integrated into our existing electronic medical record and included in our clinic workflows after a brief period of training for all stakeholders before the program launch. The order set was designed after multidisciplinary collaborator review of evidence domains for prehabilitation, including a review of existing ERAS protocols and clinical workflow. A dedicated institutional informatics team then synthesized the custom prehabilitation order set and performed beta testing for functionality. Our clinics also utilize dedicated oncology lead nurses for care coordination, and all orders were then placed in the clinic at the decision point to proceed with surgery (with or without neoadjuvant chemotherapy). Our institution maintains a robust, prospective RC and enhanced recovery after surgery (ERAS) dashboard with complications and readmission data dating back to 2017 allowing comparison of outcomes as changes to our clinical pathways are implemented over time. We will discuss details regarding specific protocols and the evidence supporting the implementation for each domain below.
2.1. Smoking cessation
All patients who were identified as current smokers received a brief counseling intervention regarding the importance of quitting and a referral to a dedicated smoking cessation clinic for more intense intervention. Work by Rink and colleagues demonstrated a dose-dependent relationship between smoking and postoperative outcomes after RC, with heavy long-term smokers exhibiting the worst outcomes [15]. A Cochrane review of 13 randomized controlled trials evaluating a smoking cessation intervention and surgical outcomes (including urologic surgery) demonstrated that brief interventions were neither associated with long-term smoking outcomes nor reduced postoperative complications [16]. However, more intensive interventions were observed to reduce overall postoperative complications and wound complications [16]. Prior work has demonstrated that the period around a new diagnosis of bladder cancer is an effective time to broach the topic of smoking cessation, with quit rates as much as 5 times higher in this period [17,18]. Patients attending the smoking cessation clinic received intense, personalized counseling on smoking cessation and were offered prescriptions and other quitting aids.
2.2. Urinary stoma education
Prior work by Zganjar and colleagues has characterized challenges surrounding adaptation to a urinary stoma and described an intensive “stoma boot camp” intervention to address these needs, resulting in an improvement in health-related quality of life (HRQOL) and patient understanding of ostomy adjustment and care [19]. Initial ostomy education is often performed in many centers during the period of inpatient convalescence, with many conflicting challenges to effective education and completion of daily goals of care. Overall, this area of clinical need is poorly defined. Preoperative referral to an ostomy nursing clinic for stoma marking and education has been an ongoing area of quality improvement in our group. Using our standardized order set, preoperative referral for all patients undergoing RC was made, in addition to the typical inpatient educational visit for in-person teaching of patient and family by our stoma nurse educators. Significantly, all patients also had a planned postoperative visit scheduled in the ostomy clinic in the first 2 weeks after surgery in order to perform necessary troubleshooting regarding pouch placement, fitting, or stoma care. This visit was scheduled to coordinate with the patient’s postoperative check-up to reduce additional patient burden.
2.3. Malnutrition screening and intervention
Malnutrition is prevalent in patients undergoing RC, and data supporting preoperative correction of malnutrition, anemia, and vitamin deficiency is more robust [20–23]. As part of the preoperative assessment, participating patients had standardized lab work performed. This included complete blood counts (CBC), comprehensive metabolic profile (CMP), Vitamin C, Folate, Vitamin D, and pre-albumin. Lab results were then reviewed by both the ordering surgeon and our comprehensive high-risk surgical encounter (Hi-RISE) anesthesia preoperative clinic. An experienced nurse practitioner under the supervision of an anesthesiologist prescribed indicated supplements or infusion therapy to correct vitamin deficiency or anemia as part of comprehensive optimization. Malnutrition was also identified using the previously validated Malnutrition Screening Tool [24]. A multi-system review of all medications and co-morbidities was also performed, with an emphasis on optimizing preoperative blood pressure, blood glucose control, pulmonary disease, and other modifiable comorbid conditions. By standard institutional protocol, the operating surgeon also received a summary recommendation from Hi-RISE of immediate preoperative interventions, including specific medications to continue while inpatient for optimization of pulmonary health in current or former smokers. Additionally, all patients received a preoperative nutritional supplement bundle that includes 5 days of preoperative immuno-nutrition supplements to be consumed 3 times daily up to the night before surgery, similar to the protocol previously defined by Hamilton-Reeves and colleagues [25].
2.4. Prescribed exercise, physical therapy, and rehabilitation services
The impact of preoperative exercise and improvement of functional domains remains a widespread area of surgical research interest. A 2011 meta-analysis by Valkenet and colleagues included an evaluation of studies in joint replacement, cardiac, and abdominal surgery, and concluded that preoperative exercise therapy can be effective in reducing postoperative complications [26]. A recent systematic review of studies of preoperative exercise programs for patients undergoing urologic surgery showed that these programs may result in improved cardiorespiratory fitness and quality of life, but current studies have yet to demonstrate an impact on surgical outcomes [27]. One small randomized trial in patients with bladder cancer undergoing RC demonstrated improvement in functional domains in patients who received physical therapy and prescribed exercise [12]. All patients scheduled for RC were offered referral to physical therapy or physical medicine and rehabilitation services for baseline functional assessment. We designed a 3-tiered pathway for assessing and treating functional deficits in conjunction with experts from our Department of Physical Medicine and Rehabilitation (Fig. 1). In our study, this service was offered to patients in whom either neoadjuvant chemotherapy or immediate RC was planned. Functional assessment by a trained physical therapist was then followed by either tailored therapy routines for those with functional deficits or the development of a personalized home exercise regimen for those without deficits seeking to increase overall fitness. The latter service was offered at a nominal fee for a 1-hour assessment and training regimen provided by rehabilitation services. Detailed reporting of changes in functional outcomes within each diagnostic pathway are being prospectively recorded and will be reported separately as data mature.
Fig. 1.
Cystectomy prehabilitation physical therapy and physical medicine and rehabilitation treatment referral algorithm.
6MWT = 6-minute walk test; PM&R = Physical Medicine and Rehabilitation; PROMIS = Patient-reported outcome measure-physical function instrument; PT = Physical Therapy; SLS = Single-leg stance text.
2.5. Onco-Psychology screening and referral
Prior reports have described a high prevalence of depression and anxiety among patients diagnosed with bladder cancer [28,29]. Patients planned for RC underwent screening for depressive disorders via the Patient Health Questionnaire-2 (PHQ-2) validated instrument during their initial surgical assessment [30]. Patients screening positive for depressive disorders were then offered referral to Onco-Psychology services at the Vanderbilt-Ingram Cancer Center when indicated. Safety protocols for patients in whom severe depression or suicidal ideation was present were followed per institutional policy.
2.6. Data collection
Demographic data including age, gender, self-reported race, and marital status, and clinicopathologic data including comorbidities, use of neoadjuvant chemotherapy, preoperative smoking status, basic preoperative lab work, and pathologic TNM stage were collected prospectively and then validated via an audit by 3 study authors (JT, VG, WS). Charlson Comorbidity Index (CCI) was calculated for each patient using documented comorbidities from chart review. All data were de-identified, recorded, and stored in an Institutional Review Board-approved (IRB) electronic REDCap database [31,32]. We evaluated the uptake and feasibility of the prehabilitation program by analyzing rates of adherence to the referred program services. All statistical analysis was completed using Stata version 13. IRB approval was obtained from Vanderbilt University Medical Center before study initiation (Protocol # 210319).
3. Results
A total of 82 patients were enrolled between February – December 2021, of which 67 (81%) had undergone RC at the time of data cutoff. Table 1 contains demographic characteristics, as well as more detailed data for each domain. The mean age was 68 years (SD 11) and 63 (76%) identified as male. Neoadjuvant chemotherapy (NAC) was utilized in 48 (59%) patients. The mean Charlson Comorbidity Index was 3.8 (SD 2.3). Of note, preoperative chronic kidney disease (CKD) stage III or greater was present in 24 (36%) patients who underwent RC and was the most common factor precluding use of platinum-based NAC. Importantly, all patients who received chemotherapy underwent RC within 10 weeks of completion of NAC. Regarding distance traveled for treatment and feasibility, mean and median distance traveled to VUMC as calculated by home ZIP code were 105 and 92 miles, respectively, with 23 patients presenting from out of state, and 59 patients from in-state.
Table 1.
Patient characteristics at study enrollment and adherence to prehabilitation program.
| Prehabilitation Participants | 82 |
| Completed Radical Cystectomy | 67 (82) |
| Age (years) | 68.5 ± 10.8 |
| Male | 63 (77) |
| Female | 19 (23) |
| Race | |
| White | 75 (91) |
| Black or African American | 4 (5) |
| Unknown/Not Reported | 3 (4) |
| Charlson Comorbidity Index | 3.8 (SD 2.3) |
| Preoperative Chronic Kidney Disease | 24 (36)a |
| Received Neoadjuvant Chemotherapy | 48 (59) |
| Distance < 100 miles from treatment center | 42 (51) |
| Distance > 100 miles from treatment center | 40 (49) |
| In-state residence | 59 (72) |
| Out-of-state residence | 23 (28) |
| Preoperative Malnutrition Screening | 67 (100)a |
| Preoperative immuno-nutrition drink | 55 (82)a |
| Iron Infusions | 28 (42)a |
| Vitamin C Replacement | 8 (12)a |
| Folate Replacement | 1 (1.5)a |
| Ostomy Clinic preoperatively | 65 (97)a |
| Ostomy clinic postoperatively | 49 (73)a |
| PM&R/PT preoperatively at treatment center | 35 (52)a |
| Median distance for PMR/PT participants | 103 miles |
| Median distance for PMR/PT non-participants | 147 miles |
| Smoking Status | |
| Never smoker | 29 (35) |
| Former smoker | 39 (48) |
| Current Smoker | 14 (17) |
| Preoperative smoking cessation clinic visit | 9 (64)b |
| Pharmacologic cessation aids prescribed | 2 (14)b |
| Screened positive for depression/anxiety | 3 (3.7)a |
| Attended Onco-Psychology Visit | 2 (67)c |
Data are expressed as mean and n (%).
Denominator is number of patients who have completed radical cystectomy.
Denominator is number of current smokers.
Denominator is number who screened positive for depression/anxiety.
Ostomy clinic appointments were well-attended, with 65 (97%) patients receiving stoma education and ideal stoma marking preoperatively. Likewise, in the postoperative setting 49 (73%) patients attended follow-up ostomy visits for additional education and troubleshooting. As this is a newly implemented visit in our care pathway, we do not have historical rates for comparison. There was no significant difference in mean travel distance between patients who did and did not attend postoperative ostomy clinic visits (129 vs. 127 miles, P > 0.05).
All 82 enrolled patients were screened for malnutrition, anemia, and vitamin deficiencies preoperatively, including all 67 (100%) patients who had undergone RC at the time of data analysis. Of these patients, 55 (82%) patients were prescribed and consumed immuno-nutrition supplements preoperatively. Additional common supplemental therapies included intravenous iron infusions in 28 patients (42%) before surgery, and Vitamin C and Folate replacement in 8 (12%) and 1 (1.5%) patient respectively.
Furthermore, 35 (52%) patients were referred to and attended visits with physical therapy or physical medicine and rehabilitation preoperatively due to eligible functional deficits. After initial evaluation by a physical therapist, all referred patients were triaged for further evaluation and treatment by physical therapy according to our physical therapy and physical medicine and rehabilitation treatment referral algorithm (Fig. 1). One patient had 4 PT visits preoperatively due to persistent deficits in strength; the remaining 34 (97%) patients attended 1 PT visit and then completed a self-directed independent home exercise prescription thereafter. Due to the COVID-19 pandemic and patient preference, 4/35 (11%) of these patients attended their PT visit via telehealth, with the remaining patients having in-person visits. Patients who attended PT lived significantly closer to our medical center than those who did not attend appointments (mean 147 miles vs. 103 miles, P = 0.02).
Regarding preoperative tobacco use, 14 (17%) patients identified as current smokers and 9 (64%) were referred to a smoking cessation clinic with 8/9 (89%) verified as attending the visit. Of those attending appointments, 6 patients stopped smoking by the date of surgery, and 2 patients reduced smoking frequency and volume with the assistance of quitting aids (Varenicline) before surgery. The mean travel distance among patients who attended the smoking cessation clinic was 102 miles.
Referral to onco-psychology, though operational, has had low utilization throughout enrollment, with only 3 patients (3/6%) screening positive for depression via the PHQ-2 screening instrument, and only 2 patients attending appointments. These patients received in-person consultations by a psychiatrist with specific training on the management of depression and anxiety in the setting of malignancy, and both patients were ultimately able to complete their treatment course, including RC, without treatment delay.
Complication data for this initial cohort of 67 patients who had undergone RC at the time of data analysis was also reviewed. Tables 2–4 summarize details and classification of all recorded complications within the first 90 days after surgery. The 30-day rate of postoperative complications was 56%, with the majority of these (58%) being Clavien-Dindo grade II or lower. In the year prior to implementation of cystectomy prehabilitation, at least 50% of all complications were Clavien-Dindo grade III or greater. The most prevalent complications in the 30-day time frame were infections in 18 patients (27%) and wound complications in 11 patients (16%). The 30- to 90-day rate of complications was 40%, with the vast majority (88%) being Clavien-Dindo Grade II or lower. The most frequent complications in this timeframe included infections in 15 patients (22.3%) and bowel-related complications in 6 patients (8.9%). Ninety-day postoperative mortality was 4.4%, with 1 death related to a fatal postoperative cardiac event and 2 related to acute respiratory failure. All deaths recorded occurred within 1 month of surgery, with 2 occurring in-hospital and 1 after discharge to a facility.
Table 2.
Post-Cystectomy complication data.
| 30-D Complication Rate | 56%a |
| Clavien-Dindo Grade < 3 | 22 (58) |
| Clavien-Dindo Grade ≥3 | 16 (42) |
| Wound | 11 (16) |
| Bowel | 10 (15) |
| Infection | 18 (27) |
| Cardiac | 3 (4.5) |
| Respiratory | 5 (7.5) |
| Anemia | 3 (4.5) |
| Other | 2 (3) |
| 30- to 90-D Complication Rate | 40%a |
| Clavien-Dindo Grade < 3 | 29 (88) |
| Clavien-Dindo Grade ≥3 | 4 (12) |
| Wound | 5 (7.5) |
| Bowel | 6 (9) |
| Infection | 15 (22.3) |
| Respiratory | 3 (3) |
| Anemia | 0 |
| Other | 4 (6) |
| 90-D Overall Mortality | 4.5%a |
Denominator is number of patients who have completed RC.Individual domain data are expressed as number, n and (%).
Table 4.
Summary and number of highest-grade complications, 30–90 days.
| Clavien-Dindo Grade | |||||
|---|---|---|---|---|---|
| Type of Complication | Grade I | Grade II | Grade III | Grade IV | Grade V |
| Wound | 4 | 1 | - | - | - |
| Bowel | 3 | 2 | 1 | - | - |
| Infection | 1 | 14 | - | - | - |
| Cardiac | - | - | - | - | - |
| Respiratory | - | 2 | 1 | - | - |
| Anemia | - | - | - | - | - |
| Other | - | 2 | 2 | - | - |
Our health system monitors case mix index adjusted resource length of stay (CMI-RLOS) -an operational efficiency measure that accounts for patient morbidity, complexity, resource utilization, and hospital length of stay- for all patients undergoing RC as part of a quality assurance program (Center for Medicare and Medicaid Services 2021). Case mix index, though initially designed for reimbursement, is considered a standard measure of hospital disease severity and accounts for the diagnosis-related group (DRG) weight of cases at an institution [33,34] CMI-RLOS in the 12 months before implementation of RC prehabilitation was 1.97 and had improved to 1.92 by August 2021, the mid-point of the first year of the prehabilitation program. The most recent CMI-RLOS had improved to 1.80 in the first quarter of 2022. For reference, CMI-RLOS for patients undergoing RC in the prior 2 fiscal years (FY2019, FY2020) were 2.09 and 2.06, respectively.
4. Discussion
We implemented a comprehensive prehabilitation program as the standard of care for patients undergoing RC at a high-volume bladder cancer referral center, and data suggest that this program is feasible with willing patient participation and institutional collaboration. There is growing evidence indicating the merits of prehabilitation before RC, with prior efforts primarily focusing on mono- and dual-therapy treatments. Previous studies have assessed the impact of short-term exercise regimens before RC and found improvements in postoperative mobilization and patient-reported quality of life measures [35,36]. Further studies have assessed additional preoperative interventions including nutritional and psychosocial counseling. Jensen et al. introduced physical exercise and nutritional supplementation before RC and found a significant improvement in postoperative functional status, as measured by a 6-minute walking test [36]. Furthermore, a randomized controlled trial conducted by Minnella and colleagues utilized a multimodal prehabilitation approach consisting of exercise therapy, nutrition education, and psychosocial counseling to assess postoperative functional recovery. These interventions were found to mitigate the postoperative functional decline in patients undergoing RC. [12] Our study expands upon this literature by targeting a multidisciplinary prehabilitation approach consisting of 5 domains with at least moderate evidence for efficacy. Furthermore, our program is promoting and establishing prehabilitation as a standard of care at our high-volume institution to assess if various domains are scalable within the framework of implementation science.
Prehabilitation programs have also been studied in various patient cohorts undergoing oncologic surgery. In a meta-analysis of 21 prehabilitation studies, Waterland et. al found that preoperative nutrition supplementation combined with exercise therapy reduced hospital length of stay and improved preoperative functional capacity in patients undergoing major abdominal cancer surgery [37]. As noted in our methodology, Briggs and colleagues performed a systematic review of prehabilitation exercise programs on outcomes of patients undergoing urologic cancer surgery at large and determined that though prehabilitation may improve HRQOL and cardiopulmonary fitness metrics, the effect on postoperative complications and surgical outcomes was less robust [27]. Ongoing multicenter randomized control trials within colorectal surgery will continue to elucidate the long-term outcomes related to prehabilitation [38]. Our study demonstrates that physical therapy for prehabilitation was both feasible and indicated in more than half of patients (52%) scheduled for RC. This was also feasible to be delivered in-person, over telehealth, and with community referral for patients limited by travel.
Interestingly, our results support the prior finding that the time around the diagnosis and treatment of bladder cancer is also a window of opportunity for smoking cessation. In our program, referral to a dedicated smoking cessation clinic for intense counseling and quitting aids resulted in >80% of active smokers in our cohort to either quit (6/9) or reduce smoking frequency (1/9). This further highlights the potential for risk-factor reduction and physiologic optimization before surgery in many patients undergoing RC. Though smoking frequency is declining, the multi-system effects of tobacco smoke continue to be an important modifiable patient factor.
Across multiple studies, there is no consensus on the optimal duration of prehabilitation [39]. While prior studies in colorectal cancer surgery have shown that 4 weeks is sufficient to improve physical function, studies within genitourinary cancer have used differing time frames for preoperative exercise and nutrition interventions [10,12,40]. Since many patients undergo NAC prior to surgery, patients with bladder cancer provide a unique opportunity for longer-term prehabilitation. Most of our patients required only 1 visit with physical therapy or physical medication, and then completed the remainder of therapy at home. Though data regarding the effects of NAC for bladder cancer on preoperative functional status are inconclusive, data from esophageal cancer indicates that cisplatin-based NAC leads to a decrease in preoperative muscle mass and strength [41]. If the effects of NAC are similar in patients with bladder cancer, prehabilitation could play a key role in maintaining preoperative functional status prior to major surgery. Data regarding timing of RC after NAC indicates the importance of timeliness and not delaying beyond 10–12 weeks to maintain safe oncologic outcomes [42,43]. All patients in our program had cystectomy performed within 10 weeks, indicating that even with a multi-faceted, multidisciplinary approach, timely surgery is not delayed.
Program costs, to the institution, payors, and most importantly the patient, must be considered when implementing a new prehabilitation program. Out-of-pocket costs to the patient vary widely by insurer and are therefore difficult to estimate for any individual patient. Out-of-pocket cost for physical therapy visits was typically less than $50. All patients attended a high-risk anesthesia preoperative visit for which they are charged no co-pay. Preoperative immuno-nutrition supplement therapy typically costs patients approximately $70. Costs of tobacco cessation therapy are highly variable depending on treatment and services needed. Due to the inherent complexity of bladder cancer management and the high rate of medical comorbidity in this patient population, many patients reached their out-of-pocket maximum prior to reaching the prehabilitation program and therefore receive many services at no additional out-of-pocket cost. Additional secondary costs including those related to travel, accommodation, caregivers, and time off work, are all important to consider for individual patients participating in a prehabilitation program and may hinder program success depending on the patient population.
There are several limitations to our current study. First, due to the recent implementation of the prehabilitation program, our dataset is smaller with only 82 enrolled patients. However, this program is now standard of care at our institution, allowing our dataset to grow rapidly as we continue to perform radical cystectomies for bladder cancer. Additionally, further investigation is necessary to assess the prehabilitation program’s impact on resource utilization, operative outcomes, complications, and long-term oncologic and survival outcomes. As previously mentioned, our group maintains a robust, prospective RC and ERAS dashboard dating back to 2017, allowing future comparison of outcomes as the prehabilitation program continues to mature. Our complication frequency during the first year of this program is consistent with previously reported large series in RC [1,2]. Nonetheless, the rate of 30-day complications decreased from the prior fiscal year before implementation of prehabilitation in terms of overall rate, at 56% at 30 days compared to 58% in FY 2020. Additionally, the overall grade of complications has shifted to a greater proportion of minor (Clavien-Dindo Grade II or lower) complications at 58% since implementation of our program, compared to 50% and 49% the prior 2 years. Though this may seem to be a subtle improvement, the shift to lower grade and less frequent complications has vast implications regarding resource utilization and costs surrounding RC. As noted above, our CMI-RLOS has significantly improved since the implementation of this program. Given no other major changes in RC perioperative care during this period, implementation of this program may be improving overall perioperative operational efficiency and LOS, even if complication rates remain similar. However, it is important to acknowledge the inherent limitation that a small overall small sample size could influence the variation in true case mix during the study period, and not a true difference in resource utilization and complications. Another potential confounder is the impact of the concurrent COVID-19 pandemic during the study period. Due to the overall climate of austerity during this period that included persistent bed shortages, patient access barriers, staffing issues, and global resource and supply limitations, there may be system influences outside of prehabilitation efforts that impacted both the case mix index and resource length of stay. These factors warrant further continued validation in the larger ongoing study population to account for normal year-to-year variability in case mix. Continued cost and protocol analyses are also underway to ensure optimization, generalizability, and scalability of prehabilitation practices across genitourinary cancer care. Finally, one of these domains -stoma education- is not technically prehabilitation as there is no inherent correction of a pre-existing physiologic or psychosocial abnormality. However, this up-front education provides substantial standardized and scalable anticipatory guidance to patients before surgery. The inherent goal of this intervention is to decrease postoperative complications related to adapting to life with a stoma, a major patient-identified quality of life issue in prior studies [19]. Future analysis could assess the impact of the timing of stoma education on patient-reported understanding of stoma troubleshooting.
5. Conclusions
Our experience demonstrates that implementation of a comprehensive prehabilitation program at a high-volume bladder cancer referral center is feasible and has a modest effect on resource consumption and complications. Additionally, establishing this program as the standard of care has reduced inpatient resource utilization and had a modest impact on complication frequency and grade. Keys to success include willing collaboration from consultants and allied healthcare providers, streamlined clinical workflows leveraging pre-defined electronic medical record order sets for multidisciplinary referral, and implementation of a select number of scalable, evidence-based domains. Long-term outcomes on the impact of our comprehensive prehabilitation program on perioperative complications and oncologic outcomes will further define the efficacy and future optimization of this program.
Table 3.
Summary and number of highest-grade complications, 30-days.
| Clavien-Dindo Grade | |||||
|---|---|---|---|---|---|
| Type of Complication | Grade I | Grade II | Grade III | Grade IV | Grade V |
| Wound | 2 | 2 | 2 | - | - |
| Bowel | 3 | 1 | 2 | 1 | - |
| Infection | 3 | 5 | 4 | - | - |
| Cardiac | 2 | - | - | - | 1 |
| Respiratory | - | 1 | 1 | 1 | 2 |
| Anemia | - | 2 | 1 | - | - |
| Other | 1 | - | 1 | - | - |
Acknowledgment
We wish to acknowledge the support of the leadership of the Vanderbilt-Ingram Cancer Center and the Dayani Rehabilitation Center in making this project feasible. We thank all patients dealing with the affliction of bladder cancer who took part in this study.
Footnotes
Declaration of Competing Interest
None.
References
- [1].Shabsigh A, Korets R, Vora KC, et al. Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol 2009;55(1):164–74. 10.1016/j.eururo.2008.07.031. [DOI] [PubMed] [Google Scholar]
- [2].Maibom SL, Joensen UN, Poulsen AM, et al. Short-term morbidity and mortality following radical cystectomy: a systematic review. BMJ Open 2021;11:e043266. 10.1136/bmjopen-2020-043266. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [3].Campbell JG, Smelser WW, Lee EK. Contemporary preoperative and intraoperative management of the radical cystectomy patient. Urol Clin North Am 2018;45(2):169–81. 10.1016/j.ucl.2017.12.003. [DOI] [PubMed] [Google Scholar]
- [4].Woldu SL, Sanli O, Clinton TN, Lotan Y. Validating the predictors of outcomes after radical cystectomy for bladder cancer. Cancer 2019;125(2):223–31. 10.1002/cncr.31799. [DOI] [PubMed] [Google Scholar]
- [5].Razdan S, Sljivich M, Pfail J, Wiklund PK, Sfakianos JP, Waingankar N. Predicting morbidity and mortality after radical cystectomy using risk calculators: a comprehensive review of the literature. Urol Oncol 2021;39(2):109–20. 10.1016/j.urolonc.2020.09.032. [DOI] [PubMed] [Google Scholar]
- [6].Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56(3):M146–56. 10.1093/gerona/56.3.m146. [DOI] [PubMed] [Google Scholar]
- [7].Pearl JA, Patil D, Filson CP, et al. Patient frailty and discharge disposition following radical cystectomy. Clin Genitourin Cancer 2017;15(4):e615–21. 10.1016/j.clgc.2016.12.013. [DOI] [PubMed] [Google Scholar]
- [8].Pozo C, Shariat SF, D’Andrea D, Fajkovic H, Abufaraj M. Enhanced recovery after radical cystectomy. Curr Opin Urol 2019;29(3):227–38. 10.1097/MOU.0000000000000594. [DOI] [PubMed] [Google Scholar]
- [9].Matulewicz RS, Brennan J, Pruthi RS, Kundu SD, Gonzalez CM, Meeks JJ. Radical cystectomy perioperative care redesign. Urology 2015;86(6):1076–86. 10.1016/j.urology.2015.09.001. [DOI] [PubMed] [Google Scholar]
- [10].Jensen BT, Petersen AK, Jensen JB, Laustsen S, Borre M. Efficacy of a multiprofessional rehabilitation programme in radical cystectomy pathways: a prospective randomized controlled trial. Scand J Urol 2015;49(2):133–41. 10.3109/21681805.2014.967810. [DOI] [PubMed] [Google Scholar]
- [11].Jensen BT, Lauridsen SV, Scheede-Bergdahl C. The potential of prehabilitation in radical cystectomy pathways: where are we now? Semin Oncol Nurs 2021;37(1):151107. 10.1016/j.soncn.2020.151107. [DOI] [PubMed] [Google Scholar]
- [12].Minnella EM, Awasthi R, Bousquet-Dion G, et al. Multimodal prehabilitation to enhance functional capacity following radical cystectomy: a randomized controlled rial. Eur Urol Focus 2021;7(1):132–8. 10.1016/J.EUF.2019.05.016. [DOI] [PubMed] [Google Scholar]
- [13].Chang SS, Bochner BH, Chou R, et al. Treatment of non-metastatic muscle-invasive bladder cancer: AUA/ASCO/ASTRO/SUO guideline [published correction appears in J Urol. 2017 Nov;198(5):1175]. J Urol 2017;198(3):552–9. 10.1016/j.juro.2017.04.086: Nov;198(5):1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [14].Souwer ETD, Bastiaannet E, de Bruijn S, et al. Comprehensive multi-disciplinary care program for elderly colorectal cancer patients: “from prehabilitation to independence”. Eur J Surg Oncol 2018;44(12):1894–900. 10.1016/j.ejso.2018.08.028. [DOI] [PubMed] [Google Scholar]
- [15].Rink M, Crivelli JJ, Shariat SF, Chun FK, Messing EM, Soloway MS. Smoking and bladder cancer: a systematic review of risk and outcomes. Eur Urol Focus 2015;1(1):17–27. 10.1016/j.euf.2014.11.001. [DOI] [PubMed] [Google Scholar]
- [16].Thomsen T, Villebro N, Møller AM. Interventions for preoperative smoking cessation. Cochrane Database Syst Rev 2014;2014(3):CD002294. 10.1002/14651858.CD002294.pub4:Published 2014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [17].Bassett JC, Gore JL, Chi AC, et al. Impact of a bladder cancer diagnosis on smoking behavior. J Clin Oncol 2012;30(15):1871–8. 10.1200/JCO.2011.36.6518. [DOI] [PubMed] [Google Scholar]
- [18].Bassett JC, Matulewicz RS, Kwan L, McCarthy WJ, Gore JL, Saigal CS. Prevalence and correlates of successful smoking cessation in bladder cancer survivors. Urology 2021;153:236–43. 10.1016/j.urology.2020.12.033. [DOI] [PubMed] [Google Scholar]
- [19].Zganjar A, Glavin K, Mann K, et al. Intensive preoperative ostomy education for the radical cystectomy patient [published online ahead of print, 2021 Jun 14]. Urol Oncol 2021;S1078–1439(21)00182–4. 10.1016/j.urolonc.2021.04.025. [DOI] [PubMed] [Google Scholar]
- [20].Gregg JR, Cookson MS, Phillips S, et al. Effect of preoperative nutritional deficiency on mortality after radical cystectomy for bladder cancer. J Urol 2011;185(1):90–6. 10.1016/j.juro.2010.09.021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [21].Robertson HL, Michel C, Bartl L, Hamilton-Reeves JM. Sarcopenia in urologic oncology: identification and strategies to improve patient outcomes [published online ahead of print, 2020 May 24]. Urol Oncol 2020;S1078–1439(20)30197–6. 10.1016/j.urolonc.2020.05.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [22].Ritch CR, Cookson MS, Clark PE, et al. Perioperative oral nutrition supplementation reduces prevalence of sarcopenia following radical cystectomy: results of a prospective randomized controlled trial. J Urol 2019;201(3):470–7. 10.1016/j.juro.2018.10.010. [DOI] [PubMed] [Google Scholar]
- [23].Xia L, Guzzo TJ. Preoperative anemia and low hemoglobin level are associated with worse clinical outcomes in patients with bladder cancer undergoing radical cystectomy: a meta-analysis. Clin Genitourin Cancer 2017;15(2):263–272.e4. 10.1016/j.clgc.2016.08.017. [DOI] [PubMed] [Google Scholar]
- [24].Ferguson M, Capra S, Bauer J, Banks M. Development of a valid and reliable malnutrition screening tool for adult acute hospital patients. Nutrition 1999;15(6):458–64. 10.1016/s0899-9007(99)00084-2. [DOI] [PubMed] [Google Scholar]
- [25].Hamilton-Reeves JM, Stanley A, Bechtel MD, et al. Perioperative Immunonutrition modulates inflammatory response after radical cystectomy: results of a pilot randomized controlled clinical trial. J Urol 2018;200(2):292–301. 10.1016/j.juro.2018.03.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [26].Valkenet K, van de Port IG, Dronkers JJ, de Vries WR, Lindeman E, Backx FJ. The effects of preoperative exercise therapy on postoperative outcome: a systematic review. Clin Rehabil 2011;25(2):99–111. 10.1177/0269215510380830. [DOI] [PubMed] [Google Scholar]
- [27].Briggs LG, Reitblat C, Bain PA, et al. Prehabilitation exercise before urologic cancer surgery: a systematic and interdisciplinary review. Eur Urol 2022;81(2):157–67. 10.1016/j.eur-uro.2021.05.015. [DOI] [PubMed] [Google Scholar]
- [28].Vartolomei L, Ferro M, Mirone V, Shariat SF, Vartolomei MD. Systematic review: depression and anxiety prevalence in bladder cancer patients. Bladder Cancer 2018;4(3):319–26. Published 2018. 10.3233/BLC-180181. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [29].Vartolomei L, Vartolomei MD, Shariat SF. Bladder cancer: depression, anxiety, and suicidality among the highest-risk oncology patients. Eur Urol Focus 2020;6(6):1158–61. 10.1016/j.euf.2019.10.008. [DOI] [PubMed] [Google Scholar]
- [30].Kroenke K, Spitzer RL, Williams JB. The patient health questionnaire-2: validity of a two-item depression screener. Medical Care 2003;41:1284–92. [DOI] [PubMed] [Google Scholar]
- [31].Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)−a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42(2):377–81. 10.1016/j.jbi.2008.08.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [32].Harris PA, Taylor R, Minor BL, et al. The REDCap consortium: building an international community of software platform partners. J Biomed Inform 2019;95:103208. 10.1016/j.jbi.2019.103208. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [33].Center for Medicare and Medicaid Services. Case Mix Index. Online. https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/AcuteInpatientPPS/Acute-Inpatient-Files-for-Download-Items/CMS022630. Accessed 6/6/2022.
- [34].Mendez CM, Harrington DW, Christenson P, Spellberg B. Impact of hospital variables on case mix index as a marker of disease severity. Popul Health Manag 2014;17(1):28–34. 10.1089/pop.2013.0002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [35].Kaye DR, Schafer C, Thelen-Perry S, et al. The feasibility and impact of a presurgical exercise intervention program (Prehabilitation) for patients undergoing cystectomy for bladder cancer. Urology 2020;145:106–12. 10.1016/J.UROLOGY.2020.05.104. [DOI] [PubMed] [Google Scholar]
- [36].Jensen BT, Jensen J, Love-Betinger N, Bowker M, Betinger C, Dalbagni G. Implementing a multimodal prehabilitation program prior to radical cystectomy in a comprehensive cancer center: a pilot study to assess feasibility and outcomes. Urol Nurs 2019;39(6):303–13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [37].Waterland JL, McCourt O, Edbrooke L, et al. Efficacy of prehabilitation including exercise on postoperative outcomes following abdominal cancer surgery: a systematic review and meta-analysis. Front Surg 2021;8:55. 10.3389/FSURG.2021.628848/BIB-TEX. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [38].Van Rooijen S, Carli F, Dalton S, et al. Multimodal prehabilitation in colorectal cancer patients to improve functional capacity and reduce postoperative complications: the first international randomized controlled trial for multimodal prehabilitation. BMC Cancer 2019;19(1):1–11. 10.1186/S12885-018-5232. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [39].Gillis C, Buhler K, Bresee L, et al. Effects of nutritional prehabilitation, with and without exercise, on outcomes of patients who undergo colorectal surgery: a systematic review and meta-analysis. Gastroenterology 2018;155(2):391–410.e4. 10.1053/J.GASTRO.2018.05.012. [DOI] [PubMed] [Google Scholar]
- [40].Chen BP, Awasthi R, Sweet SN, et al. Four-week prehabilitation program is sufficient to modify exercise behaviors and improve preoperative functional walking capacity in patients with colorectal cancer. Support Care Cancer 2017;25(1):33–40. 10.1007/S00520-016-3379-8/FIGURES/3. [DOI] [PubMed] [Google Scholar]
- [41].Guinan EM, Doyle SL, Bennett AE, et al. Sarcopenia during neoadjuvant therapy for oesophageal cancer: characterizing the impact on muscle strength and physical performance. Support Care Cancer 2018;26(5):1569–76. 10.1007/S00520-017-3993-0. [DOI] [PubMed] [Google Scholar]
- [42].Mmeje CO, Benson CR, Nogueras-González GM, et al. Determining the optimal time for radical cystectomy after neoadjuvant chemotherapy. BJU Int 2018;122(1):89–98. 10.1111/bju.14211. [DOI] [PubMed] [Google Scholar]
- [43].Boeri L, Soligo M, Frank I, et al. Delaying radical cystectomy after neoadjuvant chemotherapy for muscle-invasive bladder cancer is associated with adverse survival outcomes. Eur Urol Oncol 2019;2(4):390–6. 10.1016/j.euo.2018.09.004. [DOI] [PubMed] [Google Scholar]