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Economic Burden Associated with Hospitalization for Radiation Cystitis: Results from a Statewide Inpatient Database
urologypracticejournal.com
Economic Burden Associated with Hospitalization for Radiation Cystitis: Results from a Statewide Inpatient Database Jonathan E. Kiechle, Simon P. Kim,* James B. Yu, Matthew J. Maurice, Shan Dong, Edward E. Cherullo and Robert Abouassalyy From the University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Urology Institute, Cleveland, Ohio (JEK, SPK, MJM, SD, EEC, RA), and Department of Therapeutic Radiology, Yale University, New Haven, Connecticut (JBY)
Abstract
Abbreviations and Acronyms
Introduction: Radiation cystitis is associated with a significant burden to patients and the health care system. However, the regional burden of treatment and its associated costs remains poorly described. We assessed the health care costs and need for intervention among patients admitted to the hospital with radiation cystitis.
LOS = length of stay RC = radiation induced hemorrhagic cystitis
Methods: Using data from the Ohio Hospital Association we identified patients admitted with a diagnosis of radiation cystitis from 2009 to 2013. The primary outcome was the adjusted inpatient cost (adjusted to 2013 U.S. dollars) associated with in-hospital treatment of radiation cystitis. Secondary outcomes included percentage of patients requiring endoscopic urological procedures, blood transfusions and nephrostomy tubes. We used a generalized estimating equation model to determine in-hospital costs. Multivariate logistic regression analyses were used to determine factors associated with requiring an invasive procedure. Results: We identified 1,111 patients admitted to Ohio hospitals between 2009 and 2013 with a diagnosis of radiation cystitis. Mean patient age (SD) was 73.9 (12.5) years. Median length of stay was 4 days (IQR 3e8). The adjusted median cost of hospitalization per admission in 2013 for these patients was $7,151 (IQR $4,251e$16,569). Overall 28.9% of patients required blood transfusions, 34.4% required endourological procedures and 3.4% required nephrostomy tubes. The odds of undergoing an invasive procedure were associated with increasing length of stay, need for blood transfusion and male gender. Conclusions: This study is the first population based study to our knowledge to assess the treatment burden and health care costs from radiation cystitis. A diagnosis of radiation cystitis carries with it a significant economic and treatment associated burden. Key Words: cystitis; radiation injuries; economics, medical
Submitted for publication August 18, 2015. No direct or indirect commercial incentive associated with publishing this article. The corresponding author certifies that, when applicable, a statement(s) has been included in the manuscript documenting institutional review board, ethics committee or ethical review board study approval; principles of Helsinki Declaration were followed in lieu of formal ethics committee approval; institutional animal care and use committee approval; all human subjects provided 2352-0779/16/36-437/0 UROLOGY PRACTICE Ó 2016 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
written informed consent with guarantees of confidentiality; IRB approved protocol number; animal approved project number. * Supported by the Conquer Cancer FoundationÒ of the American Society of Clinical Oncology. y Correspondence: University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Urology Institute, 11100 Euclid Ave., Lakeside Building, Suite 4554, Mailstop LKS 5046, Cleveland, Ohio 44106 (FAX: 216-844-1900; e-mail address: [email protected]).
RESEARCH, INC.
http://dx.doi.org/10.1016/j.urpr.2015.10.007 Vol. 3, 437-442, November 2016 Published by Elsevier
438
Economic Burden of Radiation Cystitis
Clinical practice guidelines recommend external beam radiation or brachytherapy for the primary or adjuvant treatment of various abdominopelvic malignancies, including prostate, cervical, uterine and colon cancers.1e4 Radiation induced hemorrhagic cystitis is a known complication of pelvic radiation that can first present years after initial radiation therapy.5,6 The estimated incidence of RC is 5% to 10% after pelvic radiation.6 Symptoms of RC range from microscopic hematuria to recurrent, recalcitrant gross hematuria with clots.7 Due to the wide range of symptomatology and the failure of any conservative treatment to be 100% effective, a wide range of treatment options has been proposed, including oral or intravenous medications, intravesical irrigations, hyperbaric oxygen therapy, internal iliac embolization, endoscopic clot evacuation and fulguration and, in the most severe cases, cystectomy with urinary diversion.8,9 While many studies have been published evaluating novel treatment methods for RC, no population based studies have been published examining the large scale economic and treatment associated burden that accompanies a diagnosis of RC.7,10 In the modern health care environment where economics and reimbursement have an increasingly important role in health care policy, it is imperative to have information about the economic impact that specific disease states have on the health care system. We believe that the inpatient treatment of radiation cystitis was likely associated with substantial economic cost and procedural burden to the health care system. To determine this burden we identified patients with radiation cystitis in Ohio and assessed the economic and procedural burden associated with inpatient treatment. Materials and Methods
code 595.82 was included in the first 5 diagnosis codes on admission. We only included patients with the diagnosis of RC among the first 5 diagnosis codes to try to limit the number of patients included in the cohort with a history of RC but without current symptoms. We chose to include patients with RC up to diagnosis code 5 based on ICD-9 coding standards that allow symptom diagnosis codes (acute blood loss anemia) to be listed above the underlying problem (gross hematuria and radiation cystitis).11 Overall RC was the primary diagnosis for 59.1% of the cohort and a secondary diagnosis for 14.8%. Pediatric patients (younger than 18 years) were excluded from the cohort. Patients were also excluded if they had a secondary diagnosis of bladder cancer (133), leaving a total of 1,111 patients in the cohort. These 133 patients were excluded to limit the confounding from bladder cancer associated hematuria and blood loss anemia. Patients were evaluated by diagnosis or history of various pelvic malignancies, including prostate cancer, ovarian cancer, uterine cancer, cervical cancer and colon cancer. These diagnoses were determined using appropriate ICD-9-CM diagnosis codes. Cases were also stratified by the need for blood transfusion or invasive procedures including cystoscopy, cystoscopy with biopsy, cystoscopy with fulguration and percutaneous nephrostomy tube placement. These procedures were also determined using appropriate ICD-9-CM codes. Further information regarding the ICD-9-CM codes used for analysis can be found in the supplementary Appendix (http://urologypracticejournal.com/). Adjusted in-hospital costs were determined using total hospital charges. Charges from each year were standardized to 2013 dollars using the Consumer Price Index inflation calculator.12 Costs were then calculated from charges using the fiscal year 2013 average operating cost-to-charge ratio for urban acute care hospitals in Ohio.13
Data Source
We used the Ohio Hospital Association inpatient survey to identify patients admitted to hospitals in Ohio with a diagnosis of radiation cystitis. The Ohio Hospital Association inpatient survey contains data from 238 participating hospitals, including community, county and academic institutions. Patient information in the database includes gender, age, insurance information, ICD-9 diagnosis and procedure codes, hospital charges, admission and discharge dates, and geographic information.
Covariates and Outcomes
Covariates used in this study included gender, age at admission, diagnosis of pelvic malignancy, Elixhauser comorbidity index, insurance status, year of admission, LOS and need for blood transfusion or invasive procedures.14 The primary outcome was the median adjusted in-hospital cost associated with admission for patients with RC. Secondary outcomes included the number of patients requiring endourological procedures, blood transfusions and nephrostomy tube placement.
Study Population
We identified 1,244 patients older than 18 years admitted to participating Ohio hospitals with a diagnosis of RC from 2009 to 2013. Patients were identified as having RC if ICD-9
Statistical Analysis
Multivariable logistic regression analyses were performed to determine if covariates influenced the likelihood of
439
Economic Burden of Radiation Cystitis
Results
We identified 1,111 patients with a mean age of 73.9 years (12.5) admitted to participating Ohio hospitals with a diagnosis of radiation cystitis from 2009 to 2013 (table 1). Median LOS was 4 days (IQR 3e8, range 1 to 56) and median cost of hospitalization in 2013 was $7,151 Table 1. Patient characteristics No. (%) Age: 18e49 50e59 60e69 70e79 80þ Gender: M F Insurance: Private Medicaid Medicare Self-pay/unknown/other Elixhauser comorbidity: 0 1 2 3 4 or Greater History of selected pelvic malignancy: Colorectal Ca Prostate Ca Uterine Ca Cervical Ca Not reported/unknown Yr: 2009 2010 2011 2012 2013 Treatment required: Endoscopic procedure Nephrostomy tube Blood transfusion
56 (5.0) 84 (7.6) 200 (18.0) 351 (31.6) 420 (37.8) 799 (71.9) 312 (28.1) 136 (12.2) 60 (5.4) 879 (79.1) 36 (3.2) 85 (7.7) 200 (18.0) 259 (23.3) 242 (21.8) 325 (29.3) 75 (6.6) 520 (46.8) 41 (3.7) 109 (9.8) 366 (32.9) 290 258 277 149 137
(26.1) (23.3) (24.9) (13.4) (12.3)
382 (34.4) 38 (3.4) 321 (28.9)
(IQR $4,251e$16,569; see figure). In 2013 the estimated inpatient cost of treating patients with radiation cystitis in Ohio was $979,687. Using a general estimating equation model, increasing LOS and undergoing an endoscopic procedure or percutaneous nephrostomy were associated with an increased in-hospital cost. Mean hospitalization cost for patients undergoing an inpatient endoscopic procedure was $11,100 (IQR $9,948e$12,254) and mean cost for patients requiring percutaneous nephrostomy tube placement was $16,644 (IQR $12,935e$20,354). There was no association between cost and transfusion status, age, gender, insurance status, year of treatment or Elixhauser comorbidity index (table 2). We also found that 34.4% of patients admitted to the hospital underwent an endourological procedure during hospitalization, 28.9% received a blood a transfusion and 3.4% required nephrostomy tube placement. On multivariate analysis undergoing an invasive procedure (endourological or nephrostomy tube) was associated with increasing LOS, male gender (OR 1.59, 95% CI 1.02e2.47) and receiving a blood transfusion during hospitalization (OR 1.67, 95% CI 1.26e2.21, table 3). There was no association between undergoing an invasive procedure and age, Elixhauser comorbidity score or insurance status.
Discussion
In this analysis of a statewide inpatient hospital database we assessed the economic and treatment associated burden associated with a diagnosis of RC when admitted to the hospital. Our study clearly demonstrates that the inpatient care of patients with a diagnosis of RC leads to significant economic costs. These costs are comparable to the inpatient costs associated with the treatment of neutropenic fever, another cancer related treatment complication. Dulisse et al reported a mean inpatient treatment cost of $18,880 and a Adjusted median In-patient hospital costs ($)
undergoing blood transfusion or invasive procedures when admitted with RC. A generalized estimating equation model was used to determine median adjusted in-hospital costs based on covariates associated with inpatient admission for RC. The generalized estimating equation is a generalized linear model that determines the correlation between independent variables (ie predictors) and a continuous dependent variable (ie cost), and also allows for determination of mean values for this variable.15 StataMPÔ version 11.2 was used to perform all statistical analyses and a 2-sided p <0.05 was used to determine statistical significance.
8000 7800 7600 7400 7200 7000 6800 6600 6400 6200 6000
Adjusted median InpaƟent hospital costs ($)
2009
2010
2011
2012
2013
6692
7019
7370
6880
7151
Figure. Trends in median adjusted in-hospital costs (2013 dollars) for inpatient treatment of patients admitted with RC.
440
Economic Burden of Radiation Cystitis
Table 2. Multivariate generalized estimating equation model of median cost associated with inpatient admission with RC Covariate (reference) Yr (2009): 2010 2011 2012 2013 Gender (M): F LOS (0e2 days): 3e4 days 5e7 days 8 or More days Elixhauser comorbidity index (0): 1 2 3 4 or Greater Insurance (private): Medicaid Medicare Other/unknown Endoscopic procedure (none): Performed Nephrostomy tube (none): Performed Blood transfusion (none): Performed
Coefficient (95% CI) 0.006 0.079 0.122 0.106
0.104) 0.187) 0.255) 0.239)
0.93 0.15 0.07 0.12
0.009 (0.122, 0.140)
0.89
0.436 0.867 1.68 0.126 0.140 0.104 0.128
(0.114, (0.02, (0.010, (0.02,
p Value
(0.327, 0.544) (0.752, 0.982) (1.56, 1.80) (0.040, (0.021, (0.061, (0.034,
<0.001 <0.001 <0.001
0.293) 0.302) 0.270) 0.290)
0.14 0.09 0.22 0.12
0.069 (0.284, 0.146) 0.020 (0.166, 0.127) 0.051 (0.295, 0.192)
0.53 0.79 0.68
0.165
(0.083, 0.247)
<0.001
0.549
(0.334, 0.765)
<0.001
0.029 (0.064, 0.122)
0.55
mean LOS of 8.6 days in a retrospective cohort of 16,273 patients hospitalized with neutropenic fever.16 Similarly, Hendricks et al reported a mean hospitalization cost of $10,143 in their cohort of 57 inpatient treatment episodes for neutropenic fever.17 Table 3. Multivariable logistic regression of undergoing an invasive procedure when hospitalized with RC Covariate (referent) LOS (0e2 days): 3e4 days 5e7 days 8 or More days Transfusion status (no): Yes Insurance (private): Medicaid Medicare Other Elixhauser comorbidity score (0): 1 2 3 4 or Greater Age (60e69): 18e49 50e59 70e79 80 or Greater Gender (F): M
OR (95% CI)
p Value
1.45 (0.99e2.12) 1.94 (1.32e2.86) 2.29 (1.55e3.40)
0.06 0.001 <0.001
1.67 (1.26e2.21)
<0.001
1.01 (0.49e2.07) 1.23 (0.77e1.98) 1.46 (0.66e3.20)
0.98 0.39 0.35
1.08 0.88 0.91 0.99
(0.62e1.89) (0.51e1.51) (0.52e1.57) (0.58e1.69)
0.78 0.63 0.73 0.97
0.59 0.79 0.83 0.71
(0.28e1.27) (0.44e1.45) (0.55e1.24) (0.48e1.07)
0.18 0.45 0.36 0.10
1.59 (1.02e2.47)
0.04
In addition, RC has a known rehospitalization rate of approximately 33% occurring at a median of 3.5 months after discharge.5 Developing systems to correlate hospital readmission rates with Medicare reimbursement remains a key component of the Affordable Care Act.18 Given the significant cost of treatment for patients with RC and the known readmission rate, it is important that physicians and key stakeholders continue to work with legislators and health policy decision makers to ensure that hospitals and physicians are not penalized for providing necessary care to patients with a condition that can require chronic rehospitalization and expensive long-term care. Similarly, in the modern health care environment the costs of managing cancer related treatment complications must be considered when evaluating the cost-effectiveness of cancer treatment modalities. We also found that in-hospital treatment of RC is associated with a significant risk of undergoing an invasive procedure during hospitalization. A third of the patients in our cohort required an invasive procedure during their inpatient stay. Furthermore, on multivariate analysis undergoing an invasive procedure was associated with a longer LOS and requiring a blood transfusion during hospitalization. Thus, patients needing invasive procedures most likely have more severe symptoms from RC. Kaplan and Wolf reported a mortality rate of 9.1% from complications of hemorrhagic cystitis (cyclophosphamide and radiation induced) in patients who required a cystoscopic procedure during hospitalization.19 Given the significant mortality rate associated with RC necessitating surgical intervention, the continued development of novel treatment modalities for RC is necessary. New treatment modalities may also help decrease the overall cost associated with the treatment of RC, as a recently published study showed that treatment with hyperbaric oxygen therapy helped decrease subsequent expenditures for RC associated treatment.20 In addition, we found that more than 25% of patients admitted with RC required blood transfusions during hospitalization. While we were not able to elucidate the underlying cause necessitating transfusion from the data set, other studies have reported transfusion rates of 14% to 25% for patients undergoing treatment for RC.21,22 Similarly, in their prospective study of hyperbaric oxygen treatment for RC Bevers et al classified 18 of 40 patients in their cohort as having severe hematuria (requiring more than 6 units of packed red blood cells during the previous 3 months).23 Therefore, while we were not able to determine the underlying reason for needing transfusion in our cohort, we believe that our data fall within historic parameters for patients with RC.
Economic Burden of Radiation Cystitis
Our study had several limitations. It was completed using a statewide inpatient database and, therefore, was retrospective. We were also limited in the analysis of patient factors affecting cost and procedure use to those factors that are collected in the database. Similarly, we were not able to accurately determine the causative diagnosis requiring pelvic radiation for all patients in the database due to the nature of the data set used in the analysis. Our cost analysis was somewhat limited by our database not containing hospital specific cost-to-charge ratios.24 However, Medicare insured 79% of patients in our cohort and, therefore, we believe the statewide Medicare cost-to-charge ratio was a reasonable method of determining cost from hospital charges. Due to the inpatient only nature of the database we were not able to determine the global cost of care for patients with RC since we could not account for outpatient costs, including the costs of outpatient treatment like hyperbaric oxygen therapy. Similarly, we were not able to include hidden economic costs in our analysis such as lost work hours. We were also unable to adjust for hospital characteristics such as academic or community settings that may have some impact on total cost or procedure use in this cohort. Finally, we were not able to adjust for physician characteristics that could also affect treatment decisions. In this study we present the first statewide, population based analysis of the economic and treatment burden associated with the inpatient treatment of RC. Further research will be required to identify treatments that can limit this significant burden for patients with RC. However, it is possible that increasing awareness of the substantial economic and procedural costs associated with radiation cystitis could lead to improved early diagnosis in the primary care setting, allowing for earlier referral to urologists for specialist management of these complex cases and perhaps limiting the number requiring inpatient admission.
Conclusions
Radiation induced hemorrhagic cystitis is a serious complication of pelvic radiation. Patients admitted to the hospital with a diagnosis of radiation cystitis are at substantial risk for requiring invasive procedures during the course of their admission. The diagnosis is also associated with significant inpatient economic costs. It is vital that physicians, patients and key stakeholders consider these economic and treatment related costs when recommending pelvic radiation for the treatment of malignancy and in further determination of health care policy as it relates to the treatment of chronic conditions.
441
References 1. Mohler J, Bahnson RR, Boston B et al: NCCN clinical practice guidelines in oncology: prostate cancer. J Natl Compr Canc Netw 2010; 8: 162. 2. Koh WJ, Greer BE, Abu-Rustum NR et al: Cervical cancer, version 2.2015. J Natl Compr Canc Netw 2015; 13: 395. 3. Koh WJ, Greer BE, Abu-Rustum NR et al: Uterine neoplasms, version 1.2014. J Natl Compr Canc Netw 2014; 12: 248. 4. Benson AB 3rd, Venook AP, Bekaii-Saab T et al: Colon cancer, version 3.2014. J Natl Compr Canc Netw 2014; 12: 1028. 5. Levenback C, Eifel PJ, Burke TW et al: Hemorrhagic cystitis following radiotherapy for stage Ib cancer of the cervix. Gynecol Oncol 1994; 55: 206. 6. Denton AS, Clarke NW and Maher EJ: Non-surgical interventions for late radiation cystitis in patients who have received radical radiotherapy to the pelvis. Cochrane Database Syst Rev 2002; 3: CD001773. 7. Payne H, Adamson A, Bahl A et al: Chemical- and radiationinduced haemorrhagic cystitis: current treatments and challenges. BJU Int 2013; 112: 885. 8. Crew JP, Jephcott CR and Reynard JM: Radiation-induced haemorrhagic cystitis. Eur Urol 2001; 40: 111. 9. Linder BJ, Tarrell RF and Boorjian SA: Cystectomy for refractory hemorrhagic cystitis: contemporary etiology, presentation and outcomes. J Urol 2014; 192: 1687. 10. Talab SS, McDougal WS, Wu CL et al: Mucosa-sparing, KTP laser coagulation of submucosal telangiectatic vessels in patients with radiation-induced cystitis: a novel approach. Urology 2014; 84: 478. 11. Kennedy JS: Coding Clinic Update: Cancer staging forms, pressure ulcer guidance, and more in second quarter 2010. Clinical Documentation Improvement Journal 2010. 12. Bureau of Labor Statistics: CPI Inflation Calculator. Washington, D.C.: United States Department of Labor 2015. 13. Centers for Medicare & Medicaid Services: Files for FY 2013 Final Rule and Correction Notice. Baltimore, Maryland: Centers for Medicare & Medicaid Services 2015. 14. Elixhauser A, Steiner C, Harris DR et al: Comorbidity measures for use with administrative data. Med Care 1998; 36: 8. 15. Hanley JA, Negassa A, Edwardes MD et al: Statistical analysis of correlated data using generalized estimating equations: an orientation. Am J Epidemiol 2003; 157: 364. 16. Dulisse B, Li X, Gayle JA et al: A retrospective study of the clinical and economic burden during hospitalizations among cancer patients with febrile neutropenia. J Med Econ 2013; 16: 720. 17. Hendricks AM, Loggers ET and Talcott JA: Costs of home versus inpatient treatment for fever and neutropenia: analysis of a multicenter randomized trial. J Clin Oncol 2011; 29: 3984. 18. Centers for Medicare & Medicaid Services: Readmissions Reduction Program. Baltimore, Maryland: Centers for Medicare & Medicare Services 2015.
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Economic Burden of Radiation Cystitis
19. Kaplan JR and Wolf JS Jr: Efficacy and survival associated with cystoscopy and clot evacuation for radiation or cyclophosphamide induced hemorrhagic cystitis. J Urol 2009; 181: 641. 20. Smart D and Wallington M: A cost-analysis case study of radiation cystitis treatment including hyperbaric oxygen therapy. Diving Hyperb Med 2012; 42: 92. 21. Veerasarn V, Khorprasert C, Lorvidhaya V et al: Reduced recurrence of late hemorrhagic radiation cystitis by WF10 therapy in cervical cancer patients: a multicenter, randomized, two-arm, open-label trial. Radiother Oncol 2004; 73: 179.
22. Veerasarn V, Boonnuch W and Kakanaporn C: A phase II study to evaluate WF10 in patients with late hemorrhagic radiation cystitis and proctitis. Gynecol Oncol 2006; 100: 179. 23. Bevers RF, Bakker DJ and Kurth KH: Hyperbaric oxygen treatment for haemorrhagic radiation cystitis. Lancet 1995; 346: 803. 24. Healthcare Cost and Utilization Project: Cost-to-Charge Ratio Files. Rockville, Maryland: Agency for Healthcare Research and Quality 2015.
Editorial Commentary
Accurate health care cost data are as elusive as they are critical to payment and delivery system reform. As value based purchasing supplants fee-for-service, the costs of therapies and their complications will be juxtaposed to measures of quality in an attempt to quantify value. Accurate cost data will also inform the calculation of fair price points for treatment bundles and episodes of care. Hospital charge masters obfuscate the true costs of health care goods and services. To estimate the cost of inpatient treatment of radiation cystitis, the authors use an average cost-to-charge ratio for urban acute care hospitals in Ohio, an unsatisfying estimation. Defining cost with greater accuracy is essential going forward. There is a growing body of literature using time driven, activity based costing, a more accurate, if labor intensive, method of defining the true cost of health care services.1,2 With the converging forces of public demand for price and quality transparency, and increasing patient cost sharing through higher copays and deductibles, the ability to ascertain accurate costs will improve and value will be increasingly patient defined. Future economic analyses of radiation cystitis therapy should consider 1) the impact of hyperbaric oxygen
therapy on the need for hospital admission, 2) the impact of intravesical therapy on LOS and the need for transfusion or procedural therapy, and 3) the impact of these interventions on the all cause 30-day readmission rate, which the Centers for Medicare & Medicaid Services has deemed a reliable and sufficiently granular quality indicator that it has been using it to reduce provider payments since 2012. Mark T. Edney Peninsula Urology Associates Salisbury, Maryland
References 1. Kaplan AL, Agarwal N, Setlur NP et al: Measuring the cost of care in benign prostatic hyperplasia using time-driven activity-based costing (TDABC). Healthc (Amst) 2015; 3: 43. 2. McLaughlin N, Burke MA, Setlur NP et al: Time-driven activity-based costing: a driver for provider engagement in costing activities and redesign initiatives. Neurosurg Focus 2014; 37: E3.
Economic Burden Associated with Hospitalization for Radiation Cystitis: Results from a Statewide Inpatient Database Jonathan E. Kiechle, Simon P. Kim,* James B. Yu, Matthew J. Maurice, Shan Dong, Edward E. Cherullo and Robert Abouassalyy From the University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Urology Institute, Cleveland, Ohio (JEK, SPK, MJM, SD, EEC, RA), and Department of Therapeutic Radiology, Yale University, New Haven, Connecticut (JBY)
Abstract
Abbreviations and Acronyms
Introduction: Radiation cystitis is associated with a significant burden to patients and the health care system. However, the regional burden of treatment and its associated costs remains poorly described. We assessed the health care costs and need for intervention among patients admitted to the hospital with radiation cystitis.
LOS = length of stay RC = radiation induced hemorrhagic cystitis
Methods: Using data from the Ohio Hospital Association we identified patients admitted with a diagnosis of radiation cystitis from 2009 to 2013. The primary outcome was the adjusted inpatient cost (adjusted to 2013 U.S. dollars) associated with in-hospital treatment of radiation cystitis. Secondary outcomes included percentage of patients requiring endoscopic urological procedures, blood transfusions and nephrostomy tubes. We used a generalized estimating equation model to determine in-hospital costs. Multivariate logistic regression analyses were used to determine factors associated with requiring an invasive procedure. Results: We identified 1,111 patients admitted to Ohio hospitals between 2009 and 2013 with a diagnosis of radiation cystitis. Mean patient age (SD) was 73.9 (12.5) years. Median length of stay was 4 days (IQR 3e8). The adjusted median cost of hospitalization per admission in 2013 for these patients was $7,151 (IQR $4,251e$16,569). Overall 28.9% of patients required blood transfusions, 34.4% required endourological procedures and 3.4% required nephrostomy tubes. The odds of undergoing an invasive procedure were associated with increasing length of stay, need for blood transfusion and male gender. Conclusions: This study is the first population based study to our knowledge to assess the treatment burden and health care costs from radiation cystitis. A diagnosis of radiation cystitis carries with it a significant economic and treatment associated burden. Key Words: cystitis; radiation injuries; economics, medical
Submitted for publication August 18, 2015. No direct or indirect commercial incentive associated with publishing this article. The corresponding author certifies that, when applicable, a statement(s) has been included in the manuscript documenting institutional review board, ethics committee or ethical review board study approval; principles of Helsinki Declaration were followed in lieu of formal ethics committee approval; institutional animal care and use committee approval; all human subjects provided 2352-0779/16/36-437/0 UROLOGY PRACTICE Ó 2016 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
written informed consent with guarantees of confidentiality; IRB approved protocol number; animal approved project number. * Supported by the Conquer Cancer FoundationÒ of the American Society of Clinical Oncology. y Correspondence: University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Urology Institute, 11100 Euclid Ave., Lakeside Building, Suite 4554, Mailstop LKS 5046, Cleveland, Ohio 44106 (FAX: 216-844-1900; e-mail address: [email protected]).
RESEARCH, INC.
http://dx.doi.org/10.1016/j.urpr.2015.10.007 Vol. 3, 437-442, November 2016 Published by Elsevier
438
Economic Burden of Radiation Cystitis
Clinical practice guidelines recommend external beam radiation or brachytherapy for the primary or adjuvant treatment of various abdominopelvic malignancies, including prostate, cervical, uterine and colon cancers.1e4 Radiation induced hemorrhagic cystitis is a known complication of pelvic radiation that can first present years after initial radiation therapy.5,6 The estimated incidence of RC is 5% to 10% after pelvic radiation.6 Symptoms of RC range from microscopic hematuria to recurrent, recalcitrant gross hematuria with clots.7 Due to the wide range of symptomatology and the failure of any conservative treatment to be 100% effective, a wide range of treatment options has been proposed, including oral or intravenous medications, intravesical irrigations, hyperbaric oxygen therapy, internal iliac embolization, endoscopic clot evacuation and fulguration and, in the most severe cases, cystectomy with urinary diversion.8,9 While many studies have been published evaluating novel treatment methods for RC, no population based studies have been published examining the large scale economic and treatment associated burden that accompanies a diagnosis of RC.7,10 In the modern health care environment where economics and reimbursement have an increasingly important role in health care policy, it is imperative to have information about the economic impact that specific disease states have on the health care system. We believe that the inpatient treatment of radiation cystitis was likely associated with substantial economic cost and procedural burden to the health care system. To determine this burden we identified patients with radiation cystitis in Ohio and assessed the economic and procedural burden associated with inpatient treatment. Materials and Methods
code 595.82 was included in the first 5 diagnosis codes on admission. We only included patients with the diagnosis of RC among the first 5 diagnosis codes to try to limit the number of patients included in the cohort with a history of RC but without current symptoms. We chose to include patients with RC up to diagnosis code 5 based on ICD-9 coding standards that allow symptom diagnosis codes (acute blood loss anemia) to be listed above the underlying problem (gross hematuria and radiation cystitis).11 Overall RC was the primary diagnosis for 59.1% of the cohort and a secondary diagnosis for 14.8%. Pediatric patients (younger than 18 years) were excluded from the cohort. Patients were also excluded if they had a secondary diagnosis of bladder cancer (133), leaving a total of 1,111 patients in the cohort. These 133 patients were excluded to limit the confounding from bladder cancer associated hematuria and blood loss anemia. Patients were evaluated by diagnosis or history of various pelvic malignancies, including prostate cancer, ovarian cancer, uterine cancer, cervical cancer and colon cancer. These diagnoses were determined using appropriate ICD-9-CM diagnosis codes. Cases were also stratified by the need for blood transfusion or invasive procedures including cystoscopy, cystoscopy with biopsy, cystoscopy with fulguration and percutaneous nephrostomy tube placement. These procedures were also determined using appropriate ICD-9-CM codes. Further information regarding the ICD-9-CM codes used for analysis can be found in the supplementary Appendix (http://urologypracticejournal.com/). Adjusted in-hospital costs were determined using total hospital charges. Charges from each year were standardized to 2013 dollars using the Consumer Price Index inflation calculator.12 Costs were then calculated from charges using the fiscal year 2013 average operating cost-to-charge ratio for urban acute care hospitals in Ohio.13
Data Source
We used the Ohio Hospital Association inpatient survey to identify patients admitted to hospitals in Ohio with a diagnosis of radiation cystitis. The Ohio Hospital Association inpatient survey contains data from 238 participating hospitals, including community, county and academic institutions. Patient information in the database includes gender, age, insurance information, ICD-9 diagnosis and procedure codes, hospital charges, admission and discharge dates, and geographic information.
Covariates and Outcomes
Covariates used in this study included gender, age at admission, diagnosis of pelvic malignancy, Elixhauser comorbidity index, insurance status, year of admission, LOS and need for blood transfusion or invasive procedures.14 The primary outcome was the median adjusted in-hospital cost associated with admission for patients with RC. Secondary outcomes included the number of patients requiring endourological procedures, blood transfusions and nephrostomy tube placement.
Study Population
We identified 1,244 patients older than 18 years admitted to participating Ohio hospitals with a diagnosis of RC from 2009 to 2013. Patients were identified as having RC if ICD-9
Statistical Analysis
Multivariable logistic regression analyses were performed to determine if covariates influenced the likelihood of
439
Economic Burden of Radiation Cystitis
Results
We identified 1,111 patients with a mean age of 73.9 years (12.5) admitted to participating Ohio hospitals with a diagnosis of radiation cystitis from 2009 to 2013 (table 1). Median LOS was 4 days (IQR 3e8, range 1 to 56) and median cost of hospitalization in 2013 was $7,151 Table 1. Patient characteristics No. (%) Age: 18e49 50e59 60e69 70e79 80þ Gender: M F Insurance: Private Medicaid Medicare Self-pay/unknown/other Elixhauser comorbidity: 0 1 2 3 4 or Greater History of selected pelvic malignancy: Colorectal Ca Prostate Ca Uterine Ca Cervical Ca Not reported/unknown Yr: 2009 2010 2011 2012 2013 Treatment required: Endoscopic procedure Nephrostomy tube Blood transfusion
56 (5.0) 84 (7.6) 200 (18.0) 351 (31.6) 420 (37.8) 799 (71.9) 312 (28.1) 136 (12.2) 60 (5.4) 879 (79.1) 36 (3.2) 85 (7.7) 200 (18.0) 259 (23.3) 242 (21.8) 325 (29.3) 75 (6.6) 520 (46.8) 41 (3.7) 109 (9.8) 366 (32.9) 290 258 277 149 137
(26.1) (23.3) (24.9) (13.4) (12.3)
382 (34.4) 38 (3.4) 321 (28.9)
(IQR $4,251e$16,569; see figure). In 2013 the estimated inpatient cost of treating patients with radiation cystitis in Ohio was $979,687. Using a general estimating equation model, increasing LOS and undergoing an endoscopic procedure or percutaneous nephrostomy were associated with an increased in-hospital cost. Mean hospitalization cost for patients undergoing an inpatient endoscopic procedure was $11,100 (IQR $9,948e$12,254) and mean cost for patients requiring percutaneous nephrostomy tube placement was $16,644 (IQR $12,935e$20,354). There was no association between cost and transfusion status, age, gender, insurance status, year of treatment or Elixhauser comorbidity index (table 2). We also found that 34.4% of patients admitted to the hospital underwent an endourological procedure during hospitalization, 28.9% received a blood a transfusion and 3.4% required nephrostomy tube placement. On multivariate analysis undergoing an invasive procedure (endourological or nephrostomy tube) was associated with increasing LOS, male gender (OR 1.59, 95% CI 1.02e2.47) and receiving a blood transfusion during hospitalization (OR 1.67, 95% CI 1.26e2.21, table 3). There was no association between undergoing an invasive procedure and age, Elixhauser comorbidity score or insurance status.
Discussion
In this analysis of a statewide inpatient hospital database we assessed the economic and treatment associated burden associated with a diagnosis of RC when admitted to the hospital. Our study clearly demonstrates that the inpatient care of patients with a diagnosis of RC leads to significant economic costs. These costs are comparable to the inpatient costs associated with the treatment of neutropenic fever, another cancer related treatment complication. Dulisse et al reported a mean inpatient treatment cost of $18,880 and a Adjusted median In-patient hospital costs ($)
undergoing blood transfusion or invasive procedures when admitted with RC. A generalized estimating equation model was used to determine median adjusted in-hospital costs based on covariates associated with inpatient admission for RC. The generalized estimating equation is a generalized linear model that determines the correlation between independent variables (ie predictors) and a continuous dependent variable (ie cost), and also allows for determination of mean values for this variable.15 StataMPÔ version 11.2 was used to perform all statistical analyses and a 2-sided p <0.05 was used to determine statistical significance.
8000 7800 7600 7400 7200 7000 6800 6600 6400 6200 6000
Adjusted median InpaƟent hospital costs ($)
2009
2010
2011
2012
2013
6692
7019
7370
6880
7151
Figure. Trends in median adjusted in-hospital costs (2013 dollars) for inpatient treatment of patients admitted with RC.
440
Economic Burden of Radiation Cystitis
Table 2. Multivariate generalized estimating equation model of median cost associated with inpatient admission with RC Covariate (reference) Yr (2009): 2010 2011 2012 2013 Gender (M): F LOS (0e2 days): 3e4 days 5e7 days 8 or More days Elixhauser comorbidity index (0): 1 2 3 4 or Greater Insurance (private): Medicaid Medicare Other/unknown Endoscopic procedure (none): Performed Nephrostomy tube (none): Performed Blood transfusion (none): Performed
Coefficient (95% CI) 0.006 0.079 0.122 0.106
0.104) 0.187) 0.255) 0.239)
0.93 0.15 0.07 0.12
0.009 (0.122, 0.140)
0.89
0.436 0.867 1.68 0.126 0.140 0.104 0.128
(0.114, (0.02, (0.010, (0.02,
p Value
(0.327, 0.544) (0.752, 0.982) (1.56, 1.80) (0.040, (0.021, (0.061, (0.034,
<0.001 <0.001 <0.001
0.293) 0.302) 0.270) 0.290)
0.14 0.09 0.22 0.12
0.069 (0.284, 0.146) 0.020 (0.166, 0.127) 0.051 (0.295, 0.192)
0.53 0.79 0.68
0.165
(0.083, 0.247)
<0.001
0.549
(0.334, 0.765)
<0.001
0.029 (0.064, 0.122)
0.55
mean LOS of 8.6 days in a retrospective cohort of 16,273 patients hospitalized with neutropenic fever.16 Similarly, Hendricks et al reported a mean hospitalization cost of $10,143 in their cohort of 57 inpatient treatment episodes for neutropenic fever.17 Table 3. Multivariable logistic regression of undergoing an invasive procedure when hospitalized with RC Covariate (referent) LOS (0e2 days): 3e4 days 5e7 days 8 or More days Transfusion status (no): Yes Insurance (private): Medicaid Medicare Other Elixhauser comorbidity score (0): 1 2 3 4 or Greater Age (60e69): 18e49 50e59 70e79 80 or Greater Gender (F): M
OR (95% CI)
p Value
1.45 (0.99e2.12) 1.94 (1.32e2.86) 2.29 (1.55e3.40)
0.06 0.001 <0.001
1.67 (1.26e2.21)
<0.001
1.01 (0.49e2.07) 1.23 (0.77e1.98) 1.46 (0.66e3.20)
0.98 0.39 0.35
1.08 0.88 0.91 0.99
(0.62e1.89) (0.51e1.51) (0.52e1.57) (0.58e1.69)
0.78 0.63 0.73 0.97
0.59 0.79 0.83 0.71
(0.28e1.27) (0.44e1.45) (0.55e1.24) (0.48e1.07)
0.18 0.45 0.36 0.10
1.59 (1.02e2.47)
0.04
In addition, RC has a known rehospitalization rate of approximately 33% occurring at a median of 3.5 months after discharge.5 Developing systems to correlate hospital readmission rates with Medicare reimbursement remains a key component of the Affordable Care Act.18 Given the significant cost of treatment for patients with RC and the known readmission rate, it is important that physicians and key stakeholders continue to work with legislators and health policy decision makers to ensure that hospitals and physicians are not penalized for providing necessary care to patients with a condition that can require chronic rehospitalization and expensive long-term care. Similarly, in the modern health care environment the costs of managing cancer related treatment complications must be considered when evaluating the cost-effectiveness of cancer treatment modalities. We also found that in-hospital treatment of RC is associated with a significant risk of undergoing an invasive procedure during hospitalization. A third of the patients in our cohort required an invasive procedure during their inpatient stay. Furthermore, on multivariate analysis undergoing an invasive procedure was associated with a longer LOS and requiring a blood transfusion during hospitalization. Thus, patients needing invasive procedures most likely have more severe symptoms from RC. Kaplan and Wolf reported a mortality rate of 9.1% from complications of hemorrhagic cystitis (cyclophosphamide and radiation induced) in patients who required a cystoscopic procedure during hospitalization.19 Given the significant mortality rate associated with RC necessitating surgical intervention, the continued development of novel treatment modalities for RC is necessary. New treatment modalities may also help decrease the overall cost associated with the treatment of RC, as a recently published study showed that treatment with hyperbaric oxygen therapy helped decrease subsequent expenditures for RC associated treatment.20 In addition, we found that more than 25% of patients admitted with RC required blood transfusions during hospitalization. While we were not able to elucidate the underlying cause necessitating transfusion from the data set, other studies have reported transfusion rates of 14% to 25% for patients undergoing treatment for RC.21,22 Similarly, in their prospective study of hyperbaric oxygen treatment for RC Bevers et al classified 18 of 40 patients in their cohort as having severe hematuria (requiring more than 6 units of packed red blood cells during the previous 3 months).23 Therefore, while we were not able to determine the underlying reason for needing transfusion in our cohort, we believe that our data fall within historic parameters for patients with RC.
Economic Burden of Radiation Cystitis
Our study had several limitations. It was completed using a statewide inpatient database and, therefore, was retrospective. We were also limited in the analysis of patient factors affecting cost and procedure use to those factors that are collected in the database. Similarly, we were not able to accurately determine the causative diagnosis requiring pelvic radiation for all patients in the database due to the nature of the data set used in the analysis. Our cost analysis was somewhat limited by our database not containing hospital specific cost-to-charge ratios.24 However, Medicare insured 79% of patients in our cohort and, therefore, we believe the statewide Medicare cost-to-charge ratio was a reasonable method of determining cost from hospital charges. Due to the inpatient only nature of the database we were not able to determine the global cost of care for patients with RC since we could not account for outpatient costs, including the costs of outpatient treatment like hyperbaric oxygen therapy. Similarly, we were not able to include hidden economic costs in our analysis such as lost work hours. We were also unable to adjust for hospital characteristics such as academic or community settings that may have some impact on total cost or procedure use in this cohort. Finally, we were not able to adjust for physician characteristics that could also affect treatment decisions. In this study we present the first statewide, population based analysis of the economic and treatment burden associated with the inpatient treatment of RC. Further research will be required to identify treatments that can limit this significant burden for patients with RC. However, it is possible that increasing awareness of the substantial economic and procedural costs associated with radiation cystitis could lead to improved early diagnosis in the primary care setting, allowing for earlier referral to urologists for specialist management of these complex cases and perhaps limiting the number requiring inpatient admission.
Conclusions
Radiation induced hemorrhagic cystitis is a serious complication of pelvic radiation. Patients admitted to the hospital with a diagnosis of radiation cystitis are at substantial risk for requiring invasive procedures during the course of their admission. The diagnosis is also associated with significant inpatient economic costs. It is vital that physicians, patients and key stakeholders consider these economic and treatment related costs when recommending pelvic radiation for the treatment of malignancy and in further determination of health care policy as it relates to the treatment of chronic conditions.
441
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Economic Burden of Radiation Cystitis
19. Kaplan JR and Wolf JS Jr: Efficacy and survival associated with cystoscopy and clot evacuation for radiation or cyclophosphamide induced hemorrhagic cystitis. J Urol 2009; 181: 641. 20. Smart D and Wallington M: A cost-analysis case study of radiation cystitis treatment including hyperbaric oxygen therapy. Diving Hyperb Med 2012; 42: 92. 21. Veerasarn V, Khorprasert C, Lorvidhaya V et al: Reduced recurrence of late hemorrhagic radiation cystitis by WF10 therapy in cervical cancer patients: a multicenter, randomized, two-arm, open-label trial. Radiother Oncol 2004; 73: 179.
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Editorial Commentary
Accurate health care cost data are as elusive as they are critical to payment and delivery system reform. As value based purchasing supplants fee-for-service, the costs of therapies and their complications will be juxtaposed to measures of quality in an attempt to quantify value. Accurate cost data will also inform the calculation of fair price points for treatment bundles and episodes of care. Hospital charge masters obfuscate the true costs of health care goods and services. To estimate the cost of inpatient treatment of radiation cystitis, the authors use an average cost-to-charge ratio for urban acute care hospitals in Ohio, an unsatisfying estimation. Defining cost with greater accuracy is essential going forward. There is a growing body of literature using time driven, activity based costing, a more accurate, if labor intensive, method of defining the true cost of health care services.1,2 With the converging forces of public demand for price and quality transparency, and increasing patient cost sharing through higher copays and deductibles, the ability to ascertain accurate costs will improve and value will be increasingly patient defined. Future economic analyses of radiation cystitis therapy should consider 1) the impact of hyperbaric oxygen
therapy on the need for hospital admission, 2) the impact of intravesical therapy on LOS and the need for transfusion or procedural therapy, and 3) the impact of these interventions on the all cause 30-day readmission rate, which the Centers for Medicare & Medicaid Services has deemed a reliable and sufficiently granular quality indicator that it has been using it to reduce provider payments since 2012. Mark T. Edney Peninsula Urology Associates Salisbury, Maryland
References 1. Kaplan AL, Agarwal N, Setlur NP et al: Measuring the cost of care in benign prostatic hyperplasia using time-driven activity-based costing (TDABC). Healthc (Amst) 2015; 3: 43. 2. McLaughlin N, Burke MA, Setlur NP et al: Time-driven activity-based costing: a driver for provider engagement in costing activities and redesign initiatives. Neurosurg Focus 2014; 37: E3.