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The Management of Newly-Diagnosed Non-muscle Invasive Bladder Cancer in Veterans Integrated Services Network 02 of the Veterans Health Administration

The Management of Newly-Diagnosed Non-muscle Invasive Bladder Cancer in Veterans Integrated... Abstract Introduction Over 1,500 bladder cancers were diagnosed among US Veterans in 2010, the majority of which were non-muscle invasive bladder cancer (NMIBC). Little is known about NMIBC treatment within the Veterans Health Administration. The objective of the study was to assess the quality of care for Veterans with newly-diagnosed NMIBC within Veterans Integrated Service Network (VISN) 02. Materials and Methods We used ICD-9 and ICD-10 codes to identify patients with newly-diagnosed bladder cancer from 1/2016–8/2017. We risk-stratified the patients into low, intermediate, and high-risk based on the 2016 American Urological Association Guidelines on NMIBC. Our primary objectives were percentages of transurethral resection of bladder tumors (TURBTs) with detrusor, repeat TURBT in high-risk and T1 disease, high-risk NMIBC treated with induction intravesical therapy (IVT), and responders treated with maintenance IVT. We performed logistic regression for association between distance to diagnosing hospital and receipt of induction IVT in high-risk patients. Results There were 121 newly-diagnosed NMIBC patients; 16% low-risk, 28% intermediate-risk, and 56% high-risk. Detrusor was present in 80% of all initial TURBTs and 84% of high-risk patients. Repeat TURBT was performed in 56% of high-risk NMIBC and 60% of T1. Induction IVT was given to 66% of high-risk patients and maintenance IVT was given to 59% of responders. On multivariate logistic regression, distance to medical center was not associated with receipt of induction IVT (OR = 0.99, 95% CI [0.97,1.01], p = 0.52). Conclusions We observed high rates of sampling of detrusor in the first TURBT specimen, utilization of repeat TURBT, and administration of induction and maintenance intravesical BCG for high-risk patients among a regional cohort of US Veterans with NMIBC. While not a comparative study, our findings suggest high quality NMIBC care in VA VISN 02. Non-muscle invasive bladder cancer, Guidelines, Veterans Health Administration, Compliance, Quality indicators INTRODUCTION Bladder cancer is a highly prevalent disease with nearly 80,000 new diagnoses in 2017 and almost 17,000 deaths.1 About 75% of patients present with non-muscle invasive disease at time of diagnosis and require multiple invasive procedures for treatment and surveillance.1 The 2016 joint American Urological Association (AUA) and Society of Urologic Oncology (SUO) Guidelines on the Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer (NMIBC) offer several recommendations on the management of NMIBC at the time of diagnosis.2 Such recommendations work to optimize staging, treatment, and follow-up of patients with NMIBC. Among them are use of repeat transurethral resection of bladder tumor (TURBT) for patients with T1 tumors, initial upper tract imaging for all patients, and administration of intravesical therapy (IVT) for patients with intermediate and high-risk disease.2 These Guidelines also emphasize that absence of detrusor in the TURBT specimen is associated with understaging and inferior cancer outcomes, and many consider presence of detrusor in the specimen a metric for surgical quality.3 Approximately 20 million US Veterans are eligible for treatment through the Veterans Health Administration (VHA), with 6 million receiving healthcare.4 This number is expected to rise as an aging Veteran population seeks healthcare in the VHA. An analysis of the Veterans Affairs (VA) Central Cancer Registry in 2010 reported over 1,500 bladder cancers diagnosed among US Veterans, representing the sixth most common cancer.5 Despite this, very little is known about how bladder cancer is treated in the VHA population and whether bladder cancer care is concordant with current AUA guidelines.2,6 Non-Veteran literature7 has shown guideline discordant care for patients with non-muscle invasive bladder cancer. As a means to identify areas for improvement in care, we sought to describe the quality of care for Veterans with newly-diagnosed NMIBC within Veterans Integrated Service Network (VISN) 02, a regional district of the VHA. The primary objective of this study was to describe the use of guideline-concordant care of patients in VA VISN 02 with newly-diagnosed NMBIC. We focused on specific important treatment recommendations including the percentage of TURBTs with detrusor muscle, the use of repeat TURBT, and the use of induction and maintenance IVT. The secondary objective was to determine if distance to diagnosing VA medical center (VAMC) was associated with receipt of induction IVT for high-risk patients. We hypothesized that patients who lived further from their diagnosing VAMC would be less likely to receive induction IVT. MATERIALS AND METHODS Cohort The current study was approved by the James J. Peters VA Medical Center’s Institutional Review Board (IRB) to perform a complete chart review for all patients diagnosed with bladder cancer in VISN 02 from January 2016 through August 2017. Participant consent was waived by the IRB. We identified all patients who were assigned a new diagnosis of bladder cancer in VISN 02 using ICD-9 (188.0, 188.1, 188.2, 188.3, 188.4, 188.5, 188.6, 188.8, 188.9, 233.7, 239.4, 236.7) and ICD-10 (C67.0, C67.1, C67.2, C67.3, C67.4, C67.5, C67.6, C67.8, C67.9, D09.0, D41.4, D49.4) codes (N = 529). Patients were excluded if they had a prior diagnosis of bladder cancer, muscle invasive bladder cancer, concomitant upper tract urothelial malignancy, or diagnosis and/or management of their bladder cancer outside of the VA (N = 389, Fig. 1). Smoking status was obtained and patients were described as either current smoker, former smoker, or never smoker. Elixhauser comorbidity was calculated for all patients using relevant diagnosis codes.8 Figure 1 Open in new tabDownload slide Study Pathway. Figure 1 Open in new tabDownload slide Study Pathway. VISNs are regional health systems comprised of rural and urban medical facilities that work to meet local healthcare needs and provide greater access to care.4 VISN 02 is the New York/New Jersey Healthcare Network composed of four VHA healthcare systems including Western New York, New Jersey, Hudson Valley, and New York Harbor. Each of these systems includes numerous outpatient clinics and medical centers. A chart review was performed on all identified patients, with follow-up through August 2018. We reviewed pathology reports and inpatient, outpatient, operative, and telephone notes. We queried pathology records to identify histology, stage, and grade of the tumor, as well as the presence of detrusor muscle. Focality and size of tumor were derived from the operative note of the initial TURBT. We used pathological and operative findings to assign risk group for the NMIBC patients based on the AUA Guidelines.2 We defined low-risk as patients with papillary urothelial neoplasm of low malignant potential (PUNLMP) or solitary low-grade (LG) Ta ≤3 cm; intermediate-risk as solitary LG Ta > 3 cm, multifocal LG Ta, high-grade (HG) Ta ≤3 cm, or LG T1; and high-risk as HG T1, multifocal or >3 cm HG Ta, any carcinoma in situ (CIS), or variant histology. We reviewed medical records to determine the use of repeat transurethral resection, use of induction and maintenance IVT, and utilization of computed topography abdominal/pelvic imaging at the time of diagnosis. Repeat TURBT was defined as any TURBT performed within 6 weeks of an initial TURBT for staging purposes before any treatment plan was decided. Induction IVT was defined as 6 weeks of induction intravesical bacillus calmette-guerin (BCG) or chemotherapy within 6 weeks of TURBT.2 Patients with a negative cystoscopy and cytology or a negative bladder biopsy after induction IVT were considered complete responders. Maintenance BCG status was defined as at least one 3-week course of IVT with the plan to continue a complete schedule specified in the Guidelines.2 CT imaging was considered if it was used in the initial evaluation for hematuria and/or staging purposes. We did not limit it to a certain time window from initial diagnosis. Statistical Analysis We calculated the percentage of initial TURBTs that included detrusor in the sample, and stratified this by NMIBC risk group. We calculated percentage of T1, HG T1, and high-risk, high-grade Ta patients that underwent repeat resection. We also calculated rates of repeat TURBT for each NMIBC risk group and for patients who did not have muscle in the initial TURBT. We calculated the percentage of patients in each NMIBC risk group that received IVT. We also described the percentage of BCG responders who received at least one maintenance course of BCG. We used the straight-line measure function in Google Maps to calculate distance from the patient’s home address to the VAMC of bladder cancer diagnosis. This measure has been previously validated.9 We performed a logistic regression analysis to test if distance to diagnosing VAMC from the patient’s home was related to receipt of induction IVT for high-risk NMIBC patients. We considered age and comorbidity as covariates and p < 0.05 statistically significant. All statistics were performed with R. RESULTS We identified 121 newly-diagnosed NMIBC patients (Table I). All patients were male with a median age of 71 (IQR = 68–80). The majority (79%) had a smoking history. The Western New York system made up 64% of the cohort as it consists of 3 large medical centers (Buffalo, Albany, and Syracuse). New York Harbor comprised the least at 8% with the Manhattan medical center contributing the vast majority to this system. More than half had an Elixhauser comorbidity score of 3+. According to AUA NMIBC risk group, 19/121 (16%) were low-risk, 34/121 (28%) were intermediate-risk, and 68/121 (56%) were high-risk. Ninety three patients (77%) had computed topography (CT) imaging of the abdomen and pelvis performed for evaluation or staging, of which 84 (90%) were contrasted studies. Table I Patient Characteristics (N = 121) Characteristic N (%) Age Median Age [IQR] 71 [68–80] Gender Male 121 (100) Healthcare System Western New York 78 (64) Hudson Valley 19 (16) New Jersey 14 (12) New York Harbor 10 (8) Race Caucasian 107 (88) African American 9 (8) Other 5 (4) Smoking Status Never Smoker 25 (21) Smoker 96 (79) Current Smoker 36 (38) Former Smoker 60 (62) Elixhauser Index 0 15 (12) 1 17 (14) 2 20 (17) 3+ 69 (57) CT Imaging Yes 93 (77) Contrast 84 (90) TURBT Stage PUNLMP 2 (1) Ta 60 (50) Any T1 52 (43) T1 + cis 10 (8) Any cis 17 (14) Grade High 75 (62) Low 46 (38) Focality Unifocal 63 (52) Multifocal 58 (48) NMIBC Risk Group High 68 (56) Intermediate 34 (28) Low 19 (16) Characteristic N (%) Age Median Age [IQR] 71 [68–80] Gender Male 121 (100) Healthcare System Western New York 78 (64) Hudson Valley 19 (16) New Jersey 14 (12) New York Harbor 10 (8) Race Caucasian 107 (88) African American 9 (8) Other 5 (4) Smoking Status Never Smoker 25 (21) Smoker 96 (79) Current Smoker 36 (38) Former Smoker 60 (62) Elixhauser Index 0 15 (12) 1 17 (14) 2 20 (17) 3+ 69 (57) CT Imaging Yes 93 (77) Contrast 84 (90) TURBT Stage PUNLMP 2 (1) Ta 60 (50) Any T1 52 (43) T1 + cis 10 (8) Any cis 17 (14) Grade High 75 (62) Low 46 (38) Focality Unifocal 63 (52) Multifocal 58 (48) NMIBC Risk Group High 68 (56) Intermediate 34 (28) Low 19 (16) Open in new tab Table I Patient Characteristics (N = 121) Characteristic N (%) Age Median Age [IQR] 71 [68–80] Gender Male 121 (100) Healthcare System Western New York 78 (64) Hudson Valley 19 (16) New Jersey 14 (12) New York Harbor 10 (8) Race Caucasian 107 (88) African American 9 (8) Other 5 (4) Smoking Status Never Smoker 25 (21) Smoker 96 (79) Current Smoker 36 (38) Former Smoker 60 (62) Elixhauser Index 0 15 (12) 1 17 (14) 2 20 (17) 3+ 69 (57) CT Imaging Yes 93 (77) Contrast 84 (90) TURBT Stage PUNLMP 2 (1) Ta 60 (50) Any T1 52 (43) T1 + cis 10 (8) Any cis 17 (14) Grade High 75 (62) Low 46 (38) Focality Unifocal 63 (52) Multifocal 58 (48) NMIBC Risk Group High 68 (56) Intermediate 34 (28) Low 19 (16) Characteristic N (%) Age Median Age [IQR] 71 [68–80] Gender Male 121 (100) Healthcare System Western New York 78 (64) Hudson Valley 19 (16) New Jersey 14 (12) New York Harbor 10 (8) Race Caucasian 107 (88) African American 9 (8) Other 5 (4) Smoking Status Never Smoker 25 (21) Smoker 96 (79) Current Smoker 36 (38) Former Smoker 60 (62) Elixhauser Index 0 15 (12) 1 17 (14) 2 20 (17) 3+ 69 (57) CT Imaging Yes 93 (77) Contrast 84 (90) TURBT Stage PUNLMP 2 (1) Ta 60 (50) Any T1 52 (43) T1 + cis 10 (8) Any cis 17 (14) Grade High 75 (62) Low 46 (38) Focality Unifocal 63 (52) Multifocal 58 (48) NMIBC Risk Group High 68 (56) Intermediate 34 (28) Low 19 (16) Open in new tab Detrusor was present in the initial TURBT in 80% (97/121) of all NMIBC patients, including 84% (57/68) of high-risk patients, 74% (25/34) of intermediate-risk patients, and 79% (15/19) of the low-risk patients (Table II). Repeat TURBT was performed in 56% (38/68) of all high-risk patients, 60% (31/52) of patients with any T1 disease, 70% (31/44) of patients with HG T1, and 29% (5/17) of high-risk Ta tumors. There were low rates of repeat TURBT in the low- and intermediate risk patients (5% and 9% respectively). The majority of the high-risk (8/11) and T1 (5/6) patients who did not have muscle in their initial resection specimen had a repeat TURBT. Induction IVT was given to 0% (0/19) of low-risk, 24% (8/34) of intermediate-risk, and 66% (45/68) of high-risk patients (Table II). Only one of the intermediate-risk patients received induction intravesical Mitomycin C for IVT, and the remainder of intermediate-risk and all high-risk patients received BCG. The majority (69%) of intermediate-risk patients who were not given induction IVT had LG Ta tumors. Three of the 53 patients who received induction IVT did not follow-up. Of those who did, 64% (32/50) had a complete response to induction IVT. Fifty nine percent (16/27) of high-risk BCG responders were initiated on maintenance BCG (Table II). Among high-risk patients who did not receive induction BCG (N = 23), 8 patients had documented reasons for not receiving treatment. Common reasons for not having induction IVT were long distance to VA (N = 6) and difficulty contacting the patient (N = 2). In the high-risk NMIBC patients, the mean distance to diagnosing VAMC from home address was 32.5 (±26.9) miles for those who received induction BCG compared to 33.4 miles (±30.2) miles for those who did not receive induction BCG. After adjusting for age and comorbidities, distance to diagnosing VAMC was not significantly associated with receipt of induction BCG on multivariate logistic regression (OR = 0.99, 95% CI [0.97–1.01], p = 0.52). Table II Rates of Detrusor in the Initial TURBT Specimen, Use of Repeat TURBT, and Use of Induction and Maintenance IVT by NMIBC Risk Group Risk group Detrusor present Repeat TURBT Induction IVT Maintenance BCG N (%) N (%) N (%) N (%) High (N = 68) 57 (84) 38 (56) 45 (66) 16 (59)† Intermediate (N = 34) 25 (74) 3 (9) 8 (24) 2 (40)‡ Low (N = 19) 15 (79) 1 (5) 0 (0) NA Risk group Detrusor present Repeat TURBT Induction IVT Maintenance BCG N (%) N (%) N (%) N (%) High (N = 68) 57 (84) 38 (56) 45 (66) 16 (59)† Intermediate (N = 34) 25 (74) 3 (9) 8 (24) 2 (40)‡ Low (N = 19) 15 (79) 1 (5) 0 (0) NA † of the 27 high-risk NMIBC who responded to induction IVT. ‡ of the 5 intermediate-risk NMIBC who responded to induction IVT. Open in new tab Table II Rates of Detrusor in the Initial TURBT Specimen, Use of Repeat TURBT, and Use of Induction and Maintenance IVT by NMIBC Risk Group Risk group Detrusor present Repeat TURBT Induction IVT Maintenance BCG N (%) N (%) N (%) N (%) High (N = 68) 57 (84) 38 (56) 45 (66) 16 (59)† Intermediate (N = 34) 25 (74) 3 (9) 8 (24) 2 (40)‡ Low (N = 19) 15 (79) 1 (5) 0 (0) NA Risk group Detrusor present Repeat TURBT Induction IVT Maintenance BCG N (%) N (%) N (%) N (%) High (N = 68) 57 (84) 38 (56) 45 (66) 16 (59)† Intermediate (N = 34) 25 (74) 3 (9) 8 (24) 2 (40)‡ Low (N = 19) 15 (79) 1 (5) 0 (0) NA † of the 27 high-risk NMIBC who responded to induction IVT. ‡ of the 5 intermediate-risk NMIBC who responded to induction IVT. Open in new tab DISCUSSION The 2016 American Urological Association Guidelines on the Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer provides recommendations on disease risk stratification, use of repeat TURBT, and administration of induction and maintenance IVT.2 Several of these metrics have been endorsed as quality measures, as they are associated with improved disease staging and control.10 Still, non-guideline concordant NMIBC treatment and evaluation is common.7,11,12 In the non-VA population, a large retrospective study using the SEER-Medicare database observed that astonishingly few patients received complete guideline-concordant care, including use of radiologic imaging and utilization of IVT, and this was largely attributed to surgeon variation.7 Witjes et al.12 reported that although 50% of high-risk NMIBC patients received intravesical BCG, 12.5% also received intravesical chemotherapy which has been shown to be inferior to BCG13–15 and not recommended in the current guidelines. Non-adherence to guideline care for patients with NMIBC puts patients at higher risk for recurrence and progression. Prior to our study, there was limited information on the quality of NMIBC care among US Veterans. Detrusor muscle in the specimen is a measure of resection quality, since the presence of muscle in the pathologic specimen decreases the risk of under-staging and lowers recurrence rates.3 We found that 80% of NMIBC patients had detrusor muscle sampled in their initial resection. This is similar to the 60–70% reported in prior cohort studies.3,16 While we expected that surgeons would sample detrusor less often for low-risk patients, as has previously been reported,3,17 we observed a high rate (79%) of detrusor sampling for this group. Given the 15–30% risk of understaging, and the nearly 50% risk of residual disease after a visually complete resection,18–22 the AUA Guidelines recommend a restaging TURBT for all T1 patients, especially those without muscle in the initial resection, and to consider a repeat TURBT for high-risk Ta disease.2 Repeat TURBT not only improves initial staging, but also improves response to IVT.23,24 We observed that 60% of patients with T1 disease had a repeat TURBT and 83% of T1 patients without muscle in the original specimen had a repeat TURBT. The use of repeat TURBT for high-risk Ta was considerably lower at 29%. It was reassuring to observe that the majority of the high-risk (8/11) and T1 (5/6) patients who did not have muscle in their initial resection specimen had a repeat TURBT. Although some have suggested that repeat TURBT should have a more limited role if the initial TURBT was done by experienced surgeons and muscle was obtained, others have proposed a benchmark of 90% utilization of repeat TURBT in patients with higher risk NMIBC.10,19 A retrospective study of 600 HG T1 patients using the Alberta Cancer Registry found that only 28% had an early repeat TURBT, with a modest increase in utilization over time, from 27.4% in 2007 to 37.8% in 2011.25 An Australian group reported a similar rate at 22.4% for 380 HG Ta and any T1 specimens.26 A large population based study of Medicare beneficiaries in the US reported an even lower rate of 7.9% of T1 patients undergoing a repeat TURBT.27 While there may be an opportunity to improve the use of repeat TURBT among Veterans with HG T1, we observed high utilization relative to what has been reported in other large non-VA cohorts. The AUA Guidelines recommend induction intravesical BCG for patients with high-risk disease and consideration of intravesical BCG or chemotherapy for patients with intermediate-risk disease.2 We observed that 66% of high-risk NMIBC patients appropriately received induction BCG. This finding meets a proposed quality benchmark of at least 60%.10 A retrospective study using the SEER-Medicare database found that less than 40% of patients ≥65 years old with poorly differentiated or undifferentiated NIMBC were treated with BCG within 6 months of diagnosis.28 The use of induction IVT in intermediate-risk NMIBC patients is more controversial due to the heterogeneity within the group.2,29 We observed 24% of the intermediate-risk patients received induction BCG. It has been shown that additional dosages of intravesical chemotherapy do not offer recurrence or progression benefits for low-risk NMIBC,30,31 and appropriately, none of the low-risk patients had induction therapy administered. Our findings suggest relatively high utilization of induction IVT among the highest risk patients in our cohort. Maintenance BCG should be offered to NMIBC patients who respond to induction therapy.2,32 We observed a response rate to induction IVT similar to what has been reported by others.33–35 We also found that 59% of the high-risk BCG responders were given at least one dose of maintenance therapy. A large retrospective cohort study using the SEER-Medicare dataset reported that only 7.5% of patients received any maintenance BCG.36 We sought to identify the reasons patients did not receive IVT when it was indicated. Albeit among a small group of patients, the most common documented reasons for not receiving induction BCG among high-risk patients were long distance to a VA medical center and inability of the treating physician to contact the patient. Given the centralization of the VA system, there may be patients who have difficulty accessing care due to their location of residence. This is especially important in the management of NMIBC where certain treatments, such as TURBT and IVT, may not be available at all VA facilities. We hypothesized that patient location would impact receipt of IVT, but did not observe a statistically significant difference in receipt of induction BCG according to distance from the diagnosing VAMC. Further study is required to identify barriers to receipt of induction and maintenance BCG from a surgeon and patient level. Our study is not without limitations. Our cohort is relatively small in numbers, which limits the precision of the results. Also, our findings are not directly generalizable to the national VA cohort as our cohort is based in a single geographic region in the Northeast. We relied upon operative notes to help assign NMIBC risk group, however certain disease characteristics may not have been documented consistently. Our follow-up was limited to one year, and therefore we could not report on completion of maintenance therapy. We estimated patient distance to VAMC using straight line distance, which may not correlate well with travel time. Further, we estimated patient distance to the hospital that diagnosed their bladder cancer as a possible exposure for non-receipt of IVT, although distance to a closer satellite VA facility that had the capacity to administer IVT may have been a more appropriate measure. Finally, as this is not a comparative study, it is not possible to determine if our findings are different from non-VA NMIBC patients living in the same region. CONCLUSIONS Among a regional cohort of US Veterans with NMIBC, we observed high rates of sampling of detrusor in the first TURBT specimen, utilization of repeat TURBT, and administration of induction and maintenance intravesical BCG for high-risk patients. While not a comparative study, our findings suggest high quality NMIBC care in VA VISN 02. The views expressed are solely those of the authors and do not reflect the official policy or position of the US Army, US Navy, US Air Force, the Department of Defense, or the US Government. References 1. Siegel RL , Miller KD , Jemal A : Cancer Statistics, 2017 . CA Cancer J Clin 2017 ; 67 ( 1 ): 7 – 30 . Google Scholar Crossref Search ADS PubMed WorldCat 2. Chang SS , Boorjian SA , Chou R , et al. : Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO Guideline . J Urol 2016 ; 196 ( 4 ): 1021 – 1029 . Google Scholar Crossref Search ADS PubMed WorldCat 3. 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Urology 2011 ; 78 ( 6 ): 1345 – 9 . Google Scholar Crossref Search ADS PubMed WorldCat 28. Spencer BA , McBride RB , Hershman DL , et al. : Adjuvant intravesical bacillus calmette-guerin therapy and survival among elderly patients with non-muscle-invasive bladder cancer . J Oncol Pract 2013 ; 9 ( 2 ): 92 – 8 . Google Scholar Crossref Search ADS PubMed WorldCat 29. Kamat AM , Witjes JA , Brausi M , et al. : Defining and treating the spectrum of intermediate risk nonmuscle invasive bladder cancer . J Urol 2014 ; 192 ( 2 ): 305 – 15 . Google Scholar Crossref Search ADS PubMed WorldCat 30. Tolley DA , Parmar MK , Grigor KM , et al. : The effect of intravesical mitomycin C on recurrence of newly diagnosed superficial bladder cancer: a further report with 7 years of follow up . J Urol 1996 ; 155 ( 4 ): 1233 – 8 . Google Scholar Crossref Search ADS PubMed WorldCat 31. Liu B , Wang Z , Chen B , et al. : Randomized study of single instillation of epirubicin for superficial bladder carcinoma: long-term clinical outcomes . Cancer Invest 2006 ; 24 ( 2 ): 160 – 3 . Google Scholar Crossref Search ADS PubMed WorldCat 32. Oddens J , Brausi M , Sylvester R , et al. : Final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Guerin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of maintenance . Eur Urol 2013 ; 63 ( 3 ): 462 – 72 . Google Scholar Crossref Search ADS PubMed WorldCat 33. Herr HW , Schwalb DM , Zhang ZF , et al. : Intravesical bacillus Calmette-Guerin therapy prevents tumor progression and death from superficial bladder cancer: ten-year follow-up of a prospective randomized trial . J Clin Oncol 1995 ; 13 ( 6 ): 1404 – 8 . Google Scholar Crossref Search ADS PubMed WorldCat 34. Lamm DL , Blumenstein BA , Crissman JD , et al. : Maintenance bacillus Calmette-Guerin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study . J Urol 2000 ; 163 ( 4 ): 1124 – 9 . Google Scholar Crossref Search ADS PubMed WorldCat 35. Weizer AZ , Tallman C , Montgomery JS : Long-term outcomes of intravesical therapy for non-muscle invasive bladder cancer . World J Urol 2011 ; 29 ( 1 ): 59 – 71 . Google Scholar Crossref Search ADS PubMed WorldCat 36. Lenis AT , Donin NM , Litwin MS , et al. : Association between number of endoscopic resections and utilization of bacillus Calmette-Guerin therapy for patients with high-grade, non-muscle-invasive bladder cancer . Clin Genitourin Cancer 2017 ; 15 ( 1 ): e25 – 31 . Google Scholar Crossref Search ADS PubMed WorldCat © Association of Military Surgeons of the United States 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Military Medicine Oxford University Press

The Management of Newly-Diagnosed Non-muscle Invasive Bladder Cancer in Veterans Integrated Services Network 02 of the Veterans Health Administration

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Abstract

Abstract Introduction Over 1,500 bladder cancers were diagnosed among US Veterans in 2010, the majority of which were non-muscle invasive bladder cancer (NMIBC). Little is known about NMIBC treatment within the Veterans Health Administration. The objective of the study was to assess the quality of care for Veterans with newly-diagnosed NMIBC within Veterans Integrated Service Network (VISN) 02. Materials and Methods We used ICD-9 and ICD-10 codes to identify patients with newly-diagnosed bladder cancer from 1/2016–8/2017. We risk-stratified the patients into low, intermediate, and high-risk based on the 2016 American Urological Association Guidelines on NMIBC. Our primary objectives were percentages of transurethral resection of bladder tumors (TURBTs) with detrusor, repeat TURBT in high-risk and T1 disease, high-risk NMIBC treated with induction intravesical therapy (IVT), and responders treated with maintenance IVT. We performed logistic regression for association between distance to diagnosing hospital and receipt of induction IVT in high-risk patients. Results There were 121 newly-diagnosed NMIBC patients; 16% low-risk, 28% intermediate-risk, and 56% high-risk. Detrusor was present in 80% of all initial TURBTs and 84% of high-risk patients. Repeat TURBT was performed in 56% of high-risk NMIBC and 60% of T1. Induction IVT was given to 66% of high-risk patients and maintenance IVT was given to 59% of responders. On multivariate logistic regression, distance to medical center was not associated with receipt of induction IVT (OR = 0.99, 95% CI [0.97,1.01], p = 0.52). Conclusions We observed high rates of sampling of detrusor in the first TURBT specimen, utilization of repeat TURBT, and administration of induction and maintenance intravesical BCG for high-risk patients among a regional cohort of US Veterans with NMIBC. While not a comparative study, our findings suggest high quality NMIBC care in VA VISN 02. Non-muscle invasive bladder cancer, Guidelines, Veterans Health Administration, Compliance, Quality indicators INTRODUCTION Bladder cancer is a highly prevalent disease with nearly 80,000 new diagnoses in 2017 and almost 17,000 deaths.1 About 75% of patients present with non-muscle invasive disease at time of diagnosis and require multiple invasive procedures for treatment and surveillance.1 The 2016 joint American Urological Association (AUA) and Society of Urologic Oncology (SUO) Guidelines on the Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer (NMIBC) offer several recommendations on the management of NMIBC at the time of diagnosis.2 Such recommendations work to optimize staging, treatment, and follow-up of patients with NMIBC. Among them are use of repeat transurethral resection of bladder tumor (TURBT) for patients with T1 tumors, initial upper tract imaging for all patients, and administration of intravesical therapy (IVT) for patients with intermediate and high-risk disease.2 These Guidelines also emphasize that absence of detrusor in the TURBT specimen is associated with understaging and inferior cancer outcomes, and many consider presence of detrusor in the specimen a metric for surgical quality.3 Approximately 20 million US Veterans are eligible for treatment through the Veterans Health Administration (VHA), with 6 million receiving healthcare.4 This number is expected to rise as an aging Veteran population seeks healthcare in the VHA. An analysis of the Veterans Affairs (VA) Central Cancer Registry in 2010 reported over 1,500 bladder cancers diagnosed among US Veterans, representing the sixth most common cancer.5 Despite this, very little is known about how bladder cancer is treated in the VHA population and whether bladder cancer care is concordant with current AUA guidelines.2,6 Non-Veteran literature7 has shown guideline discordant care for patients with non-muscle invasive bladder cancer. As a means to identify areas for improvement in care, we sought to describe the quality of care for Veterans with newly-diagnosed NMIBC within Veterans Integrated Service Network (VISN) 02, a regional district of the VHA. The primary objective of this study was to describe the use of guideline-concordant care of patients in VA VISN 02 with newly-diagnosed NMBIC. We focused on specific important treatment recommendations including the percentage of TURBTs with detrusor muscle, the use of repeat TURBT, and the use of induction and maintenance IVT. The secondary objective was to determine if distance to diagnosing VA medical center (VAMC) was associated with receipt of induction IVT for high-risk patients. We hypothesized that patients who lived further from their diagnosing VAMC would be less likely to receive induction IVT. MATERIALS AND METHODS Cohort The current study was approved by the James J. Peters VA Medical Center’s Institutional Review Board (IRB) to perform a complete chart review for all patients diagnosed with bladder cancer in VISN 02 from January 2016 through August 2017. Participant consent was waived by the IRB. We identified all patients who were assigned a new diagnosis of bladder cancer in VISN 02 using ICD-9 (188.0, 188.1, 188.2, 188.3, 188.4, 188.5, 188.6, 188.8, 188.9, 233.7, 239.4, 236.7) and ICD-10 (C67.0, C67.1, C67.2, C67.3, C67.4, C67.5, C67.6, C67.8, C67.9, D09.0, D41.4, D49.4) codes (N = 529). Patients were excluded if they had a prior diagnosis of bladder cancer, muscle invasive bladder cancer, concomitant upper tract urothelial malignancy, or diagnosis and/or management of their bladder cancer outside of the VA (N = 389, Fig. 1). Smoking status was obtained and patients were described as either current smoker, former smoker, or never smoker. Elixhauser comorbidity was calculated for all patients using relevant diagnosis codes.8 Figure 1 Open in new tabDownload slide Study Pathway. Figure 1 Open in new tabDownload slide Study Pathway. VISNs are regional health systems comprised of rural and urban medical facilities that work to meet local healthcare needs and provide greater access to care.4 VISN 02 is the New York/New Jersey Healthcare Network composed of four VHA healthcare systems including Western New York, New Jersey, Hudson Valley, and New York Harbor. Each of these systems includes numerous outpatient clinics and medical centers. A chart review was performed on all identified patients, with follow-up through August 2018. We reviewed pathology reports and inpatient, outpatient, operative, and telephone notes. We queried pathology records to identify histology, stage, and grade of the tumor, as well as the presence of detrusor muscle. Focality and size of tumor were derived from the operative note of the initial TURBT. We used pathological and operative findings to assign risk group for the NMIBC patients based on the AUA Guidelines.2 We defined low-risk as patients with papillary urothelial neoplasm of low malignant potential (PUNLMP) or solitary low-grade (LG) Ta ≤3 cm; intermediate-risk as solitary LG Ta > 3 cm, multifocal LG Ta, high-grade (HG) Ta ≤3 cm, or LG T1; and high-risk as HG T1, multifocal or >3 cm HG Ta, any carcinoma in situ (CIS), or variant histology. We reviewed medical records to determine the use of repeat transurethral resection, use of induction and maintenance IVT, and utilization of computed topography abdominal/pelvic imaging at the time of diagnosis. Repeat TURBT was defined as any TURBT performed within 6 weeks of an initial TURBT for staging purposes before any treatment plan was decided. Induction IVT was defined as 6 weeks of induction intravesical bacillus calmette-guerin (BCG) or chemotherapy within 6 weeks of TURBT.2 Patients with a negative cystoscopy and cytology or a negative bladder biopsy after induction IVT were considered complete responders. Maintenance BCG status was defined as at least one 3-week course of IVT with the plan to continue a complete schedule specified in the Guidelines.2 CT imaging was considered if it was used in the initial evaluation for hematuria and/or staging purposes. We did not limit it to a certain time window from initial diagnosis. Statistical Analysis We calculated the percentage of initial TURBTs that included detrusor in the sample, and stratified this by NMIBC risk group. We calculated percentage of T1, HG T1, and high-risk, high-grade Ta patients that underwent repeat resection. We also calculated rates of repeat TURBT for each NMIBC risk group and for patients who did not have muscle in the initial TURBT. We calculated the percentage of patients in each NMIBC risk group that received IVT. We also described the percentage of BCG responders who received at least one maintenance course of BCG. We used the straight-line measure function in Google Maps to calculate distance from the patient’s home address to the VAMC of bladder cancer diagnosis. This measure has been previously validated.9 We performed a logistic regression analysis to test if distance to diagnosing VAMC from the patient’s home was related to receipt of induction IVT for high-risk NMIBC patients. We considered age and comorbidity as covariates and p < 0.05 statistically significant. All statistics were performed with R. RESULTS We identified 121 newly-diagnosed NMIBC patients (Table I). All patients were male with a median age of 71 (IQR = 68–80). The majority (79%) had a smoking history. The Western New York system made up 64% of the cohort as it consists of 3 large medical centers (Buffalo, Albany, and Syracuse). New York Harbor comprised the least at 8% with the Manhattan medical center contributing the vast majority to this system. More than half had an Elixhauser comorbidity score of 3+. According to AUA NMIBC risk group, 19/121 (16%) were low-risk, 34/121 (28%) were intermediate-risk, and 68/121 (56%) were high-risk. Ninety three patients (77%) had computed topography (CT) imaging of the abdomen and pelvis performed for evaluation or staging, of which 84 (90%) were contrasted studies. Table I Patient Characteristics (N = 121) Characteristic N (%) Age Median Age [IQR] 71 [68–80] Gender Male 121 (100) Healthcare System Western New York 78 (64) Hudson Valley 19 (16) New Jersey 14 (12) New York Harbor 10 (8) Race Caucasian 107 (88) African American 9 (8) Other 5 (4) Smoking Status Never Smoker 25 (21) Smoker 96 (79) Current Smoker 36 (38) Former Smoker 60 (62) Elixhauser Index 0 15 (12) 1 17 (14) 2 20 (17) 3+ 69 (57) CT Imaging Yes 93 (77) Contrast 84 (90) TURBT Stage PUNLMP 2 (1) Ta 60 (50) Any T1 52 (43) T1 + cis 10 (8) Any cis 17 (14) Grade High 75 (62) Low 46 (38) Focality Unifocal 63 (52) Multifocal 58 (48) NMIBC Risk Group High 68 (56) Intermediate 34 (28) Low 19 (16) Characteristic N (%) Age Median Age [IQR] 71 [68–80] Gender Male 121 (100) Healthcare System Western New York 78 (64) Hudson Valley 19 (16) New Jersey 14 (12) New York Harbor 10 (8) Race Caucasian 107 (88) African American 9 (8) Other 5 (4) Smoking Status Never Smoker 25 (21) Smoker 96 (79) Current Smoker 36 (38) Former Smoker 60 (62) Elixhauser Index 0 15 (12) 1 17 (14) 2 20 (17) 3+ 69 (57) CT Imaging Yes 93 (77) Contrast 84 (90) TURBT Stage PUNLMP 2 (1) Ta 60 (50) Any T1 52 (43) T1 + cis 10 (8) Any cis 17 (14) Grade High 75 (62) Low 46 (38) Focality Unifocal 63 (52) Multifocal 58 (48) NMIBC Risk Group High 68 (56) Intermediate 34 (28) Low 19 (16) Open in new tab Table I Patient Characteristics (N = 121) Characteristic N (%) Age Median Age [IQR] 71 [68–80] Gender Male 121 (100) Healthcare System Western New York 78 (64) Hudson Valley 19 (16) New Jersey 14 (12) New York Harbor 10 (8) Race Caucasian 107 (88) African American 9 (8) Other 5 (4) Smoking Status Never Smoker 25 (21) Smoker 96 (79) Current Smoker 36 (38) Former Smoker 60 (62) Elixhauser Index 0 15 (12) 1 17 (14) 2 20 (17) 3+ 69 (57) CT Imaging Yes 93 (77) Contrast 84 (90) TURBT Stage PUNLMP 2 (1) Ta 60 (50) Any T1 52 (43) T1 + cis 10 (8) Any cis 17 (14) Grade High 75 (62) Low 46 (38) Focality Unifocal 63 (52) Multifocal 58 (48) NMIBC Risk Group High 68 (56) Intermediate 34 (28) Low 19 (16) Characteristic N (%) Age Median Age [IQR] 71 [68–80] Gender Male 121 (100) Healthcare System Western New York 78 (64) Hudson Valley 19 (16) New Jersey 14 (12) New York Harbor 10 (8) Race Caucasian 107 (88) African American 9 (8) Other 5 (4) Smoking Status Never Smoker 25 (21) Smoker 96 (79) Current Smoker 36 (38) Former Smoker 60 (62) Elixhauser Index 0 15 (12) 1 17 (14) 2 20 (17) 3+ 69 (57) CT Imaging Yes 93 (77) Contrast 84 (90) TURBT Stage PUNLMP 2 (1) Ta 60 (50) Any T1 52 (43) T1 + cis 10 (8) Any cis 17 (14) Grade High 75 (62) Low 46 (38) Focality Unifocal 63 (52) Multifocal 58 (48) NMIBC Risk Group High 68 (56) Intermediate 34 (28) Low 19 (16) Open in new tab Detrusor was present in the initial TURBT in 80% (97/121) of all NMIBC patients, including 84% (57/68) of high-risk patients, 74% (25/34) of intermediate-risk patients, and 79% (15/19) of the low-risk patients (Table II). Repeat TURBT was performed in 56% (38/68) of all high-risk patients, 60% (31/52) of patients with any T1 disease, 70% (31/44) of patients with HG T1, and 29% (5/17) of high-risk Ta tumors. There were low rates of repeat TURBT in the low- and intermediate risk patients (5% and 9% respectively). The majority of the high-risk (8/11) and T1 (5/6) patients who did not have muscle in their initial resection specimen had a repeat TURBT. Induction IVT was given to 0% (0/19) of low-risk, 24% (8/34) of intermediate-risk, and 66% (45/68) of high-risk patients (Table II). Only one of the intermediate-risk patients received induction intravesical Mitomycin C for IVT, and the remainder of intermediate-risk and all high-risk patients received BCG. The majority (69%) of intermediate-risk patients who were not given induction IVT had LG Ta tumors. Three of the 53 patients who received induction IVT did not follow-up. Of those who did, 64% (32/50) had a complete response to induction IVT. Fifty nine percent (16/27) of high-risk BCG responders were initiated on maintenance BCG (Table II). Among high-risk patients who did not receive induction BCG (N = 23), 8 patients had documented reasons for not receiving treatment. Common reasons for not having induction IVT were long distance to VA (N = 6) and difficulty contacting the patient (N = 2). In the high-risk NMIBC patients, the mean distance to diagnosing VAMC from home address was 32.5 (±26.9) miles for those who received induction BCG compared to 33.4 miles (±30.2) miles for those who did not receive induction BCG. After adjusting for age and comorbidities, distance to diagnosing VAMC was not significantly associated with receipt of induction BCG on multivariate logistic regression (OR = 0.99, 95% CI [0.97–1.01], p = 0.52). Table II Rates of Detrusor in the Initial TURBT Specimen, Use of Repeat TURBT, and Use of Induction and Maintenance IVT by NMIBC Risk Group Risk group Detrusor present Repeat TURBT Induction IVT Maintenance BCG N (%) N (%) N (%) N (%) High (N = 68) 57 (84) 38 (56) 45 (66) 16 (59)† Intermediate (N = 34) 25 (74) 3 (9) 8 (24) 2 (40)‡ Low (N = 19) 15 (79) 1 (5) 0 (0) NA Risk group Detrusor present Repeat TURBT Induction IVT Maintenance BCG N (%) N (%) N (%) N (%) High (N = 68) 57 (84) 38 (56) 45 (66) 16 (59)† Intermediate (N = 34) 25 (74) 3 (9) 8 (24) 2 (40)‡ Low (N = 19) 15 (79) 1 (5) 0 (0) NA † of the 27 high-risk NMIBC who responded to induction IVT. ‡ of the 5 intermediate-risk NMIBC who responded to induction IVT. Open in new tab Table II Rates of Detrusor in the Initial TURBT Specimen, Use of Repeat TURBT, and Use of Induction and Maintenance IVT by NMIBC Risk Group Risk group Detrusor present Repeat TURBT Induction IVT Maintenance BCG N (%) N (%) N (%) N (%) High (N = 68) 57 (84) 38 (56) 45 (66) 16 (59)† Intermediate (N = 34) 25 (74) 3 (9) 8 (24) 2 (40)‡ Low (N = 19) 15 (79) 1 (5) 0 (0) NA Risk group Detrusor present Repeat TURBT Induction IVT Maintenance BCG N (%) N (%) N (%) N (%) High (N = 68) 57 (84) 38 (56) 45 (66) 16 (59)† Intermediate (N = 34) 25 (74) 3 (9) 8 (24) 2 (40)‡ Low (N = 19) 15 (79) 1 (5) 0 (0) NA † of the 27 high-risk NMIBC who responded to induction IVT. ‡ of the 5 intermediate-risk NMIBC who responded to induction IVT. Open in new tab DISCUSSION The 2016 American Urological Association Guidelines on the Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer provides recommendations on disease risk stratification, use of repeat TURBT, and administration of induction and maintenance IVT.2 Several of these metrics have been endorsed as quality measures, as they are associated with improved disease staging and control.10 Still, non-guideline concordant NMIBC treatment and evaluation is common.7,11,12 In the non-VA population, a large retrospective study using the SEER-Medicare database observed that astonishingly few patients received complete guideline-concordant care, including use of radiologic imaging and utilization of IVT, and this was largely attributed to surgeon variation.7 Witjes et al.12 reported that although 50% of high-risk NMIBC patients received intravesical BCG, 12.5% also received intravesical chemotherapy which has been shown to be inferior to BCG13–15 and not recommended in the current guidelines. Non-adherence to guideline care for patients with NMIBC puts patients at higher risk for recurrence and progression. Prior to our study, there was limited information on the quality of NMIBC care among US Veterans. Detrusor muscle in the specimen is a measure of resection quality, since the presence of muscle in the pathologic specimen decreases the risk of under-staging and lowers recurrence rates.3 We found that 80% of NMIBC patients had detrusor muscle sampled in their initial resection. This is similar to the 60–70% reported in prior cohort studies.3,16 While we expected that surgeons would sample detrusor less often for low-risk patients, as has previously been reported,3,17 we observed a high rate (79%) of detrusor sampling for this group. Given the 15–30% risk of understaging, and the nearly 50% risk of residual disease after a visually complete resection,18–22 the AUA Guidelines recommend a restaging TURBT for all T1 patients, especially those without muscle in the initial resection, and to consider a repeat TURBT for high-risk Ta disease.2 Repeat TURBT not only improves initial staging, but also improves response to IVT.23,24 We observed that 60% of patients with T1 disease had a repeat TURBT and 83% of T1 patients without muscle in the original specimen had a repeat TURBT. The use of repeat TURBT for high-risk Ta was considerably lower at 29%. It was reassuring to observe that the majority of the high-risk (8/11) and T1 (5/6) patients who did not have muscle in their initial resection specimen had a repeat TURBT. Although some have suggested that repeat TURBT should have a more limited role if the initial TURBT was done by experienced surgeons and muscle was obtained, others have proposed a benchmark of 90% utilization of repeat TURBT in patients with higher risk NMIBC.10,19 A retrospective study of 600 HG T1 patients using the Alberta Cancer Registry found that only 28% had an early repeat TURBT, with a modest increase in utilization over time, from 27.4% in 2007 to 37.8% in 2011.25 An Australian group reported a similar rate at 22.4% for 380 HG Ta and any T1 specimens.26 A large population based study of Medicare beneficiaries in the US reported an even lower rate of 7.9% of T1 patients undergoing a repeat TURBT.27 While there may be an opportunity to improve the use of repeat TURBT among Veterans with HG T1, we observed high utilization relative to what has been reported in other large non-VA cohorts. The AUA Guidelines recommend induction intravesical BCG for patients with high-risk disease and consideration of intravesical BCG or chemotherapy for patients with intermediate-risk disease.2 We observed that 66% of high-risk NMIBC patients appropriately received induction BCG. This finding meets a proposed quality benchmark of at least 60%.10 A retrospective study using the SEER-Medicare database found that less than 40% of patients ≥65 years old with poorly differentiated or undifferentiated NIMBC were treated with BCG within 6 months of diagnosis.28 The use of induction IVT in intermediate-risk NMIBC patients is more controversial due to the heterogeneity within the group.2,29 We observed 24% of the intermediate-risk patients received induction BCG. It has been shown that additional dosages of intravesical chemotherapy do not offer recurrence or progression benefits for low-risk NMIBC,30,31 and appropriately, none of the low-risk patients had induction therapy administered. Our findings suggest relatively high utilization of induction IVT among the highest risk patients in our cohort. Maintenance BCG should be offered to NMIBC patients who respond to induction therapy.2,32 We observed a response rate to induction IVT similar to what has been reported by others.33–35 We also found that 59% of the high-risk BCG responders were given at least one dose of maintenance therapy. A large retrospective cohort study using the SEER-Medicare dataset reported that only 7.5% of patients received any maintenance BCG.36 We sought to identify the reasons patients did not receive IVT when it was indicated. Albeit among a small group of patients, the most common documented reasons for not receiving induction BCG among high-risk patients were long distance to a VA medical center and inability of the treating physician to contact the patient. Given the centralization of the VA system, there may be patients who have difficulty accessing care due to their location of residence. This is especially important in the management of NMIBC where certain treatments, such as TURBT and IVT, may not be available at all VA facilities. We hypothesized that patient location would impact receipt of IVT, but did not observe a statistically significant difference in receipt of induction BCG according to distance from the diagnosing VAMC. Further study is required to identify barriers to receipt of induction and maintenance BCG from a surgeon and patient level. Our study is not without limitations. Our cohort is relatively small in numbers, which limits the precision of the results. Also, our findings are not directly generalizable to the national VA cohort as our cohort is based in a single geographic region in the Northeast. We relied upon operative notes to help assign NMIBC risk group, however certain disease characteristics may not have been documented consistently. Our follow-up was limited to one year, and therefore we could not report on completion of maintenance therapy. We estimated patient distance to VAMC using straight line distance, which may not correlate well with travel time. Further, we estimated patient distance to the hospital that diagnosed their bladder cancer as a possible exposure for non-receipt of IVT, although distance to a closer satellite VA facility that had the capacity to administer IVT may have been a more appropriate measure. Finally, as this is not a comparative study, it is not possible to determine if our findings are different from non-VA NMIBC patients living in the same region. CONCLUSIONS Among a regional cohort of US Veterans with NMIBC, we observed high rates of sampling of detrusor in the first TURBT specimen, utilization of repeat TURBT, and administration of induction and maintenance intravesical BCG for high-risk patients. While not a comparative study, our findings suggest high quality NMIBC care in VA VISN 02. The views expressed are solely those of the authors and do not reflect the official policy or position of the US Army, US Navy, US Air Force, the Department of Defense, or the US Government. References 1. Siegel RL , Miller KD , Jemal A : Cancer Statistics, 2017 . CA Cancer J Clin 2017 ; 67 ( 1 ): 7 – 30 . Google Scholar Crossref Search ADS PubMed WorldCat 2. Chang SS , Boorjian SA , Chou R , et al. : Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO Guideline . J Urol 2016 ; 196 ( 4 ): 1021 – 1029 . Google Scholar Crossref Search ADS PubMed WorldCat 3. Mariappan P , Zachou A , Grigor KM , Edinburgh Uro-Oncology G : Detrusor muscle in the first, apparently complete transurethral resection of bladder tumor specimen is a surrogate marker of resection quality, predicts risk of early recurrence, and is dependent on operator experience . Eur Urol 2010 ; 57 ( 5 ): 843 – 9 . Google Scholar Crossref Search ADS PubMed WorldCat 4. Affairs USDoV . National Center for Veterans Analysis and Statistics. https://www.va.gov/vetdata/. Accessed May, 2019. 5. Zullig LL , Sims KJ , McNeil R , et al. : Cancer incidence among patients of the U.S. veterans affairs health care system: 2010 Update . Mil Med 2017 ; 182 ( 7 ): e1883 – 91 . Google Scholar Crossref Search ADS PubMed WorldCat 6. Chang SS , Bochner BH , Chou R , et al. : Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/ASTRO/SUO Guideline . J Urol 2017 ; 198 ( 3 ): 552 – 9 . Google Scholar Crossref Search ADS PubMed WorldCat 7. Chamie K , Saigal CS , Lai J , et al. : Compliance with guidelines for patients with bladder cancer: variation in the delivery of care . Cancer. 2011 ; 117 ( 23 ): 5392 – 5401 . Google Scholar Crossref Search ADS PubMed WorldCat 8. van Walraven C , Austin PC , Jennings A , Quan H , Forster AJ : A modification of the Elixhauser comorbidity measures into a point system for hospital death using administrative data . Med Care 2009 ; 47 ( 6 ): 626 – 33 . Google Scholar Crossref Search ADS PubMed WorldCat 9. Boscoe FP , Henry KA , Zdeb MS : A nationwide comparison of driving distance versus straight-line distance to hospitals . Prof Geogr 2012 ; 64 ( 2 ):188–96. WorldCat 10. Montgomery JS , Miller DC , Weizer AZ : Quality indicators in the management of bladder cancer . J Natl Compr Canc Netw 2013 ; 11 ( 4 ): 492 – 500 . Google Scholar Crossref Search ADS PubMed WorldCat 11. 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Military Medicine – Oxford University Press

Published: Feb 13, 2020

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