- Email: [email protected]
Comparative Evaluation of Bladder-specific Health-related Quality of Life Instruments for Bladder Cancer
Accepted Manuscript Title: Comparative Evaluation of Bladder Specific Health Related Quality of Life (HRQOL) Instruments for Bladder Cancer Author: Moncrief TJ, Balaji P, Lindgren B, Weight CJ, Konety BR PII: DOI: Reference:
S0090-4295(17)30698-2 http://dx.doi.org/doi: 10.1016/j.urology.2017.06.032 URL 20530
To appear in:
Urology
Received date: Accepted date:
17-2-2017 20-6-2017
Please cite this article as: Moncrief TJ, Balaji P, Lindgren B, Weight CJ, Konety BR, Comparative Evaluation of Bladder Specific Health Related Quality of Life (HRQOL) Instruments for Bladder Cancer, Urology (2017), http://dx.doi.org/doi: 10.1016/j.urology.2017.06.032. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Comparative Evaluation of Bladder Specific Health Related Quality of Life (HRQOL) Instruments for Bladder Cancer Moncrief TJ, Balaji P, Lindgren B, Weight CJ, Konety BR University of Minnesota Department of Urology, Minneapolis, MN
Address correspondence to: Badrinath R Konety, MD Department of Urology MMC394 420 Delaware St Minneapolis, MN 55455 Ph: 612 625 1655 Fax: 612 624 4430 Email: [email protected]
Abstract Objective: To compare two bladder cancer specific health related quality of life instruments (HRQOL) in the same patient population. Previous HRQOL studies in cystectomy patients have yielded conflicting results. Using a cross sectional study design we examined the only two validated Bladder Cancer Specific (HRQOL) measures. METHODS: Of the 256 patients who had undergone (RC) from 2009-2014, 131 met both inclusion and exclusion criteria. The Functional Assessment Cancer Therapy-Vanderbilt Cystectomy Index (FACT-VCI) and Bladder Cancer Index (BCI) were mailed to these patients. Overall HRQOL and individual domain scores were compared between the two instruments with
1 Page 1 of 17
a Spearman correlation coefficient. HRQOL scores were compared by urinary diversion type as well using a non-parametric Wilcoxon rank sum test. RESULTS: The response rate of 49% with 31 IC and 33 ON patients. Overall, there was a moderate correlation between the FACT-VCI and BCI survey (r=0.57, p<0.001). Responses on the BCI domains were strongly correlated with responses on the bladder cancer specific domain of the FACT VCI (r=0.74, p<0.001). The BCI scores for urinary function were significantly better in the IC group (p=0.002). No significant difference was found between IC and ON using the FACT VCI. CONCLUSIONS: The FACT-VCI and BCI instruments correlate well within the same patient cohort but capture different aspects of HRQOL. By focusing exclusively on bladder cancer treatment concerns, the BCI appears to be a better tool for assessing and counseling patients on expected treatment specific changes after diversion type.
Key Words: cystectomy, health related quality of life, bladder cancer Word Count: Manuscript: 3433, Abstract: 240
Introduction: There will be an estimated 79,030 new cases of bladder cancer and 6870 will die as a result in 20171. For muscle invasive disease, radical cystectomy remains the gold standard for treatment followed by reconstruction with either an orthotopic neobladder (ON) or ileal conduit (IC). Both types of urinary diversion have been shown to result in similar outcomes in terms of perioperative complication rates, cancer recurrence and morbidity2–4. Continent diversion approaches such as ONs are thought to be preferable to IC due to a greater semblance to normal voiding4. As a result they are becoming increasingly common, especially at large tertiary care centers in carefully selected 2 Page 2 of 17
patients5. Remarkably, there is no consistent evidence in the health related quality of life (HRQOL) literature to support one diversion approach over another. The urologic oncology community has placed increasing emphasis on HRQOL to assess the psychological stressors and altered lifestyle patients experienced after different types of urinary diversion. HRQOL instruments attempt to quantify the impact a treatment type has on a patient’s health state taking into account physical, emotional, social and functional domains. Initially, HRQOL assessment is typically conducted in most studies using well established generic instruments that were developed to evaluate overall quality of life independent of disease state. A recent meta-analysis concluded that ON provides better HRQOL than IC but most of the assessments were performed using generic instruments and the magnitude of the difference was small6. There is concern that in exchange for their widespread applicability, generic HRQOL instruments may lose sensitivity in distinguishing disease specific effects of bladder cancer treatment that are important to patients. As a result several disease specific instruments have been developed and have subsequently been validated in an attempt to capture disease specific effects on quality of life. The two most widely accepted in the United States are the Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index (FACT-VCI) and the Bladder Cancer Index (BCI). To date the FACT-VCI and BCI are the only validated disease specific measures with known psychometric properties. However, there are several distinct differences between the two surveys. The BCI attempts to evaluate a broader swath of patients including those undergoing bladder sparing treatment and post radical cystectomy whereas the FACT-VCI is meant to only assess patients post radical cystectomy. The 3 Page 3 of 17
BCI also relies on treatment specific domains while the FACT-VCI includes several generic quality of life domains. To date, both instruments have been independently evaluated and validated but have not been compared within the same population which limits the ability to compare studies that have utilized these two instruments separately. A third HRQOL instrument (EORTC – QLQ-NMIBC24 and QLLQ-BLM30) that has versions to separately measure QOL in patients with NMIBC (QLQ-NMIBC24) and those post radical cystectomy (QLQ-BLM30) has been developed. It is undergoing validation through clinical trials of the EORTC and the complete validation has not yet been reported at the time of this study. Hence it was not included in the current study. The aim of the present study was to correlate the performance of the two available, validated, disease specific HRQOL instruments by evaluating each of the measures within the same patient cohort.
Materials and Methods: Patient Selection: Using an IRB approved institutional database, we identified 256 patients who had undergone a radical cystectomy with orthotopic neobladder or ileal conduit reconstruction for invasive bladder cancer at our institution between 2009-2014. We then selected those individuals who had completed at least one year of post-operative follow-up. Patients were excluded from the study if they had evidence of metastatic or recurrent disease, received adjuvant chemotherapy, were deceased or received radiation therapy to the pelvis. The 131 patients that met both inclusion and exclusion 4 Page 4 of 17
criteria were sent a mailing with a cover letter describing the study and providing instructions to complete the instrument questionnaires, a disease status and treatment history form, and two HRQOL instruments including two disease specific instrumentsthe FACT-VCI and the BCI enclosed. In the mailing the documents were consistently in the above order. A repeated mailing was sent 6 weeks after the initial mailing to nonresponders. Four weeks after the second mailing patients were contacted by phone to ask for their participation when possible. Study Instruments: Initial patient demographic information and disease related factors such as age, sex, DOB, stage of cancer at diagnosis and subsequent treatments were obtained via electronic medical record review. Updated information regarding patient condition and further treatment was obtained from a patient survey sent out with HRQOL instruments. Information was also obtained from the electronic medical records for patients who did not respond to the survey request to serve as a basis of comparison. This included patient demographic information, diversion type, cancer stage, use of neoadjuvant chemotherapy, postoperative course and continence status at last postoperative visit. Patient quality of life was measured using the self-administration of two previously validated bladder cancer specific HRQOL instruments. The FACT-VCI is a bladder specific instrument that is comprised of the Functional Assessment of Cancer TherapyGeneral form with the addition of 17 additional questions that pertain to bladder cancer specific quality of life. The questions are scored on a 5 point Likert score as previously described in the literature7,8. The BCI is an instrument that contains three disease
5 Page 5 of 17
specific domains (bladder, bowel, sexual domains) along with function and bother subdomains. The BCI is scored as a 5 point Likert scale as previously described in the literature9,10. Supplementary Figures 1 and 2 provide copies of the FACT VCI and BCI questions respectively. Statistical Analysis: Each domain score was calculated by determining the mean of the standardized items that comprised the domain. Higher scores represented better health states across all domains within each instrument. Likert scores range from 1 to 5 for the BCI and from 0 to 4 for the FACT VCI. The scoring is performed as previously described in the literature with a higher score denoting better quality of life for both instruments 7,11. Domain scores were omitted when greater than 20% of items within a domain were missing. Statistical analysis was performed using SPSS software (manufacturer). Spearman Correlation Coefficient scores were calculated for the total and five domains of the FACT-VCI questionnaire with the total and three domains of the BCI. For both instruments the total score is the sum of the individual domains where each domain is given equal weight. The ON and IC groups were then compared within each domain of both instruments using a non-parametric Wilcoxon rank sum test. Significance was defined at p<0.05. Demographic information including patient age, sex, race, income and education were also compared between the IC and ON groups with an unpaired two sample t-test. Clinical and pathologic outcomes were then compared between those who returned a
6 Page 6 of 17
questionnaire and those who did not using a two sample t-test for continuous variables and chi square test for categorical. Results: Patient Characteristics: Of the 256 patients initially identified using our database, 125 in total were excluded with surveys being sent to 131 total patients. Of the 125 patients excluded 66 were deceased, 40 had progressive disease and 19 had a history of prior radiation. 64 of the 131 patients returned completed questionnaires for a response rate of 49%. The demographic makeup of the participants is presented in Table 1. The ON group was significantly younger than the IC group. There were no other significant differences in socioeconomic status between the two groups. The overall median follow up time was 2.3 years (range: 3m-5yrs) Supplementary Table 1 summarizes and compares the patient characteristics of responders and non-responders. Of the non-responders the median length of follow up was 1.8 years (range: 3m-6yrs). The responders were younger and had a higher likelihood of lower stage disease. The non-responders had a higher likelihood of harboring T3 or greater disease as compared to the responders. Only a small percentage of the non-responders had node positive disease. There was no significant difference in complication rates between the two groups with lower grade complications predominating. From a review of the electronic medical records, fifty percent of nonresponders with ON had minimal to no incontinence defined as using 0-1 pads/day with relatively few (12%) having severe incontinence defined as use of >3 pads/day. Among 7 Page 7 of 17
the patients with neobladders, 12% experienced urinary retention requiring self catheterization. Correlation between Different HRQOL Instruments: Overall, there was a moderate correlation between the FACT-VCI and BCI survey (r=0.57, p<0.001). Comparison of individual domains between each survey revealed that responses on the BCI domains were strongly correlated with responses on the bladder cancer specific domain of the FACT VCI (r=0.74, p<0.001). In contrast the generic domains of the FACT-VCI showed weaker correlation with the BCI survey. The one exception was physical well-being which appeared to have a stronger correlation with the BCI survey (Table 2) IC vs ON with FACT-VCI: Figure 1 summarizes the scores between the IC and ON groups with the FACT-VCI. There was no statistically significant difference in all five domains between the two groups. Generally, both the IC and ON groups reported high scores within all five domains of the FACT VCI. IC vs ON with BCI: Figure 2 summarizes the scores between the IC and ON group with the BCI. There were no significant difference between groups for the total score (p=0.447), bowel habits (p=0.772), sexual function (p=0.172) or for the bowel and sexual function and bother subdomains (all p-values>0.127). However, the urinary function was significantly higher (better QOL) for IC than ON (p=0.002), as was the function subdomain
8 Page 8 of 17
(p<0.001), but not the bother subdomain (p=0.502). The sexually function was generally low and bowel function was generally high in both groups. Discussion: There is increasing interest in using bladder specific instruments when assessing HRQOL in patients after radical cystectomy, as they may better capture issues most relevant to this patient population12. There are no studies comparing different quality of life instruments in the same bladder cancer patient population. Two instruments; the FACT-VCI and BCI, are the only two validated bladder specific HRQOL instruments that have been described in the literature7–10. We administered both instruments within the same cohort to determine how well they correlated with one another. The FACT-VCI and BCI had a modest to strong correlation with each other. These results suggest that HRQOL following radical cystectomy and urinary diversion measured by the FACT-VCI and BCI yield similar overall results. The ultimate goal of defining quality of life in patients after undergoing radical cystectomy with reconstruction is to help define preoperative expectations for patients. The BCI appears to be a better tool for assessing and counseling patients on expected treatment specific changes after urinary diversion. In contrast the FACT portion of the VCI provides more general measures of HRQOL and failed to show any difference between the two groups. Each reconstruction option presents a unique set of challenges but likely affects quality of life to a similar magnitude. This likely accounts for the lack of difference in HRQOL found between IC and ON groups when using the FACT VCI. It would also explain why the disease specific questions of the FACT VCI
9 Page 9 of 17
correlate more strongly with the BCI than any other FACT VCI domain. Patients experience a trade off in disease related symptoms depending on whether they choose an IC or ON, but these symptoms appear to affect general quality of life to a similar magnitude. Therefore, it becomes more important for patients to understand what disease related symptoms can be expected prior to surgery so they can make an informed decision that maximizes their quality of life after surgery. In this context, we recommend the BCI as a better instrument for assessing quality of life in patients after cystectomy. Analysis of the BCI revealed significantly lower urinary function scores in the ON group but no statistically difference in urinary bother consistent with previously published works9,10. In addition there was no difference between ON and IC groups for each of the five domains of the FACT –VCI similar to what has been previously published7,8. These data suggest that although these two instruments generally correlate well with one another, there are specific aspects of bladder cancer that disease specific instruments can tease out. Namely, by separating the bladder cancer specific concerns into three domains the BCI provides insight into what aspects of reconstruction after radical cystectomy patients will find most distressing. It has also been postulated that the quality of life differences in urinary function as determined by the BCI may be attributed to preoperative expectations in ON patients13. These results would suggest that developing more standardized approaches to counseling patients prior to surgery may counter the reduced HRQOL experienced by some patients. To our knowledge there is no study to date addressing this.
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It is of interest that the BCI and FACT-VCI were strongly correlated despite having significant differences in both their composition and their specificity. The BCI is meant to be used in patients undergoing bladder sparing treatments and post radical cystectomy whereas the FACT-VCI is explicitly meant to measure differences in post radical cystectomy HRQOL. One reason for stronger correlation may be that questions in the BCI seem most applicable to radical cystectomy patients with few questions specifically addressing bladder sparing treatments. It has been noted that the BCI may be less useful in measuring HRQOL in patients undergoing bladder sparing treatments, but there is only limited data on bladder sparing treatment related quality of life to date7,14. It may also be that generic HRQOL factors such as family support, body image and selfconfidence are less sensitive and discriminatory than the bladder specific scales. By separating out several bladder specific domains the BCI may be able to better tease out which components to each patient’s quality of life are most significantly affected by urinary diversion choice. This suggests that the FACT-VCI remains less sensitive because it keeps the generic domains of the original FACT. Conversely, because worse symptoms do not necessarily equate to a worse quality of life the BCI bother scores may be the most important aspect of the instrument which were not statistically significant between the two groups. Additional larger scale prospective studies incorporating both surveys with pre and post treatment measurements would help to further define their applicability. There were several limitations to this study. Its retrospective design fails to account for the baseline quality of life of patients prior to surgery. However our purpose was to 11 Page 11 of 17
compare the two instruments at a single point in time and not to evaluate progressive change over time. We plan to do that in a future study. There have been several small prospective studies published to date13,15,16. Interestingly, a study using the BCI revealed that body image worsened immediately after surgery but improved over a one year period of time. It then stabilized to baseline for the IC group while the ON group never returned to baseline16. The patients who elected for ON were also younger and healthier on average than the IC group. Expectations for post treatment QOL may have been higher in the younger patients undergoing ON which may have led to a greater decrease in HRQOL in these patients post cystectomy. This may have led to a relatively higher QOL in the IC group. Another limitation was the lower response rate of around 50%. This limitation was mitigated by a chart review that showed the demographic, oncologic and functional characteristics of the non-responder group are similar to the general cystectomy population17,18. Of note, the non-responders were significantly older and had a higher stage than the responders but the magnitude of this difference was small. Another limitation is the small sample size which may impact the differences observed between the two groups. Another limitation is we do not have the reason for why non-responders failed to fill out the questionnaires and this introduces a non-response bias. Also, the demographic makeup of the participants was predominantly Caucasian males which reflect the demographic makeup of the surrounding population. However, caution should be exercised in extrapolating these results to other ethnic groups. Conclusions:
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Data from this study suggest that BCSHRQOL assessment can vary based on the instrument used. Specifically, the BCI appears to better capture the difference in HRQOL experienced by patients after RC. The comparative analysis between IC and ON was consistent with previous studies. We recommend the BCI as it appears to be better suited for capturing the differences in symptom specific quality of life in patients after cystectomy. This in turn allows for better preoperative counseling. These results need to be validated by larger prospective studies. References: 1.
Society AC: Bladder Cancer Statistics. 2016.
2.
Hautmann RE, Abol-Enein H, Hafez K, et al: Urinary diversion. Urology 2007; 69: 17–49.
3.
Cody JD, Nabi G, Dublin N, et al: Urinary diversion and bladder reconstruction/replacement using intestinal segments for intractable incontinence or following cystectomy. Cochrane Database Syst. Rev. 2012; 2:.
4.
Nagele U, Anastasiadis AG, Stenzl A, et al: Radical cystectomy with orthotopic neobladder for invasive bladder cancer: a critical analysis of long-term oncological, functional, and quality of life results. World J. Urol. 2012; 30: 725–32.
5.
Cooperberg MR, Porter MP and Konety BR: Candidate quality of care indicators for localized bladder cancer. Urol. Oncol. 2009; 27: 435–42.
6.
Cerruto MA, D’Elia C, Siracusano S, et al: Systematic review and meta-analysis of non RCT’s on health related quality of life after radical cystectomy using validated questionnaires: Better results with orthotopic neobladder versus ileal conduit. Eur. J. Surg. Oncol. 2015; 42.
7.
Anderson CB, Feurer ID, Large MC, et al: Psychometric characteristics of a condition-specific, health-related quality-of-life survey: the FACT-Vanderbilt Cystectomy Index. Urology 2012; 80: 77–83.
8.
Cookson MS, Dutta SC, Chang SAMS, et al: HEALTH RELATED QUALITY OF LIFE IN PATIENTS TREATED WITH RADICAL CYSTECTOMY AND URINARY DIVERSION FOR UROTHELIAL CARCINOMA OF THE BLADDER : DEVELOPMENT AND VALIDATION OF A NEW DISEASE SPECIFIC QUESTIONNAIRE. 2003; 170: 1926–1930.
9.
Gilbert SM, Wood DP, Dunn RL, et al: Measuring health-related quality of life outcomes in bladder cancer patients using the Bladder Cancer Index (BCI). Cancer 2007; 109: 1756–62. 13 Page 13 of 17
10.
Gilbert SM, Dunn RL, Hollenbeck BK, et al: Development and validation of the Bladder Cancer Index: a comprehensive, disease specific measure of health related quality of life in patients with localized bladder cancer. J. Urol. 2010; 183: 1764–9.
11.
Gilbert SM, Dunn RL, Hollenbeck BK, et al: Development and validation of the Bladder Cancer Index: a comprehensive, disease specific measure of health related quality of life in patients with localized bladder cancer. J. Urol. 2010; 183: 1764–9.
12.
Shih C and Porter MP: Health-related quality of life after cystectomy and urinary diversion for bladder cancer. Adv. Urol. 2011; 2011: 715892.
13.
Somani BK, Gimlin D, Fayers P, et al: Quality of life and body image for bladder cancer patients undergoing radical cystectomy and urinary diversion--a prospective cohort study with a systematic review of literature. Urology 2009; 74: 1138–43.
14.
Allareddy V, Kennedy J, West MM, et al: Quality of life in long-term survivors of bladder cancer. Cancer 2006; 106: 2355–62.
15.
Hardt J, Filipas D, Hohenfellner R, et al: Quality of life in patients with bladder carcinoma after cystectomy: first results of a prospective study. Qual. Life Res. 2000; 9: 1–12.
16.
Hedgepeth RC, Gilbert SM, He C, et al: Body image and bladder cancer specific quality of life in patients with ileal conduit and neobladder urinary diversions. Urology 2010; 76: 671–5.
17.
Yuh B, Wilson T, Bochner B, et al: Systematic review and cumulative analysis of oncologic and functional outcomes after robot-assisted radical cystectomy. Eur. Urol. 2015; 67: 402–422.
18.
Novara G, Catto JWF, Wilson T, et al: Systematic review and cumulative analysis of perioperative outcomes and complications after robot-assisted radical cystectomy. Eur. Urol. 2015; 67: 376–401.
Figure 1: Score range 0-4 A higher number represents a better state of health FACT-VCI: Functional Assessment of Cancer Therapy – Vanderbilt
14 Page 14 of 17
Figure 2: Score range 0-100 A higher number represents a better state of health BCI: Bladder Cancer Index
15 Page 15 of 17
Table 1: Comparative Profile of Patients in IC and ON Groups Characteristic Number Median Age Gender: Male Female
IC (%) 31 72
ON (%) 33 63
p<0.05
26(84%) 5(16%)
22(67%) 11(33%)
p=0.1121
p=0.0008
16 Page 16 of 17
Race: White Black Other
30(97%) 0 1(3%)
31(97%) 1(3%) 0
p=0.37
< $50,000 > or =$50,000
20(65%) 11(35%)
14(44%) 18(66%)
p=0.17
Less than High School High School College or Advanced Degree
5(16%) 14(45%) 12(39%)
7(22%) 16(50%) 9(28%)
p=0.64
19(61%) 12(39%)
22(69%) 10(31%)
P=0.21
Income level:
Education:
Living Status: Married Single IC: ileal conduit; ON: orthotopic neobladder
Table 2: Correlation of FACT-VCI and BCI FACT-VCI Domains
BCI Domains
Physical WellBeing
Social WellBeing
Emotional Functional Bladder WellWellSpecific Being Being Concerns
Urinary Domain
r=0.44
r=0.49
r=0.65
r=0.45
r=0.69
r=0.66
Bowel Domain
r=0.54
r=0.24
r=0.26
r=0.44
r=0.45
r=0.46
Sexual Domain
r=0.39
r=0.15
r=0.10
r=0.25
r=0.30
r=0.24
Total Score
r=0.66
r=0.40
r=0.42
r=0.53
r=0.74
r=0.57
Total Score
Spearman Correlation Coefficients for each domain comparing FACT-VCI and BCI
17 Page 17 of 17
S0090-4295(17)30698-2 http://dx.doi.org/doi: 10.1016/j.urology.2017.06.032 URL 20530
To appear in:
Urology
Received date: Accepted date:
17-2-2017 20-6-2017
Please cite this article as: Moncrief TJ, Balaji P, Lindgren B, Weight CJ, Konety BR, Comparative Evaluation of Bladder Specific Health Related Quality of Life (HRQOL) Instruments for Bladder Cancer, Urology (2017), http://dx.doi.org/doi: 10.1016/j.urology.2017.06.032. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Comparative Evaluation of Bladder Specific Health Related Quality of Life (HRQOL) Instruments for Bladder Cancer Moncrief TJ, Balaji P, Lindgren B, Weight CJ, Konety BR University of Minnesota Department of Urology, Minneapolis, MN
Address correspondence to: Badrinath R Konety, MD Department of Urology MMC394 420 Delaware St Minneapolis, MN 55455 Ph: 612 625 1655 Fax: 612 624 4430 Email: [email protected]
Abstract Objective: To compare two bladder cancer specific health related quality of life instruments (HRQOL) in the same patient population. Previous HRQOL studies in cystectomy patients have yielded conflicting results. Using a cross sectional study design we examined the only two validated Bladder Cancer Specific (HRQOL) measures. METHODS: Of the 256 patients who had undergone (RC) from 2009-2014, 131 met both inclusion and exclusion criteria. The Functional Assessment Cancer Therapy-Vanderbilt Cystectomy Index (FACT-VCI) and Bladder Cancer Index (BCI) were mailed to these patients. Overall HRQOL and individual domain scores were compared between the two instruments with
1 Page 1 of 17
a Spearman correlation coefficient. HRQOL scores were compared by urinary diversion type as well using a non-parametric Wilcoxon rank sum test. RESULTS: The response rate of 49% with 31 IC and 33 ON patients. Overall, there was a moderate correlation between the FACT-VCI and BCI survey (r=0.57, p<0.001). Responses on the BCI domains were strongly correlated with responses on the bladder cancer specific domain of the FACT VCI (r=0.74, p<0.001). The BCI scores for urinary function were significantly better in the IC group (p=0.002). No significant difference was found between IC and ON using the FACT VCI. CONCLUSIONS: The FACT-VCI and BCI instruments correlate well within the same patient cohort but capture different aspects of HRQOL. By focusing exclusively on bladder cancer treatment concerns, the BCI appears to be a better tool for assessing and counseling patients on expected treatment specific changes after diversion type.
Key Words: cystectomy, health related quality of life, bladder cancer Word Count: Manuscript: 3433, Abstract: 240
Introduction: There will be an estimated 79,030 new cases of bladder cancer and 6870 will die as a result in 20171. For muscle invasive disease, radical cystectomy remains the gold standard for treatment followed by reconstruction with either an orthotopic neobladder (ON) or ileal conduit (IC). Both types of urinary diversion have been shown to result in similar outcomes in terms of perioperative complication rates, cancer recurrence and morbidity2–4. Continent diversion approaches such as ONs are thought to be preferable to IC due to a greater semblance to normal voiding4. As a result they are becoming increasingly common, especially at large tertiary care centers in carefully selected 2 Page 2 of 17
patients5. Remarkably, there is no consistent evidence in the health related quality of life (HRQOL) literature to support one diversion approach over another. The urologic oncology community has placed increasing emphasis on HRQOL to assess the psychological stressors and altered lifestyle patients experienced after different types of urinary diversion. HRQOL instruments attempt to quantify the impact a treatment type has on a patient’s health state taking into account physical, emotional, social and functional domains. Initially, HRQOL assessment is typically conducted in most studies using well established generic instruments that were developed to evaluate overall quality of life independent of disease state. A recent meta-analysis concluded that ON provides better HRQOL than IC but most of the assessments were performed using generic instruments and the magnitude of the difference was small6. There is concern that in exchange for their widespread applicability, generic HRQOL instruments may lose sensitivity in distinguishing disease specific effects of bladder cancer treatment that are important to patients. As a result several disease specific instruments have been developed and have subsequently been validated in an attempt to capture disease specific effects on quality of life. The two most widely accepted in the United States are the Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index (FACT-VCI) and the Bladder Cancer Index (BCI). To date the FACT-VCI and BCI are the only validated disease specific measures with known psychometric properties. However, there are several distinct differences between the two surveys. The BCI attempts to evaluate a broader swath of patients including those undergoing bladder sparing treatment and post radical cystectomy whereas the FACT-VCI is meant to only assess patients post radical cystectomy. The 3 Page 3 of 17
BCI also relies on treatment specific domains while the FACT-VCI includes several generic quality of life domains. To date, both instruments have been independently evaluated and validated but have not been compared within the same population which limits the ability to compare studies that have utilized these two instruments separately. A third HRQOL instrument (EORTC – QLQ-NMIBC24 and QLLQ-BLM30) that has versions to separately measure QOL in patients with NMIBC (QLQ-NMIBC24) and those post radical cystectomy (QLQ-BLM30) has been developed. It is undergoing validation through clinical trials of the EORTC and the complete validation has not yet been reported at the time of this study. Hence it was not included in the current study. The aim of the present study was to correlate the performance of the two available, validated, disease specific HRQOL instruments by evaluating each of the measures within the same patient cohort.
Materials and Methods: Patient Selection: Using an IRB approved institutional database, we identified 256 patients who had undergone a radical cystectomy with orthotopic neobladder or ileal conduit reconstruction for invasive bladder cancer at our institution between 2009-2014. We then selected those individuals who had completed at least one year of post-operative follow-up. Patients were excluded from the study if they had evidence of metastatic or recurrent disease, received adjuvant chemotherapy, were deceased or received radiation therapy to the pelvis. The 131 patients that met both inclusion and exclusion 4 Page 4 of 17
criteria were sent a mailing with a cover letter describing the study and providing instructions to complete the instrument questionnaires, a disease status and treatment history form, and two HRQOL instruments including two disease specific instrumentsthe FACT-VCI and the BCI enclosed. In the mailing the documents were consistently in the above order. A repeated mailing was sent 6 weeks after the initial mailing to nonresponders. Four weeks after the second mailing patients were contacted by phone to ask for their participation when possible. Study Instruments: Initial patient demographic information and disease related factors such as age, sex, DOB, stage of cancer at diagnosis and subsequent treatments were obtained via electronic medical record review. Updated information regarding patient condition and further treatment was obtained from a patient survey sent out with HRQOL instruments. Information was also obtained from the electronic medical records for patients who did not respond to the survey request to serve as a basis of comparison. This included patient demographic information, diversion type, cancer stage, use of neoadjuvant chemotherapy, postoperative course and continence status at last postoperative visit. Patient quality of life was measured using the self-administration of two previously validated bladder cancer specific HRQOL instruments. The FACT-VCI is a bladder specific instrument that is comprised of the Functional Assessment of Cancer TherapyGeneral form with the addition of 17 additional questions that pertain to bladder cancer specific quality of life. The questions are scored on a 5 point Likert score as previously described in the literature7,8. The BCI is an instrument that contains three disease
5 Page 5 of 17
specific domains (bladder, bowel, sexual domains) along with function and bother subdomains. The BCI is scored as a 5 point Likert scale as previously described in the literature9,10. Supplementary Figures 1 and 2 provide copies of the FACT VCI and BCI questions respectively. Statistical Analysis: Each domain score was calculated by determining the mean of the standardized items that comprised the domain. Higher scores represented better health states across all domains within each instrument. Likert scores range from 1 to 5 for the BCI and from 0 to 4 for the FACT VCI. The scoring is performed as previously described in the literature with a higher score denoting better quality of life for both instruments 7,11. Domain scores were omitted when greater than 20% of items within a domain were missing. Statistical analysis was performed using SPSS software (manufacturer). Spearman Correlation Coefficient scores were calculated for the total and five domains of the FACT-VCI questionnaire with the total and three domains of the BCI. For both instruments the total score is the sum of the individual domains where each domain is given equal weight. The ON and IC groups were then compared within each domain of both instruments using a non-parametric Wilcoxon rank sum test. Significance was defined at p<0.05. Demographic information including patient age, sex, race, income and education were also compared between the IC and ON groups with an unpaired two sample t-test. Clinical and pathologic outcomes were then compared between those who returned a
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questionnaire and those who did not using a two sample t-test for continuous variables and chi square test for categorical. Results: Patient Characteristics: Of the 256 patients initially identified using our database, 125 in total were excluded with surveys being sent to 131 total patients. Of the 125 patients excluded 66 were deceased, 40 had progressive disease and 19 had a history of prior radiation. 64 of the 131 patients returned completed questionnaires for a response rate of 49%. The demographic makeup of the participants is presented in Table 1. The ON group was significantly younger than the IC group. There were no other significant differences in socioeconomic status between the two groups. The overall median follow up time was 2.3 years (range: 3m-5yrs) Supplementary Table 1 summarizes and compares the patient characteristics of responders and non-responders. Of the non-responders the median length of follow up was 1.8 years (range: 3m-6yrs). The responders were younger and had a higher likelihood of lower stage disease. The non-responders had a higher likelihood of harboring T3 or greater disease as compared to the responders. Only a small percentage of the non-responders had node positive disease. There was no significant difference in complication rates between the two groups with lower grade complications predominating. From a review of the electronic medical records, fifty percent of nonresponders with ON had minimal to no incontinence defined as using 0-1 pads/day with relatively few (12%) having severe incontinence defined as use of >3 pads/day. Among 7 Page 7 of 17
the patients with neobladders, 12% experienced urinary retention requiring self catheterization. Correlation between Different HRQOL Instruments: Overall, there was a moderate correlation between the FACT-VCI and BCI survey (r=0.57, p<0.001). Comparison of individual domains between each survey revealed that responses on the BCI domains were strongly correlated with responses on the bladder cancer specific domain of the FACT VCI (r=0.74, p<0.001). In contrast the generic domains of the FACT-VCI showed weaker correlation with the BCI survey. The one exception was physical well-being which appeared to have a stronger correlation with the BCI survey (Table 2) IC vs ON with FACT-VCI: Figure 1 summarizes the scores between the IC and ON groups with the FACT-VCI. There was no statistically significant difference in all five domains between the two groups. Generally, both the IC and ON groups reported high scores within all five domains of the FACT VCI. IC vs ON with BCI: Figure 2 summarizes the scores between the IC and ON group with the BCI. There were no significant difference between groups for the total score (p=0.447), bowel habits (p=0.772), sexual function (p=0.172) or for the bowel and sexual function and bother subdomains (all p-values>0.127). However, the urinary function was significantly higher (better QOL) for IC than ON (p=0.002), as was the function subdomain
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(p<0.001), but not the bother subdomain (p=0.502). The sexually function was generally low and bowel function was generally high in both groups. Discussion: There is increasing interest in using bladder specific instruments when assessing HRQOL in patients after radical cystectomy, as they may better capture issues most relevant to this patient population12. There are no studies comparing different quality of life instruments in the same bladder cancer patient population. Two instruments; the FACT-VCI and BCI, are the only two validated bladder specific HRQOL instruments that have been described in the literature7–10. We administered both instruments within the same cohort to determine how well they correlated with one another. The FACT-VCI and BCI had a modest to strong correlation with each other. These results suggest that HRQOL following radical cystectomy and urinary diversion measured by the FACT-VCI and BCI yield similar overall results. The ultimate goal of defining quality of life in patients after undergoing radical cystectomy with reconstruction is to help define preoperative expectations for patients. The BCI appears to be a better tool for assessing and counseling patients on expected treatment specific changes after urinary diversion. In contrast the FACT portion of the VCI provides more general measures of HRQOL and failed to show any difference between the two groups. Each reconstruction option presents a unique set of challenges but likely affects quality of life to a similar magnitude. This likely accounts for the lack of difference in HRQOL found between IC and ON groups when using the FACT VCI. It would also explain why the disease specific questions of the FACT VCI
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correlate more strongly with the BCI than any other FACT VCI domain. Patients experience a trade off in disease related symptoms depending on whether they choose an IC or ON, but these symptoms appear to affect general quality of life to a similar magnitude. Therefore, it becomes more important for patients to understand what disease related symptoms can be expected prior to surgery so they can make an informed decision that maximizes their quality of life after surgery. In this context, we recommend the BCI as a better instrument for assessing quality of life in patients after cystectomy. Analysis of the BCI revealed significantly lower urinary function scores in the ON group but no statistically difference in urinary bother consistent with previously published works9,10. In addition there was no difference between ON and IC groups for each of the five domains of the FACT –VCI similar to what has been previously published7,8. These data suggest that although these two instruments generally correlate well with one another, there are specific aspects of bladder cancer that disease specific instruments can tease out. Namely, by separating the bladder cancer specific concerns into three domains the BCI provides insight into what aspects of reconstruction after radical cystectomy patients will find most distressing. It has also been postulated that the quality of life differences in urinary function as determined by the BCI may be attributed to preoperative expectations in ON patients13. These results would suggest that developing more standardized approaches to counseling patients prior to surgery may counter the reduced HRQOL experienced by some patients. To our knowledge there is no study to date addressing this.
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It is of interest that the BCI and FACT-VCI were strongly correlated despite having significant differences in both their composition and their specificity. The BCI is meant to be used in patients undergoing bladder sparing treatments and post radical cystectomy whereas the FACT-VCI is explicitly meant to measure differences in post radical cystectomy HRQOL. One reason for stronger correlation may be that questions in the BCI seem most applicable to radical cystectomy patients with few questions specifically addressing bladder sparing treatments. It has been noted that the BCI may be less useful in measuring HRQOL in patients undergoing bladder sparing treatments, but there is only limited data on bladder sparing treatment related quality of life to date7,14. It may also be that generic HRQOL factors such as family support, body image and selfconfidence are less sensitive and discriminatory than the bladder specific scales. By separating out several bladder specific domains the BCI may be able to better tease out which components to each patient’s quality of life are most significantly affected by urinary diversion choice. This suggests that the FACT-VCI remains less sensitive because it keeps the generic domains of the original FACT. Conversely, because worse symptoms do not necessarily equate to a worse quality of life the BCI bother scores may be the most important aspect of the instrument which were not statistically significant between the two groups. Additional larger scale prospective studies incorporating both surveys with pre and post treatment measurements would help to further define their applicability. There were several limitations to this study. Its retrospective design fails to account for the baseline quality of life of patients prior to surgery. However our purpose was to 11 Page 11 of 17
compare the two instruments at a single point in time and not to evaluate progressive change over time. We plan to do that in a future study. There have been several small prospective studies published to date13,15,16. Interestingly, a study using the BCI revealed that body image worsened immediately after surgery but improved over a one year period of time. It then stabilized to baseline for the IC group while the ON group never returned to baseline16. The patients who elected for ON were also younger and healthier on average than the IC group. Expectations for post treatment QOL may have been higher in the younger patients undergoing ON which may have led to a greater decrease in HRQOL in these patients post cystectomy. This may have led to a relatively higher QOL in the IC group. Another limitation was the lower response rate of around 50%. This limitation was mitigated by a chart review that showed the demographic, oncologic and functional characteristics of the non-responder group are similar to the general cystectomy population17,18. Of note, the non-responders were significantly older and had a higher stage than the responders but the magnitude of this difference was small. Another limitation is the small sample size which may impact the differences observed between the two groups. Another limitation is we do not have the reason for why non-responders failed to fill out the questionnaires and this introduces a non-response bias. Also, the demographic makeup of the participants was predominantly Caucasian males which reflect the demographic makeup of the surrounding population. However, caution should be exercised in extrapolating these results to other ethnic groups. Conclusions:
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Data from this study suggest that BCSHRQOL assessment can vary based on the instrument used. Specifically, the BCI appears to better capture the difference in HRQOL experienced by patients after RC. The comparative analysis between IC and ON was consistent with previous studies. We recommend the BCI as it appears to be better suited for capturing the differences in symptom specific quality of life in patients after cystectomy. This in turn allows for better preoperative counseling. These results need to be validated by larger prospective studies. References: 1.
Society AC: Bladder Cancer Statistics. 2016.
2.
Hautmann RE, Abol-Enein H, Hafez K, et al: Urinary diversion. Urology 2007; 69: 17–49.
3.
Cody JD, Nabi G, Dublin N, et al: Urinary diversion and bladder reconstruction/replacement using intestinal segments for intractable incontinence or following cystectomy. Cochrane Database Syst. Rev. 2012; 2:.
4.
Nagele U, Anastasiadis AG, Stenzl A, et al: Radical cystectomy with orthotopic neobladder for invasive bladder cancer: a critical analysis of long-term oncological, functional, and quality of life results. World J. Urol. 2012; 30: 725–32.
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Cooperberg MR, Porter MP and Konety BR: Candidate quality of care indicators for localized bladder cancer. Urol. Oncol. 2009; 27: 435–42.
6.
Cerruto MA, D’Elia C, Siracusano S, et al: Systematic review and meta-analysis of non RCT’s on health related quality of life after radical cystectomy using validated questionnaires: Better results with orthotopic neobladder versus ileal conduit. Eur. J. Surg. Oncol. 2015; 42.
7.
Anderson CB, Feurer ID, Large MC, et al: Psychometric characteristics of a condition-specific, health-related quality-of-life survey: the FACT-Vanderbilt Cystectomy Index. Urology 2012; 80: 77–83.
8.
Cookson MS, Dutta SC, Chang SAMS, et al: HEALTH RELATED QUALITY OF LIFE IN PATIENTS TREATED WITH RADICAL CYSTECTOMY AND URINARY DIVERSION FOR UROTHELIAL CARCINOMA OF THE BLADDER : DEVELOPMENT AND VALIDATION OF A NEW DISEASE SPECIFIC QUESTIONNAIRE. 2003; 170: 1926–1930.
9.
Gilbert SM, Wood DP, Dunn RL, et al: Measuring health-related quality of life outcomes in bladder cancer patients using the Bladder Cancer Index (BCI). Cancer 2007; 109: 1756–62. 13 Page 13 of 17
10.
Gilbert SM, Dunn RL, Hollenbeck BK, et al: Development and validation of the Bladder Cancer Index: a comprehensive, disease specific measure of health related quality of life in patients with localized bladder cancer. J. Urol. 2010; 183: 1764–9.
11.
Gilbert SM, Dunn RL, Hollenbeck BK, et al: Development and validation of the Bladder Cancer Index: a comprehensive, disease specific measure of health related quality of life in patients with localized bladder cancer. J. Urol. 2010; 183: 1764–9.
12.
Shih C and Porter MP: Health-related quality of life after cystectomy and urinary diversion for bladder cancer. Adv. Urol. 2011; 2011: 715892.
13.
Somani BK, Gimlin D, Fayers P, et al: Quality of life and body image for bladder cancer patients undergoing radical cystectomy and urinary diversion--a prospective cohort study with a systematic review of literature. Urology 2009; 74: 1138–43.
14.
Allareddy V, Kennedy J, West MM, et al: Quality of life in long-term survivors of bladder cancer. Cancer 2006; 106: 2355–62.
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Hardt J, Filipas D, Hohenfellner R, et al: Quality of life in patients with bladder carcinoma after cystectomy: first results of a prospective study. Qual. Life Res. 2000; 9: 1–12.
16.
Hedgepeth RC, Gilbert SM, He C, et al: Body image and bladder cancer specific quality of life in patients with ileal conduit and neobladder urinary diversions. Urology 2010; 76: 671–5.
17.
Yuh B, Wilson T, Bochner B, et al: Systematic review and cumulative analysis of oncologic and functional outcomes after robot-assisted radical cystectomy. Eur. Urol. 2015; 67: 402–422.
18.
Novara G, Catto JWF, Wilson T, et al: Systematic review and cumulative analysis of perioperative outcomes and complications after robot-assisted radical cystectomy. Eur. Urol. 2015; 67: 376–401.
Figure 1: Score range 0-4 A higher number represents a better state of health FACT-VCI: Functional Assessment of Cancer Therapy – Vanderbilt
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Figure 2: Score range 0-100 A higher number represents a better state of health BCI: Bladder Cancer Index
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Table 1: Comparative Profile of Patients in IC and ON Groups Characteristic Number Median Age Gender: Male Female
IC (%) 31 72
ON (%) 33 63
p<0.05
26(84%) 5(16%)
22(67%) 11(33%)
p=0.1121
p=0.0008
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Race: White Black Other
30(97%) 0 1(3%)
31(97%) 1(3%) 0
p=0.37
< $50,000 > or =$50,000
20(65%) 11(35%)
14(44%) 18(66%)
p=0.17
Less than High School High School College or Advanced Degree
5(16%) 14(45%) 12(39%)
7(22%) 16(50%) 9(28%)
p=0.64
19(61%) 12(39%)
22(69%) 10(31%)
P=0.21
Income level:
Education:
Living Status: Married Single IC: ileal conduit; ON: orthotopic neobladder
Table 2: Correlation of FACT-VCI and BCI FACT-VCI Domains
BCI Domains
Physical WellBeing
Social WellBeing
Emotional Functional Bladder WellWellSpecific Being Being Concerns
Urinary Domain
r=0.44
r=0.49
r=0.65
r=0.45
r=0.69
r=0.66
Bowel Domain
r=0.54
r=0.24
r=0.26
r=0.44
r=0.45
r=0.46
Sexual Domain
r=0.39
r=0.15
r=0.10
r=0.25
r=0.30
r=0.24
Total Score
r=0.66
r=0.40
r=0.42
r=0.53
r=0.74
r=0.57
Total Score
Spearman Correlation Coefficients for each domain comparing FACT-VCI and BCI
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