Quality of Life in Bladder Cancer Patients

Chapter 28

Quality of Life in Bladder Cancer Patients Chang Wook Jeong Seoul National University Hospital, Seoul, South Korea

Chapter Outline Introduction Health-Related QoL Measurement Utilities and Disutilities Associated With Bladder Cancer Related Conditions Impact of Bladder Cancer Diagnosis on HRQOL Non-Muscle-Invasive Bladder Cancer Radical Cystectomy for Muscle-Invasive Bladder Cancer

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509 511 511

Bladder Preservation Therapy and Robotic Surgery for Muscle-Invasive Bladder Cancer 517 Chemotherapy for Advanced or Metastatic Bladder Cancer 517 QoL in Long-Term Survivors 519 Conclusion 519 References 519

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INTRODUCTION Bladder cancer is the ninth most common cancer, worldwide, with an estimated 430,000 new cases diagnosed in 2012 [1]. In the United States, it is the fourth most common cancer, with 76,960 new cases estimated to be diagnosed during 2016 [2]. Because more than 70% of patients with bladder cancer are initially diagnosed with non-muscle-invasive cancer, there are many bladder cancer survivors. An estimated 765,950 bladder cancer survivors live in the United States [3]. For non-muscle-invasive bladder cancers, transurethral resection of the bladder tumor (TURBT), followed by intravesical chemotherapy (22%) or immunotherapy with bacillus Calmette Guerin (BCG, 29%), is the most common treatment [3]. After surgery, surveillance, including regular cystoscopy, is crucial due to the high recurrence rate of non-muscle-invasive bladder cancers. For muscle-invasive disease, a combination of radical cystectomy, chemotherapy, and radiation therapy is a common treatment option. Such treatments can

Bladder Cancer. DOI: http://dx.doi.org/10.1016/B978-0-12-809939-1.00028-X © 2018 Elsevier Inc. All rights reserved.

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induce serious complications and greatly impact the patient’s body image and quality of life (QoL). For metastatic bladder cancers, chemotherapy is a potential therapy option; however, curative treatment is very rare and its efficacy is limited. For all cancer stages, combined, the 5-year overall survival rate is 77%. For in situ urinary bladder cancer, which accounts for 51% of cases, the 5-year relative survival rate is 96%. The 5-year survival rate is 70% (81% for those with non-muscle-invasive disease and 47% for those with muscleinvasive disease). Based on epidemiologic and treatment characteristics, QoL issues are noted to be very important for patients with bladder cancer. These issues can be summarized as follows: (1) surgical treatment varies from minimally invasive endoscopic surgery to complex radical cystectomy, which is associated with a substantial rate of serious complications; (2) the frequent recurrence of bladder cancer and the necessity of stringent surveillance might influence QoL; and (3) survival outcomes vary markedly, according to disease stage. Thus, preventing progression is very important. The clinician should consider not only the impact of the possible treatments but also their impact on the patient’s disease status and QoL. The ultimate treatment choice should be thoroughly discussed with the patient to ensure shared decision-making for this type of complex treatment scenario. However, QoL research among patients with bladder cancer has been minimal. In this review, we discuss QoL measurements, the impact of related conditions, and QoL comparisons for specific situations associated with bladder cancer.

HEALTH-RELATED QoL MEASUREMENT The World Health Organization defines health-related quality of life (HRQOL) as an individual’s perception of their position in life, within the context of their culture and value system and in relation to their goals, expectations, standards, and concerns [4]. HRQOL is a multidimensional concept that incorporates both the individual’s functional status and their perception of their health. HRQOL measurements are important patientcentered outcome parameters. However, a consensus does not exist regarding the measurement of QoL in patients with bladder cancer. This lack of consensus makes interstudy comparisons difficult. Questionnaires used to assess QoL in patients with bladder cancer can be categorized as general instruments, surgery-specific instruments, cancer-specific instruments, or bladder cancer specific instruments. General measures are intended to be relevant to a wide range of patient groups and are deliberately broad in their scope of assessed domains. Surgery-specific instruments measure postsurgical convalescence and its impact on QoL [5]; relatively short-term QoL measures can be evaluated and compared following various surgical techniques. Cancer-specific

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instruments have the advantage of addressing problems that are specific to a given cancer patient population and may permit cross-study comparisons. Bladder cancer specific instruments have recently become available; however, they have not been tested as extensively as other more generally applicable cancer-specific instruments. Additionally, almost all clinical QoL studies involving patients with bladder cancer have used ad hoc questionnaires with untested validity and reliability. The Functional Assessment of Cancer Therapy (FACT) Bladder Cancer (FACT-BL) instrument consists of the FACT-general version (FACT-G) plus 12 bladder cancer specific items (including incontinence, diarrhea, body image, sexual function, and stoma care) [6]. The FACT-Vanderbilt Cystectomy Index (FACT-VCI) was developed for patients following radical cystectomy [7]. It contains the FACT-G, with an additional 17 bladder cancer- and treatment-related items (including incontinence, diarrhea, body image, sexual function, and perception of patient status). The Bladder Cancer Index (BCI) instrument is applicable to all bladder cancer patients, independent of tumor course or treatment [8]. It assesses 36 items across three (urinary, bowel, and sexual) domains. The European Organization for Research and Treatment of Cancer (EORTC) developed two bladder cancer modules, a 24-item questionnaire (EORTC QLQ-NMIBC24) for patients with non-muscle-invasive bladder cancer (Ta, T1, carcinoma in situ) and a 30-item questionnaire (EORTC QLQ-BLM30) for patients with muscleinvasive bladder cancer (T2, T3, T4a, and T4b) [9]. The two modules share a number of common items and scales, including those assessing urinary and bowel symptoms and sexual functioning. The EORTC QLQ-NMIBC24 contains items assessing the side effects of intravesical treatment (fever, malaise, and the convenience and worry caused by repeated cystoscopies). The EORTC QLQ-BLM30 contains items assessing problems associated with urostomy, catheter use, and body image. The currently available QoL instruments for patients with bladder cancer are listed in Table 28.1. In many HRQOL studies, a combination of bladder cancer specific and general and/or cancer-specific instruments are usually used. The purpose, number of questions, and validation of both the original and translated versions should be considered when selecting an instrument.

UTILITIES AND DISUTILITIES ASSOCIATED WITH BLADDER CANCER RELATED CONDITIONS Utilities represent a quantification of QoL adjustments, with perfect health assigned a value of 1.0 and death equal to 0. They represent the strength of a person’s preference for a health-related outcome, which is based on both the health state and survival duration. Utilities are clearly different from descriptive HRQOL measurements. HRQOL instruments are often summarized into scores representing several different domains, whereas a utility reflects how

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TABLE 28.1 Available HRQOL Instruments for Use in Bladder Cancer Instruments

No. of Items

General EuroQol (EQ) Five Dimensions Questionnaire (5D) and Visual Analog Scale (VAS)

5

RAND Short Form (36) Health Survey (SF-36)

36

Nottingham Health Profile (NHP)

38

Sickness Impact Profile (SIP)

136

Quality of well-being scale

18

Hospital Anxiety and Depression (HAD) scale

14

Beck Depression Inventory (BDI)

13

Profile of Mood States (POMS)

6

Psychosocial Adjustment to Illness Scale (PAIS)

45

Surgery-Specific Convalescence and Recovery Evaluation (CARE)

27

Cancer-Specific Functional Assessment of Cancer Therapy-general version (FACT-G)

28

European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)

30

Functional Living Index-Cancer (FLIC)

22

Cancer Inventory Problem Scale (CIPS)

145

Rotterdam Symptoms Checklist (RSCL)

34

Cancer Rehabilitation Evaluation System (CARES)

139

Cancer Rehabilitation Evaluation System-short form (CARES-SF)

59

Bladder Cancer Specific Functional Assessment of Cancer Therapy-Bladder Cancer (FACT-BL)

39

FACT-Vanderbilt Cystectomy Index (FACT-VCI) 30

45

Bladder Cancer Index (BCI)

36

EORTC-QLQ-NMIBC24 (non-muscle-invasive bladder cancer specific)

24

EORTC-QLQ-BLM30 (muscle-invasive bladder cancer specific)

30

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a respondent values a health state, not just the characteristics of that health state. Thus, a utility is a summarized, weighted value of the HRQOL for a certain health state. A utility is used to calculate quality-adjusted life years (QALYs), which are composite outcomes of survival and HRQOLs [10]. QALYs combine quality and quantity of life and the answer to the “How long a person lives, how well?” question. QALYs are fundamental outcomes for various qualityadjusted survival and medical decision analyses, such as clinical decision analyses, cost utility analyses, and cost effectiveness analyses. A utility value can be indirectly calculated using general, multiattribute utility instruments, such as EQ-5D, or converted using mapping formulae from disease-specific QoL instruments. However, a direct measurement would be more appropriate. Common methods for this include the standard gamble, time tradeoff, and visual analog rating scale [11]. Because of the lack of QoL-related studies in patients with bladder cancer, some utilities have been extrapolated from studies involving patients with similar conditions and complications. Table 28.2 presents published examples of bladder cancer related utility or disutility values used for QoL outcome research.

IMPACT OF BLADDER CANCER DIAGNOSIS ON HRQOL A cross-sectional study, from the United States, compared patient HRQOL measures before and after receiving a bladder cancer diagnosis [17]. Using the Surveillance, Epidemiology, and End Results (SEER) Medical Health Outcome Survey linkage database, between 1998 and 2007, 1476 patients with bladder cancer, 65 years or older, were selected. The study assessed differences in physical and mental component summary scores, before and after the bladder cancer diagnosis. The results showed statistically significant differences in physical and mental scores between the pre- and postdiagnosis scores. In patients with non-muscle-invasive bladder cancer, the physical and mental score differences were 21.9 (P , 0.01) and 21.4 (P 5 0.01), respectively. In those with muscle-invasive bladder cancer, there was a significant difference in the physical (25.3; P , 0.01) but not the mental score (22.7; P 5 0.07). This physical domain difference continued for 10 years after the diagnosis of muscle-invasive bladder cancer. Patients with bladder cancer, in addition to $ 4 comorbid medical conditions and $ 1 daily living activity deficit, were most at risk for low physical component summary scores.

NON-MUSCLE-INVASIVE BLADDER CANCER HRQOL studies involving patients with non-muscle-invasive bladder cancer are very rare. One prospective cohort study addressed HRQOL in this patient group [18]. A total of 244 patients from seven hospitals were followed for 1

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TABLE 28.2 Utility or Disutility Values Related to Bladder Cancer Reference

Condition

Utility or Disutility

Stevenson et al. [12]

Cystectomy (short term)

0.8

Post cystectomy (urinary diversion) state

0.96

TURBT

0.90

Chemotherapy

0.64

Disease recurrence or progression

0.62

Complications: prolonged ileus

0.65

Complications: small bowel obstruction with conservative management

0.65

Complications: small bowel obstruction with surgical intervention

0.55

Complications: total peripheral nutrition

0.65

Complications: atrial fibrillation/arrhythmia

0.99

Complications: delirium

0.51

Complications: urinary tract infection

0.73

Complications: fluid collection/abscess with conservative management

0.64

Complications: fluid collection/abscess with surgical intervention

0.64

Complications: fever not otherwise specified

0.64

Complications: pneumonia

0.85

Complications: urinary obstruction requiring percutaneous nephrostomy tube or stent

0.75

Complications: deep vein thrombosis

0.67

Complications: pulmonary embolism

0.62

Complications: impotence

0.9

Complications: incontinence

0.76

Complications: neutropenia

0.64

Complications: acute illness (cellulitis, line infection, wound infection)

0.64

Complications: severe illness and hospitalization (bacteremia, endocarditis, osteomyelitis, and septic shock)

0.53

Complications: acute sepsis

0.47 (Continued )

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TABLE 28.2 (Continued) Reference

Green et al. [13]

Kulkarni et al. [14,15]

Feenstra et al. [16]

Condition

Utility or Disutility

Complications: kidney infections

0.66

Complications: urinary or fecal fistula

0.68

TURBT

20.1

Cystoscopy

0.997

Fulguration

20.05

Cystectomy

0.8

GI complication after cystectomy

0.97

GU complication after cystectomy

0.93

Impotence after cystectomy

0.91

Metastases responsive to chemotherapy

0.62

Metastases unresponsive to chemotherapy

0.3

Surveillance cystoscopy

0.997

Postcystectomy state

0.96

Cystectomy complication

20.3

Chemotherapy

20.36

Chemotherapy complication

20.54

BCG therapy—induction

20.02

BCG complication

20.2

TURBT

20.10

TURBT for low risk Ta lesions

20.06

Bladder cancer in women

0.89

Bladder cancer in men

0.91

year using both a general instrument, the RAND Short Form-36 (SF-36), and a bladder cancer-specific instrument, the BCI. Physical health, measured using the SF-36, was comparable to the age-referenced US population group at baseline and during a 12-month follow-up. Mental health was significantly worse than the SF-36 reference values at the time of diagnosis (mean,

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49.7 vs. 53.3; 95% confidence interval [CI], 52.5 54.2). The urinary domain improved significantly after diagnosis (mean, 85.2; 95% CI, 82.9 87.4) to the 12-month evaluation (mean, 90.2; 95% CI, 87.7 92.8), whereas the sexual domain showed deterioration from a mean value of 56.4 (95% CI, 52.8 59.9) to 53.7 (95% CI, 50.0 57.4). The adjusted HRQOL score from baseline to the 12-month follow-up, estimated using generalized estimating equation models, showed improvement in the following parameters: urinary domain after TURBT with or without intravesical therapy (mean, 3.9; 95% CI, 0.1 7.7), bowel domain following TURBT and BCG therapy (mean, 7.0; 95% CI, 2.4 11.5), and sexual domain following TURBT and mitomycin C treatment (mean, 13.1; 95% CI, 5.9 20.2). A prospective, longitudinal, pilot study measured the HRQOL in 30 patients with non-muscle-invasive bladder cancer using the modified Munich Life Dimension List before, during, and after intravesical BCG therapy [19]. The results showed that although side effects occurred, QoL was not impaired. In a similar setting, Mack and Frick [20] attempted to determine the impact of BCG intravesical therapy on the physical, psychological, and social well-being of patients with non-muscle-invasive bladder cancer during the initial treatment cycle and during maintenance therapy. Although most patients had an acute QoL deterioration during induction, maintenance therapy was better tolerated. A Japanese multicenter research group performed a randomized controlled trial to compare efficacy, safety, and QoL outcomes following low-dose (40 mg) or standard-dose (80 mg) BCG instillation and induction therapy (weekly, eight times) [21]. They measured QoL using the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30). The noninferiority of low-dose BCG was not proven. However, low-dose BCG instillation was associated with lower toxicity and higher QoL compared with the standard dose. Another multicenter, prospective, randomized, Phase II study compared HRQOL measures in patients with non-muscle-invasive bladder cancer receiving adjuvant intravesical gemcitabine or one-third dose BCG [22]. The HRQOL-related effects were measured using the EORTC QLQ-C30 and QLQ-NMIBC24 questionnaires. Local and systemic side effects were more frequently reported in the BCG arm. However, multivariate analyses showed no significant differences between the two groups in any QoL dimension. Furthermore, no significant changes, over time, in the QoL domains were detected for patients on BCG and gemcitabine, except for physical functioning, which decreased significantly in both groups. Cost-effectiveness comparisons between office-based fulgurations and TURBT, with or without perioperative intravesical chemotherapy, for nonmuscle-invasive bladder cancer have been reported [13]. The study used a Markov state-transition model with 20 cycles, which is equivalent to 5 years of follow-up after the initial TURBT. The perioperative intravesical therapy with fulguration strategy showed the best QALY (14.50) and TURBT

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without intravesical therapy rendered the worst QALY (14.34). Fulguration without perioperative intravesical therapy was the most cost-effective strategy in this setting. The limitation of the study was its lack of direct utility data for TURBT and an oversimplification of the Markov model. Al Hussein Al Awamlh et al. reported a similar analysis comparing office-based fulguration with operating room based TURBT [23]. The results were similar; fulguration was both more effective (QALYs of 14.94 or 14.91, respectively) as well as less expensive ($17,494 vs $18,005, respectively) than TURBT. High-grade T1 bladder cancer carries a poor prognosis and higher incidences of recurrence and progression than other non-muscle-invasive bladder cancers. Thus, controversy continues to exist regarding whether a conservative or an aggressive treatment strategy is better. The conservative option involves intravesical instillation of BCG after TURBT. Patients who respond to BCG can preserve their bladders; however, they may also have worse oncologic outcomes. In fact, the 3-year recurrence and/or tumor progression rates are 80% and 35% 48%, respectively [24]. By contrast, early cystectomy offers the highest probability of disease-specific and overall survival but may be associated with worse QoL outcomes than the conservative management strategy. One clinical decision analysis addressed this issue using a base case of a 60-year-old man [14]. The mean QALYs for the early cystectomy and BCG treatment were 12.32 and 11.97, respectively. Worsening patient comorbidity diminished the benefit of early cystectomy but altered the QALY-based preferred treatment for patients older than 65 years. A sensitivity analysis showed that elderly (.70 years) patients and those strongly averse to the loss of sexual function, gastrointestinal dysfunction, or life without a bladder had higher QALYs following BCG intravesical therapy. Thus, the authors concluded that the decision should be based on discussions that consider patient age, comorbid status, and the individual’s preferences. The same research team expanded this issue to include a costeffectiveness analysis [15]. Early cystectomies in average patients with T1 high-grade bladder cancer demonstrated better QALYs and lower costs than BCG treatment. Early cystectomy was the dominant therapy for patients younger than 60 years, whereas BCG intravesical treatment was dominant for patients older than 75 years, in terms of cost-effectiveness. With increasing comorbidity, BCG treatment was more effective at lower age thresholds.

RADICAL CYSTECTOMY FOR MUSCLE-INVASIVE BLADDER CANCER QoL outcomes, following treatment for muscle invasive bladder cancer, have not been comprehensively studied, despite improved treatment outcomes. The majority of the published studies are retrospective with low levels of evidence.

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The most widely studied issue in muscle-invasive bladder cancer is QoL outcomes following radical cystectomy and urinary diversion. Because of its high complication rate and impacts on body image and sexual function, radical cystectomies may result in poorer QoL outcomes than many other cancer operations. The type of urinary diversion can also affect the patient’s postsurgical QoL. The ileal conduit has remained the most commonly performed urinary diversion technique; however, a variety of continent urinary diversions have been developed to provide better body image and QoL outcomes. Over the past decade, the orthotopic neobladder has become a clinically accepted alternative to the ileal conduit. Of course, both have advantages and disadvantages. The ileal conduit procedure usually has a lower complication rate, shorter operating time, and a reduced hospital stay than orthotopic neobladder surgery. However, patients undergoing an ileal conduit procedure, after cystectomy, may be psychologically affected due to body image concerns associated with the stoma. A Cochrane review of randomized or quasi-randomized controlled trials on this issue did not find any evidence that bladder replacement was better than the use of an ileal conduit [25]. Only five studies met the inclusion criteria, involving a total of 355 patients. These were small, moderate, or poor quality studies, and they reported few of the preselected outcome measures. A more recent systematic review and meta-analysis compared the QoL after continent versus incontinent urinary diversion in radical cystectomy patients [26]. Twenty-nine studies, involving 3754 patients, were selected for review. The patients reported poor postsurgical urinary and sexual functioning, compared with the general population. However, the overall QoL outcomes were similar between the two groups. A subgroup analysis demonstrated a greater improvement in physical health associated with incontinent, compared to continent diversions but no differences in mental and social health. Qualitative analyses showed that patients with orthotopic neobladders had superior emotional functioning and body image, compared with those undergoing cutaneous diversions. The authors concluded that the patient’s preference should be a key factor in the diversion type selection. A prospective cohort study evaluated QoL and body image for patients with bladder cancer undergoing radical cystectomy [27]. The EORTC QLQC30 and the Satisfaction with Life Scale (SWLS) questionnaires were administered before and 9 12 months after surgery. There was no significant change in the overall QoL evident with either the EORTC QLQ-C30 or the SWLS. Family, relationships, health, and finance were the most important determinants of QoL, whereas body image was not mentioned. Thus, the authors suggested that health and body image may not be important QoL considerations for patients undergoing cystectomy. One cross-sectional survey study assessed QoL predictors after ileal conduit surgery [28]. Poor sexual life satisfaction was common among responders.

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Social support and stoma self-management were associated with improved QoL measures. Female gender, younger age (,60 years), continuing to work, higher family income, longer postoperative periods, and the absence of stoma complications were predictors of better QoL outcomes.

BLADDER PRESERVATION THERAPY AND ROBOTIC SURGERY FOR MUSCLE-INVASIVE BLADDER CANCER A multimodal strategy, using radical TURBT, chemotherapy, and radiation, may be an alternative to radical cystectomy in selected patients. Some patients may experience disease progression, but many remain disease-free with intact bladders. Thus, this approach is claimed to provide favorable HRQOL outcomes; however, only a small number of retrospective studies have been reported, to date [29 31]. The overall HRQOL in the bladder preservation group was reported to be higher than in the radical cystectomy group [29,30]. However, patients undergoing this treatment had lower QoL scores than did patients with non-muscle-invasive bladder cancer who underwent TURBT [31]. Robot-assisted radical cystectomy (RARC) is another modality that is gaining traction as a surgical approach for patients with muscle-invasive bladder cancer. However, only one retrospective study has evaluated HRQOL impacts and short-term convalescence among patients undergoing open radical cystectomy and RARC [32]. For the HRQOL assessment, the BCI instrument was used and short-term convalescence was evaluated using a surgery-specific instrument, the CARE questionnaire. Within 1 postsurgical year, the HRQOL score recoveries, across all BCI domains, were comparable, with scores returning to near baseline for all patients. The CARE scores at 4 weeks revealed that patients treated with open surgery had better pain (29.1 vs 20.0, P 5 0.02) domain scores compared with patients undergoing RARC; these differences abated by Week 6. The authors concluded that QoL recovery and short-term convalescence were similar in these cohorts, following RARC and open radical cystectomy. The high rate of ileal conduit use was noted as one of the study’s limitations. More than 75% of the patients in the RARC group and almost 70% of the patients in the open surgery group underwent ileal conduit procedures. Furthermore, all of the diversions in the RARC group were performed using an extracorporeal approach, whereas a completely intracorporeal approach may be necessary to realize the full benefits of the minimally invasive RARC.

CHEMOTHERAPY FOR ADVANCED OR METASTATIC BLADDER CANCER Radical cystectomy is the standard treatment for patients with muscleinvasive bladder cancer. However, it only provides a 5-year survival of

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approximately 50% [33]. To improve this unsatisfactory oncologic result, neoadjuvant chemotherapy has been adopted. Platinum-based neoadjuvant chemotherapy, before radical cystectomy, has been shown to improve survival outcomes in these patients [34 36]. Only one cost-effectiveness analysis addressed a QoL comparison between neoadjuvant chemotherapy, before cystectomy, and cystectomy alone for muscle-invasive bladder cancer [12]. The study retrospectively examined data from a single institution to compare QALYs and cost-effectiveness. A total of 119 patients (65.4%) underwent radical cystectomy alone, and 63 (34.6%) also received neoadjuvant chemotherapy. The median overall survival times were 26.6 and 46.2 months, respectively; the median quality-adjusted life months (QALM) were 21.9 and 40.4 months, respectively. The additional cost, per QALM gained by neoadjuvant chemotherapy, was approximately $6000. The study concluded that neoadjuvant chemotherapy improves QoL and is cost-effective. For decades, systemic chemotherapy with methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) has been a standard treatment for advanced or metastatic bladder cancer [33]. However, because the report of a Phase III trial comparing a new combination therapy using gemcitabine plus cisplatin (GC) with MVAC [37], GC chemotherapy has been replacing MVAC as the treatment of choice for advanced or metastatic bladder cancer. The overall survival of patients treated with GC (median, 13.8 months; 95% CI, 12.3 15.8) was comparable to that for patients assigned to the MVAC group (median, 14.8 months; 95% CI, 13.2 16.8); however, GC was better tolerated than MVAC. In the GC arm, 63% of cycles were administered without dose adjustment compared with only 37% in the MVAC arm, indicating that GC has less treatment-related toxicity than MVAC. Patients in the MVAC arm experienced more Grade 3 or 4 neutropenia (MVAC, 82%; GC, 71%), significantly more neutropenic fever (MVAC, 14%; GC, 2%; P , 0.001), and significantly more neutropenic sepsis (MVAC, 12%; GC, 1%; P , 0.001) than did those in the GC arm. Grade 3 or 4 mucositis was also significantly more common in the MVAC arm (22%) than in the GC arm (1%, P , 0.001). Furthermore, patients in the GC arm gained significantly more weight after treatment than did patients in the MVAC arm. In addition, a higher percentage of patients in the GC arm showed a performance status improvement of $10 points over a period of at least 4 weeks, compared with those receiving MVAC (GC: 5, 37%; MVAC: 5, 31%). The investigators measured QoL using the EORTC QLQ-C30 instrument. Overall, the QoL profiles were similar in both arms, with the exception of fatigue. Ad hoc analysis of this Phase III trial showed that HRQOL parameters, such as physical and role functioning and anorexia, were the significant and independent prognostic factors for advanced or metastatic bladder cancer [38].

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QoL IN LONG-TERM SURVIVORS A population-based survey evaluated HRQOL among long-term survivors following a diagnosis of bladder cancer [39]. The study identified a cohort of bladder cancer (either non-muscle invasive or muscle invasive) patients from the Iowa data registry of the SEER program. The median time since diagnosis for the participants was 99.8 months. They used a validated bladder cancer specific instrument, FACT-BL, in the study. There were no significant differences in general QoL scores between patients undergoing radical cystectomy and those with intact bladders. However, patients undergoing radical cystectomy had worse sexual function scores. Of the patients undergoing radical cystectomy, the QoL scores were not significantly different between those with ileal conduits or orthotopic neobladders. Of the patients with intact bladders, the QoL scores tended to decrease with increasing age. The presence of comorbidities also lowered the HRQOL scores.

CONCLUSION Increased awareness of QoL may increase our understanding of the impact of bladder cancer and may help to choose the treatment option. However, bladder cancer QoL research is relatively inactive. Therefore, high-level evidence is very limited in across all bladder cancer stages and treatments. However, many dedicated researchers have established the foundation for HRQOL studies through efforts such as the development of bladder cancer specific QoL questionnaires. It is the time now to perform welldesigned, prospective, comparative QoL studies among bladder cancer patients. We also need high-quality studies to determine utility values for various bladder cancer situations. Furthermore, quality-adjusted bladder cancer survival analyses will support many medical decision analyses, including clinical decision analyses, cost utility analyses, and cost effectiveness analyses.

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