Katja Goossens

General discussion, and future perspective

which a multidisciplinary approach is required. For this purpose co-morbidity, and the functional and physiological reserves per person should be analysed in order to propose the most appropriate treatment plan. The objective, aim and outline of this thesis were presented.

Part II

Quality of Life (QoL)
Nowadays, because QoL is associated with QoC, QoL has become an important outcome measure of care. Before answering the third research question, first some background information is offered on how QoL in bladder cancer patients can be measured. Quality of life is the perception people have on their position in life within the context of the cultural and value systems in which they live, and in relation to their goals, expectations, values and concerns [2]. Therefore, QoL is a multidimensional concept involving much more than being simply concerned with direct health-related aspects [2]. In other words, QoL refers to a person’s satisfaction with his functioning in various aspects of his life and is not a direct reflection of his performance. QoL is often confused with functional status and health status (HS). Functional status represents a person’s physical functioning, whereas HS refers to the influence of disease on a person’s physical, social and psychological functioning. HS is also multidimensional and directly reflects functioning. Furthermore, the concept health-related quality of life is QoL, but solely on the three main domains of QoL: i.e., physical, social, and psychological [3,4]. QoL, functional status and HS are patient reported outcomes (PROs). Patient-reported outcomes are self-reports, thus the answers come directly from patients about how they feel, function, are bothered in relation to a health condition and its therapy without the opinion of healthcare professionals or anyone else. PROs can relate to symptoms, signs, functional status, perceptions, or other aspects, such as convenience and tolerability [5].

For patients undergoing a radical cystectomy we are interested in the PRO QoL, i.e. how the person experiences the various aspects of his or her life. This is illustrated by the following example. A person has arthritis and cannot use a staircase properly (functional status). This has reduced his functioning, or his health (health status). When measuring this person’s QoL, we measure whether this person finds it problematic that he can no longer climb the stairs. Perhaps he lives in an apartment with an elevator and does not need to use the staircase.

Chapter 2 presents our results of a multicentre prospective baseline study (level 2) on QoL, HS, sexual function and trait anxiety in patients with primary hematuria of whom some later appear to have bladder cancer. These patients are compared with another group with hematuria who later appear to have a different (non-malignant) diagnosis. Bladder cancer was found in 17% of the patients. Chapter 3 is the follow-up case-control study on QoL and HS among patients with MIBC undergoing cystectomy from a prediagnostic baseline measurement until one year postcystectomy compared to patients with non-malignant diagnosis.

QoL questionnaires
Some previous studies compared different questionnaires for QoL vs. HS to see whether the outcome scores are interchangeable [6-8]. These studies show that different questionnaires do not result in the same conclusions. This stresses the importance of using the correct questionnaire to address one’s research hypothesis. For our study, we decided to use the following questionnaires: the World Health Organization Quality of Life (abbreviated version) WHOQOL-Bref, which is a general questionnaire to evaluate QoL [9,10]. To measure Health Status we chose the SF-12 questionnaire, also known as the short version of the Rand 36 [11]. Both WHOQOL-Bref and SF-12 are generic questionnaires, that can be used to measure PROs in the general population. Postcystectomy, the Functional Assessment of Cancer Therapy - Bladder Cancer (FACT-BL), a bladder cancer specific questionnaire was used to compare the results with the WHOQOL-Bref and SF-12 results postcystectomy. Although better mental health status was reported by patients with an unknown diagnosis of bladder cancer, they were as satisfied with their QoL as patients with other causes of hematuria (chapter 2). When comparing the results between QoL and HS questionnaires, in comparison to the QoL vs. HS studies performed in patients with liver disease, intermittent claudication or breast cancer [12], the differences between the two separate questionnaires are not so evident (chapter 2 and 3). This may be due to the use of the SF-12 and the WHOQOL abbreviated versions, making it more difficult to detect possible differences.

Personality
QoL is known to be influenced by health [2], socio-economic status [13], culture [14] and personality [15,16]. Especially the personality factor ‘trait anxiety’ is associated with QoL, but data on bladder cancer is sparse. The State-Trait Anxiety Inventory (STAI-TRAIT) questionnaire was used to score trait anxiety [17,18]. In both chapter 2 and 3, the trend of a lower score on trait anxiety for bladder cancer patients was found. Between bladder cancer patients and other causes the difference in a high score for a patient on anxiety was 16.5% and 24.7% respectively. For the patients undergoing a cystectomy vs. the case-control patients, this was even more evident, 5.6% vs. 20%. Further research is needed for confirmation of this finding. If low scores on trait anxiety correlate with presence of bladder cancer, the need to increase awareness of hematuria as a possible symptom of undiagnosed bladder cancer, and of the importance to expediently analyse the cause of such hematuria, is self-evident.

In addition to choosing what concept to measure, different questionnaires are available which specify QoL or HS even further.
1) Generic questionnaires (WHOQOL-100/Bref; SF-36/12)
2) Disease-specific questionnaire (the FACT-General; Functional Assessment of Cancer Therapy or the EORTC QLQ CPO)
3) Cancer specific/treatment specific questionnaire (for bladder cancer; the FACT-BL)
The downside of disease-specific questionnaires is that they are not applicable to matched controlled patients, patients before a cancer diagnosis, or “healthy” individuals. This limits the choice in what measurement time-points and control group to use. In chapter 3 the results of the FACT-BL, measured postcystectomy, showed a physical score that is stable over time, and functional well-being decreased slightly. This in contrast to the WHOQOL-Bref and SF-12 which both showed a decreasing physical score. However, the question is whether the disease-specific FACT-BL should have been applied in this specific study knowing the ideal baseline cannot be used. As the generic questionnaires, with ideal baseline abilities, can be used, the FACT-BL is made redundant.

Sexuality
To measure sexuality, the International Index of Erectile Function (IIEF) questionnaire for erectile functioning was added to our study [19]. No validated questionnaire was available for female sexuality when our study started. So, three items of the WHOQOL-100 were added to the WHOQOL-Bref to assessing sexual satisfaction. This “facet” sexual activity can be answered by both female and male patients, in contrast to the IIEF. Because the IIEF is a widely used questionnaire, it was remarkable that this questionnaire was a reason for many patients not to participate in our study. Of the patients who did participate despite the IIEF, only 40% answered the questions of the IIEF, in comparison to the 99.5% of the participants answering the facet sexual activity (chapter 2). Apparently the more general questions about satisfaction with sexual activity of the WHOQOL-Bref were experienced as less intense than the specific questions on the IIEF erectile function. The results of chapter 2 and 3 on this subject showed sexual and erectile dysfunction was highest in patients with bladder cancer. This may well be explained by a relationship with preexistent comorbidity (cardiovascular, as a result of smoking), although this cannot be confirmed in the present study because we did not collect information on patients’ comorbidity status.

Quality of Life studies for bladder cancer
In the urologic oncology community there is no standardised assessment protocol for QoL studies, and there is a wide variation in QoL outcome studies [20]. Three systematic reviews on QoL show that none of the performed studies exceed level 3-4 studies [21-23]. A second major limitation is that the few prospective studies all report a ‘baseline’ assessment of HS and/or QoL that is measured only after MIBC has been confirmed [24-26]. However, receiving a diagnosis of cancer will almost certainly impact one’s QoL. It was our aim to assess QoL and HS before diagnosis in order to get a more realistic baseline assessment. This had implications for the choice of PRO to measure and which questionnaire to use, as the FACT-BL could not be used for baseline measurement, and perhaps the motivation of the patients to answer questions on their sexuality was lower not being aware of the diagnosis behind the hematuria.

In earlier studies, psychological HS and health-related QoL measures, returned to or exceeded baseline values 12 months after cystectomy [21-26]. However, as stated earlier, none of these studies measured QoL before the diagnosis of bladder cancer; being diagnosed with cancer will almost certainly cause a changed perspective on QoL. A baseline QoL measurement point before diagnosis should give a more accurate reflection of a patient’s baseline QoL. The aim of this prospective longitudinal case-control study (chapter 3) was to measure QoL and HS in patients with an unknown diagnosed bladder cancer (eventually) undergoing cystectomy, and to evaluate co-variables like age, gender, and mental anxiety. This was the first case-control study measuring QoL before the diagnosis bladder cancer is known. The results of this study imply that radical cystectomy patients have a better prediagnostic QoL and HS than postcystectomy, even one year after surgery. The disease and cystectomy thus have a major impact on patients’ lives. Therefore, one should be careful to give clinical advice to individual patients concerning their QoL postcystectomy based on earlier studies with a QoL measurement immediately before undergoing cystectomy [24-26]. One other factor that could explain the difference in outcome could be the use of different questionnaires, in these earlier studies just before and postcystectomy the FACT-BL, European Organization for Research and Treatment of Cancer QLQ-CPO [27] or personal interviews were used. As stated before, the FACT-BL in the present study was only used postcystectomy. And the EORTC QLQ-30 is a generic cancer questionnaire [27], which would not apply before diagnosis is known. Furthermore, prediagnostic, the HS physical component scale, i.e., physical functioning and sexual satisfaction for patients undergoing radical cystectomy were lower, and the domain physical health shows a clinical difference in comparison to patients with other causes for hematuria. A limitation of our study is not comparing the cystectomy to other treatment modalities of MIBC, e.g., EBRT and IRT. A second limitation is the number of patients “lost-to-follow-up” as a result of hospitalization due to complications or spread of the disease, or death due to bladder cancer.

Future perspective QoL
When considering our initial research question, i.e., to what extent is QoL in patients with muscle-invasive bladder carcinoma affected by undergoing a radical cystectomy, the answer is that QoL is negatively influenced by undergoing cystectomy. It is not yet clear if this is solely contributable to the cystectomy. The research should be expanded with a larger population including comorbidity and smoking history. In this high-risk, low-volume procedure, with a 52% 5-year survival rate (chapter 6), the decrease in postsurgical QoL is yet another issue to discuss with patients. As the cystectomy remains the gold standard treatment, it will probably not change the choice of the patients to undergo surgery. However, although surgery is a feasible option for the fit older patient, some patients may on the basis of this new information consider that chances of prolonged survival will not outweigh the loss of QoL, and as a result choose not to undergo surgery in favour of EBRT. For the patients who would choose cystectomy, physical training and screening for psychological problems and, if indicated, subsequent psychological counseling may improve their QoL and HS.

Part III Quality of Care

Background to development of indicators in the Netherlands
In 2005 new financial arrangements were made in the Dutch healthcare system, aiming to control the increasing costs and thus, the affordability of the system. These increasing costs are mainly caused by the expanding use and possibilities of modern technical diagnostic and treatment options, together with an increasing number of older citizens with complex medical problems. The financing system is based on demand-driven care with detailed product financing. The ratio of price, volume and quality is supposed to be accounted for by the healthcare provider using so-called indicators, i.e. measurable elements of caregiving that give an idea about the extent of the QoC provided. These indicators are called performance indicators and are generally used to describe the processes within the professionals own institution (so-called internal indicators), and for offering accountability to other parties (so-called external indicators).

In 2006 a project called ‘Kwaliteit van Zorg in de etalage’ (‘QoC on display’) was started by the Quality Institute for Healthcare (CBO) and the Order of the Medical Specialists, commissioned by the Netherlands Organisation for Health Research and Development (ZON-MW) [28]. Steering groups were formed to develop disease-specific performance indicators [29]. The purpose of these external indicators was to provide insight into effectiveness and safety levels of the QoC provided by an institution, which insight -ideally- could be used in negotiations with the insurance companies. Since 2010 the Netherlands Health Care Inspectorate requires all hospitals to provide information on these annual external quality indicators, one of them being the number of cystectomies performed per hospital on a yearly basis.

During the process of the development of these external indicators, the Dutch Association of Urologists became actively involved and took increasing responsibility. This was because some member-urologists felt that the external indicators tended to raise more questions rather than improving the transparency in the healthcare system. According to them the use of external indicators may not improve the effectiveness and safety of care for patients with bladder cancer. Questions were raised as to whether volume standards alone would lead to the desired QoC or whether other crucial factors should be involved; the need for and interest in internal QoC indicators became more apparent. The initial studies presented in this thesis were designed to answer these questions.

QoC is defined as the degree to which healthcare services for individuals and populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge [30]. Chapter 4 describes the process of developing QoC indicators/internal indicators to use at hospital level to measure the QoC given. At the start of this study in 2006, there was a complete lack of QoC indicators (QIs) or a QoC registration system for MIBC. Therefore in this study QIs were defined and selected by a multidisciplinary project group based on recent literature, guidelines, and/or consensus within the project group. In a retrospective study a baseline for each QI was assessed and compared to a predefined benchmark. Afterwards the QIs were measured again (data not published). With regard to the first research question, it was shown that it is possible to measure and improve the QoC at hospital level by using QIs. This QoC registration method might thus have served as a first step in defining applicable and useful QIs for implementation in clinical practice.

In the Netherlands, as stated earlier, there is an ongoing debate about the use of performance indicators in general. When the target for a performance indicator has not been reached this could lead to financial consequences, e.g. the hospital will not get paid for certain treatments provided. Therefore, when QIs are used in clinical practice there must be increased awareness to prevent indicator-motivated actions, i.e. interventions applied only to reach that QIs target. The sole purpose of internal QIs is to raise QoC to a higher standard. Ultimately QIs should be used as a surrogate measure for:
- 1) oncologic outcomes (cancer-specific and overall survival),
- 2) patient QoL outcomes,
- 3) healthcare expenditures.
As stated in chapter 3, before QIs are implemented and standardised into oncologic practice, it seems essential to document correlations between QoC and the above-mentioned outcome factors.

In chapter 5, 6 and 8 and answer is given to the second research question: Is the outcome for treatment of muscle-invasive bladder cancer through radical cystectomy in the Netherlands influenced by the volume of the procedures? Early 2007, commissioned by the Dutch Cancer Society, the Quality of Cancer Care Task Force of the ‘Signalling Committee-Cancer’ of the Dutch Cancer Society was formed. A project was started on “Kwaliteit van kankerzorg in Nederland” (Quality of Cancer Care in the Netherlands) [31]. The task force decided to include also a urological-oncological condition which became MIBC. Subsequently, extensive (inter)national