Bladder Cancer

The prognosis for bladder cancer has been relatively unchanged over the last decades, but patient treatment has become gentler for the different types of intervention. However, in general it is found that there is much to be gained in regard to diagnostics, treatment and sequelae.

The objective of research into bladder cancer and bladder tumours at the Research Unit at the Department of Urology is to cover all aspects of the disease from the smallest papilloma to advanced bladder cancer with metastases, as well as from early detection over molecular medicine methods to rehabilitation following major surgery.

The research unit wishes to be among the world leaders in the field of bladder cancer research and a leader in new treatment methods.

As a general principle, patients with bladder tumours who are treated at the Department of Urology should be offered participation in a minimum of one research project if they so wish, as this enables the continuous development of the area for the benefit of the both the individual and future patients.

PhD projects

The optimal handling of T1 bladder cancer. The clinical relevance of the sub-classification of T1 bladder cancer

Background:

Bladder cancer is the tenth most common cancer disease worldwide. In Denmark (DK), approx. 2,000 patients are diagnosed with bladder cancer annually. Of these, half are non-invasive polyps, 25 per cent are connective tissue- invasive tumours, and 25 per cent are muscle-invasive tumours. The non-invasive polyps are treated by the removal of the polymer and a minimum of five years of monitoring. The muscle-invasive tumours are treated by surgically removing the urinary bladder (cystectomy) and the placing of dry or wet urostomy or curative radiotherapy. The treatment of the connective tissue-invasive tumours, also known as T1 bladder cancer (BC), is a topic of discussion worldwide.

The vast majority of countries, including Sweden, treat T1 BC with the resection of the bladder tumour TURB and subsequent outpatient bladder infusion with Bacillus Calmette-Guérin (BCG) vaccine. The regime for dealing with T1 BK in DK is significantly different from that of other countries.

In DK, T1 BC is subdivided into two sub-phases, T1a and T1b, respectively. T1A is superficially invasive in the connective tissue, while T1b is deeply invasive in the connective tissue. First-time T1 BC is treated with TURB and BCG infusion, while repeated T1a and/or T1a with concomitant carcinoma in situ, is treated with cystectomy. T1B BC is treated with cystectomy. The Danish guidelines in which this regimen is recommended are based on old studies, and the subdivision into T1a and T1b is very sparsely defined in the Danish standard definition (SD). During the preparations for this PhD project, a new definition (ND) was developed, in which the distinction between T1a and T1b is more clearly defined.

Objective: For this PhD project there will be three studies, each with their own objective.

- Study 1: Examining the prognostic value of T1 BC's sub-classification as used in DK, and investigating the prognostic value of BCG infusion in patients diagnosed with T1a and T1b BC, respectively.

- Study 2: To compare the prognosis for patients diagnosed with T1 BC in DK and Sweden, respectively.

- Study 3: To clarify the clinical relevance of ND, and to examine the reproducibility of the T1 stage with ND.

Method:

Study 1: All T1 BC patients in DK diagnosed in the period 1 September 2012 to 31 August 2018 are identified via the Danish Bladder Cancer Database (DaBlaCa-data), along with information on subclassification, treatment, relapse, progression and death. Data for T1a patients will be compared with data for T1b patients. Primary outcome will be 1-and 5-year general (GO), relapse-free- (RFO) and progression-free survival (PFO).

Study 2: All T1 BC patients from DK and Sweden over the same period as in Study 1 will be identified via the DaBlaCa data and the Swedish BladderBaSe database, together with information about treatment, relapse, progression and death. Data for Danish T1 BC patients will be compared with data for Swedish T1 BC patients. The primary outcome will be 1-and 5-year GO, RFO and FFO.

Study 3: All pathology drugs diagnosed in the same period as in Study 1 from two large urological-pathological wards in DK, identified via DaBlaCa-data. The drugs are revised by two highly dedicated urology pathologists in accordance with the new definition. Patients who are reclassified are compared to patients who keep the same sub-classification.

Statistics:

In study 1, 2 and 3, GO, RFO and PFO will be compared by performing Cox proportional hazard regression analyses adjusted for treatment, gender, age and comorbidity. In study 3, the Interrater agreement will be calculated using Cohen’s Kappa.

Perspectives:

The study is expected to clarify whether T1 BC sub-classification in T1a and T1b, and ND, and the Danish treatment regimen should recommend at international level. As a minimum, the results of the study are expected to be published as three articles in international peer-reviewed journals.

PhD student: Erik Hansen

Principal supervisor: Jørgen Bjerggaard Jensen

Use of 15O-H2O PET/MR-scans and ctDNA to assess the effect of neoadjuvant chemotherapy in the treatment of patients with muscle-invasive bladder cancer.

Treatment of muscle-invasive bladder cancer is cystectomy possibly in combination with neoadjuvant chemotherapy, which has shown that it extends survival.

It is known that 50-60 per cent of patients with muscle-invasive bladder cancer who receive neoadjuvant chemotherapy are free of tumour tissue in the bladder when the tissue is examined following cystectomy. Unfortunately, there are currently no optimum methods for assessing whether the patient has recurring disease or not prior to cystectomy.

The objective of this PhD project is to study whether 15O-H2O PET/MR combined with tumour DNA (ctDNA) circulating in the blood and urine can be used to predict who will be free of rest tumours following neoadjuvant chemotherapy and who can potentially be offered treatment to preserve the bladder.

The project will include 54 patients from the Department of Urology at AUH, who have muscle-invasive bladder cancer and are undergoing treatment with neoadjuvant chemotherapy and cystectomy. The test subjects will undergo a 15O-H2O PET/MR scan before the start of neoadjuvant chemotherapy and again after the final chemotherapy, but prior to a cystectomy. Blood- and urine samples are taken on an ongoing basis for ctDNA analysis. The scans and ctDNA will be compared against the pathological result after cystectomy.

The hypothesis is that 15O-H2O PET/MR combined with ctDNA in blood and urine will enable identification of the patients who have completely local response to neoadjuvant chemotherapy. This is a research project which is thus expected to lead to further studies in the future and which at the end of the day can potentially change the monitoring and treatment of bladder cancer patients, as well as giving them the opportunity of treatment to preserve the bladder.

PhD student: Stefanie Korsgaard Körner

Principal supervisor: Jørgen Bjerggaard Jensen

Benign stricture formation after cystectomy and urinary dissipation among bladder cancer patients - aetiology, treatment and prevention

Cystectomy and benign strictures

Cystectomy with urinary dissipation is one of the major interventions undertaken in urology, and it is carried out approx. 400 times a year in Denmark, with bladder cancer as an indication of treatment. Stricture in the ureters is diagnosed in 15 per cent of the cystectomy patients. In the form of both infection and pain, it is often necessary to relieve the ureter strictures multiple times, with a lot of discomfort for the patient in the form of infection and pain to follow.

The objective of this PhD project is to shed light on the stricture formation after cystectomy from more angles.

Register-based studies: Risk factors and treatment options

This part of the project will be a larger register-based study that includes patients who have been treated for bladder cancer with cystectomy and urinary dissipation at AUH and Herlev Hospital. Here we will compare patients who developed stricture with those who did not, in an attempt to identify risk factors. We hope to identify subtypes of strictures on the basis of the length and location of the strictures on the ureters, while at the same time finding correlations to different risk factors.

In addition, we will map the different attempts to treat the strictures in an attempt to find the optimum treatment for the individual subtype in the future.

Randomised controlled trial: MOSAIC

The MOSAIC study will be a large randomised controlled trial in which we include 300 patients distributed around all five centres in Denmark. The control group receives the classic Bricker diversion and the intervention group receives an extension of the urinary tract, in which the urinary tract extends behind the sigmoid, thereby creating gentler conditions for the left ureter. We expect to see a fall in strictures, specifically for the left ureter in the intervention group, where seventy per cent of all strictures normally develop. This is expected due to less mobilisation of the left ureter and due to the increased resection, which lowers the risk of distal ischemia of the left ureter.

PhD student: Simone Buchardt Brandt

Principal supervisor: Jørgen Bjerggaard Jensen

Impact of hormonal treatment on bladder cancer - occurrence, prognosis and functional result

Bladder cancer is one of the most common forms of cancer around the world and in Denmark. The disease is seen more frequently in men than women. Part of the reason can probably be explained based on smoking history and occupational exposure, but after adjusting for this, there remains a difference in the incidence among men and women, which has led to a hypotheses that hormone receptors and hormones in general play a role in the development of the disease.

The objective of this PhD project is to examine whether anti-hormonal treatment can reduce the incidence of bladder cancer. In the first two parts of the project, a large register-based study will be carried out, including patients with anti-hormonal treatment for prostate-, breast- and endometrial cancer. Previous studies suggest that this particular treatment can help to reduce the incidence of bladder cancer. The study will furthermore examine whether the incidence and prognosis of bladder cancer is dependent on the type of anti-hormonal therapy the patient has received. This will be one of the largest register-based studies in this area to date.

In addition, a clinical pilot study will be conducted as part of the project with the aim investigating whether anti-hormonal treatment (in particular Degarelix (Firmagon)) can reduce the side effects of radiotherapy treatment of bladder cancer. The project will include patients who receive radiotherapy for their invasive bladder cancer, both with and without anti-hormonal therapy for prostate cancer. Following their treatment, the patients will be given a follow-up bladder biopsy, urodynamic examinations and questionnaires to assess side effects related to radiation damage. The hypothesis is that the patients who have received Degarelix during the radiotherapy will have fewer side effects and less fibrosis in the bladder, as a study has shown that this drug has the property to protect stem cells in e.g. the bladder, and thus heal better after radiotherapy. Patients will be included from Aarhus, Herlev and Odense.

PhD student: Josephine Maria Hyldgaard

Principal supervisor: Jørgen Bjerggaard Jensen

Recurrence of non-muscle-invasive bladder cancer - risk stratification and monitoring using urinary markers

Cancer in the urinary bladder is a frequent cancer disease in the western world. The majority of patients with bladder cancer have a so-called non-muscle invasive disease, where the cancer node/nodes are only found locally in the urinary bladder. The cancerous nodes can be divided into tissue types depending on how cells look in a microscope – there are cells with a lot of deviation from normal (high grade) and cells with less deviation from normal (low grade). There is a risk that a non-muscle invasive tumour can grow and become invasive, which is why rapid diagnosis and treatment are important. This risk is higher for high grade than low grade.

In recent years, molecular diagnostic tests have been developed so that urine samples can be used to detect small molecules from cancer cells (mRNA) and in this way see if cancer remains in the urinary bladder after the aforementioned surgical and possible chemotherapy treatment. It will thus be possible to monitor the patients less intrusively via the use of urine samples rather than endoscopic examinations of the urine bladder Xpert® Bladder Cancer Monitor is such a test and it has proved useful in finding cancerous tumours with high-grade tissue type, in particular. However, the majority of studies have been conducted on patients with the first case of non-muscle-invasive cancer in the urinary bladder, and the test's ability to find relapses has thus not been examined.

The PhD project is formally divided into three parts:

Study #1 is a register-based study in which data regarding the stage of the disease, tissue samples and treatment from all Danish patients since 2002 with non-invasive bladder cancer will be used to examine which patients suffer relapses of their non-invasive bladder cancer and when this occurs.

Study #2 is a study of all patients in the Central Denmark Region in 2014 & 2015 who suffered their first case of non-invasive bladder cancer. These patients will be followed from their first case of the disease until now. Information about the stage of the disease, tumour size, tissue samples, number of tumours, treatments and tumour appearance for the first case of the disease and any relapses will be retrieved from the patients' electronic records.

Study #3 is a randomised clinical trial to compare two ways of monitoring patients with high grade non-muscle-invasive cancer in the urine bladder for relapse. Control using molecular test of urine samples (intervention) is compared with the current form of control which uses endoscopy and urinary cytology (standard treatment), in order to study whether the molecular test of the urine can be used to replace the standard treatment in this group of patients.

PhD student: Thomas Karmark Dreyer

Principal supervisor: Jørgen Bjerggaard Jensen

Clinical and functional consequences of photodynamic diagnostics (PDD) and intravesical installation therapy

Bladder cancer affects approx. 2,000 people annually in Denmark. Of these, 75 per cent are diagnosed at an early stage, where the cancer has not yet grown into the musculature of the bladder. This is called non-muscle-invasive bladder cancer (NMIBC). After treatment, the patients begin a monitoring process with repeated endoscopic examinations of the bladder. For some, these monitoring processes are life-long. The annual risk of relapses with NMIBC is 35 per cent.

Due to the repeated relapses and monitoring, NMIBC is one of the most expensive cancer types from diagnosis until death.

In Denmark, the urology departments have had different treatment strategies for NMIBC. Thus, there is a difference between the use of trace material (photodynamic diagnosis, PDD) during keyhole surgery and the use of chemotherapy for bladder infusion treatments.

The objective of this PhD programme is to investigate whether one treatment strategy for NMIBC is superior to the other. Both in relation to the number of relapses and development in the cancer stage over time, but also in relation to the bladder symptoms and the effect of the bladder function that the patients experience due to the treatment. Finding an optimal treatment strategy in relation to this will lead to improved patient pathways and thus increased quality of life for this large group of patients in the future.

The PhD programme will be carried out in part as a register-based national cohort study and partly as a descriptive study on a small group of patients. The patients are identified using national databases, and the Danish urology departments are classified according to their treatment strategy based on questionnaires. The use of bladder-related medicine is utilised as a surrogate target for bladder symptoms, while bladder function is determined by means of a detailed bladder examination (urodynamic examination) performed by the PhD student on selected patients.

No studies have previously been conducted to link NMIBC treatment with the sequelae that patients experience. The results of this PhD are therefore expected to be essential for future NMIBC treatment strategies. This will help to weigh the advantages and disadvantages of different treatments, both in relation to the effect in regard to relapses, but also with regard to the influence on bladder function and thus quality of life.

PhD student: Linea Blichert-Refsgaard

Principal supervisor: Jørgen Bjerggaard Jensen

Robotic surgery in clinical practice. The importance of formalised training and technical simulation

Background

Since the turn of the millennium, there has been focus on the introduction of robot-assisted surgery, which combines the minimally invasive intervention we know from laparoscopy with the optimal mobility known from open surgery. The number of open interventions has been sharply reduced in connection with the introduction of laparoscopic interventions in recent decades. At the same time as an increased sub-specialisation, this has led to a concern in relation to a laparoscopic-trained surgeon's ability to convert to open surgery in the event of a lack of progression or bleeding that makes conversion necessary. Similarly, the even larger proportion of current minimal invasive procedures (laparoscopy and robotic surgical interventions) have reduced the number of classical open interventions to a minimum, which has increased concern that this may compromise patient safety due to a lack of routine in a converted intervention without having the necessary expertise in open surgery. In theory, a robot operator will not face a similar problem when converting, as a robot surgical intervention is much more reminiscent of an open procedure than a laparoscopic intervention in terms of visualisation, handling of instruments and the use of assistant. Thus, an increased use of robotic surgery to benefit laparoscopy will theoretically be an advantage - also from a patient-safety perspective.

The biggest drawback of robot surgery is presumably the costs associated with the procurement and operation of the robots. This has led to increased focus on the use of robot-assisted surgery to ensure optimum utilisation of the limited resources in the healthcare system with greater morbidity.

Objective

Study 1: To study the clinical effect of the introduction of robotic surgery in the clinic – both during and after the learning curve at surgeon- and department level.

Study 2: To study the ability to convert to open surgery from laparoscopic and robotic surgical procedure in relation to specific simulation-based training targeted at a single modality.

Method

Study 1: Existing data from the BI portal from the Central Denmark Region is used. Representative interventions are selected within surgery, urology and gynaecology, respectively, where the selection criteria are:

· Minimum 25 annual procedures

· Carried out in the period 2012-2017 with at least two of the three different modalities (open surgery, laparoscopy, robot)

· Fully or partially introduced as robotic surgical intervention in the period 2012-2017

A paired analysis is conducted of the peri- and postoperative outcome (time use, transfusion needs, complication rate and survival) between robot surgical intervention and laparoscopic and/or open surgery with correction for any differences in age, gender, BMI and comorbidity. The analyses are carried out independently for the entire period and with division into the presumed implementation period (learning curve) after this, respectively.

Study 2: A total of 36 voluntary medicine students at Aarhus University are used, and all of them are characterised by not having surgical experience, although they show interest in a career in the specialist surgical area. The test subjects are randomised in three groups of 12 people, with each group undergoing intensive simulation-based training at MidtSim in either open surgery, laparoscopy or robotic surgery. After intensive training using simulation models, all test subjects are tested in the same conversion simulation exercise from laparoscopy to open surgery due to acute bleeding in the pig model. The participants are assessed by three independent observers who are blinded to the test subjects’ previous training modality.

Thus, it will be possible to assess whether a specific training in robotic surgery is advantageous in a conversion situation compared to specific training in laparoscopy. Both are assessed in the same way in regard to training specifically in open surgery.

Perspectives

The project will provide the opportunity to obtain evidence of the clinical use of robotic surgery, and to shed light on the extent to which robotic surgical techniques can optimise the clinical pathways which will be able to save patients from morbidity and potentially save costs in the healthcare system. A further aim is to clarify whether there is a need to continue to have dedicated open surgeons, or whether this is less necessary when using robotic surgery to a greater extent than a unilateral focus on conventional laparoscopic interventions.

PhD student: Maria Ordell Sundelin

Principal supervisor: Jørgen Bjerggaard Jensen

DaBlaCa-13 Neoadjuvant, short-term, intensive chemo-section compared to standard adjuvant installation therapy in the bladder with non-muscle invasive bladder tumours - NICSA

Non-muscle invasive bladder tumours are a frequent bladder disease with many relapses despite treatment. In addition, there is a risk of developing malignant disease, which is why fast and effective treatment is important. Non-muscle invasive bladder tumours can be treated by keyhole surgery (TURB), possibly in combination with bladder infusion treatment with chemotherapy.
The latter is liberally recommended in the Danish and, in particular, the European guidelines.

Some patients never experience relapses, while others experience repeated cases despite both TURB and infusion treatment.
Today, we cannot distinguish between susceptible and resistant tumours and some patients are therefore exposed to chemotherapy with side-effects without benefiting from it.
There is thus a need for both more effective treatment as well as methods to individualise the treatment.

Mitomycin C is a chemotherapeutic agent that damages tumour cells in the urinary bladder by inhibiting their cell division. The treatment is mainly used for preventative measures such as outpatient and weekly bladder infusion.

In order to predict the treatment effect of Mitomycin C, the composition of different biomarkers on the tumour have previously been studied. A final tool has not yet been developed, but the results are promising.

The aim of this PhD project is:

  • to study the efficacy of primary, short-term, intensive bladder infusion with Mitomycin C compared to the standard treatment with TURB and preventative bladder infusion.
  • to study the efficacy of primary, short-term, intensive bladder infusion with Mitomycin C compared to the standard treatment.
  • to study the correlation between tumour associated biomarkers and the treatment efficacy of Mitomycin C.

See protocol (pdf):

Publication

PhD student: Maria Skydt Lindgren

Principal supervisor: Jørgen Bjerggaard Jensen

En bloc-resection of non-muscle-invasive bladder tumours

An en-bloc study with the full title "An en-bloc-resection of non-muscle invasive bladder tumours" is a randomised, controlled multicentre trial, with the objective of studying the benefits of en-bloc resection, i.e. the removal of a tumour in one piece, rather than conventional TURB, where the tumour is removed by resection.

The study’s hypothesis is that an en-bloc resection is superior to conventional TURB, both when it comes to the pathological quality of the drug as well as relapse-free survival.

Conventional TURB is the standard in both treatment and diagnostics of non-muscle invasive bladder tumours. However, the method runs counter to traditional principles for cancer surgery, which aim for radical removal of tumours with free margins. With TURB, the tumour is fragmented, which in theory can be part of the cause of the very high relapse rate seen in bladder cancer compared with other types of cancer.

An en-bloc resection can potentially reduce the relapse rate for non-muscle invasive bladder tumours. We hope to be able to demonstrate this with this study.

The study is expected to commence inclusion at the end of 2021. Prior to the start-up of inclusion, patient records from previous TURB operations are reviewed to assess how large a proportion of all patients with bladder tumour could be a candidate for an en-bloc resection.

PhD student: Ninna Kjær Nielsen.

Principal supervisor: Jørgen Bjerggaard Jensen.

NORTH-REG Dwell-Time Study: Use of an adverse reaction-based algorithm for dwell-time of BCG infusion for non-muscle-invasive bladder cancer and carcinoma in-situ in the Nordic region.

As a starting point, non-muscle-invasive bladder cancer is treated with an operation, after which the patients are offered infusion treatment with Bacillus Calmette-Guérin vaccine (BCG), which has shown an improved survival rate if the patients complete the treatments. In addition, the primary treatment of carcinoma in situ is also BCG infusion.

This treatment is used all over the world and dates all the way back to 1979. The treatment is given as six weekly treatments and then as maintenance treatments after 3, 6 and 12 months. Each of these is given as three weekly treatments.

The downside of this treatment is that patients sometimes have severe and disabling side effects from the BCG infusion. This includes incontinence, pain, fever, etc. The side effects of the BCG infusions may be so severe that the patients stop before all the treatments are given. Attempts have been made to address these side effects by changing the regime for how the infusions should be given, without this having a particularly great effect on the side effects.

My PhD project will clarify whether the reduced dwell time (the time during which the BCG infusion fluid must remain in the bladder) can reduce the side effects and thereby increase the feasibility. My study will be run in the Nordic region, including Sweden, Norway and Iceland as well as several Danish sites. A total of 314 patients will be included.

PhD student: Lene Munk

Principal supervisor: Jørgen Bjerggaard Jensen

Other clinical projects

Treatment Of Metastatic Bladder cancer at the time Of biochemical reLApse following radical cystectomy - TOMBOLA

TOMBOLA - 'Treatment Of Metastatic Bladder cancer at the time Of biochemical reLApse following radical cystectomy' – is a national multi-centre study being carried out at five selected centres around Denmark, which undertake highly-specialised treatment of patients with prostate cancer. The project is carried out in close collaboration between the Departments of Urology, Cancer and Molecular Medicine at Aarhus University Hospital.

The initiators behind the study (Sponsor Investigator, Consultant, Professor Jørgen Bjerggaard Jensen from the Department of Urology, Professor and Team Leader Lars Dyrskjøt Andersen from the Department of Molecular Medicine and Consultant and Head of the Uro-oncology team at the Department of Cancer Mads Agerbæk) wish to examine the effect of early treatment on patients who, after the removal of the urinary bladder due to bladder cancer, have a detected relapse of circular tumour DNA in the blood (ctDNA).

It is known from previous studies that demonstrating ctDNA in the patient group in question is a certain sign of relapse of the cancer.

Prior to cystectomy a number of patients whose health allows undergo pre-treatment with chemotherapy (neoadjuvant chemotherapy). The purpose of this treatment is to remove any non-visible spread of the disease, thereby reducing the risk of relapses in the long term.

Up to 45 per cent of the current patient group will have a proven relapse of the cancer during the monitoring process. This relapse is usually demonstrated by one of the regular CT scans that take place in the first years after cystectomy. If a relapse is detected, the patient will be offered supplementary treatment at the cancer department.

Several factors affect the offer of treatment in the event of relapses of bladder cancer. The standard offer to patients with relapse is either chemotherapy, immunotherapy or radiotherapy, depending on whether the individual patient has undergone neoadjuvant chemotherapy prior to cystectomy or not, and current general condition, etc.

In this research project we wish to study the effect of immunotherapy for patients with relapses who have previously undergone neoadjuvant chemotherapy.

Objective:

The study’s objective is to identify new health-related grounds to begin immunotherapy with metastatic bladder cancer, while also investigating whether previous treatment with immunotherapy gives a better treatment effect and survival.

In the study, the patients are offered treatment with immunotherapy at the time that ctDNA is detected in a blood sample. This means that the patients in the study are offered targeted treatment far earlier than would otherwise be the case, as the standard today is to first offer immunotherapy when a relapse is shown by diagnostic imaging.

The study is the first of its kind in which blood samples are used as the basis for offering patients early treatment - rather than basing supplementary treatment on more uncertain predictions or already proven disease.

It is thus a study which has the ability to completely change the way in which patients are monitored and treated after operations for cancer of the urine bladder. The assumption is that carrying out this tailor-made monitoring and treatment will show that far more patients can experience an effect, thereby improving survival after surgery for cancer in the urinary bladder. Finally, it is expected to be able to show that the side-effects worsen when treatment is given to patients with minimal metastatic burden of illness compared to patients with a large metastatic burden of illness.

EpiCheck

Non-muscle invasive bladder tumours are a frequent bladder disease with many relapses despite treatment. In addition, there is a risk of developing malignant disease, which is why effective treatment is important. Treatment of non-invasive tumours in the urinary bladder is most often by an operation and, in certain situations, also chemotherapy in the bladder. The chemotherapy called Mitomycin is given as weekly bladder infusions for six consecutive weeks.

In a few patients where surgery is not desirable, the choice is instead made to treat them using primary bladder infusion treatment with chemotherapy. Mitomycin, which is a cell poison that inhibits the division of cells in the urinary bladder, is also used here, leading to damage to the tumour cells. When Mitomycin is used as primary treatment, the bladder infusions are administered briefly and intensively, i.e. three times a week over two consecutive weeks.

A subsequent monitoring process for this group of patients consists of an endoscopic examination of the bladder under local anaesthesia, either every four months for two years or at increasing intervals of four to eight to twelve months, depending on the aggressiveness of the tumour. In the case of aggressive tumours, microscopy is also performed on the patient's urine sample with a view to assessing visible tumour cells.

For the patients, treatment and monitoring are associated with nuisance and risk, while also incurring high costs for the hospitals.

Method

In recent years, different urine studies have been developed in the form of so-called molecular diagnostic tests. In the case of tumour tissue in the bladder, these tests can find small tumour molecules in a urine sample. There are high hopes that in the long-term these tests can be instead of an endoscopic examination of the bladder to monitor for new tumours. In the same way, the hope for this project is that a urine test can monitor the treatment effect both during and after treatment with primary bladder infusion treatment.

The rationale is that in the event of relapses with tumours in the bladder, rejected cells or molecules from the tumour will be found in the urine.

The objective of this project is to study whether the urine examination method EpiCheck can mirror the effect of ongoing treatment with primary chemotherapy in the bladder.

It is expected to include 22 participants in total. The study uses the urine samples that the patient submits in connection with a treatment visit. In the study, we will collect and use these for the EpiCheck test. If the EpiCheck test is positive for a patient before the start of the treatment, the test is repeated four times during the course of treatment. If the EpiCheck test is negative, no further examinations will be conducted in the study.

Perspectives

If it is shown that the test can be used to assess the treatment effect, it will in the longer term be possible to avoid both endoscopic examinations and bladder infusions. The latter is avoided because it is possible to discontinue treatment when the test becomes negative instead of completing the full series. The amount and size of tumours varies from patient to patient, and it will therefore be advantageous to be able to adapt the treatment to the individual. In this way, some of the treatment visits - which can be both time-consuming and accompanied by side effects - can be avoided.

MOB

The Molecular Oncology of the Bladder

Since 1994, systematic collection of tissue biopsies from bladder tumours for freezing has taken place in connection with the MOB project.
Approx. 4,100 patients participate in the MOB project, donating blood-, urine- and tissue samples from bladder cancer to the biobank.

The main purpose of this is to build a tissue biobank with associated clinical data and with the help of existing and newly-developed molecular-biological methods to study human bladder cancer.

The MOB project is an interdisciplinary collaboration between clinicians and biochemical/biological researchers, and the goal is to develop new molecular-biological technology to help diagnose, predict, treat and follow-up bladder cancer.

All patients who are suspected of having or are monitored for bladder tumours at the Department of Urology at Aarhus University Hospital can be included in the project.

All bladder tumour patients who have an endoscopic examination of the bladder or undergo surgery for bladder cancer in some other way may be included in the project, if there is tumour tissue present.

The MOB project is being carried out in close collaboration with the Department of Molecular Medicine MOMA. Read more about the project here.

Clinical responsibility: Professor, Consultant, DMSc Jørgen Bjerggaard Jensen

Funding: The MOB project is financially supported by The Danish Cancer Society.

PAGER

Clinically relevant biomarkers for predicting the progression of disease and therapy responses in patients with bladder cancer have still not been identified despite intensive research efforts. New technological advances in the mapping of our genome have made it possible to identify genomic changes which are specific to the individual patient's tumour. It is therefore now possible to use these technological advances for better monitoring of the individual patient's disease.

The purpose of this project is to use Next Generation Sequencing (NGS) to identify mutations and genomic changes in the genome of tumours from patients with bladder cancer. The changes will be used as patient-specific markers to follow the development of the disease over time. The specific objective of the project is:

  1. Identification of specific markers for testing of urine samples in patients with non-muscle invasive bladder tumour which is followed with cystoscopy procedures.
  2. Identification of specific markers for testing of blood samples in patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy and subsequent cystectomy.
  3. Identification of specific markers for testing of blood samples in patients with advanced muscle-invasive bladder cancer treated with chemotherapy.

With this project, we will shed light on whether it is possible to identify disease recurrence and disease exacerbation at an earlier point in time with the help of urine- and blood samples, thereby improving the survival rate of patients with bladder cancer. In addition, we will examine whether we can use personal biomarkers to avoid repeated endoscopic examinations of the bladder, thereby enabling patients to avoid the pain and side effects of this, and saving the large costs associated with the current monitoring examinations. In addition, the project will shed light on whether we can identify the spread of the disease earlier. This will make it possible to initiate chemotherapy at an earlier stage, which will ultimately improve patient survival. Finally, the measurement of chemotherapy effectiveness will ultimately ensure that the patients are offered the relevant treatment.

The PAGER project is being carried out in collaboration with the Department of Molecular Medicine (MOMA)

Clinical responsibility: Professor, Consultant, DMSc Jørgen Bjerggaard Jensen

Research coordinator for bladder cancer projects

Research nurse

Bente Thoft Jensen, PhD

benjense@skejby.rm.dk

Project nurses

Anna Munk Nielsen

Tel: +45 78 45 26 22/ +45 30 91 54 59
Email: annanils@rm.dk

Michael Pilemand Hjørnholm

Tel: +45 30 91 57 50
Email: micott@rm.dk

Vibeke Juul Morrison

Email: vimorr@rm.dk

PhD students

Project biomedical laboratory scientists

Jameela Safi

Tel: +45 30 91 56 32
Email: jamesafi@rm.dk

Birgitte Nielsen

Tel: +45 30 91 54 20
Email: birgitte.nielsen@aarhus.rm.dk

 

Professor secretary