Bladder Cancer Clinical Trial
Official title:
A New Prognostic Model for Predicting the Outcome of Patients With Non-muscle Invasive Bladder Cancer Using Clinical Histopathological and Biological Markers
A prospective observational study to re-establish a new prognostic model for predicting the outcome in patients with non-muscle invasive bladder cancer (NMIBC) using the current recommendation regimen for intermediate and high risk groups and including all potential and highly prognostic factors.
Bladder urothelial carcinoma is the most common cancer of the urinary tract and is the 7th
most common cancer in males and the 7th most common cancer in females. Most of newly
diagnosed cases of urothelial cancer of the bladder are non-muscle invasive (NMIBC), and
including stages Ta, T1, or Carcinoma in situ (CIS). The initial management is endoscopic
resection, aiming at complete removal of all visible papillary lesions, and accurate staging
of the bladder tumor. The future plan is determined based on the results of
histopathological diagnosis and included either re-resection or adjuvant immunotherapy.
The incidence of recurrence and progression to muscle invasive disease after resection of
NMIBC reaches up to 42 % and 21%, respectively, concluding that alternative treatments are
urgently required. Therefore, the development of prognostic models is of ultimate importance
to minimize long-term morbidity and improve the outcome. The most commonly used
stratification systems are the European Organization for Research and Treatment of Cancer
(EORTC) risk tables and the The Club Urologico Espanol de Tratamiento Oncologico (CUETO)
scoring model. The EORTC risk tables have been constructed based on 2596 patients diagnosed
with Ta/T1 urothelial bladder carcinoma. Nevertheless, there were low number of patients
treated with BCG (7%), as well as immediate postoperative instillation of chemotherapy
(<10%); in addition, there was no second-look transurethral resection (re-TUR) of the
bladder was performed. The CUETO scoring model has been built based on a retrospective
analysis of 1,062 patients underwent TUR of bladder tumor followed by 6-month BCG
maintenance therapy. Nevertheless, the study was limited by the relatively old grading
systems, lack of re-TUR or immediate intravesical instillation, and inadequacy for
determining the time of recurrence.
Pan et al have developed a prognostic nomogram from the retrospective analysis of 1366
patients with NMIBC classified according to the 2004 World Health Organization
WHO/International Society of Urologic Pathology grading system. Similarly, this study was
limited by the retrospective nature, lack of the current recommendations of immediate
intravesical instillation, and lack of studying other different prognostic factors .
Ali-El-Dein et al have constructed a nomogram for recurrence and progression based on a
retrospective analysis of more than 1000 patients from a single institution. Nevertheless,
there was heterogeneity on the adjuvant regimens, in addition, re-TUR were not performed in
all patients.
Recently, Cambier et al have published their nomograms and risk stratification systems based
on a data from 1812 patients with intermediate risk and high risk NMIBC with adjuvant BCG
maintenance therapy 1-3 years. Although this study presents the first prognostic factor
analysis in NMIBC patients receiving the currently recommended 1-3 yr of maintenance BCG, it
has several limitations. There was no repeat transurethral resection in high risk patients
during the study period. In addition, there was no central pathology review, and there was
no data on upper tract status at time of recurrence or progression.
Although all previously mentioned nomograms have demonstrated significant ability for
detecting the outcome after transurethral resection of bladder tumor. Neither of these
papers has included any other biological markers that have been proven to improve the
predictive ability. Recently, special emphasis has been focused on the relation between
smoking with recurrence and progression of NMIBC. It has been shown that smoking not only
increases the risk of disease recurrence and progression, but also Current and heavy
long-term smokers seem to be at the greatest risk for both end points. In addition, Ogihara
et al have shown that a positive smoking history was an independent predictor for NMIBC
recurrence and refraining from smoking for 15 years or more reduced the risk of tumor
recurrence in former smokers with regardless of the intensity or duration of smoking.
Inflammation in the tumor microenvironment plays a crucial role in the proliferation and
survival of malignant cells through enhanced angiogenesis, invasion, and metastasis. The
underlying mechanisms include recruitment of T lymphocytes, chemokines, activated cytokines,
secretion of CRP, and neutrophilia . In a recent meta-analysis, Masson-Lecomte et al have
shown that among different inflammatory predictors, serum levels of C-reactive protein
(CRP), Neutrophil to lymphocyte ratio (NLR), and urinary and serum interleukin levels were
the most prognostic factors for bladder cancer prognosis. Furthermore, Kamat et al have
shown that a cytokine panel had the potential for identifying patients at risk of tumor
recurrence during BCG treatment. In addition, interleukin IL-2 have been shown to be the
most prognostic biomarker for response to BCG therapy.
In a recent meta-analysis including 15,215 patients, Martin-Doyle et al have shown that the
highest impact risk factor was depth of invasion into lamina propria. In addition,
lymphovascular invasion, associated carcinoma in situ, tumor size > 3 cm, and older age were
independent predictors for progression and cancer specific survival.
Currently, all publications investigating the outcome after treatment of NMIBC lack several
factors including the re-staging TUR, maintenance BCG therapy, inclusion of other highly
prognostic factors e.g. smoking, inflammatory biomarkers, depth of lamina invasion.
Therefore, this protocol is constructed to combine all clinically affordable biomarkers into
a prognostic model for predicting the outcome after NMIBC.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Not yet recruiting |
NCT06034015 -
A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of APL-1501 Extended Release (ER) Capsules Compared to APL-1202 Immediate Release (IR) Tablets in Healthy Volunteers
|
Phase 1 | |
Recruiting |
NCT04235764 -
En-bloc Transurethral Resection of Bladder Tumor (En-bloc TURBT) Specimens Using a Redesigned Surgical Resectoscope Device
|
||
Completed |
NCT02371447 -
VPM1002BC in Recurrent Non-muscle Invasive Bladder Cancer
|
Phase 1/Phase 2 | |
Recruiting |
NCT04081246 -
Transurethral Modified En Bloc Resection For Large Bladder Tumours.
|
N/A | |
Recruiting |
NCT06059547 -
Neoadjuvant Immunotherapy in Combination With the Anti-GDF-15 Antibody Visugromab (CTL-002) for Treatment of Muscle Invasive Bladder Cancer
|
Phase 2 | |
Terminated |
NCT04779489 -
Checkpoint Inhibitor and Radiation Therapy in Bulky, Node-Positive Bladder Cancer
|
N/A | |
Not yet recruiting |
NCT04493489 -
Propranolol Adjuvant Treatment of Bladder Cancer
|
Phase 2 | |
Completed |
NCT03520231 -
Study Comparing Denosumab With Standard Treatment in Urothelial Cancer Patients With Bone Metastases
|
Phase 2 | |
Recruiting |
NCT04537221 -
Nordic Cystectomy Study III - Transfusion
|
||
Withdrawn |
NCT03007771 -
Magnetic Resonance-guided High-Intensity Focused Ultrasound (MR-HIFU) Used for Mild Hyperthermia
|
Phase 1 | |
Completed |
NCT01955408 -
Severity of Overactive Bladder Symptoms in Patients After Synergo Treatment
|
N/A | |
Completed |
NCT04487457 -
Prospective Study to Evaluate the Blood Kinetics of Immune Cells and Immunosuppressive Cytokines After Exposure to an Immunity Checkpoint Inhibitor (ICI): Study of the Impact of Chemotherapy
|
||
Active, not recruiting |
NCT04383210 -
Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Advanced Solid Tumors
|
Phase 2 | |
Recruiting |
NCT05562791 -
A Study of 68Gallium PSMA-PET/CT Scans in People With Bladder Cancer
|
Phase 1 | |
Completed |
NCT00199849 -
NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine
|
Phase 1 | |
Completed |
NCT02781428 -
To Detect the Sensitivity of the UroMark Assay
|
||
Recruiting |
NCT04738630 -
Study of HX008 for the Treatment of BCG-Unresponsive Non-muscle Invasive Bladder Cancer
|
Phase 2 | |
Completed |
NCT03980041 -
Study to Evaluate the Efficacy/Safety of IPI-549 in Combination With Nivolumab in Patients With Advanced Urothelial Carcinoma (MARIO-275)
|
Phase 2 | |
Active, not recruiting |
NCT03978624 -
Window of Opportunity Study of Pembrolizumab Alone and in Combinations in Bladder Cancer
|
Phase 2 | |
Completed |
NCT04534309 -
Behavioral Weight Loss Program for Cancer Survivors in Maryland
|
N/A |