To assess whether a complete pathological respons (cPR) after neo-adjuvant chemotherapy can be predicted based on clinical, radiological, and histological variables and on a wide set of tissue and blood/urine (liquid biopsy) biomarkers (DNA/RNA).…
ID
Source
Brief title
Condition
- Bladder and bladder neck disorders (excl calculi)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The correlation between the clinical response during and after neo-adjuvant
chemotherapy (as assessed by clinical variables, radiological imaging, urine
cytology and histological examination on peroperative TUR) and the final
pathological response in the radical cystectomy (and lymph-node) resection
specimen.
Secondary outcome
1. The number of pathological complete responses (defined as ypT0N0 or ypTaN0
disease) after neo-adjuvant chemotherapy,
2. The number of participants in whom RC could have been withheld if clinical
response evaluation (CRE) and histological examination of TUR material after
neo-adjuvant chemotherapy correctly predicted a pathological complete response,
3. Predictors of complete pathological response such as age, gender, clinical
tumor stage, histological subtype, tumor size, radiological imaging, and a
wideset of tissue and liquid biopsy genetic biomarkers.
Background summary
Muscle-invasive bladder cancer (MIBC) is a highly aggressive disease with a
5-year mortality rate of 40-50%. The gold standard of treatment of MIBC is
neo-adjuvant chemotherapy plus radical cystectomy (RC), especially in those
with advanced stage disease. Interestingly, it is observed that following
neo-adjuvant chemotherapy and after RC, a subset of patients (approximately
20-40%) has no evidence of disease in the resected bladder or in the resected
lymphnodes. It might well be that a subset of patients following neo-adjuvant
chemotherapy might not benefit from radical surgery. These patients are
candidates for bladder preservation and active, close surveillance. For now, it
is not yet possible to properly identify patients in whom radical surgery could
be withheld.
In recent years, research is done on different predictive and prognostic
factors determined in tissue, blood, and urine and that may influence the
outcome of neo-adjuvant chemotherapy with respect to pathological complete
response. Somatic mutations, mutational burden, and molecular subtypes are
associated with a favorable response to neo-adjuvant chemotherapy or otherwise,
to chemoresistance.
Study objective
To assess whether a complete pathological respons (cPR) after neo-adjuvant
chemotherapy can be predicted based on clinical, radiological, and histological
variables and on a wide set of tissue and blood/urine (liquid biopsy)
biomarkers (DNA/RNA).
The results of this study will inform us about the number and percentage of
patients with a cPR after neo-adjuvant chemotherapy and will help to estimate
the number of patients needed for a subsequent randomized controlled trial. The
future so-called PREVENCYS trial will randomize patients into 2 strategy
groups: (1) neo-adjuvant chemotherapy plus surgery, and (2) neo-adjuvant
chemotherapy followed by an active surveillance.
Study design
Prospective multicenter cohort study, 36 months of inclusion
Study burden and risks
1. All participants will be asked to give 2 extra tubes of blood (approximately
30 mL) and urine during regularly foreseen blood collections at clinical and
outpatient visits. Urine is collected at similarly planned visits. These tissue
collections are scheduled (1) before start of neo-adjuvant chemotherapy at the
time of first diagnosis, (2) after completion of all four neo-adjuvant
chemotherapy cycles.
2. There are no additional site visits foreseen.
3. No questionnaires will be delivered.
4. Just prior to RC on the day of surgery with the patient under general
anesthesia, participants will undergo per-operative cystoscopy with bimanual
examination and TUR/biopsy of all visible lesions and/or scar tissue. This is
different than regular care. The risks of complications of this procedure (e.g.
marginal bleeding/bladder perforation) are negligibly low as the bladder is
also resected (by radical cystectomy) in the same procedure. The total
operation time will probably be increased by an estimated 30 minutes with a
total regular operating time of RC of 4 to 5 hours.
*
De Boelelaan 1117
Amsterdam 1007MB
NL
De Boelelaan 1117
Amsterdam 1007MB
NL
Listed location countries
Age
Inclusion criteria
- 18 year and older,
- Able to understand patient information form (PIF),
- Written informed consent, on study participation and genomic testing,
- Histological diagnosis of MIBC, i.e. cT2-T4a, WHO G1-G3 grade urothelial cell
carcinoma of the bladder, locally confined or locally advanced,
- Predominant histology is urothelial cell carcinoma (>50%),
- No evidence of regional or distant metastases, except for a single node in
the surgical template of extended pelvic lymph-node dissection (cN1), on
staging FDG-PET/CT before initiation of neo-adjuvant chemotherapy,
- Indication for neo-adjuvant chemotherapy and RC, as determined by local
multidisciplenary board,
- Cisplatinum-based chemotherapy, i.e. ddMVAC or Gem-Cis per local hospital
protocol,
- Clinical response evaluation (CRE) by CT abdomen/thorax with contrast after
the second cycle of neo-adjuvant chemotherapy (CRE1), and after completion of
neo-adjuvant chemotherapy (CRE2) should show stable disease or a partial local
radiological response (subgroup 1),
- CRE1 or CRE2 by CT scanning should show no evidence of residual tumor disease
(a complete radiological response), which is defined as pelvic lymph nodes <10
mm in diameter showing no contrast enhancement and a bladder wall of <10 mm
showing no contrast enhancement (RECIST criteria)(subgroup 2),
- CRE1 or CRE2 by CT scanning should show no evidence of pulmonary, osseous,
he-patic, or non-regional lymph-node metastases.
Exclusion criteria
- Not being able to receive neo-adjuvant chemotherapy as determined by the
Galsky criteria,
- Received less than three cycles of cisplatin-based chemotherapy,
- Not being able to undergo RC,
- Concomitant extensive CIS at diagnosis,
- Poor kidney function, under 60 ml/min/kg,
- Concomitant tumors of the upper urinary tract,
- Tumors of the urachus
- A known additional malignancy with the exception of basal cell carcinoma of
the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast
carcinoma), cervical cancer in situ that have undergone potentially curative
therapy,
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL70863.029.19 |