Identification of muscle-invasive bladder cancer patients who will not benefit from neoadjuvant chemotherapy using circulating tumor cells.

Background of the study:

Non-metastatic muscle-invasive bladder cancer (MIBC) is a potential lethal disease as half of the patients develop metastases after curative treatment. Neoadjuvant chemotherapy followed by radical treatment gives a statistically significant, though limited survival benefit (hazard ratio 0.84 (95% CI, 0.72-0.99) at 10 years). However, as neoadjuvant chemotherapy can be accompanied by severe toxicity, physicians are reluctant to embed neoadjuvant chemotherapy leading to different treatment approaches across centers. Identification of patients who will and who will not benefit from neoadjuvant chemotherapy is therefore of great clinical relevance.



Objective of the study:

Primary study objective is to prospectively assess whether the presence of CTCs in the peripheral blood of nonmetastatic MIBC patients can identify patients with such a good prognosis not justifying neoadjuvant chemotherapy.



Secondary study objectives include the association of CTC-positivity or negativity with cancer-specific survival, relapsefree
survival, local relapse-free survival and metastasis-free survival, as well as assessing the prognostic value of a 20-
gene expression profile in non-metastatic MIBC patients and its added value to a CTC count.



Study design:

Prospective, open study.



Study population:

Patients with stage T2-T4aN0-1M0 urothelial carcinoma of the bladder who are candidate for radical local treatment (radical cystectomy).



Primary study parameters/outcome of the study:

The primary endpoint for this study will be the 2-year overall survival rate in nonmetastatic MIBC patients without
detectable CTCs treated with radical local treatment without prior neoadjuvant chemotherapy.



Secundary study parameters/outcome of the study:

Secondary endpoints include 2-year overall survival in the remaining patients and cancer-specific survival, relapse-free
survival, local relapse-free survival and metastasis-free survival for all the patients. In addition, the expression pattern of the 20-gene panel is also a secondary endpoint.



Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
In all patients, 10 mL blood for CTC enumeration will be drawn at baseline during another blood draw that is already
required for standard care. It is hypothesized that patients without detectable CTCs will not benefit from neoadjuvant chemotherapy, sparing this
particular group of patients from a toxic and expensive treatment.

Patients without detectable CTCs will not benefit from neoadjuvant chemotherapy.

- 2-year overall survival rate in nonmetastatic MIBC patients without
detectable CTCs treated with radical local treatment without prior neoadjuvant chemotherapy.

- 2-year overall survival in the remaining patients and cancer-specific survival, relapse-free survival, local relapse-free survival and metastasis-free survival for all the patients.

In all patients, CTCs will be enumerated. If no CTCs are detected, the patient will proceed to undergo local radical treatment (radical cystectomy) and will not receive neoadjuvant chemotherapy. In the case CTCs are detected, patients may undergo neoadjuvant chemotherapy followed by radical local treatment, dependent on the local guidelines.