Challenges that derail oncology programs and how to anticipate them earlier
Bladder cancer programs don’t fail because of one big mistake. They stall from a series of small, predictable risks whose effects compound. Below are the risks we see most often in early‑phase oncology programs and what to do differently.
Trial design versus standard-of-care shifts
Risk: Bladder cancer (BC) is not one disease, and standard of care (SOC) keeps shifting across non-muscle invasive BC, muscle invasive BC, and metastatic settings.
- Control arms lose relevance mid‑study. New approvals or label expansions can render comparators less ethical or less attractive to investigators and patients.
- Endpoints carry operational consequences. Recurrence-free survival (RFS), disease-free survival (DFS), and event-free survival (EFS) mean very different visit schedules, cystoscopy frequency, imaging cadence, and adjudication needs.
What to do: Before finalizing the protocol build an amendment‑ready design (decision trees, pre‑defined contingency language) and stress‑test endpoints for operational load.
Site saturation & competition
Risk: Leading uro‑oncology centers can support only a finite number of bladder studies at any given time, and large pharma often reserves capacity early. Overlapping inclusion/exclusion (I/E) criteria, similar visit schedules, and tight prior‑treatment windows compress the patient-eligible pool and slow enrollment.
What to do: Pair a few flagship centers with high‑performing community urology groups and large urology networks. Use performance data (not reputation) to select sites and stagger activations to protect your patient screen‑to‑randomize flow.
Urology workflow mismatch
Risk: Bladder cancer trials are procedure‑heavy and often run in clinics optimized for volume, not research throughput.
- Catheterization, intravesical administration, and retention monitoring disrupt typical clinic flow.
- Research‑naïve sites may lack dedicated coordinators or standard operating procedures (SOPs) for investigational product (IP) handling and documentation.
What to do: Prioritize intravesical‑experienced sites (or provide targeted training and mock runs), define retention‑monitoring SOPs, and validate coordinator capacity before site initiation visit (SIV) not after first patient first visit (FPFV).
Biomarker feasibility traps
Risk: Biomarker requirements narrow the pool of patients, and sponsors often overestimate patient enrollment rates.
- Fibroblast growth factor receptor (FGFR) alteration prevalence in the actual enrolling population at chosen sites/regions.
- PD‑L1 alignment, including assay selection, scoring, cutoffs, and turnaround times (TATs) that push out screening decisions.
- Tissue adequacy considerations versus archival samples are insufficient. Re‑biopsy can add delays and screen fails.
What to do: Model realistic prevalence with site‑level historical data, lock alignment with central/local labs, and pre‑clear tissue workflows, such as couriers, pathology release forms, and backup plans for re‑biopsy.
Patients access realities
Risk: With bladder cancer, median age is high; comorbidities, transportation barriers, and polypharmacy are common. Protocols written for ideal candidates drive avoidable screen fails, visit non‑compliance, and retention issues—especially with cystoscopy‑heavy schedules.
What to do: Design pragmatic visit schedules, allow visit windows where possible, enable tele‑touchpoints for non‑procedural visits, and build in transport support.
Procedural data variability
Risk: Quality gaps rarely show in the synopsis but can manifest months later as delays and added costs.
- Cystoscopy documentation, such as photos, measurements, or lesion mapping, is inconsistent across sites.
- Transurethral resection of bladder tumor (TURBT) notes may lack eligibility‑critical detail.
- Intravesical logs that contain dose prep, dwell time, retention confirmation, or interruptions are often incomplete.
What to do: Standardize procedure templates, create quick‑reference photo documentation guides, and implement source checklists for intravesical visits. Audit early during SIV and in the first several patients.
Amendments and rescue efforts
Risk: One small upstream decision like a narrow biomarker, inflexible comparator, or rigid visit windows cascades into amendments, site retraining, re‑consent, and restart‑up—each one adding costs, friction, and recruitment delays.
What to do: Run a feasibility‑first design review with pressure‑tests that include expected screen‑fail drivers, SOC volatility, competing‑trial load at target sites, lab TAT assumptions, and operational math (e.g., coordinator hours per visit schedule).
What’s next?
Don’t let underestimated risks derail your development timeline. Connect with Catalyst Oncology experts to de‑risk your bladder cancer trial design.
