Dr. Beije began by laying the groundwork and rationale for the study. Disease-free survival (DFS) and overall survival for muscle-invasive bladder cancer remain poor despite surgical intervention. There is level one evidence supporting the use of neoadjuvant chemotherapy, demonstrating ~5-6% survival benefit at 5-10 years – yet utilization remains poor (~20% in the Netherlands). There is a need for biomarkers to guide treatment decision-making for these patients. CTCs, as a liquid biopsy, have been shown to be a strong prognostic marker for overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CSS).
Therefore, they hypothesized that patients without CTCs have such a good prognosis that they would not need Neoadjuvant chemotherapy (NAC). This was the basis of the CirGuidance Study, which was a multi-center CTC-driven intervention trial. Eligible patients are those with CT2-4a, N0-1, M0 urothelial carcinoma of the bladder.
The intervention was broken down into 2 arms, based on CTC status:
1) CTC negative: recommended for immediate cystectomy
2) CTC positive: advised to give NAC prior to cystectomy
They expected a 2-year OS of >75% in CTC negative patients for this to be considered a positive study.
However, it should be noted that most patients (192/203) who were CTC negative underwent immediate cystectomy. But, 47/70 patients who were CTC positive underwent immediate cystectomy – only 18 patients received NAC and cystectomy.
Unfortunately due to technical issues, he was not able to share the slides of his final results. He verbally relayed the final results as below:
- The study did NOT meet the primary overall survival endpoint
- 2-year OS was 69.5% - did not meet the prespecified cutoff
- However, CTC positive patients had better OS when they received NAC
His main conclusion, while the CirGuidance study was negative, CTC continues to be an interesting biomarker to use.
Dr. Roupret then gave his talk at this time.
He again reiterated the rationale for perioperative chemotherapy. Deaths from cancer are not typically due to local events; patients died of metastatic disease. Multi-agent chemotherapy can cure some patients with metastatic bladder cancer. Systemic therapy can eradicate micrometastatic disease; hence it can potentially improve cure rates.
Despite guideline recommendations for NAC, utilization remains poor. The underutilization of chemotherapy is sometimes due to patient ineligibility (renal function), but a significant proportion may be due to patient hesitancy or surgeon hesitancy (up to 33% in some studies).
He did touch a bit on the molecular classification system of urothelial carcinoma and the potential for a future treatment paradigm. However, he didn’t also note that this probably isn’t ready for primetime as testing for molecular classification has not yet reached the clinic. Current EAU guidelines support this by stating that treatment decisions cannot be made on molecular markers.
There is significant potential for a liquid biopsy, either cell-free DNA (cfDNA) or CTCs. CTCs were prognostic of CSS and RFS in prior retrospective series. He then reviewed the CirGuidance conclusions. Ultimately, while a negative study, he noted that CTC status was associated with improved survival in patients who were CTC positive and either got NAC/cystectomy or cystectomy alone. CTCs may be of us as an additional criterion next to clinical characteristics.
As a simple blood test and less invasive than a tissue biopsy, CTCs hold a lot of promise.
Presented by: Nick Beije, MD, Ph.D, Department of Medical Oncology and Cancer Genomics at Erasmus Medical Center Cancer Institute in Rotterdam, Netherlands
Discussant: Morgan Roupret, MD, Ph.D., Professor in the Academic Urology Department of the Pitie-Salpetriere Hospital in Paris, France at the Faculty of Medicine Pierre at Marie Curie, University Paris
Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Assistant Professor of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, @tchandra_uromd on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.