(UroToday.com) The 2024 European Association of Urology (EAU) annual congress held in Paris, France between April 5th and 8th was host to a plenary session addressing imaging-related controversies for the staging of genitourinary cancers. Professor Toine van der Heijden discussed why transurethral resection of bladder tumor (TURBT) is essential for the initial staging of bladder cancer and mandatory before any treatment.
TURBT is a technique first described in 1910 by Edwin Beer. The treatment of bladder tumors changed tremendously when it was found that bladder tumors could be eradicated using electrocoagulation through a cystoscope.
TURBT remains essential for histologic diagnosis. It helps determine:
- Presence/absence of histologic variants.
- Presence/absence of carcinoma in situ (CIS)
- Degree of tumor heterogeneity
- Presence/absence of prostatic urethral involvement
- Presence/absence of lymphovascular invasion
The current EAU guidelines for muscle invasive and metastatic bladder cancer currently recommend the following: “In case muscle invasive bladder cancer is suspected, tumors need to be resected separately in parts, which include the exophytic part of the tumour, the underlying bladder wall with the detrusor muscle, and the edges of the resection area.”
While imaging with computed tomography (CT) is an essential component of staging muscle-invasive disease, allowing for the evaluation of the extent of local tumor extension, potential spread to lymph nodes, and potential distant metastatic spread, relying on imaging alone in the diagnostic setting has significant limitations:
- Inability to differentiate between T1 and T3a tumors
- Only reliable for detecting invasion into the perivesical fat (cT3b) and adjacent organs (cT4)
- Accuracy of 55–92% in identifying extravesical tumor extension
As such, Professor van der Heijden argued that there is no role for relying on CT alone in the diagnostic work-up, in lieu of TURBT.
In addition to providing a histologic diagnosis, TURBT is crucial for the treatment of muscle invasive bladder cancer, specifically with regard to neoadjuvant chemotherapy and trimodality treatment. With regards to neoadjuvant chemotherapy, the EAU guidelines currently recommend offering neoadjuvant cisplatin-based combination chemotherapy to cisplatin-eligible patients with evidence of muscle-invasive disease (cT2-4aN0M0). However, there are important considerations should variant histology be present:
- Muscle-invasive pure squamous cell carcinoma of the bladder should be treated with primary radical cystectomy and lymphadenectomy
- Muscle-invasive pure adenocarcinoma of the bladder should be treated with primary radical cystectomy and lymphadenectomy
- T1 high-grade bladder urothelial cancer with micropapillary histology should be treated with immediate radical cystectomy and lymphadenectomy
These recommendations highlight the significance of TURBT in the treatment decision making paradigm given the importance of TURBT-derived histology for muscle-invasive disease treatment decision-making.
What about the impact of TURBT, namely radical TURBT, for trimodality therapy? Irrespective of whether patients undergo split or continuous course trimodality treatment regimens, a maximal TURBT is the first step in either paradigm.
The completeness of TURBT via visual assessment has important survival implications for patients undergoing trimodality therapy. In 2012, Efstathiou et al.1 demonstrated that patients that had a visibly complete TURBT, compared to those that did not, have superior:
- Complete response rates (79% versus 57%)
- 5- and 10-year overall survival rates (57% versus 43% and 39% versus 29%, respectively)
These results were confirmed in an updated report from the same cohort in 2017 that demonstrated that patients with complete TURBTs had improved overall and disease-specific survivals.2
While we have established that TURBT has important diagnostic and therapeutic advantages, there are notable limitations/disadvantages to TURBT:
- Can significantly delay definitive treatment while patients await and recover from the procedure (minority of patients)
- Can release circulating tumor cells via the hydrostatic pressure and opening of blood vessels during the procedure
- May be associated with staging errors (e.g., re-staging TURBT required for HGT1 patients due to risk of missing muscle-invasive disease)
In order to overcome delays to treatment with TURBT-directed pathways, the UK-based BladderPath trial was conducted to evaluate the role of magnetic resonance imaging (MRI) for bladder cancer staging. The study investigators enrolled patients with suspected bladder cancer through a hematuria clinic. Based on the potential for muscle invasive disease (assessed on a Likert scale at flexible cystoscopy), patients were enrolled and randomized to standard of care with TURBT assessment (Pathway 1) or MRI-based assessment (Pathway 2) with tumor biopsy. Patients who were felt, based on cystoscopy, to have probable non-muscle invasive disease all underwent TURBT.
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Patients in the MRI-based pathway had a median time to correct MIBC treatment of 53 days, compared to 98 days in for patients in the TURBT-based traditional pathway (p=0.0046). This equates to a 45 day delay with TURBT-based pathways.
While these results do not necessarily translate across all healthcare settings, they do highlight some of the unnecessary delays that do occur with TURBT-based management pathways for patients with muscle-invasive bladder cancer.
There is evidence to support the statement that TURBT leads to the release of circulating tumor cells into the bloodstream. Circulating tumor cells are vehicles for metastasis and display significant heterogeneity (epithelial, mesenchymal, or stem cells-like phenotypes). Such cells may cluster, becoming more resistant to stress, which leads to a higher clonal survival advantage and worse metastatic potential.
In 2015, Engilbertsson et al. demonstrated that the circulating tumor cell count in the cardiovascular system increases during TURBTs, supporting the tumor cell shedding theory.3
Indirect evidence to further support this theory comes from a study by Huang et al. that demonstrated that among patients with pT3-4 disease at cystectomy, patients who underwent cystoscopic biopsy had superior survival outcomes compared to those who underwent a TURBT,4 which may be due to tumor cells being shed into the blood stream via TURBTs.
Understaging with TURBT remains a concern. A 2010 systematic review of the literature by Kulkarni et al. demonstrated that 26 to 50% of patients with HGT1 bladder cancer managed with immediate or early radical cystectomy are pathologically upstaged.5
Given that TURBT has been around since 1910, is it time for innovation in this space? Professor van der Heijden highlighted BladParadigm (NCT05779631), which is a two-arm multicenter randomized controlled trial in patients suspected to have muscle-invasive bladder cancer:
- Arm 1: Standard TURBT
- Arm 2: mpMRI + bladder biopsy
This study will enroll patients between 2023 and 2028. The study endpoints are as follows:
- 2-year progression-free survival after diagnosis
- Time to definitive treatment
- Quality of life
- Cost effectiveness
Until additional results are available, Professor van der Heijden emphasized that it remains essential to perform a TURBT.
Presented by: Professor Toine van der Heijden, MD, PhD, Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 European Association of Urology (EAU) annual congress, Paris, France, April 5th – April 8th, 2024
References:
- Efstathiou JA, Spiegel DY, Shipley WU, et al. Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the MGH experience. Eur Urol. 2012;61(4): 705-11.
- Giacalone NJ, Shipley WU, Clayman RH, et al. Long-term Outcomes After Bladder-preserving Tri-modality Therapy for Patients with Muscle-invasive Bladder Cancer: An Updated Analysis of the Massachusetts General Hospital Experience. Eur Urol. 2017;71(6): 952-960.
- Engilbertsson H, Aaltonen KE, Bjornsson S, et al. Transurethral bladder tumor resection can cause seeding of cancer cells into the bloodstream. J Urol. 2015;193(1): 53-7.
- Huan H, Liu Z, Li X, et al. Impact of preoperative diagnostic TURBT on progression-free survival in patients with pathological high-grade, stage T3/T4 bladder urothelial carcinoma. Oncotarget. 2017;8(51): 89228-89235.
- Kulkarni GS, Hakenberg OW, Gschwend JE, et al. An updated critical analysis of the treatment strategy for newly diagnosed high-grade T1 (previously T1G3) bladder cancer. Eur Urol. 2010;57(1): 60-70.