(UroToday.com) The 2023 EAU annual meeting included a rapid fire session discussing common problems and controversies in bladder cancer, featuring a debate assessing whether we should be switching all patients to en-bloc TURBT.
Case Presentation
Dr. Paolo Gontero started with a case presentation of a 73 year old female, in overall good health (BMI 26), with a medical history of valvular hypertensive heart disease and breast cancer (treated with surgery and radiation), who presented with one episode of gross hematuria in August 2022. Bladder ultrasound suggested two lesions near the bladder trigone of 1 and 2 cm, cytology was atypical, and findings on cystoscopy showed multiple papillary looking lesions (main lesion 2 cm) grouped together in a 3 square cm area lateral to the right ureteral orifice. The question for the debaters: How best to resect this tumor?
Should we be Switching all Patients to En-bloc TURBT? Yes, Since it Follows Oncologic Principles
The position of switching all patients to en-bloc TURBT was taken by Dr. Georgios Gakis, who stated that several basic oncologic principles across multiple tumor types is to: (i) “resect en bloc”, (ii) “no touch”, and (iii) “early clamping”. One of the benefits of en bloc TURBT is to potentially provide T1 substaging with an appropriate specimen:1
Additionally, there is the importance of understanding lymphovascular invasion for T1 tumors, which may improve the selection of those T1 patients who should be offered early radical treatment. Dr. Gakis notes that there are several techniques of en-bloc resection of bladder tumors, including:
- Electric: mono vs bipolar, sling vs J-/TW-electrode
- Laser: Ho-YAG (13-30W, 20Hz), Th-YAG (15-30W), and KTP (30-120W)
- Water jet-assisted: hybrid instrument, monopolar
Yanagisawa et al. recently published a meta-analysis assessing the current evidence, with a focus on the pathological benefits of en bloc resection, for non-muscle-invasive bladder cancer.2 Among 13 randomized controlled trials, the pooled 12- and 24-month recurrence risk ratios were not statistically different between the 2 surgical techniques (0.96, 95% CI 0.74-1.23 and 0.83, 95% CI 0.55-1.23, respectively):
The pooled risk ratio for bladder perforation was 0.13 (95% CI 0.05-0.34) in favor of en bloc resection:
In randomized controlled trials, the differential rates of detrusor muscle presence (pooled RR 1.31, 95% CI 1.19-1.43) and of detectable muscularis mucosae (pooled RR 2.69, 95% CI 1.81-3.97) were more likely in patients receiving en bloc resection:
Patients who underwent en bloc resection had a lower rate of residual tumor at repeat transurethral resection than those treated with conventional transurethral resection of bladder tumors in 1 randomized controlled trial and 3 observational studies (pooled RR 0.47, 95% CI 0.31-0.71):
The EAU guidelines on non-muscle invasive bladder cancer suggest that we should perform en-bloc resection or resection in fractions (exophytic part of the tumor, the underlying bladder wall, and the edges of the resection area). The presence of detrusor muscle in the specimen is required in all cases except for TaG1/low grade tumors (strength of evidence: strong). Dr. Gagkis notes that there may be some technical limitations to this, including extent of the tumor base, lack of tangential view on the resection surface, and multiplicity (> 4 lesions).
Dr. Gakis concluded his presentation in favor for en bloc resection with the following conclusions:
- En bloc resection is underused and should be performed whenever technically feasible
- There is no data on superiority of a specific modality of en bloc resection
- En bloc resection improves the quality of bladder tumor resection
- It is important to keep the limitations of the technique in mind (location, tumor morphology, and extent)
Should we be Switching all Patients to En-bloc TURBT? No, Standard TUR is Sufficient, Plus En-bloc TURBT is not Possible in Many Cases
The position that standard TUR is sufficient, given that TUR en bloc resection is not possible in many cases was taken by Dr. Seth Lerner. Dr. Lerner started by highlighting several of the AUA guideline recommendations for initial diagnosis TURBT:
- Clinical Principle 1: At the time of resection, perform a thorough cystoscopic examination of a patient’s entire urethra and bladder documenting the tumor size, location, configuration, number and mucosal abnormalities
- Clinical principle 2: Complete visual resection of the bladder tumors, when technically feasible. Incomplete TURBT is likely a significant contributing factor to early bladder cancer recurrences, as tumors are seen at first surveillance cystoscopy in up to 45% of patients
- Clinical Principle: In a patient with non-muscle invasive disease who underwent incomplete initial resection (not all visible tumors treated), a clinician should perform repeat transurethral resection or endoscopic treatment of all remaining tumors, if technically feasible
Dr. Lerner emphasized that staged vs en bloc resection is a nuanced approach, as not one technique is perfect in all circumstances. There are several limitations to en bloc resection, as highlighted by Dr. Lerner:
- It is not necessary to resect detrusor muscle in patients with Ta low grade disease as long as the tumor is resected
- Ta high grade disease, according to the AUA guidelines, should be considered for repeat transurethral resection of the primary tumor within 6 weeks of initial TURBT
- En bloc resection is not always feasible and is often dictated by tumor location
- Larger specimens can be difficult to extract
- En bloc resection may result in deep resection into the fat and potentially limit the use of peri-operative single dose intravesical chemotherapy
- En bloc resection does not consistently improve recurrence free survival or significantly increase detrusor muscle in the specimen
Teoh and colleagues in 2020 published an International Collaborative Consensus Statement on en bloc resection of bladder tumor,3 incorporating two systematic reviews, a two-round Delphi survey, and a consensus meeting. They noted that en bloc resection was favored with regard to operative time, irrigation time, and bladder perforation rate, but there was no difference in recurrence at 0-12 months, 13-24 months, and 25-36 months.
Dr. Lerner concluded his portion of the case debate by highlighting several open questions/points and ongoing clinical trials:
- We need more clinical trials to focus on high grade disease
- We need better tools to identify patients likely harboring T1 disease
- Is en bloc TURB predictive of persistent/recurrent disease?
- Ongoing clinical trials are as follows:
- NCT05223491 (Aarhus): eligible for 2-6 cm papillary tumors (n = 220)
- NCT04712201 (Barcelona): eligible for <3 cm papillary tumors (n = 300)
- NCT04839029 (Egypt): any NMIBC is eligible; bipolar vs monopolar en bloc resection (n = 200)
- NCT05027412 (Madrid): eligible for 1-3 cm papillary tumors (n = 80)
Case Presented by: Paolo Gontero, San Giovanni Battista Hospital, University of Turin, Turin, Italy
Debater 1: Georgios Gakis, University Hospital of Wurzbug, Wurzburg, Germany
Debater 2: Seth Lerner, Baylor College of Medicine, Houston, Texas
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 European Association of Urology (EAU) Annual Meeting, Milan, IT, Fri, Mar 10 – Mon, Mar 13, 2023.
References:
- Jordan B, Meeks JJ. T1 bladder cancer: Current Considerations for diagnosis and management. Nat Rev Urol. 2019 Jan;16(1):23-34.
- Yanagisawa T, Mori K, Motlagh RS, et al. En bloc resection for bladder tumors: An updated systematic review and meta-analysis of its differential effect on safety, recurrence and histopathology. J Urol. 2022 Apr;207(4):754-768.
- Teoh JYC, MacLennan S, Chan VWS, et al. An International Collaborative Consensus Statement on En Bloc Resection of Bladder Tumour Incorporating Two Systematic Reviews, a Two-round Delphi Survey, and a Consensus Meeting. Eur Urol. 2020 Oct;78(4):546-569.