En bloc resection of bladder tumor: Is it the way forward?

More than 2 centuries ago, Philipp Bozzini invented the Lichtleiter, allowing urologists to visualize what is inside the bladder.¹ About 1 century ago, Maximilian Stern invented the first resectoscope, which allows us to remove a bladder tumor with electrocautery.² These 2 crucial elements empowered urologists to perform transurethral resection of bladder tumor (TURBT), a highly revolutionary approach given the limited resources that urologists had at that time.

Jeremy Teoh, MBBS, FRCSEd (Urol), FCSHK, FHKAM (Surgery)

The conventional method of performing TURBT is to resect the bladder tumor with a top-down approach in a piecemeal manner. This is probably the only procedure that violates 2 major oncological principles. First, although we try to avoid manipulating or touching the tumor in most other cancer surgeries, in conventional TURBT, we actively resect the bladder tumor and retrieve the tumor fragments after resection. This piecemeal resection approach creates many floating tumor cells that can reimplant into the bladder wall, leading to early disease recurrence.³ Previous genomic studies have shown that in patients with multiple bladder tumors, the bladder tumors seem to share the same clonal origin.^4,5 This is indirect evidence showing that tumor seeding within the bladder can occur. Second, as surgeons, we are always obsessed with resection margins. In conventional TURBT, with the tumor fragments that we get, we can never assess the resection margin properly.³ Whether a complete resection has been achieved is dependent on the surgeon’s bare vision, which is prone to error due to possible cautery artefact and desmoplastic reactions. Instead of using resection margins, we rely on surrogates such as the presence of detrusor muscle as a quality indicator.⁶ We even offer second-look TURBT as a maneuver to compensate for the first TURBT.⁷ Perhaps with advancements in technology and surgical techniques, we should develop new and better ways of performing this common and important procedure.

Transurethral en bloc resection of bladder tumor (ERBT) has been proposed as a potentially superior surgical technique in performing the tumor resection procedure.⁸ With the current bipolar and laser technology, it has become much easier to perform the ERBT procedure. The procedure starts with a comprehensive inspection of the whole bladder, preferably with enhanced imaging such as narrow-band imaging, IMAGE1 S, or photodynamic diagnosis. We then mark the intended circumferential resection margin, about 5 mm from any visible bladder tumor. The mucosa is then incised circumferentially down to the detrusor muscle. Mucosa and submucosa are soft, and the detrusor muscle is more fixed at the resection bed. Hence, after the whole circumferential incision, you will notice that the entire bladder tumor will shrink into the center of the resection bed. The tumor base is then incised at the level of the detrusor muscle by both blunt dissection and sharp incision. You will appreciate the natural anatomical plane between the submucosa and detrusor muscle; hence, the incision depth can be extremely precise. In a way, ERBT is a surgical approach that reinforces the surgeon’s need to be more systematic throughout the entire resection procedure, from the periphery to the center, from normal to abnormal, and to achieve a decent resection in an en bloc manner. By removing the bladder tumor in a single piece, we can avoid tumor fragmentation and minimize the risk of tumor reimplantation after the procedure. Moreover, the en bloc specimen can be properly inked to assess the resection margins. A negative resection margin can determine whether a complete local resection has been achieved. The next important question is, is there any solid evidence to support this approach?

The EB-StaR study (NCT02993211), which is a multicenter randomized phase 3 trial comparing ERBT with conventional TURBT in bladder tumors smaller than 3 cm was published in 2024.⁹ This study involved 13 hospitals and included 350 patients. The study found that, in patients with non–muscle-invasive bladder cancer (NMIBC), ERBT could reduce the 1-year recurrence rate from 38.1% to 28.5%. Upon subgroup analysis, patients with a single tumor, a 1-cm to 3-cm bladder tumor, Ta disease, or intermediate-risk NMIBC benefited the most from the ERBT procedure. We found that the surgical benefit appears to occur as early as 3 months, which is understandable given the goals of achieving a complete local tumor resection and minimizing tumor reimplantation. However, we also observed a jump in tumor recurrence at the 1-year time point, presumably due to tumor factors such as multifocality, carcinoma in situ, and field change cancerization.³ We further looked into the subgroup of ERBT plus intravesical BCG therapy group. Interestingly, we found that ERBT could offer short-term oncological control, and the addition of intravesical BCG therapy could offer additional longer-term oncological control. Although the sample size in this subgroup was just 43 patients, we are excited to see a 5% recurrence rate at 1 year and a 10% recurrence rate at 2 years in patients with high-risk NMIBC following ERBT plus intravesical BCG therapy. We believe a good surgery with ERBT, plus a good adjuvant therapy with intravesical BCG or other novel agents, is the key to cure for the majority of NMIBC cases.

The international collaborative consensus statement on ERBT serves as a good reference standard for urologists who would like to perform ERBT.¹⁰ As urologists, we are the gatekeepers, and we must always perform the best possible surgery to optimize oncological outcomes. TURBT is and will always be the cornerstone treatment of NMIBC. The historical question about ERBT has always been, “Why should I do it?” With the increasing evidence and the potential benefits that we see, perhaps we should ask ourselves, “Why not?” •

References

1. Engel RM. Philipp Bozzini--the father of endoscopy. J Endourol. 2003;17(10):859-862. doi:10.1089/089277903772036145

2. Herr HW. Early history of endoscopic treatment of bladder tumors from Grunfeld’s polypenkneipe to the Stern-McCarthy resectoscope. J Endourol. 2006;20(2):85-91. doi:10.1089/end.2006.20.85

3. Teoh JY, Kamat AM, Black PC, Grivas P, Shariat SF, Babjuk M. Recurrence mechanisms of non-muscle-invasive bladder cancer - a clinical perspective. Nat Rev Urol. 2022;19(5):280-294. doi:10.1038/s41585-022-00578-1

4. Simon R, Eltze E, Schafer KL, et al. Cytogenetic analysis of multifocal bladder cancer supports a monoclonal origin and intraepithelial spread of tumor cells. Cancer Res. 2001;61(1):355-362.

5. Acar O, Özkurt E, Demir G, et al. Determining the origin of synchronous multifocal bladder cancer by exome sequencing. BMC Cancer. 2015:15:871. doi:10.1186/s12885-015-1859-8

6. Mariappan P, Zachou A, Grigor KM, Edinburgh Uro-Oncology G. Detrusor muscle in the first, apparently complete transurethral resection of bladder tumor specimen is a surrogate marker of resection quality, predicts risk of early recurrence, and is dependent on operator experience. Eur Urol. 2010;57(5):843-849. doi:10.1016/j.eururo.2009.05.047

7. Yanagisawa T, Kawada T, von Deimling M, et al. Repeat transurethral resection for non-muscle-invasive bladder cancer: an updated systematic review and meta-analysis in the contemporary era. Eur Urol Focus. 2024;10(1):41-56. doi:10.1016/j.euf.2023.07.002

8. Teoh JY, D’Andrea D, Gallioli A, et al. En bloc resection of bladder tumor: the rebirth of past through reminiscence. World J Urol. 2023;41(10):2599-2606. doi:10.1007/s00345-023-04547-0

9. Teoh JY, Cheng CH, Tsang CF, et al. Transurethral en bloc resection versus standard resection of bladder tumor: a randomised, multicentre, phase 3 trial. Eur Urol. 2024;86(2):103-111. doi:10.1016/j.eururo.2024.04.015

10. Teoh JY, MacLennan S, Chan VW, et al. An international collaborative consensus statement on en bloc resection of bladder tumor incorporating two systematic reviews, a two-round delphi survey, and a consensus meeting. Eur Urol. 2020;78(4):546-569. doi:10.1016/j.eururo.2020.04.059