En Bloc Transurethral Resection of Bladder Tumors: A New Standard?

Abstract

Objective:

To assess safety and efficacy, namely pathological assessment of the specimen and recurrence rate, of en bloc transurethral resection (EBTUR) of bladder tumor.

Materials and Methods:

We performed a systematic review of the available literature on PubMed. Seventeen articles, mainly prospective case series, were found. EBTUR is performed with a great variety of equipments, whereas the resection technique is similar.

Results:

Overall, 895 patients have been submitted to EBTUR, accounting for 1191 lesions. Forty complications (4%) were computed. Only 10 (1%) were grade III, mostly bladder perforation or bleeding. Fifty-nine conversions (6.5%) to conventional transurethral resection (TUR) have been reported because of difficult locations of tumors or failure to extract the specimen. Several series, accounting for 763 patients, report about incidence of detrusor muscle in the specimen. Overall, 731 (96%) cases with detrusor muscle were computed. Tumor stage remained uncertain only in 12 (1.5%) cases. Follow-up data were available for 544 patients. Mean follow-up ranged from 9.3 to 40 months. Recurrence rate varied from 6% to 55%. Most of the recurrence occurred outside primary tumor site. Mean weighted follow-up across all series was 20 months, whereas overall recurrence rate was 23%.

Conclusions:

Irrespective of the technique adopted, EBTUR is a safe procedure. The presence of detrusor muscle in the specimen is high if compared with historical series of conventional TUR. Indeed, recurrence rate is comparable. The objective advantage of a proper histological assessment suggests to perform EBTUR instead of conventional TUR, when feasible.

Introduction

Transurethral resection (TUR) is one of the most frequent procedures performed in urology. Indeed, it is one of the most controversial.¹ It clearly violates oncological basic principles inasmuch as tumor must be fragmented to be resected and retrieved from the bladder. Fragmentation is at the base of two major flaws. First, the pathological examination of the specimen is frankly impaired. Margins cannot be properly assessed and infiltration of the suburothelial connective or of the muscular tissue may be underestimated or even missed. Second, seeding of urothelial cancerous cells, which may lead to recurrence, may easily occur after tumor resection and fragmentation.

En bloc transurethral resection (EBTUR) is supposed to overcome the major flaws of conventional TUR. It is not a new procedure since it has been described (the first time) in 1980 in Japan,² but only in the last decade the interest in technical improvements of TUR has been renewed.¹ We performed a literature review to assess up-to-date results of EBTUR and to answer the question if EBTUR may be considered as the new golden standard for endoscopic treatment of bladder tumors.

Materials and Methods

We performed a systematic review of the available literature about EBTUR. A search across PUBMED was performed with the following keys “bladder cancer” [MESH term] and “en bloc” and “en bloc resection bladder tumor” on July 20, 2016. Respectively, 132 and 160 articles were found. After reading the abstract, 118 and 141 were excluded by authors because they were off-topic reviews and opinions. After matching the list of the remaining 14 and 20 items, 14 were excluded because they were duplicates, 2 because they were case reports, and 2 because they were not written in English. Thus, a list of 16 original articles was included in the review.^{3

–18} Finally, after reading thoroughly the references of selected articles, one more significant item was added.¹⁹

Main outcomes were safety (complication rate), pathological assessment (incidence of detrusor muscle in the specimen and rate of appropriate staging), and oncological control (recurrence rate, surgical margins, rate of residual disease).

Results

Quality of the evidence

Three articles were retrospective case series analyses,^11,18,19 11 were prospective observational studies.^{3,4,6
–8,12

–17} Only three prospective randomized studies^5,9,10 compared EBTUR with TUR, assessing, respectively, recurrence rate^5,9 and detrusor muscle presence in the specimens.¹⁰ As a matter of fact, EBTUR comprises many different techniques so that a discrete heterogeneity should be taken into account when reporting pooled results, especially about recurrence.

Technicalities and surgical techniques

A great variety of techniques have been described to resect, en bloc, the lesions.

All authors except one¹¹ report the use of 24F/26F resectoscope. Many energy sources were employed: monopolar or bipolar electrocautery, various types of lasers (holmium, thulium, green light KTP), and water-jet hydrodissection. Concerning electrocautery, authors used standard loop, 45° or 90° bended loop, J-shaped electrode, Collins loop, and snare.

Irrespective of technicalities, the tumor was usually dissected surrounding its base with an incision that leaves a precautionary margin of apparently healthy tissue. The dissection is progressively deepened through the bladder wall while getting closer to the base of the lesion, including a thick layer of muscular fibers in the specimen. The location of the tumor may be technically demanding and sometimes requires modifications to the technique, especially at the bladder neck, at the anterior wall of the bladder, or in proximity of ureteral orifices.

Indeed, specimen extraction varies among the studies. It is performed with syringe or Ellik evacuator through the resectoscope sheath or with forceps, grasps, or retrieval bags through the sheath or through the urethra. The main limit is the dimension of the specimen and its consistency, inasmuch as papillary tumors may be extracted grasping their base and are compliant to some degree of stretching where solid tumors are not. Many authors overcome the problem avoiding to resect tumors greater than a certain dimension,^{3,4,6,7,11,12,14} generally fixed at 2/3 cm. Some authors propose to extract noncompliant lesion in a divisional manner, cutting the specimen in 2 or 4 pieces.^4,8,16 Some others indeed propose to use nets or bags to maintain tumor integrity while avoiding tumor spillage during extraction.^6,11,13,15 Overall, extraction's feasibility of intact lesion as much as 4 to 5 cm has been demonstrated in some series, even without dividing the specimen.^11
–13 A detailed description of resection and extraction equipment has been reported in Table 1.

Table 1.

Characteristics of Selected Studies

References	Study type	Patients number	Resection equipment (unless specified it has been used a 24F/26F resectoscope)	Extraction equipment
Hurle et al.³	Prospective observational	74	Collins loop	Ellik evacuator through resectoscope sheath/laparoscopic grasp through nephroscope sheath
Migliari et al.⁴	Prospective observational	58	Multipulse Tm +1470 thulium laser, diode+thulium laser fiber	Not reported
Chen et al.⁵	Prospective randomized	71	Tm:YAG 2 μm continuous wave laser fiber set at 30 to 50 W	Not reported
Kramer et al.⁶	Prospective observational	221	Laser and electrical	Forceps, retrieval bags
He et al.⁷	Prospective observational	45	Green light KTP laser with a front-firing fiber set at 30 W	Ellik evacuator through resectoscope sheath
Muto et al.⁸	Prospective observational	55	Tm:YAG 2 μm continuous wave laser fiber set at 30 W	Grasper through resectoscope sheath
Sureka et al.⁹	Prospective randomized	30	Loop bent at 45°	Grasping forceps through nephroscope sheath
Upadhyay et al.¹⁰	Prospective randomized	21	Loop bent at 45°	Syringe through resectoscope sheath
Maurice et al.¹¹	Retrospective	9	21F rigid cystoscope/7F monopolar polypectomy snare	Multipurpose endoscopic mesh net retrieved with the scope through urethra
Naselli et al.¹²	Prospective observational	26	Collins loop	Laparoscopic 5-mm clamp retrieved with the scope through urethra
Fritsche et al.¹³	Prospective observational	17	Water-jet hydrodissection	Endobag
Wolters et al.¹⁴	Prospective observational	6	Tm:YAG laser fiber set at 10 to 15 W	Grasper through resectoscope sheath
Nagele et al.¹⁵	Prospective observational	5	Water-jet hydrodissection	Prototype nylon retrieval bag
Ukai et al.¹⁶	Prospective observational	97	J-shaped electrode	Biopsy forceps through resectoscope sheath
Lodde et al.¹⁷	Prospective observational	37	Flat loop	Syringe through resectoscope sheath
Saito¹⁸	Retrospective	35	Holmium fiber laser at bladder neck; Collins electrode other locations	Loop electrode through resectoscope sheath
Ukai et al.¹⁹	Retrospective	88	J-shaped electrode	Biopsy forceps through resectoscope sheath

Feasibility and safety

Overall, 895 patients have been submitted to EBTUR,^{3

–19} accounting for 1191 lesions. Among 17 reports, the complication rate was negligible. It ranged from zero to a maximum of 26% grade I–II and 3% grade III,⁶ according to Clavien–Dindo classification. Forty complications of 895 cases (4%) were computed.^{3

–19} Only 10 (1%) were grade III, mostly bladder perforation or bleeding. Interestingly, 59 conversions (6.5%) to conventional TUR have been reported. The causes of conversion were mainly (1) a difficult location of the tumor, namely anterior wall, bladder neck, or ureteral orifice, and (2) failure to extract the specimen.^{3

–19}

Pathological examination

Several series, accounting for 763 patients, report the presence of detrusor muscle in the specimen.^{3,4,6

–11,13

–17,19} Overall, 731 (96%) cases with detrusor muscle were computed. As a whole, tumor stage remained uncertain in 12 (1.5%) cases only. Upadhyay and associates compared, in a prospective randomized study, detrusor muscle incidence in a group of patients submitted to EBTUR or conventional TUR. Characteristics of the tumor were similar in the two groups, whereas incidence of detrusor muscle was 20/21 (95%) in cases treated with EBTUR vs 15/25 (60%) with standard TUR.¹⁰

Oncological control

Rate of residual disease after reTUR (second look) of the resection bed was ∼0% (only 1 case of 119) when assessed for study protocol.^4,8,14

Despite assessment of the margins being possible, it has not always been reported.^{3,6,13

–16} Overall, 7 (1.7%) positive margins were found of 420 patients.

Follow-up data were available for 544 patients. Mean follow-up ranged from 9.3 to 40 months. Recurrence rate varied from 6% to 55%. Mean weighted follow-up across all series was 20 months, whereas overall recurrence rate was 23%.^{3

–19} Two prospective randomized studies were designed to disclose a difference in recurrence rate in favor of EBTUR.^5,9 The expected reduction was 40% with a recurrence rate of 60% for standard TUR in one study,⁹ whereas it has not been reported in the other.⁵ Both failed to demonstrate any significant advantage. However, it must be emphasized that when data are available most of the recurrences, namely 58/75 (77%), were outside the primary tumor site.^3

–6,8,9

Discussion

Conventional TUR of bladder tumor is generally performed with a 24F/26F continuous flow resectoscope and standard loop. Tumor is fragmented in chips by the incise and scatter technique and extracted with a syringe or an Ellik evacuator through the working channel. Cell seeding may occur during resection as well as during extraction of tumor. Moreover, tumor fragmentation impairs pathological examination. There is no clear orientation of the specimen, muscular or subconnective tissue infiltration may be underestimated or even missed as well as a proper assessment of surgical margins is impossible, even if additional biopsies of the resection bed and of perilesional margins are performed.^1,20,21 Nevertheless, it is yet one of the most common procedures performed in urology without any significant innovation beyond optical technologies.²¹

Conversely, EBTUR respects the oncological principle of specimen integrity with a safety margin of healthy tissue. Even if the first article about EBTUR has been printed in the eighties,² it is yet in its infancy, inasmuch as only about a thousand of cases have been published to date.

Despite a similar surgical technique, a great variety of equipments for resection and for specimen extraction have been used, adding heterogeneity to the result interpretation.^{3

–19}

Concerning the surgical technique, urological surgeons incise bladder mucosa surrounding the tumor base using a safe margin of healthy tissue. The resection is then completed, dissecting deeper through the bladder wall toward the lesion base to obtain a specimen, including a thick portion of muscular fibers.

Irrespective of the equipment, it is possible to resect without fragmentation lesions of 4 to 5 cm,^{3

–19} whereas the biggest lesion ever treated was 7 cm.¹³ Optical technologies may help in defining the safe margin of healthy mucosa when available.²¹ Photodynamic enhancement has been used for the purpose.¹³ Indeed, we found it useful to assist EBTUR with narrow band imaging to detect and include little satellite tumors and to improve perilesional margins' definition.

Most concerns regard specimen extraction, especially in the male. It is well known that through a standard 26F resectoscope, lesions greater than 2 cm cannot be removed from the bladder with a syringe or with an Ellik evacuator. Some authors proposed to cut specimens in 2/4 smaller pieces. Despite that architecture of the tumor may be reconstructed once outside bladder, one of the main advantages of en bloc resection, namely specimen integrity, would be theoretically lost. However, using forceps or clamps, through a standard or a larger working channel adapted for morcellation or through a nephroscope, greater lesions can be easily extracted. Otherwise, the specimen may be retrieved by means of a net or bag through the urethra, under visual control of the resectoscope.^6,11,13,15 Maurice and associates adopted an endoscopic mesh net.¹¹ Nevertheless, it is reasonable to hypothesize that tumor spillage may occur through the net during manipulation of the tumor. Alternatively, a nylon prototype bag¹⁵ or endoscopic retrieval endobags designed for gastroenterology procedures¹³ were employed. Endobags seem to be the safest oncological option overall.

Beyond technicalities, two main aspects must be underlined. First, EBTUR is safe; the risk of serious complications is negligible, whereas the overall risk of complications is comparable with historical TUR series.²⁰ Second, pathological assessment is by any means far more precise. The incidence of detrusor muscle in the specimen, about 95%, and the rate of appropriate staging, about 99%, are really high if compared with standard TUR.^20,21 Pathological assessment of lateral and deep margins is also possible thanks to specimen integrity. Despite it being theoretically one of the major advantages of EBTUR, it has been underused,^{3,6,13

–16} maybe due to a certain reluctance of pathologists to change their routine reports.

Thus, EBTUR has a clear advantage with respect to conventional TUR. Somehow, it forces the surgeon to perform a complete resection while pathological stage is easily assessed, reducing the risk of understaging and missing eventually fatal diseases. Concerning oncological control, the rate of residual disease after a second look performed for protocol was close to 0%,^4,8,14 which is significantly lower than historical TUR series,^20,21 as well as the incidence of recurrence in the bed of the primary tumor, which is about 20% in EBTUR series.^3

–6,8,9

Nevertheless, overall recurrence rate appears to be similar, about 20% over a 2-year period.^{3

–19} Particularly, two prospective randomized studies included in our analysis failed to demonstrate superiority of EBTUR.^5,9 The study design assumed a reduction of the recurrence rate of about 40% in the EBTUR group in one study over a period of time (which has not been disclosed) presumably of 4 years.⁹ The objective was reached with a study population of about 45 cases.⁹ Recurrence rate was indeed similar in EBTUR and TUR groups in a population of 125 patients followed up for 18 months. However, the expected difference, which may explain the population size, has not been reported in the methods.⁵ Both studies have many flaws and do not comply with many items of the CONSORT checklist, resulting in a low quality of the evidence.²² As a matter of fact, the poor methodological quality does not allow drawing any significant conclusion to date.^5,9

Indeed, we may expect that an appropriately designed and conducted randomized study should disclose an advantage for EBTUR because the residual disease rate and the rate of recurrence in the primary tumor site are both extremely low if compared with conventional TUR.

Conclusions

EBTUR is safe and feasible. Pathological assessment of en bloc specimen makes the difference with respect to conventional TUR, even if a clear statement on the matter is still to be reported by pathologists, who should change their way of describing the specimen, including margins, as in any oncological histology report. Indeed, no advantages in terms of recurrence rate have been disclosed yet. What we do really need now is a standardization of the technique, especially when it comes to specimen extraction, and larger randomized study adequately designed to observe an oncological advantage. In the meanwhile, when it is possible, every urologist should adopt EBTUR to ensure the best histological assessment possible.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Abbreviations Used

References

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