Transurethral Resection of Bladder Cancer and Its Applications
Transurethral resection of bladder tumors (TURBT) is a procedure performed to diagnose and stage bladder cancer (BCa) and to resect all visible tumors. This chapter is focused on TURBT surgical technique, possible complications, and available tools which can improve the quality of resection to correctly stage the neoplasm and to reduce recurrences and progressions of non-muscle-invasive BCa.
Transurethral resection of bladder tumors (TURBT) is a procedure which represents the initial treatment to diagnose, stage, and resect all visible tumors if technically possible and to perform biopsies of suspicious areas. TURBT is not only a diagnostic procedure but also a therapeutic procedure. In case of a suspicious bladder tumor, TURBT remains crucial in order to obtain a histopathological confirmed diagnosis of a bladder. Furthermore, TURBT is the essential procedure to decide whether an organ sparing approach in case of non-muscle-invasive disease is sufficient or a radical cystectomy is required in case of a muscle-invasive disease or high-risk non-muscle-invasive disease. Taking this all into consideration, TURBT is a key step in the treatment of bladder cancer.
The indication for a TURBT is a suspicious finding of bladder tumor via cystoscopy or imagings. Preoperative laboratory evaluation of coagulation and kidney parameters, respectively, should be performed. A preoperative ultrasound examination of the kidneys should be done in order to exclude hydronephrosis and if necessary to perform a urinary diversion via nephrostomy before TURBT. Further imagings via CT/MRI of the abdomen and chest should be performed after histopathological evaluation in case of a locally advanced disease to exclude an extraorgan extension and metastases, respectively.
The aim of the anesthesia is to enable a safe resection with appropriate analgesia and relaxation of the pelvic floor, the abdominal wall, and the bladder. A general or a regional anesthesia or a combination between the two can be equally used. Regional anesthesia can be performed as an epidural or spinal blockade and they provide the advantage of an awake patient in case of intraperitoneal bladder perforation which can be identified by the appearance of abdominal pain. The stimulation of the obturator nerve, which is located close to the lateral wall of the bladder during the TURBT can provoke an obturator nerve-reflex with contraction of the adductor muscle of the leg, which consequently determines a sudden movement of the leg that can lead to a bladder perforation. Two options are available to prevent this phenomenon; one method consists of paralyzing the patient with a short-acting depolarizing drug that, however, can be only used only if the patient is in general anesthesia. The second method consists of the “obturator nerve block” which can be obtained with several techniques. One of them consist of the direct injection of Lidocain through a long needle, inserted 2 cm lateral and caudal to the pubic tubercle and the needle is walked off the inferior border of the superior ramus of the nerve and it enables to block the main trunk before it divides. Another technique consists on the transvesical block; after using a nerve stimulator to detect the nerve on the lateral bladder wall, 10 ml of 1% lidocaine are slowly injected through the working channel of a cystoscope. According to own clinical experience, a semi-filled bladder reduces the risk of an obturator nerve reflex during resection of the tumor at the lateral walls of the bladder.
Intravenous antibiotic prophylaxis at the time of anesthesia is recommended for this surgery to prevent infectious complications. The type of antibiotic prophylaxis should be decided on the base of the resistance profile within the region of the treating hospital. A preoperative urine culture should be performed in case of suspicious urine assessed via dip-stick, and any detected infection should be treated before the procedure according to the pathogen spectrum.
Tumors in Bladder Diverticulum
By definition, tumors in bladder diverticulum do not have a muscular layer between themselves and the serosa. This feature makes the resection of this type of tumors challenging due to the high risk of bladder perforation. In general, small lesions with the appearance of low-grade tumors can be treated safely with a combination of resection and fulguration whereas large or high-grade tumors should be treated with diverticulectomy, partial or radical cystectomy.
Involvement of the Ureteral Orifices
Resection can be safely performed to remove tumors located close to the ureteral orifices, whereas cautery should be used as little as possible, given the high risk of subsequent stenosis.
Tumors in Bladder Dome
Biopsies During TURBT
Biopsies are recommended for all suspicious areas detected during a TURBT. Moreover, random biopsies of a unsuspicious bladder urothelium should be performed especially in patients with previous or suspected CIS (van der Meijden et al. 1999) since it can be present also in a normal-looking mucosa or in case of discordance between cytology and cystoscopy. Biopsies of the prostatic urethra should be taken in case of known or suspected CIS, tumors located on the bladder neck, positive cytology with macroscopic negative bladder (Mungan et al. 2005), or when are alterations of urethral mucosa are visible.
Complications of TURBT
The overall rate of complications of TURBT is low. The most frequent minor complications are development of irritative symptoms and minor bleeding which can occur in the immediate postoperative period. Major complications are rarer and consist mainly of uncontrolled hematuria and bladder wall perforations which are more frequently extraperitoneal, treated with a prolonged maintenance of the transurethral catheter. On the contrary, intraperitoneal perforations require a surgical repair.
Photodynamic Diagnosis (PDD) and Narrow Band Imaging (NBI)
Conventionally, cystoscopy and TURBT are performed with a white light. Given the high rates of residual or recurrent tumors after a white light cystoscopy, new technologies have been developed to improve the visualization and the detection of bladder diseases.
PDD consists of preoperative intravesical instillation of a fluorophore that is a precursor in the heme biosynthesis pathway. Hexylaminolevulinate (HAL) and 5-aminolevulinic acid (5-ALA) have been used for this technique. The 5-ALA is converted in all nucleated cells into an active fluorescent molecule, the protoporphyrin IX (PPIX), which in normal conditions is rapidly converted to heme. Tumor cells have a different metabolism compared to those of a normal urothelium, and these differences lead to a selective accumulation of PPIX which is about five times higher in neoplastic cells (Krieg et al. 2000). The fluorescence of PPIX is achieved by the presence of pyrol rings, and PPIX emits red light (635 nm) when exposed to a blue light (around 400 nm). About 1 h before the planned TURBT, 50 ml of solution of a fluorophore is instilled into the bladder through a transurethral catheter. The fluorescent cystoscopy is performed with a rigid cystoscope combined with a light source called D-light and should be done with an empty bladder. PDD showed a higher sensitivity and a lower specificity compared to white light endoscopy in detection of BCa, with a high rate of false-positive (Mowatt et al. 2011) even if artifact fluorescence is usually less intense than the one determined by a tumor. Moreover, a recent meta-analysis demonstrated a reduced recurrence rate in patients who underwent PDD-guided TURBT (Chou et al. 2017) compared to those treated with the white light endoscopy. The use of PDD is currently recommended in several cases. Firstly, in every patient with a new presentation of non-muscle-invasive BCa. Therefore, tumor detection is higher in patients evaluated with white light plus PDD compared to those evaluated with the white light alone (Mowatt et al. 2011), and as already mentioned, recurrence and progression rates are significantly lower (Chou et al. 2017; Gakis and Fahmy 2016). Moreover, PDD is particularly helpful in detection of CIS (Daneshmand et al. 2018) and improves quality of resection (Geavlete et al. 2010). Secondly, in patients with positive cytology and negative white light cystoscopy since it has been shown that PDD detect tumors in approximately 30% of patients with this condition. And finally, PDD is indicated for the treatment of multifocal recurrent tumors.
NBI takes advantage of the hypervascular nature of bladder cancer to enhance the contrast with the normal urothelium. It consists of modified optical filters applied to the light source of a video endoscope system which filter the light into two bandwidths of 415 and 540 nm. The intensities of blue and green light are increased, and these two narrow bandwidths are strongly absorbed by hemoglobin in hypervascular neoplastic tissues. Several studies reported the advantage of NBI in detection of non-muscle-invasive BCa compared to white light endoscopy and in recurrence especially in patients with low-risk tumors (pTa low grade, <30 mm, no CIS) (Naito et al. 2016).
Role of re-TURBT
It is not always possible to achieve a complete resection of the tumors since often the lesions are too big or located in areas difficult to reach with the resectoscope. Sometimes the incompleteness of the TURBT is caused by the necessity of a limited anesthesiologic time due to patient’s comorbidity or to the need to interrupt the procedure for the occurrence of intraoperative complications. In any case, the rates of residual tumors after the initial TURBT are high and variable according to grade of the lesions (higher for T1 high grade tumors) (Gontero et al. 2016). Moreover, several studies have demonstrated that the understaging of tumors during the initial TURBT is common and the probability increases when the muscle is absent in the pathologic specimen (Herr 1999). A re-TURBT is recommended in all cases of macroscopic incomplete initial resection, when the muscle is not present at pathologic evaluation and in all T1 and high-grade tumors, because in these cases, a re-TURBT decreases rates of recurrences and progressions (Gontero et al. 2016). When indicated, the second TURBT should be performed 2–6 weeks after the first operation.
- Chou R, Selph S, Buckley DI, Fu R, Griffin JC, Grusing S, Gore JL. Comparative Effectiveness of Fluorescent Versus White Light Cystoscopy for Initial Diagnosis or Surveillance of Bladder Cancer on Clinical Outcomes: Systematic Review and Meta-Analysis. J Urol. 2017;197:548–558. https://doi.org/10.1016/j.juro.2016.10.061CrossRefGoogle Scholar
- Daneshmand S, Bazargani ST, Bivalacqua TJ, Holzbeierlein JM, Willard B, Taylor JM, Liao JC, Pohar K, Tierney J, Konety B, Blue Light Cystoscopy with Cysview Registry Group. Blue light cystoscopy for the diagnosis of bladder cancer: Results from the US prospective multicenter registry. Urol Oncol. 2018;36:361.e1–361.e6. https://doi.org/10.1016/j.urolonc.2018.04.013CrossRefGoogle Scholar
- Gontero P, Sylvester R, Pisano F, Joniau S, Oderda M, Serretta V, Larré S, Di Stasi S, Van Rhijn B, Witjes AJ, Grotenhuis AJ, Colombo R, Briganti A, Babjuk M, Soukup V, Malmström P-U, Irani J, Malats N, Baniel J, Mano R, Cai T, Cha EK, Ardelt P, Vakarakis J, Bartoletti R, Dalbagni G, Shariat SF, Xylinas E, Karnes RJ, Palou J. The impact of re-transurethral resection on clinical outcomes in a large multicentre cohort of patients with T1 high-grade/Grade 3 bladder cancer treated with bacille Calmette-Guérin. BJU Int. 2016;118: 44–52. https://doi.org/10.1111/bju.13354CrossRefGoogle Scholar
- Mowatt G, N’Dow J, Vale L, Nabi G, Boachie C, Cook JA, Fraser C, Griffiths TRL, Aberdeen Technology Assessment Review (TAR) Group. Photodynamic diagnosis of bladder cancer compared with white light cystoscopy: Systematic review and meta-analysis. Int J Technol Assess Health Care. 2011;27:3–10. https://doi.org/10.1017/S0266462310001364CrossRefGoogle Scholar
- Naito S, Algaba F, Babjuk M, Bryan RT, Sun Y-H, Valiquette L, de la Rosette J, CROES Narrow Band Imaging Global Study Group. The Clinical Research Office of the Endourological Society (CROES) Multicentre Randomised Trial of Narrow Band Imaging-Assisted Transurethral Resection of Bladder Tumour (TURBT) Versus Conventional White Light Imaging-Assisted TURBT in Primary Non-Muscle-invasive Bladder Cancer Patients: Trial Protocol and 1-year Results. Eur Urol. 2016;70: 506–515. https://doi.org/10.1016/j.eururo.2016.03.053CrossRefGoogle Scholar
- van der Meijden A, Oosterlinck W, Brausi M, Kurth KH, Sylvester R, de Balincourt C. Significance of bladder biopsies in Ta,T1 bladder tumors: a report from the EORTC Genito-Urinary Tract Cancer Cooperative Group. EORTC-GU Group Superficial Bladder Committee. Eur Urol. 1999;35: 267–271.Google Scholar