UrologySchool.com

BLADDER CANCER: TRANSURETHRAL AND OPEN SURGERY FOR BLADDER CANCER

TURBT

Bimanual examination under anesthesia prior to resection

Bimanual examination of the bladder with the patient under anesthesia is done before preparation and draping (unless the tumor is clearly small and noninvasive), and repeated after resection
The dominant hand is placed on the suprapubic region and one or two fingers from the nondominant hand in the rectum (males) or vagina (females).
Fixation or persistence of a palpable mass after resection suggests locally advanced disease
The additional value of this maneuver in the era of modern imaging appears limited and may even be misleading

11% clinical overstaging and a 31% clinical understaging rate

Staging based on bimanual examination (as per EAU Guidelines)

T2a: nonpalpable
T2b: induration but no 3D mass
T3: 3D mass that is mobile
T4a: invading adjacent structures such as the prostate, vagina, or rectum
T4b: fixed to pelvic sidewall and not mobile

Guideline perspective on role of bimanual examination:

2015 CUA NMIBC guidelines: a valuable staging component of the TURBT procedure (Level of Evidence 3)
2016 AUA NMIBC guidelines: can assist with clinical staging

Antibiotic prophylaxis

CUA/AUA Guidelines recommend prophylaxis for all patients undergoing TUR of bladder tumors, and it should be administered within 1 hour of the procedure

At the time of TURBT, a thorough cystoscopic examination of a patient’s entire urethra and bladder should be performed that evaluates tumor size, location, configuration, number, and mucosal abnormalities
Lens

A thorough visual inspection involves using the 30° lens to examine the urethra and then to perform a preliminary evaluation of the bladder mucosa and ureteral orifices. A 70° lens should then be used to completely evaluate the bladder again with particular attention to the bladder neck, dome, and anterior wall.

The most common lenses used during a typical rigid cystourethroscopy are the 30° and 70° lens.
The urethra is best visualized using the 0 to 12° lens.
A 30° lens is most often used for therapeutic purposes.
Resection is performed using a 12- or 30° lens because this deflection allows visualization of the cutting loop.
The 70° or 120° lens are often required to inspect the anterior and inferolateral walls, dome, and neck of the bladder.

Irrigation fluid

Traditionally, TUR has been performed in sterile water because saline solutions conduct electricity and disperse energy from the monopolar cautery cutting loop
1.5% glycine is more expensive, and there is no evidence of its benefit in this setting compared with water

Obturator nerve reflex

When tumors are encountered on the lateral wall, there is the risk of an obturator reflex whereby the cautery current stimulates the obturator nerve, causing the ipsilateral leg to aDDuct
This can lead to inadvertent deflection of the instrument laterally and can cause perforation.
Techniques to reduce the risk of an obturator reflex (5):
1. Minimize distention of the bladder
2. Using bipolar over monopolar cautery
3. If the patient is under a general anesthetic, administer a general muscle relaxant
4. Direct injection of local anesthetic (20-30 mL lidocaine) into the obturator nerve and its canal
5. Tapping the peddle during resection

Advantages of bipolar TURP (compared to monopolar)
1. Reduced risk of postoperative electrolyte abnormalities since bipolar uses 0.9% NS as irrigation
2. Reduced risk of triggering an obturator reflex for tumours overlying the lateral walls of the bladder.
3. [Reduced bleeding, increased resection time]
Resection

Performed piecemeal, delaying transection of any stalk until most tumor has been resected, to maintain countertraction. Friable, low-grade tumors can often be removed without the use of electrical energy because the nonpowered cutting loop will break off many low-grade tumors. This minimizes the chance of bladder perforation and unnecessary cautery damage or loss of specimens. Higher-grade, more solid tumors and the base of all tumors require the use of cutting current; cautery yields hemostasis once the entire tumor has been resected. Lifting the tumor edge away from detrusor lessens the chance of perforation
Histologically, bladder tumors frequently exhibit growth beyond the visible edge and, as such, resection should include an approximate 2-cm margin of normal-appearing tissue.
For tumours overlying a ureteral orifice, only cutting current should be used and resection strokes should be as quick as possible to minimize the possibility of cauterizing the ureteral orifice closed. Data suggest routine stenting is not necessary following ureteral orifice resection.
2016 AUA NMIBC Guidelines: During resection, tumors of significant size should be resected and labeled
2015 CUA NMIBC Guidelines: Complete resection of all visible tumours with adequate depth to include muscularis propria should be performed, when feasible

Campbell’s: The necessity of obtaining detrusor muscle in the surgical specimen is widely taught but not established in benefit. For example, the potential for muscle invasion for low-grade disease is essentially nonexistent, so a transmural biopsy offers little potential benefit compared with the risk of bladder perforation incurred

Small tumors may be resected using the cold-cup biopsy forceps alone. This is especially helpful in elderly women, who are predisposed to perforation owing to their thin-walled bladders. If perforation occurs, the cup causes a smaller hole than does the cutting loop. A Bugbee electrode facilitates hemostasis.
In a patient with a history of TaLG disease and a noted sub-centimeter papillary tumor(s), a clinician may consider in-office fulguration as an alternative to resection under anesthesia.

A fulguration approach that does not obtain tissue for pathologic evaluation should not be utilized unless a diagnosis of TaLG disease or PUNLMP has been previously established and should be restricted to those patients in whom the lesion is papillary in appearance, rather than sessile or flat, and ≤ 1 cm in size. Furthermore, patients in whom a urinary cytology is suspicious for urothelial carcinoma are at higher risk for harboring occult high-grade disease and warrant pathologic evaluation of any visible lesion.

Many small, low-grade tumors can be safely observed until they exhibit significant growth because of the minimal risk of progression

Diverticular tumours

Because the underlying detrusor is absent, accurate staging is difficult and increased risk of bladder wall perforation
Invasion beyond the diverticular lamina propria immediately involves perivesical fat (stage T3a by definition)
Treatment

Low-grade diverticular tumors are best treated with a combination of resection and fulguration of the base. Conservative resection can be followed with subsequent repeat resection if the final pathologic interpretation is high grade.
High-grade tumors require adequate sampling of the tumor base, often including perivesical fat, despite the near certainty of bladder perforation. An indwelling catheter usually allows healing within a few days. Partial or radical cystectomy should be strongly considered for high-grade diverticular lesions

Anterior wall tumors and tumors at the dome

Can be difficult to reach in patients with large bladders
Minimal bladder filling combined with manual compression of the lower abdominal wall to bring the tumor toward the resectoscope facilitates removal. Digital manipulation through the rectum or vagina can occasionally facilitate resection
Modern resectoscopes are long enough to reach the entirety of most bladders; creation of a temporary perineal urethrostomy offers deeper access but is rarely necessary except in the obese patient with an inaccessible tumor

Complications:

Intra-operative

Perforation

Occurs in <5% of cases
The risk of tumor seeding from perforation appears to be low
The vast majority of perforations are extraperitoneal

Intraperitoneal perforation associated with posterior and dome tumors; resections elsewhere in the bladder are more likely to result in an extraperitoneal perforation

Findings during resection suggestive of an intraperitoneal rupture:

Loss of bladder distention
Visualization of a defect posteriorly or at the dome
Palpable distention of the abdomen; an increase in abdominal girth or fullness

When suspected, confirmation can be obtained with a cystogram at the same setting
Management

Extraperitoneal: Foley catheter drainage and observation
Intraperitoneal:
1. Abdominal exploration
2. Meticulous inspection of the bowel
3. Repair of the injury with both a Foley catheter and abdominal drainage
Decisions for surgical correction should be made based on the extent of the perforation and the clinical status of the patient.

Injury to ureteric orifice

As long as resection of the ureteral orifice is performed with pure cutting current, scarring is minimal and obstruction unlikely.
Cystoscopy to visualize efflux, which is occasionally aided by intravenous administration of indigo carmine or methylene blue or retrograde ureteropyelography, can determine presence or absence of obstruction

Early post-operative

Irritative symptoms

Common

Bleeding

Minor bleeding is common; uncontrolled hematuria occurs in <5% of cases

TUR syndrome

Managed in the same manner as during TURP
Risk factors for TUR syndrome:

Long resection time >90 mins
Large glands >45g
Increased pressure of irrigation fluid

Late post-operative

Urethral stricture disease

Tumour resection can also be done with laser therapy. The most significant complication of laser therapy is forward scatter of laser energy to adjacent structures, resulting in perforation of a hollow, viscous organ such as overlying bowel. Because there is no tissue available for pathologic inspection, the optimal candidate for laser therapy is the patient with recurrent, low-grade lesions whose biology is already known
In the presence of a bladder tumor, selective upper tract cytology may be falsely positive and is not recommended for most patients
The use of random biopsies to identify CIS in otherwise normal-appearing mucosa remains controversial. The current consensus is that random biopsies are not indicated in low-risk patients (i.e., those with low-grade papillary tumors and negative cytology), but there remains no consensus with regard to patients with high-grade disease, and most urologists perform random biopsies in this setting.
Prostatic urethral biopsy using the cutting loop may be performed at the time of TURBT, especially if neobladder creation is anticipated for high-risk disease, but bleeding may be more common
Traditional teaching is that TURP and TURBT of a low-grade bladder tumor may be performed at the same setting but that resection of a high-grade bladder tumor should not be performed coincident to TURP to avoid tumor seeding and possible intravasation of tumor cells

Radical Cystectomy

Includes excision of perivesical soft tissue and:

Men (2):
1. Prostate
2. Seminal vesicles
Women (4)
1. Ovaries
2. Fallopian tubes
3. Uterus with cervix
4. Anterior vagina
In male patients, a nerve-sparing procedure can be safely offered to select patients interested in preserving sexual function.
In female patients, a female organ sparing (i.e. uterus, ovaries and/or vagina) operation can be offered to women interested in preserving sexual and/or reproductive function in situations where the tumour location allows (i.e. anterior tumours)

Bilateral pelvic lymph node dissection

The primary lymphatic drainage sites for bladder cancer include:
1. Obturator
2. Internal iliac
3. External iliac
4. Presacral lymph nodes
Secondary drainage sites include higher echelon nodes, including the common iliac, para-aortic, interaortocaval, and paracaval lymph nodes
≈25% of patients will have pathologic lymph node metastases at the time of cystectomy, and lymph node status is the most powerful surrogate for long-term recurrence-free and overall survival following radical cystectomy
The absolute number of nodes removed has been shown to provide important prognostic information and staging accuracy both in lymph node positive and lymph node negative patients; removing > 10 nodes is recommended [AUA MIBC Guidelines say >12] based on observational studies evaluating node count and survival
CUA: Bilateral pelvic lymph node dissection with removal, at minimum, of the obturator, internal iliac and external iliac lymph nodes should be performed in all patients undergoing radical cystectomy
Standard template:

Superiorly by the ureter/bifurcation of the common iliac artery
Inferiorly by the circumflex iliac vein and Cloquet’s node/Cooper ligament at the femoral canal
Laterally by the genitofemoral nerve
Medially by the bladder and internal iliac artery
Posteriorly by the obturator nerve/fossa

Many retrospective studies have suggested a survival benefit of extending the cystectomy lymph node dissection boundaries to a level as high as the inferior mesenteric artery. Campbell’s: in cases of advanced disease, an extended dissection inclusive of the entire common iliac lymph node packet and the presacral lymph node packet can be obtained

LEA AUO AB 25/02

Population: 401 patients with locally resectable T1G3 or muscle-invasive urothelial BCa (T2-T4aM0)
Randomized to limited (obturator, and internal and external iliac nodes) vs. extended LND (in addition, deep obturator, common iliac, presacral, paracaval, interaortocaval, and para-aortal nodes up to the inferior mesenteric artery).
Results:

The median number of dissected nodes was 19 in the limited and 31 in the extended arm.
No difference in RFS (5-yr RFS 65% extended vs 59%; p=0.36), CSS (5-yr CSS 76% vs 65%; p=0.10), and OS (5-yr OS 59% vs 50%; p=0.12).
Clavien grade ≥3 lymphoceles were more frequently reported in the extended LND group within 90d after surgery.

Gschwend, Jürgen E., et al. "Extended versus limited lymph node dissection in bladder cancer patients undergoing radical cystectomy: survival results from a prospective, randomized trial." European urology 75.4 (2019): 604-611. https://www.ncbi.nlm.nih.gov/pubmed/30337060

Both laparoscopic/robotic and open approaches are acceptable methods to perform radical cystectomy with comparable cancer outcomes.

RAZOR trial

Population: 360 patients with T1–T4, N0–N1, M0 bladder cancer or refractory carcinoma in situ
Randomized to robotic vs. open radical cystectomy
Results:

Robotic cystectomy was non-inferior to open on 2-year PFS [similar results at 3 years]
Adverse event were not significantly different between groups (67% robotic vs. 69% open)

No difference in risk of post-operative ileus (22% robotic vs. 20% open)

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)30996-6/fulltext

Patient preparation

Prostate cancer screening (DRE and PSA)
- If concerned for prostate cancer, attention at the time of cystectomy will be needed for complete oncologic removal of the prostate
Marking stoma site

Careful marking of the ostomy site to avoid interference, both in a standing and in a seated position, is performed to maximize appliance fit and to minimize stomal irritation.

Patients with a planned continent diversion should be made aware of the rare possibility of receiving an ileal conduit urinary diversion
Bowel preparation

Based on data from colorectal surgery, routine bowel preparation is not recommended for patients undergoing radical cystectomy with urinary diversion, especially if only ileal segments are to be used

Antibiotic prophylaxis:
- The choice of antibiotic should include both gram-positive coverage (skin flora) and gram-negative aerobes and anaerobes (distal small bowel and large bowel flora)
- 2019 AUA Best Practice Statement: Urologic Procedures and Antimicrobial Prophylaxis recommends single dose of cefazolin within 1 hour of surgical incision.
Thromboembolic prophylaxis

Patients should undergo both mechanical thromboembolic prophylaxis (stockings and pneumatic compression) and pharmacologic prophylaxis before the induction of general or spinal anesthesia.

μ opioid receptor antagonist

A randomized trial has demonstrated that the μ opioid receptor antagonist alvimopan can be administered 30 to 90 minutes before surgery and daily thereafter to improve functional bowel recovery and reduce length of hospitalization. Lee, Cheryl T., et al. "Alvimopan accelerates gastrointestinal recovery after radical cystectomy: a multicenter randomized placebo-controlled trial." European urology 66.2 (2014): 265-272. https://www.ncbi.nlm.nih.gov/pubmed/24630419

Surgical technique

Male patients should be positioned supine with anterior superior iliac spine at or just below the flexion point of the table. Female patients should be positioned in a low lithotomy position with the aid of stirrups or the use of spreader bars provides access to the vagina. In female patients, table flexion is generally not possible.
The abdomen should be prepared from the level of the xiphoid to the upper portion of the thighs. The genital organs, including the vagina in women, and the perineum should be prepared as well

A lower midline incision is made sharply extending distally from the level of the symphysis pubis to the umbilicus superiorly

Upward retraction of the umbilicus (toward the ceiling) aids in the identification of the linea alba. After the midline is identified, the fascia is divided and the space of Retzius is entered. Blunt dissection is performed to mobilize the bladder from the pelvic sidewall attachments anteriorly and bilaterally. This is carried superiorly to the level of the vas deferens in men and the round ligament in women.
At this point, a peritonotomy is made lateral to either medial umbilical ligament and the urachus is controlled and divided.
The peritoneum is incised lateral to the medial umbilical ligaments bilaterally to the level of the internal inguinal rings at which point the vas deferentia in men and the round ligaments in women will be identified and are divided

With the aid of a self-retaining retractor such as a Bookwalter, exposure is maximized and the bowel retracted cephalad. Communication with the anesthesiologist at this point is vital to ensure that inadvertent compression of the vena cava has not resulted. A moistened laparotomy pad or pads should be placed behind retractor blades to protect the abdominal contents.
After adequate exposure is achieved, the bilateral ureters are identified and dissected free from their attachments beginning a few cm above where they cross the iliac arteries to the level of the detrusor hiatus. Care should be used to ensure that adequate ureteral adventitia is maintained. The superior vesical artery should be ligated and divided before completing the ureteral dissection as this aids in maximizing ureteral length. The ureter is then controlled with either suture ties or suture ligature and is divided.

Although controversial, the distal ureteral margin can be sent for frozen section analysis to evaluate for the presence of urothelial carcinoma. Studies have shown a correlation between findings of carcinoma in the ureteral margin and subsequent upper tract recurrence, however, an impact on survival has not been well established

The lateral vascular pedicles are ligated. If sealing instruments are used, the heat they generate can transmit and may injure the rectum if in close proximity. With a gloved finger surgeons should shield the rectum from the tips of such instruments while in use
After completely ligating the lateral vascular pedicles, attention is turned to the posterior dissection. The rectal cul-de-sac is identified and the peritoneum is incised where it overlies the seminal vesicles

The rectum is dissected free with either blunt dissection or sharp dissection in the midline and is carried to the level of the prostate, at which point Denonvilliers fascia is encountered and incised.

At this point, attention can be turned to the anterior dissection in a fashion similar to a radical prostatectomy. The endopelvic fascia overlying the levator muscles is incised sharply, allowing for identification of the confluence between the urethra and the dorsal venous complex. Ligation and division of the dorsal venous complex allows for visualization of the anterior urethra, which is then incised
If a continent ileal neobladder urinary diversion is planned, adequate urethral length must be maintained and a frozen section analysis of the urethral margin performed. Orthotopic neobladder is contraindicated patients with a positive urethral margin due to risk of urethral recurrence
The role of preservation of the neurovascular bundles, unlike in radical prostatectomy, remains controversial in radical cystectomy. A technique analogous to radical prostatectomy can be used, however, the functional outcomes remain significantly worse than radical prostatectomy.
Female cystectomy:

The initial steps for bowel mobilization, anterior bladder mobilization, and ureteral dissection are the same in men and in women with the exception of the gonadal vessels. In female patients the ovarian vessels should be identified during the bowel mobilization and ligated with a 2-0 silk suture distally, and both a 2-0 silk suture ligature and a tie proximally, and then divided.
Anterior pelvic exenteration begins with identification of the posterior cervical fornix (Fig. 95-14A), and the vaginal cuff is incised at this position (Fig. 95-14B).
After gaining entry to the vaginal canal, control the lateral and posterior vascular pedicles to the bladder. According to surgeon preference, vascular staplers, sealing devices, or clips are applied and the specimen can be dissected free inclusive of the uterus, cervix, anterior vaginal cuff, and bladder.
The urethral meatus is then incised, either antegrade from the pelvis or externally from the vaginal introitus, and the specimen is removed (Fig. 95-15A and B). Care should be taken to ensure that sufficient vaginal mucosa is maintained above the urethral meatus to allow for closure of the vaginal defect in subsequent steps.
Because of the vascular nature of the female pelvis and the sinusoidal nature of the vascular pedicles as they pass over the lateral vaginal wall, care is needed to ensure hemostasis
To complete the vaginal closure with a 2-0 polyglactin suture, the posterior vaginal wall must be released from the rectum. The posterior vaginal flap is then closed to the corresponding mucosae of the introitus in a clamshell fashion to maintain vaginal girth at the cost of some vaginal length. Bothersome drainage of peritoneal fluid will result if the vaginal closure is not watertight, and an interrupted closure is preferred.
A vaginal packing is then placed with the dual purpose of distending the vagina and tamponading any residual vaginal wall hemorrhage (particularly useful if vaginal sparing is performed; discussed later) and aids in the identification of unrecognized defect in the closure. This packing should be removed within two postoperative days.

Radical cystectomy in the female patient historically included total anterior pelvic exenteration inclusive of the bladder, urethra, anterior vagina, uterus, and cervix. However, in the absence of bladder neck involvement and the presence of low-stage disease (≤cT2), orthotopic neobladder can be considered. This necessitates urethral sparing with adequate length proximal to the striated sphincter and anterior vaginal wall sparing to provide support to the neobladder.
Lateral vascular pedicles are intimate with the lateral wall of the vagina and to control these vessels properly they must be separated from the vagina before ligation. This can be achieved either after removal of the cervix and uterus at the level of the cervical fornix (Fig. 95-16A) or while they are still in place. A vaginal packing during this step can aid in defining the plane of separation between the bladder and the anterior vaginal wall in the midline. After development this space is extended laterally, separating the lateral vascular pedicles from the lateral vaginal wall. To ensure that an adequate bladder margin is maintained, the vessels should not be divided until the midpoint of the lateral vaginal wall, in the anterior posterior plane, has been reached. This dissection is carried to the level of the bladder neck, which can easily be identified by use of the Foley catheter balloon as a guide.
Maintaining the integrity of the striated sphincter, the specimen is removed at this level and a frozen section of the urethral margin is sent and managed in the same fashion as in male neobladder candidates. Again, if the urethral margin analysis demonstrated malignancy, orthotopic diversion is contraindicated.
The vaginal apex is closed with 2-0 polyglactin sutures and urethral anastomotic sutures placed

Partial cystectomy

See 2019 CUA MIBC Guidelines
For those with solitary lesions of small size and who lack concurrent carcinoma in situ (CIS), results from partial cystectomy are similar to those of radical cystectomy
Patients initially treated with partial cystectomy can be salvaged with radical cystectomy
Procedure:

Cystotomy is performed in an area away from the tumor.
The tumor is then excised including the underlying bladder wall and perivesical fat with a mucosal margin of 1 to 2 cm and confirmation of resection adequacy with frozen section analysis. If necessary, the ureteral orifice or intramural ureter can be excised and a reimplantation performed.
After excision of the tumor the cystotomy is closed with 2-0 polyglactin suture in 2 or 3 layers, and an instillation of fluid via a Foley catheter is performed to ensure a watertight closure.
Copious warm water irrigation of the surgical field is performed to minimize the possibility of pelvic seeding.
A closed suction drain should be placed and the cystotomy closure interrogated with a cystogram on postoperative day 7 before removal of the Foley catheter.

Although rare, primary adenocarcinoma arising from the urachus requires additional resection. These tumors are most commonly confined to the dome of the bladder although they may grow by direct extension to involve other areas. Complete excision includes the umbilicus, the urachus, and the dome of the bladder with a visual margin free from tumor

Postoperative care

0.9% inpatient mortality rate and a 2.7% 90-day mortality rate following radical cystectomy

Mortality after radical cystectomy is typically < 5%, but may increase substantially in the elderly with 90-day mortality rates over 10% in patients > 75 years of age and almost 20% in octagenarians.

The incidence of symptomatic venous thromboembolism in short-term follow-up after radical cystectomy is 3-12%, of which > 50% of cases will occur after hospital discharge.

Meta-analyses of clinical trials in patients undergoing major abdominal oncologic operations suggest a decreased risk of venous thromboembolisms for patients receiving extended (4 weeks) venous thromboembolism prophylaxis.
Extended prophylaxis should be considered in all radical cystectomy cases. Although the relative risk of bleeding also increases, the overall net benefit of extended prophylaxis clearly favors use for at least 28 days postoperatively.
Extrarenal eliminated prophylaxis agents are preferred given the risk of renal insufficiency in radical cystectomy cases, with newer oral anticoagulants providing an alternative route of administration.
Klaassen, Zachary, et al. "Extended venous thromboembolism prophylaxis after radical cystectomy: A call for adherence to current guidelines." The Journal of urology 199.4 (2018): 906-914.

References

Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, chap 95