Campbell Management of Muscle-Invasive and Metastatic Bladder CA

Question 1

_____ of patients will present with muscle-invasive bladder cancer at the time of initial presentation.

_____ will progress to muscle-invasive disease after an initial diagnosis of non–muscle-invasive bladder cancer.

if left untreated, MIBC will result in mortality
within 2 years of diagnosis in _____% of cases.

Answer 1

Twenty percent to 30%

A smaller subset (approximately 20%)

85% of cases

Question 2

The majority of primary bladder cancers are _____, representing more than ____ of all bladder tumors.

Squamous cell comprises ____% of all bladder cancers in the Western world, but more common in the ____ and ____ due to infection with ____

Answer 2

urothelial carcinomas

90%

5% SCCA
Middle East and Africa
Schistosomal parasites

Question 3

_____ variants of bladder cancer are relatively rare but highly aggressive, and they typically present at high pathologic stages or with metastatic disease.

Standard treatment: ____
Paraneoplastic syndromes: (3) _____

Answer 3

Pure neuroendocrine
NAC + RC
PNS: ectopic adrenocorticotropic hormone production, hypercalcemia, and hypophosphatemia.

Question 4

Variant histologies of UC (4):

Answer 4

Micropapillary: aggressive, resemble papillary serous CA of the ovary
Sarcomatoid
Squamous
Glandular differentiation

** subtypes are considered aggressive - early definitive therapy

Question 5

_____ is the gold standard method for establishing the diagnosis of muscle-invasive bladder cancer

Answer 5

TUR

Question 6

Prostatic urethra biopsy

Answer 6

Using a resectoscope, a full loop of tissue is taken from the midprostate (or bladder neck in shorter prostates) to the mid- to distal verumontanum and 5 and 7 o’clock adjacent to the verumontanum.

** This is the site of the highest concentration of prostatic ducts and the area where carcinoma in situ (CIS) is most likely to be found

Question 7

Bimanual Examination under Anesthesia

Answer 7

• Dominant hand on the suprapubic region and one or two fingers from the nondominant hand in the rectum (males) or vagina.
• Should be done before and after
  resection
• Performed with the bladder drained and without a Foley catheter in place to maximize palpation of the bladder

Question 8

It is optimal to obtain cross-sectional imaging ____ TUR.

If imaging is obtained AFTER TUR, it should be delayed ____ post-procedure to minimize inflammatory artifact (can be mistaken for T3 disease).

Answer 8

BEFORE TUR

7 days delay

Question 9

Baladder CA T staging

Answer 9

TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Ta Noninvasive papillary carcinoma
Tis Carcinoma in situ: “flat tumor”
T1 Tumor invades subepithelial connective tissue
T2 Tumor invades muscularis propria
pT2a Tumor invades superficial muscularis propria (inner
half)
pT2b Tumor invades deep muscularis propria (outer half)
T3 Tumor invades perivesical tissue
pT3a Microscopically
pT3b Macroscopically (extravesical mass)
T4 Tumor invades any of the following: prostatic
stroma, seminal vesicles, uterus, vagina, pelvic
wall, abdominal wall
T4a Tumor invades prostatic stroma, uterus, vagina
T4b Tumor invades pelvic wall, abdominal wall

Question 10

Bladder CA N staging

Answer 10

Nx Lymph nodes cannot be assessed
N0 No lymph node metastasis
N1 Single regional lymph node metastasis in the true
pelvis (hypogastric, obturator, external iliac,
perivesical, or presacral lymph node)
N2 Multiple regional lymph node metastasis in the true
pelvic (hypogastric, obturator, external iliac, or
presacral lymph node metastasis)
N3 Lymph node metastasis to the common iliac lymph
nodes

Question 11

Bladder CA M staging

Answer 11

M0 No distant metastasis

M1 Distant metastasis

Question 12

Anatomic Stage/Prognostic Groups

Answer 12

Stage 0a Ta N0 M0
Stage 0is Tis N0 M0

Stage I T1 N0 M0

Stage II T2a N0 M0
T2b N0 M0

Stage III T3a N0 M0
T3b N0 M0
T4a N0 M0

Stage IV T4b N0 M0
Any T N1-3 M0
Any T Any N M1

Question 13

For patients with clinical T2–T4a, N0, M0 disease, _____ remains the gold standard therapy.

Answer 13

radical cystectomy and bilateral pelvic lymph node dissection

Question 14

Risks of Delaying RC

Higher proportion of extravesical tumors, nodal metastasis, and poorer survival in patients in which cystectomy was DELAYED more
than _____.

Answer 14

12 weeks

Question 15

RC in Men: _____

RC in Women: _____

Answer 15

RC in Men: bladder, perivesical soft tissue, prostate, and seminal vesicles

RC in Women: bladder, ovaries, uterus with cervix, and anterior vagina.

Question 16

Unless there is _____, a complete urethrectomy can be omitted at the time of cystectomy, allowing for orthotopic bladder substitution in women.

Although an anterior exenteration has classically been advocated in women at
the time of radical cystectomy, urothelial carcinoma rarely involves the gynecologic organs, with an overall incidence of approximately _____.

Answer 16

tumor involvement of the bladder neck

5% of cases

*** carefully selected patients can also forgo removal of the uterus and anterior vagina, which potentially allows for better anatomic support for a neobladder and preserves the autonomous nerves.

Question 17

BPLND: essential component of radical cystectomy

_____ of patients will have pathologic lymph node metastases at the time of cystectomy.

Lymph node status is the most powerful surrogate for ____ and ____ following radical cystectomy.

Answer 17

Approximately 25%

Long-term recurrence-free and OS

Question 18

The primary lymphatic drainage site for bladder cancer includes: (4)

Secondary drainage sites: (4)

Answer 18

The primary lymphatic drainage site for bladder cancer includes: internal iliac, external iliac, obturator, and presacral lymph nodes.

Secondary drainage sites: common iliac, para-aortic, interaortocaval, and paracaval lymph nodes

Question 19

Standard PLND during RC: _____

Extended PLND: _____

Superextended PLND: _____

Answer 19

Standard PLND during RC: lymph node packets from the external iliac lymph vessels up to the level of the common iliac bifurcation cephalad and the genitofemoral nerve laterally to the ureter medially

Extended PLND: include the tissue extending
above the common iliac bifurcation to the aortic bifurcation and presacral region.

Superextended PLND: up to the level of the inferior mesenteric artery should be
included

Question 20

PLND: Threshold number of LNs associated with risk for pelvic failure

Answer 20

10 lymph nodes

Question 21

For patients with clinically positive lymph nodes, the standard of care is _____.

Patients who have a radiographic complete or partial response to are candidates for and should be evaluated for _____.

Answer 21

cisplatin-based systemic chemotherapy

cystectomy

Question 22

overwhelming majority of patients who initially respond to chemotherapy but do not have
surgery are destined to recur:

THEREFORE: _____

Answer 22

consolidative cystectomy should be strongly considered in appropriate surgical candidates who respond to systemic therapy.

Question 23

INTRAOP: Cystectomy is NOT performed (aborted) when: (4)

Answer 23

Lymph node metastases are unresectable because of bulk
Extensive periureteral disease
Bladder is fixed to the pelvic sidewall
Tumor is invading the rectosigmoid colon

** If RC is aborted, prognosis is poor.

Question 24

The extent of prostatic involvement is also predictive of urethral recurrence.

____ is associated with the highest risk (as high as 30%) compared with that of prostatic urethral CIS and ductal or acinar involvement

Answer 24

Prostatic stromal invasion

Question 25

URETHRECTOMY should be considered in men with _____.

Answer 25

Diffuse CIS of the prostatic urethra or ducts or if there is prostatic stromal invasion **Given the modest value of preoperative urethral biopsy, some experts advocate for urethrectomy only in the setting of a positive apical urethral margin.

Question 26

_____ has demonstrated high correlation with final urethral margin and should be performed in all women in which orthotopic bladder substitution is being considered.

Answer 26

Frozen-section analysis of the distal urethra

Question 27

____% of patients with muscle-invasive bladder cancer treated with cystectomy ALONE will progress to metastatic disease.

Answer 27

Nearly 50% * Surgery alone is not sufficient therapy in a large number of patients with invasive bladder cancer

Question 28

Arguments for/advantages of NAC (cisplatin-based) for MIBC: (4)

Answer 28

1. Systemic chemo better tolerated before surgery (post-op debilitation/complications) 2. Micrometastatic disease will receive therapy when burden of disease is potentially low 3. NAC has potential to downstage bulky and locally advanced tumors - higher likelihood of negative surgical margins 4. NAC allows clinician to assess individual's response to therapy

Question 29

Patients with _____ disease are known to be at high risk for recurrence following cystectomy. _____ has been used in this population in an attempt to treat micrometastatic disease and to improve survival.

Answer 29

pT3–T4 or node-positive Adjuvant chemotherapy

Question 30

A major limitation of ADJUVANT chemotherapy is ____.

Answer 30

that it is often difficult or impossible for patients to undergo systemic therapy following cystectomy secondary to surgical deconditioning, deteriorating renal function, or perioperative complications.

Question 31

Currently the NCCN guidelines favor neoadjuvant chemotherapy instead of adjuvant chemotherapy based on higher-level evidence data; HOWEVER, the guidelines do suggest considering adjuvant chemotherapy in the setting of _____ disease based on the available data. EAU: _____

Answer 31

pT3–4 or node-positive EAU: adjuvant chemotherapy within clinical trials but not as a routine therapeutic option

Question 32

Adjunctive radiation can increase risk for _____. The strongest case for its use can be made for patients with _____, but there are several ongoing prospective studies specifically studying its role for patients with pT3–4 primary tumors, less than 10 nodes identified, and N+ disease.

Answer 32

postoperative small bowel obstruction positive soft-tissue surgical margins

Question 33

Bladder PRESERVATION is a curative intent | paradigm that should be considered in two (2) distinct populations: _____

Answer 33

(1) patients who have high operative risks as a result of comorbidities and frailty and (2) patients who are fit for radical cystectomy but have limited burden of disease, adequate normal bladder urothelial and function, and are motivated to retain their bladder

Question 34

The most rigorously studied approach to bladder preservation is: _____

Answer 34

Trimodality therapy: a maximal safe and ideally visibly complete TUR, chemotherapy, and radiation

Question 35

Two basic strategies for trimodal bladder preservation: (2)

Answer 35

SPLIT-COURSE: patients are administered induction chemoradiation therapy to approximately 40 Gy, which is followed by restaging with cross sectional imaging and endoscopic evaluation. If persistent invasive disease is noted, radical cystectomy is recommended; for surgically fit patients eligible for immediate salvage cystectomy CONTINUOUS-COURSE: full course of chemoradiation therapy followed by an endoscopic restaging examination 3 to 4 months after therapy to allow time for an adequate response to therapy; for BOTH surgically fit and unfit patients

Question 36

Appropriate candidates for trimodality bladder preservation: (3)

Answer 36

Limited burden of disease: unifocal, small (<4 cm maximal dimension), without frank extravesicular extension on imaging, no hydronephrosis, can be totally resected with TUR Adequate normal bladder urothelium and function Motivated to retain their bladder

Question 37

Trimodality bladder preservation: _____ of patients will ultimately have salvage cystectomy in the long-term as a result of muscle-invasive recurrences

Answer 37

25% to 30%

Question 38

A major limitation of radical TUR monotherapy is the significant risk for _____. _____ has been noted in cT2 cystectomy specimens in up to 40% and 9% of patients, respectively.

Answer 38

occult extravesical disease noted in patients with clinical T2 disease Pathologic T3 and pT4 disease **Therefore, TUR monotherapy in upward of 50% of patients presenting with muscle-invasive bladder cancer would be undertreatment.

Question 39

If a patient is going to elect TUR monotherapy (RADICAL TUR), that patient should be properly informed regarding the risk for recurrent disease and should be appropriately selected based on clinical criteria including: (5)

Answer 39

``` a negative restaging TUR no hydronephrosis no evidence of adenopathy tumor size less than3 cm lack of multifocal disease ```

Question 40

Ideal candidates for partial cystectomy include those with (3):

Answer 40

Small, solitary tumors amenable to wide resection with 2-cm margins Ideally the tumor should be away from the ureteral orifices to avoid reimplantation. Tumor is in a location that allows for complete resection while maintaining adequate functional bladder capacity.

Question 41

_____ is the standard of care for patients with metastatic urothelial bladder cancer. Firstline systemic regimens include: _____

Answer 41

Systemic cisplatin-based combination chemotherapy MVAC, HD-MVAC, and gemcitabine/ cisplatin

Question 42

NOT cisplatin candidates (5): _____

Answer 42

ANY of the following: - a World Health Organization or Eastern Cooperative Oncology Group performance status greater than 2 - creatinine clearance less than 60 mL/min, - grade 2 or above audiometric hearing loss - grade 2 or above peripheral neuropathy, - a New York Heart Association Class III or higher heart failure

Question 43

When cisplatin therapy is contraindicated, ____ has been substituted with the benefit of improved tolerability, but with the cost of decreased efficacy

Answer 43

Carboplatin

Question 44

Stomach for urinary diversion: ADVANTAGES: ____ ELECTROLYTE IMBALANCE: ____ COMPLICATIONS: ____

Answer 44

ADVANTAGES: less permeable to urinary solutes, it has a net excretion of chloride and protons rather than a net absorption of them, and it produces less mucus. HYPOCHLOREMIC metabolic ALKALOSIS Hematuria-dysuria syndrome Rare: severe ulcerative complications

Question 45

Jejunum for urinary diversion ADVANTAGES: ____ ELECTROLYTE IMBALANCE: ____ COMPLICATIONS: ____

Answer 45

The jejunum is usually not used for reconstruction of the urinary system because it may result in severe electrolyte imbalance, most concerningly HYPERKalemia If it is the only segment available: USE DISTAL SEGMENT to minimize electrolyte abnormalities

Question 46

Ileum for urinary diversion ADVANTAGES: ____ ELECTROLYTE IMBALANCE: ____ COMPLICATIONS: ____

Answer 46

ADV: mobile and of small diameter, has a constant blood supply, and serves well for ureteral replacement and the formation of conduits. ELECTROLYTE IMBALANCE: COMPLICATIONS: Lack of B12 absorption, diarrhea (lack of bile salt absorption), and fat malabsorption; 10% chance of postop bowel obstruction