MANAGEMENT OF BLADDER CANCER: A SURGEON'S PERSPECTIVE
From the 28th Annual Jackson Hole Urologic Conference
John Peter Stein, MD, Professor of Urology, Keck School of Medicine of the University of Southern California, Los Angeles
Educational Objectives
| The goal of this program is to elucidate current concepts in the surgical management of bladder cancer. After hearing
and assimilating this program, the clinician will be better able to:
|
 | 1. Assess the rationale for performing early cystectomy in patients with grade 3 T1 tumors.
|
| 2. Implement an appropriate treatment for grade 3 T1 tumors.
|
| 3. Compare the relative clinical merits of radical cystectomy and prostate-sparing cystectomy.
|
| 4. Evaluate the long-term results of standard radical cystectomy for invasive bladder cancer.
|
| 5. Discuss techniques for managing urethral disease after radical cystectomy.
|
Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the
planning committee to disclose relevant financial relationships within the past 12 months that might create any personal
conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes
quality in health care and not a proprietary business or commercial interest. For this program, Dr. Stein reported nothing
to disclose.
Acknowledgements
Dr. Stein gave his scientific lectures at the 28th Annual Jackson Hole Urologic Conference, presented January 26 to
February 1, 2008, in Jackson Hole, WY, by the University of Colorado School of Medicine and Jackson Hole Seminars,
Inc. The Audio-Digest Foundation thanks Dr. Stein and the sponsors for their cooperation in the production of
this program.
| EARLY CYSTECTOMY FOR GRADE 3 T1 TUMORS
|
| Grade 3 T1 tumors: lethal; progress to invasion; constitute ≈25% of all bladder cancers; patients with combination of T1
tumor and carcinoma in situ (CIS)—constitute ≈50% of cases; at risk for progression, recurrence, and death; data—extravesical
recurrences can develop in upper urinary tract and prostatic urethra; bacillus Calmette–Guérin (BCG) therapy
does not provide durable progression-free benefit; rule of one-thirds—one-third of patients never develop recurrence and
can retain their bladders; one-third die of bladder cancer; one-third require cystectomy; assessing risk for progression—
depth of disease penetration into muscularis mucosae; CIS; lymphovascular invasion; early response to intravesical therapy;
persistent T1 disease on transurethral resection (TUR); molecular markers (conventional markers do not identify true
malignant potential of T1 tumor)
|
| Cystectomy: given similar outcomes, bladder preservation with TUR and intravesical therapy preferable to cystectomy;
rationale for cystectomy—risk for clinical understaging associated with T1 disease; continued risk for local and distant
disease progression; improvement in morbidity and mortality rates; provides pathologic staging data and indices to determine
need for adjuvant therapy; ability of orthotopic and nerve-sparing procedure to improve patient’s quality of life
(QOL)
|
| Observations on radical cystectomy: patients who have been clinically understaged do less well (counsel surgical
candidates with T1 disease that 14%-15% of cystectomy patients have lymph node-positive disease at surgery and face
increased risk for progression); upper tract and prostatic urethral involvement—incidence ≈20%; difficult to treat with
conservative therapy; outcomes—long-term survival excellent after radical cystectomy for local, bladder-confined, node-
negative disease; when it occurs, local recurrence tends to be lethal; combination of cystectomy and orthotopic
diversion—reduces risk for urethral recurrence; eliminates need for stoma and urostomy appliance; enables most patients
to void to completion and achieve good daytime and nighttime continence; point—early cystectomy achieves better
survival rates than postponing surgery until muscle invasion occurs
|
| Conservative therapy: considerations when contemplating bladder preservation—tumors can progress; one-third of
patients die of disease; patients require long-term follow-up; TUR and multiple intravesical therapies may be necessary;
recommendations—be diligent with follow-up; understand tumor biology and natural progression; know when to abandon
conservative therapy in favor of more aggressive treatment
|
| Early cystectomy: risk factors suggesting need for procedure—large T1 tumor (if unresectable by TUR, proceed with
cystectomy); T1 tumor with associated CIS; lymphovascular invasion; pathologic subtypes of concern (eg, aggressive micropapillary,
neuroendocrine and small-cell tumors; may require systemic chemotherapy before cystectomy; intravesical
chemotherapy contraindicated); invasion deep into lamina propria; involvement of prostate and prostatic urethra (in 30%-
50% of patients, disease involves prostatic urethra, ducts, or stroma); persistent T1 disease on repeat TUR; early failure
after intravesical therapy; surgeon should—review tissue slides with pathologist; be familiar with risk factors, including
lymphovascular invasion and deep penetration through muscularis mucosae; rationale for performing early cystectomy—
risk for progression and death after intravesical therapy; risk for clinical understaging; superior survival rate and local
control; ability to use accurate pathologic staging to determine need for adjuvant therapy; improvements in QOL provided
by orthotopic diversion and nerve-sparing technique
|
Treatment Algorithm
| RADICAL CYSTECTOMY vs PROSTATE-SPARING CYSTECTOMY
|
| High-grade invasive bladder cancer: lethal; >50% of patients who undergo cystectomy have extravesical tumor extension
and node-positive disease; issues to consider when selecting therapy—oncology; functional outcomes; QOL; fertility
|
| Prostate-sparing cystectomy (PSC): improves continence rates and potency; may allow for future fertility; does not
violate oncologic principles; patient selection not problematic
|
| Conclusions from review of oncologic data: prostate cancer in men undergoing cystectomy, and bladder cancer involving
prostate—incidence high; tumors significant and difficult to identify; cystectomy—required when preserving prostate
in men with bladder cancer; requirement has profound oncologic implications for younger men considering PSC
|
| Oncologic concerns with PSC: long-term follow-up necessary to determine true oncologic implications; data show—
pelvic recurrences tend to be lethal; dramatic increase in risk for distant metastases in young men who had preoperative
transurethral resection of prostate (TURP); compared to men with pathologic organ-confined disease who underwent
standard radical cystectomy, men undergoing PSC had higher rate of distant failure (problem may be related to
venous emboli of tumor)
|
| Standard radical cystectomy with nerve-sparing approach: patient selection critical; potency rates 30% to
50% (may be higher in young patients); local recurrences lethal; appropriate lymphadenectomy required for all patients;
urethral anastomosis can be performed in patients undergoing radical cystectomy; local recurrence rates not compromised
by—frozen section analysis of urethral margin in candidates for standard cystectomy; nerve-sparing cystectomy (postoperative
potency rates related to patient age)
|
| Standard radical cystectomy: daytime and nighttime continence good after cystectomy with orthotopic neobladder;
points—if patients followed long enough after cystectomy, physician will likely see development of hypercontinence in
some men; PSC achieves outstanding continence rate and offers clear benefit of preserving potency; radical cystoprostatectomy
with orthotopic neobladder associated with good QOL
|
| Radical cystoprostatectomy: best oncologic operation; orthotopic diversion performed easily and achieves excellent
outcomes; nerve-sparing approach performed in appropriately selected patients; achieves good QOL; fertility—not major
concern with cystoprostatectomy (mean patient age, 66-67 yr); problems with prostate-sparing approach designed to
minimize risk to continence and potency without compromising oncologic outcome—technique for dividing bladder neck
increases potential for tumor spill; prostate cancer difficult to detect preoperatively; bladder cancer can involve prostate
and stroma; cure rate poor; no good oncologic reason for preserving seminal vesicles; accuracy of frozen section analysis
difficult to assess
|
| Conclusions: radical cystoprostatectomy vs PSC—long-term oncologic outcomes excellent with standard radical cystectomy,
questionable with PSC; daytime continence similar for both procedures (often age-dependent); nighttime continence
improved with radical surgery; potency better in prostate-sparing group; QOL similar in both groups; patient
selection easier for those individuals undergoing standard radical cystoprostatectomy; radical cystoprostatectomy best
therapeutic option
|
| RADICAL CYSTECTOMY FOR INVASIVE BLADDER CANCER: LONG-TERM RESULTS OF A STANDARD
PROCEDURE
|
| Radical cystectomy for high-grade invasive bladder cancer: provides best survival and lowest local recurrence
rates; technical advances have reduced surgery-related morbidity and mortality; urinary tract reconstruction improves
QOL; no equally effective therapeutic alternative available
|
| Data from patients who underwent radical cystectomy: therapy—included extended lymph node dissection followed by
adjuvant chemotherapy in postoperative setting; adjuvant irradiation ineffective; caveats—necessary to advise patients
of 2% to 3% mortality rate; one-third of patients develop postoperative complications (dehydration most common
problem requiring hospitalization); complications—no difference in perioperative morbidity and mortality among patients
undergoing incontinent vs continent urinary diversion; postoperative complication rates similar, regardless of
whether adjuvant therapy administered; survival curve data—most deaths occurring during first 2.5 to 3.0 yr related to
bladder cancer; at ≥3 yr, comorbid disease primary cause of death; radical cystectomy achieves durable results (late recurrences
uncommon); pathologic stage—key risk factor in patients undergoing cystectomy; recurrence-free rate 82% in
patients with organ-confined lymph node-negative disease (no difference in outcomes between P1 and P2 disease confined
to bladder wall); good results in patients with extravesical lymph node-negative disease; prognosis worst for patients
with lymph node-positive disease
|
| Recurrence: defined as local or distant (both potentially fatal); local control good, ie, recurrence after radical cystectomy
≈5%; recurrence stratified by pathologic subgroup—lymph node-positive disease (good local control achieved with appropriate
lymph node dissection); organ-confined disease (local recurrence rate 2%)
|
| Lymph node-positive disease: found in ≈25% of patients during cystectomy; incidence correlates with increasing primary
bladder tumor stage; risk factors—tumor burden; number of positive lymph nodes (chance of survival varies inversely
with number of positive nodes); primary bladder tumor (patients with organ-confined tumor have better long-term survival
than individuals with extravesical disease); lymph node density—key concept; defined as number of lymph nodes involved,
divided by number of lymph nodes removed; helps stratify patients with node-positive disease; lymph node packets—when
compared to en bloc excision, removing lymph node packets for evaluation increased total number of lymph nodes removed
at time of cystectomy; extended lymph node dissection—important to overall outcome; takes longer to accomplish but can
cure one-third of patients with node-positive disease; systemic chemotherapy—ineffective and cannot compensate for poor
surgery
|
| Cystectomy: computed tomography (CT)—obtain before surgery; look for obvious nodal disease preoperatively; evaluate
accessory lower pole renal arteries
|
| Additional considerations: orthotopic diversion—performed in most patients; achieves good continence results; does
not compromise local and urethral recurrence rates; clinical observations about successful surgery—surgical factors, not
neoadjuvant chemotherapy, considered most important predictors of outcome; extended lymph node dissection and surgical
margin status especially important for achieving success; pathologic stage and lymph node status also contribute to
outcome
|
| Conclusions about treatment of high-grade invasive bladder cancer: radical cystectomy—ideal therapy;
achieves excellent local control; reduces local recurrence and incidence of distant metastases, compared to other options;
improved technique and orthotopic reconstruction have enhanced QOL; point—chemotherapy will not cover surgical errors
and mistakes; surgery remains key to successful outcome
|
| URETHRAL MANAGEMENT AFTER RADICAL CYSTECTOMY
|
| Introduction: with evolution of urinary diversion, urethral management becoming more important; orthotopic
diversion—performed in 80% to 90% of patients; changing management of patients who have undergone radical cystectomy
|
| Urethral recurrence: 9% to 10% incidence ; etiology difficult to define—synchronous (unrecognized transitional cell
carcinoma [TCC] at time of cystectomy; positive margin; tumor spillage or implantation); metachronous (most common
cause; may be related to de novo panurothelial disease); risk factors in men—multifocality; CIS; involvement of bladder
neck; upper tract TCC; form of urinary diversion; prostatic involvement
|
| Recurrence in men who underwent radical cystectomy, followed by orthotopic or cutaneous diversion:
similar pathologic characteristics, pathologic stage, and prostate involvement in both groups; independent predictors
of urethral recurrence include prostatic involvement (stromal involvement associated with greatest risk) and form of
urinary diversion (estimated probability of recurrence highest in men undergoing cutaneous diversion)
|
| Key points: orthotopic diversion associated with lower risk for urethral recurrence; intraoperative frozen section analysis
of urethra considered appropriate and accurate method of selecting candidates for reconstruction; prostatic involvement
does not exclude patient from undergoing orthotopic diversion (patient selection depends on results of frozen section
analysis)
|
| Management: ≈60% of patients with urethral recurrence present with symptoms (one-third have positive cytology);
complaints at presentation—blood from urethra; pain; palpable mass; change in voiding pattern; total urethrectomy—
preferred; outcomes mandate aggressive approach; options—distal urethrectomy alone or intraurethral 5-flurouracil
cream not recommended; systemic chemotherapy; points—symptomatic patient does not have worse outcome than patient
whose cancer detected by urinary cytology; outcomes not affected by method or time to diagnosis, and primary
pathologic subgroup of urethral recurrence; points—urethral recurrence, not stage of bladder disease, drives mortality
rates; presence of superficial (vs invasive) disease determines survival
|
| Conclusions: urethral recurrence lethal long-term problem requiring careful follow-up; most patients symptomatic; prostatic
involvement high-risk situation, requiring aggressive management and annual cystoscopic evaluation; ≥80% of patients
who have undergone orthotopic diversion have some red blood cells in urine (any patient with gross hematuria and
blood spotting should undergo cystoscopy); points—outcomes generally poor; patients require urethrectomy; urethral invasion
probably most important prognostic factor determining overall survival
|
Suggested Reading
Clark PE et al: The management of urethral transitional cell carcinoma after radical cystectomy for invasive bladder
cancer. J Urol 172:1342, 2004; Cookson MS et al: The treated natural history of high risk superficial bladder cancer: 15
year outcome. J Urol 158:62, 1997; Hautmann RE, Stein JP: Neobladder with prostatic capsule and seminal–sparing
cystectomy for bladder cancer: a step in the wrong direction. Urol Clin N Am 32:177, 2005; Herr HW et al: Impact of
the number of lymph nodes retrieved on outcome in patients with muscle invasive bladder cancer. J Urol 167:1295, 2002;
Herr HW, Donat SM: Prostatic tumor relapse in patient with superficial bladder tumors: 15 year outcome. J Urol
161:1854, 1999; Herr HW, Sogani PC: Does early cystectomy improve the survival of patient with high risk superficial
bladder tumors. J Urol 166:12960, 2001; Stein JP: Indications for early cystectomy. Urology 62:591, 2003; Stein JP et
al: Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1054 patients. J Clin Oncol 19:666,
2001; Stein JP et al: Risk factors for patients with pelvic lymph node metastases following radical cystectomy with en
bloc cystectomy: the concept of lymph node density. J Urol 170:35, 2003; Stein JP et al: Urethral tumor recurrence following
cystectomy and urinary diversion: clinical and pathological characteristics in 768 male patients. J Urol 173:1163,
2005; Vallancien G et al: Cystectomy with prostate sparing for bladder cancer in 100 patients: 10-year experience. J
Urol 168:2413, 2002.
|
