Bjoern G. Volkmer

Postoperative nomogram predicting risk of recurrence after radical cystectomy for bladder cancer

PURPOSE Radical cystectomy and pelvic lymphadenectomy (PLND) remains the standard treatment for localized and regionally advanced invasive bladder cancers. We have constructed an international bladder cancer database from centers of excellence in the management of bladder cancer consisting of patients treated with radical cystectomy and PLND. The goal of this study was the development of a prognostic outcomes nomogram to predict the 5-year disease recurrence risk after radical cystectomy. PATIENTS AND METHODS Institutional radical cystectomy databases containing detailed information on bladder cancer patients were obtained from 12 centers of excellence worldwide. Data were collected on more than 9,000 postoperative patients and combined into a relational database formatted with patient characteristics, pathologic details of the pre- and postcystectomy specimens, and recurrence and survival status. Patients with available information for all selected study criteria were included in the formation of the final prognostic nomogram designed to predict 5-year progression-free probability. RESULTS The final nomogram included information on patient age, sex, time from diagnosis to surgery, pathologic tumor stage and grade, tumor histologic subtype, and regional lymph node status. The predictive accuracy of the constructed international nomogram (concordance index, 0.75) was significantly better than standard American Joint Committee on Cancer TNM (concordance index, 0.68; P < .001) or standard pathologic subgroupings (concordance index, 0.62; P < .001). CONCLUSION We have developed an international bladder cancer nomogram predicting recurrence risk after radical cystectomy for bladder cancer. The nomogram outperformed prognostic models that use standard pathologic subgroupings and should improve our ability to provide accurate risk assessments to patients after the surgical management of bladder cancer.

Radical Cystectomy for Urothelial Carcinoma of the Bladder Without Neoadjuvant or Adjuvant Therapy: Long-Term Results in 1100 Patients

BACKGROUND The optimal treatment strategy for muscle-invasive bladder cancer (BCa) remains controversial. OBJECTIVE Better define the long-term outcomes of radical cystectomy (RC) alone for BCa and determine the impact of pathologic downstaging after transurethral resection in a large and homogeneous single-center series. DESIGN, SETTING, AND PARTICIPANTS A cohort of 1100 patients undergoing RC with pelvic lymph node dissection (PLND) without neoadjuvant therapy for urothelial carcinoma of the bladder between January 1, 1986, and December 2009 was evaluated. Patients with other than metastases to the pelvic lymph nodes were excluded. Median age was 65 yr. Clinical course, pathologic characteristics, and long-term outcomes were evaluated. Follow-up was obtained until December 2009 with a median of 38 mo and a completeness of 96.5%. INTERVENTION RC with PLND; urinary diversion with ileal neobladder whenever possible. MEASUREMENTS Primary end points were disease-specific survival (DSS), recurrence-free survival (RFS), and overall survival (OS) according to the tumor stage of the RC specimen versus the maximum tumor stage. The log-rank test was used to compare subgroups. RESULTS AND LIMITATIONS The 30-d (90-d) mortality rate was 3.2% (5.2%). The 10-yr OS, DSS, and RFS rates were 44.3%, 66.8%, and 65.5%, respectively. Based on the tumor stage of the RC specimen, the 10-yr DSS rate was pT0/a/is/1 pN0: 90.5%, pT2a/b pN0: 66.8%, pT3a/b pN0: 59.7%, pT4a/b pN0: 36.6%, and pTall pN+: 16.7%. Downstaging by transurethral resection of the prostate was observed in 382 patients. Patients with maximum tumor stage pT2a/b pN0 had distinctly better 10-yr DSS rates than those with pT2a/b pN0 in the RC specimen: pT2a pN0: 92.2% versus 73.8%; pT2b: 75.0% versus 62.0%. A total of 49% female and 80% male patients received an ileal neobladder. CONCLUSIONS This contemporary and homogeneous single-center series found acceptable OS, DFS, and RFS for patients undergoing RC. Pathologic downstaging had a significant impact on survival.

25 Years of Experience With 1,000 Neobladders: Long-Term Complications

PURPOSE We analyzed the long-term complications (greater than 90 days postoperatively) in a large, single center series of patients who underwent cystectomy and substitution with an ileal neobladder. MATERIALS AND METHODS A total of 1,540 radical cystectomies were performed at our center between January 1986 and September 2008. Of the patients 1,013 received an ileal neobladder. Only the 923 patients with followup longer than 90 days (median 72 months, range 3 to 267) were included in analysis. All long-term complications were identified. The complication rate was calculated using the Kaplan-Meier method. RESULTS The overall survival rate was 65.5%, 49.8% and 28.3% at 5, 10 and 20 years, respectively. The overall long-term complication rate was 40.8% with 3 neobladder related deaths. Hydronephrosis, incisional hernia, ileus or small bowel obstruction and feverish urinary tract infection were observed in 16.9%, 6.4%, 3.6% and 5.7% of patients, respectively, 20 years postoperatively. Subneovesical obstruction in 3.1% of cases was due to local tumor recurrence in 1.1%, neovesicourethral anastomotic stricture in 1.2% and urethral stricture in 0.9%. Chronic diarrhea was noted in 9 patients. Vitamin B12 was substituted in 2 patients. Episodes of severe metabolic acidosis occurred in 11 patients and 307 of 923 required long-term bicarbonate substitution. Rare complications included cutaneous neobladder fistulas in 2 cases, and intestinal neobladder fistulas, iatrogenic neobladder perforation, spontaneous perforation and necrotizing pyocystis in 1 each. CONCLUSIONS Even in experienced hands the long-term complication rate of radical cystectomy and neobladder formation are not negligible. Most complications are diversion related. The challenge of optimum care for these elderly patients with comorbidities is best mastered at high volume hospitals by high volume surgeons.

ICUD-EAU International Consultation on Bladder Cancer 2012: Urinary diversion.

CONTEXT A summary of the 2nd International Consultation on Bladder Cancer recommendations on the reconstructive options after radical cystectomy (RC), their outcomes, and their complications. OBJECTIVE To review the literature regarding indications, surgical details, postoperative care, complications, functional outcomes, as well as quality-of-life measures of patients with different forms of urinary diversion (UD). EVIDENCE ACQUISITION An English-language literature review of data published between 1970 and 2012 on patients with UD following RC for bladder cancer was undertaken. No randomized controlled studies comparing conduit diversion with neobladder or continent cutaneous diversion have been performed. Consequently, almost all studies used in this report are of level 3 evidence. Therefore, the recommendations given here are grade C only, meaning expert opinion delivered without a formal analysis. EVIDENCE SYNTHESIS Indications and patient selection criteria have significantly changed over the past 2 decades. Renal function impairment is primarily caused by obstruction. Complications such as stone formation, urine outflow, and obstruction at any level must be recognized early and treated. In patients with orthotopic bladder substitution, daytime and nocturnal continence is achieved in 85-90% and 60-80%, respectively. Continence is inferior in elderly patients with orthotopic reconstruction. Urinary retention remains significant in female patients, ranging from 7% to 50%. CONCLUSIONS RC and subsequent UD have been assessed as the most difficult surgical procedure in urology. Significant disparity on how the surgical complications were reported makes it impossible to compare postoperative morbidity results. Complications rates overall following RC and UD are significant, and when strict reporting criteria are incorporated, they are much higher than previously published. Fortunately, most complications are minor (Clavien grade 1 or 2). Complications can occur up to 20 yr after surgery, emphasizing the need for lifelong monitoring. Evidence suggests an association between surgical volume and outcome in RC; the challenge of optimum care for elderly patients with comorbidities is best mastered at high-volume hospitals by high-volume surgeons. Preoperative patient information, patient selection, surgical techniques, and careful postoperative follow-up are the cornerstones to achieve good long-term results.

Lessons Learned From 1,000 Neobladders: The 90-Day Complication Rate

PURPOSE We report the 90-day morbidity of the ileal neobladder in a large, contemporary, homogenous series of patients who underwent radical cystectomy at a tertiary academic referral center using a standard approach. MATERIALS AND METHODS Between January 1986 and September 2008 we performed 1,540 radical cystectomies. A total of 281 patients had an absolute contraindication for orthotopic reconstruction. The remaining 1,259 patients were candidates for a neobladder. Of these patients 1,013 (66%) finally received a neobladder and form the basis of this report. All patients had a thorough followup until December 2008 or until death. All complications within 90 days of surgery were defined, categorized and classified by an established 5 grade and 11 domain modification of the original Clavien system. RESULTS Of 1,013 patients 587 (58%) experienced at least 1 complication within 90 days of surgery. Infectious complications were most common (24%) followed by genitourinary (17%), gastrointestinal (15%) and wound related complications (9%). The 90-day mortality rate was 2.3%. Of the patients 36% had minor (grade 1 to 2) and 22% had major (grade 3 to 5) complications. On univariate analysis the incidence and severity of the 90-day complications rate correlate highly significantly with age, tumor stage, American Society of Anesthesiologists score and preoperative comorbidity. CONCLUSIONS Radical cystectomy and ileal neobladder formation represent a major surgery with potential relevant early complications even in the most experienced hands. The rate of severe and lethal complications is acceptably low.

Soft Tissue Surgical Margin Status is a Powerful Predictor of Outcomes After Radical Cystectomy: A Multicenter Study of More Than 4,400 Patients

PURPOSE We evaluated the association of soft tissue surgical margins with characteristics and outcomes of patients treated with radical cystectomy for urothelial carcinoma of the bladder. MATERIALS AND METHODS We retrospectively collected the data of 4,410 patients treated with radical cystectomy and pelvic lymphadenectomy without neoadjuvant chemotherapy at 12 academic centers in the United States, Canada and Europe. A positive soft tissue surgical margin was defined as presence of tumor at inked areas of soft tissue on the radical cystectomy specimen. RESULTS Positive soft tissue surgical margins were identified in 278 patients (6.3%). On univariate analysis positive soft tissue surgical margin was significantly associated with advanced pT stage, higher tumor grade, lymphovascular invasion and lymph node metastasis (p <0.001). Actuarial 5-year recurrence-free and cancer specific survival probabilities were 62.8% +/- 0.8% and 69% +/- 0.8% for patients without soft tissue surgical margins vs 21.6% +/- 3.1% and 26.4% +/- 3.3% for those with positive soft tissue surgical margins (p <0.001). On multivariable analyses adjusting for the effect of standard clinicopathological features and adjuvant chemotherapy positive soft tissue surgical margin was an independent predictor of disease recurrence and cancer specific mortality (HR 1.52 and HR 1.51, p <0.001, respectively). Soft tissue surgical margin retained independent predictive value in subgroups with advanced disease such as pT3Nany, pT4Nany or Npositive. CONCLUSIONS Positive soft tissue surgical margin is a strong predictor of recurrence and eventual death from urothelial carcinoma of the bladder. Soft tissue surgical margin status should always be reported in the pathological reports after radical cystectomy. Due to uniformly poor outcomes patients with positive soft tissue surgical margins should be considered for studies on adjuvant local and/or systemic therapy.

International validation of the prognostic value of lymphovascular invasion in patients treated with radical cystectomy.

Study Type – Prognosis (retrospective cohort)
Level of Evidence 2b

Oncological Followup After Radical Cystectomy for Bladder Cancer—Is There Any Benefit?

PURPOSE Tumor recurrence after radical cystectomy for bladder cancer can be detected in an asymptomatic patient by regular followup or in a symptomatic patient by symptom guided examination. To our knowledge it is still unknown whether detecting tumor recurrence at an asymptomatic stage offers a better survival rate. MATERIALS AND METHODS A total of 1,270 radical cystectomies for bladder cancer were performed at a single institution between January 1, 1986 and December 2006. All patients had regular followup examinations with chest x-ray and abdominal ultrasound every 3 months, computerized tomography of the abdomen every 6 months, and bone scan and excretory urography every 12 months. Additional examinations were required for symptomatic disease. We analyzed the first site and date of tumor recurrence. Survival was compared using the log rank test. RESULTS The 20-year recurrence rate was 48.6% in the complete series. Tumor recurrence developed in 444 patients, including 154 asymptomatic and 290 symptomatic patients, with a mean time after radical cystectomy of 20 and 17.5 months, respectively. The most frequent symptoms were pain, ileus, acute urinary retention, hydronephrosis with flank pain, hematuria, neurological symptoms and a palpable mass. Of the 444 patients 182 (41%) had local recurrence and 324 (73%) had distant failure at the time of first recurrence. The overall survival rate 1, 2 and 5 years after first recurrence was 22.5%, 10.1% and 5.5% in asymptomatic patients, and 18.9%, 8.2% and 2.9% in symptomatic patients, respectively (log rank not significant). CONCLUSIONS This study fails to demonstrate a survival benefit for detecting tumor recurrence early at an asymptomatic stage by regular followup examinations. These data show that symptom guided followup examinations may provide similar results at lower cost.

Surgical intervention for complications of tension-free vaginal tape procedure.

PURPOSE The tension-free vaginal tape procedure has become a state of the art operation for female stress urinary incontinence. Cases of complications requiring surgical revision are reported to be rare. We report on 6 patients with complications necessitating surgery. MATERIALS AND METHODS Six patients who previously underwent the tension-free vaginal tape procedure required surgical management of complications, including intravesical polypropylene mesh tape with incrustation and chronic urinary tract infection in 2, vaginal mucosal mesh erosion of the vaginal incision in 1 and permanent urinary retention in 3. RESULTS The intravesical tapes were resected via a suprapubic approach. In the case of disturbed wound healing the periurethral part of the tape was resected transvaginally. A patient in urinary retention underwent resection of the periurethral sling, while in the other 2 the tapes were transected transvaginally. Two patients in whom incontinence recurred were successfully treated with a repeat tension-free vaginal tape procedure during followup. CONCLUSIONS Complications of the tension-free vaginal tape procedure that require surgical intervention are rare. The surgeon must be aware that this operation may lead to an additional surgical procedure, significantly increasing morbidity.

Discrepancy between clinical and pathological stage: External validation of the impact on prognosis in an international radical cystectomy cohort

Study Type – Prognosis (case series) Level of Evidence 4