Michael S. Cookson

The diagnosis and subsequent management of bladder cancer often involves transurethral resection of bladder tumor (TURBT). Risks of TURBT include perioperative complications such as bleeding, pain and perforation. We aimed to determine TURBT complication rates and risk factors in a contemporary series. From 2002 to 2011, 505 patients underwent TURBT either for suspected bladder cancer or during follow up at a single institution. Baseline patient characteristics and complications within 2 weeks of surgery were extracted from the electronic medical record for all TURBTs. Patient and tumor characteristics were evaluated for associations with complication using univariate analysis. A multivariable logistic regression was fit to further examine associations between TURBT related characteristics and complication. A total of 910 TURBTs were performed on 505 patients. Overall complication rate was 8.1%. The most common complications were pain or spasm (3.0%), retention (2.8%), and infection (2.1%), and 0.5% of TURBTs had perforation. Over 85% of complications were Clavien-Dindo grade I or II. Forty-three patients had a complication after their first TURBT, while 25 had complications after subsequent TURBTs. Prior complication and single tumor, but not other patient or tumor-related characteristics, were associated with complication. Only prior complication (p < 0.01) was associated with subsequent complication after TURBT on multivariable analysis. Complication rate after TURBT is 8.1% and complications are generally not severe in nature. Prior short term complication is likely associated with subsequent complication. Further studies are needed to validate these results and determine patient groups most at risk for intraoperative and post TURBT complications.

The objective was to conduct a US multicenter, retrospective medical record study examining the effectiveness, safety, and patterns of use of valrubicin for treatment of nonmuscle-invasive bladder cancer (NMIBC) by clinicians since the 2009 reintroduction of valrubicin. Patients ≥ 18 years with NMIBC who received had one or more instillations of valrubicin (October 2009– September 2011) were eligible. The primary endpoint was event-free survival (EFS). Safety and tolerability were also assessed. The medical records of 113 patients met the inclusion criteria; 100 patients (88.5%) completed valrubicin treatment. The median age was 75 years (range 42–95 years). The median NMIBC duration was 31 months since diagnosis: 51.3% (58/113) had carcinoma in situ (CIS) alone, and 31.9% (36/113) had unspecified NMIBC. Most patients, 94.7% (107/113), had more than three valrubicin instillations and 70.8% (80/113) completed a full course. The EFS rate (95% confidence interval) was 51.6% (40.9–61.3%), 30.4% (20.4–41.1%), and 16.4% (7.9–27.5%) at 3, 6, and 12 months, respectively. Median time to an event was 3.5 (2.5–4.0) months after the first valrubicin instillation. Local adverse reactions (LARs) were experienced by 49.6% (56/113) of patients; most LARs were mild (93.6%). The most frequent LARs were hematuria, pollakiuria, micturition urgency, bladder spasm, and dysuria. In total, 4.4% (5/113) of patients discontinued valrubicin because of adverse events or LARs. Data from the present retrospective study are consistent with previous prospective clinical trials that demonstrated valrubicin effectiveness and tolerability for select patients with CIS, before considering cystectomy. Additional prospective studies are warranted to evaluate valrubicin safety and efficacy in the broader patient population with NMIBC.

296 Background: Valrubicin was approved in the United States in 1998, removed from the market in 2002 because of manufacturing issues, and reintroduced in 2009. We report secondary outcomes and concomitant medication use from a US multicenter, observational, retrospective study. Methods: Medical records of adult patients with non–muscle-invasive bladder cancer (NMIBC) who used valrubicin were abstracted (March–September 2011). Kaplan-Meier analyses were performed for disease-free survival (DFS), progression-free survival (PFS), worsening-free survival (WFS), cystectomy-free survival (CFS), and time to cystectomy. Results: 113 patients (mean age, 73.7 years) received intravesical valrubicin (median, 6 instillations [range, 2–18]). 107 patients (94.7%) received >3 instillations; 97 (85.8%) completed the full course of therapy (≥6 instillations). DFS was 51.6% (95% CI, 40.9%–61.3%) at 3 months, 30.4% (95% CI, 20.4%–41.1%) at 6 months, and median DFS was 3.5 months (95% CI, 2.5–4.0). PFS was 97.6% (95% CI, 90.9%–99.4%) at 3 months, 87.2% (95% CI, 75.4%–93.5%) at 6 months, and median PFS was 18.2 months (95% CI, 17.2–19.0). WFS was 47.4% (95% CI, 37.2%–57.0%) at 3 months and 28.1% (95% CI, 18.8%–38.2%) at 6 months. CFS was 98.0% (95% CI, 92.2%–99.5%) at 3 months and 93.7% (95% CI, 85.2%–97.4%) at 6 months. Median CFS was not reached; only 13.3% of patients underwent radical cystectomy after starting valrubicin. 56 patients (49.6%) experienced ≥1 local adverse reaction; the most common were hematuria and pollakiuria (both 17.7%), micturition urgency (15.9%), and bladder spasm (14.2%). 55 patients (48.7%) used ≥1 concomitant medication for local adverse reactions; the most commonly used were urinary antispasmodics (21.2%), fluoroquinolones (14.2%), and other urologicals (14.2%). Conclusions: In patients with NMIBC treated with intravesical valrubicin, median DFS and PFS were 3.5 and 18.2 months, respectively, and median CFS was not reached as only 13% of patients underwent radical cystectomy. Valrubicin was well tolerated, and most patients received the full course of 6 instillations. Funding: Research and abstract were supported by Endo Pharmaceuticals Inc.

309 Background: Valrubicin was approved in the United States in 1998, removed from the market in 2002 because of manufacturing issues, and reintroduced in 2009. We report the effectiveness and safety of valrubicin, stratified by patient age, from a US multicenter, observational, retrospective study. Methods: Medical records of adults with non–muscle-invasive bladder cancer (NMIBC) who used valrubicin were abstracted between March and September 2011. The median age (75 [range 42–95] years) was the stratification cutoff. Kaplan-Meier analyses were performed for event-free survival (EFS), worsening-free survival (WFS), and progression-free survival (PFS). Results: 113 patients (mean age, 73.7 years) received intravesical valrubicin (median, 6 [range, 2–18] instillations). Median EFS, WFS, and PFS were similar in patients ≤75 vs >75 years old (see Table); 1-year rates were 17.8% vs 15.4%, respectively, for EFS; 16.1% vs 14.3% for WFS; and 80.2% vs 81.4% for PFS. 11 (19%) patients aged ≤75 years vs 4 (7%) aged >75 years underwent radical cystectomy; 28 (48%) vs 28 (51%), respectively, experienced ≥1 local adverse reaction; 3 (5%) vs 4 (7%) experienced ≥1 serious adverse event; and 4 (7%) vs 1 (2%) discontinued as a result. Conclusions: In patients with NMIBC treated with intravesical valrubicin, effectiveness and safety are similar in patients aged ≤75 and >75 years. Funding: Research and abstract were supported by Endo Pharmaceuticals Inc. [Table: see text]

317 Background: IVe valrubicin is indicated for bacillus Calmette-Guérin (BCG)-refractory CIS when cystectomy is not an option. An ongoing retrospective clinical-practice chart review is being conducted to examine use of valrubicin since its reintroduction (Oct 2009). Methods: Records were analyzed for adults with non-muscle invasive bladder cancer (NMIBC) treated with valrubicin. Results: In this ongoing study, 62 patients received valrubicin (date range; 10/7/2009-6/10/2011). Most were male (52, 84%) and white (49, 79%); median age was 79 y (range, 49–89). 49 patients (79%) had a history of CIS + papillary tumors, 8 had CIS (13%), 4 had papillary (7%), 1 had NMIBC unspecified (1%). 57 patients (92%) received prior IVe therapy (median [range], 2 [0–11] courses); 13 patients (21%) received 1 course, 16 (26%) 2 courses, and 28 (45%) ≥3 courses. Immunotherapy (eg, BCG, unspecified) was the most common prior treatment (54 patients, 87%; median [range], 2 [0–7] courses); 17 patients (27%) received 1 course, 15 (24%) 2 courses, and 22 (35%) ≥3 courses. Prior IVe chemotherapy was less common (21 patients, 34%). 47 patients (76%) had ≥1 transurethral resection of the bladder tumor (median [range], 2 [0–9] for n=62 patients). Fewer had undergone ≥1 fulguration procedures (27, 44%). Most valrubicin courses (49/67, 73%) used the recommended 6 instillations (median [range], 6 [2–7]). Retention time (median [range], 120 [0–180] min) was recorded for 89/381 instillations (23%). Adverse events (AEs) were observed for 31 patients (50%); most AEs (102/106, 96%) were mild or moderate. 3 patients (5%) had serious AEs (treatment-relationship unknown). Median followup for all patients was 5.2 mo (range, 0–13.9). 13 patients (21%) underwent cystectomy at a median of 5.3 mo (range, 1-13) from the last valrubicin dose. 2 patients died, at 1.1 (metastatic disease) and 11.9 mo after finishing valrubicin. Conclusions: Patients treated with valrubicin in clinical practice often had concomitant papillary tumors and were heavily pretreated. One in 8 patients had no record of previous immunotherapy. Drug administration adhered closely to labeled instructions and was well tolerated. Funding: Endo Pharmaceuticals.

Pelvic lymph node dissection (PLND) represents the standard for detection of occult pelvic nodal metastases from prostate cancer, and may be performed separately from or at the time of radical prostatectomy. In addition to its potential for diagnostic staging, a PLND may be therapeutic in some patients. However, considerable debate centers on the appropriate candidates for the procedure, the extent and proper boundaries of dissection, optimal surgical approach, and absolute oncologic benefit. Several series suggest that there likely is limited benefit of PLND in low-risk patients and that PLND can be safely omitted in a high percentage of men undergoing contemporary radical prostatectomy. Furthermore, the value of PLND in patients with intermediate- and high-risk disease must be balanced against the potential morbidity of the procedure. In the setting of this debate, concern over morbidity directly attributable to this procedure is of paramount importance. This review focuses on the complications associated with PLND, including lymphocele, thromboembolic events, ureteral injury, nerve injury, vascular injury, and lymphedema.