Faculty Bibliography

OBJECTIVE:To examine the functional outcomes after radical (RN) and partial nephrectomy (PN) stratified by variables before and after surgery, using estimated glomerular filtration rate (eGFR), as nephrectomy is the standard treatment for localized renal tumours, but the risk of developing chronic kidney disease (CKD) increases after surgery. PATIENTS AND METHODS/METHODS:We retrospectively analysed patients treated with PN or RN for renal cancer at one institution from 1988 to 2008. Chronic renal function before and after surgery was measured using the eGFR computed using the Modification of Diet in Renal Disease equation. Four outcomes were measured: (i) presence of new-onset renal insufficiency (eGFR <60 mL/min/1.73m(2)); (ii) the percentage change in eGFR; (iii) the change in CKD stage; and (iv) the presence of CKD upstaging. Regression models were used to determine the effect of surgical procedure (RN vs PN), access technique (open vs laparoscopic) and several preoperative characteristics on functional outcomes. RESULTS:In all, 276 patients met the inclusion criteria (174 RN and 102 PN) of whom 209 had a preoperative eGFR of >60 mL/min/1.73m(2). After >or=3 months from surgery, 108/209 (52%) patients developed new-onset eGFR of <60 mL/min/1.73m(2). On multivariate analysis, preoperative CKD stage (P < 0.001) and procedure (P= 0.001) were both independent predictors of all four functional outcomes measured. Also, hypertension was an independent predictor of CKD upstaging (P= 0.02). Surgical access technique was not an independent predictor of any of the renal functional outcomes measured. CONCLUSION/CONCLUSIONS:Patients undergoing renal surgery have a high rate of new-onset CKD afterward. After controlling for preoperative risk factors, patients undergoing RN are at greater risk of a decline in renal function. However, surgical access technique was not a significant predictor for renal impairment.

OBJECTIVES/OBJECTIVE:To evaluate the effects of age at radical prostatectomy (RP) on recurrence-free survival (RFS) in patients with prostate cancer stratified by established preoperative risk factors (such as prostate-specific antigen (PSA) level, Gleason score, and tumour stage), as increasing age has been associated with more indolent behaviour in some cancers. PATIENTS AND METHODS/METHODS:A retrospective analysis of men treated with RP from 1988 to 2008 was conducted. Patients were divided into two groups by age at the time of RP, and RFS rates were analysed using Kaplan-Meier survival curves. The subgroups were stratified by preoperative PSA level, biopsy Gleason score, and clinical stage; multivariate analyses with Cox proportional hazards models were used to identify independent predictors of recurrence. Recurrence was defined as a single PSA level of > or =0.2 ng/mL at least 28 days after RP. RESULTS:In all, 1984 patients met inclusion criteria and were divided into groups 1 (1325 men aged 40-64 years) and 2 (659 men aged > or =65 years). The 5-year RFS rates were 80.6% (confidence interval, CI 78.0-82.9%) and 75.6% (CI 71.5-79.1%) for groups 1 and 2, respectively. In the univariate model, advanced age was significantly associated with an increased overall risk of recurrence (hazard ratio, HR 1.30, P = 0.012). However, in multivariate analyses accounting for PSA level, Gleason score, and clinical stage, age was not an independent predictor of recurrence (HR 1.04, P = 0.76). CONCLUSION/CONCLUSIONS:Older patients who undergo RP appear to have an increased risk of recurrence. However, age is not an independent predictor of recurrence when accounting for PSA level, grade, and stage.

OBJECTIVES/OBJECTIVE:To determine whether the decreased short-term morbidity associated with minimally invasive surgery (MIS) has resulted in an alteration in the disease-specific risk profile of prostatectomy patients. MIS in many fields has resulted in an expansion in the pool of patients willing to undergo surgery. METHODS:The Columbia Urologic Oncology Database was queried, and 1751 patients undergoing radical prostatectomy between 2000 and 2007 were identified. The cohort was divided into 2 groups: patients who received surgery before or after the initiation of robotic-assisted laparoscopic radical prostatectomy (RALRP) at our institution (from 2003 onward). Age at surgery, Kattan Nomogram (KN) score, prostate-specific antigen (PSA), Gleason score sum, and tumor stage were compared using unpaired t tests with Welch correction and Mann-Whitney tests. RESULTS:A total of 663 patients underwent prostatectomy from 2000 to 2002 ("pre-MIS era"), and 1088 patients had surgery in 2003 or later ("MIS era"), of which 519 and 569 underwent RALRP and open prostatectomy, respectively. There was no significant difference between the 2 eras regarding age, Kattan Nomogram score, or tumor stage. However, there was a significant difference in preoperative PSA (P = .01) and Gleason sum (P = .0002). In a comparison of the pre-MIS era with RALRP patients, only PSA differed significantly (P = .0002). CONCLUSIONS:The advent of MIS for prostate cancer did not significantly alter the characteristics of patients undergoing prostatectomy at our institution. Although advancements in surgical techniques may improve clinical outcomes, this study does not suggest a consequential effect on the risk stratification of patients choosing surgery for prostate cancer.

OBJECTIVES/OBJECTIVE:To report the long-term clinical outcomes and durability of response after treatment with induction intravesical docetaxel. Most novel agents used to treat bacillus Calmette-Guerin refractory high-grade non-muscle-invasive (NMI) bladder cancer are evaluated only after short follow-up periods. Our previously published phase I trial demonstrated that docetaxel is a safe agent for intravesical therapy with minimal toxicity and no detectable systemic absorption. We sought to determine long-term clinical outcomes after treatment with intravesical docetaxel. METHODS:Eighteen patients with recurrent Ta (n = 7), T1 (n = 5), and Tis (n = 6) transitional cell carcinoma who experienced treatment failure with at least 1 prior intravesical therapy completed the phase I trial. Docetaxel was administered as 6 weekly intravesical instillations using a dose-escalation model terminated at 0.75 mg/mL. Efficacy was evaluated by interval cystoscopy with biopsies when indicated, cytology, and computed tomography imaging. Follow-up consisted of quarterly cystoscopy, cytology, computed tomography, and biopsy when indicated. RESULTS:With a median follow-up of 48.3 months, 4 patients (22%) have demonstrated a complete durable response and currently remain disease-free without further treatment. Three patients (17%) had a partial response, defined as a single NMI recurrence with no further therapy for bladder cancer. Eleven patients (61%) failed treatment, and required another intervention. One patient developed stage progression. No delayed toxicities were noted. The median disease-free survival time was 13.3 months. CONCLUSIONS:After 4 years of follow-up without maintenance therapy, intravesical docetaxel has demonstrated the ability to prevent recurrence in a select number of patients with refractory NMI bladder cancer and warrants further investigation.

The definitive treatment for patients with non-muscle-invasive bladder cancer (NMIBC) who fail to respond to intravesical BCG is cystectomy. When a patient is deemed BCG-refractory and cannot or will not undergo cystectomy, alternative intravesical therapy may be the most effective way to minimize recurrence and progression. A number of immunotherapeutic and chemotherapeutic agents have been given intravesically over the years, and several recently and currently investigated novel agents appear to be particularly promising for the management of BCG-refractory NMIBC. The most effective treatments in the future will likely utilize targeted therapies based on the underlying genetic mutations associated with each individual diagnosis of NMIBC.

OBJECTIVE:To analyse the durability of response for patients with non-muscle-invasive bladder cancer (NMIBC) refractory to bacille Calmette-Guérin (BCG) therapy and treated with intravesical docetaxel in a combined induction and maintenance regimen. PATIENTS AND METHODS/METHODS:A previous phase I trial showed docetaxel to be safe for intravesical therapy, with no systemic absorption and minimal toxicity after six weekly instillations for patients with BCG-refractory NMIBC. In that trial, docetaxel gave a 56% complete response (CR) rate at 12 weeks, but the durability was only 22%. Thus a second group of patients was treated with a 6-week induction and then given monthly maintenance therapy with intravesical docetaxel. Thirteen patients with BCG-refractory Ta, T1, or Tis transitional cell carcinoma were treated. Induction therapy was administered as six weekly intravesical instillations of 75 mg followed by single-dose monthly maintenance therapy for nine additional instillations in patients who had a CR. The initial response at 12 weeks from the start of induction therapy was evaluated by cystoscopy with biopsy, and urine cytology. The follow-up consisted of quarterly cystoscopy with biopsy and cytology, and periodic imaging. RESULTS:The median follow-up was 13 months; 10 of 13 patients had a CR after induction, and six have remained disease-free during the follow-up. Of those in who the treatment failed, six had transurethral resection of the tumour and one a cystectomy. All 10 initial responders completed at least three instillations of maintenance therapy to date (median nine instillations), of whom six have remained recurrence-free. CONCLUSION/CONCLUSIONS:Monthly maintenance therapy with intravesical docetaxel appears to extend the durability of response to induction treatment for a selected group of patients with BCG-refractory NMIBC, and might decrease the overall risk of recurrence in high-risk NMIBC.

OBJECTIVES/OBJECTIVE:Since the success of our Phase I trial of intravesical docetaxel for treatment-refractory non-muscle invasive bladder cancer (NMIBC), we have found this agent to be a favorable alternative for BCG-refractory patients unable or unwilling to undergo cystectomy. This study analyzes the safety and efficacy of intravesical docetaxel in a larger patient population with extended follow-up. METHODS:A retrospective analysis of all patients who received salvage intravesical docetaxel at our institution was conducted, including 18 patients treated during the Phase I trial and 15 patients treated after the trial's completion. Toxicity, efficacy and recurrence-free survival were analyzed. RESULTS:Thirty-three patients with refractory NMIBC received salvage intravesical docetaxel therapy between 2003 and 2008 at a single institution. Twenty of thirty-three (61%) patients had a complete response (CR) after six weekly induction treatments. Ten patients with CRs were given maintenance docetaxel therapy, and one patient received maintenance BCG and interferon. With a median follow-up of 29 months, 1 and 2-year recurrence-free survival rates were and 45 and 32%, respectively. Twelve of thirty-three patients (36%) had Grade 1 or 2 local toxicities. No patients experienced Grade 3 or 4 toxicities. CONCLUSIONS:Docetaxel is a promising intravesical agent with minimal toxicity and significant efficacy and durability for the management of BCG-refractory NMIBC.