Alana M. Murphy

Cryosurgical ablation of the prostate : high risk patient outcomes

The authors report their experience with cryosurgical ablation of the prostate in men with high‐risk features for prostate carcinoma who were unwilling to undergo radical surgery or radiation therapy.

Phase I Trial of Intravesical Docetaxel in the Management of Superficial Bladder Cancer Refractory to Standard Intravesical Therapy

Purpose Up to 50% of patients treated with intravesical agents for superficial bladder cancer will experience recurrence. Response rates to second-line intravesical therapies range from 20% to 40%. For these high-risk patients, novel agents are necessary to prevent recurrence. Docetaxel is a microtubule depolymerization inhibitor with unique physiochemical properties, making it an excellent candidate for investigation as an intravesical agent. Patients and Methods This phase I trial included patients with recurrent Ta, T1, and Tis transitional cell carcinoma who experienced treatment failure with at least one prior intravesical treatment. Docetaxel was administered as six weekly instillations at a starting dose of 5 mg, with a dose-escalation model used until a maximum tolerated dose (MTD) was achieved. Primary end points were dose-limiting toxicity (DLT) and MTD. Efficacy was evaluated by cystoscopy with biopsy, cytology, and computed tomography imaging. Results Eighteen patients (100%) completed the trial, and the distribution of stages included six patients with Tis, seven with Ta, and five with T1 disease. No grade 3 or 4 DLTs occurred in 108 infusions, and no patient had systemic absorption of docetaxel. Eight (44%) of 18 patients experienced grade 1 or 2 toxicities, with dysuria being the most common. Ten (56%) of 18 patients had no evidence of disease at their post-treatment cystoscopy and biopsy. None of the patients who experienced relapse had disease progression. Conclusion Intravesical docetaxel exhibited minimal toxicity and no systemic absorption in the first human intravesical clinical trial. This suggests that docetaxel is a safe agent for further evaluation of efficacy in a phase II trial.

Increasing Detection Rate of Benign Renal Tumors: Evaluation of Factors Predicting for Benign Tumor Histologic Features During Past Two Decades

OBJECTIVES To determine whether the detection of benign renal tumors is increasing and to identity the predictors of benign histologic features. The detection of renal cortical tumors has increased with the increased use of abdominal imaging. Current imaging and biopsy techniques cannot predict the renal tumor histologic features with complete accuracy, and many patients undergo surgery for benign lesions. METHODS The Columbia Urologic Oncology Database was reviewed, and 1244 patients who had undergone partial or radical nephrectomy from 1988 to 2007 were identified. A cohort of 775 patients with a tumor diameter of <or.0 cm, nonmetastatic disease, and nonfamilial disease was selected. Univariate and multivariate logarithmic regression analyses were used to determine the parameters to predict for benign histologic features. RESULTS The proportion of renal surgery for benign tumors of <or.0 cm in diameter has increased annually. When patients were stratified by the year of surgery, the proportion of benign tumors was 5.0% before 1998, 15.2% from 1998 to 2003, and 21.2% from 2004 to 2007. The mean diameter of benign and malignant tumors was 3.0 and 3.5 cm, respectively, and the mean tumor diameter significantly decreased during the study period (P = .006). Using multivariate analysis, the year of surgery, tumor diameter, and female sex were independent predictors of benign histologic features (P < .05). Age, incidental diagnosis, body mass index, and race were not significant predictors (P > .05). CONCLUSIONS Even when controlling for tumor diameter and sex, the incidence of benign tumors detected at renal surgery at our institution has increased significantly in the past 2 decades.

Long-term clinical outcomes of a phase I trial of intravesical docetaxel in the management of non-muscle-invasive bladder cancer refractory to standard intravesical therapy.

OBJECTIVES 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 NUMBER OF NEGATIVE PELVIC LYMPH NODES REMOVED DOES NOT AFFECT THE RISK OF BIOCHEMICAL FAILURE AFTER RADICAL PROSTATECTOMY

1 4 7 8 J O U R N A L C O M P I L A T I O N

Re-evaluation of the Tumour-Node-Metastasis staging of locally advanced renal cortical tumours: absolute size (T2) is more significant than renal capsular invasion (T3a)

Authors from Iowa City report on the incidence of RCC; they compared the rate of these tumours at autopsy and felt that the decrease found was a result of better antemortem detection, and an increase with time in the frequency of clinically detected renal cancer.

A comparison of the outcomes of neoadjuvant and adjuvant chemotherapy for clinical T2-T4aN0-N2M0 bladder cancer.

Despite evidence supporting perioperative chemotherapy, few randomized studies compare neoadjuvant and adjuvant chemotherapy for bladder cancer. Consequently, the standard of care regarding the timing of chemotherapy for locally advanced bladder cancer remains controversial. We compared patient outcomes following neoadjuvant or adjuvant systemic chemotherapy for cT2‐T4aN0‐N2M0 bladder cancer.

Treatment of overactive bladder: what is on the horizon?

There is still a need to develop additional effective and well-tolerated therapies for the treatment of overactive bladder (OAB). The purpose of this review is to discuss alternative therapies for idiopathic OAB that employ a unique mechanism of action or offer a novel application of an existing therapy. We performed a comprehensive literature review to identify alternative therapies and potential future treatments for idiopathic OAB. The use of botulinumtoxin for idiopathic OAB is on the rise and FDA approval will likely be granted in the future. New innovations in neuromodulation hold the promise of less invasive and more patient-controlled therapies. A number of novel medications, such as β-adrenoreceptor agonists, or medications with alternative indications, such as phosphodiesterase inhibitors, have been identified as potential therapies for OAB. In addition, novel drug delivery systems, such as vaginal inserts, are also in development and may provide an attractive mechanism to deliver medications with proven efficacy. While conservative measures such as behavioral modification and pelvic floor exercises remain first-line therapy for OAB, anti-muscarinics are the mainstay of medical treatment. For patients with idiopathic OAB refractory to traditional first-line therapies, a number of promising new treatments are on the horizon.

The clinical utility and safety of the endoscopic treatment of vesicoureteral reflux in patients with duplex ureters

OBJECTIVE A systemic review of published literature on the use of bulking agents in the treatment of vesicoureteral reflux (VUR) in patients with duplex systems was performed in order to evaluate the diagnostic challenges; determine success rates, and compare with use in single systems; and evaluate safety, in particular of Deflux. METHODS A PubMed/Medline search was conducted for index articles discussing duplex ureters published in 1963-2007. All types of publications were included. A multiple linear regression analysis was performed. RESULTS Overall, 28 different treatment arms originating in 17 separate studies (19 publications) satisfied the inclusion criteria for linear regression efficacy analysis. Data were available on 2879 patients: 2400 with single and 479 with duplex systems. Ten publications provided information on the frequency of failure to diagnose duplex systems using specific techniques. An overall 18% failure rate to detect duplex systems was reported for combined techniques. For patients in whom favorable anatomic location of ureters allowed successful endoscopic injection of a bulking agent, correction of VUR was achieved in 53-100% of cases. A univariant analysis showed no difference in success rate between single and duplex systems with the use of Deflux, or other bulking agent. The predicted probability of success in a single system was 68% and in a duplex system 64%. CONCLUSIONS There is significant potential for failing to detect duplex systems prior to preparing an individual for either open or endoscopic treatment. From the studies available, endoscopic injection of bulking agents is highly successful in correcting mild-to-moderate VUR in duplex systems, with no reports of serious or clinically significant adverse effects. At a minimum, duplex systems would not seem to be a contraindication to the use of Deflux or any other bulking agent.

Reoperative retroperitoneal lymph-node dissection for testicular germ cell tumor

PurposeWe sought to discuss the indications for reoperative retroperitoneal surgery, preoperative evaluation of patients, distribution of retroperitoneal recurrences and technical considerations for reoperative procedures. In addition, the histologic findings, clinical outcomes and perioperative complications were reviewed.MethodsA PubMED and Medline search was performed to identify reoperative retroperitoneal surgery series for patients with nonseminomatous germ cell tumor.ResultsA reliance on cisplatin-based chemotherapy to treat residual disease after RPLND is inadequate for most patients. If retroperitoneal failure does occur, reoperative RPLND should be considered as the recurrence can harbor viable GCT or teratoma, which both necessitate surgical excision. The left para-aortic and left renal hilar regions are the most common sites of retroperitoneal failure. Reoperative retroperitoneal surgery can be performed with an acceptable morbidity as long as surgeons are equipped to handle significant intraoperative complications. Clinical outcomes after reoperative RPLND are influenced by serum tumor markers, histologic findings and completeness of surgical resection.ConclusionsOverall survival rates in men requiring redo RPLND appear significantly lower than similar patients who are successfully treated with their initial RPLND. Given the potential complexity of this operation and its impact on a patient’s prognosis, reoperative RPLND surgery should be limited to specialized quaternary care centers.