Carvell T. Nguyen

Surgical Salvage of Renal Cell Carcinoma Recurrence After Thermal Ablative Therapy

PURPOSE Thermal ablative therapies, including cryoablation and radio frequency ablation, have become viable options for the management of small renal tumors. However, initial data have suggested higher local recurrence rates for ablation compared to partial nephrectomy. We evaluated options for salvage of ipsilateral tumor recurrence after previous ablation. MATERIALS AND METHODS Records of renal surgeries performed at our institution between September 1997 and December 2006 were reviewed to identify patients with ipsilateral tumor recurrence after radio frequency ablation or cryoablation, and clinical characteristics and treatment were defined. RESULTS Recurrence rates at our hospital were 13 of 175 (7.4%) after cryoablation and 26 of 104 (25%) after radio frequency ablation, and 3 additional cases of post-cryoablation recurrence were referred from elsewhere. Overall repeat ablation was performed in 26 patients who experienced post-ablative recurrence. However, 12 patients (33%) were not candidates for repeat ablation due to large tumor size, disease progression or repeat ablative failure. In this group 1 patient received systemic therapy, 1 refused further treatment and 10 underwent attempted extirpation. Partial nephrectomy was only possible in 2 patients and both required an open approach. Remaining patients were treated with radical nephrectomy (7) or had the procedure aborted due to strong patient preference to avoid dialysis (1). Laparoscopic surgery was only possible in 4 cases. Extensive perinephric scarring was encountered in all salvage operations following cryoablation. CONCLUSIONS Primary thermal ablation for small renal masses may preclude or complicate subsequent surgical salvage. Cryoablation in particular can lead to extensive perinephric fibrosis which can complicate attempts at salvage. Appropriate patient selection for thermal ablation remains of paramount importance.

Complications of open primary and post-chemotherapy retroperitoneal lymph node dissection for testicular cancer.

OBJECTIVE Treatment decisions regarding the use of retroperitoneal lymph node dissection (RPLND) for low-stage and advanced testicular cancer may be influenced by the morbidity of the procedure. We sought to compare the complication profile of primary (P-) and post-chemotherapy (PC-) RPLND using a standardized complication grading scale. MATERIALS AND METHODS A retrospective analysis was conducted of 112 and 96 patients who underwent P-RPLND and PC-RPLND, respectively, between 1982 and 2007 for perioperative outcomes and late complications. Postoperative complications were graded using a 5-tiered scale based on the severity and/or level of intervention required for resolution. RESULTS P-RPLND patients had rates of 5%, 24%, and 7% for intraoperative, postoperative, and late complications, respectively. For PC-RPLND, these rates were 12%, 32%, and 7%, respectively (P = 0.11, 0.19, and 1, respectively). Major postoperative complications (grades III-V) were observed in 3 (3%) P-RPLND and 8 (8%) PC-RPLND patients (P = 0.15), including 1 fatal pulmonary embolus in a PC-RPLND patient. Ileus accounted for 63% and 45% of postoperative complications of P-RPLND and PC-RPLND, respectively. PC-RPLND was associated with significantly greater operative times, blood loss, and transfusion rates (P < 0.001). Compared with PC-RPLND after first-line chemotherapy for advanced NSGCT, there were no significant differences in perioperative outcomes for PC-RPLND performed in other settings. CONCLUSIONS P-RPLND and PC-RPLND are associated with low rates of serious short- and long-term complications and negligible mortality, without significant differences between the 2 procedures. The safe morbidity profile of RPLND performed by fellowship-trained urologic oncologists should be considered during treatment decision-making for low-stage and advanced testicular cancer.

Performance of Prostate Cancer Prevention Trial Risk Calculator in a Contemporary Cohort Screened for Prostate Cancer and Diagnosed by Extended Prostate Biopsy

PURPOSE Statistical models such as the Prostate Cancer Prevention Trial risk calculator have been developed to estimate the cancer risk in an individual and help determine indications for biopsy. We assessed risk calculator performance in a large contemporary cohort of patients sampled by extended biopsy schemes. MATERIALS AND METHODS The validation cohort comprised 3,482 men who underwent a total of 4,515 prostate biopsies. Calculator performance was evaluated by ROC AUC and calibration plots. A multivariate regression model was fitted to address important predictor variables in the validation data set. Prediction error was calculated as the response variable in another multivariate regression model. RESULTS Using an average of 13 cores per biopsy prostate cancer was detected in 1,862 patients. The calculator showed an AUC of 0.57 to predict all cancers and 0.60 for high grade cancer. Multivariate analysis of the predictive ability of various clinical factors revealed that race and the number of biopsy cores did not predict overall or high grade cancer at biopsy. Prior negative biopsy, patient age and free prostate specific antigen were significantly associated with prediction error for overall and high grade cancer. Race and family history had a significant association with prediction error only for high grade disease. CONCLUSIONS To our knowledge our external validation of the Prostate Cancer Prevention Trial risk calculator was done in the largest cohort of men screened for prostate cancer to date. Results suggest that the current calculator remains predictive but does not maintain initial accuracy in contemporary patients sampled by more extensive biopsy schemes. Data suggest that the predictive ability of the calculator in current clinical practice may be improved by modeling contemporary data and/or incorporating additional prognostic variables.

The Specific Definition of High Risk Prostate Cancer Has Minimal Impact on Biochemical Relapse-Free Survival

PURPOSE Accurate categorization of high risk prostate cancer cases remains elusive. Various schemes based on clincopathological criteria have been proposed to stratify cases by presumed recurrence risk. We determined whether survival outcomes are dependent on the specific definition. MATERIALS AND METHODS The study population included men who underwent radical prostatectomy from 1987 to 1995 (708) and 1996 to 2007 (3,351). Patients who received adjuvant therapy or had no postoperative prostate specific antigen were excluded from analysis. High risk patients were identified based on 6 commonly used definitions. Biochemical failure was defined as a prostate specific antigen of 0.4 ng/ml or greater and increasing or initiation of salvage therapy. Estimates of biochemical relapse-free survival were generated with the Kaplan-Meier method. Hazard ratios for disease recurrence were estimated using Cox proportional hazards analysis. RESULTS High risk patients determined by the 6 definitions demonstrated a 2.7 to 5.3-fold increased hazard of biochemical relapse, and 5 and 10-year biochemical relapse-free survival rates were 36% to 58% and 25% to 43%, respectively. When stratified by date of treatment high risk patients from 1987 to 1995 generally had worse biochemical relapse-free survival compared to those treated after 1996. Within each era the variation in biochemical relapse-free survival among various high risk definitions was not substantial. CONCLUSIONS Biochemical relapse-free survival after radical prostatectomy does not vary substantially based on the specific definition of high risk prostate cancer. There is a trend toward improved biochemical relapse-free survival in patients treated more recently, perhaps reflecting stage migration or changes in surgical technique. The data suggest that high risk prostate cancer may represent a relatively homogeneous population.

Defining the role of NMP22 in bladder cancer surveillance

Despite advances in treatment and knowledge of its pathogenesis, urothelial carcinoma of the bladder remains a significant cause of morbidity and mortality. Experience with the natural course of bladder cancer has revealed that early diagnosis of primary and recurrent disease improves patient prognosis. In this regard, cystoscopy (usually in combination with urinary cytology) has long been regarded as the gold standard for the diagnosis and surveillance of bladder cancer. However, the disadvantages inherent to cystoscopy, including invasiveness and cost, have stimulated a search for alternative methods for detecting urothelial malignancy. The ideal alternative test would duplicate the high accuracy of cystoscopy for detecting bladder tumors while eschewing its invasiveness, attendant morbidity, and high cost. The vast majority of bladder cancers arise from the urothelium, which continually sheds cells as well as intracellular contents into the urine, thereby providing a potential source of cancer-specific markers. Voided cytology and urinalysis are established tests that have been the standard tools for detection of such substances. The last decade has seen the rise of a myriad of novel urine-based bladder tumor markers, including bladder tumor antigen, urinary bladder cancer antigen, fibronectin, telomerase, and nuclear matrix proteins (e.g., NMP22). The NMP22 assay in particular has been the subject of considerable study and has demonstrated some promise as a potential adjunct to cystoscopy and cytology. Through a critical review of the literature, we seek to define the role, if any, of NMP22 in the follow-up of patients with a previous history of urothelial carcinoma of the bladder.

Choice of Operation for Clinically Localized Renal Tumor

The cornerstone of treatment for localized renal tumors is surgical excision, which until recently was accomplished primarily through radical nephrectomy. The last 2 decades have seen a rapid evolution in the surgical management of renal cell carcinoma, marked by the increased use of nephron-sparing surgery and the application of minimally invasive techniques. A plethora of surgical options now are available. This article discusses the optimal surgical approach to renal tumors in various clinical scenarios. In all these discussions we assume that a proactive approach to treatment is indicated and desired, recognizing that active surveillance is always an additional option to consider in certain subpopulations such as the elderly or infirm.

Racial Disparities in Urologic Health Care

In the United States, disparities in health care delivery and access are apparent between different racial and ethnic groups. Minorities, including African Americans, often suffer disproportionately from disease compared to Caucasians. In the urologic arena, this is apparent in urologic cancer screening, treatment choices, and survival, as well as in the arena of chronic kidney disease, transplant allocation, and transplant outcomes. Latino men also seem to be affected more often by erectile dysfunction than Caucasian counterparts. Disparities such as these have been identified as a problem in the delivery of health care in the United States, and resources have been allocated to help allay the disparity. Through organizations such as the Cleveland Clinic Minority Mens Health Center, policy initiatives, and increased cultural awareness by physicians, steps can be made to reduce and eliminate health care disparities.

How to Tell If a New Marker Improves Prediction

The ability to predict clinical outcomes accurately is critical to the proper management of any human disease. Prostate cancer, with its numerous clinical states, myriad treatment options, and uncertain natural history, has become a popular testing ground for prediction models, and the development of novel prognostic markers continues at a rapid rate. Indeed, in the current issue, Guazzoni and colleagues report on prostate-specific antigen (PSA) isoform p2PSA as a novel marker that predicts prostate cancer at biopsy [1]. What makes p2PSA or any other prognostic marker valuable? In other words, what criteria should a marker meet to justify its inclusion in the clinical decisionmaking process? Onewould expect that a candidate marker be noninvasive, cost effective, scientifically plausible, and easy to use. But, perhaps most importantly, the marker should demonstrate an incrementally improved ability to predict some clinical outcome beyondwhat is possible with established markers. Investigators presumably develop and offer novel markers in the hope that their use will lead to more accurate risk estimation and allow informed and appropriate decision making by both physicians and patients. Improved clinical outcomes, such as increased survival, reduced mortality, or avoidance of complications, are the ultimate goal andwould determine the true clinical value of a given marker. Unfortunately, such data would require follow-up studies involving long-term use of the marker. As such, surrogate means are generally used to evaluate the potential immediate value of a new marker and determine whether or not it should be used in current clinical practice. Traditionally, the value of a novel marker has been judged using several methods: proving correlation or association with established markers, demonstrating statistical significance (ie, small p value) in a univariable analysis, or

Focal therapy in the management of localized prostate cancer

What’s known on the subject? and What does the study add?

Impact of Urologic Resident Training on Patient Pain and Morbidity Associated with Office-Based Cystoscopy

OBJECTIVES To determine whether pain and morbidity experienced by patients undergoing cystoscopy were affected by whether a staff urologist or resident was the primary surgeon. METHODS Patients scheduled to undergo cystoscopy were assigned to either the staff urologist or a resident as the primary surgeon. After cystoscopy, patients were given a visual analogue scale (VAS, 0 to 100 mm) to assess pain. A two-part model was fit to investigate the effect that staff or resident had on pain scores. Confounding factors, such as age, gender, viewing of the procedure on video, and resident training year, were accounted for with multivariable regression techniques. RESULTS There was no statistically significant difference between the VAS scores for patients undergoing cystoscopy regardless of whether staff or resident performed the procedure. Further comparisons indicated no statistically significant differences in the effect that resident training year had on pain scores. CONCLUSIONS Office-based cystoscopy can be performed by residents under staff supervision, with pain and morbidity comparable to when a staff urologist performs the procedure. The impact of urologic resident training on patient care is an area that is relatively unexplored in the literature.