Jeffrey J. Tomaszewski

Gleason 6 prostate cancer: Translating biology into population health

PURPOSE Gleason 6 (3+3) is the most commonly diagnosed prostate cancer among men with prostate specific antigen screening, the most histologically well differentiated and is associated with the most favorable prognosis. Despite its prevalence, considerable debate exists regarding the genetic features, clinical significance, natural history, metastatic potential and optimal management. MATERIALS AND METHODS Members of the Young Urologic Oncologists in the Society of Urologic Oncology cooperated in a comprehensive search of the peer reviewed English medical literature on Gleason 6 prostate cancer, specifically focusing on the history of the Gleason scoring system, histological features, clinical characteristics, practice patterns and outcomes. RESULTS The Gleason scoring system was devised in the early 1960s, widely adopted by 1987 and revised in 2005 with a more restrictive definition of Gleason 6 disease. There is near consensus that Gleason 6 meets pathological definitions of cancer, but controversy about whether it meets commonly accepted molecular and genetic criteria of cancer. Multiple clinical series suggest that the metastatic potential of contemporary Gleason 6 disease is negligible but not zero. Population based studies in the U.S. suggest that more than 90% of men newly diagnosed with prostate cancer undergo treatment and are exposed to the risk of morbidity for a cancer unlikely to cause symptoms or decrease life expectancy. Efforts have been proposed to minimize the number of men diagnosed with or treated for Gleason 6 prostate cancer. These include modifications to prostate specific antigen based screening strategies such as targeting high risk populations, decreasing the frequency of screening, recommending screening cessation, incorporating remaining life expectancy estimates, using shared decision making and novel biomarkers, and eliminating prostate specific antigen screening entirely. Large nonrandomized and randomized studies have shown that active surveillance is an effective management strategy for men with Gleason 6 disease. Active surveillance dramatically reduces the number of men undergoing treatment without apparent compromise of cancer related outcomes. CONCLUSIONS The definition and clinical relevance of Gleason 6 prostate cancer have changed substantially since its introduction nearly 50 years ago. A high proportion of screen detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing the diagnosis and treatment of Gleason 6 disease is likely to have a favorable impact on the net benefit of prostate cancer screening.

Assessing the burden of complications after surgery for clinically localized kidney cancer by age and comorbidity status.

OBJECTIVE To examine the association between high-risk patient status (age >75 years or Charlson comorbidity index count >2) and postoperative complications in patients undergoing surgical management for clinically localized renal tumors. MATERIALS AND METHODS Patients undergoing radical nephrectomy (RN) or partial nephrectomy (PN) (2005-2012) for localized renal cell carcinoma were analyzed. Multivariate logistic regressions were used to test the association between high-risk status and postoperative complications adjusting for patient, tumor, and operative characteristics. RESULTS Of 1092 patients undergoing PN (71.9%) or RN (28.1%) for clinically localized renal tumors, 255 (23.4%) were classified as high risk, and 175 patients (16%) developed at least 1 complication (mean 1.6 ± 1.0). Of note, 22.4% and 14.1% of high- and low-risk patients developed a complication, respectively (P = .002). Comparing high- and low-risk patients, significant differences in Clavien I-II (20.4% vs 11.1%; P <.001) and medical (16.1% vs 8.1%, P <.001) complications were observed, whereas no differences were seen in Clavien III-V or surgical complications. No differences in complications were observed comparing patients treated with RN and PN, albeit high-risk patients were more likely to undergo RN (35.3% vs 25.9%, P = .04). After adjustment, the odds of incurring any complication were 1.9 times higher in high- compared with low-risk patients (odds ratio 1.9 [confidence interval 1.3-2.8]). CONCLUSION Regardless of surgical type, patients deemed high risk by age and comorbidity criteria were more likely to incur a postoperative complication after renal mass resection. Improved understanding of surgical risks in the elderly and infirmed will help better inform patients deciding between active surveillance and resection of renal tumors.

Upper Tract Urothelial Carcinoma: Current Treatment and Outcomes

The reference standard treatment of upper tract urothelial carcinoma is open radical nephroureterectomy. Many centers have advocated less-invasive treatment modalities. We reviewed contemporary treatments of upper tract urothelial carcinoma and their outcomes. A MEDLINE search was conducted for all relevant published data during the past 15 years. Endoscopic management is feasible for low-grade disease with strict surveillance protocols. Radical nephroureterectomy remains the reference standard for upper tract urothelial carcinoma. The intermediate-term oncologic outcomes are similar between the laparoscopic and open approaches. Controversies still exist regarding the optimal management of the distal ureter, the utility of topical therapy, and the role of lymphadenectomy.

Heterogeneity and renal mass biopsy：a review of its role and reliability

Increased abdominal imaging has led to an increase in the detection of the incidental small renal mass (SRM). With increasing recognition that the malignant potential of SRMs is heterogeneous, ranging from benign (15%-20%) to aggressive (20%), enthusiasm for more conservative management strategies in the elderly and infirmed, such as active surveillance (AS), have grown considerably. As the management of the SRM evolves to incorporate ablative techniques and AS for low risk disease, the role of renal mass biopsy (RMB) to help guide individualized therapy is evolving. Historically, the role of RMB was limited to the evaluation of suspected metastatic disease, renal abscess, or lymphoma. However, in the contemporary era, the role of biopsy has grown, most notably to identify patients who harbor benign lesions and for whom treatment, particularly the elderly or frail, may be avoided. When performing a RMB to guide initial clinical decision making for small, localized tumors, the most relevant questions are often relegated to proof of malignancy and documentation (if possible) of grade. However, significant intratumoral heterogeneity has been identified in clear cell renal cell carcinoma (ccRCC) that may lead to an underestimation of the genetic complexity of a tumor when single-biopsy procedures are used. Heterogeneous genomic landscapes and branched parallel evolution of ccRCCs with spatially separated subclones creates an illusion of clonal dominance when assessed by single biopsies and raises important questions regarding how tumors can be optimally sampled and whether future evolutionary tumor branches might be predictable and ultimately targetable. This work raises profound questions concerning the genetic landscape of cancer and how tumor heterogeneity may affect, and possibly confound, targeted diagnostic and therapeutic interventions. In this review, we discuss the current role of RMB, the implications of tumor heterogeneity on diagnostic accuracy, and highlight promising future directions.

Comparative hospital cost-analysis of open and robotic-assisted radical prostatectomy.

OBJECTIVE To perform a contemporary comparative cost-analysis of robotic-assisted laparoscopic radical prostatectomy (RARP) and open radical retropubic prostatectomy (RRP). METHODS All patients undergoing RARP (n = 115) or RRP (n = 358) by 1 of 4 surgeons at a single institution during a 15-month period were retrospectively reviewed. The hospital length of stay (LOS), operative time, hospital charges, reimbursement, and direct and indirect hospital costs were analyzed and compared. RESULTS The mean LOS between patients undergoing RARP (1.2 ± 0.6 days) and RRP (1.4 ± 0.8 days) was not significantly different. The operating room supply costs per case were almost 7 times greater for RARP (

Renal access by urologist or radiologist during percutaneous nephrolithotomy.

2852 ±

Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate.

528) than for RRP (

Coexisting Hybrid Malignancy in a Solitary Sporadic Solid Benign Renal Mass: Implications for Treating Patients Following Renal Biopsy

417 ±

Outcomes of Percutaneous Nephrolithotomy Stratified by Body Mass Index

59; P < .05). The ancillary, cardiology, imaging, administrative, laboratory, and pharmacy costs were not significantly different between the 2 approaches. The mean total costs per case for RARP exceeded the total costs for RRP by 62% (

Predictors of Immediate Postoperative Outcome of Single-tract Percutaneous Nephrolithotomy

14 006 ±