Urologic Oncology: Seminars and Original Investigations

Masthead

2010-03-01

Editorial Board

2010-03-01

Interest in conflicts anyone?

William Donald Steers — 2009-12-14

If there is no conflict in what we do as urologists, there probably is no interest in it either. Well, we're doing a lot of interesting things judging by the headlines in the New York Times and the Washington Post . One of the more disturbing blog sites is run by Gary Switzer, a professor at the University of Minnesota School of Journalism and Mass Communication, who teaches health care journalism. Frequent postings expose some urologic travesty: “Low T and CME!” “Half a million dollars to prevent one case of prostate cancer!”, “Urologists call for baseline PSAs in 40 year olds puzzles ACS chief.” These articles imply a financial self interest or industry conflict in much of what we do. Urology oriented companies aggressively market their drugs, imaging devices, automated lab testing, and therapeutic devices to urologists. In most instances, the purchase of instrumentation is accompanied by financials demonstrating a lucrative return on investment. There is nothing wrong with capitalism. Yet the temptation to over-prescribe and over-utilize is great and the topic of the much ballyhooed article by Gwande in the New Yorker on practice patterns in McAllen, Texas . The end of fee for service is near proclaim editorials .

A survey of therapy for advanced renal cell carcinoma

Michele Basso, Alessandra Cassano, Carlo Barone — 2009-07-06

Abstract: Renal cell carcinoma (RCC) is very resistant to both chemotherapy and radiotherapy. Localized disease can be cured by surgery but most patients are diagnosed when distant metastases are already present and about 30% of patients relapse after nephrectomy. Until 2 years ago, cytokine-based immunotherapy (interleukin-2 and interferon-α) was the only therapeutic option for advanced RCC patients. Fewer than 20% of patients benefit from this treatment, but some of these may experience very prolonged complete responses and progression-free intervals, suggesting a possibility of cure in a very few cases.Thanks to our expanding knowledge of the biology and pathogenesis of RCC, the treatment of this disease has recently undergone a major advance, through the development of potent angiogenesis inhibitors and targeted agents. Bevacizumab, an antibody directed against vascular endothelial growth factor (VEGF), has shown significant activity in combination with interferon-α (IFN-α). Sunitinib and sorafenib, multikinase inhibitors with proven antiangiogenic activity, have also been approved for the treatment of this tumor. Finally, temsirolimus and everolimus, which belong to the family of mammalian target of rapamycin (mTOR), have shown some activity in selected patients. The aim of this paper is to review clinical trials with these new agents, describing their activity and profiles of toxicity, and to evaluate potential future developmental strategies.

Mammalian target of rapamycin: A new target in prostate cancer

Jaskarn S. Rai, Michael J. Henley, Hari L. Ratan — 2009-06-15

Abstract: Molecular targets in prostate cancer are continually being explored, especially in the poor-prognosis androgen-independent phase of the disease, for which there are currently few therapeutic options. One such target is the mammalian target of rapamycin (mTOR) protein. Activation of mTOR results in sequential activation of downstream molecules, which ultimately results in cell division. In this review, we consider the rationale for pursuing mTOR as a therapeutic target in prostate cancer and summarize preclinical and clinical studies of mTOR inhibition in prostate cancer.

Complete remission achieved with angiogenic therapy in metastatic renal cell carcinoma including surgical intervention

2009-07-06

Abstract: Background: Former systemic therapy for metastatic renal cell cancer (mRCC) based on immunomodulation could achieve complete remissions (CR) in only some patients. Angiogenic therapy with sunitinib, sorafenib, and temsirolimus changed the paradigm of treating mRCC based on a doubled progression-free survival (PFS) and 10% to 30% of patients achieving partial remission (PR). Unfortunately, CR is rarely seen. Within our patients we could achieve some CR, which we are presenting in this study.Patients and methods: We assessed 194 consecutive patients of an institutional database that were treated for mRCC with either sorafenib or sunitinib between 05/2006 and 12/2007. Restaging with repeated high-resolution computed tomography (CT) of thorax and abdomen was performed in an 8 to 10 weeks interval. Five patients who achieved CR in repeated CT under therapy are included in this analysis.Results: Of the patients in whom we achieved CR, two were female and three were male. Median age was 63.2 years (range 52–70). All patients had clear cell histology. In three of the five patients, CR was achieved by surgery after partial remission, and in two patients it was achieved by sole medical therapy. All patients remained in CR until now with a median duration of CR of 24 months (range 24–29 months). One patient still is on therapy, while four patients do not receive any systemic treatment.Conclusions: We proof long-term confirmed CR in mRCC achieved by anti-angiogenic therapy alone or in combination with surgery. Combining surgery and anti-angiogenic therapy based on sorafenib and sunitinib could render patients free of disease even after repeated cycles of systemic treatment.

Expression of potential molecular markers in prostate cancer: Correlation with clinicopathological outcomes in patients undergoing radical prostatectomy

2008-10-13

Abstract: The objective of this study was to evaluate the expression levels of multiple potential molecular markers in prostate cancer to clarify the significance of these markers as prognostic indicators in patients undergoing radical prostatectomy (RP). This study included a total of 193 patients with clinically organ-confined prostate cancer who underwent RP without any neoadjuvant therapies. Expression levels of 12 proteins, including Ki-67, p53, androgen receptor (AR), matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor, Aurora-A, Bcl-2, clusterin, heat shock protein 27 (HSP27), HSP70, and HSP90, in RP specimens obtained from these 193 patients were measured by immunohistochemical staining. Of the 12 molecules, Ki-67, p53, AR, MMP-2, MMP-9, and HSP27 expression were significantly associated with several conventional prognostic factors. Univariate analysis identified these 6 markers as significant predictors for biochemical recurrence as well, while prostate-specific antigen, Gleason score, seminal vesicle invasion (SVI), surgical margin status (SMS), lymph node metastasis, and tumor volume were also significant. Of these significant factors, Ki-67 expression, SVI, and SMS appeared to be independently related to biochemical recurrence by multivariate analysis. Furthermore, there were significant differences in biochemical recurrence-free survival according to positive numbers of these three independent risk factors. These findings suggest that consideration of expression levels of potential molecular markers in RP specimens, in addition to conventional prognostic parameters, would contribute to accurate prediction of biochemical recurrence following RP in patients with clinically localized prostate cancer, and that combined evaluation of Ki-67 expression, SVI, and SMS would be particularly useful for further refinement of the system in predicting biochemical outcome.

Estramustine plus docetaxel as second-line therapy in patients with hormone-refractory prostate cancer resistant to docetaxel alone

2008-10-13

Abstract: Objective: Although docetaxel (DOC) plus prednisone is currently the treatment of choice for hormone-refractory prostate cancer (HRPC), no standard therapy is available for those patients who progress during DOC treatment. The aim of this study was to evaluate whether the addition of estramustine (E) can overcome DOC resistance.Methods: Patients who had not responded to DOC in a previous randomised phase II trial received a one-hour intravenous infusion of DOC 70 mg/m2 on day 2 in combination with oral E 840 mg/day divided into three daily administrations on days 1–5. The primary endpoint was a >50% decrease in PSA; the secondary endpoints were biochemical progression-free survival, overall survival, the objective response rate, and toxicity.Results: A biochemical response was observed in 52% of the 25 patients evaluable for response. The only grade 4 event was a cerebral stroke that occurred a few days after the administration of the first treatment course. Treatment discontinuation due to worsened compliance was observed in the patients who received a higher cumulative number of courses.Conclusions: Our findings suggest that the addition of E may be useful in selected HRPC patients resistant to DOC alone.

Molecular biomarkers for advanced renal cell carcinoma: Implications for prognosis and therapy

2008-11-03

Abstract: Objective: The aim of this study was to determine reliable predictive biomarkers for patients with metastatic renal cell carcinomas (RCCs) who had received cytokine therapy.Methods: Tissue specimens were obtained from 62 patients with metastatic RCCs between 1995 and 2006. Paraffin wax embedded tissues were immunostained for carbonic anhydrase IX (CAIX), cyclooxygenase-2 (COX-2), and vascular endothelial growth factor (VEGF).Results: Fifty-two specimens (84%) were assessed as clear cell type, with 5, 3, and 2 tumors showing sarcomatoid, papillary, and undifferentiated features, respectively. With a median 54 months of follow-up, 15/18 responding patients (83%) exhibited high CAIX staining compared with only 24/44 (55%) nonresponding patients (odds ratio, OR, 4.1; 95% confidence interval, CI 1.1–16.5, P = 0.04). There was a positive correlation between maximal COX-2 intensity and response for cytokine therapy (Spearman test P = 0.001; ρ = 0.408). Corrected calcium level ≤ 10 mg/dl (hazard ratio, HR, 0.1; 95% CI 0.15–0.28; P < 0.001), normal hemoglobin level (HR 0.30; 95% CI 0.15–0.50; P = 0.001), and COX-2 expression ≥ 50% (HR 0.33; 95% CI 0.15–0.70; P = 0.008) were significant predictive factors of prolonged overall survival.Conclusions: Thus, COX-2 and CAIX seem to be important predictors of outcome in patients with metastatic RCCs and might enhance the prognostic information obtained from pathology specimens.

Prostate stem cell antigen enhancer and uroplakin II promoter based bladder cancer targeted tissue-specific vector

2008-04-28

Abstract: Purpose: To construct a dual specific vector which contains prostate stem cell antigen enhancer (PSCAE) and uroplakin II (UPII) promoter targeted bladder cancer.Methods: UPII promoter and PSCAE were amplified by polymerase chain reaction (PCR). Luciferase gene (LUC) was obtained from plasmid pBK-CMV-LUC. PSCAE, UPII promoter and LUC were inserted into shuttle plasmid to create Rp-UPII-LUC and Rp-PSCAE-UPII-LUC. Rp-UPII-LUC and Rp-PSCAE-UPII-LUC were cotransfected with pCMV-β-gal into various cell lines at the presence or absence of androgen receptor agonist R1881 and androgen receptor antagonist flutamide. Luminescence was detected with luciferase assay kit and counted on liquid scintillation counter.Results: Bladder cancer cells showed higher LUC activity than non-bladder cancer cells after transfected with plasmids Rp-UPII-LUC and Rp-PSCAE-UPII-LUC. PSCAE could improve the LUC activity in both AR positive and AR negative bladder cancer cells but not in non-bladder cancer cells and normal human urothelial (NHU) cells. R1881 could increase the LUC activity in AR positive bladder cancer cells but not in AR negative bladder cancer cells and non-bladder cancer cells. Flutamide could not inactivate PSCAE in bladder cancer cells.Conclusions: PSCAE can improve target gene expression in bladder cancer cells but not in non-bladder cancer cells and NHU cells. PSCAE maintains a certain level of androgen independent activity in bladder cancer cells. PSCAE is active in both AR positive and AR negative bladder cancer cells. The results suggest that combination of PSCAE with UPII promoter is feasible in constructing bladder cancer-specific vectors.

Taxol synergizes with antioxidants in inhibiting hormal refractory prostate cancer cell growth

Szu-Yuan Ping, Tzyh-Chyuan Hour, Shinne-Ren Lin, Dah-Shyong Yu — 2008-09-26

Abstract: Taxanes are chemotherapeutic agents commonly used to treat various carcinomas. Dietary antioxidants, such as vitamin E, green tea extracts, and isoflavones have been used against prostate cancer, and exhibit anticancer effects both in vitro and in vivo. We evaluated the combined effect of taxol (paclitaxel) with pyrrolidine dithiocarbamate, vitamin E, epigallocatechin gallate, and genistein in killing hormone-refractory prostate cancer cells. Those agents were tested on the hormone-refractory prostate cancer cell line PC-3, and the viability of the cells was determined using MTT {3 (4, 5-dimethylthiazo-2-yl)-2, 5-diphenyl tetrazolium} assay after drug treatment. PC-3 cells were sensitive to these drugs with 50% inhibitory concentrations of 0.1, 23, 220, 1122, and 260 μM, for taxol, pyrrolidine dithiocarbamate, epigallocatechin gallate, genistein, and vitamin E, respectively. Genistein, pyrrolidine dithiocarbamate, and epigallocatechin gallate showed synergistic cytotoxicity to PC-3 cells when combined with 0.01 μM taxol. Only high concentration of vitamin E showed a synergistic effect with this dose of taxol. Further study revealed that 3 combinations could induce sub-G1 phase of cell cycle, induce apoptosis, and increase caspase activity and decrease Bcl-2 expression simultaneously. In conclusion, in addition to vitamin E, incorporation of these antioxidants with taxan-based cytotoxic therapies offers encouraging strategies for combating hormone-refractory prostate cancers.

Phospho-Akt pathway activation and inhibition depends on N-cadherin or phospho-EGFR expression in invasive human bladder cancer cell lines

2008-12-15

Abstract: Objectives: A particular interest in epithelial-mesenchymal transition (EMT), which takes place during embryonic development, provided potential mechanisms involved in the progression of many epithelial tumors, including bladder cancer (BC). The phospho-Akt signaling pathway is supposed to be involved in invasion and progression of human tumors, including BC. Moreover, it has been demonstrated in bladder cancer cell lines that N-cadherin or phospho-epithelial growth factor receptor (EGFR) expression are correlated to tumor progression. Our objectives were to evaluate the potential phospho-Akt pathway involvement in N-cadherin and/or phospho-EGFR positive BC cell lines and to evaluate the prognostic value of E- and N-cadherin expression in patients undergoing cystectomy for invasive BC.Materials and methods: We screened a panel of invasive and noninvasive BC cell lines for E- and N-cadherin, phospho-EGFR, and phospho-Akt expression using the Western blot technique (WB). The potential role of N-cadherin in invasion was assessed by Matrigel assays with and without the N-cadherin blocking monoclonal antibody GC-4. Then we used the Affymetrix microarray technique to evaluate the prognostic value of E- and N-cadherin expression in 30 patients undergoing a cystectomy for invasive BC.Results: N-cadherin and phospho-EGFR expression are associated with Akt activation and with invasive behavior modulation. Even if Akt activation is sufficient in promoting invasion, its inactivation by LY294002 (PI-3 kinase inhibitor) is less efficient on invasion than inhibition of N-cadherin and phospho-EGFR by GC-4 (monoclonal antibody) and gefitinib (anti-tyrosine kinase), respectively. N-cadherin and phospho-EGFR inhibition decreased phospho-Akt activation but also caused restoration and reinforcing of E-cadherin expression, respectively, while phospho-Akt inhibition did not have any impact on E-cadherin expression. In a group of high-risk bladder tumors (T1G3), N- and E-cadherin expression could be considered as a prognostic marker. In a group of patients with invasive BC (pT2-T4) undergoing cystectomy, we showed a shorter overall survival when BC expressed N-cadherin (P = 0.0064) and when E-cadherin expression was down-regulated (P = 0.00165). The N positive /E negative profile has the worst prognosis (P = 0.00153).Conclusions: We confirmed the partial responsibility of p-Akt activation in invasion of some BC cell lines expressing N-cadherin or p-EGFR and also the potential role of N-cadherin and p-EGFR as target in cancer therapy. N/E- cadherin expression profile has a significant prognostic value in invasive BC.

Prevention of urinary bladder cancer in the FHIT knock-out mouse with Rofecoxib, a Cox-2 inhibitor

2009-04-17

Abstract: Objectives: Aberrant or increased expression of cyclooxygenase-2 (COX-2) has been implicated in the pathogenesis of many diseases, including cancer. However, the exact mechanism by which COX-2 may influence tumorigenesis has yet to be described. To investigate the chemopreventive role of a COX-2 inhibitor, rofecoxib, in the development of urinary bladder cancer, we studied the effect of this drug in heterozygous and nullizygous fragile histidine triad (FHIT) gene-deficient mice in a chemically induced carcinogenesis model.Materials and methods: Two-hundred eight mice consisting of 50 FHIT +/+, 63 FHIT +/– and 95 FHIT –/–, were divided into five treatment groups and followed up for 15 weeks. Mice were treated with freshly prepared solution of 0.1% or 0.01% N-butyl-N-(-4-hydroxybutyl)-nitrosamine (BBN) in their drinking water and rofecoxib was administered in mouse chow at 150 parts per million concentration. Mice were sacrificed, and accurate histological analysis of the bladder was performed.Results: Rofecoxib treatment significantly reduced the incidence of preneoplastic lesions/bladder tumors (P = 0.016). Comparing the incidence of neoplastic lesions in mice treated with rofecoxib and BBN (22/56, 39.3%) and mice treated only with BBN (32/57, 56.1%), a protective role of rofecoxib on the BBN tumor induction has been observed (P = 0.024). A similar result (P = 0.002) has been reached observing the incidence of mild and moderate dysplasia in mice treated with a lower concentration of BBN (8/16, 50.0% vs. 20/24, 83.3%).Moreover, as previously observed, a significant increase in neoplastic lesions in the FHIT +/– and FHIT –/– vs. FHIT +/+ mice after BBN treatment has been observed (P = 0.003).Conclusions: These findings suggest that rofecoxib provides a therapeutic defense against bladder carcinogenesis in our model and confirmed that the FHIT knock-out mouse is a suitable system to study in vivo bladder carcinogenesis.

Positive surgical margins at radical prostatectomy: Do they really matter?

Samir S. Taneja — 2010-03-01

As surgical oncologists, we are taught that the primary goal of cancer removal is obtaining a wide surgical margin. In doing so, we hope to minimize the likelihood of local recurrence and provide accurate and complete staging. By nature, nerve-sparing radical prostatectomy is contradictory to the fundamental tenets of oncologic surgery. In preserving the neurovascular bundles, we potentially compromise the surgical margins by dissecting directly upon the posterolateral capsule of the gland. Despite the counterintuitive nature of nerve-sparing, the procedure has been proven historically safe and provides excellent oncologic outcomes for the most men.

Clinical significance of the positive surgical margin based upon location, grade, and stage

2010-03-01

Abstract: Prostate cancer remains a challenge due to its incidence and radical prostatectomy continues to be a major treatment option for men with potentially curable disease who have a life expectancy over a decade. This article will address the common problem of positive surgical margins and the impact of them on patient outcome. Through these we can examine relevant clinical trials that have attempted to address this issue and offer some guided to therapy among men with this clinical problem. Close margins are probably of no significance and will not be addressed. Our recommendations take into account the current level of medical evidence, and are balanced with anticipated adverse effects of treatment. They may change over time once definitive clinical trials are completed. In brief we believe those with positive margins and PT2 we advocate close observation with the aim of early salvage radiotherapy if necessary. Those with PT3a and focally positive margins with low/intermediate grade tumors are at moderate risk of biochemical failure so should be managed like PT2 patients. However those with high-grade disease should be offered adjuvant radiotherapy. Similarly those with PT3a margin positive extensive or multiple site disease should have adjuvant radiotherapy. PT3B margin positive patients should be offered radiotherapy. PT4 with bladder neck only margin positive can probably be observed.

Margin control in open radical prostatectomy: What are the real outcomes?

Michael S. Cookson, Sam S. Chang — 2010-03-01

Abstract: The complete surgical removal of the prostate gland remains a technically challenging procedure utilizing any surgical technique. As with laparoscopic techniques, open radical retropubic prostatectomy techniques have been modified and continue to evolve but biological risk factors influence outcomes as well. A positive surgical margin, regardless of number or location, is an independent predictor of not only disease recurrence but also for receiving secondary treatment. Further research is needed to examine methods to continue to improve outcomes. Follow-up and possible adjuvant therapy needs to be individualized as the optimal timing and treatment modality continue to evolve.

Margin control in robotic and laparoscopic prostatectomy: What are the REAL outcomes?

Alon Z. Weizer, Seth Strope, David P. Wood — 2010-03-01

Abstract: Our institutional experience and relevant literature on surgical margin rates with laparoscopic and robotic-assisted radical prostatectomy are summarized. Differences in surgical margins were assessed between patients undergoing open or robotic-assisted prostatectomy by experienced surgeons, and placed in context with a review of the literature. Surgical margins and location were similar between patients undergoing open or robotic prostatectomy. Pathologic stage, baseline prostate-specific antigen, and Gleason score all impacted the risk of a positive surgical margin. Experienced surgeons can achieve comparable outcomes in terms of surgical margins. Disease burden plays a significant role in positive surgical margins.

Neurovascular bundle resection: Does it improve the margins?

Herbert Lepor, Basir Tareen — 2010-03-01

Abstract: Prior to the description of the anatomic nerve sparing radical prostatectomy, most men were rendered impotent following radical perineal or retropubic prostatectomies. The fact that these “erection” nerves were localized outside the prostate suggested the feasibility of totally eradicating localized prostate cancer with preservation of erectile function in selected cases. All of these studies collectively suggest that unilateral excision of neurovascular bundles will compromise potency rates in between 15% to 20% of cases. It seems logical to report the risk of extracapsular extension independently for the two sides of the prostate, especially since independent decisions are made relative to the nerve sparing status of the different sides. Extracapsular extension is a risk factor for positive surgical margins. Positive surgical margins represent an independent risk factor for biochemical recurrence following radical prostatectomy. The surgeon is left with the dilemma of whether to maximize potency at the risk of compromising cancer control. In cases with a 30% risk of side specific extracapsular extension, using the above assumption, the risk of developing a positive surgical margin and biochemical recurrence is only 4.7% and 2%, respectively.

Radical prostatectomy: Does surgical technique influence margin control?

Matthew T. Gettman, Michael L. Blute — 2010-03-01

Abstract: The goal of radical prostatectomy (RP) is complete removal of the prostate and seminal vesicles with negative surgical margins. Regardless of approach, the occurrence of positive surgical margins (PSMs) remains a risk associated with RP. In addition, PSMs can adversely affect biochemical and cause-specific survival. With the advent of PSA screening and introduction of new RP approaches, surgical technique has become increasingly debated in relationship to margin positivity. The issue, however, is controversial, as underlying clinical and pathologic characteristics of prostate cancer also influence margin control. This article evaluates the impact of surgical technique on margin control during RP. In addition, we evaluate the influence that stage migration, the individual surgeon, new technologic adjuncts, and specimen handling have had on margin control.

CA125 for following up carcinoma of the bladder

Viroj Wiwanitkit — 2010-01-07

I read the recent publication on CA 125 by Kouba et al. with great interest . Kouba et al. reached the conclusion that “Serum CA-125 levels may serve as a useful predictor of pathologic outcomes in patients undergoing cystectomy for urothelial carcinoma of the bladder .” Indeed, the use of CA125 as a tumor marker for following up carcinoma of the bladder is still controversial. Chang et al. mentioned that “increased CA 125 was seen in approximately 11% of patients with high grade or invasive transitional cell carcinoma preoperatively ” but “recurrence-free survival was not associated with CA 125 .” Combing with other biomarkers, Margel et al. proposed for a fair predicting value for nomogram-confined bladder disease before cystectomy . In another immunohistochemistry study by Sangoi et al., the CA125 present poor specificity in differentiation of bladder cancer at different stages . In the small series by Kouba et al., the result might show a favorable prediction by using CA125, however, there are many factors to be concerned. First, the difference in CA125 that resulted from different analyzers using different techniques should be aware in following up of the patients. Second, comorbidity of the patients such as congestive heart failure or gynecologic tumor might alter the CA-125 levels.

Survey Section Editorial Board

2010-03-01

Commentary on The R.E.N.A.L. nephrometry score: A comprehensive standardized system for quantitating renal tumor size, location and depth: Kutikov A, Uzzo RG, Department of Urological Oncology, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA

Paul Russo — 2010-03-01

J Urol 2009;182:844–53 Treatment decisions for renal malignancies depend largely on qualitative data, including a description of tumor anatomy and the experience of the treating surgeon. Currently, characterization of renal tumor anatomical elements is descriptive and lacks standardization. Surgical decision making and data set comparisons would be significantly enhanced by a consistent, reproducible system that quantitates the pertinent characteristics of localized renal lesions. We have developed and propose a standardized nephrometry scoring system (R.E.N.A.L. Nephrometry Score) to quantify the anatomical characteristics of renal masses on computerized tomography/magnetic resonance imaging.

Commentary on Urinary collecting system invasion is an independent prognostic factor of organ confined renal cell carcinoma: Verhoest G, Avakian R, Bensalah K, Thuret R, Ficarra V, Artibani W, Tostain J, Guille F, Cindolo L, De La Taille A, Abbou CC, Salomon L, Rioux-Leclercq N, Patard JJ, Rennes University Hospital, Rennes, France

Paul Russo — 2010-03-01

J Urol 2009;182:854–9 We evaluated urinary collecting system invasion as a prognostic parameter of renal cell carcinoma. A total of 1,124 patients who underwent nephrectomy for a renal tumor at 5 European centers were included in this retrospective study. Several variables were analyzed, including urinary collecting system invasion, age, gender, TNM stage, Fuhrman grade, histologic subtype, Eastern Cooperative Oncology Group performance status, and cancer specific survival. There were 771 males (68.6%) and 353 females (31.4%) in this study, and median age was 61 years (range 14 to 88). Median tumor size was 6 cm (range 1–24). Tumors were organ-confined and Fuhrman grade was recorded as 1 or 2 in 67.1% and 62.3% of cases, respectively. Symptoms were present at diagnosis, and Eastern Cooperative Oncology Group performance status was 1 or more in 50.3% and 16.1% of the cases, respectively. Median follow-up was 43 months (range 1–299). At the end of follow-up, 246 patients (21.9%) died of cancer. In 132 cases (11.7%), urinary collecting system invasion was noted. Urinary collecting system invasion was associated with symptoms, TNM stage, Fuhrman grade, tumor size (P < 0.001) and Eastern Cooperative Oncology Group performance status (P = 0.003), but not with histologic subtype (P = 0.7). On univariate analysis TNM stage, Fuhrman grade, symptoms, Eastern Cooperative Oncology Group performance status, tumor size, and urinary collecting system invasion (P = 0.0001) were significant predictors of cancer-specific survival. Urinary collecting system invasion was an independent prognostic parameter only in the setting of pT1-T2 tumors. When the urinary collecting system was invaded, the 5- and 10-year probabilities of survival were 43% and 41%, respectively. Urinary collecting system invasion appears to be an independent prognostic parameter of organ-confined renal cell carcinoma. Our data support the need to integrate this parameter in further TNM revisions.

Commentary on Nephrectomy improves survival in patients with invasion of adjacent viscera and absence of nodal metastases (stage 4N0 renal cell carcinoma) Capitanio U, Perrotte P, Zini L, Jeldres C, Shariat SF, Isbarn H, Arjane P, Peloquin F, Pharand D, Montorsi F, Karakiewicz PI, Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, QC, Canada

Paul Russo — 2010-03-01

BJU Int 2009;104:795–9 To examine the cancer-specific mortality (CSM) of patients with T4N0-2M0 renal cell carcinoma (RCC) treated with either nephrectomy (RN) or no surgery (NS). Of 43,143 patients with RCC identified in the Surveillance, Epidemiology, and End Results (SEER) database, 310 had tumors involving adjacent organs with no evidence of distant metastases (T4NanyM0) and had RN (246, 79.4%) or NS (64, 20.6%). Kaplan-Meier analyses, Cox regression, and competing-risks regression models were used to compare the effect of RN vs. NS on CSS.

Commentary on Surgical resection of renal cell carcinoma after targeted therapy: Thomas AA, Rini BI, Stephenson AJ, Garcia JA, Fergany A, Krishnamurthi V, Novick AC, Gill IS, Klein EA, Zhou M, Campbell SC, Glickman Urological and Kidney Institute, Cleveland, OH

Paul Russo — 2010-03-01

J Urol 2009;182:881–6 The development of targeted agents for renal cell carcinoma has renewed interest in consolidative surgery due to the robust clinical responses seen with these agents. The integration of targeted therapy and surgery requires careful consideration due to the potential for increased perioperative morbidity.

Commentary on Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: An expanded-access trial: Gore ME, Szczylik C, Porta C, Bracarda S, Bjarnason GA, Oudard S, Hariharan S, Lee SH, Haanen J, Castellano D, Vrdoljak E, Schöffski P, Mainwaring P, Nieto A, Yuan J, Bukowski R, Royal Marsden Hospital NHS Trust, London, UK

Paul Russo — 2010-03-01

Lancet Oncol 2009;10:757–63 Results from clinical trials have established sunitinib as a standard of care for first-line treatment of advanced or metastatic renal-cell carcinoma (RCC); however, many patients, particularly those with a poorer prognosis, do not meet inclusion criteria, and little is known about the activity of sunitinib in these subgroups. The primary objective of this trial was to provide sunitinib on a compassionate-use basis to trial-ineligible patients with RCC from countries where regulatory approval had not been granted.

Commentary on Natural history, growth kinetics, and outcomes of untreated clinically localized renal tumors under active surveillance: Crispen PL, Viterbo R, Boorjian SA, Greenberg RE, Chen DY, Uzzo RG, Section of Urologic Oncology, Department of Surgical Oncology, Fox Chase Cancer Center, Temple University Medical Center, Philadelphia, PA

Paul Russo — 2010-03-01

Cancer 2009;115:2844–52 The growth kinetics of untreated solid organ malignancies are not defined. Radiographic active surveillance (AS) of renal tumors in patients unfit or unwilling to undergo intervention provides an opportunity to quantify the natural history of untreated localized tumors. The authors report the radiographic growth kinetics of renal neoplasms during a period of surveillance.

Information for Authors

2010-03-01

Urologic Oncology: Seminars and Original Investigations

Masthead

Editorial Board

Contents

Interest in conflicts anyone?

A survey of therapy for advanced renal cell carcinoma

Mammalian target of rapamycin: A new target in prostate cancer

Complete remission achieved with angiogenic therapy in metastatic renal cell carcinoma including surgical intervention

Expression of potential molecular markers in prostate cancer: Correlation with clinicopathological outcomes in patients undergoing radical prostatectomy

Estramustine plus docetaxel as second-line therapy in patients with hormone-refractory prostate cancer resistant to docetaxel alone

Molecular biomarkers for advanced renal cell carcinoma: Implications for prognosis and therapy

Prostate stem cell antigen enhancer and uroplakin II promoter based bladder cancer targeted tissue-specific vector

Taxol synergizes with antioxidants in inhibiting hormal refractory prostate cancer cell growth

Phospho-Akt pathway activation and inhibition depends on N-cadherin or phospho-EGFR expression in invasive human bladder cancer cell lines

Prevention of urinary bladder cancer in the FHIT knock-out mouse with Rofecoxib, a Cox-2 inhibitor

Positive surgical margins at radical prostatectomy: Do they really matter?

Clinical significance of the positive surgical margin based upon location, grade, and stage

Margin control in open radical prostatectomy: What are the real outcomes?

Margin control in robotic and laparoscopic prostatectomy: What are the REAL outcomes?

Neurovascular bundle resection: Does it improve the margins?

Radical prostatectomy: Does surgical technique influence margin control?

CA125 for following up carcinoma of the bladder

Survey Section Editorial Board

Commentary on The R.E.N.A.L. nephrometry score: A comprehensive standardized system for quantitating renal tumor size, location and depth: Kutikov A, Uzzo RG, Department of Urological Oncology, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA

Commentary on Surgical resection of renal cell carcinoma after targeted therapy: Thomas AA, Rini BI, Stephenson AJ, Garcia JA, Fergany A, Krishnamurthi V, Novick AC, Gill IS, Klein EA, Zhou M, Campbell SC, Glickman Urological and Kidney Institute, Cleveland, OH

Information for Authors