Urologic Oncology (UROL ONCOL-SEMIN ORI)

Publications in this journal

• Article: Independent prognostic factors for initial intravesical recurrence after laparoscopic nephroureterectomy for upper urinary tract urothelial carcinoma.

  Yuqing Liu, Jian Lu, Kai Hong, Yi Huang, Lulin Ma
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  ABSTRACT: OBJECTIVE: To elucidate clinicopathologic independent prognostic factors for intravesical recurrence after laparoscopic nephroureterectomy for primary upper urinary tract urothelial carcinoma (UUT-UC). METHODS AND MATERIALS: This study included 212 consecutive patients clinically diagnosed as localized UUT-UC and treated by retroperitoneal laparoscopic nephroureterectomy between January 2002 and October 2010, after exclusion of those with a previous or concurrent history of bladder cancer. The clinicopathologic features, risk factors, and intravesical recurrence-free survival were analyzed using the Kaplan-Meier method. Univariate and multivariate analyses by Cox proportional hazards regression model was used to identify independent risk factors for intravesical tumor recurrence. RESULTS: Of the patients, 64/212 (30.2%) developed subsequent intravesical recurrence during a median follow-up period of 39 months (range 7-78 months). Among them, 56/64 (87.5%) developed recurrent bladder cancer within 2 years after the surgery for UUT-UC, and the median interval between surgery and intravesical recurrence was 14 months (range 7-51 months). Multifocal tumors, renal insufficiency, and immunosuppression were determined as risk factors for intravesical recurrence by univariate analysis. However, by multivariate analyses, multifocality (hazard ratio = 2.060, P = 0.006) and immunosuppression (hazard ratio = 1.915, P = 0.037) were identified as independent predictors for the development of recurrent bladder cancer. CONCLUSIONS: The incidence of intravesical recurrence after laparoscopic nephroureterectomy for UUT-UC is high, and most subsequent bladder cancers recur within 2 years after surgery. Tumor multifocality and immunosuppression are significant independent risk factors in developing initial intravesical recurrence after laparoscopic surgery for primary UUT-UC.
  Urologic Oncology 04/2013;
• Article: Effect of the timing of orchiectomy on survival in patients with metastatic germ cell tumors of testis.

  Mikhail Fedyanin, Alexey Tryakin, Anatoly Bulanov, Igor Fainshtein, Tatiana Zakharova, Vsevolod Matveev, August Garin, Sergei Tjulandin
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  ABSTRACT: OBJECTIVES: Classically, orchiectomy (OE) is the first step of treatment in patients with metastatic germ cell tumors (mGCTs) of testis. However, some patients have severe symptoms of disease, which require immediate beginning of chemotherapy (CT) followed by OE. This retrospective analysis was performed to find the effect of time constraints of delayed OE on survival in patients with mGCT. METHODS AND MATERIALS: We analyzed the data of 1,483 CT-naive patients with advanced mGCT of the testis treated in our Department from 1986 to 2009. Delayed OE was performed on 71 (4.8%) patients: seminoma in 8 patients (11.2%), nonseminomatous tumor in 50 patients (70.4%), and unknown tumor histology in 13 patients (18.4%). Twenty percent, 40%, and 40% of patients belonged to good, intermediate, and poor International Germ Cell Cancer Consensus Group prognostic groups, respectively. Median time from the beginning of the CT to OE was 18 (range, 1-250) days. OE was performed on 39 (55%), 21 (29.5%), and 11 (15.5%) patients during cycle 1, cycle 2 to completion of CT, and after the finishing of induction CT, respectively. Median follow-up time was 156 (range, 3-241) months. Etoposide and cisplatin-based CTs were received by 66 patients (93%). RESULTS: Three-year overall survival (OS) of all 1,483 patients was 75%. An excellent primary tumor response to CT was observed among the patients, who had delayed OE after completion of CT (n = 11): only mature teratoma (n = 4) and tumor necrosis (n = 7) were found. The 3-year OS in patients with delayed OE was 63%. OE performed after completion of CT was associated with better prognosis. The 3-year OS in patients with delayed OE performed during the cycle 1 (group 1) was 67%, cycle 2 to completion of CT (group 2) was 39%, and after finishing of CT (group 3) was 88% (groups 1 vs. 3: hazard ratio 3.7, 95% confidence interval 0.69-10.1, P = 0.15; groups 2 vs. 3: P = 0.01, hazard ratio 8.1, 95% confidence interval 1.32-18.,72). It seems that if OE had been performed during CT, the beginning of the successive cycle was delayed and dose intensity of CT was decreased. CONCLUSIONS: In case of severe symptoms of disease, which require an immediate start of CT, performing OE simultaneously with other surgeries after completion of induction CT was associated with better OS, when compared with performing OE during induction CT.
  Urologic Oncology 04/2013;
• Article: Treating octogenarians with muscle-invasive bladder cancer: Preoperative opportunities for increasing the benefits of surgical intervention.

  Jeffrey C Bassett, Sam S Chang
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  ABSTRACT: The question posed to the authors is whether surgery is the best treatment option for octogenarians with invasive bladder cancer. Herein, we detail the rationale in favor of radical cystectomy and opportunities for improvement in the processes of care for those who may be surgical candidates.
  Urologic Oncology 04/2013;
• Article: Inhibition of presenilins attenuates proliferation and invasion in bladder cancer cells through multiple pathways.

  Jun-Wei Gai, Wasilijiang Wahafu, Ya-Ching Hsieh, Miao Liu, Liang Zhang, Sheng-Wen Li, Bei Zhang, Qun He, Hui Guo, Jie Jin
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  ABSTRACT: OBJECTIVE: Presenilin (PS)/γ-secretase is a key protease that initiates various biological processes. We investigated the effect of PS/γ-secretase on the expression and inhibition of urothelial cell carcinoma of bladder (UCB) as a potential alternative therapeutic target for UCB. MATERIALS AND METHODS: PS-1 and PS-2 were identified in normal and malignant human bladder transitional cells by immunohistochemistry. We blocked PSs using a PS/γ-secretase inhibitor N-(N-[3,5-difluorophenacetyl]-L-alanyl)-S-phenylglycine-t-butylester (DAPT), and the proliferative and invasive potential of UCB cells SW780, BIU-87, 5637, and T24, and human normal urothelial cell line SV-HUC-1 were analyzed using Western blot, cell viability test, flow cytometry, and transwell assay. All experiments were repeated at least 3 times. RESULTS: Human bladder samples of UCB, SW780, BIU-87, 5637, and T24 cells expressed higher PS-1 compared with normal ones. Cell vitality test demonstrated that DAPT attenuated UCB cell proliferation more than SV-HUC-1. Flow cytometry and transwell assay showed that T24 cells were arrested at G1/S checkpoint and its invasive ability was impaired. Western blot assay markedly showed that protein levels of CD44-intracellular domain, insulinlike growth factor-1Rβ, extracellular regulated protein kinase 1/2, cyclin D1, proliferating cell nuclear antigen, and matrix metalloproteinase-9 were downregulated by DAPT, whereas vascular endothelial growth factor receptor-2 and vascular endothelial growth factor-165 were upregulated. CONCLUSIONS: Our study revealed that PS-1 might be implicated in the proliferation and invasion of UCB, and that it may serve as a potential therapeutic target for UCB, but further studies are warranted to verify the effects of inhibition of PS/γ-secretase on angiogenesis.
  Urologic Oncology 04/2013;
• Article: A replication study examining association of rs6983267, rs10090154, and rs1447295 common single nucleotide polymorphisms in 8q24 region with prostate cancer in Siberians(☆)

  Natalia A Oskina, Ulyana A Boyarskikh, Alexandr F Lazarev, Valentina D Petrova, Dmitry I Ganov, Olga G Tonacheva, Galina I Lifshits, Maxim L Filipenko
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  ABSTRACT: INTRODUCTION: Multiple genetic studies have confirmed association of 8q24 variants with susceptibility to prostate cancer (CaP). However, the risk conferred in men living in Russia is unknown. MATERIALS AND METHODS: In this work we studied the association of rs6983267, rs10090154, and rs1447295 single nucleotide polymorphisms (SNPs) with a risk of CaP development in men of Caucasoid descent living in the Siberian region of Russia. Three 8q24 SNPs were genotyped by real-time polymerase chain reaction in histologically confirmed CaP "cases" (n = 392) and clinically evaluated "controls" (n = 344). To evaluate the SNP effects on CaP susceptibility, odds ratio (OR) and confidence interval (CI) 95% were calculated. Allele and genotype frequencies in the groups were compared using logistic regression; differences were considered statistically significant if P<0.05. RESULTS: We showed statistically significant association of the A allele of rs1447295 (OR [CI 95%] = 1.96 [1.37-2.81], P<0.0001) and the T allele of rs10090154 (OR [CI 95%] = 2.14 [1.41-3.26], P<0.0001) with CaP. The T-A rs10090154 to rs1447295 haplotype was also associated with CaP (OR [CI 95%] = 2.47 [1.59-3.85], P<0.0001). There was no significant association with the T allele of rs6983267: OR [CI 95%] = 0.9 [0.73-1.11], P> 0.05. CONCLUSION: Thus, our investigation confirms the role of chromosomal region 8q24 in the development of CaP in the Russian population.
  Urologic Oncology 04/2013;
• Article: Evaluation of anatomic and morphologic nomogram to predict malignant and high-grade disease in a cohort of patients with small renal masses.

  Aditya Bagrodia, Brian Harrow, Zhuo-Wei Liu, Ephrem O Olweny, Stephen Faddegon, Gang Yin, Yung Khan Tan, Woong Kyu Han, Yair Lotan, Vitaly Margulis, Jeffrey A Cadeddu
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  ABSTRACT: OBJECTIVE: To evaluate a nomogram using the RENAL Nephrometry Score (RENAL-NS) that was developed to characterize masses as benign vs. malignant and high vs. low grade in our patients with small renal masses treated with partial nephrectomy (PN). The nomogram was previously developed and validated in patients with widely variable tumor sizes. MATERIALS AND METHODS: Retrospective review of PN performed between 1/2003 and 7/2011. Imaging was reviewed by a urologic surgeon for RENAL-NS. Final pathology was used to classify tumors as benign or malignant and low (I/II) or high (III/IV) Fuhrman grade. Patient age, gender, and RENAL score were entered into the nomogram described by Kutikov et al. to determine probabilities of cancer and high-grade disease. Area under the curve was determined to assess agreement between observed and expected outcomes for prediction of benign vs. malignant disease and for prediction of high- vs. low-grade or benign disease. RESULTS: A total of 250 patients with 252 masses underwent PN during the study period; 179/250 (71.6%) had preoperative imaging available. RENAL-NS was assigned to 181 masses. Twenty-two percent of tumors were benign. Eighteen percent of tumors were high grade. Area under the curve was 0.648 for predicting benign vs. malignant disease and 0.955 for predicting low-grade or benign vs. high-grade disease. CONCLUSIONS: The RENAL-NS score nomogram by Kutikov does not discriminate well between benign and malignant disease for small renal masses. The nomogram may potentially be useful in identifying high-grade tumors. Further validation is required where the nomogram probability and final pathologic specimen are available.
  Urologic Oncology 04/2013;
• Article: Interferon alfa in the treatment paradigm for non-muscle-invasive bladder cancer.

  Donald Lamm, Maurizio Brausi, Michael A O'Donnell, J Alfred Witjes
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  ABSTRACT: OBJECTIVES: In this article, we review the various options for and the potential role of interferon alfa (IFN-α) in the treatment of non-muscle-invasive bladder cancer (NMIBC). METHODS: PubMed was searched for journal articles on IFN-α use in treating bladder cancer. The references listed in the National Comprehensive Cancer Network guidelines were used as a guide to identify relevant publications on treatments for NMIBC. RESULTS: Transurethral resection with adjuvant intravesical chemotherapy or immunotherapy is the standard treatment option for NMIBC. Adjuvant IFN-α therapy has limited efficacy in preventing recurrences in intermediate-risk and high-risk patients; bacillus Calmette-Guérin (BCG) monotherapy is the recommended first-line treatment in these patients. Unfortunately, cancer progression or recurrence is a common outcome; radical cystectomy, which is often the lifesaving approach in such a scenario, is associated with significant morbidity, mortality, and decreased quality of life. Current alternatives to cystectomy include repeat intravesical immunotherapy, conventional instillation chemotherapy, and device-assisted intravesical chemotherapy. The efficacy of any chemotherapy after BCG failure, either conventional or device assisted, has not been established. BCG and IFN-α combination intravesical therapy has not been investigated thoroughly; based on available data, combination therapy appears to be most effective in patients with carcinoma in situ and may be preferentially considered as an alternative to radical cystectomy for patients with intermediate-risk or high-risk NMIBC who do not tolerate the standard BCG dose or experience BCG failure after 1 year of therapy. However, this approach requires close follow-up and should only be chosen after careful consideration of all risk factors. CONCLUSIONS: There is a lack of efficacious treatment options for patients with NMIBC recurrence or progression after initial BCG treatment. There is a need for well-designed clinical trials investigating the safety and efficacy of available therapies, including BCG and IFN-α2b combination therapy.
  Urologic Oncology 04/2013;
• Article: Preoperative decision making for renal cell carcinoma: Cystic morphology in cross-sectional imaging might predict lower malignant potential.

  Johannes Huber, Alexandra Winkler, Hildegard Jakobi, Thomas Bruckner, Wilfried Roth, Peter Hallscheidt, Keivan Daneshvar, Markus Hohenfellner, Sascha Pahernik
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  ABSTRACT: OBJECTIVES: Several histologic studies showed more favorable oncologic outcome for renal cell carcinoma (RCC) with cystic change. However, there is no prognostic tool to judge on cystic RCC preoperatively. We hypothesized, that cystic morphology in cross-sectional imaging predicts lower malignant potential. MATERIALS AND METHODS: From our prospectively conducted oncologic database, we identified 825 patients who underwent surgery for malignant renal tumors between 2001 and 2010. In 348 cases (42%), adequate imaging was available for an independent review by 2 radiologists. We excluded recurrent and synchronous bilateral RCC, familial syndromes, collecting duct carcinoma, and metastases of other origin. For the resulting 319 patients, we compared clinical, pathologic, and survival outcomes. RESULTS: Median age was 63 (19-88) years and 220 (69%) patients were male. Median follow-up was 1.7 (0-9.8) years. Of 319 renal masses, 277 (86.8%) were solid and 42 (13.2%) were cystic. In cystic RCC, median tumor diameter was lower (3cm vs. 4cm, P = 0.002) and nephron-sparing surgery was more frequent (69% vs. 41.5%, P = 0.002). None of the patients with cystic RCC and 56 (20.2%) with solid RCC had synchronous systemic disease (P = 0.001). The nuclear grade of cystic RCC was more favorable (P = 0.002). Patients with cystic RCC showed better overall (P = 0.049) and cancer-specific survival (P = 0.027). In a multivariate model, only synchronous metastases, positive R status, and greater tumor diameter were independent risk factors (P≤ 0.03). CONCLUSIONS: We report the first study to show that cystic morphology in cross-sectional imaging might predict RCC with a lower malignant potential. This insight could allow less invasive treatment strategies in selected patients.
  Urologic Oncology 04/2013;
• Article: Inflammation and prostate cancer.

  Fabrizio Dal Moro, Filiberto Zattoni
  Urologic Oncology 04/2013;
• Article: Expression of CX3CR1 associates with cellular migration, metastasis, and prognosis in human clear cell renal cell carcinoma☆?>

  Xin Yao, Lifeng Qi, Xusheng Chen, Jun Du, Zhenting Zhang, Suxiang Liu
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  ABSTRACT: OBJECTIVES: The identification of critical proteins regulating cancer cell metastasis, in clear cell renal cell carcinoma (CCRCC), is important for prediction of prognosis, prevention of metastasis, and treatment of this lethal malignancy. In the present study, we evaluated the role of CX3CR1 in cellular adhesion, migration, and metastasis in CCRCC. We further investigated the downstream molecular signaling mechanism of fractalkine (FKN)-CX3CR1-induced migration and metastasis. MATERIALS AND METHODS: The expression and localization of CX3CR1 in RCC cell lines were assessed by immunofluorescence analysis. The migration of cancer cells was examined by wound healing and transwell migration assay. The expression level of CX3CR1 and FKN in 78 CCRCC individual samples, 16 normal kidney cortex tissue samples, and 16 cases of metastatic lesions of CCRCC were evaluated using immunohistochemical analysis on tissue microarray. The signal pathway of functional FKN was analyzed by the use of the western-blotting method and inhibitory migration assay. RESULTS: CX3CR1 was expressed in human RCC cell lines, and only membrane positive cells were responsible for FKN-induced cell migration. Extracellular signal-related kinases (ERK1/2) and phosphatidyl-inositide 3 kinase/Akt (PI3K/Akt) were each activated upon soluble FKN stimulation in a time-dependent manner, whereas blockades of MEK, PI3K, and G proteins prevented FKN-mediated cellular migration. Furthermore, CCRCC tissue microarray immunohistochemistry data revealed a clear association of strong CX3CR1 expression with tumor metastasis and poor prognosis. CONCLUSIONS: CX3CR1 expression is associated with the process of cellular migration in vitro and tumor metastasis of CCRCC in vivo. Both clinical and molecular cellular evidence suggest that CX3CR1 is a potential marker and therapeutic target for CCRCC prognostic prediction and treatment.
  Urologic Oncology 04/2013;
• Article: Phase II trial of first-line chemotherapy with gemcitabine, etoposide, and cisplatin for patients with advanced urothelial carcinoma.

  Shinji Urakami, Yasuhisa Fujii, Shinya Yamamoto, Takeshi Yuasa, Shinichi Kitsukawa, Mizuaki Sakura, Akihiro Yano, Kazutaka Saito, Hitoshi Masuda, Junji Yonese, Iwao Fukui
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  ABSTRACT: OBJECTIVES: This study sought to examine the combination chemotherapy of gemcitabine, etoposide, and cisplatin (GEP) as a first-line treatment for advanced urothelial carcinoma (UC) to assess its antitumor activity and toxicity. METHODS AND MATERIALS: Eligible patients with advanced UC had undergone no previous chemotherapy. Advanced UC was defined as unresectable or metastatic disease. Subsequent recurrent disease, either locally or distantly following primary radical surgery, was not excluded. GEP was recycled every 4 weeks. Etoposide and cisplatin were given on days 1 through 3 at doses of 60mg/m(2) and 20mg/m(2), respectively, and gemcitabine was given on days 1, 8, and 15 at a dose of 800mg/m(2). The primary end point was objective response rate, and the secondary end points included progression-free survival, overall survival (OS), and toxicity. RESULTS: Forty-two patients were enrolled and subsequently treated with GEP. Nineteen had visceral/bone metastases, 16 had disease restricted to the lymph nodes, and the remaining 7 had unresectable disease at the primary site. The median number of GEP courses was 4. Thirty of the 42 assessable patients (71.4%, 95% confidence interval [CI]: 56.4%-82.8%) demonstrated objective responses. At a median follow-up of 14.6 months, median progression-free survival and OS periods were 8.7 months (95% CI: 6.9-14.6mo) and 16.2 months (95% CI: 13.1-25.4mo), respectively. In the multivariate analysis, anemia and visceral/bone metastasis were significant pretreatment prognostic factors for OS. Grade 4 hematologic events were neutropenia (83.3%), thrombocytopenia (23.8%), and anemia (7.1%). There were no toxic deaths and no instances of severe nonhematologic toxicity. CONCLUSIONS: GEP as a first-line chemotherapy treatment was very active and moderately tolerable for advanced UC. Anemia and visceral/bone metastasis were important negative predictive factors of GEP for OS.
  Urologic Oncology 04/2013;
• Article: Positive surgical margins at radical prostatectomy: much ado about nothing?

  Matthew J Resnick, Michael S Cookson
  Urologic Oncology 04/2013; 31(3):285-7.
• Article: High-resolution transrectal ultrasound: Pilot study of a novel technique for imaging clinically localized prostate cancer(☆)

  Christian P Pavlovich, Toby C Cornish, Jeffrey K Mullins, Joel Fradin, Lynda Z Mettee, Jason T Connor, Adam C Reese, Frederic B Askin, Rachael Luck, Jonathan I Epstein, Harry B Burke
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  ABSTRACT: OBJECTIVES: To determine how high-resolution transrectal ultrasound (HiTRUS) compares with conventional TRUS (LoTRUS) for the visualization of prostate cancer. METHODS AND MATERIALS: Twenty-five men with known prostate cancer scheduled for radical prostatectomy were preoperatively imaged with both LoTRUS (5MHz) and HiTRUS (21MHz). Dynamic cine loops and still images for each modality were saved and subjected to blinded review by a radiologist looking for hypoechoic foci≥5mm in each sextant of the prostate. Following prostatectomy, areas of prostate cancer≥5mm on pathologic review were anatomically correlated to LoTRUS and HiTRUS findings. The accuracy of LoTRUS and HiTRUS to visualize prostate cancer in each sextant of the prostate and to identify high-grade and locally advanced disease was assessed. The McNemar test was used to compare sensitivity and specificity and paired dichotomous outcomes between imaging modalities. RESULTS: Among 69 sextants with pathologically identified cancerous foci at radical prostatecomy, HiTRUS visualized 45 and missed 24, whereas LoTRUS visualized 26 and missed 43. Compared with LoTRUS, HiTRUS demonstrated improved sensitivity (65.2% vs. 37.7%) and specificity (71.6% vs. 65.4%). HiTRUS's agreement with pathologic findings was twice as high as LoTRUS (P = 0.006). HiTRUS provided a nonsignificant increase in visualization of high-grade lesions (84% vs. 60%, P = 0.11). CONCLUSIONS: HiTRUS appears promising for prostate cancer imaging. Our initial experience suggests superiority to LoTRUS for the visualization of cancerous foci, and supports proceeding with a clinical trial in the biopsy setting.
  Urologic Oncology 04/2013;
• Article: Ensuring comprehensive assessment of urinary problems in prostate cancer through patient-physician concordance.

  David E Victorson, Penny S Brucker, Rita K Bode, David T Eton, James A Talcott, Jack A Clark, Sara J Knight, Mark S Litwin, Carol M Moinpour, Bryce B Reeve, Neil K Aaronson, Charles L Bennett, Harry W Herr, Michael McGuire, Daniel Shevrin, Kevin McVary, David Cella
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  ABSTRACT: OBJECTIVES: To examine the concordance between clinicians and men diagnosed with prostate cancer on a clinician-derived pathophysiological classification of the following self-reported urinary complications: storage (irritative), voiding (obstructive), and leakage/incontinence. MATERIALS AND METHODS: Fourteen urology experts classified 37 urinary function questionnaire items into 3 primary conceptual dimensions (e.g., storage [irritative], voiding [obstructive] and urinary leakage/incontinence) that would best reflect each item's content. In addition, 218 patient participants provided responses to the 37 items. Using classifications by experts to develop the conceptual framework, the structure was tested using confirmatory factor analyses with patient data. RESULTS: Expert consensus was achieved in the classification of 31 out of 37 items. Using the 3-factor conceptual framework and patient data, the fit indices for the overall correlated factor model suggested an acceptable overall model fit. The analyses of the separate domains showed acceptable fit for the storage/irritative domain and the leaking/incontinence domain. The dimensionality of the voiding/obstructive domain was too difficult to estimate. CONCLUSIONS: Our analysis found items that conceptually and psychometrically support 2 constructs (leaking/incontinence and storage/irritative). The consistency of this support between the groups suggests a clinical relevance that is useful in treating patients. We have conceptual support for a third hypothesis (voiding/obstructive), although there were too few items to assess this psychometrically. Relative motivating factors of bother and urinary complaints were not addressed and remain an unmet need in this field.
  Urologic Oncology 03/2013;
• Article: Active surveillance for low-risk bladder cancer.

  Albert Tiu, Lawrence C Jenkins, Mark S Soloway
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  ABSTRACT: BACKGROUND: Most newly diagnosed bladder cancers present as non-muscle invasive bladder cancer (NMIBC). NMIBC is a heterogeneous disease with varying treatment options, follow-up schedules, and oncologic outcomes. We sought to review the role of active surveillance for low risk bladder cancer in the literature. METHODS: A PubMed search was performed using the following keywords: active surveillance, low risk, bladder, transurethral resection of bladder tumor, cost, and quality of life. Relevant articles were reviewed and utilized. RESULTS: Low-risk bladder cancer-defined as pTa low-grade papillary tumors-is the type of NMIBC with the most favorable oncologic outcome and which almost never progresses to muscle invasive disease or metastasizes. Bladder cancer has the highest per patient treatment costs of all cancers. One of the reasons is the high rate of recurrence. Patients with low-grade bladder tumors often experience a recurrence after primary transurethral resection. Many patients undergo multiple resections in the hospital. CONCLUSIONS: Appropriately selected patients with recurrent low-risk bladder cancer could be managed with either office fulguration or cystoscopic surveillance. Active surveillance for patients with low-risk bladder cancer avoids or delays the surgical and anesthetic risks of a TURBT, thus optimizing quality of life without compromising the patient's risk of cancer progression.
  Urologic Oncology 03/2013;
• Article: Sargramostim (GM-CSF) and lenalidomide in castration-resistant prostate cancer (CRPC): Results from a phase I-II clinical trial(☆☆☆)

  Jorge A Garcia, Paul Elson, Allison Tyler, Pierre Triozzi, Robert Dreicer
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  ABSTRACT: BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that stimulates dendritic cells (DCs) and promotes uptake of tumor antigens by DCs leading to T-cell cross-priming. Lenalidomide (Revlimid) is an immunomodulatory analog of thalidomide with significant T-cell stimulatory and antiangiogenic properties. GM-CSF in combination with thalidomide induces prostate-specific antigen (PSA) responses in 20% to 25% of patients with castration-resistant prostate cancer (CRPC). In an effort to further evaluate the clinical and immune activity of GM-CSF and lenalidomide, we conducted a phase I-II trial in patients with CRPC. METHODS: Asymptomatic patients with CRPC were enrolled. Prior immunotherapy or chemotherapy was not allowed. All the patients received 250μg of GM-CSF administered subcutaneously 3 times weekly along with 25mg/d of lenalidomide administered orally on days 1 to 21 of a 28-day cycle. The primary end points were objective, PSA response, and safety. Exploratory end points included activation of circulating DCs, regulatory T cells, and Th1 cytokine production. RESULTS: Thirty-two patients were enrolled in the study. No dose-limiting toxicities occurred in the phase I portion of the study. Although 81% of the patients achieved a decline in the levels of PSA while on therapy, only 4 achieved a PSA level decline of≥50%. The overall response rate among 11 patients with response evaluation criteria in solid tumors-defined measurable disease was 18%. Overall toxicity was G1 and G2 in nature and included fatigue observed in 69% of the patients, nausea/vomiting in 34%, and diarrhea in 28% of the patients. Grade 3 or 4 toxicities occurred in 22% of the patients and were primarily thrombocytopenia (9%) or neutropenia (19%) or both. CONCLUSIONS: Administration of GM-CSF and lenalidomide in patients with CRPC is safe with modest evidence of antitumor activity and no immune changes observed.
  Urologic Oncology 03/2013;
• Article: Short telomeres and chromosome instability prior to histologic malignant progression and cytogenetic aneuploidy in papillary urothelial neoplasms(☆☆)

  Naotaka Izumiyama-Shimomura, Ken-Ichi Nakamura, Junko Aida, Naoshi Ishikawa, Mie Kuroiwa, Naoki Hiraishi, Mutsunori Fujiwara, Yuichi Ishikawa, Naoko Inoshita, Junji Yonese, Masaaki Matsuura, Steven S S Poon, Tomio Arai, Kaiyo Takubo
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  ABSTRACT: PURPOSE: Evaluation of the relationships existing among 3 histologic types of urothelial tumors, chromosomal instability, and telomere length. PATIENTS AND METHODS: We examined 37 consecutive cases of papillary urothelial neoplasm, from which 26 (70.3%) were suitable for karyotype analysis, comprising 7 papillary urothelial neoplasms of low malignant potential (PUNLMPs), 10 low-grade papillary urothelial carcinomas (PUCs), and 9 high-grade PUCs. We performed karyotype and anaphase bridge analyses, and measured telomere lengths by quantitative fluorescence in situ hybridization. RESULTS: PUNLMPs were always diploid and had anaphase bridges. Low-grade PUCs showed diploidy (n = 2), hypoploidy (n = 4) and polyploidy (n = 4), and high-grade PUCs showed diploidy (n = 1) and polyploidy (n = 8); both had anaphase bridges. The incidence of anaphase bridges did not differ significantly between PUNLMPs and high-grade PUCs (P = 0.105). The telomere lengths of PUNLMP, low-grade PUC, and high-grade PUC, expressed as mean telomere fluorescence units (TFU)±SD, were 7906±3197, 4893±1567, and 3299±1406, respectively. The differences among the 3 groups were significant. However, 42.9% of the PUNLMPs had shorter telomeres than the mean value for low-grade PUCs, and 30.0% of the low-grade PUCs had shorter telomeres than those for high-grade PUCs. There was an inverse correlation between telomere length and the incidence of anaphase bridges. CONCLUSIONS: PUNLMP appears to progress to low-grade PUC and high-grade PUC in association with telomere shortening and chromosomal instability. Our data suggest that critically shortened telomeres cause chromosomal instability during progression of papillary urothelial neoplasms.
  Urologic Oncology 03/2013;
• Article: Serum levels of 17-β-estradiol are not predictive of prostate cancer diagnosis and aggressiveness: Results from an Italian biopsy cohort.

  Cosimo De Nunzio, Riccardo Lombardo, Costantino Leonardo, Giorgio Franco, Mauro Gacci, Fabrizio Presicce, Fabiana Cancrini, Andrea Tubaro
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  ABSTRACT: OBJECTIVES: To explore the association between serum levels of 17-β-estradiol (17BE) and prostate cancer (PCa) risk in men undergoing prostate biopsy. METHODS AND MATERIALS: Between 2006 and 2012, we prospectively enrolled 894 patients, with no history of PCa, undergoing prostate biopsy. Before biopsy was performed, general data, digital rectal examination (DRE), body mass index, 17BE, and prostate-specific antigen (PSA) were recorded. The risk of detecting cancer and high-grade cancer was assessed as a function of 17BE using crude and adjusted logistic regressions. RESULTS: Serum levels of 17BE were not associated with an increased risk of PCa or high-grade disease. Age (odds ratio [OR] 1.05; 95% confidence interval [CI]: 1.03-1.07; P = 0.000), DRE(OR 2.81; 95% CI: 1.98-4.00; P = 0.000), and PSA(OR 1.07; 95% CI: 1.04-1.10; P = 0.000) were found to be independent predictors of PCa risk. Age (OR 1.05; 95% CI: 1.01-1.09; P = 0.007), DRE (OR 3.04; 95% CI: 1.79-5.17; P = 0.000), body mass index (OR 1.07; 95% CI: 1.01-1.150; P = 0.040), and PSA (OR 1.08; 95% CI: 1.03-1.12; P = 0.000) were found to be independent predictors of high-grade disease. CONCLUSION: In our cohort of patients, serum levels of 17BE are not predictive of PCa or high-grade disease. In patients at risk of PCa, 17BE should not be considered a reliable marker to predict poorly differentiated PCa in the setting of initial prostate biopsy.
  Urologic Oncology 03/2013;
• Article: Multi-institutional analysis of sequential intravesical gemcitabine and mitomycin C chemotherapy for non-muscle invasive bladder cancer.

  Andrew J Lightfoot, Benjamin N Breyer, Henry M Rosevear, Bradley A Erickson, Badrinath R Konety, Michael A O'Donnell
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  ABSTRACT: OBJECTIVE: Apart from cystectomy, few treatment options exist for the management of bacillus Calmette-Guerin refractory non-muscle invasive bladder cancer (NMIBC). We report a multi-institutional experience with sequential intravesical combination chemotherapy using gemcitabine and mitomycin C (MMC) for NMIBC in the treatment of high-risk patients. METHODS: We performed a retrospective review of patients who received 6 weekly treatments with sequential intravesical gemcitabine (1g) and MMC (40mg) chemotherapy for NMIBC. Gemcitabine was administered first and retained for 90 minutes and then drained. MMC was then administered directly after and retained for an additional 90 minutes. Forty-seven patients received treatment from 3 academic tertiary referral centers between 2000 and 2010. RESULTS: Forty-seven patients (median age 70, range 32-85; 36 males, 11 females) who previously failed a median of 2 intravesical treatments were reviewed. Complete response, 1-year, and 2-year recurrence-free survival rates for all patients were 68%, 48%, and 38%, respectively. Median recurrence-free survival for all patients was 9 months (range 1-80). Fourteen of 47 patients (30%) remained free of recurrence with a median time to follow-up of 26 months (range 6-80mo). Ten patients required cystectomy. CONCLUSION: Sequential intravesical combination chemotherapy using gemcitabine and MMC appears to be a useful treatment for patients with high-grade NMIBC as well as those with prior bacillus Calmette-Guerin failure. Further prospective studies are warranted.
  Urologic Oncology 03/2013;
• Article: Do racial disparities exist in the use of prostate cancer screening and detection tools in veterans?

  M'liss A Hudson, Suhong Luo, Timothy Chrusciel, Yan Yan, Robert L Grubb, Kenneth Carson, Jeffrey F Scherrer
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  ABSTRACT: OBJECTIVE: To determine whether racial disparities exist in the use of prostate cancer screening and detection tools in veterans. METHODS AND MATERIALS: Administrative data were obtained from the Corporate Data Warehouse on a national cohort of 275,831 veterans (21% African American [AA]) between the ages of 40 and 70 years who were free of heart disease, did not have an elevated prostate specific antigen (PSA) level (>4 ng/ml), did not have other clinical signs of prostate cancer, had not been diagnosed with prostate cancer, and had not received treatment for prostate cancer between January 10, 1998 and September 30, 2000. Subjects were followed up until September 30, 2007. Regular users were defined as those with at least 1 annual visit to the Veterans Healthcare Administration (VHA) between October 1, 1998 and September 30, 2000. We sought to determine if race was significantly associated with PSA testing, the time to elevated PSA detection, the time to prostate biopsy, and the time to diagnosis of prostate cancer. Chi-square tests, logistic regression, and Cox proportional hazard models were used to test for associations between race and prostate cancer variables. RESULTS: Eighty-four percent of the veterans between the ages 40 and 70 years undergo PSA testing. AA veterans are as likely as white veterans to undergo PSA testing. Screened AA veterans are more likely to have a PSA>4ng/ml, undergo prostate biopsy, and be diagnosed with prostate cancer than screened white veterans. The time intervals between undergoing a prostate biopsy and being diagnosed with prostate cancer were statistically significantly shorter (although unlikely of clinical significance) for AA veterans with a PSA level>4ng/ml than that for white veterans with a PSA level>4ng/ml. When routine care in regular VHA users was compared with that of participants in major screening trials such as Prostate, Lung, Ovarian and Colon Cancer Trial and European Study of Screening for Prostate Cancer, prostate biopsy rates were lower (30% vs. 40%-86%), prostate cancer detection rates/person biopsied were higher (49% vs. 31%-45%), and incidence of prostate cancer was 1.1% vs. 4.9% to 8.3%. CONCLUSIONS: Among regular users of the VHA for healthcare, no disparities toward AA veterans exist in the use of prostate cancer screening and detection tools. Any differences in prostate cancer treatment outcomes are not likely because of inequalities in the use of prostate cancer screening or detection tools.
  Urologic Oncology 03/2013;