Vol. 43 n. 4 Jul . Aug, 2017

Volume 43 | number 4 | July . August, 2017 The Middle Term

The Middle Term

Vol. 43 (4): 577-578, July – August, 2017

doi: 10.1590/S1677-5538.IBJU.2017.04.01

EDITORIAL in this Issue

Stênio de Cássio Zequi
Editor Associado, International Braz J Urol
Divisão de Urologia do A.C. Camargo Cancer Center
Fundação A. Prudente, São Paulo, Brasil

As it is been daily debated, the dilemmas on to treat or not to treat patients with localized prostate cancer are under the scope of the “Difference of opinion section”: Between two extremes: the radical whole gland treatments versus the active surveillance protocols, the “middle term”, probably will be arise from judicious and individualized patient selection. Using biomolecular markers, nomograms, modern magnetic resonance evaluations and the individual patient preferences and payment capacities, the urologists will be able to decide a personalized approach’s, varying from traditional whole gland therapies, passing by the emerging focal treatments until exclusive surveillance. Concomitantly, in the future, less patients will be overdiagnosed and overtreated. Our readers will be able the get their self “middle term decisions”, after reading the favorable arguments (Dell´Oglio and Sanchez Salas, from Paris) and contrary to treatment (Schulman and Polascyck, from North Carolina)…

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Most of patients with localized prostate cancer will be treated in the future? | Opinion: Yes

Vol. 43 (4): 579-583, July – August, 2017

doi: 10.1590/S1677-5538.IBJU.2017.04.02


Paolo Dell’Oglio 1,2, Rafael Sanchez-Salas 1
1 Department of Urology, Institut Mutualiste Montsouris, Paris, France; 2 Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy

Keywords: Prostatic Neoplasms; Patients; Epidemiology


Localized prostate cancer (LPCa) is an heterogeneous disease extending from individuals who harbor indolent cancer, that are highly unlikely to develop metastases, to individuals with more aggressive disease, that have higher risk of metastatic burden. This would translates into different oncologic outcomes and have implications for disease management.

Once the diagnosis of LPCa is established, remains challenging to identify those patients who may benefit from delayed or immediate treatment. Several options exist, from active surveillance (AS) to the whole-gland treatments (1). However, the optimal one is still unclear. To date, the percentage distribution of treatment for LPCa is around 8.4% for observation, 13.1% for ablative therapies, 28.1% for external beam radiotherapy (RT), 1.6% for brachytherapy, 45% for radical prostatectomy (RP) and 3.7% for primary androgen deprivation therapy (2)…

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Most of patients with localized prostate cancer will be treated in the future? | Opinion: No

Vol. 43 (4): 584-587, July – August, 2017

doi: 10.1590/S1677-5538.IBJU.2017.04.03


Ariel A. Schulman 1, Thomas J. Polascik 1
1 Division of Urology, Duke University Medical Center, Durham, NC, USA

Keywords: Prostatic Neoplasms; Patients; Epidemiology


We are in the midst of a major shift in the diagnosis and management of localized prostate cancer. The prevailing approach of the 1980’s and 1990’s focused on widespread population-based prostate specific antigen (PSA) testing and curative-intent treatment for any detected cancer. The philosophical approach in the most recent decade is now defined by risk-adapted PSA screening, and integration of novel imaging techniques and biomarkers to increase the detection of clinically significant cancer. Concomitantly, we are witnessing the expanding utilization of active surveillance and partial ablation trategies to avoid overtreatment. We believe that continued development in each of these areas will continue to decrease the number of patients with localized disease treated with traditional whole gland surgery or radiation in the future…

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Impact of local treatment on overall survival of patients with metastatic prostate cancer: systematic review and meta-analysis

Vol. 43 (4): 588-599, July – August, 2017

doi: 10.1590/S1677-5538.IBJU.2016.0483


Arie Carneiro 1,2, Willy Baccaglini 2, Felipe P.A. Glina 3, Paulo P. Kayano 1, Victor M. Nunes 4, Oren Smaletz 5, Wanderley Marques Bernardo 4, Icaro Thiago de Carvalho 6, Gustavo Caserta Lemos 1
1 Departamento de Urologia, Hospital Israelita Albert Einstein, SP, Brasil; 2 Departamento de Urologia, Faculdade de Medicina do ABC, SP, Brasil; 3 Faculdade de Ciências Médicas, Universidade Metropolitana de Santos, SP, Brasil; 4 Centro Universitário Lusiada, Faculdade de Ciências Médicas de Santos, SP, Brasil; 5 Departamento de Oncologia, Hospital Israelita Albert Einstein, São Paulo, Brasil; 6 Departamento de Radioterapia, Hospital Israelita Albert Einstein, São Paulo, Brasil

Context: Currently, standard treatment of metastatic prostatic cancer (MPCa) is androgen-deprivation therapy (ADT). Recent studies suggested that local treatment of MPCa is related to increase of survival of those patients, as observed in other tumors.

Objective: To evaluate the impact of local treatment on overall survival and cancer specific survival in 3 and 5 years in patients with MPCa.

Materials and Methods: Systematic review and meta-analysis of population studies published at PubMed, Scielo, Lilacs, Cochrane and EMBASE databases until June 2016. Several large cohorts and Post-Roc studies were included, that evaluated patients with MPCa submitted to local treatment (LT) using radiotherapy (RDT), surgery (RP) or brachytherapy (BCT) or not submitted to local treatment (NLT).

Results: 34.338 patients were analyzed in six included papers, 31.653 submitted to NLT and 2.685 to LT. Overall survival in three years was significantly higher in patients submitted to LT versus NLT (64.2% vs. 44.5%; RD 0.19, 95% CI, 0.17-0.21; p<0.00001; I²=0%), as well as in five years (51.9% vs. 23.6%; RD 0.30, 95% CI, 0.11-0.49; p<0.00001; I²=97%). Sensitive analysis according to type of local treatment showed that surgery (78.2% and 45.0%; RD 0.31, 95% CI, 0.26-0.35; p<0.00001; I²=50%) and radiotherapy (60.4% and 44.5%; RD 0.17, 95% CI, 0.12-0.22; p<0.00001; I²=67%) presented better outcomes.

Conclusion: LT using RDT, RP or BCT seems to significantly improve overall survival and cancer-specific survival of patients with metastatic prostatic cancer. Prospective and randomized studies must be performed in order to confirm our results.

Keywords: Prostate; Survival; Radiation Oncology; Prostatic Neoplasms

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High cancer detection rate using cognitive fusion – targeted transperineal prostate biopsies

Vol. 43 (4): 600-606, July – August, 2017

doi: 10.1590/S1677-5538.IBJU.2016.0511


Snir Dekalo 1, Haim Matzkin 1, Nicola J Mabjeesh 1
1 Department of Urology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Israel



Objective MRI of the prostate improves diagnostic accuracy of prostate cancer. Dif­ferent fusion approaches with transrectal ultrasound images are employed. Objective: To determine detection rate of prostate cancer in men undergoing transperineal MRI-based cognitive fusion biopsy.

Materials and Methods: One hundred and sixty-four consecutive men underwent a multiple-core prostate transperineal biopsy. Univariable and multivariable logistic re­gression analyses were used to address the relationship between clinical parameters and prostate cancer detection rate.

Results: One hundred and fourteen patients underwent mpMRI prior to the transperi­neal biopsy, 52 (45%) were diagnosed with prostate cancer, of them, 36 had Gleason score ≥7 (69%). Among these 114 patients, 82 had suspicious lesions on MRI, and 43 of them were diagnosed with cancer (52%). On multivariate analysis, the most significant independent predictive factors were PSA density (P<0.001) and suspicious MRI lesion (P=0.006). Men with a PSA density of more than 0.22 and a suspicious lesion on MRI had a detection rate of 78%. Detection rate among 50 patients with no MRI study prior to this biopsy was 26%.

Conclusions: This study showed that among a group of mostly multi-biopsied patients, the presence of mpMRI lesions and high PSA density values helped to detect clinically significant prostate cancer using cognitive MRI/TRUS fusion biopsies.

Keywords:  Magnetic Resonance Imaging; Prostatic Neoplasms; Biopsy

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The awareness of patients with non – muscle invasive bladder cancer regarding the importance of smoking cessation and their access to smoking cessation programs

Vol. 43 (4): 607-614, July – August, 2017

doi: 10.1590/S1677-5538.IBJU.2016.0014


Emrah Yuruk 1, Murat Tuken 1, Aykut Colakerol 1, Ege Can Serefoglu 1
1 Department of Urology, Bagcilar Training and Research Hospital, Istanbul, Turkey


Objectives: Smoking is the most important risk factor for bladder cancer and smoking cessation is associated with reduced risk of tumor recurrence and progression. The aim of this study is to assess the awareness of non-muscle invasive bladder cancer (NMIBC) patients regarding the importance of smoking cessation, determine their access to smoking cessation programs and the effects of smoking cessation on recurrence rates of NMIBC.

Materials and Methods: NMIBC patients who were followed with cystoscopy were included in the study. Their demographic properties were recorded, along with their smoking habits, awareness regarding the effects of smoking on bladder cancer and previous attempts for smoking cessation. Moreover, the patients were asked whether they applied for a smoking cessation program. Recurrence of bladder cancer during the follow-up period was also noted.

Results: A total of 187 patients were included in the study. The mean age was 64.68±12.05 (range: 15-90) and the male to female ratio was 167/20. At the time of diagnosis, 114 patients (61.0%) were active smokers, 35 patients (18.7%) were ex-smokers and 38 patients (20.3%) had never smoked before. After the diagnosis, 83.3% of the actively smoking patients were advised to quit smoking and 57.9% of them quit smoking. At the time of the study, 46.52% of the NMIBC patients were aware of the link between smoking and bladder cancer, whereas only 4.1% of the smoking patients were referred to smoking cessation programs. After a mean follow-up of 32.28±11.42 months, 84 patients (44.91%) had recurrence; however, current smoking status or awareness of the causative role of smoking on NMIBC did not affect the recurrence.

Conclusion: In our study group, the majority of the NMIBC patients were not aware of the association between smoking and bladder cancer. Although most of the physicians advised patients to quit smoking, a significant amount of the patients were still active smokers during follow-up. Only a small proportion of patients were referred to smok­ing cessation programs. Urologists should take a more active role in the battle against smoking and refer those patients to smoking cessation programs. Larger study popula­tions with longer follow-up periods are needed to better demonstrate the beneficial effects of smoking cessation on recurrence rates.

Keywords: Urinary Bladder Neoplasms; Patients; Epidemiologic Studies

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Generation of potent cytotoxic T lymphocytes against in male patients with non-muscle invasive bladder cancer by dendritic cells loaded with dying T24 bladder cancer cells

Vol. 43 (4): 615-627, July – August, 2017

doi: 10.1590/S1677-5538.IBJU.2016.0274


Eu Chang Hwang 1,2, Seung Il Jung 2, Hyun-Ju Lee 1, Je-Jung Lee 1,3,4,5, Dong Deuk Kwon 2
1 Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea; 2 Department of Urology and 3 Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea; 4 Vaxcell-Bio Therapeutics, Hwasun, Jeollanamdo, Republic of Korea; 5 The Brain Korea 21 Project, Center forBiomedical Human Resources at Chonnam National University, Gwangju, Republic of Korea


Background: In order to induce a potent cytotoxic T lymphocyte (CTL) response in dendritic cell (DC)-based immunotherapy for bladder cancer, various tumor antigens can be loaded onto DCs.
Objective: The aim of this study was to establish a method of immunotherapy for male patients with non-muscle invasive bladder cancer (NMIBC), using bladder cancer-spe¬cific CTLs generated in vitro by DCs.
Materials and Methods: Monocyte-derived DCs from bladder cancer patients were in¬duced to mature in a standard cytokine cocktail (IL-1β, TNF-α, IL-6, and PGE2: standard DCs, sDCs) or anα-type 1-polarized DC (αDC1) cocktail (IL-1β, TNF-α, IFN-α, IFN-γ, and polyinosinic:polycytidylic acid) and loaded with the UVB-irradiated bladder cancer cell line, T24. Antigen-loaded αDC1s were evaluated by morphological and functional assays, and the bladder cancer-specific CTL response was analyzed by cytotoxic assay.
Results: The αDC1s significantly increased the expression of several molecules pertain¬ing to DC maturation, regardless of whether or not the αDC1s were loaded with tumor antigens, relative to sDCs. The αDC1s demonstrated increased production of interleukin-12 both during maturation and after subsequent stimulation with CD40L that was not significantly affected by loading with tumor antigens as compared to that of sDCs. Bladder cancer-specific CTLs targeting autologous bladder cancer cells were success¬fully induced by αDC1s loaded with dying T24 cells.
Conclusion: Autologous αDC1s loaded with an allogeneic bladder cancer cell line re¬sulted in increased bladder cancer-specific CTL responses as compared to that with sDCs, and therefore, may provide a novel source of DC-based vaccines that canbe used in immunotherapy for male patients with NMIBC.

Keywords: Dendritic Cells; Urinary Bladder Neoplasms; T-Lymphocytes, Cytotoxic

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Quality of Life after post-prostatectomy intensity modulated radiation therapy to the prostate bed with or without the use of gold fiducial markers for image guidance or higher total radiotherapy doses

Vol. 43 (4): 628-637, July – August, 2017

doi: 10.1590/S1677-5538.IBJU.2016.0189


Yazan A. Abuodeh 1, Arash O. Naghavi 1, Tzu-Hua Juan 1, Zhenjun Ma 1, Richard B. Wilder 2
1 Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida, USA; 2 Cancer Treatment Centers of America, Newnan, Georgia, USA


Purpose: To evaluate quality of life (QoL) after post-prostatectomy intensity modulated radiation therapy (IMRT) in the “adjuvant” setting starting within 4 months of radical prostatectomy for adverse features; and “salvage” setting for a PSA≥0.2ng/mL.

Materials and Methods: Retrospective review of 130 patients who underwent IMRT to the prostate bed±gold fiducial marker placement for image guidance to 64.8-72.0Gy (median, 70.2Gy) between 2004 and 2013. Higher doses were defined as 70.2-72.0Gy and lower doses were defined as 64.8-68.4Gy. Androgen deprivation therapy (ADT) was given to 4/48 (8%) adjuvant patients and 9/82 (11%) salvage patients. International Prostate Symptom Score (IPSS), Sexual Health Inventory for Men (SHIM), and Expanded Prostate Cancer Index Composite-26-bowel (EPIC-26-bowel) questionnaires were used to assess urinary, sexual, and bowel QoL, respectively.

Results: Median follow-up was 46 months. There were better urinary (p=0.03) and sexual (p=0.002) QoL scores with adjuvant IMRT relative to salvage IMRT. The use of prostate bed fiducial markers did not significantly affect urinary, sexual, or bowel QoL (p=0.39, p=0.49, and p=0.40, respectively). Higher total radiotherapy doses did not significantly affect urinary, sexual, or bowel QoL (p=0.21, p=0.61, and p=0.36, respectively).

Conclusions: There was no significant change in urinary, sexual, and bowel sexual QoL with post-prostatectomy IMRT regardless of whether prostate bed fiducial markers or higher total radiotherapy doses were used. QoL with IMRT in the present study compares favorably with prior reports for three-dimensional conformal radiation therapy.

Keywords: Prostate; Postoperative Care; Radiotherapy; Quality of Life

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SCUBE1: a promising biomarker in renal cell cancer

Vol. 43 (4): 638-643, July – August, 2017

doi: 10.1590/S1677-5538.IBJU.2016.0316


Ersagun Karagüzel 1, Ahmet Menteşe 2, İlke O.Kazaz 1, Selim Demir 3, Asım Örem 4, Ali Ertan Okatan 1, Diler Us Altay 5, Serap Özer Yaman 4
1 Department of Urology, Karadeniz Technical University, Faculty of Medicine, Trabzon, Turkey; 2 Program of Medical Laboratory Techniques, Karadeniz Technical University, Vocational School of Health Sciences, Trabzon, Turkey; 3 Department of Nutrition and Dietetics, Karadeniz Technical University, Faculty of Health Sciences, Trabzon, Turkey; 4 Department of Medical Biochemistry, Karadeniz Technical University, Faculty of Medicine, Trabzon, Turkey 5 Department of Chemistry and Chemical Processing Technology, Ordu University, Ulubey Vocational School, Ordu, Turkey



Purpose: To investigate the efficacy of signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) as a novel biomarker of renal tumors.

Materials and Methods: 48 individuals were included in the study. The patient group (Group-1) consisted of 23 subjects diagnosed with renal tumor, and the control group (Group-2) of 25 healthy individuals. Patients diagnosed with renal tumor received surgical treatment consisting of radical or partial nephrectomy. Blood specimens were collected following overnight fasting. Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1), soluble urokinase plasminogen activator receptor (suPAR) and carbonic anhydrase IX (CA IX) levels were measured from plasma samples. Patients in groups 1 and 2 were compared in terms of these biochemical parameters.

Results: The 23-member renal tumor group was made up of 17 (73.91%) male and 6 (26.08%) female patients with a mean age of 58.5±15.7 years (range 25 to 80). The 24-member healthy control group was made up of 16 (64%) male and 9 (36%) female subjects with a mean age of 52.4±9.12 years (range 40 to 67). Analysis revealed sig­nificant elevation in SCUBE-1 levels in the renal tumor group (p=0.005). No significant differences were detected between the groups with regard to CA IX or suPAR measure­ments (p=0.062 vs. p=0.176).

Conclusions: SCUBE-1 appears to represent a promising biomarker in the diagnosis and follow-up of patients with renal tumor.

Keywords: Carcinoma, Renal Cell; Biomarkers

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Antioxidant enzyme profile and lipid peroxidation products in semen samples of testicular germ cell tumor patients submitted to orchiectomy

Vol. 43 (4): 644-651 July – August, 2017

doi: 10.1590/S1677-5538.IBJU.2016.0323


Camila Sposito 1, Mariana Camargo 1,Danielle Spinola Tibaldi 1, Valéria Barradas 1, Agnaldo Pereira Cedenho 1, Marcílio Nichi 2, Ricardo Pimenta Bertolla 1, Deborah Montagnini Spaine 1
1 Departamento de Cirurgia, Divisão de Urologia, Setor de Reprodução Humana, Universidade Federal de São Paulo, SP, Brasil; 2 Departamento de Reprodução Animal, Faculdade de Medicina Veterinária, Universidade de São Paulo, SP, Brasil


Purpose: To determine enzymatic antioxidant and lipid peroxidation levels in seminal plasma of patients orchiectomized for testicular tumors.

Materials and Methods: The study included 52 patients: 26 control men and 26 orchi­ectomized patients for testicular tumor, of which 12 men had seminoma tumor and 14 men non-seminoma tumor. After semen analysis performed according to the WHO guidelines, an aliquot of semen was centrifuged and the seminal plasma was collected. Lipid peroxidation was performed by thiobarbituric acid reactive substances(TBARS) assay and antioxidant profile was assessed by analyzing catalase, glutathione per­oxidase (GPx) and superoxide anion (SOD) activities using colorimetric assays with a standard spectrophotometer. Data were tested for normality and compared using one-way ANOVA (p<0.05).

Results: Seminoma and non-seminoma groups presented lower sperm concentration and morphology when compared to control group (p=0.0001). Both study groups (sem­inoma and non-seminoma) presented higher TBARS levels when compared to con­trol group (p=0.0000013). No differences were observed for SOD (p=0.646) andGPx (p=0.328). It was not possible to access the enzymatic activity of catalase in any group.

Conclusion: Patients with testicular tumor present increased semen oxidative stress, but no differences were observed in antioxidant levels, even after orchiectomy. This indicates that most likely an increased generation of oxidative products takes place in these patients.

Keywords: Antioxidants; Oxidative Stress; Testicular Germ Cell Tumor; Orchiectomy; Semen

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