Prediction of response to androgen deprivation therapy and castration resistance in primary metastatic prostate cancer.

PURPOSE: We tried to establish the predictive factors influencing the initial response, as well as its duration, and time to castration resistance (CR) for primary advanced prostate cancer (PC) with bone metastasis. METHODS: We evaluated all patients initially receiving androgen deprivation therapy (ADT) for primary advanced PC with bone metastasis. A total of 982 patients with complete medical records available for analysis from 18 centers were included in this study. Age, initial PSA, Gleason score (GS) and extent of bone involvement (EBI) were recorded in a database. RESULTS: Among all the patients, 896 (91.2%) responded to ADT initially. Pretreatment PSA and EBI were significant predictors in the multivariate model. Among the 659 patients who progressed into a CR state, the mean duration of response was 22.4 months. There was a significant correlation between the CR state and nadir PSA (nPSA) level and time to nPSA. Pretreatment PSA, EBI, GS, highest tumor volume in biopsy cores (%), number of positive biopsy cores, percent positive biopsy cores and time to nPSA were proven to be significant to predict a nPSA. Pretreatment PSA, GS and EBI were statistically significant predictors of PSA normalization in multivariate analysis. The limitation of the study depends on the retrospective design and a model was developed for low standardization as a result of using multicenter data. The patients enrolled in this study were from a relatively long period of time (1989-2008). CONCLUSIONS: The results of this study indicate that it is possible to predict the initial response to ADT by pretreatment PSA levels and EBI, while the duration of response can be reflected by a multitude of clinical factors including nPSA, TTnPSA, percent positive cores, biopsy GS and EBI.

Functional roles of miR-625-5p and miR-874-3p in the progression of castration resistant prostate cancer.

AIMS: Androgen receptor (AR) signaling is important in normal prostate and prostate tumor tissues. Thus, the new therapeutic strategies targeting ARs may also be important for treatment of prostate cancer (PC) and its biology. The studies have shown that miRNAs to be dysregulated in PC progression. Therefore, in the present study, differentially expressed miRNAs that predictively target the ARs were identified and investigated by in silico analysis. MAIN METHODS: Cellular proliferation, qPCR, western blot and apoptosis assays were performed to investigate the molecular mechanism of the selected miRNAs in the PC cells. KEY FINDINGS: In our miRNA qPCR study, several miRNAs were found to be differentially regulated in castration resistant prostate cancer (CRPC) cells (LNCaP-Abl and LNCaP-104R2) compared with androgen dependent (AD) cells (LNCaP). The expression levels of miR-625-5p and miR-874-3p were significantly increased in LNCaP-Abl (2.62-fold, p = 0.0002; 4.00-fold, p = 0.00002, respectively) and LNCaP-104R2 (2.44-fold, p = 0.0455; 3.77-fold, p = 0.0383, respectively) compared with AD cells. The expression levels of AR and prostate specific antigen were increased in PC cells compared with AD cells. Furthermore, transfection of PC cells with anti-miRs suppressed their proliferation and AR protein levels (p < 0.05). SIGNIFICANCE: Several differentially regulated miRNAs were identified in CRPC cells, including miR-625-5p and miR-874-3p that are potentially involved in PC progression. These results may provide novel insights into the molecular mechanism underlying CRPC cells and miRNA applications may constitute a new and alternative method to prevent development of CRPC cells in the future.

Biochemical recurrence after radical prostatectomy: is the disease or the surgeon to blame?

PURPOSE: The PSA recurrence develops in 27 to 53% within ten years after radical prostatectomy (RP). We investigated the factors (disease grade and stage or the surgeon's expertise,) more likely to influence biochemical recurrence in men post-radical prostatectomy for organ-confined prostate cancer by different surgeons in the same institution. MATERIALS AND METHODS: A total of 510 patients that underwent radical prostatectomy were investigated retrospectively. Biochemical recurrence was defined as detection of a PSA level of ≥ 0.20 ng/mL by two subsequent measurements. The causes, which are likely to influence the development of PSA recurrence, were separated into two groups as those related to the disease and those related to the surgical technique. RESULTS: Biochemical recurrence was detected in 23.5% (120 cases) of 510 cases. The parameters most likely to influence biochemical recurrence were: PSA level (p < 0.0001), T stage (p < 0.0001), the presence of extracapsular invasion prostate (p < 0.0001), Gleason scores (p = 0.042, p < 0.0001) and the presence of biopsy with perineural invasion (p = 0.03). The only surgical factor that demonstrated relevance was inadvertent capsular incision during the surgery that influenced the PSA recurrence (p < 0.0001). CONCLUSION: The PSA recurrence was detected in 21.6% of patients who had been treated with radical prostatectomy within 5 years, which indicates that the parameters related to the disease and the patient have a pivotal role in the PSA recurrence.

Is it possible to predict sepsis, the most serious complication in prostate biopsy?

OBJECTIVE: Prostate biopsy for the diagnosis of prostate cancer by transrectal ultrasonography (TRUS) is a common procedure used in daily urology practice with a low complication rate and easy applicability. In this study, the precipitating factors and prophylaxis for sepsis, the worst complication of the procedure, were assessed. PATIENTS AND METHODS: 2,023 Patients with suspected prostate cancer who underwent biopsy by TRUS in one center were assessed retrospectively. The relationship between sepsis and age, serum total prostate-specific antigen (PSA) level, PSA density, prostate volume, number of biopsies, number of repeated biopsies, accompanying diagnosis of prostatitis, presence of urethral catheter, and presence of diabetes mellitus was assessed. Data were analyzed using the t test and logistic regression analysis. RESULTS: Of the 2,023 patients, 62 (3.06%) developed sepsis within 5 days after biopsy. There was no significant relationship between the biopsy and the above parameters using the logistic regression analysis. Using the t test, it was found that the number of biopsy cores (p < 0.001), presence of urethral catheter (p < 0.0001), and presence of diabetes mellitus (p < 0.0001) were predictive factors for sepsis. CONCLUSION: Sepsis is a rare but life-threatening complication after prostate biopsy by TRUS. Although preoperative prophylactic oral antibiotics and enema before biopsy have proven to be effective in decreasing urinary tract infection rates, patients with urethral catheter, diabetes mellitus or those to undergo biopsy from more sites than ten cores should be closely monitored after biopsy.

Comparison of the efficacy of single or double intravesical epirubicin instillation in the early postoperative period to prevent recurrences in non-muscle-invasive urothelial carcinoma of the bladder: prospective, randomized multicenter study.

OBJECTIVES: To investigate the efficacy of single or double epirubicin instillation during the early postoperative period (EPP) in intermediate-risk non-muscle-invasive urothelial cancer. METHODS: Patients with primary and solitary or multiple (3 or less) Ta (grade 2-3) or T1 (grade 1-2) tumors were enrolled. Patients were randomized to receive either a single dose of 100 mg epirubicin instillation within 6 h or a second 100 mg epirubicin instillation during the 12th-18th hours after a complete TUR-BT. At the end of the 60-month follow-up period, the available data were statistically analyzed. The end-points of the study were determined as disease-free survival, progression and recurrence rates, time to recurrence, and time to progression. RESULTS: A total of 299 patients from 24 institutions were randomized between January 2002 and June 2004. There were 143 patients from 18 institutions who met the eligibility criteria. The follow-up and disease-free survival periods were 16.9 months and 16 months, respectively. There was no statistical difference in the demographic properties and the end-points between the groups. CONCLUSIONS: A single dose of intravesical 100 mg epirubicin chemotherapy during the early postoperative period for primary intermediate-risk non-muscle-invasive urothelial cancer achieved 16 months of mean disease-free survival. A second intravesical epirubicin instillation did not provide any significant benefit.

Correlation of Prostate-Imaging Reporting and Data Scoring System scoring on multiparametric prostate magnetic resonance imaging with histopathological factors in radical prostatectomy material in Turkish prostate cancer patients: a multicenter study of the Urooncology Association.

BACKGROUND: Histopathological features after radical prostatectomy (RP) provide important information for the prognosis of prostate cancer (PCa). The possible correlations between Prostate-Imaging Reporting and Data Scoring System (PIRADS) scores in multiparametric magnetic resonance imaging (mpMRI) may also be predictive for prognosis. In this study, we aimed to evaluate the correlation of PIRADS scores with histopathological data. METHODS: A total of 177 patients who underwent preoperative mpMRI and RP for PCa from eight institutions were included in the study. Correlation of PIRADS score in preoperative mpMRI with adverse histopathological factors in RP specimen was investigated using univariate and multivariate analyses. RESULTS: The relationship between PIRADS score and postoperative extracapsular extension, lymphovascular invasion, and seminal vesicle involvement was significant (P < 0.001, P = 0.032, and P = 0.007, respectively). Although the PIRADS score was significantly correlated with the number of dissected lymph nodes (p = 0.026), it had no significant correlation with the number of positive nodes (P = 0.611). Total Gleason score, extracapsular extension, seminal vesicle invasion, and number of lymph nodes were found to be independent factors, which correlated with high PIRADS scores in ordinal logistic regression analysis. CONCLUSION: PIRADS scoring system in mpMRI showed a statistically significant correlation with adverse histopathological factors in RP specimen. A higher PIRADS score may help to predict a higher Gleason score, indicating clinically important PCa as well as poor prognotic factors such as extracapsular extension, lymphovascular invasion, and seminal vesicle invasion that may indicate a higher risk of recurrence and the need for additional treatment.

Cancer Stem Cells in Urooncology.

The aging of society has led to an increase in the incidence of urological cancers. Surgery, radiotherapy, and chemotherapeutic agents are widely used treatment options, in addition to minimally invasive new therapeutical approaches developed in the past decade. Unfortunately, we are still a long way from preventing mortality due to urological cancers or to achieving long-term progression-free disease control. Extensive research in recent years has established the presence of a relatively small population of cancer stem cells, which may be targeted to reach these goals. Mounting evidence points to the role of CSCs in metastasis, treatment resistance, and recurrence. In this chapter, we review the presence of CSCs in bladder, prostate, and kidney cancers with emphasis on their identification and clinical relevance.

P21 and p27 Immunoexpression in Upper Urinary Tract Urothelial Carcinomas.

p21 and p27 are members of cyclin-dependent kinase family, which function as tumor suppressors and they are involved in development and progression of several malignancies. We investigated their expression in upper urinary tract urothelial carcinoma (UUTUC). Radical nephroureterectomy materials of 34 patients were assessed by immunohistochemistry to evaluate expression of p21 and p27 in UUTUC. Results were correlated with various clinicopathological variables as age, gender, tumor grade and stage, tumor architecture, multifocality, subsequent bladder carcinoma development and clinical outcome.p21 and p27 expression was observed in 52.9 % (n = 18) and 88.2 % (n = 30), respectively. A total of 21 tumors (61.7 %) showed either total loss of p21 expression (n = 16, 47 %) or lower expression (n = 5, 14.7 %). No correlation was found between p21 expression and clinicopathologic variables. Cases showing total loss or lower p27 expression (11.7 % and <25.6 %, respectively) (n = 19, 55.8 %) constituted 67.6 % (n = 23) of the cases totally. This loss or lower p27 expression correlated with a shorter overall survival in both univariate and multivariate analysis (p = 0.039 and p = 0.037, respectively). None of the noninvasive tumors (papillary and nodular tumors) showed loss of p27 (p = 0.016) while 33.3 % of invasive ones showed p27 loss. Noninvasive tumor architecture also correlated with subsequent bladder carcinoma development (p = 0.032) while invasive tumor architecture correlated with advanced stage (T3 and T4) (p = 0.003). p27 is widely expressed in UUTUC, while p21 expression is observed in half of the cases. Loss of p27 expression correlated with tumor architecture and overall survival in UUTUC. However, further research is needed to assess their role in UUTUC.

Does skip metastasis or other lymph node parameters have additional effects on survival of patients undergoing radical cystectomy for bladder cancer?

PURPOSE: To investigate the effects of lymph node metastasis, skip metastasis, and other factors related to lymph node status on survival in patients who underwent radical cystectomy (RC) and extended lymph node dissection (eLND). MATERIALS AND METHODS: RC and eLND were performed in 85 patients with a diagnosis of bladder cancer. Disease-free survival (DFS) and overall survival (OS) were determined by using a Cox proportional hazards model that included the number of excised lymph nodes, the presence of pathological lymph node metastasis, the anatomical level of positive nodes, the number of positive lymph nodes, lymph node density, and the presence of skip metastasis. RESULTS: The mean number of lymph nodes removed per patient was 29.4±9.3. Lymph node positivity was detected in 85 patients (34.1%). The mean follow-up duration was 44.9±27.4 months (2-93 months). Five-year estimated OS and DFS for the 85 patients were 62.6% and 57%, respectively. Three of 29 lymph node-positive patients (10.3%) had skip metastasis. Only lymph node positivity had a significant effect on 5-year OS and DFS (p<0.001). No difference in OS and DFS was found between the three patients with skip metastasis and other lymph node-positive patients. Other factors related to lymph node status had no significant effect on 5-year OS and DFS. CONCLUSIONS: No factors related to lymph node status predict DFS and OS, except for lymph node positivity. OS and DFS were comparable between patients with skip metastasis and other lymph node-positive patients.

Induced growth inhibition, cell cycle arrest and apoptosis in CD133+/CD44+ prostate cancer stem cells by flavopiridol.

Flavopiridol is a flavone that inhibits several cyclin­dependent kinases and exhibits potent growth­inhibitory activity, apoptosis and G1­phase arrest in a number of human tumor cell lines. Flavopiridol is currently undergoing investigation in human clinical trials. The present study focused on the effect of flavopiridol in cell proliferation, cell cycle progression and apoptosis in prostate cancer stem cells (CSCs). Therefore, cluster of differentiation 133 (CD133)(+high)/CD44(+high) prostate CSCs were isolated from the DU145 human prostate cancer cell line. The cells were treated with flavopiridol in a dose­ and time­dependent manner to determine the inhibitory effect. Cell viability and proliferation were analyzed and the efficiency of flavopiridol was assessed using the sphere­forming assay. Flavopiridol was applied to monolayer cultures of CD133(high)/CD44(high) human prostate CSCs at the following final concentrations: 100, 300, 500 and 1000 nM . The cultures were incubated for 24, 48 and 72 h. The half maximal inhibitory concentration (IC(50)) value of the drug was determined as 500 nM for monolayer cells. Dead cells were analyzed prior and subsequent to exposure to increasing flavopiridol doses. Annexin­V and immunofluorescence analyses were performed for the evaluation of apoptotic pathways. According to the results, flavopiridol treatment caused significant growth inhibition at 500 and 1000 nM when compared to the control at 24 h. G(0)/G(1) analysis showed a statistically significant difference between 100 and 500 nM (P<0.005), 100 and 1000 nM (P<0.001), 300 and 1000 nM (P<0.001), and 500 and 1000 nM (P<0.001). Flavopiridol also significantly influenced the cells in the G(2)/M phase, particularly at high­dose treatments. Flavopiridol induced growth inhibition and apoptosis at the IC(50) dose (500 nM), resulting in a significant increase in immunofluorescence staining of caspase­3, caspase­8 and p53. In conclusion, the present results indicated that flavopiridol could be a useful therapeutic agent for prostate CSCs by inhibiting tumor growth and malignant progression, and inducing apoptosis.

Public awareness of testicular cancer and self-examination in Turkey: a multicenter study of Turkish Urooncology Society.

BACKGROUND: Testicular self-examination is the easiest and cheapest way to scan testicular cancer. However, the public awareness about testicular self-examination is very low. We aimed to investigate the public awareness of Turkish people about testicular cancer and testicular self-examination. METHODS: We performed a survey consisting of 10 questions concerning testicular cancer and testicular self-examination in 799 students in the first year of 12 different medical schools. Aiming for a common method of data collection, the questionnaires were administered to the students during a class just before the lesson started. The whole data from all of the centers were pooled in a common data-base file. RESULTS: Eighty-nine (11.1%) of the participants reported that they had knowledge about testicular cancer, but only 11 (1.4%) of them answered all the questions about testicular cancer correctly. Eight (1%) of the participants reported that they had been performing testicular self-examination routinely once a month. Four (0.5%) of them were both well informed about testicular cancer and had been performing testicular self-examination once a month as suggested. CONCLUSION: The present study showed that awareness on testicular cancer and testicular self-examination is very low and suggests a need for efforts in Turkey to increase public awareness and education.

A prospective randomized multicenter study of Turkish Society of Urooncology comparing two different mechanical bowel preparation methods for radical cystectomy.

OBJECTIVE: To investigate the outcomes and complication rates of urinary diversion using mechanical bowel preparation (BP) with 3 day conventional and limited BP method through a standard perioperative care plan. MATERIALS AND METHODS: This study was designed as a prospective randomized multicenter trial. All patients were randomized to 2 groups. Patients in standard 3-day BP protocol received diet restriction, oral antibiotics to bowel flora, oral laxatives, and saline enemas over a 3-day period, whereas limited the BP arm received liberal use of liquid diet, sodium phosphate laxative, and self administered enema the day before surgery. All patients received same perioperative treatment protocol. The endpoints for the assessment of outcome were anastomotic leakage, wound infection, wound dehiscence, intraperitoneal abscess, peritonitis, sepsis, ileus, reoperation, and mortality. Bowel function recovery, including time to first bowel movement, time to first oral intake, time to regular oral intake, and length of hospital stay were also assessed. RESULTS: Fifty-six patients in 3-day BP and 56 in limited BP arm were evaluable for the study end points. Postoperatively, 1 patient in limited BP and 2 patients in 3-day BP arm died. There was no statistical difference in any of the variables assessed throughout the study, however, a favorable return of bowel function and time to discharge as well as lower complication rate were observed in limited BP group. CONCLUSIONS: Regarding all endpoints, including septic and nonseptic complications, current clinical research offers no evidence to show any advantage of 3-day BP over limited BP.

Impact of Residual Fragments following Endourological Treatments in Renal Stones.

Today, shock wave lithotripsy (SWL), percutaneous nephrolithotomy (PCNL), and flexible ureterorenoscopy (URS) are the most widely used modalities for the management of renal stones. In earlier series, treatment success of renal calculi assessed with KUB radiography, ultrasound, or intravenous pyelography which are less sensitive than CT that leads to be diversity of study results in reporting outcome. Residual fragments (RFs) after interventional therapies may cause pain, infection, or obstruction. The size and location of RFs following SWL and PCNL are the major predictors for clinical significant symptoms and stone events requiring intervention. There is no consensus regarding schedule for followup of SWL, PCNL, and flexible URS. Active monitoring can be recommended when the stones become symptomatic, increase in size, or need intervention. RFs <4 mm after SWL and <2 mm after PCNL and flexible URS could be actively monitored on an annual basis with CT. Early repeat SWL and second-look endoscopy are recommended after primary SWL and PCNL, respectively. There is insufficient data for flexible URS, but RFs can be easily treated with repeat URS. Finally, medical therapy should be tailored based on the stone analysis and metabolic workup that may be helpful to prevent regrowth of the RFs.

Prognostic factors for upper urinary tract urothelial carcinomas: stage, grade, and smoking status.

OBJECTIVES: Upper urinary tract urothelial carcinomas are relatively rare malignancies. The aim of this study was to investigate the factors affecting prognosis of patients undergoing nephroureterectomy. METHODS: Data of 140 patients undergoing nephroureterectomy were retrospectively analyzed. Age of patients, gender, focality and localization of tumor, clinical and pathological stage, relationship with bladder cancer (prior, synchronous, after), and history of smoking were retrospectively recorded. The condition of local recurrence, metastases to distant organs, and requirement of adjuvant treatment were evaluated. RESULTS: The disease-specific and recurrence-free 5-year survival rate was determined as 78.9 and 68.4%, respectively. Bladder recurrence was determined in 20 of the patients after a mean of 21 months (7-37 months). Relationship between the duration of recurrence and variables showed that patients with T2 and higher stages (P = 0.014), with high-grade tumors (P = 0.028), with multifocal tumors (P < 0.001), and patients who were cigarette smokers (P = 0.010) had significantly shorter durations of recurrence. The mean survival of the 19 (18.1%) patients who had distant metastases was 19 months. Pathological stage T2 and higher tumors (P = 0.006), nodal involvement (P = 0.04), high-grade urothelial carcinoma (P < 0.001), multifocal tumors (P < 0.001), and tumors localized in the ureter (P < 0.001) were observed to have shorter duration of metastatic development. CONCLUSIONS: Presence of T2 and higher-stage tumors, high-grade tumors, and multifocality are combined risk factors for urinary bladder recurrence and distant organ metastasis. Patients with the additional risk factors of cigarette smoking (urinary bladder recurrence) and nodal disease (distant organ metastasis) should be followed up closely after surgery.

Bowel preparation and peri-operative management for radical cystectomy in Turkey: Turkish Urooncology Association multicenter survey.

PURPOSE: To investigate the preferences and practice patterns of urooncologic surgeons in Turkey on bowel preparation and peri-operative management for radical cystectomy. MATERIALS AND METHODS: This study was conducted by Turkish Urooncology Association as a multicenter survey. Participants were asked to fill in questionnaires dispensed at annual oncologic meeting or using internet access to the website of Urooncology Association. The questionnaire consisted of multiple choice or open-ended questions related to frequency of cystectomy, surgical technique and type of diversion, bowel preparation protocol, nasogastric tube applications, antibiotic prophylaxis, and deep vein thrombosis prophylaxis. Collected data from the survey were presented descriptively. RESULTS: Forty-four questionnaires from 44 surgeons of different centers were evaluated. All participants answered that they always perform bowel preparation before cystectomy. Four participants reported that they had an experience of cystectomy without bowel preparation. Bowel preparation methods included long conservative methods, short enema protocols, and Golytely, but there were significant differences in application of each method. Of participants, 88.6% perform diversion by themselves whereas others ask help from a general surgeon. Antibiotic prophylaxis is preferred mostly by 2 agents using third-generation cephalosporins and metronidazole for a period of 5 days or more in the majority. Type, duration, and dosage of deep vein thrombosis prophylaxis differed among participants. CONCLUSION: There are significant individual differences in peri-operative management of radical cystectomy, which render deficient and sometimes inadequate patient care. There is a need to establish standard protocols for bowel preparation and adequate peri-operative management for radical cystectomy.

Prevalence of prostate cancer among men aged 40+ living in Osman Gazi health care district.

BACKGROUND: Prostate cancer is a risk for men aged 40+ even if it is rarely seen among men under the age of 50. It is asymptomatic disease in its early period and if the person does not have an enlarged prostate it will be overlooked without screening. Consequently, the only way to diagnose prostate cancer in its early period is to determine the serum PSA (prostate-specific antigen) level of men aged 40+ and to do a digital rectal examination (DRE). OBJECTIVE: The aim of this study is to determine the prevalence of prostate cancer among men aged 40+, to mention the significance of DRE and PSA by means of a training to be done with the aid of a booklet about early diagnosis, and to encourage men to consult a doctor and get the right treatment at the right time. METHODS: The research was a descriptive field study. carried out among 660 men aged 40+ out of 3,285 men who live in Osman Gazi Health Care District, connected with the Presidency of Training and Research Health Group of Bornova. This group was selected as the smallest sample size by the systematic sampling method within the frame of setting the prevalence of prostate cancer at 10%, the confidence interval as 95%, the standard error as 2%. A total of 264 men of the sample group (participation rate 40%) agreed to a survey of International Prostate Symptom Score (I-PSS) projected by the study, and underwent DRE and PSA with a blood sample. RESULTS: Increase in the serum PSA level (4 ng/mL<) was determined in 10 men. Nodules were detected in 3 men together with the increase in PSA. One further nodule was detected only in DRE one examination of 12 participants. In the light of these data, it was decided to conduct a biopsy on 25 people, who had an increase in PSE and/or whose abnormalities were detected during DRE, in company with TRUS, and prostate cancer was detected in the biopsies of 5 people (1.89%). CONCLUSIONS: It can be thought that before a decision is made on routinizing prostate cancer screening, it may be more suitable to make randomized controlled screening trials for prostate cancer.

Incidence and epidemiological features of cancers of the genitourinary tract in Izmir between 1993-2002.

BACKGROUND: There is a relative lack of epidemiological data on cancer in Turkey, which is a large country with its 71 million population, since there was not any population-based registry functioning in the country before Izmir Cancer Registry (ICR), which was founded in 1992. The present study focused on the incidence of cancers of the genitourinary tract in Izmir province over a ten year period to cover the gap in this kind of epidemiological data for this part of the world. METHODS: ICR is a population-based registry which collects data actively and is running international registration rules during procedures. We evaluated the data for 1993-2002. Annual crude and age-standardized incidence rates were calculated for the whole period and also for earlier and later periods. RESULTS: The age-standardized incidence rate (world population) for all sites was 198.3 per 100,000 for males and 116.4 per 100,000 for females. The most common primary sites for men were lung (35.6%), bladder (7.8%), colon and rectum (6.1%), larynx (5.7%) and prostate (5.4%). For women, the principal cancers were breast (28.7%), colon and rectum (7.2%), corpus uteri (5.3%), cervix uteri (4.8%) and lung (4.7%). Urogenital cancers accounted for 11.2% of all new cancer cases for the 1993-2002 period in Izmir. Of all urologic cancer cases, 89.6% were in males and 10.4% were in females. Carcinoma of the bladder was the first among the urogenital cancers in Izmir province (Age standardized incidence rate, world standard population ,17.1 per 100 000). CONCLUSIONS: Bladder cancer incidences were quite high, especially for men, and appear to be increasing. Prostate cancer has lower incidence rates as compared to western countries but the trend is for rise. There might be an underestimate of incidences, owing to an inability to use data from death certificates. Even so, the overall profile is an accurate reflection of incidence in this region of Turkey and provides much of the information required for planning strategies for cancer control.

Validation of two preoperative Kattan nomograms predicting recurrence after radical prostatectomy for localized prostate cancer in Turkey: a multicenter study of the Uro-oncology Society.

OBJECTIVES: To examine, in a multicenter validation study designed under the guidance of the Uro-Oncology Society, the predictive accuracies of the 1998 and 2006 Kattan preoperative nomograms in Turkish patients. These 2 preoperative Kattan nomograms use preoperative parameters to estimate disease recurrence after radical prostatectomy. METHODS: A total of 1261 men with clinically localized prostate cancer undergoing radical prostatectomy were included. The preoperative prostate-specific antigen level, biopsy Gleason score, clinical stage, number of positive and negative prostate biopsy cores, and postoperative recurrence status of all patients were studied. The predicted values using the Kattan nomograms and the observed values were compared. RESULTS: The patient characteristics in the cohort were comparable with those of the cohorts used to create the Kattan nomograms. The 5-year probability of freedom from recurrence was 73% using Kaplan-Meier analysis and was similar to that of the 1998 Kattan nomogram cohort. However, the 10-year probability of freedom from recurrence was 67%, slightly lower than the same estimate from the 2006 nomogram cohort. The predicted values of recurrence using Kattan nomogram and the observed rates in our cohort were similar. The estimated concordance index value was 0.698 and 0.705 for 1998 and 2006 nomograms, respectively. CONCLUSIONS: The Kattan preoperative nomograms can be used with adequate success in Turkey, because the predicted and observed rates in our cohort were similar. Our results have demonstrated satisfactory concordance index values, suggesting that both the 1998 and the 2006 Kattan preoperative nomograms can safely be used in Turkish patients with similar accuracy. Although the 2006 nomogram had slightly better discrimination, the 1998 nomogram was a little more calibrated.

Zoledronic acid effects interleukin-6 expression in hormone-independent prostate cancer cell lines.

OBJECTIVE: To investigate the inhibitory effects of zoledronic acid (ZA) on tumor related growth factor IL-6 in hormone resistant prostate cancer cell lines. The association between apoptosis and IL-6 inhibition was also assessed. MATERIALS AND METHODS: PC-3 and DU145 cell lines were treated with different concentrations of ZA (1-100 microM) at various intervals (24-72 h.). The cell viability was investigated by XTT assay and apoptotic effect was evaluated by cell death detection ELISA kit. Caspase 3/7 activity assay was performed to confirm apoptosis. IL-6 levels were measured by ELISA in the supernatant, and these data were also confirmed by IL-6 mRNA analysis using RT-PCR. RESULTS: PC-3 and DU145 cell lines were sensitive to ZA mediated cytotoxicity in a dose- and time-dependent manner. However, the apoptotic effect was significantly different among PC-3 and DU145 cells (p<0.05). IL-6 secretion was significantly lower in both cell lines, compared to the untreated control cells (p<0.05). Although the increased inhibition of IL-6 secretion was associated with increased apoptosis in DU145 cells (p=0.002), there was no similar association for PC-3 cell line (p=0.347). When compared to the untreated controls, the number of cDNA copies was significantly lower in the ZA treated DU145 cell line at doses of 30 and 90 microM (p<0.05), suggesting a reduced expression of IL-6 mRNA. CONCLUSION: ZA exhibited a time- and dose-dependent apoptotic effect on PC-3 and DU145 prostate cancer cell lines and this effect was associated with inhibited secretion of IL-6 in DU145 cell line.

Why do men refuse prostate cancer screening? Demographic analysis in Turkey.

Prostate cancer is one of the most common cancers in men, with a high incidence rates in Turkey. However, the early detection and diagnosis rates are considerably lower among Turkish men as compared with their counterparts in Western countries. This fact reflects a lack of awareness and fear of prostate cancer as well as low prevention activities. To reduce the disparities in prostate cancer survival, there is a great need to increase men's participation in screening programs. The present study was performed to assess why men do not seek screening or participate in screening programs, focusing on the demographics of men refusing a free screening program for prostate cancer.