Prevalence and incidence of clinical symptoms of the retroaortic left renal vein.

OBJECTIVE: To analyze the prevalence and incidence of clinical symptoms of retroaortic left renal vein (RLRV) diagnosed incidentally over 10 years by computed tomography (CT). PATIENTS AND METHODS: 7,929 consecutive patients (out- and inpatients) were studied with multidetector CT from January 2000 to April 2011. We retrospectively reviewed RLRV patients' medical records and analyzed their clinical characteristics. RESULTS: A total of 61 out of 7,929 patients had a RLRV, therefore the prevalence was 0.77%. Only 4 of 61 (6.6%) RLRV patients diagnosed by CT scan were clinically symptomatic. RLRV was associated with flank pain and microhematuria in one patient (1.6%), in another one with microhematuria only and in one with ureteropelvic junction obstruction. Furthermore, one patient suffered from arterial hypertension associated with a RLRV. CONCLUSIONS: RLRV is a rare finding, and only a small minority of RLRVs causes symptoms.

Final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Guérin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of maintenance.

BACKGROUND: The optimal dose and duration of intravesical bacillus Calmette-Guérin (BCG) in the treatment of non-muscle-invasive bladder cancer (NMIBC) are controversial. OBJECTIVE: To determine if a one-third dose (1/3D) is not inferior to the full dose (FD), if 1 yr of maintenance is not inferior to 3 yr of maintenance, and if 1/3D and 1 yr of maintenance are associated with less toxicity. DESIGN, SETTING, AND PARTICIPANTS: After transurethral resection, intermediate- and high-risk NMIBC patients were randomized to one of four BCG groups: 1/3D-1 yr, 1/3D-3 yr, FD-1 yr, and FD-3 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The trial was designed as a noninferiority study with the null hypothesis of a 10% decrease in the disease-free rate at 5 yr. Times to events were estimated using cumulative incidence functions and compared using the Cox proportional hazards regression model. RESULTS AND LIMITATIONS: In an intention-to-treat analysis of 1355 patients with a median follow-up of 7.1 yr, there were no significant differences in toxicity between 1/3D and FD. The null hypotheses of inferiority of the disease-free interval for both 1/3D and 1 yr could not be rejected. We found that 1/3D-1 yr is suboptimal compared with FD-3 yr (hazard ratio [HR]: 0.75; 95% confidence interval [CI], 0.59-0.94; p=0.01). Intermediate-risk patients treated with FD do not benefit from an additional 2 yr of BCG. In high-risk patients, 3 yr is associated with a reduction in recurrence (HR: 1.61; 95% CI, 1.13-2.30; p=0.009) but only when given at FD. There were no differences in progression or survival. CONCLUSIONS: There were no differences in toxicity between 1/3D and FD. Intermediate-risk patients should be treated with FD-1 yr. In high-risk patients, FD-3 yr reduces recurrences as compared with FD-1 yr but not progressions or deaths. The benefit of the two additional years of maintenance should be weighed against its added costs and inconvenience. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov, number NCT00002990; http://clinicaltrials.gov/ct2/show/record/NCT00002990.

Long-term efficacy results of EORTC genito-urinary group randomized phase 3 study 30911 comparing intravesical instillations of epirubicin, bacillus Calmette-Guérin, and bacillus Calmette-Guérin plus isoniazid in patients with intermediate- and high-risk stage Ta T1 urothelial carcinoma of the bladder.

BACKGROUND: Intravesical chemotherapy and bacillus Calmette-Guérin (BCG) reduce the recurrence rate in patients with stage Ta T1 urothelial bladder cancer; however, the benefit of BCG relative to chemotherapy for long-term end points is controversial, especially in intermediate-risk patients. OBJECTIVE: The aim of the study was to compare the long-term efficacy of BCG and epirubicin. DESIGN, SETTING, AND PARTICIPANTS: From January 1992 to February 1997, 957 patients with intermediate- or high-risk stage Ta T1 urothelial bladder cancer were randomized after transurethral resection to one of three treatment groups in the European Organization for Research and Treatment of Cancer Genito-Urinary Group phase 3 trial 30911. INTERVENTION: Patients received six weekly instillations of epirubicin, BCG, or BCG plus isoniazid (INH) followed by three weekly maintenance instillations at months 3, 6, 12, 18, 24, 30, and 36. MEASUREMENTS: End points were time to recurrence, progression, distant metastases, overall survival, and disease-specific survival. RESULTS AND LIMITATIONS: With 837 eligible patients and a median follow-up of 9.2 yr, time to first recurrence (p<0.001), distant metastases (p=0.046), overall survival (p=0.023), and disease-specific survival (p=0.026) were significantly longer in the two BCG arms combined as compared with epirubicin; however, there was no difference for progression. Three hundred twenty-three patients with stage T1 or grade 3 tumors were high risk, and the remaining 497 patients were intermediate risk. The observed treatment benefit was at least as large, if not larger, in the intermediate-risk patients compared with the high-risk patients. CONCLUSIONS: In patients with intermediate- and high-risk stage Ta and T1 urothelial bladder cancer, intravesical BCG with or without INH is superior to intravesical epirubicin not only for time to first recurrence but also for time to distant metastases, overall survival, and disease-specific survival. The benefit of BCG is not limited to just high-risk patients; intermediate-risk patients also benefit from BCG. TRIAL REGISTRATION: This study was registered with the US National Cancer Institute clinical trials database [protocol ID: EORTC-30911]. http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=77075&version=HealthProfessional&protocolsearchid=6540260.

PSA testing in Austria: induced morbidity and saved mortality.

Opportunistic screening of healthy men by prostate-specific antigen (PSA) testing led to a steep increase of prostate cancer incidence in Austria. The objective of this study was to quantify how many additional men are diagnosed with prostate cancer by PSA testing, to save one man from prostate cancer death. Regression models for incidence and mortality for the time periods 1983-1991 and 1992-2003 by age groups 50-59 and 60-69 years were estimated. For 1992-2003, expected numbers of incidence and mortality were calculated. The first estimates for the years 1992-2003 were calculated using the regression model including the years 1983-1991. The second estimates were also calculated using the regression model, but including only the years 1992-2003. The difference between estimates was then summed up for 1992-2003. The corresponding sums of incidence and mortality were compared to provide estimates for the effect of the introduction of PSA screening on incidence/mortality ratio. According to our calculation for the time period 1992-2003, in age group 50-69 years, a total of 512 expected prostate cancer deaths were prevented because of opportunistic PSA screening, whereas PSA testing identified a total of 9648 additional men with asymptomatic prostate cancer. In conclusion, to save one man in the age group 50-69 years in the time period 1992-2003 from prostate cancer death by PSA testing, a total of 18.8 men with asymptomatic prostate cancer had to be identified. Although this study probably underestimates the benefit (reduced mortality) and overestimates excess incidence of prostate cancer, it is far from sure that in all of these additionally identified men prostate cancer would ever have surfaced as a clinical disease, if not screened for.

European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): part II.

OBJECTIVES: The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, The Netherlands. METHODS: Medical oncologists, urologic surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference and incorporated the new data into updated and revised guidelines. As for the first meeting the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. RESULTS: The second part of the consensus paper includes the treatment of metastasised disease, residual tumour resection, salvage therapy, follow-up, and late toxicities. CONCLUSIONS: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early-stage as well as of advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged.

European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus group (EGCCCG): part I.

OBJECTIVES: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, Amsterdam, The Netherlands. METHODS: Medical oncologists, urological surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference, and incorporated the new data into updated and revised guidelines. As for the first meeting, the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. RESULTS: The first part of the consensus paper describes the clinical presentation of the primary tumor, its treatment, the importance and treatment of testicular intraepithelial neoplasia (TIN), histological classification, staging and prognostic factors, and treatment of stage I seminoma and non-seminoma. CONCLUSIONS: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early- and advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged.

Effect of NIH-IV prostatitis on free and free-to-total PSA.

OBJECTIVE: To examine the effect of asymptomatic prostatic inflammation (NIH category IV prostatitis) on total PSA (tPSA), free serum PSA (fPSA) and the ratio of free-to-total prostate specific antigen (%fPSA). The role of free and %fPSA as a diagnostic tool for distinguishing between cancer and non-malignant diseases of the prostate was also investigated. MATERIAL AND METHODS: In a retrospective study 1090 prostate biopsies performed between January 2000 and September 2003 were evaluated and the levels of serum total and free PSA as well as the f/tPSA ratio were determined in samples obtained immediately before biopsy. 404 patients with full clinical and histological records were included in the study. All patients underwent 6 or 8 core primary prostate needle biopsies. RESULTS: A total of 404 patients were included in the analysis. 100 prostate cancer (PCa) (24.8%), 137 NIH-IV prostatitis (33.9%) and 143 patients with benign prostatic hyperplasias (BPH) (35.4%) were identified. 24 (5.9%) patients presented with both PCa and prostatitis on histology and were excluded from further analysis. The mean (median) levels of tPSA, fPSA and %fPSA were 11.94 ng/ml (8.0), 1.31 ng/ml (1.07) and 0.15 (0.14) for NIH-IV prostatitis; 11.94 ng/ml (8.35), 1.54 ng/ml and 0.13 (0.11) for prostate cancer; and 8.19 ng/ml (7.0), 1.48 ng/ml (1.03) and 0.18 (0.15) for BPH. No significant difference was found in tPSA levels between PCa and prostatitis (p = 0.32), while the difference in tPSA levels between PCa and BPH was significant (p = 0.007). Free PSA alone had no diagnostic power in distinguishing PCa from prostatitis (p = 0. 37) and BPH (p = 0. 61). By contrast, the f/tPSA ratio showed significant between-group differences (PCa versus prostatitis (p = 0. 011), PCa versus BPH (p = 0.0001). CONCLUSIONS: Chronic asymptomatic prostatitis NIH category IV has similar effects on total PSA and free PSA levels in serum as PCa. fPSA alone cannot distinguish prostate cancer from non-malignant inflammatory disease of the prostate. The ratio of free-to-total PSA is significantly different in PCa and NIH category IV prostatitis.

The side effects of Bacillus Calmette-Guerin in the treatment of Ta T1 bladder cancer do not predict its efficacy: results from a European Organisation for Research and Treatment of Cancer Genito-Urinary Group Phase III Trial.

OBJECTIVES: Previous publications have suggested that patients developing local and/or systemic side effects to Bacillus Calmette-Guerin (BCG) have a better clinical result, however it is necessary to determine if toxicity is responsible for improved efficacy. METHODS: After transurethral resection, intravesical instillations of BCG were given during a 6-week induction course followed by 3-weekly maintenance courses at 3, 6, 12, 18, 24, 30 and 36 months. The prognostic importance of delaying or stopping BCG due to local and/or systemic side effects was assessed in 487 patients. RESULTS: Patients with local BCG side effects had a significantly longer time to first recurrence, suggesting that side effects are related to efficacy. However patients with a better outcome remain on study for a longer period of time and receive more BCG, thus increasing their risk to develop side effects. To prove whether toxicity is responsible for improved efficacy, the prognostic importance of toxicity occurring prior to the 6 month instillations was assessed using the landmark method. Neither local nor systemic BCG toxicity prior to 6 months was related to subsequent recurrence. CONCLUSIONS: While a correlation between BCG toxicity and efficacy exists, this study does not confirm that BCG toxicity is actually responsible for an improved outcome.

Maintenance Bacillus Calmette-Guerin for Ta T1 bladder tumors is not associated with increased toxicity: results from a European Organisation for Research and Treatment of Cancer Genito-Urinary Group Phase III Trial.

OBJECTIVES: After transurethral resection, the local and systemic side effects of Bacillus Calmette-Guerin (BCG) instillations were assessed during a 6-week induction course followed by 3 weekly maintenance instillations at 3, 6, 12, 18, 24, 30 and 36 months to determine if BCG toxicity increases over time. METHODS: 487 patients who received BCG in a multicenter phase III trial were included. Side effects were divided into 5 different treatment periods: the first 6 weeks induction, months 3 and 6, month 12, the second year, and the third year. RESULTS: 99 (20.3%) patients stopped BCG due to side effects. 72 (14.8%) stopped due to local side effects, including 59 for BCG induced cystitis, 33 during the first 6 months. 46 (9.4%) stopped due to systemic side effects: 23 due to fever, 19 within 6 months, and 15 due to general malaise, 12 within 6 months. 68% who stopped due to side effects did so during the first 6 months. The percent stopping after 6 months due to local side effects does not increase and actually decreases for systemic side effects. CONCLUSIONS: The majority of local and systemic side effects are seen already during the induction and the first half-year of maintenance. During further maintenance BCG toxicity does not increase and instillations are generally well tolerated.