J.A. Witjes

Variability in the Recurrence Rate at First Follow-up Cystoscopy after TUR in Stage Ta T1 Transitional Cell Carcinoma of the Bladder: A Combined Analysis of Seven EORTC Studies

OBJECTIVES To assess the variability between institutions in the recurrence rate at the first follow-up cystoscopy (RR-FFC) after transurethral resection (TUR) in patients with stage Ta T1 bladder cancer. METHODS A total of 2410 patients from seven EORTC phase III trials conducted between 1979 and 1989 were included. Patients with single and with multiple tumors were analyzed separately according to whether or not they received adjuvant intravesical treatment. RESULTS The RR-FFC varied greatly between institutions. For patients with a single tumor, it ranged from 3.4% to 20.6% for patients not receiving any intravesical adjuvant treatment and from 0% to 15.4% in those receiving it. In patients with multiple tumors who had adjuvant treatment, it varied between 7.4% and 45.8%. There was a slight decrease over time in the recurrence rate for patients with single tumors, particularly in those receiving adjuvant intravesical treatment. CONCLUSIONS For both patients with single and with multiple tumors, the percentage of patients with a recurrence in the bladder at the first follow-up cystoscopy after TUR varies substantially between institutions and cannot be explained by the factors that were assessed. It is suggested that the quality of the TUR performed by the individual surgeons may be responsible.

Relationship between Apparent Diffusion Coefficients at 3.0-T MR Imaging and Gleason Grade in Peripheral Zone Prostate Cancer

PURPOSE To retrospectively determine the relationship between apparent diffusion coefficients (ADCs) obtained with 3.0-T diffusion-weighted (DW) magnetic resonance (MR) imaging and Gleason grades in peripheral zone prostate cancer. MATERIALS AND METHODS The requirement to obtain institutional review board approval was waived. Fifty-one patients with prostate cancer underwent MR imaging before prostatectomy, including DW MR imaging with b values of 0, 50, 500, and 800 sec/mm(2). In prostatectomy specimens, separate slice-by-slice determinations of Gleason grade groups were performed according to primary, secondary, and tertiary Gleason grades. In addition, tumors were classified into qualitative grade groups (low-, intermediate-, or high-grade tumors). ADC maps were aligned to step-sections and regions of interest annotated for each tumor slice. The median ADC of tumors was related to qualitative grade groups with linear mixed-model regression analysis. The accuracy of the median ADC in the most aggressive tumor component in the differentiation of low- from combined intermediate- and high-grade tumors was summarized by using the area under the receiver operating characteristic (ROC) curve (A(z)). RESULTS In 51 prostatectomy specimens, 62 different tumors and 251 step-section tumor lesions were identified. The median ADC in the tumors showed a negative relationship with Gleason grade group, and differences among the three qualitative grade groups were statistically significant (P < .001). Overall, with an increase of one qualitative grade group, the median ADC (±standard deviation) decreased 0.18 × 10(-3) mm(2)/sec ± 0.02. Low-, intermediate-, and high-grade tumors had a median ADC of 1.30 × 10(-3) mm(2)/sec ± 0.30, 1.07 × 10(-3) mm(2)/sec ± 0.30, and 0.94 × 10(-3) mm(2)/sec ± 0.30, respectively. ROC analysis showed a discriminatory performance of A(z) = 0.90 in discerning low-grade from combined intermediate- and high-grade lesions. CONCLUSION ADCs at 3.0 T showed an inverse relationship to Gleason grades in peripheral zone prostate cancer. A high discriminatory performance was achieved in the differentiation of low-, intermediate-, and high-grade cancer.

Detection of TMPRSS2-ERG Fusion Transcripts and Prostate Cancer Antigen 3 in Urinary Sediments May Improve Diagnosis of Prostate Cancer

Purpose: Early detection of prostate cancer can increase the curative success rate for prostate cancer. We studied the diagnostic usefulness of TMPRSS2-ERG fusion transcripts as well as the combination of prostate cancer antigen 3 (PCA3) RNA and TMPRSS2-ERG fusion transcripts in urinary sediments after digital rectal examination (DRE). Experimental Design: A total of 78 men with prostate cancer–positive biopsies and 30 men with prostate cancer–negative biopsies were included in this study. After DRE, the first voided urine was collected, and urinary sediments were obtained. We used semiquantitative reverse transcription-PCR (RT-PCR) analysis followed by Southern blot hybridization with a radiolabeled probe for the detection TMPRSS2-ERG fusion transcripts in these urinary sediments. A quantitative RT-PCR assay for PCA3 was used to determine the PCA3 score in the same sediments. Results: TMPRSS2-ERG fusion transcripts can be detected in the urine after DRE with a sensitivity of 37%. In this cohort of patients, the PCA3-based assay had a sensitivity of 62%. When both markers were combined, the sensitivity increased to 73%. Especially in the cohort of men with persistently elevated serum prostate-specific antigen levels and history of negative biopsies, the high positive predictive value of 94% of TMPRSS2-ERG fusion transcripts could give a better indication which patients require repeat biopsies. Conclusion: In this report, we used for the first time the combination of the prostate cancer–specific biomarkers TMPRSS2-ERG and PCA3, which significantly improves the sensitivity for prostate cancer diagnosis.

Predictability of Recurrent and Progressive Disease in Individual Patients with Primary Superficial Bladder Cancer

The ultimate goal of prognostic assessment is optimization of individual counseling. Often, however, studies on prognostic factors focus on discriminating between high risk and low risk subgroups without considering the relevance of 1 or more factors for predicting disease outcome in individual patients. We quantified the accuracy of prediction of future recurrences and disease progression in individual patients with primary superficial bladder cancer. The study cohort consisted of 1,674 patients who were followed prospectively between 1983 and 1991 in the Netherlands. By analyzing half of the patients with proportional hazards regression, we computed relative risks of recurrence and progression. A prognostic index score based on these relative risks was then applied to the other half of the patients to determine whether group outcome could be predicted accurately. To assess the accuracy of prediction in individuals we used a method similar to the construction of receiver operating characteristic curves in diagnostic test assessment. The 3-year risk of first recurrence was 55% (95% confidence interval 51 to 59%). The 3-year risk of first progressive disease was 10% (95% confidence interval 8 to 12%). For the risk of first recurrence, tumor stage, tumor extent and multicentricity had statistically significant prognostic ability. Prognostic factors for the risk of disease progression were tumor stage, grade, multicentricity and the result of random biopsies from cystoscopically normal-appearing urothelium. For patients with a prognostic index score that suggested a low risk for recurrent and progressive disease the predicted 3-year risk of first recurrence was still 44% but the predicted 3-year risk of progression was only 3%. For patients with a prognostic index score that suggested a high risk the predicted risks were 74% and 22%, respectively. These predicted risks appeared to be fairly accurate when applied to the other half of our case series. However, in any 2 patients chosen at random the chance that the patient with the worst predicted prognosis would have a shorter recurrence-free and progression-free followup was calculated to be only 58% and 67%, respectively. Although the available prognostic factors in superficial bladder cancer may be useful to identify high risk and low risk subgroups, predictability in individuals is highly inaccurate. More relevant prognostic factors are needed to decrease current overtreatment and undertreatment rates, and to improve the followup policy.

Initial experience of 3 tesla endorectal coil magnetic resonance imaging and 1H-spectroscopic imaging of the prostate.

Rationale and Objectives:We sought to explore the feasibility of magnetic resonance imaging (MRI) of the prostate at 3T, with the knowledge of potential drawbacks of MRI at high field strengths. Material and Methods:MRI, dynamic MRI, and 1H-MR spectroscopic imaging were performed in 10 patients with prostate cancer on 1.5T and 3T whole-body scanners. Comparable scan protocols were used, and additional high-resolution measurements at 3T were acquired. For both field strengths the signal-to-noise ratio was calculated and image quality was assessed. Results:At 3T the signal-to-noise ratio improved. This resulted in increased spatial MRI resolution, which significantly improved anatomic detail. The increased spectral resolution improved the separation of individual resonances in MRSI. Contrast-enhanced time-concentration curves could be obtained with a doubled temporal resolution. Conclusions:Initial results of endorectal 3T 1H-MR spectroscopic imaging in prostate cancer patients showed potential advantages: the increase in spatial, temporal, and spectral resolution at higher field strength may result in an improved accuracy in delineating and staging prostate cancer.

Transition Zone Prostate Cancer: Detection and Localization with 3-T Multiparametric MR Imaging

PURPOSE To retrospectively compare transition zone (TZ) cancer detection and localization accuracy of 3-T T2-weighted magnetic resonance (MR) imaging with that of multiparametric (MP) MR imaging, with radical prostatectomy specimens as the reference standard. MATERIALS AND METHODS The informed consent requirement was waived by the institutional review board. Inclusion criteria were radical prostatectomy specimen TZ cancer larger than 0.5 cm(3) and 3-T endorectal presurgery MP MR imaging (T2-weighted imaging, diffusion-weighted [DW] imaging apparent diffusion coefficient [ADC] maps [b < 1000 sec/mm(2)], and dynamic contrast material-enhanced [DCE] MR imaging). From 197 patients with radical prostatectomy specimens, 28 patients with TZ cancer were included. Thirty-five patients without TZ cancer were randomly selected as a control group. Four radiologists randomly scored T2-weighted and DW ADC images, T2-weighted and DCE MR images, and T2-weighted, DW ADC, and DCE MR images. TZ cancer suspicion was rated on a five-point scale in six TZ regions of interest (ROIs). A score of 4-5 was considered a positive finding. A score of 4 or higher for any ROI containing TZ cancer was considered a positive detection result at the patient level. Generalized estimating equations were used to analyze detection and localization accuracy by using ROI-receiver operating characteristics (ROC) curve analyses for the latter. Gleason grade (GG) 4-5 and GG 2-3 cancers were analyzed separately. RESULTS Detection accuracy did not differ between T2-weighted and MP MR imaging for all TZ cancers (68% vs 66%, P = .85), GG 4-5 TZ cancers (79% vs 72%-75%, P = .13), and GG 2-3 TZ cancers (66% vs 62%-65%, P = .47). MP MR imaging (area under the ROC curve, 0.70-0.77) did not improve T2-weighted imaging localization accuracy (AUC = 0.72) (P > .05). CONCLUSION Use of 3-T MP MR imaging, consisting of T2-weighted imaging, DW imaging ADC maps (b values, 50, 500, and 800 sec/mm(2)), and DCE MR imaging may not improve TZ cancer detection and localization accuracy compared with T2-weighted imaging. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120281/-/DC1.

The clinical epidemiology of superficial bladder cancer. Dutch South-East Cooperative Urological Group.

Even though the majority of patients with bladder malignancies initially present with low stage disease, the clinical epidemiology of these so-called superficial bladder tumours is not well known. In this paper, disease characteristics at initial presentation and during follow-up are described in 1,745 primary cases documented prospectively in the Netherlands. The risk of recurrent disease after primary treatment is very high: in 60% of cases, at least one recurrence is diagnosed within 5 years (95% CI: 58-62%). In patients with a small solitary pTa grade 1 tumour, the 3-year recurrence risk is 37%. In patients with multiple large high grade pT1 tumours, this risk is as high as 77%, despite a significant beneficial effect of adjuvant intravesical chemotherapy. The actuarial risk of disease progression is 10.2% after 3 years (95% CI: 8.6-11.8%). This risk of progression depends on the patients age at diagnosis, tumour stage, grade, multiplicity and the presence of dysplasia or CIS in random urothelium biopsies. The use of intravesical instillations with chemotherapy or BCG vaccine after TUR does not prevent progressive disease, although this finding is difficult to interpret from a non-randomised study. The 5-year relative survival in patients with superficial TCC of the bladder is 86% (95% CI: 84-88%).

The role of (18)fluoro-2-deoxyglucose positron emission tomography in initial staging and re-staging after chemotherapy for testicular germ cell tumours.

Objective To investigate the role of 18fluoro‐2‐deoxyglucose positron emission tomography (FDG‐PET) in the initial staging of clinical stage I and II nonseminomatous germ cell tumours (NSGCTs) and in re‐staging (non)seminomatous GCTs after chemotherapy.

Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers

Background Colorectal, endometrial and upper urinary tract tumours are characteristic for Lynch syndrome (hereditary non-polyposis colon carcinoma, HNPCC). The aim of the present study was to establish whether carriers of mutations in mismatch repair genes MLH1, MSH2 or MSH6 are at increased risk of urinary bladder cancer. Methods Carriers and first degree relatives of 95 families with a germline mutation in the MLH1 (n=26), MSH2 (n=43), or MSH6 (n=26) gene were systematically questioned about the occurrence of carcinoma. The cumulative risk of cancer occurring before the age of 70 years (CR70) was compared to the CR70 of the general Dutch population. Microsatellite instability (MSI) testing and/or immunohistochemistry (IHC) for mismatch repair proteins was performed on bladder tumour tissue. Results Bladder cancer was diagnosed in 21 patients (90% men) from 19 Lynch syndrome families (2 MLH1, 15 MSH2, and 4 MSH6). CR70 for bladder cancer was 7.5% (95% CI 3.1% to 11.9%) for men and 1.0% (95% CI 0% to 2.4%) for women, resulting in relative risks for mutation carriers and first degree relatives of 4.2 (95% CI 2.2 to 7.2) for men and 2.2 (95% CI 0.3 to 8.0) for women. Men carrying an MSH2 mutation and their first degree relatives were at highest risks: CR70 for bladder and upper urinary tract cancer being 12.3% (95% CI 4.3% to 20.3%) and 5.9% (95% CI 0.7% to 11.1%). Bladder cancer tissue was MSI positive in 6/7 tumours and loss of IHC staining was found in 14/17 tumours, indicating Lynch syndrome aetiology. Conclusion Patients with Lynch syndrome carrying an MSH2 mutation are at increased risk of urinary tract cancer including bladder cancer. In these cases surveillance should be considered.

RESULTS OF A RANDOMIZED PHASE III TRIAL OF SEQUENTIAL INTRAVESICAL THERAPY WITH MITOMYCIN C AND BACILLUS CALMETTE-GUERIN VERSUS MITOMYCIN C ALONE IN PATIENTS WITH SUPERFICIAL BLADDER CANCER

PURPOSE We study toxicity and efficacy of sequential intravesical therapy with mitomycin C and bacillus Calmette-Guerin (BCG) in patients with intermediate or high risk superficial bladder cancer compared to the use of intravesical mitomycin C alone. MATERIALS AND METHODS Patients with intermediate and high risk papillary superficial bladder cancer and carcinoma in situ were randomized after transurethral resection between 4 weekly instillations with 40 mg. mitomycin C followed by 6 weekly instillations with BCG (group 1, 90 patients) or 10 weekly instillations with mitomycin C (group 2, 92 patients). RESULTS The frequency of bacterial and chemical cystitis, and other local side effects was similar in both groups. Allergic reactions, including skin rash, were more frequent in the mitomycin C only group (12 of 92 patients versus 5 of 90, p = 0.08), and other systemic side effects were more frequent in the sequential group (16 of 90 versus 8 of 92, p = 0.07). After a median followup of 32 months the number of recurrences (sequential 35 of 90 patients versus mitomycin C only 42 of 92, p = 0.36) and progression (5 of 90 versus 4 of 92 respectively, p = 0.70) were similar in both groups. CONCLUSIONS We did not find any major differences in toxicity or treatment efficacy with intravesical mitomycin C and the sequential use of BCG or mitomycin C for intermediate and high risk superficial papillary bladder cancer.