The value of 18F-fluorodeoxyglucose positron-emission-tomography-computed tomography (FDG-PET/CT) for staging patients with (very) high-risk non-muscle invasive bladder cancer (NMIBC) is unknown.... Show moreThe value of 18F-fluorodeoxyglucose positron-emission-tomography-computed tomography (FDG-PET/CT) for staging patients with (very) high-risk non-muscle invasive bladder cancer (NMIBC) is unknown. In this study among NMIBC patients referred for RC, FDG-PET/CT detected metastases that were not detected by CT, leading to treatment changes in 10% of patients. However, the use of FDG-PET/CT should be weighed against its disad-vantages, including false-positive lesions. Introduction and Objectives: 18F-fluorodeoxyglucose positron-emission tomography-computed tomography (FDG-PET/CT) is increasingly used in the preoperative staging of patients with muscle-invasive bladder cancer. The clinical added value of FDG-PET/CT in high-risk non-muscle invasive bladder cancer (NMIBC) is unknown. In this study, the value of FDG-PET/CT in addition to contrast enhanced (CE)-CT was evaluated in high-risk NMIBC before radical cystec-tomy (RC). Materials and Methods: This is a retrospective analysis of consecutive patients with high risk and very-high risk urothelial NMIBC scheduled for RC in a tertiary referral center between 2011 and 2020. Patients underwent staging with CE-CT (chest and abdomen/pelvis) and FDG-PET/CT. We assessed the clinical disease stage before and after FDG-PET/CT and the treatment recommendation based on the stage before and after FDG-PET/CT. The accuracy of CT and FDG-PET/CT for identifying metastatic disease was defined by the receiver-operating curve using a reference -standard including histopathology/cytology (if available), imaging and follow-up. Results: A total of 92 patients were identified (median age: 71 years). In 14/92 (15%) patients, FDG-PET/CT detected metastasis (12 suspicious lymph nodes and 4 distant metastases). The disease stage changed in 11/92 (12%) patients based on additional FDG-PET/CT findings. FDG-PET/CT led to a different treatment in 9/92 (10%) patients. According to the reference standard, 25/92 (27%) patients had metastases. The sensitivit y, specificit y and accuracy of FDG-PET/CT was 36%, 93% and 77% respectively, versus 12%, 97% and 74% of CE-CT only. The area under the ROC curve was 0.643 for FDG-PET/CT and 0.545 for CT, P = .036. Conclusion: The addition of FDG-PET/CT to CE-CT imaging changed the treatment in 10% of patients and proved to be a valuable diagnostic tool in a selected subgroup of NMIBC patients scheduled for RC. Show less
Hoogstraten, L.M.C. van; Gennep, E.J. van; Kiemeney, L.A.L.M.; Witjes, J.A.; Voskuilen, C.S.; Deelen, M.; ... ; BlaZIB Study Grp 2021
Purpose Little is known about the prevalence of occult lymph node metastases (LNM) in muscle-invasive bladder cancer (MIBC) patients with pathological downstaging of the primary tumor. We aimed to... Show morePurpose Little is known about the prevalence of occult lymph node metastases (LNM) in muscle-invasive bladder cancer (MIBC) patients with pathological downstaging of the primary tumor. We aimed to estimate the prevalence of occult LNM in patients without residual MIBC at radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) or neoadjuvant radiotherapy (NAR), and to assess overall survival (OS). Methods Patients with cT2-T4aN0M0 urothelial MIBC who underwent RC plus pelvic lymph node dissection (PLND) with curative intent between January 1995-December 2013 (retrospective Netherlands Cancer Registry (NCR) cohort) and November 2017-October 2019 (prospective NCR-BlaZIB cohort (acronym in Dutch: BlaaskankerZorg In Beeld; in English: Insight into bladder cancer care)) were identified from the nationwide NCR. The prevalence of occult LNM was calculated and OS of patients with y)pT2N0 vs. y)pT2N+ disease was estimated by the Kaplan-Meier method. Results In total, 4657 patients from the NCR cohort and 760 patients from the NCR-BlaZIB cohort were included. Of 1374 patients downstaged to y)pT2, 4.3% (N = 59) had occult LNM 4.1% (N = 49) of patients with cT2-disease and 5.6% (N = 10) with cT3-4a-disease. This was 4.0% (N = 44) in patients without NAC or NAR, 4.5% (N = 10) in patients with NAC, and 13.5% (N = 5) in patients with NAR but number of patients treated with NAR and downstaged disease was small. The prevalence of y)pT2N+ disease was 4.2% (N = 48) in the NCR cohort and 4.6% (N = 11) in the NCR-BlaZIB cohort. For patients with y)pT2N+ and y)pT2N0, median OS was 3.5 years (95% CI 2.5-8.9) versus 12.9 years (95% CI 11.7-14.0), respectively. Conclusion Occult LNM were found in 4.3% of patients with cT2-4aN0M0 MIBC with (near-) complete downstaging of the primary tumor following RC plus PLND. This was regardless of NAC or clinical T-stage. Patients with occult LNM showed considerable worse survival. These results can help in counseling patients for bladder-sparing treatments. Show less
Albers, L.F.; Tillier, C.N.; Muilekom, E. van; Werkhoven, E. van; Elzevier, H.W.; Rhijn, B.W.G. van; ... ; Hendricksen, K. 2021
Background: Preservation of erectile function is an important postoperative quality of life concern for patients after robot-assisted radical prostatectomy (RARP) for prostate cancer. Although... Show moreBackground: Preservation of erectile function is an important postoperative quality of life concern for patients after robot-assisted radical prostatectomy (RARP) for prostate cancer. Although erectile function may recover, many men continue to suffer from erectile dysfunction (ED).Aim: This study aims to determine whether satisfaction with sexual life improves in patients with ED after RARP and which factors are associated with satisfaction during follow-up.Methods: A review was carried out of a prospectively maintained database of patients with prostate cancer who underwent a RARP between 2006 and 2019. The 'International Index of Erectile Function' questionnaire was used to describe ED (range 5-25), overall satisfaction with sexual life and sexual desire (range for both: 2-10). Patients with ED due to RARP were compared with those without ED after RARP. Mixed effect model was used to test differences in satisfaction over time. Mann-Whitney U tests and multiple logistic regression were used to assess factors associated with being satisfied at 24 and 36 months.Outcomes: The main outcomes of this study are the overall satisfaction with sexual life score over time and factors which influence sexual satisfaction.Results: Data of 2808 patients were reviewed. Patients whose erectile function was not known (n = 643) or who had ED at the baseline (n = 1281) were excluded. About 884 patients were included for analysis. They had an overall satisfaction score of 8.4. Patients with ED due to RARP had mean overall satisfaction scores of 4.8, 4.8, 4.9, and 4.6 at 6 mo, 12 mo, 24 mo, and 36 mo. These scores were significantly lower than those of patients without ED at every time point. In multiple regression analysis, higher overall satisfaction score at the baseline and higher sexual desire at 24 and 36 months' follow-up were associated with satisfaction with sexual life at 24 and 36 months? follow-up. No association was found for erectile function.Clinical implications: Interventions focusing on adjustment to the changes in sexual functioning might improve sexual satisfaction; especially for those men who continue to suffer from ED.Strengths & Limitations: Strengths of this study are the large number of patients, time of follow-up, and use of multiple validated questionnaires. Our results must be interpreted within the limits of retrospectively collected, observational data.Conclusion: Satisfaction with sexual life in men with ED due to RARP may take a long time to improve. One could counsel patients that sexual satisfaction is based on individual baseline sexual satisfaction and the return of sexual desire after RARP. Copyright (C) 2020, The Authors. Published by Elsevier Inc. on behalf of the International Society for Sexual Medicine. Show less
Einerhand, S.M.H.; Gennep, E.J. van; Mertens, L.S.; Hendricksen, K.; Donswijk, M.L.; Poel, H.G. van der; Rhijn, B.W.G. van 2020
Purpose of review In this narrative review, we assessed the role of(18)F-fluoro-2-deoxy-D-glucose-positron emission tomography/CT (FDG-PET/CT) in preoperative staging and response evaluation of... Show morePurpose of review In this narrative review, we assessed the role of(18)F-fluoro-2-deoxy-D-glucose-positron emission tomography/CT (FDG-PET/CT) in preoperative staging and response evaluation of neoadjuvant chemotherapy in muscle-invasive bladder carcinoma (MIBC), and to assess its incremental value to contrast-enhanced (CE)CT and MRI in terms of patient management at initial diagnosis and detection of recurrence. Recent findings A literature search in PubMed yielded 46 original reports, of which 15 compared FDG-PET/CT with CECT and one with MRI. For primary tumor assessment, FDG-PET/CT proved not accurate enough (13 reports;n = 7-70). For lymph node assessment, sensitivity of FDG-PET/CT is superior to CT with comparable specificity in 19 studies (n = 15-233). For detection of distant metastases, data from eight studies (n = 43-79) suggests that FDG-PET/CT is accurate, although comparative studies are lacking. Limited evidence (four studies,n = 19-50) suggests that FDG-PET/CT is not accurate for response evaluation of neoadjuvant chemotherapy. FDG-PET/CT incited change(s) in patient management in 18-68% of patients (five reports;n = 57-103). For detection of recurrence, seven studies (n = 29-287) indicated that FDG-PET/CT is accurate. Most studies evaluated FDG-PET/CT for lymph node assessment and reported higher sensitivity than CT, with comparable specificity. FDG-PET/CT showed incremental value to CECT for recurrence and often incited change(s) in patient management. Show less
BACKGROUND Fifty percent of patients with muscle-invasive bladder cancer (MI-BC) die from their disease and current chemotherapy treatment only marginally increases survival. Novel therapies... Show moreBACKGROUND Fifty percent of patients with muscle-invasive bladder cancer (MI-BC) die from their disease and current chemotherapy treatment only marginally increases survival. Novel therapies targeting receptor tyrosine kinases or activated oncogenes may improve outcome. Hence, it is necessary to stratify patients based on mutations in relevant oncogenes. Patients with non-muscle-invasive bladder cancer (NMI-BC) have excellent survival, however two-thirds develop recurrences. Tumor specific mutations can be used to detect recurrences in urine assays, presenting a more patient-friendly diagnostic procedure than cystoscopy. METHODOLOGY/PRINCIPAL FINDINGS To address these issues, we developed a mutation assay for the simultaneous detection of 19 possible mutations in the HRAS, KRAS, and NRAS genes. With this assay and mutation assays for the FGFR3 and PIK3CA oncogenes, we screened primary bladder tumors of 257 patients and 184 recurrences from 54 patients. Additionally, in primary tumors p53 expression was obtained by immunohistochemistry. Of primary tumors 64% were mutant for FGFR3, 11% for RAS, 24% for PIK3CA, and 26% for p53. FGFR3 mutations were mutually exclusive with RAS mutations (p = 0.001) and co-occurred with PIK3CA mutations (p = 0.016). P53 overexpression was mutually exclusive with PIK3CA and FGFR3 mutations (p≤0.029). Mutations in the RAS and PIK3CA genes were not predictors for recurrence-free, progression-free and disease-specific survival. In patients presenting with NMI-BC grade 3 and MI-BC, 33 and 36% of the primary tumors were mutant. In patients with low-grade NMI-BC, 88% of the primary tumors carried a mutation and 88% of the recurrences were mutant. CONCLUSIONS/SIGNIFICANCE The mutation assays present a companion diagnostic to define patients for targeted therapies. In addition, the assays are a potential biomarker to detect recurrences during surveillance. We showed that 88% of patients presenting with low-grade NMI-BC are eligible for such a follow-up. This may contribute to a reduction in the number of cystoscopical examinations. Show less
Aa, M.N.M. van der; Steyerberg, E.W.; Bangma, C.; Rhijn, B.W.G. van; Zwarthoff, E.C.; Kwast, T.H. van der 2010
PURPOSE: We evaluated the influence of knowledge of urine test outcome on the accuracy of cystoscopy (diagnostic review bias) during surveillance in patients with low grade, nonmuscle invasive... Show morePURPOSE: We evaluated the influence of knowledge of urine test outcome on the accuracy of cystoscopy (diagnostic review bias) during surveillance in patients with low grade, nonmuscle invasive urothelial carcinoma. MATERIALS AND METHODS: We performed a prospective, single-blind, randomized, multicenter clinical trial of surveillance by microsatellite analysis urine test in 448 patients with nonmuscle invasive (pTa, pT1, G1, G2) urothelial carcinoma. Positive or negative urine test results were only communicated to the urologist in the intervention arm of 226 patients, in which cystoscopy was done if the test was positive, and at 3, 12 and 24 months. Urine test results were not communicated in the control arm of 222 patients who underwent standard 3-month cystoscopy. The primary outcome measure was the number of histologically proven bladder cancer recurrences. RESULTS: At a median 34-month followup 218 recurrences were detected in the intervention arm compared to 163 in the control arm (p <0.001). Of 131 cystoscopies done with knowledge of a positive urine test 42 recurrences were detected. Only 6 recurrences were found in the 120 cystoscopies done without information on the positive test result (chi-square p <0.001). There was no difference in recurrence detection when urine test results were negative in the intervention and control arms (18 of 260 patients or 7% and 18 of 326 or 6%, respectively, p = 0.45). CONCLUSIONS: Diagnostic review bias should be considered in the evaluation of point of care urine tests for bladder cancer monitoring. Awareness of a positive urine test result significantly improves the urothelial carcinoma detection rate using cystoscopy. Show less
