Staging Of Muscle-invasive Bladder Cancer Research Articles

MRI/RNA-Seq-Based Radiogenomics and Artificial Intelligence for More Accurate Staging of Muscle-Invasive Bladder Cancer.

Accurate staging of bladder cancer assists in identifying optimal treatment (e.g., transurethral resection vs. radical cystectomy vs. bladder preservation). However, currently, about one-third of patients are over-staged and one-third are under-staged. There is a pressing need for a more accurate staging modality to evaluate patients with bladder cancer to assist clinical decision-making. We hypothesize that MRI/RNA-seq-based radiogenomics and artificial intelligence can more accurately stage bladder cancer. A total of 40 magnetic resonance imaging (MRI) and matched formalin-fixed paraffin-embedded (FFPE) tissues were available for analysis. Twenty-eight (28) MRI and their matched FFPE tissues were available for training analysis, and 12 matched MRI and FFPE tissues were used for validation. FFPE samples were subjected to bulk RNA-seq, followed by bioinformatics analysis. In the radiomics, several hundred image-based features from bladder tumors in MRI were extracted and analyzed. Overall, the model obtained mean sensitivity, specificity, and accuracy of 94%, 88%, and 92%, respectively, in differentiating intra- vs. extra-bladder cancer. The proposed model demonstrated improvement in the three matrices by 17%, 33%, and 25% and 17%, 16%, and 17% as compared to the genetic- and radiomic-based models alone, respectively. The radiogenomics of bladder cancer provides insight into discriminative features capable of more accurately staging bladder cancer. Additional studies are underway.

2361MO Impact of positron emission tomography (PET) imaging on staging of muscle-invasive bladder cancer (MIBC) [PET-MUSE

2361MO Impact of positron emission tomography (PET) imaging on staging of muscle-invasive bladder cancer (MIBC) [PET-MUSE

A proof-of-concept study on endoscopic ultrasound-guided biopsy of detrusor muscle in porcine bladders.

Conventionally, we rely on transurethral resection of bladder tumour (TURBT) for local staging of muscle-invasive bladder cancer (MIBC). However, the procedure is limited by its staging inaccuracy which may delay the definitive treatment of MIBC. We conducted a proof-of concept study on endoscopic ultrasound (EUS)-guided biopsy of detrusor muscle in porcine bladders. Five porcine bladders were used in this experiment. Upon EUS, four layers of tissue including the mucosa (hypoechoic), submucosa (hyperechoic), detrusor muscle (hypoechoic) and serosa (hyperechoic) could be identified. A total of 37 EUS-guided biopsies were taken from 15 sites (three sites per bladder), and the mean number of biopsies taken from each site was 2.47±0.64. Among the 37 biopsies, 30 of them (81.1%) obtained detrusor muscle in the biopsy specimen. For the per biopsy site analysis, detrusor muscle was obtained in 73.3% if only one biopsy was taken, and 100% if two or more biopsies were taken from the same biopsy site. Overall, detrusor muscle was successfully obtained from all 15 biopsy sites (100%). No bladder perforation was observed throughout all biopsy processes. EUS-guided biopsy of the detrusor muscle could be performed during the initial cystoscopy session, thus expediting the histological diagnosis and subsequent treatment of MIBC.

MP14-03 VIRTUAL MONITORING OF BLADDER CANCER PROGRESSION IN MICE WITH INTRAVESICAL CONTRAST ENHANCED MAGNETIC RESONANCE IMAGING (ICE-MRI)

You have accessJournal of UrologyCME1 Apr 2023MP14-03 VIRTUAL MONITORING OF BLADDER CANCER PROGRESSION IN MICE WITH INTRAVESICAL CONTRAST ENHANCED MAGNETIC RESONANCE IMAGING (ICE-MRI) Anirban Ganguly, Lesley Foley, T. Kevin Hitchens, Jodi Maranchie, Youko Ikeda, Irina Zabbarova, Anthony Kanai, Naoki Yoshimura, and Pradeep Tyagi Anirban GangulyAnirban Ganguly More articles by this author , Lesley FoleyLesley Foley More articles by this author , T. Kevin HitchensT. Kevin Hitchens More articles by this author , Jodi MaranchieJodi Maranchie More articles by this author , Youko IkedaYouko Ikeda More articles by this author , Irina ZabbarovaIrina Zabbarova More articles by this author , Anthony KanaiAnthony Kanai More articles by this author , Naoki YoshimuraNaoki Yoshimura More articles by this author , and Pradeep TyagiPradeep Tyagi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003234.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Here, we examined the potential of intravesical contrast enhanced magnetic resonance imaging (ICE-MRI) for virtually monitoring the bladder tumor progression from 2-12 weeks, induced in mice fed water containing tobacco carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) that alkylates DNA to elicit the mutational burden and basal subtype cell markers of muscle invasive bladder cancer (MIBC) as well as reflect the four-fold higher cancer risk in past and current smokers. METHODS: 6 weeks old immunocompetent female mice of B6D2F1 strain (n=20) were fed ad libitum water or water containing 0.05% BBN for upto 12 weeks and imaged by ICE-MRI at 7 T under isoflurane anesthesia, before and after 0.05 mL transurethral instillation of Gadobutrol (4 mM) and Ferumoxytol (5 mM) for a 30 min period. Multi slice, axial T1 weighted images were acquired at variable repetition time of 400-7500 ms for voxel-wise T1 mapping with echo time -6.5 ms, slice thickness 0.8 mm, field of view 28*28 mm2, acquisition matrix 218×218, and number of averages=1. RESULTS: While urinary excretion of Gadobutrol injected i.v. for DCE-MRI generates pseudo layering in lumen, ICE-MRI accomplishes uniform image contrast in lumen with steep concentration gradient that resists dilution from fresh urine for size dependent paracellular diffusion of 0.8 nm sized Gadobutrol while lumen is darkened from retention of 30 nm Ferumoxytol. Paracellular diffusion exclusively of Gadobutrol and not Ferumoxytol across perturbed tight junction complex of cancerous cells shortens T1 relaxation times of water protons for differentiating normal bladder wall (2909 ms) from cancer foci (1048 ms) in color coded T1 maps (attached Figure 1). BBN fed mice exhibit superficial tumor after 2-3 weeks that progresses to MIBC stage (∼4 mm length) at multiple foci by 12 weeks in 50% of BBN mice having bladder wall twice the thickness of water fed mice. CONCLUSIONS: Here, we show that ICE-MRI can visualize small polyps and MIBC owing to tumoritropic infiltration of Gadobutrol. ICE-MRI leverages perturbed tight junction complex of cancer foci relative to normal regions for differential contrast enhancement to perform non-surgical surveillance of indolent cancer growth, detect recurrence and stage MIBC without transurethral resection. Source of Funding: NCI- CA263243, CA251341, P30CA047904 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e183 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anirban Ganguly More articles by this author Lesley Foley More articles by this author T. Kevin Hitchens More articles by this author Jodi Maranchie More articles by this author Youko Ikeda More articles by this author Irina Zabbarova More articles by this author Anthony Kanai More articles by this author Naoki Yoshimura More articles by this author Pradeep Tyagi More articles by this author Expand All Advertisement PDF downloadLoading ...

Update of the Diagnostic and Therapeutic Role of the Pelvic Lymph Node Dissection Boundaries During Radical Cystectomy in Muscle Invasive Bladder Cancer

Radical cystectomy (RC) is the gold standard treatment option for muscle invasive bladder cancer (MIBC). However, up to 25% of patients who undergo RC show metastatic lymph node deposits during the procedure. In such cases, the 5-year survival rate is reported to be 25%–30%. Pelvic lymph node dissection (PLND) can also provide useful prognostic information, including data regarding the disease burden, lymph node density, and extracapsular extension of metastatic lymph nodes. Accordingly, the National Comprehensive Cancer Network guidelines recommend that PLND that includes the common iliac lymph node should be performed at the time of RC to allow reliable staging of MIBC. In addition to its diagnostic role, many studies have reported the potential therapeutic role of PLND. Data from clinical trials indicate a substantial oncological advantage in PLND cohorts compared to non-PLND cohorts, regardless of pathological nodal status, as a result of removal of metastatic and micrometastatic tumor cells nested in lymph nodes. As such, despite the diagnostic and therapeutic role of PLND in MIBC, the optimal PLND template remains controversial. Currently, extended PLND (E-PLND) is recommended for diagnostic purposes, however, E-PLND did not show therapeutic effectiveness in some recent preliminary randomized controlled trials. In this review, we will discuss the appropriate range of PLND for RC in terms of its diagnostic and therapeutic importance, and propose an appropriate range of PLNDs based on the evidence and randomized trials so far.

Management of Localized Muscle-Invasive Bladder Cancer from a Multidisciplinary Perspective: Current Position of the Spanish Oncology Genitourinary (SOGUG) Working Group.

This review presents challenges and recommendations on different aspects related to the management of patients with localized muscle-invasive bladder cancer (MIBC), which were discussed by a group of experts of a Spanish Oncology Genitourinary (SOGUG) Working Group within the framework of the Genitourinary Alliance project (12GU). It is necessary to clearly define which patients are candidates for radical cystectomy and which are candidates for undergoing bladder-sparing procedures. In older patients, it is necessary to include a geriatric assessment and evaluation of comorbidities. The pathological report should include a classification of the histopathological variant of MIBC, particularly the identification of subtypes with prognostic, molecular and therapeutic implications. Improvement of clinical staging, better definition of prognostic groups based on molecular subtypes, and identification of biomarkers potentially associated with maximum benefit from neoadjuvant chemotherapy are areas for further research. A current challenge in the management of MIBC is improving the selection of patients likely to be candidates for immunotherapy with checkpoint inhibitors in the neoadjuvant setting. Optimization of FDG-PET/CT reliability in staging of MIBC and the selection of patients is necessary, as well as the design of prospective studies aimed to compare the value of different imaging techniques in parallel.

PET–CT for staging patients with muscle invasive bladder cancer: is it more than just a fancy tool?

We aim to evaluate the diagnostic accuracy of PET–CT/MRI in the local and distant staging of patients with muscle invasive bladder cancer (MIBC). Medline, Pubmed and EMBASE were searched for studies evaluating the diagnostic performance of PET–CT/MRI in the primary staging of MIBC patients. The pooled sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR, respectively) and diagnostic odds ratio (DOR = PLR/NLR) are reported. We retrieved 35 articles. For local staging, a pooled sensitivity and specificity of 88% (95% CI: 81–92%) and 68% (95% CI: 50–82%), respectively, were found. The PLR and NLR are 2.88 (95% CI: 1.71–4.73) and 0.19 (95% CI: 0.12–0.30) resulting in a DOR of 16.60 (95% CI: 5.98–37.50). For regional lymph node staging, the pooled sensitivity and specificity are 57% (95% CI: 5–63%) and 89% (95% CI: 83–3%). The PLR is 5.33 (95% CI: 3.44–8.09) and NLR is 0.48 (95% CI: 0.42–0.55). The corresponding DOR is 11.10 (95% CI: 6.62–17.60). For distant metastases, a pooled sensitivity and specificity of 89% (95% CI: 61–98%) and 95% (95% CI: 80–99%), respectively, were found. The PLR is 23.70 (95% CI: 4.19–72.10) and the NLR is 0.13 (95% CI: 0.02–0.36) with a DOR of 236.00 (95% CI: 38.00–871.00). PET–CT/MRI appears to have higher diagnostic accuracy than CT or MRI for local and distant staging of MIBC but it cannot (yet) be recommended in clinical practice because the quality of the evidence is insufficient and the effects on treatment decisions and patient’s outcome remain unclear.

Upregulation of lncRNA plasmacytoma variant translocation 1 predicts poor prognosis in patients with muscle-invasive bladder cancer.

LncRNA plasmacytoma variant translocation 1 (PVT1) has been recognized as an oncogenic lncRNA, which participates in the migration and invasion of many kinds of cancer cells and the development of cancers. In the present study, we explored its clinical significance and prognostic value in muscle invasive bladder cancer (MIBC).A total of 98 MIBC patients’ samples were collected, who had undergone radical cystectomy from the March 2013 to December 2018. The associations between PVT1 expression and clinical data were calculated using the Chi2-test. Overall survival curves were determined by the Kaplan–Meier technique and contrasted via log-rank test. We utilized univariate and multivariate Cox proportional hazard models to examine the HR and 95% CI.The expression levels of PVT1 were significantly higher in MIBC tissues than that in normal bladder tissues (P < .001). PVT1 expression was significantly correlated with tumor grade (P = .009), margin (P = .002), T stage (P = .02), and lymph node metastasis (P < .001). MIBC patients with high PVT1 expression level had shorter overall survival than those with low PVT1 expression level (log-rank test, P = .004). Multivariate Cox regression analysis showed that PVT1 expression level (HR = 2.381, 95% CI: 1.821–7.012, P = .014) was an independent factor in predicting the overall survival of MIBC patients.In summary, increased PVT1 expression in MIBC patients is correlated with a higher MIBC stage and is significantly associated with poor prognosis for MIBC patients, which may provide new insights into new therapeutic strategy and postoperative intervention against bladder cancer.

Impact of histology and toxicities on outcomes of patients with muscle invasive bladder cancer receiving neoadjuvant chemotherapy.

540 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) extends survival in muscle invasive bladder cancer (MIBC) patients (pts). Pathologic complete response (pCR) is associated with survival. We conducted a retrospective study to examine the prognostic impact of other variables including histologic subtype, location, multifocality, margins, size of tumor and toxicities. Methods: Pts who underwent RC at Dana-Farber for MIBC stage T2-T4N0-1 were studied. Data were collected for demographics, clinical and pathologic variables. Descriptive stats were reported, and Cox proportional hazards regression analyses were conducted to examine the association with recurrence-free survival (RFS) and overall survival (OS). Results: From 2002 to 2018, 150 patients were available. The median age was 66 (range 36-89) and 102 (68%) were male. MVAC/dose dense MVAC, GC and other non-standard regimens were given in 42 (28%), 85 (56.7%) and 23 (15.3%) pts, respectively. The 2-yr RFS was 63.6%, the 5-yr OS was 68.7% and pCR occurred in 38 pts (25.3%). Multivariable analysis identified pure urothelial carcinoma in the residual tumor and absence of pathologic response to be associated with poor RFS and OS. Positive margins were associated with poor RFS, while grade ≥3 toxicities were associated with poor OS. Conclusions: Pure urothelial carcinoma histology was associated with worse RFS and OS following RC after NAC for MIBC, suggesting molecular studies may be useful in these cases. The association of severe toxicities with poor OS suggests that optimal pt selection for NAC and early recognition of toxicities is important.[Table: see text]

Impact of 18FDG-PET CT in the management of invasive bladder cancer.

444 Background: Guidelines do not recommend FDG-Positron Emission Tomography (PET) Computed Tomography (CT) for the staging of Muscle Invasive Bladder Cancer (MIBC), but rather CT scan for lymph node (LN) and metastatic staging, despite its low accuracy. We performed a retrospective analysis of patients (pts) with MIBC who had a FDG-PET CT for staging, indicated by multidisciplinary team, in two centers, and analyzed its utility in this setting. Methods: All pts who had a FDG-PET CT performed at the time of diagnosis of MIBC from 01/2005 to 12/2017 in Bordeaux (Bergonie Institute and University Hospital) were retrospectively reviewed. Nodal and metastatic staging on CT and FDG-PET CT were done independently according to the 8th TNM classification. The aims of the study were to evaluate the accuracy of the FDG-PET CT for LN staging and to determine the rate of treatment modification (neoadjuvant chemotherapy for curative intent, no surgery for metastatic disease), according to FDG-PET CT results. Results: Among the 130 pts included, with a median age of 65 years, 74% were considered free from nodal metastasis (N0) by CT whereas only 44% were N0 from FDG-PET CT. Based on CT results, 88% of pts were free from distant metastasis (M0) but only 75% were classified M0, on FDG-PET CT. Accuracy of LN staging for CT and FDG-PET CT at initial diagnosis were analyzed for 85 pts (including 70 pts treated with neoadjuvant chemotherapy) and compared to pathological examination of resected LN. Sensitivity of FDG-PET CT was better than CT (respectively 80.8% versus 26.9%) but the specificity was low (respectively 54.2% versus 83.1%). Youden index was better for FDG-PET CT (0.35; 0.1 for CT), being more accurate for determining LN staging of MIBC. FDG-PET CT findings allowed a treatment decision modification in 34/130 pts (26.1%): therapeutic intensification in 12 pts (9.2%), including surgery not previously indicated, modified radiotherapy; or de-escalation in 22 pts (16.9%), mostly avoiding surgery. Conclusions: FDG-PET CT is more sensitive to detect LN involvement at initial diagnosis of MIBC than standard CT scan. Moreover, in the present study, treatment decisions were modified, according to FDG-PET CT results, in a quarter of pts according to LN and distant metastatic staging.

Pilot Study of [18F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET)/Magnetic Resonance Imaging (MRI) for Staging of Muscle-invasive Bladder Cancer (MIBC).

Computed tomography (CT) has limited diagnostic accuracy for staging of muscle-invasive bladder cancer (MIBC). [18F] Fluorodeoxyglucose positron emission tomography (FDG-PET)/magnetic resonance imaging (MRI) is a novel imaging modality incorporating functional imaging with improved soft tissue characterization. This pilot study evaluated the use of preoperative FDG-PET/MRI for staging of MIBC. Twenty-one patients with MIBC with planned radical cystectomy were enrolled. Two teams of radiologists reviewed FDG-PET/MRI scans to determine: (1) presence of primary bladder tumor; and (2) lymph node involvement and distant metastases. FDG-PET/MRI was compared with cystectomy pathology and computed tomography (CT). Eighteen patients were included in the final analysis, most (72.2%) of whom received neoadjuvant chemotherapy. Final pathology revealed 10 (56%) patients with muscle invasion and only 3 (17%) patients with lymph node involvement. Clustered analysis of FDG-PET/MRI radiology team reads revealed a sensitivity of 0.80 and a specificity of 0.56 for detection of the primary tumor with a sensitivity of 0 and a specificity of 1.00 for detection of lymph node involvement when compared with cystectomy pathology. CT imaging demonstrated similar rates in evaluation of the primary tumor (sensitivity, 0.91; specificity, 0.43) and lymph node involvement (sensitivity, 0; specificity, 0.93) when compared with pathology. This pilot single-institution experience of FDG-PET/MRI for preoperative staging of MIBC performed similar to CT for the detection of the primary tumor; however, the determination of lymph node status was limited by few patients with true pathologic lymph node involvement. Further studies are needed to evaluate the potential role for FDG-PET/MRI in the staging of MIBC.

Pilot Study of [18F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET)/Magnetic Resonance Imaging (MRI) for Staging of Muscle-invasive Bladder Cancer (MIBC)

Pilot Study of [18F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET)/Magnetic Resonance Imaging (MRI) for Staging of Muscle-invasive Bladder Cancer (MIBC)

Survival of Patients with Muscle-Invasive Urothelial Cancer of the Bladder with Residual Disease at Time of Cystectomy: A Comparative Survival Analysis of Treatment Modalities in the National Cancer Database

PURPOSE: Data have indicated that residual disease after neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) may be associated with poor outcomes. OBJECTIVE: Analyze differences in overall survival (OS) of patients with residual MIBC treated with NAC + Radical cystectomy (RC), RC alone, or RC + Adjuvant Chemotherapy(AC). MATERIALS AND METHODS: The National Cancer Database was queried for patients who underwent RC alone, NAC + RC, or RC + AC for MIBC stage cT2-4aN0M0 from 2004-2015. Covariates were balanced using propensity score (PS) weighting. Time to death was evaluated from diagnosis. Weighted cox proportional hazards models and Kaplan-Meier survival curves were created to analyze differences in OS. RESULTS: 8,288 patients were included for analysis, 1,899 (23%) received NAC + RC, 5,529 (67%) received RC alone, and 860 (10%) received RC + AC. Patients were sub-stratified based on pathological staging (≤pT2 or &gt;pT2) and compared against treatment with RC alone. In the ≤pT2 cohort, NAC + RC was associated with a decreased risk of death (HR:0.85, 95% CI:0.79–0.91) and RC + AC was associated with an increased risk of death (HR:1.46, 95% CI:1.34–1.60, both p &lt; 0.001) compared to RC alone. In the &gt;pT2 cohort, these associations reversed, with an increased risk of death seen in the NAC + RC group (HR:1.11, 95% CI:1.05–1.18) and a decreased risk of death in the RC + AC group (HR:0.74, 95% CI:0.7–0.77, both p &lt; 0.001). CONCLUSIONS: Patients with &gt;ypT2 disease after NAC experienced a significant increased risk of death when compared to pathological stage-matched patients who underwent RC alone or RC + AC. Biomarkers predictive of NAC resistance may be important to optimize NAC usage and establish treatment algorithms.

931P - Potential role of a clinical, taxonomical classification and RNA expression integrated signature to predict response to neoadjuvant platinum-based chemotherapy in muscle-invasive bladder cancer (MIBC) patients

BackgroundNeoadjuvant chemotherapy (NAC) followed by cystectomy is the standard of care in MIBC patients, although a limited survival benefit has been obtained compared with cystectomy alone. Pathologic response has been associated with survival, but, unfortunately, neither baseline clinical or pathological variables have demonstrated ability to predict which patients will benefit from NAC, pointing to the need of predictive biomarkers of NAC response to guide treatment decisions. The objective of this retrospective study was to identify a NAC response prediction signature integrating baseline clinical features, taxonomic subtypes, and RNA expression profile in MIBC patients. MethodsFormalin-fixed paraffin-embedded pre-treatment tumor samples were collected by transurethral resection from 112 patients with MIBC stage T2-4N0/+M0 treated with NAC followed by cystectomy. Immunohistochemical-based taxonomic subtypes (BASQ-like, luminal-like, mixed) were established. Gene expression analysis was performed on the Nano String nCounter platform. A custom code set of a 41-gene panel involved in the DNA damage repair (DDR) and immune response pathways was used. Lasso and elastic net penalized logistic regression were performed to identify a predictive signature. Calculation of the area under the ROC curve (AUC) was used to assess the predictive ability of the signature. ResultsA nine-gene RNA expression signature (RAD51, CXCL9, PARP, 53BP1, HERC2, ERCC2, CHEK1, Ku80 and RNF 168 genes) was associated with pathologic response. The highest predictive ability was observed with the integrated clinical-taxonomical-RNA signature with an AUC of 0.66, in comparison to the clinical-taxonomical classification (AUC=0.58) or the clinical signature alone (AUC=0.52). Furthermore, the integrated signature was significantly associated with overall survival (p=0.013). ConclusionsWe have identified a nine-gene RNA expression signature that can help to predict response in MIBC patients treated with NAC. Prospective studies are warranted to validate these results. Legal entity responsible for the studyThe authors. FundingAECC. DisclosureAll authors have declared no conflicts of interest.

Patient-Friendly Summary of the ACR Appropriateness Criteria: Pretreatment Staging of Muscle-Invasive Bladder Cancer

Patient-Friendly Summary of the ACR Appropriateness Criteria: Pretreatment Staging of Muscle-Invasive Bladder Cancer

Pilot study of [18F] fluorodexoyglucose positron emission tomography-magnetic resonance imaging (FDG-PET-MRI) for staging of muscle-invasive bladder cancer.

e16002 Background: Standard of care imaging for staging MIBC is computed tomography (CT) abdomen and pelvis despite poor diagnostic accuracy. The addition of FDG-PET to evaluate biologic activity has been shown to improve detection of metastatic bladder cancer. Better soft tissue characterization with MRI may improve detection of local disease. We hypothesized that simultaneous acquisition of FDG-PET and MRI images (PET-MRI) would allow for more accurate preoperative staging in patients with MIBC. Methods: 21 patients with MIBC and planned radical cystectomy with lymph node dissection were enrolled. Four radiologists (2 senior, 2 junior) with expertise in MRI and PET independently reviewed MRI and FDG-PET scans, respectively, to determine: 1) extent of the primary bladder tumor; and 2) involvement of local lymph nodes and distant sites of disease. Combined radiologist reads were performed (senior MRI and junior PET and vice versa). Imaging results were compared to surgical pathology. Results: 18 patients were included in the final analysis (3 PET-MRI scans excluded due to technical pitfalls with image acquisition). Final pathology revealed 10 patients (56%) with muscle invasion and only 2 patients (11%) with lymph node involvement. Combined analyses of PET-MRI accurately detected the extent of the primary tumor (sensitivity 0.84, specificity 0.50, PPV 0.70, NPV 0.70), but was less accurate for the detection of lymph node involvement (sensitivity 0.00, specificity 1.00, no calculable PPV, NPV 0.91). Senior MRI radiologist had improved PPV and NPV for extent of primary tumor compared to junior MRI radiologist (PPV 0.71 vs 0.56, NPV 0.83 vs. 0.50), and senior PET radiologist had improved PPV with similar NPV for extent of primary tumor (PPV 1.00 vs 0.78, NPV 0.50 vs 0.55). No patient was determined to have distant metastatic disease. Conclusions: To our knowledge, this is the first study exploring the use of PET-MRI for staging MIBC. This novel imaging modality demonstrated promise in detecting the extent of the primary tumor. Further investigation of FDG-PET-MRI is needed to better determine its potential utility in staging MIBC.

Downstream Studies Following the Use of Bone Scan in the Staging of Muscle-invasive Bladder Cancer

ObjectiveTo quantify the use of downstream studies following staging bone scans in patients with muscle-invasive bladder cancer. Bone scans may be obtained in high-risk bladder cancer patients prior to radical cystectomy to exclude bone metastases. However, false-positive bone scans can occur, resulting in the need for additional studies. Patients and MethodsUsing Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified 4404 patients diagnosed with muscle-invasive bladder cancer from 2004 to 2011. We further identified those who underwent a bone scan prior to treatment within 6 months of diagnosis and prior to any treatment with cystectomy, radiotherapy, or chemotherapy. We determined the proportion of patients who underwent a subsequent study (bone X-ray, bone CT, bone MRI, and/or bone biopsy) within 3 months of the bone scan and prior to treatment. ResultsAmong patients diagnosed with muscle-invasive bladder cancer, 1373 (31%) had a staging bone scan of whom 26% received a downstream study (n = 213). Overall, 61 patients (7%) received downstream bone-specific X-rays, more than 141 patients (>17%) received bone-specific CTs, and 28 patients (3%) received bone-specific MRIs. The use of bone biopsy was rare (n < 11; <1%). The total cost of all downstream studies was $103,468. Furthermore, there was a one-month delay in treatment for those who received a downstream study compared to those who did not (P < 0.001). ConclusionUse of bone scan in the staging of muscle-invasive bladder cancer often results in the need for additional downstream studies. The delay in treatment and cost burden of downstream studies highlights a potential disadvantage of the routine use of this staging modality.

PD32-09 DOWNSTREAM PROCEDURES FOLLOWING THE USE OF BONE SCAN IN THE STAGING OF MUSCLE-INVASIVE BLADDER CANCER

You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Value of Care: Cost and Outcomes Measures III1 Apr 2017PD32-09 DOWNSTREAM PROCEDURES FOLLOWING THE USE OF BONE SCAN IN THE STAGING OF MUSCLE-INVASIVE BLADDER CANCER Robert Turner II, Jonathan Yabes, Benjamin Davies, Dwight Heron, and Bruce Jacobs Robert Turner IIRobert Turner II More articles by this author , Jonathan YabesJonathan Yabes More articles by this author , Benjamin DaviesBenjamin Davies More articles by this author , Dwight HeronDwight Heron More articles by this author , and Bruce JacobsBruce Jacobs More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1400AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A bone scan may be considered prior to radical cystectomy to exclude bone metastases in high-risk patients. However, false positive bone scans can occur due to tracer uptake in benign bone lesions with reactive osteoblastic change, resulting in the need for additional procedures such as x-ray, computed tomography (CT), magnetic resonance imaging (MRI), and bone biopsy to further evaluate bone scan findings. The current burden of these downstream procedures is unknown. We aim to quantify the use of downstream procedures following staging bone scans in patients with muscle-invasive bladder cancer. METHODS Using Surveillance, Epidemiology, and End Results (SEER)- Medicare data, we identified 4404 patients diagnosed with muscle-invasive bladder cancer from 2004-2011. We further identified those who underwent a bone scan prior to treatment within 6 months of diagnosis. Using outpatient and carrier claims files, we determined the proportion of patients who underwent a subsequent x-ray, CT, MRI, and/or bone biopsy within 3 months of the bone scan and prior to treatment. RESULTS Among patients diagnosed with muscle-invasive bladder cancer during the study period, 1373 (31%) were identified as having completed a staging bone scan. Overall, 231 patients (17%) received downstream bone-specific x-rays, 340 patients (25%) received bone-specific CTs, and 103 patients (8%) received bone-specific MRIs. The use of bone biopsy was rare (n = 17; 1%). CONCLUSIONS Use of bone scan in the staging of muscle-invasive bladder cancer often results in the need for additional downstream imaging. The cost burden of this downstream imaging highlights a potential disadvantage of the routine use of this staging modality. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e591-e592 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Robert Turner II More articles by this author Jonathan Yabes More articles by this author Benjamin Davies More articles by this author Dwight Heron More articles by this author Bruce Jacobs More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

A reported 20-gene expression signature to predict lymph node-positive disease at radical cystectomy for muscle-invasive bladder cancer is clinically not applicable.

BackgroundNeoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) provides a small but significant survival benefit. Nevertheless, controversies on applying NAC remain because the limited benefit must be weight against chemotherapy-related toxicity and the delay of definitive local treatment. Therefore, there is a clear clinical need for tools to guide treatment decisions on NAC in MIBC. Here, we aimed to validate a previously reported 20-gene expression signature that predicted lymph node-positive disease at radical cystectomy in clinically node-negative MIBC patients, which would be a justification for upfront chemotherapy.MethodsWe studied diagnostic transurethral resection of bladder tumors (dTURBT) of 150 MIBC patients (urothelial carcinoma) who were subsequently treated by radical cystectomy and pelvic lymph node dissection. RNA was isolated and the expression level of the 20 genes was determined on a qRT-PCR platform. Normalized Ct values were used to calculate a risk score to predict the presence of node-positive disease. The Cancer Genome Atlas (TCGA) RNA expression data was analyzed to subsequently validate the results.ResultsIn a univariate regression analysis, none of the 20 genes significantly correlated with node-positive disease. The area under the curve of the risk score calculated by the 20-gene expression signature was 0.54 (95% Confidence Interval: 0.44-0.65) versus 0.67 for the model published by Smith et al. Node-negative patients had a significantly lower tumor grade at TURBT (p = 0.03), a lower pT stage (p<0.01) and less frequent lymphovascular invasion (13% versus 38%, p<0.01) at radical cystectomy than node-positive patients. In addition, in the TCGA data, none of the 20 genes was differentially expressed in node-negative versus node-positive patients.ConclusionsWe conclude that a 20-gene expression signature developed for nodal staging of MIBC at radical cystectomy could not be validated on a qRT-PCR platform in a large cohort of dTURBT specimens.

SEOM Clinical Guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2016).

The goal of this article is to provide recommendations for the diagnosis and treatment of muscle-invasive and metastatic bladder cancer. The diagnosis of muscle-invasive bladder cancer is made by pathologic evaluation after transurethral resection. Recently, a molecular classification has been proposed. Staging of muscle-invasive bladder cancer must be done by computed tomography scans of the chest, abdomen and pelvis and classified on the basis of UICC system. Radical cystectomy and lymph node dissection are the treatment of choice. In muscle-invasive bladder cancer, neoadjuvant chemotherapy should be recommended in patients with good performance status and no renal function impairment. Although there is insufficient evidence for use of adjuvant chemotherapy, its use must be considered when neoadjuvant therapy had not been administered in high-risk patients. Multimodality bladder-preserving treatment in localized disease is an alternative in selected and compliant patients for whom cystectomy is not considered for clinical or personal reasons. In metastatic disease, the first-line treatment for patients must be based on cisplatin-containing combination. Vinflunine is the only drug approved for use in second line in Europe. Recently, immunotherapy treatment has demonstrated activity in this setting.