Publications by authors named "Siamak Daneshmand"

309 Publications

Safety and feasibility of urological procedures in Jehovah's Witness patients.

Int J Urol 2021 Oct 12. Epub 2021 Oct 12.

Department of Urology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA.

Objectives: To describe the safety and feasibility of urological transfusion-free surgeries in Jehovah's Witness patients.

Methods: An institutional review board-approved, retrospective review of Jehovah's Witness patients who underwent urological transfusion-free surgeries between 2003 and 2019 was carried out. Surgeries were stratified into low, intermediate and high risk based on complexity, invasiveness and bleeding potential. Patient demographics, perioperative data and clinical outcomes are reported.

Results: A total of 161 Jehovah's Witness patients (median age 63.4 years) underwent 171 transfusion-free surgeries, including 57 (33.3%) in low-, 82 (47.9%) in intermediate- and 32 (18.8%) in high-risk categories. The mean estimated blood loss increased with risk category at 48 mL (range 10-50 mL), 150 mL (range 50-200 mL) and 388 mL (range 137-500 mL), respectively (P < 0.001). Implementing blood augmentation and conservation techniques increased with each risk category (3.5% vs 29% vs 69%, respectively; P < 0.001). Average length of stay increased concordantly at 1.6 days (range 0-12 days), 2.9 days (range 1-13 days) and 5.6 days (range 2-12 days), respectively (P ≤ 0.001). However, there was no increase in complication rates and readmission rates attributed to bleeding among the risk categories at 30 days (P = 0.9 and 0.4, respectively) and 90 days (P = 0.7 and 0.7, respectively).

Conclusions: Transfusion free urological surgery can be safely carried out on Jehovah's Witness patients using contemporary perioperative optimization. Additionally, these techniques can be expanded for use in the general patient population to avoid short- and long-term consequences of perioperative blood transfusion.
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http://dx.doi.org/10.1111/iju.14721DOI Listing
October 2021

Role of Blue Light Cystoscopy in Detecting Invasive Bladder Tumor: Data from Multi-Institutional Registry.

BJU Int 2021 Oct 12. Epub 2021 Oct 12.

Department of Urology, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.

Objectives: To evaluate the role of blue light (BL) cystoscopy in detecting invasive tumors that were not visible on white light (WL) cystoscopy.

Materials And Methods: Using the multi-institutional Cysview registry database, patients who had at least one white light negative/blue light positive lesion with invasive pathology (≥T1) as highest stage tumor were identified. All white light negative/blue light positive lesions and all invasive tumors in the database were used as denominators. Relevant baseline and outcome data were collected.

Results: Of the 3514 lesions (1257 unique patients), 818 (23.2%) lesions were WL negative (WL-)/BL positive (BL+), of those, 55 (7%) lesions were invasive (48 T1,7 T2) (47 unique patients) including 28/55 (51%) de novo invasive lesions (26 unique patients). 21/47 (45%) patients had WL-/BL+ concommitant CIS and/or another T1 lesions. Of 22 patients with WL-/BL+ lesion who underwent cystectomy, high risk pathologic features leading to cystectomy was only visible on BL cystoscopy in 18 (82%) patients. At time of cystectomy, 11/22 (50%) patients showed pathologic upstaging including 4/22 (18%) patients with node positive disease.

Conclusions: A considerable proportion of invasive lesions are only detectable by BL cystoscopy and rate of pathologic upstaging is significant. Our findings suggest an additional benefit of BL cystoscopy in detection of invasive bladder tumors that has implications for treatment approach.
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http://dx.doi.org/10.1111/bju.15614DOI Listing
October 2021

An emerging role for immuno-nutrition in patients undergoing radical cystectomy.

Nat Rev Urol 2021 Oct 5. Epub 2021 Oct 5.

USC Department of Urology, USC/Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.

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http://dx.doi.org/10.1038/s41585-021-00529-2DOI Listing
October 2021

Performance of Narrow Band Imaging (NBI) and Photodynamic Diagnosis (PDD) Fluorescence Imaging Compared to White Light Cystoscopy (WLC) in Detecting Non-Muscle Invasive Bladder Cancer: A Systematic Review and Lesion-Level Diagnostic Meta-Analysis.

Cancers (Basel) 2021 Aug 30;13(17). Epub 2021 Aug 30.

Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.

Despite early detection and regular surveillance of non-muscle invasive bladder cancer (NMIBC), recurrence and progression rates remain exceedingly high for this highly prevalent malignancy. Limited visualization of malignant lesions with standard cystoscopy and associated false-negative biopsy rates have been the driving force for investigating alternative and adjunctive technologies for improved cystoscopy. The aim of our systematic review and meta-analysis was to compare the sensitivity, specificity, and oncologic outcomes of photodynamic diagnosis (PDD) fluorescence, narrow band imaging (NBI), and conventional white light cystoscopy (WLC) in detecting NMIBC. Out of 1,087 studies reviewed, 17 prospective non-randomized and randomized controlled trials met inclusion criteria for the study. We demonstrated that tumor resection with either PDD and NBI exhibited lower recurrence rates and greater diagnostic sensitivity compared to WLC alone. NBI demonstrated superior disease sensitivity and specificity as compared to WLC and an overall greater hierarchical summary receiver operative characteristic. Our findings are consistent with emerging guidelines and underscore the value of integrating these enhanced technologies as a part of the standard care for patients with suspected or confirmed NMIBC.
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http://dx.doi.org/10.3390/cancers13174378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431313PMC
August 2021

Identifying the Optimal Number of Neoadjuvant Chemotherapy Cycles in Patients with Muscle Invasive Bladder Cancer.

J Urol 2021 Aug 27:101097JU0000000000002190. Epub 2021 Aug 27.

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

Purpose: We investigated the pathological response rates and survival associated with 3 vs 4 cycles of cisplatin-based neoadjuvant chemotherapy (NAC) in patients with cT2-4N0M0 muscle invasive bladder cancer.

Materials And Methods: In this cohort study we analyzed clinical data of 828 patients treated with NAC and radical cystectomy between 2000 and 2020. A total of 384 and 444 patients were treated with 3 and 4 cycles of NAC, respectively. Pathological objective response (pOR; ypT0-Ta-Tis-T1 N0), pathological complete response (pCR; ypT0 N0), cancer-specific survival and overall survival were investigated.

Results: pOR and pCR were achieved in 378 (45%; 95% CI 42, 49) and 207 (25%; 95% CI 22, 28) patients, respectively. Patients treated with 4 cycles of NAC had higher pOR (49% vs 42%, p=0.03) and pCR (28% vs 21%, p=0.02) rates compared to those treated with 3 cycles. This effect was confirmed on multivariable logistic regression analysis (pOR OR 1.46 p=0.008, pCR OR 1.57, p=0.007). On multivariable Cox regression analysis, 4 cycles of NAC were significantly associated with overall survival (HR 0.68; 95% CI 0.49, 0.94; p=0.02) but not with cancer-specific survival (HR 0.72; 95% CI 0.50, 1.04; p=0.08).

Conclusions: Four cycles of NAC achieved better pathological response and survival compared to 3 cycles. These findings may aid clinicians in counseling patients and serve as a benchmark for prospective trials. Prospective validation of these findings and assessment of cumulative toxicity derived from an increased number of cycles are needed.
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http://dx.doi.org/10.1097/JU.0000000000002190DOI Listing
August 2021

Vena Cava Tumor Thrombus Associated With Renal Angiomyolipoma in a Jehovah's Witness Patient.

Urology 2021 Aug 18. Epub 2021 Aug 18.

Department of Urology, USC/Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA. Electronic address:

We present a case of a young premenopausal female patient who was found to have a left-sided renal mass consistent with angiomyolipoma (AML) with Mayo Level IIIa vena caval tumor thrombus. The patient is of Jehovah's witness faith and would not accept blood transfusion. The following case report discusses workup and treatment for AML with tumor thrombus extension, as well as pre-operative optimization and intra-operative techniques during nephrectomy and thrombectomy to minimize blood loss in a patient unaccepting of blood transfusion.
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http://dx.doi.org/10.1016/j.urology.2021.08.005DOI Listing
August 2021

Association of age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer.

World J Urol 2021 Aug 9. Epub 2021 Aug 9.

Department of Urology, The James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD, USA.

Purpose: To assess the association of patient age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC).

Materials And Methods: We analyzed data from 1105 patients with MIBC. Patients age was evaluated as continuous variable and stratified in quartiles. Pathologic objective response (pOR; ypT0-Ta-Tis-T1N0) and pathologic complete response (pCR; ypT0N0), as well survival outcomes were assessed. We used data of 395 patients from The Cancer Genome Atlas (TCGA) to investigate the prevalence of TCGA molecular subtypes and DNA damage repair (DDR) gene alterations according to patient age.

Results: pOR was achieved in 40% of patients. There was no difference in distribution of pOR or pCR between age quartiles. On univariable logistic regression analysis, patient age was not associated with pOR or pCR when evaluated as continuous variables or stratified in quartiles (all p > 0.3). Median follow-up was 18 months (IQR 6-37). On Cox regression and competing risk regression analyses, age was not associated with survival outcomes (all p > 0.05). In the TCGA cohort, patient with age ≤ 60 years has 7% less DDR gene mutations (p = 0.59). We found higher age distribution in patients with luminal (p < 0.001) and luminal infiltrated (p = 0.002) compared to those with luminal papillary subtype.

Conclusions: While younger patients may have less mutational tumor burden, our analysis failed to show an association of age with response to preoperative chemotherapy or survival outcomes. Therefore, the use of preoperative chemotherapy should be considered regardless of patient age.
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http://dx.doi.org/10.1007/s00345-021-03793-4DOI Listing
August 2021

The Diagnostic Performance of Cxbladder Resolve, Alone and in Combination with Other Cxbladder Tests, in the Identification and Priority Evaluation of Patients at Risk for Urothelial Carcinoma.

J Urol 2021 Aug 5:101097JU0000000000002135. Epub 2021 Aug 5.

Kaiser Permanente, Pasadena, California.

Purpose: Cxbladder (Cxb) tests combine genomic biomarkers in urine with phenotypic and clinical data to classify hematuria patients into those at low/high probability of urothelial carcinoma (UC). Cxbladder Resolve (CxbR) is designed for use after Cxb Triage (CxbT) and Detect (CxbD), where CxbT-positive tests reflex to CxbD and CxbD-positive to CxbR to identify patients at high probability of high-impact tumors (HIT; high grade Ta, Tis or T1-T3). This study validated the diagnostic performance of CxbR in identifying HIT, and validated the algorithm of Cxb tests to segregate high-impact from low-impact tumors.

Materials And Methods: CxbR was developed in 863 hematuria patients in 3 studies in United States, Australia and New Zealand. CxbR, separately and combined with other Cxb tests, was validated in a prospective, observational U.S. study in 548 hematuria patients. All UC diagnoses were confirmed by histopathology.

Results: In the development data set, CxbR sensitivity was 92.4% (95% CI 83.3-96.7) and specificity 93.8% (95% CI 86.8-97.2) for identifying HIT within the high priority category. During external validation, sequential Cxb tests correctly ruled out 87.6% of patients from further workup (negative predictive value 99.4%); 100% of HIT were correctly identified (specificity 96.3%), and 3 low-grade tumors were missed. In both studies, all patients with HIT were correctly assigned to prioritized evaluation.

Conclusions: CxbR has high sensitivity and specificity, correctly identifying all HIT. Sequential Cxb tests accurately segregate patients with a low vs high probability of HIT, focusing resources on those patients, with a diagnostic yield 4.8-fold higher than American Urological Association guideline stratification.
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http://dx.doi.org/10.1097/JU.0000000000002135DOI Listing
August 2021

The Diagnostic Performance of Cxbladder Resolve, Alone and in Combination with Other Cxbladder Tests, in the Identification and Priority Evaluation of Patients at Risk for Urothelial Carcinoma.

J Urol 2021 Aug 5:101097JU0000000000002135. Epub 2021 Aug 5.

Kaiser Permanente, Pasadena, California.

Purpose: Cxbladder (Cxb) tests combine genomic biomarkers in urine with phenotypic and clinical data to classify hematuria patients into those at low/high probability of urothelial carcinoma (UC). Cxbladder Resolve (CxbR) is designed for use after Cxb Triage (CxbT) and Detect (CxbD), where CxbT-positive tests reflex to CxbD and CxbD-positive to CxbR to identify patients at high probability of high-impact tumors (HIT; high grade Ta, Tis or T1-T3). This study validated the diagnostic performance of CxbR in identifying HIT, and validated the algorithm of Cxb tests to segregate high-impact from low-impact tumors.

Materials And Methods: CxbR was developed in 863 hematuria patients in 3 studies in United States, Australia and New Zealand. CxbR, separately and combined with other Cxb tests, was validated in a prospective, observational U.S. study in 548 hematuria patients. All UC diagnoses were confirmed by histopathology.

Results: In the development data set, CxbR sensitivity was 92.4% (95% CI 83.3-96.7) and specificity 93.8% (95% CI 86.8-97.2) for identifying HIT within the high priority category. During external validation, sequential Cxb tests correctly ruled out 87.6% of patients from further workup (negative predictive value 99.4%); 100% of HIT were correctly identified (specificity 96.3%), and 3 low-grade tumors were missed. In both studies, all patients with HIT were correctly assigned to prioritized evaluation.

Conclusions: CxbR has high sensitivity and specificity, correctly identifying all HIT. Sequential Cxb tests accurately segregate patients with a low vs high probability of HIT, focusing resources on those patients, with a diagnostic yield 4.8-fold higher than American Urological Association guideline stratification.
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http://dx.doi.org/10.1097/JU.0000000000002135DOI Listing
August 2021

Role of Ki-67, MRE11, and PD-L1 as Predictive Biomarkers for Recurrence Pattern in Muscle-invasive Bladder Cancer.

Anticancer Res 2021 Aug;41(8):3851-3857

Department of Radiation Oncology, Keck School of Medicine of USC, Los Angeles, CA, U.S.A.

Background/aim: Muscle invasive bladder cancer (MIBC) is an aggressive disease with high rates of local recurrence following radical cystectomy (RC). Currently, there are no clinically validated biomarkers to predict local only recurrence (LOR) and guide adjuvant treatment decisions. This pilot study evaluated the role of Ki-67, MRE11 and PD-L1 as predictive biomarkers for recurrence patterns in patients undergoing RC for MIBC.

Patients And Methods: Our institutional cystectomy database containing cases from 1992-2014 was queried for patients with local only recurrence (LOR), and case-matched to patients with distant recurrence (DR) and no recurrence (NR). Clinicopathological data were collected and a tissue microarray was analyzed for presence of Ki-67, MRE11, and PD-L1 using immunofluorescence and immunohistochemistry.

Results: Pathologic specimens from 42 patients (18 NR, 16 LOR, and 8 DR) were reviewed. Compared to normal bladder tissue, tumors had increased expression of Ki-67 (p<0.01) and PD-L1 (p<0.05). High Ki-67 was associated with recurrence pattern (local vs. distant) on univariate analysis (p<0.05). Ki-67 cell density varied by recurrence type: LOR (1354 cells/mm), DR (557 cells/mm) and NR (1111 cells/mm) (p=0.034).

Conclusion: Our selected biomarkers could distinguish MIBC from normal bladder tissue but could not classify samples by recurrence pattern.
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http://dx.doi.org/10.21873/anticanres.15178DOI Listing
August 2021

Macro and microeconomics of blue light cystoscopy with CYSVIEW® in non-muscle invasive bladder cancer.

Urol Oncol 2021 Jun 20. Epub 2021 Jun 20.

Department of Urology, MD Anderson Cancer Center, Houston, TX.

Objective: To determine the estimated budget impact to practices that incorporate blue light cystoscopy (BLC) with hexaminolevulinate HCl (HAL) for the surveillance of non-muscle-invasive bladder cancer (NMIBC) in the clinic setting. With the introduction of advanced technologies in the clinic setting such as HAL, further cost comparative research is needed to justify HAL as a high value option.

Material And Methods: A budget impact model was developed from the facility perspective assessing projected costs at 2 years for a simulated facility with 50 newly diagnosed bladder cancer patients. Treatment and surveillance cystoscopy intervals were based on clinical guidelines. Clinical inputs, including tumor stage and grade at diagnosis, rates of recurrence and relative risk reduction when using BLC with HAL, were derived from published studies. Cost inputs were based on Medicare reimbursement rates and facility costs.

Results: Use of BLC identified 9 additional recurrences over two years compared to white light cystoscopy alone. Use of flexible BLC for surveillance marginally increased costs to the practice, with a net difference of $0.76 per cystoscopy over 2 years.

Conclusions: From the office/clinic perspective, the model suggests that the use of flexible BLC for the surveillance of NMIBC may not impact cost per cystoscopy and identifies 9 recurrences over 2 years that would be missed using white light cystoscopy alone. These findings could have important implications in the management of NIMBC and help guide clinical practice guidelines that promote cost-effective care and improved patient outcomes.
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http://dx.doi.org/10.1016/j.urolonc.2021.05.023DOI Listing
June 2021

ctDNA guiding adjuvant immunotherapy in urothelial carcinoma.

Nature 2021 07 16;595(7867):432-437. Epub 2021 Jun 16.

Roche/Genentech, South San Francisco, CA, USA.

Minimally invasive approaches to detect residual disease after surgery are needed to identify patients with cancer who are at risk for metastatic relapse. Circulating tumour DNA (ctDNA) holds promise as a biomarker for molecular residual disease and relapse. We evaluated outcomes in 581 patients who had undergone surgery and were evaluable for ctDNA from a randomized phase III trial of adjuvant atezolizumab versus observation in operable urothelial cancer. This trial did not reach its efficacy end point in the intention-to-treat population. Here we show that ctDNA testing at the start of therapy (cycle 1 day 1) identified 214 (37%) patients who were positive for ctDNA and who had poor prognosis (observation arm hazard ratio = 6.3 (95% confidence interval: 4.45-8.92); P < 0.0001). Notably, patients who were positive for ctDNA had improved disease-free survival and overall survival in the atezolizumab arm versus the observation arm (disease-free survival hazard ratio = 0.58 (95% confidence interval: 0.43-0.79); P = 0.0024, overall survival hazard ratio = 0.59 (95% confidence interval: 0.41-0.86)). No difference in disease-free survival or overall survival between treatment arms was noted for patients who were negative for ctDNA. The rate of ctDNA clearance at week 6 was higher in the atezolizumab arm (18%) than in the observation arm (4%) (P = 0.0204). Transcriptomic analysis of tumours from patients who were positive for ctDNA revealed higher expression levels of cell-cycle and keratin genes. For patients who were positive for ctDNA and who were treated with atezolizumab, non-relapse was associated with immune response signatures and basal-squamous gene features, whereas relapse was associated with angiogenesis and fibroblast TGFβ signatures. These data suggest that adjuvant atezolizumab may be associated with improved outcomes compared with observation in patients who are positive for ctDNA and who are at a high risk of relapse. These findings, if validated in other settings, would shift approaches to postoperative cancer care.
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http://dx.doi.org/10.1038/s41586-021-03642-9DOI Listing
July 2021

Perioperative outcomes of goal-directed versus conventional fluid therapy in radical cystectomy with enhanced recovery protocol.

Int Urol Nephrol 2021 Sep 4;53(9):1827-1833. Epub 2021 Jun 4.

Institute of Urology, Norris Comprehensive Cancer Center, University of Southern California, USC, 1441 Eastlake Ave. NOR 7416, Los Angeles, CA, 90089, USA.

Purpose: The aim of this study is to evaluate the intra/perioperative fluid management and early postoperative outcomes of patients who underwent radical cystectomy with Enhanced Recovery After Surgery protocol, using goal-directed fluid therapy compared to conventional fluid therapy.

Methods: This cohort study included patients who underwent open RC for urothelial bladder carcinoma with intent to cure and Enhanced Recovery After Surgery protocol between May 2012 and August 2019. Patients who had palliative or salvage cystectomy and/or adjunct procedures, as well as those with missing detailed perioperative data were excluded. Data were compared between patients who received goal-directed fluid therapy using stroke volume variation by FloTrac™/Vigileo system (n = 119) and conventional fluid therapy based on the anesthesiologist discretion (n = 192). Primary outcome variable was 90-day complications and secondary outcome measures included in-hospital GFR trend, length of stay, and 90-day readmission.

Results: The goal-directed fluid therapy group received less total and net intra/perioperative fluid, yet early postoperative glomerular filtration rate trends were similar between both groups (p = 0.7). Estimated blood loss, blood transfusion, index hospital stay, 90-day complication and readmission rates were also comparable between the two groups. Multivariable logistic regression showed no significant association between perioperative fluid management method and 90-day complication rate (OR 1.4, 95% CI 0.8-2.4, p = 0.2).

Conclusion: Stroke volume variation guided goal-directed fluid therapy is safe in radical cystectomy without compromising the renal function. It is associated with less intra- and perioperative fluid infusion; however, no association with hospital stay, 90-day complication or readmission rates were noted.
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http://dx.doi.org/10.1007/s11255-021-02903-wDOI Listing
September 2021

Evaluation of Bowel Function Following Radical Cystectomy and Urinary Diversion Using Two Validated Questionnaires: What Are the Effects on Quality of Life?

Urology 2021 May 28. Epub 2021 May 28.

USC Institute of Urology, USC/Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA. Electronic address:

Objective: To assess both short- and long-term constipation symptoms and their impact on quality of life in patients who underwent radical cystectomy (RC) with three different types of urinary diversion: orthotopic neobladder (ONB), continent cutaneous diversion (CCD), and ileal conduit (IC).

Materials And Methods: The validated Patient Assessment of Constipation Symptoms (PAC-SYM) and Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaires were administered to all patients at follow-up greater than 30 days from surgery. Clinical and pathological characteristics were prospectively recorded in an institutional review board approved bladder cancer database. Using multivariable linear regression analyses, we determined significant predictors of improved constipation symptoms and quality of life scores.

Results: A total of 198 patients completed 255 PAC-SYM and PAC-QOL questionnaires with a median follow-up time of 1.7 years (IQR: 0.7 - 3.0 years). ONB, CCD, and IC were performed in 78%, 5.5%, and 16.5% of patients, respectively. Higher bowel function scores (i.e. worse symptoms) were noted at 3 months post-operatively, while these scores significantly improved over time for PAC-SYM total score (P = .004), abdominal subscore (P = .001), and rectal subscore (P = .018). On multivariable analysis, we found that patients <70 years old (B -2.1, P = .004), with follow-up >1 year (B -4.8, P = .001), and who received an IC (B -2.4, P = .02) had significantly lower PAC-SYM scores.

Conclusion: Patients have few constipation symptoms and are overall satisfied with their bowel function at long-term follow-up after RC. While patients with IC have significantly fewer constipation symptoms compared to those with ONB or CCD, all patients had significant improvement one year after the surgery.
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http://dx.doi.org/10.1016/j.urology.2021.04.044DOI Listing
May 2021

A Massive Penile Tumor.

Urology 2021 Aug 25;154:e5-e6. Epub 2021 May 25.

USC Institute of Urology, USC/Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA. Electronic address:

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http://dx.doi.org/10.1016/j.urology.2021.05.024DOI Listing
August 2021

Enhanced recovery after cystectomy in patients with preoperative narcotic use.

Can Urol Assoc J 2021 Oct;15(10):E563-E568

Institute of Urology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, United States.

Introduction: The aim of this study was to evaluate the outcomes of radical cystectomy with an enhanced recovery after surgery (ERAS) protocol in patients with a history of chronic preoperative narcotic use compared to narcotic-naive patients.

Methods: We identified 553 patients who underwent open radical cystectomy with ERAS. Preoperative narcotic use was identified in 34 patients who were then matched to 68 narcotic-naive patients. Postoperative outcomes, opioid use, and visual analog scale (VAS) pain scores were analyzed and compared. All routes of opioid use were recorded and converted to a morphine equivalent dose (MED).

Results: Patients with preoperative narcotic use reported higher median VAS pain scores per day (postoperative day [POD1]: 5.2 vs. 3.9, p=0.003; POD2: 5.1 vs. 3.6, p<0.001; POD3: 4.6 vs. 3.8, p=0.004) and used significantly more opioids (median MED) per day (POD1: 13.2 vs. 10.0, p=0.02; POD2: 11.3 vs. 6.4, p=0.003; POD3: 10.2 vs. 5.0, p=0.005) following surgery. Preoperative narcotic users were noted to have a significantly higher incidence of 90-day re-admissions (41.2% vs. 20.6%, p=0.03). There was no difference in median hospital stay (4 vs. 4 days, p=0.6), 30-or 90-day complications (64.7% vs. 60.3%, p=0.8 and 82.4% vs. 75.0%, p=0.4, respectively) or gastrointestinal complications (29.4% vs. 26.5%, p=0.8), including postoperative ileus (11.8% vs. 20.6%, p=0.2).

Conclusions: Patients with preoperative narcotic exposure report higher pain scores and require more opioid use following radical cystectomy with ERAS and are more likely to be re-admitted within 90 days. However, there was no observed difference in hospital stay or complications.
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http://dx.doi.org/10.5489/cuaj.7007DOI Listing
October 2021

Validation of the COBRA nomogram for the prediction of cancer specific survival in patients treated with radical cystectomy for bladder cancer: An international wide cohort study.

Eur J Surg Oncol 2021 Oct 30;47(10):2646-2650. Epub 2021 Apr 30.

Ospedale Sant'Andrea, Sapienza University of Rome, Roma, Italy.

Background: Recently, the Cancer of the Bladder Risk Assessment (COBRA) score has been introduced to estimate cancer specific survival (CSS) after radical cystectomy for bladder cancer.

Objectives: Aim of our study was to validate the COBRA score, assessing the effect of age, tumor stage and lymph-nodes status on CSS after cystectomy in patients with bladder cancer.

Design, Setting, And Participants: A consecutive series of 2395 patients with primitive or recurrent bladder cancer treated with radical cystectomy in 4 centers were evaluated.

Outcome Measurements And Statistical Analysis: The role of COBRA score as predictor of CSS was assessed using the Kaplan Meier and Cox proportional hazards analyses. Accuracy of COBRA score was evaluated by Harrell's C test.

Results And Limitations: Median age was 66 (IQR 58/73) years. Overall, at a median follow-up of 48 (IQR 22/92) months, 642 patients (27%) died of bladder cancer. On Cox proportional hazards analyses, COBRA score was a significant predictor of CSS (HR 1.54, 95%CI 1.47-1.61) (Table 1). The predictive accuracy of the COBRA score was 0.71. A sub analysis including pooled COBRA score (0 vs 1-3 vs 4 vs 5-7) improved the clinical applicability with the same accuracy.

Conclusion: In our experience, the COBRA score is an excellent tool to predict cancer specific survival. The COBRA Score represents a practical and easy tool that may help urologists to classify the CSS of patients treated with radical cystectomy, to predict the oncological outcome and finally to counsel bladder cancer patients.
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http://dx.doi.org/10.1016/j.ejso.2021.04.035DOI Listing
October 2021

Diagnosis and Staging of Bladder Cancer.

Hematol Oncol Clin North Am 2021 Jun 15;35(3):531-541. Epub 2021 Apr 15.

Department of Urology, University of Southern California/Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Suite 7416, Los Angeles, CA 90089, USA; USC/Norris Comprehensive Cancer Center, USC Institute of Urology, 1441 Eastlake Avenue, Suite 7416, Los Angeles, CA 90089, USA. Electronic address:

Cystoscopic examination remains the gold standard technique for initial diagnosis of bladder cancer (BCa). Despite significant progress in enhanced cystoscopic techniques, blue light cystoscopy and narrow band imaging are the only ones well supported by high-level evidence and, if available, should be used during initial staging of BCa. Multiparametric MRI could be an important imaging tool in local staging of BCa. With ever-expanding targeted therapy and immunotherapy options in both muscle-invasive and non-muscle-invasive BCa, molecular subtyping could become an essential part of initial histologic staging in the near future.
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http://dx.doi.org/10.1016/j.hoc.2021.02.004DOI Listing
June 2021

Clinical evaluation of Bladder CARE, a new epigenetic test for bladder cancer detection in urine samples.

Clin Epigenetics 2021 04 21;13(1):84. Epub 2021 Apr 21.

Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Background: Bladder cancer (BC) is the 5th most common cancer in the USA. Non-muscle invasive bladder cancer represents about 70% of all cases and has generally a favorable outcome. However, recurrence rates as high as 60 to 70% and progression rates of 10 to 20% necessitate intensive surveillance with cystoscopy. The invasiveness and high cost of cystoscopy poses significant burden on BC patients as well as on the healthcare system. In this study we test the feasibility of a simple, sensitive, and non-invasive detection of BC using Bladder CARE test in urine samples.

Results: Urine from 136 healthy and 77 BC subjects was collected using the at-home Bladder CARE Urine Collection Kit and analyzed with Bladder CARE test. The test measures the methylation level of three BC-specific biomarkers and two internal controls using methylation-sensitive restriction enzymes coupled with qPCR. Bladder CARE showed an overall sensitivity of 93.5%, a specificity of 92.6%, and a PPV and NPV of 87.8% and 96.2%, respectively. Bladder CARE has an LOD as low as 0.046%, which equates to detecting 1 cancer cell for every 2,200 cells analyzed. We also provided evidence that bisulfite-free methods to assess DNA methylation, like Bladder CARE, are advantageous compared to conventional methods that rely on bisulfite conversion of the DNA.

Conclusion: Highly sensitive detection of BC in urine samples is possible using Bladder CARE. The low LOD of the test and the measurement of epigenetic biomarkers make Bladder CARE a good candidate for the early detection of BC and possibly for the routine screening and surveillance of BC patients. Bladder CARE and the at-home urine sample collection system have the potential to (1) reduce unnecessary invasive testing for BC (2) reduce the burden of surveillance on patients and on the healthcare system, (3) improve the detection of early stage BC, and (4) allow physicians to streamline the monitoring of patients.
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http://dx.doi.org/10.1186/s13148-021-01029-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059345PMC
April 2021

Disparities in male versus female oncologic outcomes following bladder preservation: A population-based cohort study.

Cancer Med 2021 05 28;10(9):3004-3012. Epub 2021 Mar 28.

Department of Preventative Medicine, Keck School of Medicine, University of Southern CA, Los Angeles, CA, USA.

Introduction: In surgical series of muscle-invasive bladder cancer (MIBC), women have higher recurrence rates, disease progression, and mortality following radical cystectomy than men. Similar reports of oncologic differences between men and women following trimodality therapy (TMT) are rare. Our hypothesis was that there would be no difference in overall survival (OS) between sexes receiving TMT.

Methods: We queried the National Cancer Database (NCDB) for patients diagnosed with clinical stage T2-T4aN0 M0 MIBC between 2004-2016. We considered patients to have received TMT if they received 55 Gy in 20 fractions or 59.4-70.2 Gy of radiotherapy with concurrent chemotherapy following a transurethral resection of bladder tumor (TURBT). We used multivariable Cox proportional hazard models to determine whether sex was associated with risk of mortality. In addition to OS, we calculated relative survival (RS) to adjust for the fact that females generally survive longer than males.

Results: Of the patients, 1960 underwent TMT and had survival data. Less than one quarter were female. In the first year following treatment, women had worse OS and RS than men (p = 0.093 and p = 0.030, respectively). However, overall and relative survival differences between sexes were not statistically significantly different in Years 2 and later. Unlike with OS, the RS between sexes remained significant at 9 years; in multivariable analysis based on RS, women were 43% more likely to die than men (p < 0.001).

Conclusions: Women had a higher initial risk of death than men in the first year following TMT. However, long-term survival between sexes was similar. TMT is an important treatment option in both men and women seeking bladder preservation.
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http://dx.doi.org/10.1002/cam4.3835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085939PMC
May 2021

Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (IMvigor010): a multicentre, open-label, randomised, phase 3 trial.

Lancet Oncol 2021 04 12;22(4):525-537. Epub 2021 Mar 12.

Barts Cancer Institute, Queen Mary University of London, St Bartholomew's Hospital, London, UK.

Background: Despite standard curative-intent treatment with neoadjuvant cisplatin-based chemotherapy, followed by radical surgery in eligible patients, muscle-invasive urothelial carcinoma has a high recurrence rate and no level 1 evidence for adjuvant therapy. We aimed to evaluate atezolizumab as adjuvant therapy in patients with high-risk muscle-invasive urothelial carcinoma.

Method: In the IMvigor010 study, a multicentre, open-label, randomised, phase 3 trial done in 192 hospitals, academic centres, and community oncology practices across 24 countries or regions, patients aged 18 years and older with histologically confirmed muscle-invasive urothelial carcinoma and an Eastern Cooperative Oncology Group performance status of 0, 1, or 2 were enrolled within 14 weeks after radical cystectomy or nephroureterectomy with lymph node dissection. Patients had ypT2-4a or ypN+ tumours following neoadjuvant chemotherapy or pT3-4a or pN+ tumours if no neoadjuvant chemotherapy was received. Patients not treated with neoadjuvant chemotherapy must have been ineligible for or declined cisplatin-based adjuvant chemotherapy. No post-surgical radiotherapy or previous adjuvant chemotherapy was allowed. Patients were randomly assigned (1:1) using a permuted block (block size of four) method and interactive voice-web response system to receive 1200 mg atezolizumab given intravenously every 3 weeks for 16 cycles or up to 1 year, whichever occurred first, or to observation. Randomisation was stratified by previous neoadjuvant chemotherapy use, number of lymph nodes resected, pathological nodal status, tumour stage, and PD-L1 expression on tumour-infiltrating immune cells. The primary endpoint was disease-free survival in the intention-to-treat population. Safety was assessed in patients who either received at least one dose of atezolizumab or had at least one post-baseline safety assessment. This trial is registered with ClinicalTrials.gov, NCT02450331, and is ongoing but not recruiting patients.

Findings: Between Oct 5, 2015, and July 30, 2018, we enrolled 809 patients, of whom 406 were assigned to the atezolizumab group and 403 were assigned to the observation group. Median follow-up was 21·9 months (IQR 13·2-29·8). Median disease-free survival was 19·4 months (95% CI 15·9-24·8) with atezolizumab and 16·6 months (11·2-24·8) with observation (stratified hazard ratio 0·89 [95% CI 0·74-1·08]; p=0·24). The most common grade 3 or 4 adverse events were urinary tract infection (31 [8%] of 390 patients in the atezolizumab group vs 20 [5%] of 397 patients in the observation group), pyelonephritis (12 [3%]) vs 14 [4%]), and anaemia (eight [2%] vs seven [2%]). Serious adverse events occurred in 122 (31%) patients who received atezolizumab and 71 (18%) who underwent observation. 63 (16%) patients who received atezolizumab had a treatment-related grade 3 or 4 adverse event. One treatment-related death, due to acute respiratory distress syndrome, occurred in the atezolizumab group.

Interpretation: To our knowledge, IMvigor010 is the largest, first-completed phase 3 adjuvant study to evaluate the role of a checkpoint inhibitor in muscle-invasive urothelial carcinoma. The trial did not meet its primary endpoint of improved disease-free survival in the atezolizumab group over observation. Atezolizumab was generally tolerable, with no new safety signals; however, higher frequencies of adverse events leading to discontinuation were reported than in metastatic urothelial carcinoma studies. These data do not support the use of adjuvant checkpoint inhibitor therapy in the setting evaluated in IMvigor010 at this time.

Funding: F Hoffmann-La Roche/Genentech.
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http://dx.doi.org/10.1016/S1470-2045(21)00004-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495594PMC
April 2021

A Novel DNA Methylation Signature as an Independent Prognostic Factor in Muscle-Invasive Bladder Cancer.

Front Oncol 2021 15;11:614927. Epub 2021 Feb 15.

USC Institute of Urology and Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.

Background: Muscle-invasive bladder cancer (MIBC) accounts for approximately 20% of all urothelial bladder carcinomas (UBC) at time of diagnosis, and up to 30% of patients with non-muscle invasive UBC will progress to MIBC over time. An increasing body of evidence has revealed a strong correlation between aberrant DNA methylation and tumorigenesis in MIBC.

Results: Using The Cancer Genome Atlas (TCGA) molecular data for 413 patients, we described a DNA methylation-based signature as a prognostic factor for overall survival (OS) in MIBC patients. By using a least absolute shrinkage and selection operator (LASSO) model, differentially methylated regions were first identified using multiple criteria followed by survival and LASSO analyses to identify DNA methylation probes related to OS and build a classifier to stratify patients with MIBC. The prognostic value of the classifier, referred to as risk score (RS), was validated in a held-out testing set from the TCGA MIBC cohort. Finally, receiver operating characteristic (ROC) analysis was used to compare the prognostic accuracy of the models built with RS alone, RS plus clinicopathologic features, and clinicopathologic features alone. We found that our seven-probe classifier-based RS stratifies patients into high- and low-risk groups for overall survival (OS) in the testing set (n = 137) (AUC at 3 years, 0.65; AUC at 5 years, 0.65). In addition, RS significantly improved the prognostic model when it was combined with clinical information including age, smoking status, Tumor (T) stage, and Lymph node metastasis (N) stage.

Conclusions: The DNA methylation-based RS can be a useful tool to predict the accuracy of preoperative and/or post-cystectomy models of OS in MIBC patients.
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http://dx.doi.org/10.3389/fonc.2021.614927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917237PMC
February 2021

A Randomized Phase II Study of Coexpression Extrapolation (COXEN) with Neoadjuvant Chemotherapy for Bladder Cancer (SWOG S1314; NCT02177695).

Clin Cancer Res 2021 May 10;27(9):2435-2441. Epub 2021 Feb 10.

CHRISTUS Medical Center Hospital, University of Texas Health Science Center at San Antonio, San Antonio, Texas.

Purpose: Dose-dense methotrexate-vinblastine-adriamycin-cisplatin (ddMVAC) and gemcitabine-cisplatin (GC) are accepted neoadjuvant regimens for muscle-invasive bladder cancer. The aim of this study was to validate the score from a coexpression extrapolation (COXEN) algorithm-generated gene expression model (GEM) as a biomarker in patients undergoing radical cystectomy.

Patients And Methods: Eligibility included cT2-T4a N0 M0, urothelial bladder cancer, ≥ 5 mm of viable tumor, cisplatin eligible, with plan for cystectomy; 237 patients were randomized between ddMVAC, given every 14 days for four cycles, and GC, given every 21 days for four cycles. The primary objective assessed prespecified dichotomous treatment-specific COXEN score as predictive of pT0 rate or ≤ pT1 (downstaging) at surgery.

Results: Among 167 evaluable patients, the OR for pT0 with the GC GEM score in GC-treated patients was 2.63 [ = 0.10; 95% confidence interval (CI), 0.82-8.36]; for the ddMVAC COXEN GEM score with ddMVAC treatment, the OR was 1.12 ( = 0.82, 95% CI, 0.42-2.95). The GC GEM score was applied to pooled arms (GC and ddMVAC) for downstaging with an OR of 2.33 ( = 0.02; 95% CI, 1.11-4.89). In an intention-to-treat analysis of eligible patients ( = 227), pT0 rates for ddMVAC and GC were 28% and 30% ( = 0.75); downstaging was 47% and 40% ( = 0.27), respectively.

Conclusions: Treatment-specific COXEN scores were not significantly predictive for response to individual chemotherapy treatment. The COXEN GEM GC score was significantly associated with downstaging in the pooled arms. Additional biomarker development is planned.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-2409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219246PMC
May 2021

Multiparametric cystoscopy: is the future here yet?

Transl Androl Urol 2021 Jan;10(1):1-6

Department of Urology, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, USA.

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http://dx.doi.org/10.21037/tau-20-1012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844506PMC
January 2021

Genetic Differences Between Bladder and Upper Urinary Tract Carcinoma: Implications for Therapy.

Eur Urol Oncol 2021 Apr 30;4(2):170-179. Epub 2020 Dec 30.

Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.

Context: Bladder urothelial carcinoma (BUC) and upper tract urothelial carcinoma (UTUC) have genetic differences, which may influence therapy.

Objective: The aim of the current review was to summarize the current genetic understanding of upper tract and BUC.

Evidence Acquisition: PubMed, Cochrane, and Web of Science online databases were searched systematically up to February 2020, using the following keywords: urothelial carcinomas, upper urinary tract, renal pelvis, ureter, bladder cancer, and genetics.

Evidence Synthesis: UTUC and BUC share mutations in similar genes, such as FGFR3, TP53, and HRAS, and epigenetic genes, such as KDM6A and KMT2A-C, but at varying frequencies. Furthermore, subtyping of UTUC and BUC has identified similar expression subtypes, but UTUC is more often luminal with more T-cell depletion. Clonal studies indicate that BUC after UTUC is also likely luminal, while UTUC after BUC is often basal.

Conclusions: UTUC and BUC share many genomic alterations, but at different frequencies, which recapitulate with their metachronous recurrences. These differences likely contribute to the behavior of these two cancers and imply that they and their metachronous recurrences should be treated as two related yet distinct entities.

Patient Summary: Urothelial carcinoma of the bladder has distinct genomic features, which are different from distinct genomic features of urothelial carcinoma of the renal pelvis and/or ureter. These features can be used for tailored treatment options specific to tumors of different locations.
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http://dx.doi.org/10.1016/j.euo.2020.12.007DOI Listing
April 2021

Predictors of need for catheterisation and urinary retention after radical cystectomy and orthotopic neobladder in male patients.

BJU Int 2021 Sep 20;128(3):304-310. Epub 2021 Jan 20.

Department of Urology, USC/Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.

Objectives: To investigate the prevalence of catheterisation and urinary retention in male patients with bladder cancer after radical cystectomy (RC) and orthotopic neobladder (ONB) and to identify potential predictors.

Patients And Methods: Using an Institutional Review Board approved, prospectively maintained bladder cancer database, we collected information using a diversion-related questionnaire from 299 consecutive male patients with bladder cancer upon postoperative clinic visit. Urinary retention was defined as ≥3 catheterisations/day or a self-reported inability to void without a catheter. Uni- and multivariable Cox regression analysis was performed to identify predictors of catheterisation and urinary retention.

Results: Self-catheterisation was reported in 51 patients (17%), of whom, 22 (7.4% of the total patients) were in retention. Freedom from any catheterisation at 3, 5, and 10 years after RC was 85%, 77%, and 62%, respectively. Freedom from retention at 3, 5, and 10 years after RC was 93%, 88%, and 79%, respectively. Multivariable Cox regression showed that higher body mass index (BMI; ≥27 kg/m ) significantly increased the need for catheterisation (hazard ratio [HR] 2.34, 95% confidence interval [CI] 1.26-4.32) as well as retention (HR 5.20, 95% CI 1.74-15.51). Greater medical comorbidity (Charlson Comorbidity Index score ≥2) correlated with the need for any catheterisation (HR 1.84, 95% CI 1.02-3.3), but not retention. Pathological stage and type of diversion were not significant predictors of the need to catheterise or urinary retention.

Conclusion: In males undergoing RC with ONB, retention requiring catheterisation to void is uncommon. Patients with a BMI of ≥27 kg/m are at significantly increased risk of retention and need for self-catheterisation.
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http://dx.doi.org/10.1111/bju.15329DOI Listing
September 2021

Enhanced Endoscopy with IMAGE1 S CHROMA Improves Detection of Nonmuscle Invasive Bladder Cancer During Transurethral Resection.

J Endourol 2021 05 4;35(5):647-651. Epub 2020 Dec 4.

Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

We assessed the ability of enhanced cystoscopy with CHROMA image enhancement (Karl Storz SE & Co. KG, Tuttlingen, Germany) to improve cancer detection during transurethral resection of bladder tumors (TURBT) in patients with known or suspected nonmuscle invasive bladder cancer (NMIBC). A total of 49 patients (82% men) with a median age of 71 years underwent TURBT for known or suspected NMIBC. Bladders were assessed first with conventional white light imaging and then with CHROMA enhancement. We quantified the number of tumors seen with white light and any additional tumors seen with CHROMA and correlated with pathologic results. A total of 165 tumors were viewed in 47 patients; of these, 25 were only seen using CHROMA. Use of CHROMA yielded additional tumors not appreciated on white light in 14 of 39 patients with underlying malignancy, for an additional detection rate (ADR) of 36% (95% confidence interval, 21%-53%). CHROMA improved detection of tumors in the setting of both low-grade (LG) and high-grade (HG) disease with equal efficacy (ADR 43% in LG and 44% in HG,  = 0.98, Barnard exact test). Cystoscopy with CHROMA contrast enhancement facilitates detection of bladder tumors that are not readily appreciated using conventional white light cystoscopy. The technology integrates seamlessly with current practice and can serve as an adjunct to other novel technologies.
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http://dx.doi.org/10.1089/end.2020.0821DOI Listing
May 2021

Integrated Expression of Circulating miR375 and miR371 to Identify Teratoma and Active Germ Cell Malignancy Components in Malignant Germ Cell Tumors.

Eur Urol 2021 01 4;79(1):16-19. Epub 2020 Nov 4.

Department of Medicine, Medical Oncology Division, BC Cancer, Vancouver Centre, University of British Columbia, Vancouver, BC, Canada. Electronic address:

Active germ cell malignancies express high levels of specific circulating micro-RNAs (miRNAs), including miR-371a-3p (miR371), which is undetectable in teratoma. Teratoma markers are urgently needed for theselection of patients and treatments because of the risk of malignant transformation and growing teratoma syndrome. To assess the accuracy of plasma miR375 alone or in combination with miR371 in detecting teratoma, 100 germ cell tumor patients, divided into two cohorts, were enrolled in a prospective multi-institutional study. In the discovery cohort, patients with pure teratoma and with no/low risk of harboring teratoma were compared; the validation cohort included patients with confirmed teratoma, active germ cell malignancy, or complete response after chemotherapy. The area under the receiver operating characteristic curve values for miR375, miR371, and miR371-miR375 were, respectively, 0.93 (95% confidence interval [CI]: 0.87-0.99), 0.59 (95% CI: 0.44-0.73), and 0.95 (95% CI: 0.90-0.99) in the discovery cohort and 0.55 (95% CI: 0.36-0.74), 0.74 (95% CI: 0.58-0.91), and 0.77 (95% CI: 0.62-0.93) in the validation cohort. Our study demonstrated that the plasma miR371-miR375 integrated evaluation is highly accurate to detect teratoma. PATIENT SUMMARY: The evaluation of two micro-RNAs (miR375-miR371) in the blood of patients with germ cell tumors is promising to predict teratoma. This test could be particularly relevant to the identification of teratoma in patients with postchemotherapy residual disease.
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http://dx.doi.org/10.1016/j.eururo.2020.10.024DOI Listing
January 2021

Neoadjuvant chemotherapy plus radical cystectomy versus radical cystectomy alone in clinical T2 bladder cancer without hydronephrosis.

BJU Int 2021 Jul 21;128(1):79-87. Epub 2020 Nov 21.

Division of Urology, Department of Surgical Sciences, Torino School of Medicine, Torino, Italy.

Objectives: To assess the efficacy of neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in a retrospective multicentre cohort of patients with cT2N0M0 bladder cancer (BCa) without preoperative hydronephrosis.

Patients And Methods: This was a propensity-based analysis of 619 patients. Of these, 316 were treated with NAC followed by RC and 303 with upfront RC. After multiple imputations, inverse probability of treatment weighting (IPTW) was used to account for potential selection bias. Multivariable logistic regression analysis was performed to evaluate the impact of NAC on pathological complete response and downstaging at RC, while IPTW-adjusted Kaplan-Meier curves and Cox regression models were built to evaluate the impact of NAC on overall survival (OS).

Results: After IPTW-adjusted analysis, standardised differences between groups were <15%. A complete response (pT0N0) at final pathology was achieved in 94 (30%) patients receiving NAC and nine (3%) undergoing upfront RC. Downstaging to non-muscle-invasive disease (
Conclusions: In patients with cT2N0 BCa and no preoperative hydronephrosis, NAC increased the rate of pathological complete response and downstaging.
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http://dx.doi.org/10.1111/bju.15289DOI Listing
July 2021

Impact of Non-guideline-directed Care on Quality of Life in Testicular Cancer Survivors.

Eur Urol Focus 2020 Oct 26. Epub 2020 Oct 26.

Section of Urology, University of Chicago Medicine, Chicago, IL, USA. Electronic address:

Background: Non-guideline-directed care (NGDC) is seen in ∼30% of testicular cancer patients and has been identified as a significant predictor of relapse. However, the potential impact of mismanagement on patient quality of life (QoL) is yet to be established.

Objective: To explore the impact of NGDC on long-term QoL in testicular cancer survivors (TCSs).

Design, Setting, And Participants: A retrospective review of TCSs, who completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) in person or via mail ≥6 mo after completion of treatment, was conducted.

Outcome Measurements And Statistical Analysis: The validated questionnaire evaluates global health status (GHS); cognitive, social, physical, emotional, and role functioning; financial burden; and treatment-specific side effects.

Results And Limitations: A total of 120 men with a median age of 31.5 (interquartile range: 24-42) yr completed the questionnaire. Thirty-four (28%) men received NGDC: overtreatment (44%), improper imaging (32%), and undertreatment (29%). Men with NGDC presented with a more advanced clinical stage (≥IIA: 64% vs 32%, p = 0.007) and were less likely to undergo surveillance (19% vs 37%, p = 0.016). Patients receiving guideline-directed care reported higher GHS (84.1 vs 77.5, p = 0.015), higher physical function scores (98.5 vs 91.2, p = 0.013), and fewer financial difficulties (5.8 vs 18.6, p = 0.006) than those receiving NGDC. Multivariable linear regression showed a significant association between NGDC and poorer GHS (p = 0.002). Limitations of the study include its retrospective nature, modest sample size due to a 21% response rate, and quality-of-life assessment at a single time point rather than serially over time.

Conclusions: In addition to treatment delay, avoidable morbidity, and higher rates of relapse, NGDC leads to inferior global QoL, worse physical functioning, and more financial stress.

Patient Summary: We have previously shown how mismanagement of testicular cancer results in a higher rate of disease relapse. In this study, we emphasize how the lack of adherence to standard treatment guidelines can lead to worse quality of life outcomes and financial stress in testicular cancer survivors.
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http://dx.doi.org/10.1016/j.euf.2020.10.005DOI Listing
October 2020
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