Publications by authors named "Vitaly Margulis"

319 Publications

Single stage Xi® robotic radical nephroureterectomy for upper tract urothelial carcinoma: surgical technique and outcomes.

Minerva Urol Nephrol 2021 Mar 29. Epub 2021 Mar 29.

Division of Urology, VCU Health System, Richmond, VA, USA -

Background: Radical nephroureterectomy (RNU) represents the standard of care for high grade upper tract urothelial carcinoma (UTUC). Open and laparoscopic approaches are well-established treatments, but evidence regarding robotic RANU is growing. The introduction of the Xi® system facilitates the implementation of this multi-quadrant procedure. The aim of this video-article is to describe the surgical steps and the outcomes of Xi® robotic RNU.

Methods: Single stage Xi® robotic RNU without patients repositioning and robot re-docking were done between 2015 and 2019 and collected in a large worldwide multi-institutional study, the ROBotic surgery for Upper tract Urothelial cancer STudy (ROBUUST). Institutional review board approval and data share agreement were obtained at each center. Surgical technique is described in detail in the accompanying video. Descriptive statistics of baseline characteristics and surgical, pathological, and oncological outcomes were analyzed. RESULTSː Overall, 148 patients were included in the analysis; 14% had an ECOG >1 and 68.2% ASA ≥3. Median tumor dimension was 3.0 (IQR:2.0-4.2) cm and 34.5% showed hydronephrosis at diagnosis. Forty-eight% were cT1 tumors. Bladder cuff excision and lymph node dissection were performed in 96% and 38.1% of the procedures, respectively. Median operative time and estimated blood loss were 215.5 (IQR:160.5-290.0) minutes and 100.0 (IQR: 50.0-150.0) mL, respectively. Approximately 56% of patients took opioids during hospital stay for a total morphine equivalent dose of 22.9 (IQR:16.0-60.0) milligrams equivalent. Postoperative complications were 26 (17.7%), with 4 major (15.4%). Seven patients underwent adjuvant chemotherapy, with median number of cycles of 4.0 (IQR:3.0-6.0).

Conclusions: Single stage Xi® RNU is a reproducible and safe minimally invasive procedure for treatment of UTUC. Additional potential advantages of the robot might be a wider implementation of LND with a minimally invasive approach.
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http://dx.doi.org/10.23736/S2724-6051.21.04247-8DOI Listing
March 2021

Prognostic effect of preoperative systemic immune-inflammation index in patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma.

Minerva Urol Nephrol 2021 Mar 26. Epub 2021 Mar 26.

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

Background: Identifying those of patients with metastatic renal cell carcinoma (mRCC) who are most likely to benefit from cytoreductive nephrectomy (CN) is challenging. We tested the association between preoperative value of systemic immune-inflammation index (SII) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN.

Methods: mRCC patients treated with CN at different institutions were included. After assessing for the optimal pretreatment SII cut-off value, we found 710 to have the maximum Youden index value. The overall population was therefore divided into two SII groups using this cut-off (low, <710 vs high, ≥710). Univariable and multivariable Cox regression analyses tested the association SII and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's concordance index (C-index). The clinical value of the SII was evaluated with decision curve analysis (DCA).

Results: Among 613 mRCC patients, 298 (49%) patients had a SII ≥ 710. Median follow-up was 31 (IQR 16-58) months. On univariable analysis, high preoperative serum SII was significantly associated with worse OS (HR: 1.28, 95%CI: 1.07-1.54, p=0.01) and CSS (HR: 1.29, 95%CI: 1.08-1.55, p=0.01). On multivariable analysis, which adjusted for the effect of established clinicopathologic features, SII≥ 710 was associated with OS (HR: 1.25, 95%CI: 1.04-1.50, p=0.02) and CSS (HR: 1.26, 95%CI: 1.05-1.52, p=0.01). The addition of SII only slightly improved the discrimination of a base model that included established clinicopathologic features (C-index = 0.637 vs C-index = 0.629). On DCA, the inclusion of SII did not improve the net-benefit of the prognostic model. On multivariable analyses, SII ≥ 710 remained independently associated with the worse OS and CSS in IMDC intermediate risk group (both: HR: 1.31, 95%CI: 1.02 - 1.67, p = 0.03). In the subgroup analyses based on the BMI, among patients with BMI ≥ 25, SII was significantly associated with OS (HR: 1.29, 95%CI: 1.04 - 1.61, p = 0.02) and CSS (HR: 1.31, 95%CI: 1.05 - 1.63, p = 0.02).

Conclusions: We found an independent association of high SII prior to CN with unfavorable clinical outcomes, particularly in patients with intermediate risk mRCC and patients with increased BMI. Despite these results, it does not seem to add any prognostic or clinical benefit beyond that obtained by currently available clinicopathologic characteristics as sole worker.
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http://dx.doi.org/10.23736/S2724-6051.21.04023-6DOI Listing
March 2021

Prognostic effect of preoperative serum albumin to globulin ratio in patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma.

Transl Androl Urol 2021 Feb;10(2):609-619

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

Background: Accurate identification of ideal candidates for cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is an unmet need. We tested the association between preoperative value of systemic albumin to globulin ratio (AGR) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN.

Methods: mRCC patients treated with CN were included. The overall population was therefore divided into two AGR groups using cut-off of 1.43 (low, <1.43 high, ≥1.43). Univariable and multivariable Cox regression analyses tested the association between AGR and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's concordance index (C-index). The clinical value of the AGR was evaluated with decision curve analysis (DCA).

Results: Among 613 mRCC patients, 159 (26%) patients had an AGR <1.43. Median follow-up was 31 (IQR: 16-58) months. On univariable analysis, low preoperative serum AGR was significantly associated with both OS (HR: 1.55, 95% CI: 1.26-1.89, P<0.001) and CSS (HR: 1.55, 95% CI: 1.27-1.90, P<0.001). On multivariable analysis, AGR <1.43 was associated with worse OS (HR: 1.51, 95% CI: 1.23-1.85, P<0.001) and CSS (HR: 1.52, 95% CI: 1.24-1.86, P<0.001). The addition of AGR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index=0.640 C-index=0.629). On DCA, the inclusion of AGR marginally improved the net benefit of the prognostic model. Low AGR remained independently associated with OS and CSS in the IMDC intermediate risk group (HR: 1.52, 95% CI: 1.16-1.99, P=0.002).

Conclusions: In our study, low AGR before CN was associated with worse OS and CSS, particularly in intermediate risk patients.
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http://dx.doi.org/10.21037/tau-20-1101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947468PMC
February 2021

Prognostic value of the preoperative albumin-globulin ratio in patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy: results from a large multicenter international collaboration.

Jpn J Clin Oncol 2021 Feb 27. Epub 2021 Feb 27.

Department of Urology, Medical University of Vienna, Vienna, Austria.

Objective: To assess the value of preoperative albumin to globulin ratio for predicting pathologic and oncological outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy in a large multi-institutional cohort.

Materials And Methods: Preoperative albumin to globulin ratio was assessed in a multi-institutional cohort of 2492 patients. Logistic regression analyses were performed to assess the association of the albumin to globulin ratio with pathologic features. Cox proportional hazards regression models were performed for survival endpoints.

Results: The optimal cut-off value was determined to be 1.4 according to a receiver operating curve analysis. Lower albumin to globulin ratios were observed in 797 patients (33.6%) compared with other patients. In a preoperative model, low preoperative albumin to globulin ratio was independently associated with nonorgan-confined diseases (odds ratio 1.32, P = 0.002). Patients with low albumin to globulin ratios had worse recurrence-free survival (P < 0.001), cancer-specific survival (P = 0.001) and overall survival (P = 0.020) in univariable and multivariable analyses after adjusting for the effect of standard preoperative prognostic factors (recurrence-free survival: hazard ratio (HR) 1.31, P = 0.001; cancer-specific survival: HR 1.31, P = 0.002 and overall survival: HR 1.18, P = 0.024).

Conclusions: Lower preoperative albumin to globulin ratio is associated with locally advanced disease and worse clinical outcomes in patients treated with radical nephroureterectomy for upper tract urothelial carcinoma. As it is difficult to stage disease entity, low preoperative serum albumin to globulin ratio may help identify those most likely to benefit from intensified care, such as perioperative systemic therapy, and the extent and type of surgery.
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http://dx.doi.org/10.1093/jjco/hyab023DOI Listing
February 2021

Fibroblast growth factor receptor: A systematic review and meta-analysis of prognostic value and therapeutic options in patients with urothelial bladder carcinoma.

Urol Oncol 2021 Feb 25. Epub 2021 Feb 25.

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Department of Urology, Weill Cornell Medical College, New York, NY; Department of Urology, Second Faculty of Medicine, Charles University, Prag, Czech Republic; Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia; Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan; European Association of Urology research foundation, Arnhem, The Netherlands. Electronic address:

To evaluate the oncologic prognostic value of fibroblast growth factor receptor (FGFR) and to assess the safety and efficacy of its inhibitors in patients with urothelial bladder carcinoma. A literature search using PubMed, Scopus, and Cochrane Library was conducted on June 2020 to identify relevant studies according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. The pooled recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS) were calculated using a fixed or random effects model in patients with nonmuscle invasive bladder cancer (NMIBC). Overall, 62 studies comprising 9,229 patients were eligible and included in this systematic review and meta-analysis. Both FGFR3 mutation and protein overexpression were significantly associated with RFS, PFS, CSS, and overall survival. FGFR3 mutation was associated with worse RFS and better PFS (pooled hazard ratio: 1.30; 95% confidence interval: 1.08-1.57, and pooled hazard ratio: 0.62; 95% confidence interval: 0.42-0.92, respectively) in patients with NMIBC. In 11 studies reporting on the response to FGFR inhibitors, complete response rates, disease control rates, and overall response rate of 0% to 8%, 59.3% to 64.2%, and 40% were reported for dovitinib, infigratinib, and erdafitinib, respectively. Based on this study, FGFR3 mutation is a statistically significant prognostic factor for RFS in NMIBC. FGFR inhibitors have measurable benefit in patients with advanced and metastatic urothelial carcinoma. However, the results of ongoing RCTs and future well-designed studies are awaited to capture the differential biologic and clinical behavior of tumors harboring FGFR while helping to identify those who are most likely to benefit from FGFR inhibitors.
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http://dx.doi.org/10.1016/j.urolonc.2021.01.025DOI Listing
February 2021

Prognostic role of the systemic immune-inflammation index in upper tract urothelial carcinoma treated with radical nephroureterectomy: results from a large multicenter international collaboration.

Cancer Immunol Immunother 2021 Feb 16. Epub 2021 Feb 16.

Department of Urology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Purpose: To investigate the prognostic role of the preoperative systemic immune-inflammation index (SII) in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU).

Materials And Methods: We retrospectively analyzed our multi-institutional database to identify 2492 patients. SII was calculated as platelet count × neutrophil/lymphocyte count and evaluated at a cutoff of 485. Logistic regression analyses were performed to investigate the association of SII with muscle-invasive and non-organ-confined (NOC) disease. Cox regression analyses were performed to investigate the association of SII with recurrence-free, cancer-specific, and overall survival (RFS/CSS/OS).

Results: Overall, 986 (41.6%) patients had an SII > 485. On univariable logistic regression analyses, SII > 485 was associated with a higher risk of muscle-invasive (P = 0.004) and NOC (P = 0.03) disease at RNU. On multivariable logistic regression, SII remained independently associated with muscle-invasive disease (P = 0.01). On univariable Cox regression analyses, SII > 485 was associated with shorter RFS (P = 0.002), CSS (P = 0.002) and OS (P = 0.004). On multivariable Cox regression analyses SII remained independently associated with survival outcomes (all P < 0.05). Addition of SII to the multivariable models improved their discrimination of the models for predicting muscle-invasive disease (P = 0.02). However, all area under the curve and C-indexes increased by < 0.02 and it did not improve net benefit on decision curve analysis.

Conclusions: Preoperative altered SII is significantly associated with higher pathologic stages and worse survival outcomes in patients treated with RNU for UTUC. However, the SII appears to have relatively limited incremental additive value in clinical use. Further study of SII in prognosticating UTUC is warranted before routine use in clinical algorithms.
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http://dx.doi.org/10.1007/s00262-021-02884-wDOI Listing
February 2021

Neoadjuvant SABR for Renal Cell Carcinoma Inferior Vena Cava Tumor Thrombus-Safety Lead-in Results of a Phase 2 Trial.

Int J Radiat Oncol Biol Phys 2021 Feb 5. Epub 2021 Feb 5.

Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address:

Purpose: To evaluate the feasibility, safety, oncologic outcomes, and immune effect of neoadjuvant stereotactic radiation (Neo-SAbR) followed by radical nephrectomy and thrombectomy (RN-IVCT).

Methods And Materials: These are results from the safety lead-in portion of a single-arm phase 1 and 2 trial. Patients with kidney cancer (renal cell carcinoma [RCC]) and inferior vena cava (IVC) tumor thrombus (TT) underwent Neo-SAbR (40 Gy in 5 fractions) to the IVC-TT followed by open RN-IVCT. Absence of grade 4 to 5 adverse events (AEs) within 90 days of RN-IVCT was the primary endpoint. Exploratory studies included pathologic and immunologic alterations attributable to SAbR.

Results: Six patients were included in the final analysis. No grade 4 to 5 AEs were observed. A total of 81 AEs were reported within 90 days of surgery: 73% (59/81) were grade 1, 23% (19/81) were grade 2, and 4% (3/81) were grade 3. After a median follow-up of 24 months, all patients are alive. One patient developed de novo metastatic disease. Of 3 patients with metastasis at diagnosis, 1 had a complete and another had a partial abscopal response without the concurrent use of systemic therapy. Neo-SABR led to decreased Ki-67 and increased PD-L1 expression in the IVC-TT. Inflammatory cytokines and autoantibody titers reflecting better host immune status were observed in patients with nonprogressive disease.

Conclusions: Neo-SAbR followed by RN-IVCT for RCC IVC-TT is feasible and safe. Favorable host immune environment correlated with abscopal response to SABR and RCC relapse-free survival, though direct causal relation to SABR has yet to be established.
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http://dx.doi.org/10.1016/j.ijrobp.2021.01.054DOI Listing
February 2021

A Preoperative Nomogram to Predict Renal Function Insufficiency for Cisplatin-based Adjuvant Chemotherapy Following Minimally Invasive Radical Nephroureterectomy (ROBUUST Collaborative Group).

Eur Urol Focus 2021 Feb 3. Epub 2021 Feb 3.

Department of Urology, Changzheng Hospital, Naval Medical University, Shanghai, China. Electronic address:

Background: Postoperative renal function impairment represents a main limitation for delivering adjuvant chemotherapy after radical nephroureterectomy (RNU).

Objective: To create a model predicting renal function decline after minimally invasive RNU.

Design, Setting, And Participants: A total of 490 patients with nonmetastatic UTUC who underwent minimally invasive RNU were identified from a collaborative database including 17 institutions worldwide (February 2006 to March 2020). Renal function insufficiency for cisplatin-based regimen was defined as estimated glomerular filtration rate (eGFR) <50 ml/min/1.73 m at 3 mo after RNU. Patients with baseline eGFR >50 ml/min/1.73 m (n = 361) were geographically divided into a training set (n = 226) and an independent external validation set (n = 135) for further analysis.

Outcome Measurements And Statistical Analysis: Using transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) guidelines, a nomogram to predict postoperative eGFR <50 ml/min/1.73 m was built based on the coefficients of the least absolute shrinkage and selection operation (LASSO) logistic regression. The discrimination, calibration, and clinical use of the nomogram were investigated.

Results And Limitations: The model that incorporated age, body mass index, preoperative eGFR, and hydroureteronephrosis was developed with an area under the curve of 0.771, which was confirmed to be 0.773 in the external validation set. The calibration curve demonstrated good agreement. Besides, the model was converted into a risk score with a cutoff value of 0.583, and the difference between the low- and high-risk groups both in overall death risk (hazard ratio [HR]: 4.59, p < 0.001) and cancer-specific death risk (HR: 5.19, p < 0.001) was statistically significant. The limitation mainly lies in its retrospective design.

Conclusions: A nomogram incorporating immediately available clinical variables can accurately predict renal insufficiency for cisplatin-based adjuvant chemotherapy after minimally invasive RNU and may serve as a tool facilitating patient selection.

Patient Summary: We have developed a model for the prediction of renal function loss after radical nephroureterectomy to facilitate patient selection for perioperative chemotherapy.
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http://dx.doi.org/10.1016/j.euf.2021.01.014DOI Listing
February 2021

Safety, Efficacy, and Impact on Quality of Life of Palliative Robotic Cystectomy for Advanced Prostate Cancer.

Clin Genitourin Cancer 2020 Nov 2. Epub 2020 Nov 2.

Department of Urology, University of Texas Southwestern, Dallas, TX. Electronic address:

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http://dx.doi.org/10.1016/j.clgc.2020.09.008DOI Listing
November 2020

Impact of circulating microRNA test (miRNA-371a-3p) on appropriateness of treatment and cost outcomes in patients with Stage I non-seminomatous germ cell tumours.

BJU Int 2020 Oct 30. Epub 2020 Oct 30.

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

Objectives: To determine whether utilisation of a serum microRNA (miRNA) test could improve treatment appropriateness and cost-effectiveness for patients with Stage I non-seminomatous germ cell tumours (NSGCTs).

Patients And Methods: A decision tree model was built to investigate treatment course, clinical and cost outcomes for patients with Stage IA (T1N0M0S0) and IB (T2-4N0M0S0) NSGCT. The model compared outcomes and cost of standard approach using histopathology, conventional serum tumour markers and radiographic staging (standard model) to a miRNA-based approach using the standard model + post-orchidectomy serum miR-371a-3p (marker model). Probabilities of expected treatment and outcomes were based on presence/absence of cancer upon entering into the model. Overtreatment was defined as adjuvant chemotherapy or primary retroperitoneal lymph node dissection in a patient without cancer. Undertreatment was defined as initial surveillance for a patient with cancer.

Results: Utilising the miRNA marker-based approach, 26% of patients avoid overtreatment and 8% avoid undertreatment in Stage IA NSGCT; 27% avoid overtreatment and 23% avoid undertreatment in Stage IB disease. Appropriate treatment decision-making increased from 65% to 94% and 50% to 92% for Stage IA and IB, respectively. The miRNA-based approach remained cost-effective over a wide range of performance characteristics with savings of ~$1400 (American dollars)/patient for both Stage IA and IB disease.

Conclusion: A miRNA-based approach may potentially select patients with Stage I NSGCT for correct treatment in a cost-effective manner. Identification of residual teratoma-only remains an issue. Prospective studies are necessary to validate these findings.
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http://dx.doi.org/10.1111/bju.15288DOI Listing
October 2020

Clinical outcomes of a cohort of patients with bulky, clinically node-positive bladder cancer undergoing radical cystectomy in the contemporary era.

Can Urol Assoc J 2020 Oct 27. Epub 2020 Oct 27.

Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, United States.

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http://dx.doi.org/10.5489/cuaj.6966DOI Listing
October 2020

The Significance of Preoperative Serum Sodium and Hemoglobin in Outcomes of Upper Tract Urothelial Carcinoma: Multi-Center Analysis Between China and the United States.

Cancer Manag Res 2020 8;12:9825-9836. Epub 2020 Oct 8.

Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, Beijing, People's Republic of China.

Purpose: To analyze the effect of preoperative serum sodium and hemoglobin on oncologic outcomes in upper tract urothelial carcinoma (UTUC) based on a multi-center cohort from China and the United States (U.S.).

Methods: We retrospectively reviewed the records of 775 patients with UTUC treated surgically at tertiary care medical facilities in China or the US from 1998 to 2015. We analyzed associations of preoperative serum sodium and hemoglobin with clinicopathological characteristics, overall survival (OS), cancer-specific survival (CSS) and intravesical recurrence free survival (IVRFS).

Results: The US patients had comparatively lower serum sodium and similar hemoglobin at baseline. Preoperative low serum sodium value was associated with tumor multifocality, lymph node metastasis (LNM) and lymphovascular invasion (LVI); preoperative anemia was associated with advanced age, tumor multifocality, high tumor grade and LVI. Preoperative low serum sodium was an independent predictor of worse OS in the entire cohort; preoperative anemia was an independent predictor of worse OS and CSS in the US cohort alone, Chinese cohort alone and the combined cohort. We developed a predictive nomogram for OS which exhibited better prognostic value when it included the values of sodium and anemia, and successfully validated it in different cohorts.

Conclusion: Preoperative low serum sodium and anemia could be informative in predicting worse pathologic and survival outcomes in different UTUC patient ethnic groups.
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http://dx.doi.org/10.2147/CMAR.S267969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549885PMC
October 2020

Robotic Nephroureterectomy Laparoscopic Nephroureterectomy: Increased Utilization, Rates of Lymphadenectomy, Decreased Morbidity Robotically.

J Endourol 2021 Mar 16;35(3):312-318. Epub 2020 Nov 16.

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

Robotic radical nephroureterectomy (RRNU) may offer advantages over laparoscopic radical nephroureterectomy (LRNU). The purpose of this study is to evaluate the overall survival (OS) of patients with upper tract urothelial carcinoma (UTUC) who underwent RRNU LRNU and identify factors that account for differences. The National Cancer Database was queried from 2010 to 2016 for patients with American Joint Committee on Cancer 6th/7th edition Stage I/II/III UTUC. Kaplan-Meier analysis compared LRNU and RRNU OS. Univariate analysis detected differences between the groups. Cox regression determined factors associated with mortality rate. Logistic regression identified predictors of a lymph node dissection (LND) and 90-day mortality rate. A total of 2631 patients met the criteria, 1129 of whom underwent RRNU and 1502 LRNU, with a follow-up of 33 and 35 months, respectively ( = 0.063). RRNU had a median OS of 71.1 62.6 months ( = 0.033). LRNU patients were older (72.7 71.4,  < 0.001) and had no differences in comorbidities, pathologic T stage, or grade. The LRNU cohort was less likely to undergo LND (19% 35%,  < 0.001) and had a lower median lymph node yield (3 4,  < 0.001). LRNU patients more likely underwent conversion to an open procedure, had longer hospital stays, and higher 30- and 90-day mortality rates. LRNU was independently associated with mortality rate ( = 0.030). Age, grade, positive margins, pT/pN stage were associated with mortality rate. Younger age, RRNU, surgery at an academic center, and neoadjuvant chemotherapy predicted an LND. RRNU demonstrated increased rates of LND and may offer a short-term morbidity benefit to LRNU. Survival differences may be due to improved characterization of disease through LND.
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http://dx.doi.org/10.1089/end.2020.0496DOI Listing
March 2021

Value of tumour-infiltrating immune cells in predicting response to intravesical BCG in patients with non-muscle-invasive bladder cancer: a systematic review and meta-analysis.

BJU Int 2020 Oct 18. Epub 2020 Oct 18.

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

Objective: To investigate the predictive value of tumour-infiltrating immune cells (TIICs) on oncological outcomes and response to BCG treatment in patients with non-muscle-invasive bladder cancer (NMIBC).

Materials And Methods: A systematic review and meta-analysis was performed using PubMed, Scopus and the Cochrane Library in July 2020 to identify relevant studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The pooled recurrence-free survival (RFS) rate was calculated using a fixed-effect model.

Results: We retrieved 15 studies (including 791 patients) evaluating the effect of TIICs on oncological outcomes in patients with NMIBC treated with intravesical BCG. TIICs were reported to be a significant predictor of oncological outcomes and response to BCG treatment in 10 studies. Tumour-associated macrophages were associated with worse RFS (pooled hazard ratio 2.30, 95% confidence interval 1.64-3.22).

Conclusions: Based on these data, TIICs are significant predictors of RFS and response to BCG treatment in patients with NMIBC; therefore, incorporation of TIICs into risk stratification models may help patients and physicians in the clinical decision-making process in order to achieve the maximum possible benefit from BCG treatment.
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http://dx.doi.org/10.1111/bju.15276DOI Listing
October 2020

Pre-therapy serum albumin-to-globulin ratio in patients treated with neoadjuvant chemotherapy and radical nephroureterectomy for upper tract urothelial carcinoma.

World J Urol 2020 Oct 16. Epub 2020 Oct 16.

Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Purpose: The accurate selection of patients who are most likely to benefit from neoadjuvant chemotherapy is an important challenge in oncology. Serum AGR has been found to be associated with oncological outcomes in various malignancies. We assessed the association of pre-therapy serum albumin-to-globulin ratio (AGR) with pathologic response and oncological outcomes in patients treated with neoadjuvant platin-based chemotherapy followed by radical nephroureterectomy (RNU) for clinically non-metastatic UTUC.

Methods: We retrospectively included all clinically non-metastatic patients from a multicentric database who had neoadjuvant platin-based chemotherapy and RNU for UTUC. After assessing the pretreatment AGR cut-off value, we found 1.42 to have the maximum Youden index value. The overall population was therefore divided into two AGR groups using this cut-off (low, < 1.42 vs high, ≥ 1.42). A logistic regression was performed to measure the association with pathologic response after NAC. Univariable and multivariable Cox regression analyses tested the association of AGR with OS and RFS.

Results: Of 172 patients, 58 (34%) patients had an AGR < 1.42. Median follow-up was 26 (IQR 11-56) months. In logistic regression, low AGR was not associated with pathologic response. On univariable analyses, pre-therapy serum AGR was neither associated with OS HR 1.15 (95% CI 0.77-1.74; p = 0.47) nor RFS HR 1.48 (95% CI 0.98-1.22; p = 0.06). These results remained true regardless of the response to NAC.

Conclusion: Pre-therapy low serum AGR before NAC followed by RNU for clinically high-risk UTUC was not associated with pathological response or long-term oncological outcomes. Biomarkers that can complement clinical factors in UTUC are needed as clinical staging and risk stratification are still suboptimal leading to both over and under treatment despite the availability of effective therapies.
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http://dx.doi.org/10.1007/s00345-020-03479-3DOI Listing
October 2020

Perioperative outcomes and cost of robotic vs open simple prostatectomy in the modern robotic era: results from the National Inpatient Sample.

BJU Int 2020 Sep 27. Epub 2020 Sep 27.

Department of Urology, University of Texas Southwestern, Dallas, TX, USA.

Objectives: To perform a comparative analysis of perioperative outcomes and hospitalisation cost between open (OSP) and robot-assisted simple prostatectomy (RASP) for treatment of benign prostatic hyperplasia (BPH) using the National Inpatient Sample (NIS) in the contemporary robotic era.

Materials And Methods: The NIS was queried for cases of OSP and RASP for the treatment of BPH between 2013 and 2016. Perioperative complications, unadjusted hospital cost and length of stay (LOS) were compared between RASP and OSP. Smoothed linear regression curves comparing hospitalisation cost by increasing LOS was stratified by surgical approach to identify point of cost equivalency between RASP and OSP. Multivariable linear regression analysis was used to construct a hospitalisation cost model to examine the contribution of the robotic approach and LOS to hospitalisation cost.

Results: The total analytical cohort included 2551 OSP and 704 RASP procedures. Patients undergoing RASP were younger, at a median (interquartile range [IQR]) age of 68 (63-73) vs 71 (65-77) years, and with less comorbidity (76.8% vs 86.5%, P < 0.01). RASP was associated with fewer total complications (11.1% vs 29.2%, P < 0.01) and a greater likelihood of routine discharge to home rather than another facility (88.9% vs 76.7%, P < 0.01). While LOS was shorter with RASP (median [IQR], 2 [1-3] vs 4 [3-6] days, P < 0.01), total unadjusted hospitalisation cost (in United States dollars) was greater (median [IQR], $10 855 [$7965-$15 675] vs $13 467 [$10 572-$17 722], P < 0.01). Presence of any complication increased both LOS and hospitalisation cost (P < 0.01). Linear regression modelling determined the point of cost equivalence between RASP staying a median of 2 days was an OSP case staying between 5 and 6 days. On multivariable regression analysis, the robotic approach contributed an additional $6175 (P < 0.01) to the cost model, whereas each additional day of hospitalisation contributed $1687 (P < 0.01), suggesting LOS would need to be 3-4 days shorter with RASP to offset surgical costs of the robot.

Conclusions: While RASP appears to have significantly better perioperative complication rates with shorter LOS and likely discharge to home, total hospitalisation cost remained greater, likely related to upfront operative costs. While this retrospective study is limited by selection bias for patients undergoing RASP, the benefits of improved convalescence, discharge to home, and lower rate of perioperative complications appear to justify performance of RASP in an experienced pelvic robotic centre despite relatively greater hospitalisation cost if referral to an experienced holmium laser enucleation of the prostate centre is not feasible.
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http://dx.doi.org/10.1111/bju.15258DOI Listing
September 2020

Association of preoperative serum De Ritis ratio with oncological outcomes in patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma.

Urol Oncol 2020 12 19;38(12):936.e7-936.e14. Epub 2020 Sep 19.

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia; Department of Urology, Weill Cornell Medical College, New York, NY; Department of Urology, University of Texas Southwestern, Dallas, TX; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan; European Association of Urology Research Foundation, Arnhem, Netherlands. Electronic address:

Purpose: Identifying which patients are likely to benefit from cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is important. We tested the association between preoperative serum De Ritis ratio (DRR, Aspartate Aminotransferase/Alanine Aminotransferase) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN.

Material And Methods: mRCC patients treated with CN at different institutions were included. After assessing for the optimal pretreatment DRR cut-off value, we found 1.2 to have the maximum Youden index value. The overall population was therefore divided into 2 DRR groups using this cut-off (low, <1.2 vs. high, ≥1.2). Univariable and multivariable Cox regression analyses tested the association between DRR and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's concordance index (C-index). The clinical value of the DRR was evaluated with decision curve analysis.

Results: Among 613 mRCC patients, 239 (39%) patients had a DRR ≥1.2. Median follow-up was 31 (IQR 16-58) months. On univariable analysis, high DRR was significantly associated with OS (hazard ratios [HR]: 1.22, 95% confidence interval [CI]: 1.01-1.46, P = 0.04) and CSS (HR: 1.23, 95% CI: 1.02-1.47, P = 0.03). On multivariable analysis, which adjusted for the effect of established clinicopathologic features, high DRR remained significantly associated with both OS (HR: 1.26, 95% CI: 1.04-1.52, P = 0.02) and CSS (HR: 1.26, 95% CI: 1.05-1.53, P = 0.01). The addition of DRR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index = 0.633 vs. C-index = 0.629). On decision curve analysis, the inclusion of DRR did not improve the net-benefit beyond that obtained by established subgroup analyses stratified by IMDC risk groups, type of systemic therapy, body mass index and sarcomatoid features, did not reveal any prognostic value to DRR.

Conclusion: Despite the statistically significant association between DRR and OS as well as CSS in mRCC patients treated with CN, DRR does not seem to add any further prognostic value beyond that obtained by currently available features.
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http://dx.doi.org/10.1016/j.urolonc.2020.08.013DOI Listing
December 2020

Oncologic outcomes of radical nephroureterectomy (RNU).

Transl Androl Urol 2020 Aug;9(4):1841-1852

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

Radical nephroureterectomy is the mainstay of surgical treatment for upper tract urothelial carcinoma (UTUC), a disease which comprises approximately 5% of urothelial malignancies. Minimally-invasive and nephron-sparing interventions have been explored, although thus far have not shown comparable oncologic outcomes except in a relatively narrow set of patients. Due to the relative rarity of the disease, it has taken decades and multi-disciplinary efforts to sufficiently identify prognostic factors of oncologic outcomes. Despite these efforts, however, oncologic outcomes of nephroureterectomy have remained remarkably stable over the past 30 years. New techniques, such as laparoscopic and robotic surgery, have been applied to this procedure. High level evidence regarding equivalent oncologic outcomes is lacking and open surgery remains the standard of care for high-stage disease, although there is a role for laparoscopic and robotic nephroureterectomy. The importance of bladder cuff removal in improving oncologic outcomes has been broadly accepted, although there is no consensus as to the most oncologically appropriate technique. There does appear to be evidence that endoscopic techniques confer worse oncologic control. The role of lymphadenectomy remains controversial, although there is evidence that increased nodal yield could have oncologic benefit. Given disease heterogeneity and varied technical approaches to the procedure, no consensus standardized template has been identified. There is level 1 evidence for the use of intravesical chemotherapy peri-operatively and that this intervention can improve the risk of intravesical recurrence. Advances in systemic neoadjuvant and adjuvant chemotherapy have yielded promising results and are likely to become standard of care for patients without contraindications. Immunotherapy and targeted biologic agents are also likely to improve the surgical efficacy of radical nephroureterectomy as well. Ultimately, more high level evidence is needed to identify successful surgical and medical approaches to UTUC and multi-institutional collaboration is critical to this progress.
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http://dx.doi.org/10.21037/tau.2019.12.29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475687PMC
August 2020

Incidence and preoperative predictors for major complications following radical nephroureterectomy.

Transl Androl Urol 2020 Aug;9(4):1786-1793

Department of Surgery, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA.

Background: Radical nephroureterectomy (RNU) is the referent standard for managing bulky, invasive, or high grade upper-tract urothelial carcinoma (UTUC). The UTUC patient population, however, generally harbor medical comorbidities thereby placing them at risk of surgical complications. This study reviews a large international cohort of RNU patients to define the risk of major complications and preoperative factors associated with their occurrence.

Methods: Patients undergoing RNU at 14 academic medical centers between 2002 and 2015 were retrospectively reviewed. Preoperative clinical, demographic, operative, and comorbidity indices were recorded. The modified Clavien-Dindo index was used to grade complications occurring within 30 days of surgery. The association between preoperative variables and major complications occurring after RNU was determined by multivariable logistic regression.

Results: One thousand two hundred and sixty-six patients (707 men; 559 women) with a median age of 70 years and BMI of 27 kg/m were included. Over three-quarters of the cohort was white, 50.1% had baseline chronic kidney disease (CKD) ≥ stage III, 22.4% had a Charlson comorbidity index (CCI) score >5, and 17.1% had an Eastern Cooperative Oncology Group (ECOG) performance status ≥2. Overall, 413 (32.6%) experienced a complication including 103 (8.1%) with a major event. Specific distribution of major complications included 49 Clavien III, 44 Clavien IV, and 10 Clavien V. On univariate analysis, patient age (P=0.006), hypertension (P=0.002), diabetes mellitus (P=0.023), CKD stage (P<0.001), American Society of Anesthesiologists (ASA) score (P=0.022), ECOG (P<0.001), and CCI (P<0.001) all were associated with major complications. On multivariate analysis, ECOG ≥2 (OR 2.38, 95% CI, 1.46-3.90), P=0.001), CCI >5 (OR 3.45, 95% CI, 1.41-8.33, P=0.007), and CKD stage ≥3 (OR 3.64, P=0.008) were independently associated with major complications.

Conclusions: Major complications following RNU occurred in almost 10% of patients. Impaired preoperative performance status and baseline CKD are preoperative variables associated with these major post-surgical adverse event. These easily measurable indices warrant consideration and discussion prior to proceeding with RNU.
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http://dx.doi.org/10.21037/tau.2020.01.22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475660PMC
August 2020

The value and limitations of urothelial bladder carcinoma molecular classifications to predict oncological outcomes and cancer treatment response: A systematic review and meta-analysis.

Urol Oncol 2021 01 6;39(1):15-33. Epub 2020 Sep 6.

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Departments of Urology, Weill Cornell Medical College, New York, NY; Department of Urology, Second Faculty of Medicine, Charles University, Prag, Czech Republic; Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia; Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan; European Association of Urology Research Foundation, Arnhem, Netherlands. Electronic address:

Aim: To evaluate the predictive value of molecular subtypes on oncological outcomes and response to cancer treatment in patients with urothelial bladder carcinoma (UBC).

Materials And Methods: A literature search using PubMed, Scopus, and Cochrane Library was conducted on April 2020 to identify relevant studies according to the preferred reporting items for systematic review and meta-analysis guidelines. The pooled overall survival (OS), cancer-specific survival (CSS), and progression-free survival were calculated using a fixed or random effects model.

Results: We identified 66 studies (including 21,447 molecular subtype records) evaluating the impact of molecular classification on oncologic outcomes in patients with UBC. We found significant association of different molecular subtypes with OS, CSS, progression-free survival, recurrence-free survival, and response to treatment. Totally, 11 studies were included in the meta-analysis. Basal group and NE-like subtypes were associated with worse OS (pooled HR: 1.78, 95%CI: 1.49-2.12, and pooled HR: 2.67, 95%CI: 1.08-6.60, respectively) in patients with muscle invasive bladder cancer. Luminal group was also associated with worse CSS (pooled HR of 3.67, 95%CI: 2.19-6.14).

Conclusions: Based on these data, UBC molecular classifications are significant predictors of oncological outcomes and identify patients who are most likely to benefit from intensified or different therapies. The optimal consensus on molecular classification remains to be verified in well-designed prospective studies to allow precise prognostic and predictive value assessment.
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http://dx.doi.org/10.1016/j.urolonc.2020.08.023DOI Listing
January 2021

Real-World Application of Pre-Orchiectomy miR-371a-3p Test in Testicular Germ Cell Tumor Management.

J Urol 2021 Jan 28;205(1):137-144. Epub 2020 Aug 28.

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

Purpose: Current serum tumor markers for testicular germ cell tumor are limited by low sensitivity. Growing evidence supports the use of circulating miR-371a-3p as a superior marker for malignant (viable) germ cell tumor management. We evaluated the real-world application of serum miR-371a-3p levels in detecting viable germ cell tumor among patients undergoing partial or radical orchiectomy.

Materials And Methods: Serum samples were collected from 69 consecutive patients before orchiectomy. Performance characteristics of serum miR-371a-3p were compared with conventional serum tumor markers (⍺-fetoproteinβ-human chorionic gonadotropinlactate dehydrogenase) between patients with viable germ cell tumor and those without viable germ cell tumor on orchiectomy pathology. Relative miR-371a-3p levels were correlated with clinical course. The Kruskal-Wallis test and linear and ordinal regression models were used for analysis.

Results: For detecting viable germ cell tumor, combined conventional serum tumor markers had a specificity of 100%, sensitivity of 58% and AUC of 0.79. The miR-371a-3p test showed a specificity of 100%, sensitivity of 93% and AUC of 0.978. Median relative expression of miR-371a-3p in viable germ cell tumor cases was more than 6,800-fold higher than in those lacking viable germ cell tumor. miR-371a-3p levels correlated with composite stage (p=0.006) and, among composite stage I cases, independently associated with embryonal carcinoma percentage (p=0.0012) and tumor diameter (p <0.0001). Six patients underwent orchiectomy after chemotherapy and were correctly predicted to have presence or absence of viable germ cell tumor by the miR-371a-3p test.

Conclusions: If validated, the miR-371a-3p test can be used in conjunction with conventional serum tumor markers to aid clinical decision making. A positive miR-371a-3p test in patients after preoperative chemotherapy or with solitary testes could potentially guide subsequent orchiectomy or observation.
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http://dx.doi.org/10.1097/JU.0000000000001337DOI Listing
January 2021

Feasibility and Safety of Robotic Excision of Ipsilateral Retroperitoneal Recurrence After Nephrectomy for Renal Cell Carcinoma.

Urology 2020 Nov 21;145:159-165. Epub 2020 Aug 21.

Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. Electronic address:

Objective: To determine feasibility and safety of robotic excision of local ipsilateral recurrences after nephrectomy for renal cell carcinoma (RCC). Surgical resection is an option for treatment of low burden locally recurrent RCC, potentially delaying the use of systemic therapy. This has historically been performed by open technique, which can impart significant morbidity. We present our experience with robotic excision.

Methods: We reviewed our institutional experience of patients with surgically excised RCC who underwent robotic excision of ipsilateral retroperitoneal recurrence in 2015-2018. Demographics and clinicopathological variables, including operative and postoperative outcomes, were examined.

Results: Twelve robotic excisions of ipsilateral local recurrences were performed in our hospital in 2015-2018. Mean age was 65.48 years (± standard deviation, SD: 9.51), 10 patients were male, and mean BMI 34.75 kg/m (± 6.71). Nine patients recurred after radical nephrectomy, and 3 after partial nephrectomy. Mean size of recurrence was 2.97 cm (±1.69). Mean anesthesia time, EBL, and LOS were 213 minutes (± 38.92), 152 mL (± 130.75), and 43 hours (± 12.64), respectively. All surgical margins were negative. No surgical complications were reported. Median follow-up was 19.0 months [interquartile range, IQR 12.7-30.0]. Five patients out of 12 recurred following robotic excision, these were treated with either systemic therapy, radiation, or palliative surgeries. Mean time for subsequent recurrence was 26.5 months.

Conclusion: In this small case series, robotic excision of ipsilateral RCC retroperitoneal recurrence appears safe, technically feasible, and oncologically sound in expert hands and carefully selected patients.
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http://dx.doi.org/10.1016/j.urology.2020.07.060DOI Listing
November 2020

Population-based analysis of cost and peri-operative outcomes between open and robotic primary retroperitoneal lymph node dissection for germ cell tumors.

World J Urol 2020 Aug 14. Epub 2020 Aug 14.

Department of Urology, University of Texas Southwestern, 2001 Inwood Road, 4th Floor, WBCE3, Dallas, TX, 75390, USA.

Purpose: To compare perioperative outcomes and perform the first cost analysis between open retroperitoneal lymph node dissection (O-RPLND) and Robotic-RPLND (R-RPLND) using a national all-payer inpatient care database.

Methods: Nationwide Inpatient Sample (NIS) was queried between 2013-2016 for primary RPLND and germ cell tumor. We compared cost, length of stay (LOS), and complications between O-RPLND and R-RPLND. Linear regression plots identified point of cost equivalence between R-RPLND and O-RPLND. A multivariable linear regression model was generated to analyze predictors of cost.

Results: 44 cases of R-RPLND and 319 cases of O-RPLND were identified. R-RPLND was associated with lower rate of complications (0% vs. 16.6%, p < 0.01) and shorter LOS [Median (IQR): 1.5 (1-3) days vs. 4 (3-6) days, p < 0.01]. Rates of ileus, genitourinary complications, and transfusions were lower with R-RPLND, but did not reach significance. On multivariable analysis, robotic approach independently contributed $4457, while each day of hospitalization contributed to an additional $2,431 to the overall model of cost. Linear regression plots determined point of cost equivalence between an R-RPLND staying a mean of 2 days was 4-5 days for O-RPLND, supporting the multivariable analysis. Total hospitalization cost was equivalent between R-RPLND and O-RPLND [Median (IQR): $15,681($12,735-$21,596) vs $16,718($11,799-$24,403), p = 0.48]-suggesting that the cost equivalency of R-RPLND is, at least in part, attributable to shorter LOS.

Conclusion: While O-RPLND remains the gold standard and this study is limited by selection bias of a robotic approach to RPLND, our findings suggest primary R-RPLND may represent a cost-equivalent option with decreased hospital LOS in select cases.
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http://dx.doi.org/10.1007/s00345-020-03403-9DOI Listing
August 2020

SPARC is a key mediator of TGF-β-induced renal cancer metastasis.

J Cell Physiol 2021 Mar 11;236(3):1926-1938. Epub 2020 Aug 11.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Aberrant expression of transforming growth factor-β1 (TGF-β1) is associated with renal cell carcinoma (RCC) progression by inducing cancer metastasis. However, the downstream effector(s) in TGF-β signaling pathway is not fully characterized. In the present study, the elevation of secreted protein acidic and rich in cysteine (SPARC) as a TGF-β regulated gene in RCC was identified by applying differentially expressed gene analysis and microarray analysis, we further confirmed this result in several RCC cell lines. Clinically, the expression of these two genes is positively correlated in RCC patient specimens. Furthermore, elevated SPARC expression is found in all the subtypes of RCC and positively correlated with the RCC stage and grade. In contrast, SPARC expression is inversely correlated with overall and disease-free survival of patients with RCC, suggesting SPARC as a potent prognostic marker of RCC patient survival. Knocking down SPARC significantly inhibits RCC cell invasion and metastasis both in vitro and in vivo. Similarly, in vitro cell invasion can be diminished by using a specific monoclonal antibody. Mechanistically, SPARC activates protein kinase B (AKT) pathway leading to elevated expression of matrix metalloproteinase-2 that can facilitate RCC invasion. Altogether, our data support that SPARC is a critical role of TGF-β signaling network underlying RCC progression and a potential therapeutic target as well as a prognostic marker.
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http://dx.doi.org/10.1002/jcp.29975DOI Listing
March 2021

Overcoming sociodemographic factors in the care of patients with testicular cancer at a safety net hospital.

Cancer 2020 Oct 10;126(19):4362-4370. Epub 2020 Aug 10.

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

Background: The objective of this study was to determine whether standardized treatment of germ cell tumors (GCTs) could overcome sociodemographic factors limiting patient care.

Methods: The records of all patients undergoing primary treatment for GCTs at both a public safety net hospital and an academic tertiary care center in the same metropolitan area were analyzed. Both institutions were managed by the same group of physicians in the context of multidisciplinary cancer care. Patients were grouped by care center; clinicopathologic features and outcomes were analyzed.

Results: Between 2006 and 2018, 106 and 95 patients underwent initial treatment for GCTs at the safety net hospital and the tertiary care center, respectively. Safety net patients were younger (29 vs 33 years; P = .005) and were more likely to be Hispanic (79% vs 11%), to be uninsured (80% vs 12%; P < .001), to present via the emergency department (76% vs 8%; P < .001), and to have metastatic (stage II/III) disease (42% vs 26%; P = .025). In a multivariable analysis, an absence of lymphovascular invasion (odds ratio [OR], 0.30; P = .008) and an embryonal carcinoma component (OR, 0.36; P = .02) were associated with decreased use of adjuvant treatment for stage I patients; hospital setting was not (OR, 0.67; P = .55). For patients with stage II/III nonseminomatous GCTs, there was no difference in the performance of postchemotherapy retroperitoneal lymph node dissection between the safety net hospital and the tertiary care center (52% vs 64%; P = .53). No difference in recurrence rates was observed between the cohorts (5% vs 6%; P = .76).

Conclusions: Sociodemographic factors are often associated with adverse clinical outcomes in the treatment of GCTs; they may be overcome with integrated, standardized management of testicular cancer.
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http://dx.doi.org/10.1002/cncr.33076DOI Listing
October 2020

Active Surveillance for Intermediate-Risk Prostate Cancer: Systematic Review and Meta-analysis of Current Protocols and Outcomes.

Clin Genitourin Cancer 2020 Dec 22;18(6):e739-e753. Epub 2020 May 22.

Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia.

Introduction: Current guidelines allow active surveillance for intermediate-risk prostate cancer patients but do not provide comprehensive recommendations for selection. We performed a systematic review and meta-analysis of outcomes for active surveillance in intermediate- and low-risk groups.

Methods: We performed a systematic literature search of intermediate-risk localized prostate cancer patients undergoing active surveillance using 3 literature search engines (Medline, Web of Science, and Scopus) over the past 10 years. The primary outcome was the percentage of patients who remain under surveillance. Secondary outcomes included cancer-specific survival, overall survival, and metastasis-free survival. For articles including both low- and intermediate-risk patients undergoing active surveillance, comparisons between the two groups were made.

Results: The proportion of patients who remained on active surveillance was comparable between the low- and intermediate-risk groups after 10 and 15 years' follow-up (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.83-1.14; and OR, 0.86; 95% CI, 0.65-1.13). Cancer-specific survival was worse in the intermediate-risk group after 10 years (OR, 0.47; 95% CI, 0.31-0.69) and 15 years (OR, 0.34; 95% CI, 0.2-0.58). The overall survival rate showed no statistical difference at 5 years' follow-up (OR, 0.84; 95% CI, 0.45-1.57) but was worse in the intermediate-risk group after 10 years (OR, 0.43; 95% CI, 0.35-0.53). Metastases-free survival did not significantly differ after 5 years (OR, 0.55; 95% CI, 0.2-1.53) and was worse in the intermediate-risk group after 10 years (OR, 0.46; 95% CI, 0.28-0.77).

Conclusion: Active surveillance could be offered to patients with intermediate-risk prostate cancer. However, they should be informed of the need for regular monitoring and the possibility of discontinuation as a result of a higher rate of progression. Available data indicate that 5-year survival rates between intermediate- and low-risk patients do not differ; 10-year survival rates are worse. To assess the long-term effectiveness and safety of active surveillance, it is necessary to develop unified algorithms for patient selection and management, and to prospectively conduct studies with long-term surveillance.
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http://dx.doi.org/10.1016/j.clgc.2020.05.008DOI Listing
December 2020

Does grossly complete transurethral resection improve response to neoadjuvant chemotherapy?

Urol Oncol 2020 09 17;38(9):736.e11-736.e18. Epub 2020 Jul 17.

Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address:

Introduction: There is controversy regarding the benefit of a grossly complete transurethral resection of bladder tumor (TURBT) for muscle-invasive bladder cancer (MIBC) in patients prior to neoadjuvant chemotherapy (NAC). Advocates for this approach suggest a higher response rate to NAC, while others suggest this can increase the surgical risk for no clear benefit.

Methods: We retrospectively reviewed our institutional radical cystectomy (RC) database from 2011 to 2018 for patients who received an adequate course of cisplatin-based NAC for nonmetastatic MIBC. Univariable and multivariable logistic regression analyses were performed to identify factors associated with complete response [ypT0] or no residual muscle invasive bladder cancer [ypT < 2] following NAC based on clinicopathologic characteristics and grossly complete or incomplete TURBT.

Results: A total of 167 patients received NAC followed by RC for MIBC during the study period and 100 patients were included in the analysis due to known status of the completeness of TURBT-of these 49 patients underwent complete resection while 51 patients underwent incomplete resection prior to NAC. There were no significant differences in baseline clinicopathologic characteristics between patients who had complete vs. incomplete TURBT. At the time of RC, the overall ypT0 rate was 24% (n = 24), while the overall rate of ypT < 2 was 45%. On logistic regression, there was no association between completeness of TURBT and ypT0 or ypT < 2. Age, histology, and organ-confined disease were not significantly associated with response to NAC. Only smoking status (current or prior history) was negatively associated with ypT0 on univariable and multivariable analysis (odds ratio = 0.36, 95% confidence interval: [0.14-0.91], P = 0.031).

Conclusion: We found no association between response to cisplatin-based NAC and completeness of TURBT in a cohort of MIBC patients. The study is limited by its retrospective nature and lack of ability to predict response to NAC based on TURBT tissue evaluation.
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http://dx.doi.org/10.1016/j.urolonc.2020.05.032DOI Listing
September 2020

Magnetic Resonance Imaging Radiomics Analyses for Prediction of High-Grade Histology and Necrosis in Clear Cell Renal Cell Carcinoma: Preliminary Experience.

Clin Genitourin Cancer 2021 Feb 23;19(1):12-21.e1. Epub 2020 May 23.

Department of Radiology, UT Southwestern Medical Center, Dallas, TX; Department of Urology, UT Southwestern Medical Center, Dallas, TX; Kidney Cancer Program, UT Southwestern Medical Center, Dallas, TX; Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX. Electronic address:

Introduction: Percutaneous renal mass biopsy results can accurately diagnose clear cell renal cell carcinoma (ccRCC); however, their reliability to determine nuclear grade in larger, heterogeneous tumors is limited. We assessed the ability of radiomics analyses of magnetic resonance imaging (MRI) to predict high-grade (HG) histology in ccRCC.

Patients And Methods: Seventy patients with a renal mass underwent 3 T MRI before surgery between August 2012 and August 2017. Tumor length, first-order statistics, and Haralick texture features were calculated on T2-weighted and dynamic contrast-enhanced (DCE) MRI after manual tumor segmentation. After a variable clustering algorithm was applied, tumor length, washout, and all cluster features were evaluated univariably by receiver operating characteristic curves. Three logistic regression models were constructed to assess the predictability of HG ccRCC and then cross-validated.

Results: At univariate analysis, area under the curve values of length, and DCE texture cluster 1 and cluster 3 for diagnosis of HG ccRCC were 0.7 (95% confidence interval [CI], 0.58-0.82, false discovery rate P = .008), 0.72 (95% CI, 0.59-0.84, false discovery rate P = .004), and 0.75 (95% CI, 0.63-0.87, false discovery rate P = .0009), respectively. At multivariable analysis, area under the curve for model 1 (tumor length only), model 2 (length + DCE clusters 3 and 4), and model 3 (DCE cluster 1 and 3) for diagnosis of HG ccRCC were 0.67 (95% CI, 0.54-0.79), 0.82 (95% CI, 0.71-0.92), and 0.81 (95% CI, 0.70-0.91), respectively.

Conclusion: Radiomics analysis of MRI images was superior to tumor size for the prediction of HG histology in ccRCC in our cohort.
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http://dx.doi.org/10.1016/j.clgc.2020.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680717PMC
February 2021

Prospective evaluation of blue-light flexible cystoscopy with hexaminolevulinate in non-muscle-invasive bladder cancer.

BJU Int 2021 01 6;127(1):108-113. Epub 2020 Aug 6.

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

Objectives: To evaluate the utility of blue-light flexible cystoscopy (BLFC) for surveillance of non-muscle-invasive bladder cancer (NMIBC).

Patients And Methods: Prospective cohort of consecutive patients who underwent office-based BLFC for NMIBC. Clinical information was collected including cystoscopic findings and pathological data.

Results: A total of 322 cases were performed on 190 patients. The mean age was 71 years and 83% were men. The highest stage prior to BLFC was Ta, carcinoma in situ (CIS), T1, and T2 in 45.3%, 18.4%, 30% and 2%, respectively. Prior to BLFC, 16.8%, 60.5%, and 16.8% were low grade (LG), high grade (HG), and CIS, respectively. Intravesical bacille Calmette-Guérin and intravesical chemotherapy were used in 54.2% and 18.4%, respectively. White-light cystoscopy (WLC) and BLFC were both normal in 173 (53.7%) of cases. WLC was normal and BLFC was abnormal in 26 (8%) cases. Of these, 15 had office-based biopsy and cancer was detected in 13 (87%; six CIS, four HG Ta, three LG Ta). Both WLC and BLFC were positive in 83 (25.8%) cases and 33% had additional tumours found. Cancer was found in 27 (75%) of WLC+/BLFC+ who underwent office-based biopsy including 19 LG Ta, six HG Ta, and two CIS.

Conclusions: Incorporation of BLFC in clinical practice has potential advantages of finding cancer in cases with normal WLC. BLFC detected additional cancers in 33% of patients with positive WLC and BLFC, which can improve surveillance and performance of office-based biopsy. Further research is needed to determine cost-effectiveness and impact on recurrence rates.
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http://dx.doi.org/10.1111/bju.15166DOI Listing
January 2021