Publications by authors named "Shahrokh F Shariat"

1,361 Publications

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Evaluation of the Predictive Role of Blood-Based Biomarkers in the Context of Suspicious Prostate MRI in Patients Undergoing Prostate Biopsy.

J Pers Med 2021 Nov 19;11(11). Epub 2021 Nov 19.

Department of Urology, Medical University of Vienna, 1090 Vienna, Austria.

The aim of this study was to assess the predictive value of pre-biopsy blood-based markers in patients undergoing a fusion biopsy for suspicious prostate magnetic resonance imaging (MRI). We identified 365 consecutive patients who underwent MRI-targeted and systematic prostate biopsy for an MRI scored Prostate Imaging-Reporting and Data System Version (PI-RADS) ≥ 3. We evaluated the neutrophil/lymphocyte ratio (NLR), derived neutrophil/lymphocyte ratio (dNLR), platelet/lymphocyte ratio (PLR), systemic immune inflammation index (SII), lymphocyte/monocyte ratio (LMR,) de Ritis ratio, modified Glasgow Prognostic Score (mGPS), and prognostic nutrition index (PNI). Uni- and multivariable logistic models were used to analyze the association of the biomarkers with biopsy findings. The clinical benefits of biomarkers implemented in clinical decision-making were assessed using decision curve analysis (DCA). In total, 69% and 58% of patients were diagnosed with any prostate cancer and Gleason Grade (GG) ≥ 2, respectively. On multivariable analysis, only high dNLR (odds ratio (OR) 2.61, 95% confidence interval (CI) 1.23-5.56, = 0.02) and low PNI (OR 0.48, 95% CI 0.26-0.88, = 0.02) remained independent predictors for GG ≥ 2. The logistic regression models with biomarkers reached AUCs of 0.824-0.849 for GG ≥ 2. The addition of dNLR and PNI did not enhance the net benefit of a standard clinical model. Finally, we created the nomogram that may help guide biopsy avoidance in patients with suspicious MRI. In patients with PI-RADS ≥ 3 lesions undergoing MRI-targeted and systematic biopsy, a high dNLR and low PNI were associated with unfavorable biopsy outcomes. Pre-biopsy blood-based biomarkers did not, however, significantly improve the discriminatory power and failed to add a clinical benefit beyond standard clinical factors.
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http://dx.doi.org/10.3390/jpm11111231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625876PMC
November 2021

Expression Analysis and Mutational Status of Histone Methyltransferase at Different Upper Tract Urothelial Carcinoma Locations.

J Pers Med 2021 Nov 4;11(11). Epub 2021 Nov 4.

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria.

The gene coding for histone methyltransferase KMT2D is found among the top mutated genes in upper tract urothelial carcinoma (UTUC); however, there is a lack of data regarding its association with clinicopathologic features as well as survival outcomes. Therefore, we aimed to investigate expression, mutation patterns, and their utility as prognostic biomarkers in patients with UTUC. A single-center study was conducted on tumor specimens from 51 patients treated with radical nephroureterectomy (RNU). Analysis of KMT2D protein expression was performed using immunohistochemistry (IHC). Customized next-generation sequencing (NGS) was used to assess alterations in exons. Cox regression was used to assess the relationship of protein expression and mutational status with survival outcomes. KMT2D expression was increased in patients with a previous history of bladder cancer (25% vs. 0%, = 0.02). The NGS analysis of KMT2D exons in 27 UTUC tumors revealed a significant association between pathogenic variants and tumor location ( = 0.02). Pathogenic variants were predominantly found in patients with non-pelvic or multifocal tumors (60% vs. 14%), while the majority of patients with a pelvic tumor location (81% vs. 20%) did not harbor pathogenic alterations. Both IHC and NGS analyses of failed to detect a statistically significant association between KMT2D protein or gene alteration status and clinical variables such as stage/grade of the disease or survival outcomes (all > 0.05). alterations and protein expression were associated with UTUC features such as multifocality, ureteral location, and previous bladder cancer. While KMT2D protein expression and mutational status do not seem to have prognostic value in UTUC, they appear to add information to improve clinical decision-making regarding the type of therapy.
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http://dx.doi.org/10.3390/jpm11111147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625702PMC
November 2021

Immuno-oncology therapy in metastatic bladder cancer: a systematic review and network meta-analysis.

Crit Rev Oncol Hematol 2021 Nov 22:103534. Epub 2021 Nov 22.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Context: Three first line and three second-line clinical trials tested the effect of immunotherapy (IO) relative to standard chemotherapy (CT) on overall survival. However, network meta-analysis-based comparisons have not yet been presented. We addressed this void.

Objective: To provide comparisons of overall survival (OS), progression-free survival (PFS), complete response (CR), partial response (PR), stable disease (SD), objective response rates (ORR), disease control rates (DCR) and adverse events (AEs) associated with 1 and 2 line IO-based regimens.

Materials And Methods: PubMed was searched for phase III randomized controlled trials from 2016 to 2021, including conference abstracts. We identified three first line [IMvigor130 (atezolizumab + CT vs atezolizumab vs CT), DANUBE (durvalumab vs durvalumab + tremelimumab vs CT), and KEYNOTE-361 (pembrolizumab + CT vs pembrolizumab vs CT)] and two second line [KEYNOTE-045 (pembrolizumab vs CT) and IMvigor211 (atezolizumab vs CT)] RCTs.

Results: Overall, 3,255 and 1,452 patients were respectively included in the first- and second-line settings. In 1 line setting, compared with CT, no IO-based regimen exhibited survival benefit. However, all exclusive IO regimens resulted in lower rates of grade 3+ AEs. In 2 line setting, compared with CT, only pembrolizumab improved OS benefit. Conversely, atezolizumab only showed OS benefit in exploratory analyses. Compared to second-line CT, no experimental regimen (atezolizumab or pembrolizumab) exhibited statistically significant ORR benefit. Both pembrolizumab and atezolizumab resulted in lower rates of grade 3+ AEs compared to 2 line CT.

Conclusions: In metastatic UC, IO-based regimens do not hold a survival benefit relative to CT in 1 line setting. However, pembrolizumab holds a survival benefit in 2 line compared to CT. Several IO-based clinical trials are ongoing and will provide more and possibly better treatment alternatives for locally advanced and metastatic UC.
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http://dx.doi.org/10.1016/j.critrevonc.2021.103534DOI Listing
November 2021

Impact of preoperative systemic immune-inflammation Index on oncologic outcomes in bladder cancer patients treated with radical cystectomy.

Urol Oncol 2021 Nov 20. Epub 2021 Nov 20.

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia; Department of Special Surgery, Division of Urology, Jordan University Hospital, The University of Jordan, Amman, Jordan; Karl Landsteiner Society, Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Department of Urology, Weill Cornell Medical College, New York, NY; Department of Urology, University of Texas Southwestern, Dallas, TX. Electronic address:

Purpose: To investigate the predictive and prognostic value of the preoperative systemic immune-inflammation index (SII) in patients undergoing radical cystectomy (RC) for clinically non-metastatic urothelial cancer of the bladder (UCB).

Methods: Overall, 4,335 patients were included, and the cohort was stratified in two groups according to SII using an optimal cut-off determined by the Youden index. Uni- and multivariable logistic and Cox regression analyses were performed, and the discriminatory ability by adding SII to a reference model based on available clinicopathologic variables was assessed by area under receiver operating characteristics curves (AUC) and concordance-indices. The additional clinical net-benefit was assessed using decision curve analysis (DCA).

Results: High SII was observed in 1879 (43%) patients. On multivariable preoperative logistic regression, high SII was associated with lymph node involvement (LNI; P = 0.004), pT3/4 disease (P <0.001), and non-organ confined disease (NOCD; P <0.001) with improvement of AUCs for predicting LNI (P = 0.01) and pT3/4 disease (P = 0.01). On multivariable Cox regression including preoperative available clinicopathologic values, high SII was associated with recurrence-free survival (P = 0.028), cancer-specific survival (P = 0.005), and overall survival (P = 0.006), without improvement of concordance-indices. On DCAs, the inclusion of SII did not meaningfully improve the net-benefit for clinical decision-making in all models.

Conclusion: High preoperative SII is independently associated with pathologic features of aggressive disease and worse survival outcomes. However, it did not improve the discriminatory margin of a prediction model beyond established clinicopathologic features and failed to add clinical benefit for decision making. The implementation of SII as a part of a panel of biomarkers in future studies might improve decision-making.
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http://dx.doi.org/10.1016/j.urolonc.2021.10.006DOI Listing
November 2021

Update on systemic treatment of upper tract urothelial carcinoma: a narrative review of the literature.

Transl Androl Urol 2021 Oct;10(10):4051-4061

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

Urothelial cancer (UC) is most commonly found in the urinary bladder, but can also appear in the upper urinary tract, where it is associated with several disease-specific challenges affecting its diagnosis, clinical staging, surgical management, and systemic therapy. A significant number of patients experience extra-vesical disease recurrence despite radical nephroureterectomy (RNU), leading to inevitable demise. Over the last years, the therapeutic armamentarium of UC has expanded with several systemic treatment options entering clinical care and deliver the potential to support a more individualized treatment in the near future. Currently, novel targeted therapies are emerging, accompanied with extensive biomarker research, which leads to a better understanding of the disease and therefore, reshaping the treatment landscape continuously and decisively. Though, systemic treatment of UTUC comes along with certain challenges that are specific to the disease, e.g., loss of renal function after RNU, which might result in ineligibility for a cisplatin-based chemotherapy. In this narrative review, the current standard of systemic treatment of UC in the perioperative and metastatic treatment setting are reported, with focus on UTUC. In addition, molecular aspects of UTUC, as well as future directions and specific implications for treatment of patients diagnosed with UTUC are discussed.
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http://dx.doi.org/10.21037/tau-21-47DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575594PMC
October 2021

Survival after radical prostatectomy vs. radiation therapy in ductal carcinoma of the prostate.

Int Urol Nephrol 2021 Nov 19. Epub 2021 Nov 19.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Aim: To compare cancer-specific mortality (CSM) rates between radical prostatectomy (RP) vs. external beam radiotherapy (RT) in patients with ductal carcinoma (DC) of the prostate.

Materials And Methods: Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2016), we identified 369 DC patients, of whom 303 (82%) vs. 66 (18%) were treated with RP vs. RT, respectively. Kaplan-Meier plots and uni- and stepwise multivariate Cox regression models addressed CSM in the unmatched population. After propensity score matching (PSM) and inverse probability of treatment weighting (IPTW), Kaplan-Meier curve and Cox regression models tested the effect of RP vs RT on CSM.

Results: Overall, RT patients were older, harbored higher PSA values, higher clinical T and higher Gleason grade groups. 5-year CSM rates were respectively 4.2 vs. 10% for RP vs. RT (HR 0.40, 95% CI 0.16-0.99, p = 0.048, favoring RP). At step-by-step multivariate Cox regression, after adding possible confounders, the central tendency of the HR for RP vs. RT approached 1. PSM resulted into 124 vs. 53 patients treated respectively with RP vs. RT. After PSM, as well as after IPTW, the protective effect of RP was no longer present (HR 1.16, 95% CI 0.23-5.73, p = 0.9 and 0.97, 95% CI 0.35-2.66, p = 0.9, respectively).

Conclusions: Although CSM rate of ductal carcinoma RP patients is lower of that of RT patients, this apparent benefit disappears after statistical adjustment for population differences.
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http://dx.doi.org/10.1007/s11255-021-03070-8DOI Listing
November 2021

Cancer-specific mortality after radical prostatectomy vs external beam radiotherapy in high-risk Hispanic/Latino prostate cancer patients.

Int Urol Nephrol 2021 Nov 16. Epub 2021 Nov 16.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, QC, Canada.

Purpose: To test for differences in cancer-specific mortality (CSM) rates in Hispanic/Latino prostate cancer patients according to treatment type, radical prostatectomy (RP) vs external beam radiotherapy (EBRT).

Methods: Within the Surveillance, Epidemiology, and End Results database (2010-2016), we identified 2290 NCCN (National Comprehensive Cancer Network) high-risk (HR) Hispanic/Latino prostate cancer patients. Of those, 893 (39.0%) were treated with RP vs 1397 (61.0%) with EBRT. First, cumulative incidence plots and competing risks regression models tested for CSM differences after adjustment for other cause mortality (OCM). Second, cumulative incidence plots and competing risks regression models were refitted after 1:1 propensity score matching (according to age, PSA, biopsy Gleason score, cT-stage, cN-stage).

Results: In NCCN HR patients, 5-year CSM rates for RP vs EBRT were 2.4 vs 4.7%, yielding a multivariable hazard ratio of 0.37 (95% CI 0.19-0.73, p = 0.004) favoring RP. However, after propensity score matching, the hazard ratio of 0.54 was no longer statistically significant (95% CI 0.21-1.39, p = 0.2).

Conclusion: Without the use of strictest adjustment for population differences, NCCN high-risk Hispanic/Latino prostate cancer patients appear to benefit more of RP than EBRT. However, after strictest adjustment for baseline patient and tumor characteristics between RP and EBRT cohorts, the apparent CSM benefit of RP is no longer statistically significant. In consequence, in Hispanic/Latino NCCN high-risk patients, either treatment modality results in similar CSM outcome.
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http://dx.doi.org/10.1007/s11255-021-03055-7DOI Listing
November 2021

Seasonal Variations in the Diagnosis of Testicular Germ Cell Tumors: A National Cancer Registry Study in Austria.

Cancers (Basel) 2021 Oct 27;13(21). Epub 2021 Oct 27.

Department of Urology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.

We conducted a retrospective National Cancer Registry study in Austria to assess a possible seasonal variation in the clinical diagnosis of testicular germ cell tumors (TGCT). In total, 3615 testicular cancer diagnoses were identified during an 11-year period from 2008 to 2018. Rate ratios for the monthly number of TGCT diagnoses, as well as of seasons and half-years, were assessed using a quasi-Poisson model. We identified, for the first time, a statistically significant seasonal trend ( < 0.001) in the frequency of monthly newly diagnosed cases of TGCT. In detail, clear seasonal variations with a reduction in the tumor incidence during the summer months (Apr-Sep) and an increase during the winter months (Oct-Mar) were observed ( < 0.001). Focusing on seasonality, the incidence during the months of Oct-Dec ( = 0.008) and Jan-Mar ( < 0.001) was significantly higher compared to the months of Jul-Sep, respectively. Regarding histopathological features, there is a predominating incidence in the winter months compared to summer months, mainly concerning pure seminomas ( < 0.001), but not the non-seminoma or mixed TGCT groups. In conclusion, the incidence of TGCT diagnoses in Austria has a strong seasonal pattern, with the highest rate during the winter months. These findings may be explained by a delay of self-referral during the summer months. However, the hypothetical influence of vitamin D3 in testicular carcinogenesis underlying seasonal changes in TGCT diagnosis should be the focus of further research.
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http://dx.doi.org/10.3390/cancers13215377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582382PMC
October 2021

Discordance Between Clinical and Pathological Staging and Grading in Upper Tract Urothelial Carcinoma.

Clin Genitourin Cancer 2021 Oct 10. Epub 2021 Oct 10.

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

Introduction: This study aimed to evaluate the concordance in tumor stage and grade between ureteroscopic (URS) biopsy and radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC).

Patients And Methods: Records of 1,214 UTUC patients who had undergone URS biopsy followed by RNU were included. Univariable and multivariable logistic regression analyses were performed to identify factors contributing to the pathological upstaging.

Results: The concordance between URS biopsy-based clinical and RNU pathological staging was 34.5%. Clinical understaging occurred in 59.5% patients. Upstaging to muscle-invasive disease occurred in 240 (41.7%) of 575 patients diagnosed with ≤cT1 disease. Of those diagnosed with muscle-invasive disease on final pathology, 89.6% had been clinically diagnosed with ≤cT1 disease. In the univariable analyses, computed tomography urography (CTU)-based invasion, ureter location, hydronephrosis, high-grade cytology, high-grade biopsy, sessile architecture, age, and women sex were significantly associated with pathological upstaging (P < .05). In the multivariable analyses, CTU-based invasion and hydronephrosis remained associated with pathological upstaging (P < .05). URS biopsy-based clinical and pathological gradings were concordant in 634 (54.2%) patients. Clinical undergrading occurred in 496 (42.4%) patients.

Conclusions: Clinical understaging/undergrading and upstaging to muscle-invasive disease occurred in a high proportion of UTUC patients undergoing RNU. Despite the inherent selection bias, these data underline the challenges of accurate UTUC staging and grading. In daily clinical practice, URS biopsy and CTU offer the most accurate preoperative information albeit with limited predictive value when used alone. These findings should be considered when utilizing preoperative, risk-adapted strategies.
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http://dx.doi.org/10.1016/j.clgc.2021.10.002DOI Listing
October 2021

Pretreatment clinical and hematologic prognostic factors of metastatic urothelial carcinoma treated with pembrolizumab: a systematic review and meta-analysis.

Int J Clin Oncol 2021 Nov 10. Epub 2021 Nov 10.

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Wahringer Gurtel 43 18-20, 1090, Vienna, Austria.

Pembrolizumab is the standard for the first and second lines in treating metastatic urothelial carcinoma (UC). This systematic review and meta-analysis aimed to assess the value of pretreatment clinical characteristics and hematologic biomarkers for prognosticating response to pembrolizumab in patients with metastatic UC. PUBMED, Web of Science™, and Scopus databases were searched for articles published before May 2021 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were deemed eligible if they evaluated overall survival (OS) in patients with metastatic urothelial carcinoma treated with pembrolizumab and pretreatment clinical characteristics or laboratory examination. Overall, 13 studies comprising 1311 patients were eligible for the meta-analysis. Several pretreatment patients' demographics and hematologic biomarkers were significantly associated with worse OS as follows: Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≥ 2 (Pooled hazard ratio [HR]: 3.24, 95% confidence interval [CI] 2.57-4.09), presence of visceral metastasis (Pooled HR: 1.84, 95% CI 1.42-2.38), presence of liver metastasis (Pooled HR: 4.23, 95% CI 2.18-8.20), higher neutrophil-lymphocyte ratio (NLR) (Pooled HR: 1.29, 95% CI 1.07-1.55) and, higher c-reactive protein (CRP) (Pooled HR: 2.49, 95% CI 1.52-4.07). Metastatic UC patients with poor PS, liver metastasis, higher pretreatment NLR and/or CRP have a worse survival despite pembrolizumab treatment. These findings might help to guide the prognostic tools for clinical decision-making; however, they should be interpreted carefully, owing to limitations regarding the retrospective nature of primary data.
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http://dx.doi.org/10.1007/s10147-021-02061-0DOI Listing
November 2021

Diagnostic Accuracy of Novel Urinary Biomarker Tests in Non-muscle-invasive Bladder Cancer: A Systematic Review and Network Meta-analysis.

Eur Urol Oncol 2021 Nov 6. Epub 2021 Nov 6.

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

Context: During the past decade, several urinary biomarker tests (UBTs) for bladder cancer have been developed and made commercially available. However, none of these is recommended by international guidelines so far.

Objective: To assess the diagnostic estimates of novel commercially available UBTs for diagnosis and surveillance of non-muscle-invasive bladder cancer (NMIBC) using diagnostic test accuracy (DTA) and network meta-analysis (NMA).

Evidence Acquisition: PubMed, Web of Science, and Scopus were searched up to April 2021 to identify studies addressing the diagnostic values of UBTs: Xpert bladder cancer, Adxbladder, Bladder EpiCheck, Uromonitor and Cxbladder Monitor, and Triage and Detect. The primary endpoint was to assess the pooled diagnostic values for disease recurrence in NMIBC patients using a DTA meta-analysis and to compare them with cytology using an NMA. The secondary endpoints were the diagnostic values for high-grade (HG) recurrence as well as for the initial detection of bladder cancer.

Evidence Synthesis: Twenty-one studies, comprising 7330 patients, were included in the quantitative synthesis. In most of the studies, there was an unclear risk of bias. For NMIBC surveillance, novel UBTs demonstrated promising pooled diagnostic values with sensitivities up to 93%, specificities up to 84%, positive predictive values up to 67%, and negative predictive value up to 99%. Pooled estimates for the diagnosis of HG recurrence were similar to those for the diagnosis of any-grade recurrence. The analysis of the number of cystoscopies potentially avoided during the follow-up of 1000 patients showed that UBTs might be efficient in reducing the number of avoidable interventions with up to 740 cystoscopies. The NMA revealed that diagnostic values (except specificity) of the novel UBTs were significantly higher than those of cytology for the detection of NMIBC recurrence. There were too little data on UBTs in the primary diagnosis setting to allow a statistical analysis.

Conclusions: Our analyses support high diagnostic accuracy of the studied novel UBTs, supporting their utility in the NMIBC surveillance setting. All of these might potentially help prevent unnecessary cystoscopies safely. There are not enough data to reliably assess their use in the primary diagnostic setting. These results have to be confirmed in a larger cohort as well as in head-to-head comparative studies. Nevertheless, our study might help policymakers and stakeholders evaluate the clinical and social impact of the implementation of these tests into daily practice.

Patient Summary: Novel urinary biomarker tests outperform cytology with the potential of improving routine clinical practice by preventing unnecessary cystoscopic examinations during the surveillance of non-muscle-invasive bladder cancer.
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http://dx.doi.org/10.1016/j.euo.2021.10.003DOI Listing
November 2021

Adverse events of different chemotherapy regimens in the first-line treatment of patients with advanced or metastatic urothelial cancer: A systematic review and network meta-analysis of randomized controlled trials.

Semin Oncol 2021 Jun 2;48(3):181-192. Epub 2021 Oct 2.

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, New York, USA; Department of Urology, University of Texas Southwestern, Dallas, Texas, USA; 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. Electronic address:

Introduction: The present systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) aimed to compare the mortality rates related to adverse events (AEs) and discontinuation of treatment due to toxicity as well as all AEs of currently used chemotherapy regimens for first-line therapy of advanced or metastatic urothelial carcinoma of the bladder (UCB).

Material And Methods: The MEDLINE and EMBASE databases were searched for articles published between January 2000 and June 2020 according to the Preferred Reporting Items for Systematic Review and Meta-analysis extension statement for NMA. Eligible studies included RCTs comparing different first-line chemotherapy regimens for treating advanced or metastatic UCB and AEs as outcome measures. A NMA was performed to assess the mortality rates related to AEs and discontinuation of treatment due to toxicity as well as all AEs.

Results: Fourteen trials comprising 2,615 patients met our eligibility criteria and formal NMAs were conducted. Results revealed that gemcitabine plus carboplatin had the lowest likelihood of mortality related to AEs (P score: 0.8079), while larotaxel plus cisplatin and paclitaxel, cisplatin plus gemcitabine had both a lower toxicity rate leading to discontinuation (P score: 0.7295 and P score: 0.7242, respectively). Compared with gemcitabine plus cisplatin (GC), most chemotherapy regimens were associated with a lower likelihood of thrombocytopenia, anemia, and cardiovascular toxicity. In contrast, most chemotherapy regimens compared with GC were associated with a higher likelihood of neutropenia, central (fatigue, neuropathy) and gastrointestinal AEs, infections, as well as renal and pulmonary toxicities.

Conclusion: Results of the present study demonstrated that hematological toxicity was the most prevalent AE associated with gemcitabine-containing regimens, while central AEs and febrile neutropenia were more commonly in taxane-containing regimens. GC had the lowest rate of gastrointestinal AEs, infection disorders, and pulmonary toxicities. Cisplatin-containing regimens were associated with a higher rate of renal and cardiovascular toxicity. These differential AEs may help in the detection of the personalized therapy in addition of efficacy data.
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http://dx.doi.org/10.1053/j.seminoncol.2021.09.005DOI Listing
June 2021

Urological adverse drug reactions of psychotropic medication in psychiatric inpatients - A drug surveillance report from German-speaking countries.

J Psychiatr Res 2021 Oct 27;144:412-420. Epub 2021 Oct 27.

Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.

Urological adverse drug reactions (UADR) are common during treatment with psychotropic medication. The aim of this study was to provide a systematic description of the differential profile of UADR of psychotropic drugs in a large naturalistic population. Data stems from psychiatric hospitals collected by AMSP (Arzneimittelsicherheit in der Psychiatrie), a continuous multi-center pharmacovigilance program in Austria, Germany, and Switzerland. 171 cases of severe UADR (0.037%) among a total population of 462 661 inpatients treated with psychotropic drugs in 99 psychiatric hospitals between 1993 and 2016 were examined. Urinary retention (129 cases, 0.028%) was the most common UADR followed by incontinence (23 cases, 0.005%) and nocturnal enuresis (16 cases, 0.003%). Risk of UADR was higher in patients with mania than in other diagnostic groups. Promethazine and haloperidol were the antipsychotics with the highest rate of UADR. Tricyclic antidepressants had a higher and selective serotonin reuptake inhibitors a lower risk for UADR than the respective other antidepressants. Amitriptyline and clomipramine were the most common causes of urinary retention and clozapine of urinary incontinence. This research improves our knowledge of the urological risk profiles of psychotropic drugs in inpatients and highlights compounds associated with higher or lower risk.
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http://dx.doi.org/10.1016/j.jpsychires.2021.10.026DOI Listing
October 2021

Immunotherapy-based combinations in the first-line treatment of metastatic renal cell carcinoma with sarcomatoid features: a systematic review and network meta-analysis.

Curr Opin Urol 2022 Jan;32(1):61-68

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

Purpose Of Review: To perform indirect comparisons of efficacy and safety of first-line immune checkpoint inhibitor (ICI)-based combination therapies for renal cell carcinoma with sarcomatoid features (sRCC).

Recent Findings: Five trials were included in our network meta-analyses comprising 568 patients. The combinations nivolumab plus ipilimumab and nivolumab plus cabozantinib achieved significant improvement of progression-free survival (PFS), overall survival (OS), and objective response rates (ORR). Nivolumab plus ipilimumab was associated with the highest likelihood of achieving a complete response. All the included combinations significantly improved PFS and ORR. The combinations of pembrolizumab plus axitinib did not show a statistically significant association with OS. Nivolumab plus cabozantinib had the highest likelihood of improving PFS and OS.

Summary: Our network meta-analysis demonstrates that sRCC are responsive to immune-based combinations. The dual ICI with nivolumab plus ipilimumab improved all efficacy outcomes and achieved the highest complete response rates (CRR). Although the association of nivolumab plus cabozantinib with CRR was not statistically significant, this combination demonstrated the highest likelihood of PFS and OS improvements.
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http://dx.doi.org/10.1097/MOU.0000000000000940DOI Listing
January 2022

Comparison of Clinicopathologic and Oncological Outcomes Between Transurethral En Bloc Resection and Conventional Transurethral Resection of Bladder Tumor: A Systematic Review, Meta-Analysis and Network Meta-Analysis with Focus on Different Energy Sources.

J Endourol 2021 Nov 16. Epub 2021 Nov 16.

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

It has been hypothesized that transurethral en bloc (TUEB) of bladder tumor offers benefits over conventional transurethral resection of bladder tumor (cTURBT). This study aimed to compare disease outcomes of TUEB and cTURBT with focus on the different energy sources. A systematic search was performed using PubMed and Web of Science databases in June 2021. Studies that compared the pathological (detrusor muscle presence), oncological (recurrence rates) efficacy, and safety (serious adverse events [SAEs]) of TUEB and cTURBT were included. Random- and fixed-effects meta-analytic models and Bayesian approach in the network meta-analysis was used. Seven randomized clinical trials (RCTs) and seven non-RCTs (NRCT), with a total of 2092 patients. The pooled 3- and 12-month recurrence risk ratios (RR) of five and four NRCTs were 0.46 (95% CI 0.29-0.73) and 0.56 (95% CI 0.33-0.96), respectively. The pooled 3- and 12-month recurrence RRs of four and seven RCTs were 0.57 (95% CI 0.25-1.27) and 0.89 (95% CI 0.69-1.15), respectively. The pooled RR for SAEs such as prolonged hematuria and bladder perforation of seven RCTs was 0.16 (95% CI 0.06-0.41) in benefit of TUEB. Seven RCTs ( = 1077) met our eligibility criteria for network meta-analysis. There was no difference in 12-month recurrence rates between hybridknife, laser, and bipolar TUEB compared with cTURBT. Contrary, laser TUEB was significantly associated with lower SAEs compared with cTURBT. Surface under the cumulative ranking curve ranking analyses showed with high certainty that laser TUEB was the best treatment option to access all endpoints. While NRCTs suggested a recurrence-free benefit to TUEB compared with cTURBT, RCTs failed to confirm this. Conversely, SAEs were consistently and clinically significantly better for TUEB. Network meta-analyses suggested laser TUEB has the best performance compared with other energy sources. These early findings need to be confirmed and expanded upon.
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http://dx.doi.org/10.1089/end.2021.0688DOI Listing
November 2021

Active surveillance for prostate cancer: comparison between incidental tumors vs. tumors diagnosed at prostate biopsies.

World J Urol 2021 Oct 23. Epub 2021 Oct 23.

Department of Urology, IEO European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141, Milan, Italy.

Purpose: To test discontinuation rates during Active Surveillance (AS) in patients diagnosed with incidental prostate cancers (IPCa) vs. tumors diagnosed at prostate biopsies (BxPCa).

Methods: Retrospective single center analysis of 961 vs. 121 BxPCa vs. IPCa patients (2008-2020). Kaplan-Meier plots and multivariable Cox regression models tested four different outcomes: (1) any-cause discontinuation; (2) discontinuation due to ISUP GG upgrading; (3) biopsy discontinuation due to ISUP GG upgrading or > 3 positive cores; (4) biopsy discontinuation or suspicious extraprostatic extension at surveillance mpMRI. Then, multivariable logistic regression models tested rates of clinically significant PCa (csPCa) (ISUP GG ≥ 3 or pT ≥ 3a or pN1) after radical prostatectomy (RP).

Results: Median time follow-up was 35 (19-64) months. IPCa patients were at lower risk of any-cause (3-year survival: 79.3 vs. 66%; HR: 0.5, p = 0.001) and biopsy/MRI AS discontinuation (3-year survival: 82.3 vs. 72.7%; HR: 0.5, p = 0.001), compared to BxPCa patients. Conversely, IPCa patients exhibited same rates of biopsy discontinuation and ISUP GG upgrading over time, relative to BxPCa. In multivariable logistic regression models, IPCa patients were associated with higher rates of csPCa at RP (OR: 1.4, p = 0.03), relative to their BxPCa counterparts.

Conclusion: AS represents a safe management strategy for IPCa. Compared to BxPCa, IPCa patients are less prone to experience any-cause and biopsy/MRI AS discontinuation. However, the two mentioned groups present similar rates of biopsy discontinuation and ISUP GG upgrading over time. In consequence, tailored AS protocols with scheduled repeated surveillance biopsies should be offered to all newly diagnosed IPCa patients.
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http://dx.doi.org/10.1007/s00345-021-03864-6DOI Listing
October 2021

Survival benefit of chemotherapy in a contemporary cohort of metastatic urachal carcinoma.

Urol Oncol 2021 Oct 19. Epub 2021 Oct 19.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Background: We relied on the most contemporary Surveillance, Epidemiology, and End Results (SEER) database and tested the hypothesis that chemotherapy may improve survival in metastatic urachal carcinoma (m-UraC).

Material And Methods: Within the SEER database (2004-2016), we identified m-UraC patients aged ≥ 18 years. Propensity score matching (PSM: cystectomy status, age and sex), Kaplan-Meier plots, cumulative incidence plots, Cox regression models and competing risks regression (CRR) models addressed overall mortality (OM) and cancer-specific mortality (CSM).

Results: Overall, 274 m-UraC patients were identified with a median age of 70 years. Most were male (66%) and Caucasian (72%). Overall, 32% received chemotherapy. Chemotherapy-exposed patients were younger (62 vs. 73 years, p<0.001) and more frequently underwent cystectomy (19 vs. 8%, P = 0.014). In 274 m-UraC patients, median OM and CSM were 6 (4 -10) months and 8 (6 -14) months, respectively. After 1:1 PSM, chemotherapy-exposed patients exhibited lower OM (median 16 vs. 3 months; multivariable HR 0.38, P <0.001) and lower CSM (median 17 vs. 4 months; multivariable CRR HR 0.52, P = 0.001). The association between chemotherapy and better survival was even stronger in younger (≤70 years) patients (OM HR: 0.23, P <0.001; CSM CRR HR: 0.42, P = 0.001), but not in older (≥71 years) patients (OM HR: 0.61, P = 0.2; CSM CRR HR: 1.02, P = 1), after PSM and multivariable adjustments.

Conclusion: Overall, we validated the very aggressive nature of UraC, when distant metastases are present, and observed that m-UraC patients exposed to chemotherapy exhibited lower OM and CSM.
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http://dx.doi.org/10.1016/j.urolonc.2021.09.008DOI Listing
October 2021

Selection and evaluation of preoperative systemic inflammatory response biomarkers model prior to cytoreductive nephrectomy using a machine-learning approach.

World J Urol 2021 Oct 20. Epub 2021 Oct 20.

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

Introduction: This study aimed to determine the prognostic value of a panel of SIR-biomarkers, relative to standard clinicopathological variables, to improve mRCC patient selection for cytoreductive nephrectomy (CN).

Material And Methods: A panel of preoperative SIR-biomarkers, including the albumin-globulin ratio (AGR), De Ritis ratio (DRR), and systemic immune-inflammation index (SII), was assessed in 613 patients treated with CN for mRCC. Patients were randomly divided into training and testing cohorts (65/35%). A machine learning-based variable selection approach (LASSO regression) was used for the fitting of the most informative, yet parsimonious multivariable models with respect to prognosis of cancer-specific survival (CSS). The discriminatory ability of the model was quantified using the C-index. After validation and calibration of the model, a nomogram was created, and decision curve analysis (DCA) was used to evaluate the clinical net benefit.

Results: SIR-biomarkers were selected by the machine-learning process to be of high discriminatory power during the fitting of the model. Low AGR remained significantly associated with CSS in both training (HR 1.40, 95% CI 1.07-1.82, p = 0.01) and testing (HR 1.78, 95% CI 1.26-2.51, p = 0.01) cohorts. High levels of SII (HR 1.51, 95% CI 1.10-2.08, p = 0.01) and DRR (HR 1.41, 95% CI 1.01-1.96, p = 0.04) were associated with CSS only in the testing cohort. The exclusion of the SIR-biomarkers for the prognosis of CSS did not result in a significant decrease in C-index (- 0.9%) for the training cohort, while the exclusion of SIR-biomarkers led to a reduction in C-index in the testing cohort (- 5.8%). However, SIR-biomarkers only marginally increased the discriminatory ability of the respective model in comparison to the standard model.

Conclusion: Despite the high discriminatory ability during the fitting of the model with machine-learning approach, the panel of readily available blood-based SIR-biomarkers failed to add a clinical benefit beyond the standard model.
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http://dx.doi.org/10.1007/s00345-021-03844-wDOI Listing
October 2021

Cancer-specific survival after radical prostatectomy versus external beam radiotherapy in high-risk and very high-risk African American prostate cancer patients.

Prostate 2021 Oct 18. Epub 2021 Oct 18.

Division of Urology, Cancer Prognostics and Health Outcomes Unit, University of Montréal Health Center, Montréal, Québec, Canada.

Background: To test for differences in cancer-specific mortality (CSM) rates between radical prostatectomy (RP) vs external beam radiotherapy (EBRT) in National Comprehensive Cancer Network (NCCN) high-risk African American patients, as well as Johns Hopkins University (JHU) high-risk and very high-risk patients.

Materials And Methods: Within the Surveillance, Epidemiology, and End Results database (2010-2016), we identified 4165 NCCN high-risk patients, of whom 1944 (46.7%) and 2221 (53.3%) patients qualified for JHU high-risk or very high-risk definitions. Of all 4165 patients, 1390 (33.5%) were treated with RP versus 2775 (66.6%) with EBRT. Cumulative incidence plots and competing risks regression models addressed CSM before and after 1:1 propensity score matching between RP and EBRT NCCN high-risk patients. Subsequently, analyses were repeated separately in JHU high-risk and very high-risk subgroups. Finally, all analyses were repeated after landmark analyses were applied.

Results: In the NCCN high-risk cohort, 5-year CSM rates for RP versus EBRT were 2.4 versus 5.2%, yielding a multivariable hazard ratio of 0.50 (95% confidence interval [CI] 0.30-0.84, p = 0.009) favoring RP. In JHU very high-risk patients 5-year CSM rates for RP versus EBRT were 3.7 versus 8.4%, respectively, yielding a multivariable hazard ratio of 0.51 (95% CI: 0.28-0.95, p = 0.03) favoring RP. Conversely, in JHU high-risk patients, no significant CSM difference was recorded between RP vs EBRT (5-year CSM rates: 1.3 vs 1.3%; multivariable hazard ratio: 0.55, 95% CI: 0.16-1.90, p = 0.3). Observations were confirmed in propensity score-matched and landmark analyses adjusted cohorts.

Conclusions: In JHU very high-risk African American patients, RP may hold a CSM advantage over EBRT, but not in JHU high-risk African American patients.
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http://dx.doi.org/10.1002/pros.24253DOI Listing
October 2021

Renal and Salivary Gland Functions after Three Cycles of PSMA-617 Therapy Every Four Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer.

Curr Oncol 2021 09 23;28(5):3692-3704. Epub 2021 Sep 23.

Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, 1090 Vienna, Austria.

Background: [Lu]Lu-PSMA-617 radioligand therapy (PSMA-RLT) could affect kidney and salivary gland functions in metastatic castration-resistant prostate cancer (mCRPC) patients.

Methods: We retrospectively analyzed clinical, renal, and salivary scintigraphy data and salivary [Ga]Ga-PSMA-11 ligand PET scan measures such as metabolic volume and SUVmax values of 27 mCRPC men (mean age 71 ± 7 years) before and 4 weeks after receiving three cycles of PSMA-RLT every 4 weeks. Twenty-two patients additionally obtained renal and salivary scintigraphy prior to each cycle. A one-way ANOVA, post-hoc Scheffé test and Cochran's Q test were applied to assess organ toxicity.

Results: In total, 54 PSMA PET scans, 98 kidney, and 98 salivary scintigraphy results were evaluated. There were no significant differences for the ejection fraction, peak time, and residual activity after 5 min for both parotid and submandibular glands prior to each cycle and 4 weeks after the last cycle. Similarly, no significant differences in serum creatinine and renal scintigraphy parameters were observed prior to each cycle and 4 weeks after the last treatment. Despite there being no changes in the metabolic volume of both submandibular glands, SUVmax values dropped significantly ( < 0.05).

Conclusion: Results evidenced no alterations in renal function and only minimal impairment of salivary function of mCRPC patients who acquired an intense PSMA-RLT regimen every 4 weeks.
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http://dx.doi.org/10.3390/curroncol28050315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482282PMC
September 2021

Preoperative plasma level of endoglin as a predictor for disease outcomes after radical cystectomy for nonmetastatic urothelial carcinoma of the bladder.

Mol Carcinog 2021 Sep 29. Epub 2021 Sep 29.

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

Elevated preoperative plasma level of endoglin has been associated with worse oncologic outcomes in various malignancies. The present large-scale study aimed to determine the predictive and prognostic values of preoperative endoglin with regard to clinicopathologic and survival outcomes in patients treated with radical cystectomy (RC) for nonmetastatic urothelial carcinoma of the bladder (UCB). We prospectively collected preoperative blood samples from 1036 consecutive patients treated with RC for UCB. Logistic and Cox regression analyses were undertaken to assess the correlation of endoglin levels with pathologic and survival outcomes, respectively. The AUC and C-index were used to assess the discrimination. Patients with adverse pathologic features had significantly higher median preoperative endoglin plasma levels than their counterparts. Higher preoperative endoglin level was independently associated with an increased risk for lymph node metastasis, ≥pT3 disease, and nonorgan confined disease (NOCD; all p < 0.001). Plasma endoglin level was also independently associated with cancer-specific and overall survival in both pre- and postoperative models (all p < 0.05), as well as with recurrence-free survival (RFS) in the preoperative model (p < 0.001). The addition of endoglin to the preoperative standard model improved its discrimination for prediction of lymph node metastasis, ≥pT3 disease, NOCD, and RFS (differential increases in C-indices: 10%, 5%, 5.8%, and 4%, respectively). Preoperative plasma endoglin is associated with features of biologically and clinically aggressive UCB as well as survival outcomes. Therefore, it seems to hold the potential of identifying UCB patients who may benefit from intensified therapy in addition to RC such as extended lymphadenectomy or/and preoperative systemic therapy.
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http://dx.doi.org/10.1002/mc.23355DOI Listing
September 2021

Cancer Spectrum, Family History of Cancer and Overall Survival in Men with Germline or Mutations.

J Pers Med 2021 Sep 15;11(9). Epub 2021 Sep 15.

Department of Obstetrics, Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.

Background: Men with germline mutations are not well studied compared to their female counterparts. This study evaluates the cancer characteristics, family history of cancer, and outcomes of male mutation carriers.

Methods: All men with germline / mutations who attended genetic assessment between October 1995 and October 2019 at the Medical University of Vienna were identified. Clinicohistopathological features, family history of cancer, and outcomes were assessed by mutation status.

Results: Of the 323 men included, 45 (13.9%) had a primary cancer diagnosis, many of whom were carriers (75.5%). Breast cancer (BC) was the most common cancer (57.8%) followed by prostate cancer (15.6%). Invasive ductal carcinoma and hormone receptor positive tumors were the most common. Among 26 BC-affected patients, 42% did not have any relatives with cancer. Parent of origin was only known in half of the 26 men, with 42% of them inherited through the maternal lineage versus 8% through the paternal. carriers and those with a family history of BC had worse overall survival (20 y vs. 23 y carriers; P = 0.007; 19 y vs. 21 y for those without family history of BC; P = 0.036).

Conclusion: Male BRCA2 carriers were most likely to develop cancer and had worse prognosis. In our dataset, BC was the most common cancer, likely due to referral bias. Not all mutation carriers present with BC or have a family history of cancer to warrant genetic testing.
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http://dx.doi.org/10.3390/jpm11090917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466243PMC
September 2021

Choosing the Most Efficacious and Safe Oral Treatment for Idiopathic Overactive Bladder: A Systematic Review and Network Meta-analysis.

Eur Urol Focus 2021 Sep 22. Epub 2021 Sep 22.

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Department of Urology, Weill Cornell Medical College, New York, NY, USA; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan; European Association of Urology research foundation, Arnhem, The Netherlands. Electronic address:

Context: The choice of the most efficacious drug for patients with idiopathic overactive bladder (IOAB) remains challenging.

Objective: The aim of this network meta-analysis was to determine the most efficacious oral antimuscarinic or β-adrenoceptor agonist accounting for adverse events for the management of IOAB.

Evidence Acquisition: A comprehensive electronic search was done in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Ovid for studies in any language in February 2021 considering the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. We included all randomized controlled trials assessing oral antimuscarinics or β-adrenoceptor agonists for the treatment of IOAB. We determined the effect of specific bothersome symptoms separately.

Evidence Synthesis: Fifty-four articles were included in our analysis. The most efficacious agents considering the evaluated outcomes were oxybutynin 15 mg/d in reducing incontinence episodes, imidafenacin 0.5 mg/d together with solifenacin 10 and 5 mg/d in reducing micturition episodes, fesoterodine 4 and 8 mg/d as well as solifenacin 10 mg/d in reducing urgency episodes, imidafenacin 0.5 mg/d and solifenacin 10 mg/d in reducing urgency urinary incontinence episodes, and solifenacin 10 mg/d, vibegron 50 mg/d, and fesoterodine 8 mg/d in improving the voided volume. Gastrointestinal problems, especially due to antimuscarinic agents, were the most prevalent adverse events.

Conclusions: Taken together, there is only minimal difference between the efficacy of oral antimuscarinics and that of β-adrenoceptor agonists. Although finding the best medication for all is impossible, finding the best treatment for every individual patient can be done by considering the efficacy of a medicine for the most bothersome symptom(s) in balance with drug-specific adverse events.

Patient Summary: This study aimed to find the most efficient oral medication to treat overactive bladder, taking into consideration the adverse events. Based on our study, there is a minimal difference in the efficacy between the two major drug classes used to treat overactive bladder. Gastrointestinal problems were the most common adverse events in medical treatment of overactive bladder. Selection of the best treatment is possible through shared decision-making between the doctor and the patient based on the patient's most bothersome symptom. We provide a framework for physicians to facilitate shared decision-making with each individual patient.
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http://dx.doi.org/10.1016/j.euf.2021.08.011DOI Listing
September 2021

Survival after Radical Prostatectomy versus Radiation Therapy in High-Risk and Very High-Risk Prostate Cancer.

J Urol 2021 Sep 24:101097JU0000000000002250. Epub 2021 Sep 24.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Purpose: Our goal was to compare cancer specific mortality (CSM) rates between radical prostatectomy (RP) vs external beam radiotherapy (EBRT) in National Comprehensive Cancer Network© (NCCN©) high risk (HR) patients, as well as in Johns Hopkins University (JH) HR and very high risk (VHR) subgroups.

Materials And Methods: Within the Surveillance, Epidemiology, and End Results database (2010-2016), we identified 24,407 NCCN HR patients, of whom 10,300 (42%) vs 14,107 (58%) patients that qualified for JH HR vs VHR, respectively. Overall, 9,823 (40%) underwent RP vs 14,584 (60%) EBRT. Cumulative incidence plots and competing-risks regression addressed CSM after 1:1 propensity score matching (according to age, prostate specific antigen, clinical T and N stages, and biopsy Gleason score) between RP and EBRT patients. All analyses addressed the combined NCCN HR cohort, as well as in JH HR and JH VHR subgroups.

Results: In the combined NCCN HR cohort 5-year CSM rates were 2.3% for RP vs 4.1% for EBRT and yielded a multivariate hazard ratio of 0.68 (95% CI 0.54-0.86, p <0.001) favoring RP. In VHR patients 5-year CSM rates were 3.5% for RP vs 6.0% for EBRT, yielding a multivariate hazard ratio of 0.58 (95% CI 0.44-0.77, p <0.001) favoring RP. Conversely, in HR patients no significant difference was recorded between RP vs EBRT (HR 0.7, 95% CI 0.39-1.25, p=0.2).

Conclusions: Our data suggest that RP holds a CSM advantage over EBRT in the combined NCCN HR cohort, and in its subgroup of JH VHR patients.
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http://dx.doi.org/10.1097/JU.0000000000002250DOI Listing
September 2021

External beam radiotherapy and radical prostatectomy are associated with better survival in Asian prostate cancer patients.

Int J Urol 2021 Sep 22. Epub 2021 Sep 22.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Quebec, Canada.

Objectives: To test the effect of race/ethnicity on cancer-specific mortality after radical prostatectomy or external beam radiotherapy in localized prostate cancer patients.

Methods: In the Surveillance, Epidemiology and End Results database 2004-2016, we identified intermediate-risk and high-risk white (n = 151 632), Asian (n = 11 189), Hispanic/Latino (n = 20 077) and African American (n = 32 550) localized prostate cancer patients, treated with external beam radiotherapy or radical prostatectomy. Race/ethnicity-stratified cancer-specific mortality analyses relied on competing risks regression, after propensity score matching for patient and cancer characteristics.

Results: Compared with white patients, Asian intermediate- and high-risk external beam radiotherapy patients showed lower cancer-specific mortality (hazard ratio 0.58 and 0.70, respectively, both P ≤ 0.02). Additionally, Asian high-risk radical prostatectomy patients also showed lower cancer-specific mortality than white patients (hazard ratio 0.72, P = 0.04), but not Asian intermediate-risk radical prostatectomy patients (P = 0.08). Conversely, compared with white patients, African American intermediate-risk radical prostatectomy patients showed higher cancer-specific mortality (hazard ratio 1.36, P = 0.01), but not African American high-risk radical prostatectomy or intermediate- and high-risk external beam radiotherapy patients (all P ≥ 0.2). Finally, compared with white people, no cancer-specific mortality differences were recorded for Hispanic/Latino patients after external beam radiotherapy or radical prostatectomy, in both risk levels (P ≥ 0.2).

Conclusions: Relative to white patients, an important cancer-specific mortality advantage applies to intermediate-risk and high-risk Asian prostate cancer patients treated with external beam radiotherapy, and to high-risk Asian patients treated with radical prostatectomy. These observations should be considered in pretreatment risk stratification and decision-making.
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http://dx.doi.org/10.1111/iju.14701DOI Listing
September 2021

Clinical Outcomes and Adverse Events after First-Line Treatment in Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-Analysis.

J Urol 2021 Sep 21:101097JU0000000000002252. Epub 2021 Sep 21.

Juravinski Cancer Centre, McMaster University, Hamilton, Ontario, Canada.

Purpose: Four recent first-line clinical trials leveraging immune-oncology agents demonstrated an overall survival (OS) benefit relative to sunitinib. We aimed to provide formal comparisons among immune-oncology combinations in terms of OS, progression-free survival (PFS), objective response rates (ORR) and treatment-related adverse events (AEs).

Materials And Methods: PubMed® database was searched for studies indexed from January 1, 2016 through March 6, 2021. Only phase III randomized clinical trials with proven OS benefit relative to sunitinib were included: CheckMate 214 (nivolumab plus ipilimumab [N+I]), KEYNOTE-426 (pembrolizumab plus axitinib [P+A]), CheckMate 9ER (nivolumab plus cabozantinib [N+C]) and KEYNOTE-581 (lenvatinib plus permbrolizumab [L+P]). OS represented the primary outcome. PFS, ORR and AEs represented secondary outcomes.

Results: Overall, 3,320 patients were included. Regarding OS, N+C ranked first, followed by L+P, P+A and N+I. Regarding PFS and ORR, L+P ranked first, followed by N+C, P+A and N+I. Finally, N+I ranked first with respect to lowest grade 3+ AEs, followed by P+A, N+C and L+P. Differences in followup duration, risk grouping and nephrectomy rates distinguish the studies.

Conclusions: N+C may provide the most favorable OS, L+P the most favorable PFS and ORRs, and N+I the lowest toxicity. Population differences may potentially undermine the generalizability and the robustness of findings of metastatic renal cell carcinoma.
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http://dx.doi.org/10.1097/JU.0000000000002252DOI Listing
September 2021

Improvement in overall and cancer-specific survival in contemporary, metastatic prostate cancer chemotherapy exposed patients.

Prostate 2021 Dec 15;81(16):1374-1381. Epub 2021 Sep 15.

Division of Urology, Cancer Prognostics and Health Outcomes Unit, University of Montréal Health Center, Montréal, Québec, Canada.

Introduction: Over the last decade, multiple clinical trials demonstrated improved survival after chemotherapy for metastatic prostate cancer (mPCa). However, real-world data validating this effect within large-scale epidemiological data sets are scarce. We addressed this void.

Materials And Methods: Men with de novo mPCa were identified and systemic chemotherapy status was ascertained within the Surveillance, Epidemiology, and End Results database (2004-2016). Patients were divided between historical (2004-2013) versus contemporary (2014-2016). Chemotherapy rates were plotted over time. Kaplan-Meier plots and Cox regression models with additional multivariable adjustments addressed overall and cancer-specific mortality. All tests were repeated in propensity-matched analyses.

Results: Overall, 19,913 patients had de novo mPCa between 2004 and 2016. Of those, 1838 patients received chemotherapy. Of 1838 chemotherapy-exposed patients, 903 were historical, whereas 905 were contemporary. Chemotherapy rates increased from 5% to 25% over time. Median overall survival was not reached in contemporary patients versus was 24 months in historical patients (hazard ratio [HR]: 0.55, p < 0.001). After propensity score matching and additional multivariable adjustment (age, prostate-specific antigen, GGG, cT-stage, cN-stage, cM-stage, and local treatment) a HR of 0.55 (p < 0.001) was recorded. Analyses were repeated for cancer-specific mortality after adjustment for other cause mortality in competing risks regression models and recorded virtually the same findings before and after propensity score matching (HR: 0.55, p < 0.001).

Conclusions: In mPCa patients, chemotherapy rates increased over time. A concomitant increase in survival was also recorded.
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http://dx.doi.org/10.1002/pros.24235DOI Listing
December 2021

Increased risk of postoperative in-hospital complications after radical prostatectomy in patients with prior organ transplant.

Prostate 2021 Dec 13;81(16):1294-1302. Epub 2021 Sep 13.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Canada.

Background: To analyze postoperative, in-hospital, complication rates in patients with organ transplantation before radical prostatectomy (RP).

Methods: From National Inpatient Sample (NIS) database (2000-2015) prostate cancer patients treated with RP were abstracted and stratified according to prior organ transplant versus nontransplant. Multivariable logistic regression models predicted in-hospital complications.

Results: Of all eligible 202,419 RP patients, 216 (0.1%) underwent RP after prior organ transplantation. Transplant RP patients exhibited higher proportions of Charlson comorbidity index ≥2 (13.0% vs. 3.0%), obesity (9.3% vs. 5.6%, both p < 0.05), versus to nontransplant RP. Of transplant RP patients, 96 underwent kidney (44.4%), 44 heart (20.4%), 40 liver (18.5%), 30 (13.9%) bone marrow, <11 lung (<5%), and <11 pancreatic (<5%) transplantation before RP. Within transplant RP patients, rates of lymph node dissection ranged from 37.5% (kidney transplant) to 60.0% (bone marrow transplant, p < 0.01) versus 51% in nontransplant patients. Regarding in-hospital complications, transplant patients more frequently exhibited, diabetic (31.5% vs. 11.6%, p < 0.001), major (7.9% vs. 2.9%) cardiac complications (3.2% vs. 1.2%, p = 0.01), and acute kidney failure (5.1% vs. 0.9%, p < 0.001), versus nontransplant RP. In multivariable logistic regression models, transplant RP patients were at higher risk of acute kidney failure (odds ratio [OR]: 4.83), diabetic (OR: 2.81), major (OR: 2.39), intraoperative (OR: 2.38), cardiac (OR: 2.16), transfusion (OR: 1.37), and overall complications (1.36, all p < 0.001). No in-hospital mortalities were recorded in transplant patients after RP.

Conclusions: Of all transplants before RP, kidney ranks first. RP patients with prior transplantation have an increased risk of in-hospital complications. The highest risk, relative to nontransplant RP patients appears to acute kidney failure.
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http://dx.doi.org/10.1002/pros.24224DOI Listing
December 2021
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