Publications by authors named "Pierre Karakiewicz"

1,132 Publications

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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

Treatment of Ureteral Stent-Related Symptoms.

Urol Int 2021 Nov 2:1-16. Epub 2021 Nov 2.

Division of Urology, Department of Oncology, School of Medicine, San Luigi Hospital, University of Turin, Turin, Italy.

Background: The aim of the study was to assess the effectiveness of the main classes of drugs used at reducing morbidity related to ureteric stents.

Summary: After establishing a priori protocol, a systematic electronic literature search was conducted in July 2019. The randomized clinical trials (RCTs) selection proceeded in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and was registered (PROSPERO ID 178130). The risk of bias and the quality assessment of the included RCTs were performed. Ureteral Stent Symptom Questionnaire (USSQ), International Prostate Symptom Score (IPSS), and quality of life (QoL) were pooled for meta-analysis. Mean difference and risk difference were calculated as appropriate for each outcome to determine the cumulative effect size. Fourteen RCTs were included in the analysis accounting for 2,842 patients. Alpha antagonist, antimuscarinic, and phosphodiesterase (PDE) inhibitors significatively reduced all indexes of the USSQ, the IPSS and QoL scores relative to placebo. Conversely, combination therapy (alpha antagonist plus antimuscarinic) showed in all indexes of the USSQ, IPSS, and QoL over alpha antagonist or antimuscarinic alone. On comparison with alpha blockers, PDE inhibitors were found to be equally effective for urinary symptoms, general health, and body pain parameters, but sexual health parameters improved significantly with PDE inhibitors. Finally, antimuscarinic resulted in higher decrease in all indexes of the USSQ, the IPSS, and QoL relative to alpha antagonist. Key message: Relative to placebo, alpha antagonist alone, antimuscarinics alone, and PDE inhibitors alone have beneficial effect in reducing stent-related symptoms. Furthermore, there are significant advantages of combination therapy compared with monotherapy. Finally, PDE inhibitors are comparable to alpha antagonist, and antimuscarinic seems to be more effective than alpha antagonist alone.
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http://dx.doi.org/10.1159/000518387DOI Listing
November 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

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

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

The Effect of 10 Most Common Nonurological Primary Cancers on Survival in Men With Secondary Prostate Cancer.

Front Oncol 2021 6;11:754996. Epub 2021 Oct 6.

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

Background: This study aims to test the effect of the 10 most common nonurological primary cancers (skin, rectal, colon, lymphoma, leukemia, pancreas, stomach, esophagus, liver, lung) on overall mortality (OM) after secondary prostate cancer (PCa).

Material And Methods: Within the Surveillance, Epidemiology, and End Results (SEER) database, patients with 10 most common primary cancers and concomitant secondary PCa (diagnosed 2004-2016) were identified and were matched in 1:4 fashion (age, year at diagnosis, race/ethnicity, treatment type, TNM stage) with primary PCa controls. OM was compared between secondary and primary PCa patients and was stratified according to primary cancer type, as well as according to time interval between primary cancer secondary PCa diagnoses.

Results: We identified 24,848 secondary PCa patients (skin,  = 3,871; rectal,  = 798; colon,  = 3,665; lymphoma,  = 2,583; leukemia,  = 1,102; pancreatic,  = 118; stomach,  = 361; esophagus,  = 219; liver,  = 160; lung,  = 1,328) 531,732 primary PCa patients. Secondary PCa characteristics were less favorable than those of primary PCa patients (PSA and grade), and smaller proportions of secondary PCa patients received active treatment. After 1:4 matching, all secondary PCa exhibited worse OM than primary PCa patients. Finally, subgroup analyses showed that the survival disadvantage of secondary PCa patients decreased with longer time interval since primary cancer diagnosis and subsequent secondary PCa.

Conclusion: Patients with secondary PCa are diagnosed with less favorable PSA and grade. Even after matching for PCa characteristics, secondary PCa patients still exhibit worse survival. However, the survival disadvantage is attenuated, when secondary PCa diagnosis is made after longer time interval, since primary cancer diagnosis.
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http://dx.doi.org/10.3389/fonc.2021.754996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526938PMC
October 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

Survival rates with external beam radiation therapy in newly diagnosed elderly metastatic prostate cancer patients.

Prostate 2021 Oct 11. Epub 2021 Oct 11.

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

Background: The survival benefit of primary external beam radiation therapy (EBRT) has never been formally tested in elderly men who were newly diagnosed with metastatic prostate cancer (mPCa). We hypothesized that elderly patients may not benefit of EBRT to the extent as younger newly diagnosed mPCa patients, due to shorter life expectancy.

Methods: We relied on Surveillance, Epidemiology and End Results (2004-2016) to identify elderly newly diagnosed mPCa patients, aged >75 years. Kaplan-Meier, univariable and multivariable Cox regression models, as well as Competing Risks Regression models tested the effect of EBRT versus no EBRT on overall mortality (OM) and cancer-specific mortality (CSM).

Results: Of 6556 patients, 1105 received EBRT (16.9%). M1b stage was predominant in both EBRT (n = 823; 74.5%) and no EBRT (n = 3908; 71.7%, p = 0.06) groups, followed by M1c (n = 211; 19.1% vs. n = 1042; 19.1%, p = 1) and M1a (n = 29; 2.6% vs. n = 268; 4.9%, p < 0.01). Median overall survival (OS) was 23 months for EBRT and 23 months for no EBRT (hazard ratio [HR]: 0.97, p = 0.6). Similarly, median cancer-specific survival (CSS) was 29 months for EBRT versus 30 months for no EBRT (HR: 1.04, p = 0.4). After additional multivariable adjustment, EBRT was not associated with lower OM or lower CSM in the entire cohort, as well as after stratification for M1b and M1c substages.

Conclusions: In elderly men who were newly diagnosed with mPCa, EBRT does not affect OS or CSS. In consequence, our findings question the added value of local EBRT in elderly newly diagnosed mPCa patients.
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http://dx.doi.org/10.1002/pros.24249DOI Listing
October 2021

Radical Cystectomy vs. Radiotherapy in Urothelial Bladder Cancer in Elderly and Very Elderly Patients.

Clin Genitourin Cancer 2021 Sep 1. Epub 2021 Sep 1.

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

Introduction: Controversy regarding cancer-specific mortality (CSM) of elderly and very elderly patients with muscle-invasive, non-metastatic, urothelial carcinoma of the urinary bladder (UCUB) undergoing radical cystectomy (RC) vs radiotherapy (RT) still exists.

Materials And Methods: In the 2004-2016 Surveillance, Epidemiology and End Results (SEER) database, we identified 2663 UCUB patients aged 75-79 (1808 RC vs 855 RT) and 3569 UCUB patients aged 80-89 (1551 RC vs 2018 RT). After stratification for concomitant chemotherapy, propensity score matching (PSM) between RC and RT was applied and competing-risks regression models addressed CSM and OCM.

Results: In the cohort aged 75-79, five-year CSM rates were 22.0 vs 49.0% for RC only vs RT only and yielded a HR of 0.41 (95% confidence interval (CI) 0.30-0.57, p<0.001) favoring RC only. Five-year CSM rates were 28.3 vs 44.3% for RC with chemotherapy vs trimodal therapy (TMT) and yielded a HR of 0.48 (95% CI 0.35-0.65, p<0.001) favoring RC with chemotherapy. In the cohort aged 80-89, five-year CSM rates were 24.2 vs 48.9% for RC only vs RT only and yielded a HR of 0.42 (95% CI 0.33-0.52, p<0.001) favoring RC only. Five-year CSM rates were 19.6 vs 43.2% for RC with chemotherapy vs TMT and yielded a HR of 0.43 (95% CI 0.28-0.67, p<0.001) favoring RC with chemotherapy.

Conclusions: In elderly and very elderly patients, radical cystectomy is associated with virtually half the CSM rate than radiotherapy, regardless of concomitant chemotherapy administration.
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http://dx.doi.org/10.1016/j.clgc.2021.08.003DOI Listing
September 2021

The Impact of Preoperative Double-J Stent on Perioperative Complications, Recurrence, and Quality of Life in Adult Patients Undergoing Pyeloplasty.

Urol Int 2021 Oct 1:1-8. Epub 2021 Oct 1.

Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.

Purpose: This study aimed to evaluate the impact of preoperative double-J stent (DJ) in pyeloplasty patients on perioperative complications, recurrence, and quality of life (QoL).

Methods: Pyeloplasties due to ureteropelvic junction obstructions between January 2010 and December 2020 were consecutively identified. A standardized follow-up questionnaire was used. Tabulation was made according to preoperative DJ versus no DJ. Subgroup analyses addressed primary robotic pyeloplasties.

Results: Of 95 pyeloplasty patients, 62% received a preoperative DJ. Patients with preoperative DJ exhibited higher rates of Clavien-Dindo (CD) 2 (22 vs. 11%) complications, but not of CD3 (8.5 vs. 8.3%, p = 0.5). After a median follow-up of 61 months, 9 patients exhibited a recurrence, of whom 7 had a preoperative DJ. In QoL assessment, comparable findings were made between patients with and without preoperative DJ. In robotic pyeloplasty patients (n = 73), patients with preoperative DJ (58%, n = 42) experienced higher CD3 complication rates, compared to patients without preoperative DJ (12 vs. 6.5%). Moreover, higher rates of recurrences were observed in preoperative DJ patients (12 vs. 3.2%).

Conclusion: In a contemporary pyeloplasty cohort, the midterm success rate was good with 91%. Our findings suggest that preoperative DJ is associated with higher recurrence rates. However, QoL did not differ between patients with and without preoperative DJ.
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http://dx.doi.org/10.1159/000519481DOI Listing
October 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

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

Can Negative Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Avoid the Need for Pelvic Lymph Node Dissection in Newly Diagnosed Prostate Cancer Patients? A Systematic Review and Meta-analysis with Backup Histology as Reference Standard.

Eur Urol Oncol 2021 Sep 17. Epub 2021 Sep 17.

Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.

Context: The role of positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA) in the primary staging for patients with prostate cancer (PCa) is still debated.

Objective: To analyze published studies reporting the accuracy of PSMA PET/CT for detecting lymph node invasion (LNI) at pelvic lymph node dissection (PLND).

Evidence Acquisition: A search of PubMed/MEDLINE, Cochrane library's Central, EMBASE and Scopus databases, from inception to May 2021, was conducted. The primary outcome was to evaluate the sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of PSMA PET/CT in detecting LNI on a per-patient level. As a secondary outcome, NPV of PET PSMA was tested on a per-node-level analysis. Detection rates were pooled using random-effect models. Preplanned subgroup analyses tested the diagnostic accuracy after stratification for the preoperative risk group. PPV and NPV variation over LNI prevalence was evaluated. Only studies including extended PLND (ePLND) as the reference standard test were included.

Evidence Synthesis: Twenty-seven studies, with a total of 2832 participants, were included in quantitative synthesis. The sensitivity, specificity, PPV, and NPV of PSMA PET/CT for LNI were, respectively, 58% (95% confidence interval [CI] 50-66%), 95% (95% CI 93-97%), 79% (95% CI 72-85%), and 87% (95% CI 84-89%), with overall moderate heterogeneity between studies. At bivariate analysis, the diagnostic accuracy of PSMA PET/CT estimated through summary receiver operating characteristic-derived area under the curve was 84% (95% CI 81-87%). On a per-node level, NPV of PET PSMA was 97% (95% CI 96-99%). At subgroup analyses, according to preoperative risk groups, sensitivity, specificity, PPV, and NPV were 51%, 93%, 73%, and 81%, respectively, in high-risk patients. Over the LNI prevalence range of 5-40%, PPV increased from 59% to 91%, while NPV decreased from 99% to 84%.

Conclusions: PSMA PET/CT scan provides promising accuracy in the field of primary nodal staging for PCa. The high NPV in men with a lower risk of LNI might be clinically useful to reduce the number of unnecessary PLND procedures performed. Conversely, in high-risk patients, negative PSMA PET/CT cannot replace staging ePLND.

Patient Summary: In this systematic review and meta-analysis, we demonstrated that prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) scan may optimize the primary nodal staging and surgical management of prostate cancer patients candidate to radical prostatectomy. The high negative predictive value in men with a lower risk of lymph node invasion might be clinically useful for reducing the number of useless pelvic lymph node dissection (PLND) procedures performed. Conversely, in high-risk patients, negative PSMA PET/CT cannot allow avoiding of PLND.
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http://dx.doi.org/10.1016/j.euo.2021.08.001DOI 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

Catheterization Does Not Improve Course of Disease in Female Patients with Acute Cystitis or Pyelonephritis: Retrospective Analysis of >300 In-Hospital Treated Patients.

Urol Int 2021 18;105(11-12):1104-1112. Epub 2021 Aug 18.

Department of Urology, University Hospital Frankfurt, Frankfurt, Germany.

Purpose: Females with in-hospital treatment for acute cystitis (AC) or pyelonephritis may benefit from catheterization at admission.

Methods: All female patients with AC or pyelonephritis requiring in-hospital treatment at University Hospital Frankfurt (2004-2019) were retrospectively analyzed. Logistic regression models were used to predict the catheter value.

Results: Of 310 female patients, 40% harbored AC versus 60% pyelonephritis, of whom 62% and 74% received a catheter at admission: C-reactive protein (CRP) and white blood count (WBC) were significantly elevated in AC and pyelonephritis catheter versus no catheter patients (both p < 0.05). Time to CRP and WBC nadir did not differ between the AC catheter versus no catheter group (both p > 0.05). Conversely, time to CRP nadir was prolonged in pyelonephritis catheter patients. AC and pyelonephritis catheter patients exhibited a prolonged antibiotic treatment and length of stay (LOS, both p < 0.05). In multivariable analyses, CRP >5 ng/mL was a predictor for receiving a catheter in all patients. In AC, a positive urine culture and fever predicted, respectively, prolonged LOS or antibiotic treatment (all p < 0.05).

Conclusion: Risk factors exist with regard to receiving a catheter and prolonged antibiotic treatment or LOS in females with AC or pyelonephritis. A catheter may not accelerate recovery or WBC nadir.
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http://dx.doi.org/10.1159/000518066DOI Listing
August 2021

Stage and cancer-specific mortality differ within specific Asian ethnic groups for upper tract urothelial carcinoma: North American population-based study.

Int J Urol 2021 Dec 3;28(12):1247-1252. Epub 2021 Sep 3.

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

Objectives: To examine the effect of specific Asian ethnic subgroups on stage at presentation and cancer-specific mortality in non-metastatic upper tract urothelial carcinoma among North American upper tract urothelial carcinoma Asian patients treated with radical nephroureterectomy.

Methods: We relied on the Surveillance, Epidemiology and End Results database, from 2004 to 2016. Kaplan-Meier plots and multivariable Cox regression models predicting cancer-specific mortality were used.

Results: Of 584 upper tract urothelial carcinoma patients, 173 (29.6%) were Chinese versus 130 (22.3%) Japanese versus 68 (11.6%) Korean versus 64 (11.0%) Filipino versus 40 (6.8%) Vietnamese versus 109 (18.7%) other. Vietnamese and Chinese patients showed the highest rates of T N M and/or T N M (25.0% and 18.5%, respectively), relative to other Asian ethnic subgroups. In Kaplan-Meier plots, Vietnamese patients showed the highest cancer-specific mortality rate. In multivariable models, Vietnamese ethnicity also independently predicted higher cancer-specific mortality (hazard ratio 2.15, P = 0.02 and hazard ratio 1.96, P = 0.03), relative to Japanese and Chinese patients. All other Asian ethnic subgroups showed similar cancer-specific mortality patterns.

Conclusion: Vietnamese and Chinese patients are at a stage disadvantage at upper tract urothelial carcinoma diagnosis, relative to all other Asian ethnicities. After adjustment for stage, only Vietnamese patients showed a survival disadvantage relative to all other Asian ethnic subgroups. As a result, it appears that Vietnamese patients not only present at a higher upper tract urothelial carcinoma stage, but additionally appear to harbor upper tract urothelial carcinoma that progresses at a faster rate than in other Asian ethnic subgroups.
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http://dx.doi.org/10.1111/iju.14682DOI Listing
December 2021

Association between SARS-CoV-2 infection and disease severity among prostate cancer patients on androgen deprivation therapy: a systematic review and meta-analysis.

World J Urol 2021 Sep 3. Epub 2021 Sep 3.

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

Purpose: Androgen-regulated enzymes such as the angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are involved in the SARS-CoV-2 infection process. The expression of TMPRSS2 and its fusion gene, which are increased in the epithelium of the human prostate gland during prostate carcinogenesis, are regulated by androgens. Our goal was to assess the risk of the SARS-CoV-2 infection and the severity of the disease in PCa patients treated with androgen deprivation therapy (ADT).

Methods: We conducted a systematic review and meta-analysis according to PRISMA guidelines. We queried PubMed and Web of Science databases on 1 July 2021. We used random- and/or fixed-effects meta-analytic models in the presence or absence of heterogeneity according to Cochrane's Q test and I statistic, respectively.

Results: Six retrospective studies (n = 50,220 patients) were selected after considering inclusion and exclusion criteria for qualitative evidence synthesis. Four retrospective studies were included to assess the SARS-CoV-2 infection risk in PCa patients under ADT vs. no ADT and the summarized risk ratio (RR) was 0.8 (95% confidence intervals (CI) 0.44-1.47). Five retrospective studies were included to assess the severity of coronavirus disease 2019 (COVID-19) in PCa patients under ADT versus no ADT and the summarized RR was 1.23 (95% CI 0.9-1.68).

Conclusion: We found a non-significant association between the risk of SARS-CoV-2 infection and COVID-19 severity in PCa patients treated with ADT. However, our results suggest that during the COVID-19 pandemic PCa patients can safely undergo ADT as a cancer therapy without worsening COVID-19 risk and trajectory.
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http://dx.doi.org/10.1007/s00345-021-03810-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414446PMC
September 2021

Temporal trends, tumor characteristics and stage-specific survival in penile non-squamous cell carcinoma vs. squamous cell carcinoma.

Cancer Causes Control 2021 Sep 2. Epub 2021 Sep 2.

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

Purpose: To compare Cancer-specific mortality (CSM) in patients with Squamous cell carcinoma (SCC) vs. non-SCC penile cancer, since survival outcomes may differ between histological subtypes.

Methods: Within the Surveillance, Epidemiology and End Results database (2004-2016), penile cancer patients of all stages were identified. Temporal trend analyses, cumulative incidence and Kaplan-Meier plots, multivariable Cox regression and Fine and Gray competing-risks regression analyses tested for CSM differences between non-SCC vs. SCC penile cancer patients.

Results: Of 4,120 eligible penile cancer patients, 123 (3%) harbored non-SCC vs. 4,027 (97%) SCC. Of all non-SCC patients, 51 (41%) harbored melanomas, 42 (34%) basal cell carcinomas, 10 (8%) adenocarcinomas, eight (6.5%) skin appendage malignancies, six (5%) epithelial cell neoplasms, two (1.5%) neuroendocrine tumors, two (1.5%) lymphomas, two (1.5%) sarcomas. Stage at presentation differed between non-SCC vs. SCC. In temporal trend analyses, non-SCC diagnoses neither decreased nor increased over time (p > 0.05). After stratification according to localized, locally advanced, and metastatic stage, no CSM differences were observed between non-SCC vs. SCC, with 5-year survival rates of 11 vs 11% (p = 0.9) for localized, 33 vs. 37% (p = 0.4) for locally advanced, and 1-year survival rates of 37 vs. 53% (p = 0.9) for metastatic penile cancer, respectively. After propensity score matching for patient and tumor characteristics and additional multivariable adjustment, no CSM differences between non-SCC vs. SCC were observed.

Conclusion: Non-SCC penile cancer is rare. Although exceptions exist, on average, non-SCC penile cancer has comparable CSM as SCC penile cancer patients, after stratification for localized, locally invasive, and metastatic disease.
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http://dx.doi.org/10.1007/s10552-021-01493-3DOI Listing
September 2021

Feasibility and outcome of radical prostatectomy following inductive neoadjuvant therapy in patients with suspicion of rectal infiltration.

Urol Oncol 2021 Aug 26. Epub 2021 Aug 26.

Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany.

Objective: To determine the feasibility and outcome of radical prostatectomy (RP) following neoadjuvant therapy (NAT) in patients with initial inoperable, rectum-infiltrating cT4 prostate cancer (PCa).

Methods: From 01/2018 to 12/2020, 26 patients with clinical (DRE) or radiographical (mpMRI) suspicion of rectum infiltrating PCa at diagnosis and NAT prior to RP were retrospectively identified from our prospective institutional database. Two patients were still inoperable after NAT. Downsizing was administered for at least 20 weeks and RP was performed after excluding ongoing rectal infiltration.

Results: At diagnosis, median PSA was 42.5 ng/ml (IQR: 23.0-66.1). Inductive NAT consisted of androgen deprivation therapy (ADT) in combination with chemotherapy (n = 9) or without chemotherapy (n = 14). Median preoperative PSA was 0.93 ng/ml (IQR: 0.24-0.40). Median time from NAT to RP was 6 months (IQR: 5-7). Two patients were still inoperable after NAT. Of 24 patients undergoing RP, abortion of surgery due to inoperability was observed in 2 patients (8.4%), demonstrating a total failure rate of NAT in 4 out of 26 patients (15.4%). One patient suffered a rectal injury with consecutive colostomy (4.2%). No Clavien-Dindo complication Grade IV or V were observed. Urinary continence was achieved in 16 patients (84.2%). Sufficient erection for sexual intercourse was present in 2 patients (10.5%). All patients received adjuvant ADT with or without radiation therapy. Median PSA at 13 months was 0.08 ng/ml (IQR: 0.01-0.74).

Conclusion: RP of initially rectum infiltrating PCa is feasible and safe after inductive NAT, however complications rates tend to be higher compared to standard RP.
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http://dx.doi.org/10.1016/j.urolonc.2021.07.028DOI Listing
August 2021

The Value of Preoperative Plasma VEGF Levels in Urothelial Carcinoma of the Bladder Treated with Radical Cystectomy.

Eur Urol Focus 2021 Aug 25. Epub 2021 Aug 25.

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

Background: Elevated preoperative plasma levels of the angiogenesis-related marker VEGF have been associated with worse oncological outcomes in various malignancies.

Objective: To investigate the predictive/prognostic role of VEGF in patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC).

Design, Setting, And Participants: VEGF plasma levels were measured preoperatively in 1036 patients with UCB who underwent RC.

Outcome Measurements And Statistical Analysis: The correlation between plasma VEGF levels and pathological and survival outcomes was assessed using logistic regression and Cox regression analyses. Discrimination was assessed using the concordance index (C index). The clinical net benefit was evaluated using decision curve analysis (DCA).

Results And Limitations: Patients with higher pretreatment plasma VEGF levels had poorer recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) according to log-rank tests (all p < 0.001). Higher VEGF levels were not independently associated with higher risk of lymph node metastasis, ≥pT3 disease, or non-organ-confined disease (all p > 0.05). Preoperative plasma VEGF levels were independently associated with RFS, CSS, and OS in preoperative and postoperative multivariable models. However, in all cases the C index increased by <0.02 and there was no improvement in net benefit on DCA. A limitation is that none of the patients received current elements of standard of care such as neoadjuvant chemotherapy.

Conclusions: Elevated plasma VEGF levels were associated with features of biologically and clinically aggressive disease such as worse survival outcomes among patients with UCB treated with RC. However, VEGF appears to have relatively limited incremental additive value in clinical use. Further study of VEGF for UCB prognostication is warranted before routine use in clinical algorithms.

Patient Summary: Currently available models for predicting outcomes in bladder cancer are less than optimal. A protein called vascular endothelial growth factor (VEGF), which is a marker of the formation of blood vessels (angiogenesis), may have a role in predicting survival outcomes in bladder cancer.

Take Home Message: Elevated plasma VEGF levels are associated with worse survival outcomes for patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy. VEGF could be used as a part of a biomarker panel to enhance tools currently used for risk stratification for patients with UCB.
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http://dx.doi.org/10.1016/j.euf.2021.08.006DOI Listing
August 2021

The impact of race/ethnicity on upstaging and/or upgrading rates among intermediate risk prostate cancer patients treated with radical prostatectomy.

World J Urol 2021 Aug 26. Epub 2021 Aug 26.

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

Background: Race/ethnicity may predispose to less favorable prostate cancer characteristics in intermediate risk prostate cancer (IR PCa) patients. We tested this hypothesis in a subgroup of IR PCa patients treated with radical prostatectomy (RP).

Methods: We relied on the Surveillance, Epidemiology and End Results 2004-2016. The effect of race/ethnicity was tested in univariable and multivariable logistic regression analyses predicting upstaging (pT3+/pN1) and/or upgrading (Gleason Grade Group [GGG] 4-5) at RP.

Results: Of 20,391 IR PCa patients, 15,050 (73.8%) were Caucasian, 2857 (14.0%) African-American, 1632 (8.0%) Hispanic/Latino and 852 (4.2%) Asian. Asian patients exhibited highest age (64 year), highest PSA (6.8 ng/ml) and highest rate of GGG3 (31.9%). African-Americans exhibited the highest percentage of positive cores at biopsy (41.7%) and the highest proportion of NCCN unfavorable risk group membership (54.6%). Conversely, Caucasians exhibited the highest proportion of cT2 stage (35.6%). In univariable analyses, Hispanic/Latinos exhibited the highest rates of upstaging/upgrading among all race/ethnicities, in both favorable and unfavorable groups, followed by Asians, Caucasians and African-Americans in that order. In multivariable analyses, Hispanic/Latino race/ethnicity represented an independent predictor of higher upstaging and/or upgrading in favorable IR PCa (odds ratio [OR] 1.27, p < 0.01), while African-American race/ethnicity represented an independent predictor of lower upstaging and/or upgrading in unfavorable IR PCa (OR 0.79, p < 0.001).

Conclusion: Race/ethnicity predisposes to differences in clinical, as well as in pathological characteristics in IR PCa patients. Specifically, even after full statistical adjustment, Hispanic/Latinos are at higher and African-Americans are at lower risk of upstaging and/or upgrading.
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http://dx.doi.org/10.1007/s00345-021-03816-0DOI Listing
August 2021
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