Publications by authors named "Carlotta Palumbo"

100 Publications

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

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

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

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

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

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

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

Sex- and age-related differences in the distribution of bladder cancer metastases.

Jpn J Clin Oncol 2021 Feb 9. Epub 2021 Feb 9.

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

Objective: Our objective was to investigate age- and sex-related differences in the distribution of metastases in patients with metastatic bladder cancer.

Methods: Within the National Inpatient Sample database (2008-2015), we identified 7040 patients with metastatic bladder cancer. Trend test and Chi-square test analyses were used to evaluate the relationship between age and site of metastases, according to sex.

Results: Of 7040 patients with metastatic bladder cancer, 5226 (74.2%) were men and 1814 (25.8%) were women. Thoracic, abdominal, bone and brain metastases were present in 19.5 vs. 23.0%, 43.6 vs. 46.9%, 23.9 vs. 18.7% and 2.4 vs. 2.9% of men vs. women, respectively. Bone was the most common metastatic site in men (23.9%) vs. lung in women (22.4%). Increasing age was associated with decreasing rates of abdominal (from 44.9 to 40.2%) and brain (from 3.2 to 1.4%) metastases in men vs. decreasing rates of bone (from 21.0 to 13.3%) and brain (from 5.1 to 2.0%) metastases in women (all P < 0.05). Finally, rates of metastases in multiple organs also decreased with age, in both men and women.

Conclusions: The distribution of metastases in bladder cancer varies according to sex. Moreover, differences exist according to patient age and these differences are also sex-specific. In consequence, patient age and sex should be considered in the interpretation of imaging, especially when findings are indeterminate.
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http://dx.doi.org/10.1093/jjco/hyaa273DOI Listing
February 2021

Racial differences in the distribution of bladder cancer metastases: a population-based analysis.

Cent European J Urol 2020 31;73(4):407-415. Epub 2020 Oct 31.

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

Introduction: Bladder cancer is the second most common genitourinary malignancy in the United States. The incidence of bladder cancer rises with age, and it is two times more common in Caucasians than in African-Americans (23.1 vs. 12.6 cases/100,000 persons). We aimed to investigate the racial and age-related differences in the distribution of metastasis in a large, contemporary cohort of metastatic bladder cancer patients.

Material And Methods: Within the National Inpatient Sample database (2008-2015) we identified 5,767 patients with metastatic bladder cancer. Trend test, Chi-square test and multivariable logistic regression models were used to evaluate the relationship between ethnicity, age, and site of metastasis.

Results: Of 5,767 patients with metastatic bladder cancer, 598 (10.4%) were African-American. Lung was the most common metastatic site in African-Americans (28.6%) vs. bone in Caucasians (21.7%). Overall, African-Americans showed higher rates of lung (+10.2%), liver (+7.5%) and bone (+5.2%) metastases, compared to Caucasians (all p <0.01). Brain metastases were rare in both ethnicities (3.3 vs. 2.4%; p = 0.2). Rates of exclusive bone, lung or liver metastases increased with age, but were higher in African-Americans, regardless of age strata. In the multivariable logistic regression models, African-American ethnicity independently predicted higher risk of lung (Odds ratio: 1.69), liver (odds ratio: 1.50) and bone (odds ratio: 1.27) metastases, relative to Caucasians. Moreover, a dose-response effect was found after combining the three main risk factors for developing bone metastases, namely African-American ethnicity, younger age and male gender.

Conclusions: Racial differences exist in the distribution of metastatic bladder cancer metastasis. Moreover, based on higher risk of bone metastases in African-American patients, bone imaging may be warranted in this patient population, especially in the presence of other risk factors for bone metastases, namely male gender or younger age.
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http://dx.doi.org/10.5173/ceju.2020.0269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848828PMC
October 2020

Health-related quality of life 24-month after prostate cancer diagnosis: an update from the Pros-IT CNR prospective observational study.

Minerva Urol Nefrol 2021 Jan 13. Epub 2021 Jan 13.

Urology Unit, Azienda Socio-Sanitaria Territoriale Lariana, Sant'Anna Hospital, Como, Italy.

Background: This study analyzes patient health-related quality of life (QoL) 24-month after prostate cancer (PCa) diagnosis within the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study.

Methods: Pros-IT CNR is an ongoing, longitudinal and observational study, considering a convenience sample of patients enrolled at PCa diagnosis and followed at 6, 12, 24, 36, 48 and 60 months from the diagnosis. Patients were grouped according to the treatment received: nerve sparing radical prostatectomy (NSRP), non-nerve sparing radical prostatectomy (NNSRP), radiotherapy (RT), radiotherapy plus androgen deprivation (RT plus ADT) and active surveillance (AS). QoL was measured through the Italian versions of SF-12 and UCLA-PCI questionnaires at diagnosis and at 6-12 and 24-month. The minimal clinically important difference (MCID) was defined as half a standard deviation of the baseline domain.

Results: Overall, 1 537 patients were included in the study. The decline in urinary function exceeded the MCID at each timepoint only in the NSRP and NNSRP groups (at 24 months -14.7, p<0.001 and - 19.7, p<0.001, respectively). The decline in bowel function exceeded the MCID only in the RT (-9.1, p=0.02) and RT plus ADT groups at 12 months (-10.3, p=0.001); after 24 months, most patients seem to recover their bowel complaints. The decline in sexual function exceeded the MCID at each timepoint in the NNSRP, NSRP and RT plus ADT groups (at 6 months -28.7, p<0.001, -37.8, p<0.001, -20.4, p<0.001, respectively).

Conclusions: Although all the treatments were relatively well-tolerated over the 24 month period following PCa diagnosis, each had a different impact on QoL.
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http://dx.doi.org/10.23736/S0393-2249.20.04032-1DOI Listing
January 2021

Metabolic syndrome predicts worse perioperative outcomes in patients treated with radical prostatectomy for non-metastatic prostate cancer.

Surg Oncol 2021 Jan 3;37:101519. Epub 2021 Jan 3.

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

Objectives: Metabolic syndrome (MetS) and its components (high blood pressure, BMI≥30, altered fasting glucose, low HDL cholesterol and high triglycerides) may undermine early perioperative outcomes after radical prostatectomy (RP). We tested this hypothesis.

Materials & Methods: Within the National Inpatient Sample database (2008-2015) we identified RP patients. The effect of MetS was tested in four separate univariable analyses, as well as in multivariable regression models predicting: 1) overall complications, 2) length of stay, 3) total hospital charges and 4) non-home based discharge. All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics.

Results: Of 91,618 patients: 1) 50.2% had high blood pressure, 2) 8.0% had BMI≥30, 3) 13.0% had altered fasting glucose, 4) 22.8% had high triglycerides and 5) 0.03% had low HDL cholesterol. Respectively, one vs. two vs. three vs. four MetS components were recorded in 36.2% vs. 19.0% vs. 5.5% vs. 0.8% patients. Of all patients, 6.3% exhibited ≥3 components and qualified for MetS diagnosis. The rates of MetS increased over time (EAPC:+9.8%; p < 0.001). All four tested MetS components (high blood pressure, BMI≥30, altered fasting glucose and high triglycerides) achieved independent predictor status in all four examined endpoints. Moreover, a highly statistically significant dose-response was also confirmed for all four tested endpoints.

Conclusion: MetS and its components consistently and strongly predict early adverse outcomes after RP. Moreover, the strength of the effect was directly proportional to the number of MetS components exhibited by each individual patient, even if formal MetS diagnosis of ≥3 components has not been met.
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http://dx.doi.org/10.1016/j.suronc.2020.12.013DOI Listing
January 2021

Development of a Novel Risk Score to Select the Optimal Candidate for Cytoreductive Nephrectomy Among Patients with Metastatic Renal Cell Carcinoma. Results from a Multi-institutional Registry (REMARCC).

Eur Urol Oncol 2020 Dec 29. Epub 2020 Dec 29.

Department of Urology, Fundacion Instituto Valenciano Oncologia, Valencia, Spain. Electronic address:

Background: Selection of patients for upfront cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) has to be improved.

Objective: To evaluate a new scoring system for the prediction of overall mortality (OM) in mRCC patients undergoing CN.

Design, Setting, And Participants: We identified a total of 519 patients with synchronous mRCC undergoing CN between 2005 and 2019 from a multi-institutional registry (Registry for Metastatic RCC [REMARCC]).

Outcome Measurements And Statistical Analysis: Cox proportional hazard regression was used to test the main predictors of OM. Restricted mean survival time was estimated as a measure of the average overall survival time up to 36 mo of follow-up. The concordance index (C-index) was used to determine the model's discrimination. Decision curve analyses were used to compare the net benefit from the REMARCC model with International mRCC Database Consortium (IMDC) or Memorial Sloan Kettering Cancer Center (MSKCC) risk scores.

Results And Limitations: The median follow-up period was 18 mo (interquartile range: 5.9-39.7). Our models showed lower mortality rates in obese patients (p = 0.007). Higher OM rates were recorded in those with bone (p = 0.010), liver (p = 0.002), and lung metastases (p < 0.001). Those with poor performance status (<80%) and those with more than three metastases had also higher OM rates (p = 0.026 and 0.040, respectively). The C-index of the REMARCC model was higher than that of the MSKCC and IMDC models (66.4% vs 60.4% vs 60.3%). After stratification, 113 (22.0%) patients were classified to have a favorable (no risk factors), 202 (39.5%) an intermediate (one or two risk factors), and 197 (38.5%) a poor (more than two risk factors) prognosis. Moreover, 72 (17.2%) and 51 (13.9%) patients classified as having an intermediate and a poor prognosis according to MSKCC and IMDC categories, respectively, would be reclassified as having a good prognosis according to the REMARCC score.

Conclusions: Our findings confirm the relevance of tumor and patient features for the risk stratification of mRCC patients and clinical decision-making regarding CN. Further prospective external validations are required for the scoring system proposed herein.

Patient Summary: Current stratification systems for selecting patients for kidney removal when metastatic disease is shown are controversial. We suggest a system that includes tumor and patient features besides the systems already in use, which are based on blood tests.
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http://dx.doi.org/10.1016/j.euo.2020.12.010DOI Listing
December 2020

Prostate Cancer Grade and Stage Misclassification in Active Surveillance Candidates: Black Versus White Patients.

J Natl Compr Canc Netw 2020 11 2;18(11):1492-1499. Epub 2020 Nov 2.

1Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada.

Background: Misclassification rates defined as upgrading, upstaging, and upgrading and/or upstaging have not been tested in contemporary Black patients relative to White patients who fulfilled criteria for very-low-risk, low-risk, or favorable intermediate-risk prostate cancer. This study aimed to address this void.

Methods: Within the SEER database (2010-2015), we focused on patients with very low, low, and favorable intermediate risk for prostate cancer who underwent radical prostatectomy and had available stage and grade information. Descriptive analyses, temporal trend analyses, and multivariate logistic regression analyses were used.

Results: Overall, 4,704 patients with very low risk (701 Black vs 4,003 White), 17,785 with low risk (2,696 Black vs 15,089 White), and 11,040 with favorable intermediate risk (1,693 Black vs 9,347 White) were identified. Rates of upgrading and/or upstaging in Black versus White patients were respectively 42.1% versus 37.7% (absolute Δ = +4.4%; P<.001) in those with very low risk, 48.6% versus 46.0% (absolute Δ = +2.6%; P<.001) in those with low risk, and 33.8% versus 35.3% (absolute Δ = -1.5%; P=.05) in those with favorable intermediate risk.

Conclusions: Rates of misclassification were particularly elevated in patients with very low risk and low risk, regardless of race, and ranged from 33.8% to 48.6%. Recalibration of very-low-, low-, and, to a lesser extent, favorable intermediate-risk active surveillance criteria may be required. Finally, our data indicate that Black patients may be given the same consideration as White patients when active surveillance is an option. However, further validations should ideally follow.
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http://dx.doi.org/10.6004/jnccn.2020.7580DOI Listing
November 2020

The effect of sex on disease stage and survival after radical cystectomy: a population-based analysis.

Urol Oncol 2020 Oct 6. Epub 2020 Oct 6.

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

Background: The increased awareness regarding the sex gap in bladder cancer (BCa) care over the last decade may have resulted in more timely-wise referral patterns and treatment of female patients with BCa. Thus, we tested the association of sex with disease stage at presentation, as well as with cancer-specific mortality (CSM) after radical cystectomy (RC) in a contemporary cohort of patients with nonmetastatic urothelial bladder cancer (UCUB).

Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 14,086 patients (10,879 men and 3,207 women) treated with RC for non-metastatic UCUB. Temporal trend, interaction analyses, logistic regression, cumulative incidence, and competing-risks regression analyses were used.

Results: Overall, 10,879 (77.2%) men and 3,207 (22.8%) women underwent RC between 2004 and 2016. Female gender was an independent predictor of non-organ-confined (NOC) UCUB at RC in multivariable analyses (odds ratio: 1.23; 95% confidence intervals [CI] 1.10-1.38; P < 0.001). While NOC rates in men decreased over time (from 54.8% to 45.7%; P < 0.01), NOC rates in women remained stationary (from 60.6% to 57.3%; P = 0.15) and the excess NOC rate between men and women increased from + 5.8% in 2004 to +11.6% in 2016. Moreover, in multivariable analyses adjusted for other covariates, female gender was an independent predictor of higher CSM after RC in NOC UCUB (HR: 1.14; 95%CI 1.04-1.24; P < 0.01), but not in localized UCUB (P = 0.06).

Conclusion: It is worrisome that, while in men the rate of NOC is decreasing, NOC rates in females have not improved over time. Moreover, it is also worrisome that, despite adjustment for both pathological tumor and patient characteristics, female sex remains an adverse prognostic factor for CSM. Reassessment of referral, diagnostic, and treatment patterns aimed at eliminating these sex discrepancies appears warranted.
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http://dx.doi.org/10.1016/j.urolonc.2020.09.004DOI Listing
October 2020

Primary lymphomas of the genitourinary tract: A population-based study.

Asian J Urol 2020 Oct 27;7(4):332-339. Epub 2019 Nov 27.

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

Objective: We performed a population-based analysis focusing on primary extranodal lymphoma of either testis, kidney, bladder or prostate (PGUL).

Methods: We identified all cases of localized testis, renal, bladder and prostate primary lymphomas (PL) versus primary testis, kidney, bladder and prostate cancers within the Surveillance, Epidemiology, and End Results database (1998-2015). Estimated annual proportion change methodology (EAPC), multivariable logistic regression models, cumulative incidence plots and multivariable competing risks regression models were used.

Results: The rates of testis-PL, renal-PL, bladder-PL and prostate-PL were 3.04%, 0.22%, 0.18% and 0.01%, respectively. Patients with PGUL were older and more frequently Caucasian. Annual rates significantly decreased for renal-PL (EAPC: -5.6%; =0.004) and prostate-PL (EAPC: -3.6%; =0.03). In multivariable logistic regression models, older ager independently predicted testis-PL (odds ratio [OR]: 16.4; <0.001) and renal-PL (OR: 3.5; <0.001), while female gender independently predicted bladder-PL (OR: 5.5; <0.001). In surgically treated patients, cumulative incidence plots showed significantly higher 10-year cancer-specific mortality (CSM) rates for testis-PL, renal-PL and prostate-PL versus their primary genitourinary tumors. In multivariable competing risks regression models, only testis-PL (hazard ratio [HR]: 16.7; <0.001) and renal-PL (HR: 2.52; <0.001) independently predicted higher CSM rates.

Conclusion: PGUL rates are extremely low and on the decrease in kidney and prostate but stable in testis and bladder. Relative to primary genitourinary tumors, PGUL are associated with worse CSM for testis-PL and renal-PL but not for bladder-PL and prostate-PL, even after adjustment for other-cause mortality.
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http://dx.doi.org/10.1016/j.ajur.2019.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498952PMC
October 2020

Prognostic value of preoperative albumin to globulin ratio in patients treated with salvage radical prostatectomy for radiation recurrent prostate cancer.

Minerva Urol Nefrol 2020 Sep 29. Epub 2020 Sep 29.

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

Background: Serum albumin-to-globulin ratio (AGR) has been shown to be associated with poor prognosis in different malignancies. In this study we aimed to evaluate the predictive value of preoperative AGR for oncological outcomes in patients with radiation recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP).

Methods: A retrospective review of 214 consecutive patients with radiation-recurrent PCa who underwent SRP at five referral centers. Levels of albumin and globulin were obtained before SRP and used to calculate the preoperative AGR level. The optimal cut off value of preoperative AGR was 1.4. Univariable and multivariable Cox regression analyses were performed.

Results: Overall 89 (41.6%) patients had a low preoperative AGR. Low serum AGR was associated with biochemical recurrence (BCR) in univariable Cox regression analysis (HR 1.60, 95%CI 1.06-2.43, P=0.026). When adjusted for the effects of established preoperative and postoperative clinicopathologic confounders in different multivariable Cox regression models, this association did not retain its statistical significance. Moreover, preoperative AGR was not associated with metastasis free survival (P= 0.21), overall survival (P= 0.91) or cancer specific survival (P=0.61).

Conclusions: In patients with radiation recurrent PCa undergoing SRP, low preoperative AGR was associated with the risk of BCR only in univariable analysis. There was no association with metastasis or survival outcomes. Further studies are needed to evaluate this biomarker in the setting of primary PCa and to identify the patients most likely to benefit from a local therapy.
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http://dx.doi.org/10.23736/S0393-2249.20.03938-7DOI Listing
September 2020

Effect of Age on Cancer-specific Mortality in Patients With Urothelial Carcinoma of the Urinary Bladder: A Population-based Competing-risks Analysis Across Disease Stages.

Am J Clin Oncol 2020 12;43(12):880-888

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

Objective: The objective of the study is to test the effect of age on cancer-specific mortality (CSM) in patients with urothelial carcinoma of the urinary bladder (UCUB), across all disease stages.

Materials And Methods: Within the Surveillance, Epidemiology, and End Results (SEER) registry (2004-2016), we identified 207,714 patients. Age was categorized as: below 60 versus 60 to 69 versus 70 to 79 versus 80 years and above. Multivariable competing-risks regression (CRR) models were used according to disease stage (low-risk nonmuscle invasive: TaN0M0 low grade, high-risk nonmuscle invasive: Ta high grade or Tis-1N0M0, muscle invasive: T2-3N0M0, regional: T4N0M0/TanyN1-3M0, and metastatic: TanyNanyM1).

Results: Overall, 33,970 (16.4%) versus 52,173 (25.1%) versus 64,537 (31.1%) versus 57,034 (27.4%) patients were below 60 versus 60 to 69 versus 70 to 79 versus 80 years and above, respectively. In multivariable CRR models that focused on low-risk nonmuscle invasive UCUB, advanced age was associated with higher CSM rates (hazard ratio [HR]: 7.04 in patients aged 80 y and above, relative to below 60 y; P<0.001). Moreover, advanced age was also associated with higher CSM rates in high-risk nonmuscle invasive UCUB (HR: 2.77 in patients aged 80 y and above, relative to below 60 y; P<0.001) and in muscle invasive UCUB patients (HR: 1.38 in patients aged 80 y and above, relative to below 60 y; P<0.001). Conversely, lower CSM rates with advanced age were observed in multivariable CRR that focused on regional (HR: 0.91 for patients aged 80 y and above, relative to below 60 y; P=0.02) or metastatic UCUB (HR: 0.75 for patients aged 80 y and above, relative to below 60 y; P<0.001).

Conclusions: The direction and the magnitude of the association between advanced age and CSM in UCUB patients changes according to tumor stage. In low-risk nonmuscle invasive, high-risk nonmuscle invasive, and muscle invasive UCUB, more advanced age is associated with higher CSM rates. Conversely, in regional and metastatic UCUB patients, more advanced age is associated with lower CSM rates.
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http://dx.doi.org/10.1097/COC.0000000000000766DOI Listing
December 2020

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

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

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

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

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

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

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

The long and winding road to effective immunotherapy in patients with adrenocortical carcinoma.

Future Oncol 2020 Dec 28;16(36):3017-3020. Epub 2020 Aug 28.

Medical Oncology Unit, Department of Medical & Surgical Specialties, Radiological Sciences & Public Health, University of Brescia, ASST Spedali Civili of Brescia, Brescia, 25123, Italy.

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http://dx.doi.org/10.2217/fon-2020-0686DOI Listing
December 2020

Assessment of other-cause mortality in localized renal cell carcinoma patients within 15 years: A population-based analysis.

J Surg Oncol 2020 Dec 18;122(7):1506-1513. Epub 2020 Aug 18.

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

Background And Objective: Five-year other cause mortality (OCM) after nephrectomy for non-metastatic renal cell carcinoma (RCC) should be marginal in properly selected surgical candidates. We examined 5-year OCM rates as a quality of care indicator for patient selection.

Materials And Methods: Within the Surveillance, Epidemiology, and End Results database (1997-2011), we identified 59267 RCC patients treated with either radical (n = 27 804, 46.9%) or partial nephrectomy (n = 31 463, 53.1%). Temporal trends and multivariable Cox regression analyses assessed 5-year OCM. Data were stratified according to age group, year of diagnosis, race, marital status, gender, and socio-economic status. The overall OCM rates for the entire cohort at 5 years of follow-up was 4.7% and decreased from 9.4% to 5.6% over the study span (-3.8%, P < .001). The greatest decrease in 5-year OCM rates over time was recorded in patients >70 years (17.0%-9.6%, slope, -0.6%/y), as well as in African-Americans (12.0-6.2%; slope, -0.3%/y) and in males (8.9%-4.7%; slope, -0.3%, all P < .001).

Conclusions: An important OCM decrease was recorded over the study span. Nonetheless, further improvement may be accomplished, especially in African-Americans, unmarried and older individuals, who exhibited higher OCM rates than others. These three groups may represent ideal targets for better patient selection based on OCM considerations.
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http://dx.doi.org/10.1002/jso.26149DOI Listing
December 2020

Contemporary Cytoreductive Nephrectomy Provides Survival Benefit in Clear-cell Metastatic Renal Cell Carcinoma.

Clin Genitourin Cancer 2020 Dec 20;18(6):e730-e738. Epub 2020 May 20.

Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, QC, Canada; Division of Urology, University of Montreal Hospital Center (CHUM), Montreal, QC, Canada.

Introduction: A recent randomized trial questioned the role of cytoreductive nephrectomy in clear-cell metastatic renal cell carcinoma (ccmRCC). We reassessed the effect of cytoreductive nephrectomy on survival in a contemporary population-based ccmRCC cohort.

Patients And Methods: Within the Surveillance, Epidemiology, and End Results database (2010-2015), we focused on patients with ccmRCC. The primary endpoint consisted of overall mortality. Univariable and multivariable Cox regression models were applied in the overall cohort and in patients who underwent targeted therapy. Sensitivity analyses included 1:1 propensity score matching, 3- and 6-month landmark analyses, incremental survival benefit analyses, and metastases number and location-based stratifications.

Results: Of 4062 patients with ccmRCC, 2241 (55.1%) received targeted therapy; cytoreductive nephrectomy was performed in 2226 (54.8%) patients and 1168 (52.1%) patients in the overall and targeted therapy cohorts, respectively. Cytoreductive nephrectomy was associated with lower overall mortality in the overall cohort (median survival, 30 vs. 9 months; hazard ratio [HR], 0.43; P < .001), as well as in the targeted therapy cohort (median survival, 28 vs. 12 months; HR, 0.49; P < .001). In sensitivity analyses, cytoreductive nephrectomy was associated with lower overall mortality after 1:1 propensity score-matching (HR, 0.49; P < .001), in 3- and 6-month landmark analyses (HR, 0.49; P < .001 and HR, 0.51; P < .001, respectively), in metastases number and location-based stratifications, except for exclusive liver metastases, as well as in all incremental benefit analyses.

Conclusion: Cytoreductive nephrectomy is associated with better survival in patients with ccmRCC, including those exposed to targeted therapy, after adjustment for multiple potential confounders.
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http://dx.doi.org/10.1016/j.clgc.2020.05.009DOI Listing
December 2020

Bladder cancer incidence rates and trends in young adults aged 20-39 years.

Urol Oncol 2020 Dec 9;38(12):934.e11-934.e19. Epub 2020 Jul 9.

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

Objectives: To assess contemporary gender, race and stage-specific incidence and trends of bladder cancer among young adults in the United States.

Materials And Methods: Within Surveillance, Epidemiology, and End Results database (2001-2016), all patients aged 20 to 39 years-old with histologically confirmed bladder cancer were included. Age-standardized rates (ASR per 100,000 person-years) were estimated. Temporal trends were calculated through joinpoint regression analyses to describe the average annual percent change (AAPC).

Results: From 2000 to 2016, 2,772 new cases were recorded (ASR 0.2, AAPC -1.5%, P = 0.01). ASRs were higher in males than in females (0.3 and 0.1, respectively) and decreased significantly in both genders (AAPC -1.3, P = 0.02 and -2.2% P = 0.03, respectively). non-Hispanic White (NHW) accounted for 70.7% of the cohort and had the highest incidence (ASR 0.3) that decreased over time (AAPC -1.4%, P = 0.02). Conversely, ASRs in other ethnic groups were lower and showed stable trends. The most frequent tumor characteristics were Ta/TisN0M0 stage (71.0%, ASR 0.1, AAPC -1.0%, P = 0.1), low grade (61.6%, ASR 0.1, AAPC -4.3%, P = 0.001) and urothelial histology (95.5%, ASR 0.2, AAPC -1.5%, P = 0.01).

Conclusions: Despite the rarity of bladder cancer in those aged 20 to 39 years, a standard work-up is required to avoid advanced stage at diagnosis. The current data validate initial diagnoses at earliest stage in the vast majority of young adults. Moreover, decreasing ASRs in both genders are encouraging.
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http://dx.doi.org/10.1016/j.urolonc.2020.06.009DOI Listing
December 2020

Bone Mineral Density and FRAX Score May Not Predict Fracture Risk in Patients With Cancer Undergoing Hormone Deprivation Therapies.

J Clin Oncol 2020 10 30;38(29):3363-3366. Epub 2020 Jun 30.

Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, Medical Oncology, University of Brescia at ASST Spedali Civili, Brescia, Italy.

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http://dx.doi.org/10.1200/JCO.20.00434DOI Listing
October 2020

Renal cell carcinoma incidence rates and trends in young adults aged 20-39 years.

Cancer Epidemiol 2020 08 22;67:101762. Epub 2020 Jun 22.

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

Background: The burden of renal cell carcinoma (RCC) in young adults received marginal attention. We assessed contemporary gender, race and stage-specific incidence and trends of RCC among young adults (20-39 years-old) in the United States.

Methods: Within Surveillance, Epidemiology, and End Results database (2000-2016), patients aged 20-39 years with histologically confirmed RCC were included. Age-standardized incidence rates (ASR per 100,000 person-years) were estimated. Temporal trends were calculated through joinpoint regression analyses to describe the average annual percent change (AAPC).

Results: From 2000-2016, 7767 new RCC cases were recorded (ASR 0.6, AAPC  + 5.0 %, p < 0.001). ASRs were higher in males than in females (0.7 and 0.5, respectively) and increased significantly in both genders (AAPC + 5.0 % and +4.7 % both p < 0.001, respectively). Non-Hispanic American Indian/Alaska Native had the highest incidence (ASR 1.0) vs. non-Hispanic Asian or Pacific Islander the lowest (ASR 0.3). ASRs significantly increased in all ethnic groups. T1aN0M0 and T1bN0M0 stages showed the highest incidence and increase (ASR 0.3, AAPC + 5.9 %, p < 0.001 and ASR 0.1, AAPC + 5.7 %, p < 0.001, respectively). Also regional and distant stages increased (AAPC + 3.7 %, p = 0.001 and AAPC + 1.5 %, p = 0.06). The most frequent tumor characteristics were G2 (44.4 %, ASR 0.3, AAPC + 6.3 %, p < 0.001) and G1 (13.1 %, ASR 0.1, AAPC + 1.1 %, p = 0.2), as well as clear cell histology (54.8 %, ASR 0.3, AAPC  + 7.6 %, p < 0.001).

Conclusions: RCC in young adults is rare, but increasing. This is mainly due to T1aN0M0 tumors. Nonetheless, also regional diseases are significantly increasing. Differences between ethnic groups exist and may warrant further research.
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http://dx.doi.org/10.1016/j.canep.2020.101762DOI Listing
August 2020

A Plea for Optimizing Selection in Current Adjuvant Immunotherapy Trials for High-risk Nonmetastatic Renal Cell Carcinoma According to Expected Cancer-specific Mortality.

Clin Genitourin Cancer 2020 08 5;18(4):314-321.e1. Epub 2019 Dec 5.

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

Background: Tyrosine kinase inhibitor-based adjuvant therapy showed no survival benefits for patients with high-risk nonmetastatic renal cell carcinoma (nmRCC). Five randomized immune-oncology checkpoint inhibitor trials are ongoing. We assessed the effect of stage, grade, and histologic type on cancer-specific mortality (CSM) in candidates for 1 of the 4 North American ongoing immune-oncology checkpoint inhibitor trials of high-risk nmRCC.

Patients And Methods: From the Surveillance, Epidemiology, and End Results database (2001-2015), we identified patients who had undergone surgery for nmRCC and had met the inclusion criteria for the PROSPER RCC (nivolumab in treating patients with localized kidney cancer undergoing nephrectomy), CheckMate 914 (a study comparing the combination of nivolumab and ipilimumab versus placebo in participants with localized renal cell carcinoma), KEYNOTE-564 [safety and efficacy study of pembrolizumab (MK-3475) as monotherapy in the adjuvant treatment of renal cell carcinoma post nephrectomy], or IMmotion010 [a study of atezolizumab as adjuvant therapy in participants with renal cell carcinoma (RCC) at high risk of developing metastasis following nephrectomy] trials. Kaplan-Meier and multivariable Cox regression models were used to assess the 10-year CSM rates in the overall cohort according to stage, grade, and histologic characteristics, and in 4 generated random samples according to the eligible patients for each of the 4 trials.

Results: Of 116,750 patients who had undergone surgery for nmRCC, 18,559 (15.9%) had fulfilled the inclusion criteria for 1 of the 4 trials. The greatest proportion of higher stage and grade combinations and sarcomatoid histologic features would have qualified for IMmotion010, followed by KEYNOTE-564, CheckMate 914, and PROSPER RCC. Multivariable Cox regression models demonstrated the most unfavorable prognosis for stage N1 grade 3/4 (hazard ratio [HR], 11.5; P < .001), stage T4N0 grade 3/4 (HR, 9.8; P < .001), and sarcomatoid histologic features (HR, 5.5; P < .001). Among the 4 random samples, the difference in the qualifying criteria resulted in the greatest versus progressively lower CSM rates in the IMmotion010, KEYNOTE-564, CheckMate 914, and PROSPER RCC trials, respectively (P < .001).

Conclusions: Our findings indicate that participation in adjuvant immunotherapy trials should be predominantly encouraged for patients with high-grade stage T3, T4, and N1 and patients with any stage with sarcomatoid pathologic features.
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http://dx.doi.org/10.1016/j.clgc.2019.11.010DOI Listing
August 2020

The Effect of Systemic Chemotherapy on Survival in Patients With Localized, Regional, or Metastatic Adenocarcinoma of the Urinary Bladder.

Am J Clin Oncol 2020 08;43(8):567-574

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

Objectives: To test the effect of systemic chemotherapy on cancer-specific mortality (CSM) in patients with adenocarcinoma of the urinary bladder (ADKUB).

Materials And Methods: Within the Surveillance, Epidemiology, and End Results registry (2004 to 2016), we identified patients with localized (T2-3N0M0), regional (T4N0M0/TanyN1-3M0), and metastatic (TanyNanyM1) ADKUB. Temporal trends, Kaplan-Meier plots, and multivariable Cox regression models were used before and after 1:1 propensity score matching and inverse probability of treatment weighting.

Results: Of 1537 patients with ADKUB, 834 (54.0%), 363 (23.5%), and 340 (22.5%) harbored localized, regional, and metastatic disease, respectively. The rates of chemotherapy use increased in localized (estimated annual percentage change [EAPC]: +2.7%; P=0.03) and regional ADKUB (EAPC: +2.4%; P=0.04). Conversely, chemotherapy rates remained stable in metastatic patients (EAPC: +1.6%; P=0.4). In multivariable Cox regression models, chemotherapy use was associated with lower CSM in metastatic ADKUB (hazard ratio [HR]: 0.5; P=0.003), but not in either localized (HR: 0.8; P=0.2) or in regional ADKUB (HR: 1.0; P=0.9). In metastatic ADKUB, the benefit of chemotherapy on CSM persisted after 1:1 propensity score matching (HR: 0.6; P=0.002) and after inverse probability of treatment weighting (HR: 0.4; P<0.001).

Conclusions: Chemotherapy improves survival in metastatic ADKUB. However, only one out of 2 such patients benefit from chemotherapy. In consequence, greater emphasis on chemotherapy use may be warranted in these patients. Conversely, no benefit was identified in localized or regional ADKUB.
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http://dx.doi.org/10.1097/COC.0000000000000704DOI Listing
August 2020

Contemporary Age-adjusted Incidence and Mortality Rates of Renal Cell Carcinoma: Analysis According to Gender, Race, Stage, Grade, and Histology.

Eur Urol Focus 2020 May 23. Epub 2020 May 23.

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

Background: Recent data showed that North America has the highest incidence of renal cell carcinoma (RCC) worldwide.

Objective: To assess contemporary gender-, race-, and stage-specific incidence; survival rates; and trends of RCC patients in the USA.

Design, Setting, And Participants: Within the Surveillance, Epidemiology, and End Results database (2001-2016), all patients aged ≥18 yr with histologically confirmed renal parenchymal tumors were included.

Outcome Measurements And Statistical Analysis: Age-adjusted incidence rates and 5-yr cancer-specific survival (CSS) rates were estimated. Temporal trends were calculated through Joinpoint regression analyses to describe the average annual percent change (AAPC).

Results And Limitations: The age-adjusted incidence rate of RCC was 11.3/100 000 person years (AAPC+2.0%, p<0.001). Five-year CSS rates increased from 78.4% to 84.5% (AAPC +0.8%, p<0.001). Male incidence was double that of females (15.5 and 7.7, respectively). CSS marginally favored females (84.5% vs 82.0%), but improved equally in both genders (both AAPC +0.8%). The highest incidence (14.1/100 000 person years, AAPC +2.8%) and lowest survival (80.1%) were recorded in non-Hispanic American Indian/Alaska Native populations. T1aN0M0 had the highest incidence rates (4.6/100 000 person years), the highest increase over time (AAPC +3.6%), and the highest CSS (97.6%) of all stages. Limitations include retrospective nature and lack of information on risk factors.

Conclusions: The incidence of RCC increased significantly from 2001 to 2016, and 5-yr CSS after RCC improved. This was mainly due to T1aN0M0 tumors that showed the highest increase in the incidence and highest CSS. Unfavorable outcomes in specific ethnic groups warrant further research.

Patient Summary: We examined contemporary incidence and cancer-specific survival rates of kidney cancer. Males had double the incidence rates of females, but lower survival. Natives showed the highest incidence rates and the lowest survival rates. Small renal masses showed the highest incidence and survival rates.
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http://dx.doi.org/10.1016/j.euf.2020.05.003DOI Listing
May 2020

Association Between Systemic Therapy and/or Cytoreductive Nephrectomy and Survival in Contemporary Metastatic Non-clear Cell Renal Cell Carcinoma Patients.

Eur Urol Focus 2020 May 19. Epub 2020 May 19.

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

Background: Optimal management of metastatic non-clear cell renal cell carcinoma (non-ccmRCC) remains largely unknown.

Objective: To test the effect of systemic therapy (ST) and/or cytoreductive nephrectomy (CNT) on overall mortality (OM) in patients with non-ccmRCC.

Design, Setting, And Participants: Within the Surveillance, Epidemiology and End Results (SEER) registry (2006-2015), we identified patients with papillary, chromophobe, sarcomatoid, and collecting duct metastatic renal cell carcinoma (mRCC).

Outcome Measurements And Statistical Analysis: Temporal trends (estimated annual percentage change [EAPC]), Kaplan-Meier plots, and multivariable Cox regression models were used.

Results And Limitations: Of 1573 patients with non-ccmRCC, 22%, 25%, 25%, and 28% underwent no treatment, ST, CNT, and CNT with ST, respectively. Between 2006 and 2015, rates of CNT and the combination of CNT and ST decreased (EAPC: -6.3% and -3.2%, respectively). Conversely, rates of no treatment and ST increased over time (EAPC: 4.6% and 7.5%, respectively). In multivariable Cox regression models, relative to no treatment, ST (hazard ratio [HR]: 0.5; p < 0.001), CNT (HR: 0.4; p < 0.001), and CNT with ST (HR: 0.3; p < 0.001) were associated with lower OM. Histological subtypes were associated with OM, relative to papillary renal cell carcinoma (RCC): chromophobe (HR: 0.7; p < 0.01), sarcomatoid (HR: 2.1; p < 0.001), and collecting duct RCC (HR: 1.9; p < 0.001). Limitations include the impossibility to stratify patients according to mRCC risk groups.

Conclusions: Most non-ccmRCC patients are treated with a combination of CNT and ST or CNT alone or ST alone. The rates of ST alone are increasing. Conversely, the rates of combined CNT and ST and CNT alone are decreasing. These observed temporal patterns of treatment rates are counterintuitive with respect to associated OM benefits, where combination of CNT and ST, as well as CNT alone, resulted in the lowest absolute OM, relative to ST alone, or, even worse, no treatment.

Patient Summary: We investigated the effect of treatment modalities on survival of patients with metastatic non-clear cell renal cell carcinoma. The combination of cytoreductive nephrectomy and systemic therapy confers greater benefit with respect to single treatments alone.
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http://dx.doi.org/10.1016/j.euf.2020.04.009DOI Listing
May 2020

Radical cystectomy plus chemotherapy in patients with pure squamous cell bladder carcinoma: a population-based study.

World J Urol 2020 May 18. Epub 2020 May 18.

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

Purpose: To test the effect of perioperative chemotherapy (CHT) on overall mortality (OM) and cancer-specific mortality (CSM) in patients with locally advanced or metastatic squamous cell carcinoma of the urinary bladder (SCC UB).

Methods: Within the Surveillance, Epidemiology and End Results database (1988-2016), we identified 1,018 SCC UB patients (664 TNM, 197 TanyNM and 156 TN or M), who underwent radical cystectomy with or without perioperative chemotherapy administration. Inverse probability of treatment-weighting (IPTW), Kaplan-Meier plots and Cox-regression models (CRMs) were used.

Results: CHT was administrated in 116 (17.5%) TNM, 77 (39.1%) TanyNM and 47 (30.1%) TN or M patients. IPTW-adjusted 2-year cancer-specific survival (CSS) was 66.5 vs. 71.5% (p = 0.19), 60.9 vs. 29.5% (p < 0.001) and IPTW-adjusted 1-year CSS was 46.2 vs. 31.1% (p = 0.03) for CHT vs. no CHT administration in TNM, TanyNM and TN or M, respectively. In multivariable IPTW-adjusted CRMs, chemotherapy was an independent predictor of lower CSM in TanyNM (HR 0.44) and in TN or M (HR 0.60), but not in TNM (p = 0.6) patients. Virtually the same results were obtained on OM, as well as without IPTW-adjustment and after stratification according to age and gender.

Conclusions: The use of perioperative CHT in patients with SCC UB confers survival benefit in the presence of T4b disease, lymph node or distant metastases. Conversely, patients with locally advanced disease but negative lymph node invasion do not benefit from its use. Pending higher quality data from prospective trials, these data should encourage the use of perioperative CHT in those high-risk patient groups.
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http://dx.doi.org/10.1007/s00345-020-03247-3DOI Listing
May 2020

Rates and Predictors of Perioperative Complications in Cytoreductive Nephrectomy: Analysis of the Registry for Metastatic Renal Cell Carcinoma.

Eur Urol Oncol 2020 08 12;3(4):523-529. Epub 2020 May 12.

Department of Urology, University Hospitals Leuven, Leuven, Belgium.

Background: Cytoreductive nephrectomy (CN) plays an important role in the treatment of a subgroup of metastatic renal cell carcinoma (mRCC) patients.

Objective: We aimed to evaluate morbidity associated with this procedure and identify potential predictors thereof to aid patient selection for this procedure and potentially improve patient outcomes.

Design, Setting, And Participants: Data from 736 mRCC patients undergoing CN at 14 institutions were retrospectively recorded in the Registry for Metastatic RCC (REMARCC).

Outcome Measurements And Statistical Analysis: Logistic regression analysis was used to identify predictors for intraoperative, any-grade (AGCs), low-grade, and high-grade (HGCs) postoperative complications (according to the Clavien-Dindo classification) as well as 30-d readmission rates.

Results And Limitations: Intraoperative complications were observed in 69 patients (10.9%). Thrombectomy (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.08-1.75, p = 0.009) and adjacent organ removal (OR 2.7, 95% CI 1.38-5.30) were significant predictors of intraoperative complications at multivariable analysis. Two hundred seventeen patients (29.5%) encountered AGCs, while 45 (6.1%) encountered an HGC, of whom 10 (1.4%) died. Twenty-four (3.3%) patients had multiple postoperative complications. Estimated blood loss (EBL; OR 1.49, 95% CI 1.08-2.05, p = 0.01) was a significant predictor of AGCs at multivariable analysis. CN case load (OR 0.13, 95% CI 0.03-0.59, p = 0.009) and EBL (OR 2.93, 95% CI 1.20-7.15, p = 0.02) were significant predictors solely for HGCs at multivariable analysis. Forty-one patients (11.5%) were readmitted within 30 d of surgery. No significant predictors were identified. Results were confirmed in a subanalysis focusing solely on patients treated in the contemporary targeted therapy era.

Conclusions: Morbidity associated with CN is not negligible. Predictors of high-grade postoperative morbidity are predominantly indicators of complex surgery. EBL is a strong predictor of postoperative complications. CN case load correlates with lower high-grade morbidity and highlights the benefit of centralization of complex surgery. However, risks and benefits should be balanced when considering CN in mRCC patients.

Patient Summary: We studied patients with metastatic renal cancer to evaluate the outcomes associated with the surgical removal of the primary kidney tumor. We found that this procedure is often complex and adverse events are not uncommon. High intraoperative blood loss and a small number of cases performed at the treating center are associated with a higher rate of postoperative complications.
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http://dx.doi.org/10.1016/j.euo.2020.04.006DOI Listing
August 2020

Efficacy of the EDP-M Scheme Plus Adjunctive Surgery in the Management of Patients with Advanced Adrenocortical Carcinoma: The Brescia Experience.

Cancers (Basel) 2020 Apr 10;12(4). Epub 2020 Apr 10.

Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia at ASST Spedali Civili, 25123 Brescia, Italy.

Etoposide, doxorubicin and cisplatin plus oral mitotane (EDP-M) comprise the reference regimen in the management of patients with adrenocortical carcinoma (ACC). In this paper, we described the outcome of 58 patients with advanced/metastatic ACC consecutively treated with EDP-M in a reference center for this rare disease in Italy. In this series, EDP-M obtained a partial response in 50% of patients; median progression free survival (PFS) and overall survival were 10.1 months (95% Confidence Interval [CI 95%] 8.1-12.8) and 18.7 months (95% CI: 14.6-22.8), respectively. EDP-M was not interrupted in five patients showing disease progression after two cycles without the appearance of new lesions and mitotane levels below the therapeutic range. In two of them, the disease remained stable at further imaging evaluations and the other three obtained a partial response. Twenty-six responding patients underwent surgery of residual disease and 13 of them became disease free. Surgery identified a pathological complete response (pCR) in four patients (7%) and Ki67 expression in post-chemotherapy tumor specimens, inferior to 15% (median value), was associated with better PFS and survival. In the present study, the EDP-M regimen is confirmed to have a limited efficacy. Early disease progression does not mean treatment inefficacy. Surgery of residual disease in partially responding patients allows for the detection of pCR in few of them and this condition is predictive of long-term survival. Ki67 expression of post-chemotherapy residual disease could be an additional prognostic factor that deserves to be studied further.
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http://dx.doi.org/10.3390/cancers12040941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226395PMC
April 2020

Comparison of survival outcomes in patients with metastatic papillary vs. clear-cell renal cell carcinoma: a propensity-score analysis.

World J Urol 2021 Feb 6;39(2):461-472. Epub 2020 Apr 6.

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

Background: To compare survival outcomes of metastatic patients harbouring either papillary (pRCC) or clear-cell (ccRCC) renal cell carcinoma in overall population and according to treatment modality.

Methods: Within the Surveillance, Epidemiology and End Results database (2006-2015), we identified 6800 patients (585 papillary and 6215 clear-cell) with metastatic RCC. Propensity-score (PS) matching, Kaplan-Meier plots and multivariable Cox-regression models (CRMs) were used.

Results: Overall, 585 (8.6%) patients harboured pRCC. Rates of nodal metastases were higher in patients with pRCC (49.7 vs. 23.3%; p < 0.001). Median overall survival (OS) was 13 vs. 18 months for pRCC vs. ccRCC patients. After multivariable adjustments, no difference in OS was recorded. Furthermore, after propensity-score matching, virtually the same results were recorded. Median OS of pRCC vs. ccRCC was 8 vs. 4 months for no treatment (NT), 11 vs. 12 months for targeted therapy alone (TT), 17 vs. 35 months for cytoreductive nephrectomy alone (CN) and 18 vs. 25 months for combination of CN with TT.

Conclusions: Metastatic pRCC patients exhibit poor survival, regardless of treatment received. Moreover, pRCC patients are more likely to present nodal metastases, compared to ccRCC patients, as demonstrated by twofold higher rates of lymph node invasion at diagnosis. These observations indicate that papillary variant represents more prognostically unfavorable tumor histology, in the context of metastatic RCC.
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http://dx.doi.org/10.1007/s00345-020-03187-yDOI Listing
February 2021

Renal Cell Carcinoma: Comparison between Variant Histology and Clear Cell Carcinoma across All Stages and Treatment Modalities.

J Urol 2020 10 6;204(4):671-676. Epub 2020 Apr 6.

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

Purpose: We evaluated stage at presentation and cancer specific mortality according to variant histology relative to clear cell renal cell carcinoma.

Materials And Methods: Within the Surveillance, Epidemiology, and End Results registry (2001-2016) we identified variant histology and clear cell renal cell carcinoma cases. Cumulative incidence plots, multivariate Cox regression models matched for stage, grade and other patient characteristics addressed cancer specific mortality. Subgroup analyses relied on inverse probability treatment weighting according to nephrectomy type.

Results: Of all 69,785 patients with renal cell carcinoma 2,495 harbored variant histology (3.6%). Of patients with variant histology 70.1% (1,748) harbored sarcomatoid vs 11.2% (280) collecting duct vs 7.6% (190) mesenchymal vs 3.8% (94) neuroendocrine vs 2.9% (72) renal medullary vs 2.5% (62) mucinous tubular and spindle cell, and 2.0% (49) rhabdoid tumors. All patients with variant histology exhibited more advanced TNM stage at diagnosis than clear cell renal cell carcinoma, except for mucinous tubular and spindle cell. After matching with G4 clear cell renal cell carcinoma, collecting duct (multivariate HR 1.6, p <0.01), sarcomatoid (HR 1.8, p <0.01), renal medullary (HR 1.7, p=0.1) and rhabdoid variant histology (HR 1.5, p=0.1) showed higher cancer specific mortality than clear cell renal cell carcinoma. No cancer specific mortality differences were recorded for mesenchymal, neuroendocrine and mucinous tubular and spindle cell variant histology. In nephrectomy subgroup higher cancer specific mortality was recorded after partial nephrectomy than radical nephrectomy in sarcomatoid variant histology after inverse probability treatment weighting and multivariate adjustment (HR 1.2, p=0.02).

Conclusions: TNM stage at diagnosis is universally more advanced in patients with variant histology, except for mucinous tubular and spindle cell. Cancer specific mortality is higher in collecting duct, sarcomatoid, rhabdoid and renal medullary variant histology, but not in other variant histology. Partial nephrectomy is associated with worse survival in sarcomatoid variant histology but could not be assessed in other variant histology due to small sample size.
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http://dx.doi.org/10.1097/JU.0000000000001063DOI Listing
October 2020

Rates of other-cause mortality after radical cystectomy are decreasing over time-A population-based analysis over two decades.

J Surg Oncol 2020 Jun 4;121(8):1329-1336. Epub 2020 Apr 4.

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

Background And Objectives: To investigate other-cause mortality (OCM) rates over time according to several baseline characteristics in bladder cancer (BCa) patients treated with radical cystectomy (RC).

Methods: Within the Surveillance, Epidemiology, and End Results database (1988-2011), we identified 7702 T N M urothelial BCa patients treated with RC. Temporal trends and multivariable Cox regression (MCR) analyses assessed 5-year OCM. Data were stratified according to the year of diagnosis (1988-1995 vs 1996-2000 vs 2001-2004 vs 2005-2008 vs 2009-2011), age group (<60 vs 60-75 vs >75 years), sex, race, marital status, and socioeconomic status.

Results: Overall, OCM rates decreased from 13.9% in 1988-1995 to 8.6% in 2009-2011. The greatest decrease was recorded in elderly (>75) patients (32%-16%, slope: -0.55% per year; P = .01), followed by patients aged 60 to 75 (21%-5%, slope: -0.35% per year; P = .01), unmarried patients (16%-10%, slope: -0.26% per year; P < .001), male patients (14%-8.9%, slope: -0.23% per year), and African Americans (16%-11%, slope: -0.27% per year; P < .001). MCR models corroborated these results.

Conclusions: Most important decrease in OCM after RC over the last decades was recorded in the elderly, unmarried, and male patients. Nonetheless, these three patient groups still represent ideal targets for efforts aimed at minimizing the morbidity and mortality after RC, as their risk of OCM is higher than in others.
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http://dx.doi.org/10.1002/jso.25919DOI Listing
June 2020

Differences in short-term outcomes between open versus robot-assisted radical cystectomy in frail malnourished patients.

Eur J Surg Oncol 2020 07 14;46(7):1347-1352. Epub 2020 Mar 14.

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

Introduction: We tested whether frail patients may benefit from robot-assisted (RARC) relative to open radical cystectomy (ORC).

Materials And Methods: Frail patients treated with RC were identified within the National Inpatient Sample database (2008-2015). The effect of RARC vs. ORC was tested in five separate multivariable models predicting: complications, failure to rescue (FTR), in-hospital mortality, length of stay (LOS) and total hospital charges (THCs). As internal validity measure, analyses were repeated among non-frail patients. All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics.

Results: Of 11,578 RC patients, 3477 (30.0%) were frail. RARC was performed in 488 (14.0%) frail patients and 1386 (17.1%) non-frail patients. Among frail, RARC was only independently associated with shorter LOS (median 8 vs. 9 days, relative ratio [RR] 0.79, p < 0.001). Conversely, among non-frail, RARC was independently associated with lower complications (57.3 vs. 59.1%, odds ratio [OR] 0.82, p = 0.004) and shorter LOS (median 6 vs. 7 days, RR 0.88, p < 0.001), but also predicted higher THCs (+2850.3 US dollars, p = 0.001).

Conclusions: In frail patients, the use of RARC did not result in better short-term outcomes except for one-day advantage in LOS. Conversely, in non-frail patients, the use of RARC resulted in lower complication rates and shorter LOS at the cost of higher THCs. In consequence, the benefit of RARC appears relatively marginal in frail patients and our data do not suggest a clear and clinically-meaningful benefit of RARC over ORC in frail radical cystectomy population.
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http://dx.doi.org/10.1016/j.ejso.2020.03.204DOI Listing
July 2020

Preoperative frailty predicts adverse short-term postoperative outcomes in patients treated with radical prostatectomy.

Prostate Cancer Prostatic Dis 2020 12 18;23(4):573-580. Epub 2020 Mar 18.

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

Background: To investigate the effect of frailty on short-term postoperative outcomes in patients with prostate cancer treated with radical prostatectomy (RP).

Methods: Within the National Inpatient Sample database, we identified 91,618 RP patients treated between 2008 and 2015. The Johns Hopkins Adjusted Clinical Groups frailty-defining indicator was applied, and we examined the rates of frailty over time, as well as its effect on overall complications, major complications, nonhome-based discharge, length of stay (LOS), and total hospital charges (THCs). Time trends and multivariable logistic, Poisson and linear regression models were applied.

Results: Overall, 12,185 (13.3%) patients were frail. Rates of frail patients increased over time (from 10.3 to 18.2%; p < 0.001). Frail patients had higher rates of overall complications (16.6 vs. 8.6%), major complications (4.9 vs. 2.6%), nonhome-based discharge (5.9 vs. 5%), longer LOS (2 vs. 1), and higher THCs ($37,186 vs. $35,241) (all p < 0.001). Moreover, frailty was an independent predictor of overall complications (OR: 1.95), major complications (OR: 1.76), nonhome-based discharge (OR: 1.20), longer LOS (RR: 1.19), and higher THCs (RR: $3160) (all p < 0.001). Of frail patients, 10,418 (85.5%) neither exhibited body mass index ≥ 30 nor Charlson comorbidity index ≥ 2.

Conclusions: On average, every seventh RP patient is frail and that proportion is on the rise. Frail individuals are at higher risk of adverse short-term postoperative outcomes, that cannot be predicted by other risk factors, such as obesity or comorbidities.
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http://dx.doi.org/10.1038/s41391-020-0225-3DOI Listing
December 2020