Publications by authors named "Quoc-Dien Trinh"

575 Publications

Defining Factors Associated with High-quality Surgery Following Radical Cystectomy: Analysis of the British Association of Urological Surgeons Cystectomy Audit.

Eur Urol Open Sci 2021 Nov 20;33:1-10. Epub 2021 Sep 20.

Division of Surgery & Interventional Science, University College London, London, UK.

Background: Radical cystectomy (RC) is associated with high morbidity.

Objective: To evaluate healthcare and surgical factors associated with high-quality RC surgery.

Design Setting And Participants: Patients within the prospective British Association of Urological Surgeons (BAUS) registry between 2014 and 2017 were included in this study.

Outcome Measurements And Statistical Analysis: High-quality surgery was defined using pathological (absence of positive surgical margins and a minimum of a level I lymph node dissection template with a minimum yield of ten or more lymph nodes), recovery (length of stay ≤10 d), and technical (intraoperative blood loss <500 ml for open and <300 ml for minimally invasive RC) variables. A multilevel hierarchical mixed-effect logistic regression model was utilised to determine the factors associated with the receipt of high-quality surgery and index admission mortality.

Results And Limitations: A total of 4654 patients with a median age of 70.0 yr underwent RC by 152 surgeons at 78 UK hospitals. The median surgeon and hospital operating volumes were 23.0 and 47.0 cases, respectively. A total of 914 patients (19.6%) received high-quality surgery. The minimum annual surgeon volume and hospital volume of ≥20 RCs/surgeon/yr and ≥68 RCs/hospital/yr, respectively, were the thresholds determined to achieve better rates of high-quality RC. The mixed-effect logistic regression model found that recent surgery (odds ratio [OR]: 1.22, 95% confidence interval [CI]: 1.11-1.34, < 0.001), laparoscopic/robotic RC (OR: 1.85, 95% CI: 1.45-2.37, < 0.001), and higher annual surgeon operating volume (23.1-33.0 cases [OR: 1.54, 95% CI: 1.16-2.05, = 0.003]; ≥33.1 cases [OR: 1.64, 95% CI: 1.18-2.29, = 0.003]) were independently associated with high-quality surgery. High-quality surgery was an independent predictor of lower index admission mortality (OR: 0.38, 95% CI: 0.16-0.87, = 0.021).

Conclusions: We report that annual surgeon operating volume and use of minimally invasive RC were predictors of high-quality surgery. Patients receiving high-quality surgery were independently associated with lower index admission mortality. Our results support the role of centralisation of complex oncology and implementation of a quality assurance programme to improve the delivery of care.

Patient Summary: In this registry study of patients treated with surgical excision of the urinary bladder for bladder cancer, we report that patients treated by a surgeon with a higher annual operative volume and a minimally invasive approach were associated with the receipt of high-quality surgery. Patients treated with high-quality surgery were more likely to be discharged alive following surgery.
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http://dx.doi.org/10.1016/j.euros.2021.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546928PMC
November 2021

Prostate Cancer Disparities in Risk Group at Presentation and Access to Treatment for Asian Americans, Native Hawaiians, and Pacific Islanders: A Study With Disaggregated Ethnic Groups.

JCO Oncol Pract 2021 Oct 28:OP2100412. Epub 2021 Oct 28.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.

Purpose: We identified (1) differences in localized prostate cancer (PCa) risk group at presentation and (2) disparities in access to initial treatment for Asian American, Native Hawaiian, and Pacific Islander (AANHPI) men with PCa after controlling for sociodemographic factors.

Methods: We assessed all patients in the National Cancer Database with localized PCa with low-, intermediate-, and high-risk disease who identified as Thai, White, Asian Indian, Chinese, Vietnamese, Korean, Japanese, Filipino, Hawaiian, Pacific Islander, Laotian, Pakistani, Kampuchean, and Hmong. Multivariable logistic regression defined adjusted odds ratios (AORs) with 95% CI of (1) presenting at progressively higher risk group and (2) receiving treatment or active surveillance with intermediate- or high-risk disease, adjusting for sociodemographic and clinical factors.

Results: Among 980,889 men (median age 66 years), all AANHPI subgroups with the exception of Thai (AOR = 0.84 [95% CI, 0.58 to 1.21], > .05), Asian Indian (AOR = 1.12 [95% CI, 1.00 to 1.25], > .05), and Pakistani (AOR = 1.34 [95% CI, 0.98 to 1.83], > .05) men had greater odds of presenting at a progressively higher PCa risk group compared with White patients (Chinese AOR = 1.18 [95% CI, 1.11 to 1.25], < .001; Japanese AOR = 1.36 [95% CI, 1.26 to 1.47], < .001; Filipino AOR = 1.37 [95% CI, 1.29 to 1.46], < .001; Korean AOR = 1.32 [95% CI, 1.18 to 1.48], < .001; Vietnamese AOR = 1.20 [95% CI, 1.07 to 1.35], = .002; Laotian AOR = 1.60 [95% CI, 1.08 to 2.36], = .018; Hmong AOR = 4.07 [95% CI, 1.54 to 10.81], = .005; Kampuchean AOR = 1.55 [95% CI, 1.03 to 2.34], = .036; Asian Indian or Pakistani AOR = 1.15 [95% CI, 1.07 to 1.24], < .001; Native Hawaiians AOR = 1.58 [95% CI, 1.38 to 1.80], < .001; and Pacific Islanders AOR = 1.58 [95% CI, 1.37 to 1.82], < .001). Additionally, Japanese Americans (AOR = 1.46 [95% CI, 1.09 to 1.97], = .013) were more likely to receive treatment compared with White patients.

Conclusion: Our findings suggest that there are differences in PCa risk group at presentation by race or ethnicity among Asian American, Native Hawaiian, and Pacific Islander subgroups and that there exist disparities in treatment patterns. Although AANHPI are often studied as a homogenous group, heterogeneity upon subgroup disaggregation underscores the importance of further study to assess and address barriers to PCa care.
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http://dx.doi.org/10.1200/OP.21.00412DOI Listing
October 2021

Analysis of Surgical Volume in Military Medical Treatment Facilities and Clinical Combat Readiness of US Military Surgeons.

JAMA Surg 2021 Oct 27. Epub 2021 Oct 27.

Center for Surgery and Public Health, Harvard Medical School, Harvard T. H. Chan School of Public Health, Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.

Importance: Low surgical volume in the US Military Health System (MHS) has been identified as a challenge to military surgeon readiness. The Uniformed Services University of Health Sciences, in partnership with the American College of Surgeons, developed the Knowledge, Skills, and Abilities (KSA) Clinical Readiness Program that includes a tool for quantifying the clinical readiness value of surgeon workload, known as the KSA metric.

Objective: To describe changes in US military general surgeon procedural volume and readiness using the KSA metric.

Design, Setting, And Participants: This cohort study analyzed general surgery workload performed across the MHS, including military and civilian facilities, between fiscal year 2015 and 2019 and the calculated KSA metric value. The surgeon-level readiness among military general surgeons was calculated based on the KSA metric readiness threshold. Data were obtained from TRICARE, the US Department of Defense health insurance product.

Main Outcomes And Measures: The main outcomes were general surgery procedural volumes and the KSA metric point value of those procedures across the MHS as well as the number of military general surgeons meeting the KSA metric readiness threshold. Aggregate facility and regional market-level claims data were used to calculate the procedural volumes and KSA metric readiness value of those procedures. Annual adjusted KSA metric points earned were used to determine the number of individual US military general surgeons meeting the readiness threshold.

Results: The number of general surgery procedures generating KSAs in military hospitals decreased 25.6%, from 128 377 in 2015 to 95 461 in 2019, with a 19.1% decrease in the number of general surgeon KSA points (from 7 155 563 to 5 790 001). From 2015 to 2019, there was a 3.2% increase in both the number of procedures (from 419 980 to 433 495) and KSA points (from 21 071 033 to 21 748 984) in civilian care settings. The proportion of military general surgeons meeting the KSA metric readiness threshold decreased from 16.7% (n = 97) in 2015 to 10.1% (n = 68) in 2019.

Conclusions And Relevance: This study noted that the number of KSA metric points and procedural volume in military hospitals has been decreasing since 2015, whereas both measures have increased in civilian facilities. The findings suggest that loss of surgical workload has resulted in further decreases in military surgeon readiness and may require substantial changes in patient care flow in the MHS to reverse the change.
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http://dx.doi.org/10.1001/jamasurg.2021.5331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552115PMC
October 2021

Measuring What Matters: Patient-Reported Outcome and Experience Measures for Men Undergoing Radical Prostatectomy.

Eur Urol Focus 2021 Sep 21;7(5):913-915. Epub 2021 Sep 21.

Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

Patient-reported outcome and experience measures capture a reliable representation of a patient's functional outcomes and quality of life. However, they are only helpful if the data are easily comprehensible to patients and are accessible to providers, patients, and payers. If we want to ensure that these metrics are fair, accurate, and relevant, then physicians should be leaders in developing and adopting these tools.
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http://dx.doi.org/10.1016/j.euf.2021.09.010DOI Listing
September 2021

Predicting survival after radical prostatectomy: Variation of machine learning performance by race.

Prostate 2021 Dec 16;81(16):1355-1364. Epub 2021 Sep 16.

Department of Urology, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Background: Robust prediction of survival can facilitate clinical decision-making and patient counselling. Non-Caucasian males are underrepresented in most prostate cancer databases. We evaluated the variation in performance of a machine learning (ML) algorithm trained to predict survival after radical prostatectomy in race subgroups.

Methods: We used the National Cancer Database (NCDB) to identify patients undergoing radical prostatectomy between 2004 and 2016. We grouped patients by race into Caucasian, African-American, or non-Caucasian, non-African-American (NCNAA) subgroups. We trained an Extreme Gradient Boosting (XGBoost) classifier to predict 5-year survival in different training samples: naturally race-imbalanced, race-specific, and synthetically race-balanced. We evaluated performance in the test sets.

Results: A total of 68,630 patients met inclusion criteria. Of these, 57,635 (84%) were Caucasian, 8173 (12%) were African-American, and 2822 (4%) were NCNAA. For the classifier trained in the naturally race-imbalanced sample, the F1 scores were 0.514 (95% confidence interval: 0.513-0.511), 0.511 (0.511-0.512), 0.545 (0.541-0.548), and 0.378 (0.378-0.389) in the race-imbalanced, Caucasian, African-American, and NCNAA test samples, respectively. For all race subgroups, the F1 scores of classifiers trained in the race-specific or synthetically race-balanced samples demonstrated similar performance compared to training in the naturally race-imbalanced sample.

Conclusions: A ML algorithm trained using NCDB data to predict survival after radical prostatectomy demonstrates variation in performance by race, regardless of whether the algorithm is trained in a naturally race-imbalanced, race-specific, or synthetically race-balanced sample. These results emphasize the importance of thoroughly evaluating ML algorithms in race subgroups before clinical deployment to avoid potential disparities in care.
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http://dx.doi.org/10.1002/pros.24233DOI Listing
December 2021

Neurotoxicities of novel non-steroidal anti-androgens for prostate cancer: A systematic review and meta-analysis.

Crit Rev Oncol Hematol 2021 Oct 27;166:103463. Epub 2021 Aug 27.

Department of Medical Oncology, Ankara University School of Medicine, Ankara, Turkey; Ankara University Cancer Research Institute, Ankara, Turkey. Electronic address:

Introduction: Novel non-steroidal anti-androgens (NSAA) are increasingly part of the management of prostate cancer. We aimed to quantify and compare the neurologic side effects of NSAA agents.

Materials And Methods: Phase III randomized controlled trials evaluating NSAAs in the treatment of prostate cancer were selected by two reviewers independently in MEDLINE. A random-effects model and the Mantel-Haenszel method were used. The Odds Ratio (OR) and its 95 % confidence interval were computed. The primary endpoints were the rates of neurologic adverse events.

Results: Eight phase III trials evaluating novel NSAAs (vs. non-NSAAs) were included. Fatigue (OR:1.66 [1.32-2.08]), falls (OR:1.76 [1.25-2.49]), headache (OR:1.74 [1.42-2.14]), and dizziness (OR:1.70 [1.33-2.19]) were found to be significantly associated with NSAA use.

Conclusions: NSAAs are associated with an increase in various neurologic adverse events. When NSAAs are prescribed, neurologic adverse event prevention and management strategies should be discussed and implemented.
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http://dx.doi.org/10.1016/j.critrevonc.2021.103463DOI Listing
October 2021

High-intensity local treatment of clinical node-positive urothelial carcinoma of the bladder alongside systemic chemotherapy improves overall survival.

Urol Oncol 2021 Aug 1. Epub 2021 Aug 1.

VCORE - Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation, Henry Ford Hospital, Detroit, Michigan; Vattikuti Urology Institute, Henry Ford Hospital, Detroit, Michigan.

Purpose: Clinical node-positive urothelial carcinoma of the bladder (cN+UCaB) is a rapidly fatal disease with limited information on comparative-effectiveness of available treatment options. We sought to examine the impact of high-intensity vs. conservative local treatment (LT) regimens in management of these patients alongside systemic chemotherapy.

Materials And Methods: We identified 3,227 patients within the National Cancer Data Base who underwent multiagent systemic chemotherapy along with either high-intensity or conservative LT for primary cN+UCaB between 2004-2016. Patients who received no LT, TURBT alone, or <50 Gy radiation therapy to the bladder were included in the conservative group, while patients that received radical cystectomy with pelvic lymphadenectomy or ≥50 Gy radiation therapy with TURBT were included in the high-intensity group. Inverse probability of treatment weighting (IPTW) adjusted Kaplan-Meier and Cox regression analyses were used to assess overall survival (OS). Additionally, to assess whether the benefit of high-intensity LT differs by baseline mortality risk, we tested an interaction between 5-year predicted life-expectancy and the LT type.

Results: Overall, 784 (24.3%) and 2,443 (75.7%) cN+UCaB patients underwent high-intensity and conservative LT, respectively. IPTW-adjusted Kaplan-Meier analysis demonstrated OS to be significantly higher in the high-intensity group compared to the conservative group: 5-year OS 28.4% vs. 18.3%, respectively (Log-rank P<0.001). IPTW-adjusted multivariable Cox regression analysis confirmed the benefit of high-intensity LT in prolonging OS (HR 0.63, P<0.001). Interaction analysis showed that high-intensity LT approach was associated with longer OS in all patients regardless of their baseline 5-year life-expectancy (P=0.79).

Conclusion: Eligible patients with cN+UCaB should be considered for aggressive local treatment alongside multiagent systemic chemotherapy. Prospective trials are needed to validate these preliminary findings.
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http://dx.doi.org/10.1016/j.urolonc.2021.07.018DOI Listing
August 2021

Cardiovascular toxicities associated with abiraterone compared to enzalutamide-A pharmacovigilance study.

EClinicalMedicine 2021 Jun 6;36:100887. Epub 2021 May 6.

Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.

Background: Androgen deprivation therapy (ADT) is standard-of-care for advanced prostate cancer. Studies have generally found increased cardiovascular risks associated with ADT, but the comparative risk of newer agents is under-characterized. We defined the cardiac risks of abiraterone and enzalutamide, using gonadotropic releasing hormone (GnRH) agonists to establish baseline ADT risk.

Methods: We used VigiBase, the World Health Organization pharmacovigilance database, to identify cardiac adverse drug reactions (ADRs) in a cohort taking GnRH agonists, abiraterone, or enzalutamide therapy for prostate cancer, comparing them to all other patients. To examine the relationship, we used an empirical Bayes estimator to screen for significance, then calculated the reporting odds ratio (ROR), a surrogate measure of association. A lower bound of a 95% confidence interval (CI) of ROR > 1 reflects a disproportionality signal that more ADRs are observed than expected due to chance.

Findings: We identified 2,433 cardiac ADRs, with higher odds for abiraterone compared to all other VigiBase drugs for overall cardiac events (ROR 1•59, 95% CI 1•48-1•71), myocardial infarction (1•35, 1•16-1•58), arrythmia (2•04, 1•82-2•30), and heart failure (3•02, 2•60-3•51), but found no signal for enzalutamide. Patients on GnRH agonists also had increased risk of cardiac events (ROR 1•21, 95% CI 1•12-1•30), myocardial infarction (1•80, 1•61-2•03) and heart failure (2•06, 1•76-2•41).

Interpretation: We found higher reported odds of cardiac events for abiraterone but not enzalutamide. Our data may suggest that patients with significant cardiac comorbidities may be better-suited for therapy with enzalutamide over abiraterone.

Funding: None.
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http://dx.doi.org/10.1016/j.eclinm.2021.100887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257986PMC
June 2021

Recovery of cancer screening tests and possible associated disparities after the first peak of the COVID-19 pandemic.

Cancer Cell 2021 08 1;39(8):1042-1044. Epub 2021 Jul 1.

Lank Center for Genitourinary Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. Electronic address:

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http://dx.doi.org/10.1016/j.ccell.2021.06.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245382PMC
August 2021

Association of the hospital readmission reduction program with readmission and mortality outcomes after coronary artery bypass graft surgery.

J Card Surg 2021 Sep 3;36(9):3251-3258. Epub 2021 Jul 3.

Center for Surgery and Public Health, Brigham and Women's Hospital, Boston, Massachusetts, USA.

The Affordable Care Act established the Hospital Readmissions Reduction Program (HRRP) to reduce payments to hospitals with excessive readmissions in an effort to link payment to the quality of hospital care. Prior studies demonstrating an association of HRRP implementation with increased mortality after heart failure discharges have prompted concern for potential unintended adverse consequences of the HRRP. We examined the impact of these policies on coronary artery bypass graft (CABG) surgery outcomes using the Nationwide Readmissions Database and found that, in line with previously observed readmission trends for CABG, readmission rates continued to decline in the era of the HRRP, but that this did not come at the expense of increased mortality. These results suggest that inclusion of surgical procedures, such as CABG in the HRRP might be an effective cost-reducing measure that does not adversely affect quality of hospital care.
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http://dx.doi.org/10.1111/jocs.15749DOI Listing
September 2021

Prognostic value of the pre-operative serum albumin to globulin ratio in patients with non-metastatic prostate cancer undergoing radical prostatectomy.

Int J Clin Oncol 2021 Sep 28;26(9):1729-1735. Epub 2021 Jun 28.

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

Purpose: To evaluate the potential predictive value of the preoperative serum albumin to globulin ratio (AGR) for oncological outcomes in patients treated with radical prostatectomy (RP) for clinically non-metastatic prostate cancer (PCa).

Methods: Pre-operative AGR was assessed in a multi-institutional cohort of 6041 patients treated with RP. Logistic regression analyses were performed to assess the association of the AGR with advanced disease. We performed Cox regression analyses to determine the relationship between AGR and biochemical recurrence (BCR).

Results: The optimal cut-off value was determined to be 1.31 according to receiver operating curve analysis. Compared to patients with a higher AGR, those with a lower preoperative AGR had worse BCR-free survival (P < 0.01) in the Kaplan-Meier analysis. Pre- and post-operative multivariable models that adjusted for the effects of established clinicopathologic features, confirmed its independent association with BCR [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.31-1.75, P < 0.01, HR 1.55, 95% CI 1.34-1.79, P < 0.01, respectively]. However, the addition of AGR to established prognostic models did not improve their discrimination.

Conclusion: While AGR is significantly associated with BCR, in the present study, the clinical impact of AGR was not large enough to affect patient management. Longer follow-up is necessary to observe the true effect of AGR.
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http://dx.doi.org/10.1007/s10147-021-01952-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364901PMC
September 2021

Cancer in the Shadow of COVID: Early-Stage Breast and Prostate Cancer Patient Perspectives on Surgical Delays Due to COVID-19.

Ann Surg Oncol 2021 Dec 25;28(13):8688-8696. Epub 2021 Jun 25.

Department of Surgery, Center for Surgery and Public Health, Brigham and Woman's Hospital, Boston, MA, USA.

Background: During the height of the coronavirus disease 2019 (COVID-19) pandemic, elective surgeries, including oncologic surgeries, were delayed. Little prospective data existed to guide practice, and professional surgical societies issued recommendations grounded mainly in common sense and expert consensus, such as medical therapy for early-stage breast and prostate cancer patients. To understand the patient experience of delay in cancer surgery during the pandemic, we interviewed breast and prostate cancer patients whose surgeries were delayed due to the pandemic.

Patients And Methods: Patients with early-stage breast or prostate cancer who suffered surgical postponement at Brigham and Women's Hospital (BWH) were invited to participate. Semi-structured telephone interviews were conducted with 21 breast and prostate cancer patients. Interviews were transcribed, and qualitative analysis using ground-theory approach was performed.

Results: Most patients reported significant distress due to cancer and COVID. Key themes that emerged included the lack of surprise and acceptance of the surgical delays but endorsed persistent cancer- and delay-related worries. Satisfaction with patient-physician communication and the availability of a delay strategy were key factors in patients' acceptance of the situation; perceived lack of communication prompted a few patients to seek care elsewhere.

Discussion: The clinical effect of delay in cancer surgery will take years to fully understand, but there are immediate steps that can be taken to improve the patient experience of delays in care, including elicitation of individual patient perspectives and ongoing communication. More work is needed to understand the wider experiences of patients, especially minority, socioeconomically disadvantaged, and uninsured patients, who encounter delays in oncologic care.
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http://dx.doi.org/10.1245/s10434-021-10319-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231084PMC
December 2021

ASO Author Reflections: How We Convey Empathy, Address Uncertainty, and Share Serious News: Challenges to Remote Surgical Care.

Ann Surg Oncol 2021 12 23;28(13):8697-8698. Epub 2021 Jun 23.

Department of Surgery, Center for Surgery and Public Health, Brigham and Woman's Hospital, Boston, MA, USA.

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http://dx.doi.org/10.1245/s10434-021-10326-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221276PMC
December 2021

Risk of Immune-related Adverse Events in Melanoma Patients With Preexisting Autoimmune Disease Treated With Immune Checkpoint Inhibitors: A Population-based Study Using SEER-Medicare Data.

Am J Clin Oncol 2021 08;44(8):413-418

Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School.

Objective: The objective of this study was to examine the risk of immune-related adverse events (irAEs) in patients with a preexisting autoimmune disease (pAID) presenting with a cutaneous melanoma receiving an immune checkpoint inhibitor (ICI) therapy.

Methods: Data from the Surveillance, Epidemiology, and End Results cancer registries and linked Medicare claims between January 2010 and December 2015 was used to identify patients diagnosed with cutaneous melanoma who had pAID or received ICI or both. Patients were then stratified into 3 groups: ICI+pAID, non-ICI+pAID, and ICI+non-pAID. Inverse probability of treatment weighted Cox proportional hazards regression models were fitted to assess the risk of cardiac, pulmonary, endocrine, and neurological irAE.

Results: In total, 3704 individuals were included in the analysis. The majority of patients consisted of non-ICI+pAID patients (N=2706/73.1%), while 106 (2.9%) patients and 892 (24.1%) were classified as ICI+pAID and ICI+non-pAID, respectively. The risk of irAE was higher in the ICI+pAID group compared with the non-ICI+pAID and ICI+non-pAID, respectively (non-ICI: cardiac: hazard ratio [HR]=3.59, 95% confidence interval [CI]: 2.83-4.55; pulmonary: HR=3.94, 95% CI: 3.23-4.81; endocrine: HR=1.72, 95% CI: 1.53-1.93; neurological: HR=3.88, 95% CI: 2.30-6.57/non-pAID: cardiac: HR=3.83, 95% CI: 3.39-4.32; pulmonary: HR=2.08, 95% CI: 1.87-2.32; endocrine: HR=1.23, 95% CI: 1.14-1.32; neurological: HR=3.77, 95% CI: 2.75-5.18).

Conclusions: Patients with a pAID face a significantly higher risk of irAEs. Further research examining the clinical impact of these events on the patients' oncological outcome and quality of life is urgently needed given our findings of significantly worse rates of adverse events.
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http://dx.doi.org/10.1097/COC.0000000000000840DOI Listing
August 2021

Nephrotoxicity in immune checkpoint inhibitor therapy: a pharmacovigilance study.

Nephrol Dial Transplant 2021 May 24. Epub 2021 May 24.

Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Background: Immune checkpoint inhibitor (ICI) therapy has demonstrated impressive clinical benefits across cancers. However, adverse drug reactions (ADR) occur in every organ system, often due to autoimmune syndromes. We sought to investigate the association between ICI therapy and nephrotoxicity using a pharmacovigilance database, hypothesizing that inflammatory nephrotoxic syndromes, would be reported more frequently in association with ICIs.

Methods: We analyzed VigiBase, the WHO pharmacovigilance database, to identify renal ADRs (rADRs), such as nephritis, nephropathy, and vascular disorders, reported in association with ICI therapy. We performed a disproportionality analysis to explore if rADRs were reported at a different rate with one of the ICI drugs compared to rADRs in the entire database, using an empirical Bayes estimator as a significance screen and defining the effect size with a reporting odds ratio (ROR).

Results: We found 2,341 rADR for all examined ICI drugs, with a disproportionality signal solely for nephritis (ROR 3.67, 95% CI: 3.34-4.04). Examining the different drugs separately, pembrolizumab, nivolumab, and ipilimumab+nivolumab combination therapy had significantly higher reporting odds of nephritis than the other ICI drugs (ROR 4.54, 95%CI: 3.81-5.4; ROR 3.94, 95%CI: 3.40-4.56; ROR 3.59, 95%CI: 2.71-4.76; respectively).

Conclusions: Using a pharmacovigilance method, we found increased odds of nephritis when examining renal ADRs associated with ICI therapy. Pembrolizumab, nivolumab, and a combination of ipilimumab plus nivolumab showed the highest odds. Clinicians should consider these findings and be aware of the increased risk of nephritis, especially in patients treated with pembrolizumab, when administering ICI therapy.
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http://dx.doi.org/10.1093/ndt/gfab187DOI Listing
May 2021

Impact of preoperative plasma levels of interleukin 6 and interleukin 6 soluble receptor on disease outcomes after radical cystectomy for bladder cancer.

Cancer Immunol Immunother 2021 May 23. Epub 2021 May 23.

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

Background: Preoperative plasma levels of Interleukin 6 (IL6) and its soluble receptor (IL6sR) have previously been associated with oncologic outcomes in urothelial carcinoma of the bladder (UCB); however, external validation in patients treated with radical cystectomy (RC) for UCB is missing.

Patients/methods: We prospectively collected preoperative plasma from 1,036 consecutive patients at two institutes. These plasma specimens were assessed for levels of IL6 and IL6sR. Logistic and Cox regression analyses were used to assess the correlation of plasma levels with pathologic and survival outcomes. The additional clinical net benefits of preoperative IL6 and IL6sR were evaluated using decision curve analysis (DCA).

Results: Median IL6 and IL6sR plasma levels were significantly higher in patients with adverse pathologic features. Elevated biomarker levels were independently associated with an increased risk for lymph node metastasis and ≥ pT3 disease. Both biomarkers were independently associated with recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). The addition to, respectively, fitted pre- and postoperative prognostic models improved the predictive accuracy for lymph node metastasis, ≥ pT3 disease, RFS and CSS on DCA.

Interpretation: We confirmed that elevated preoperative plasma levels of IL6 and IL6sR levels are associated with worse oncological disease survival in patients treated with RC for UCB in a large multicenter study. Both biomarkers hold potential in identifying patients with adverse pathological features that may benefit from intensified/multimodal therapy and warrant inclusion into predictive/prognostic models. They demonstrated the ability to improve the discriminatory power of such models and thus guide clinical decision making.
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http://dx.doi.org/10.1007/s00262-021-02953-0DOI Listing
May 2021

Racial differences in the treatment and outcomes for prostate cancer in Massachusetts.

Cancer 2021 Aug 17;127(15):2714-2723. Epub 2021 May 17.

Division of Urological Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Background: Massachusetts is a northeastern state with universally mandated health insurance since 2006. Although Black men have generally worse prostate cancer outcomes, emerging data suggest that they may experience equivalent outcomes within a fully insured system. In this setting, the authors analyzed treatments and outcomes of non-Hispanic White and Black men in Massachusetts.

Methods: White and Black men who were 20 years old or older and had been diagnosed with localized intermediate- or high-risk nonmetastatic prostate cancer in 2004-2015 were identified in the Massachusetts Cancer Registry. Adjusted logistic regression models were used to assess predictors of definitive therapy. Adjusted and unadjusted survival models compared cancer-specific mortality. Interaction terms were then used to assess whether the effect of race varied between counties.

Results: A total of 20,856 men were identified. Of these, 19,287 (92.5%) were White. There were significant county-level differences in the odds of receiving definitive therapy and survival. Survival was worse for those with high-risk cancer (adjusted hazard ratio [HR], 1.50; 95% CI, 1.4-1.60) and those with public insurance (adjusted HR for Medicaid, 1.69; 95% CI, 1.38-2.07; adjusted HR for Medicare, 1.2; 95% CI, 1.14-1.35). Black men were less likely to receive definitive therapy (adjusted odds ratio, 0.78; 95% CI, 0.74-0.83) but had a 17% lower cancer-specific mortality (adjusted HR, 0.83; 95% CI, 0.7-0.99).

Conclusions: Despite lower odds of definitive treatment, Black men experience decreased cancer-specific mortality in comparison with White men in Massachusetts. These data support the growing body of research showing that Black men may achieve outcomes equivalent to or even better than those of White men within the context of a well-insured population.

Lay Summary: There is a growing body of evidence showing that the excess risk of death among Black men with prostate cancer may be caused by disparities in access to care, with few or no disparities seen in universally insured health systems such as the Veterans Affairs and US Military Health System. Therefore, the authors sought to assess racial disparities in prostate cancer in Massachusetts, which was the earliest US state to mandate universal insurance coverage (in 2006). Despite lower odds of definitive treatment, Black men with prostate cancer experience reduced cancer-specific mortality in comparison with White men in Massachusetts. These data support the growing body of research showing that Black men may achieve outcomes equivalent to or even better than those of White men within the context of a well-insured population.
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http://dx.doi.org/10.1002/cncr.33564DOI Listing
August 2021

Effect of Medicaid Expansion on Receipt of Definitive Treatment and Time to Treatment Initiation by Racial and Ethnic Minorities and at Minority-Serving Hospitals: A Patient-Level and Facility-Level Analysis of Breast, Colon, Lung, and Prostate Cancer.

JCO Oncol Pract 2021 05;17(5):e654-e665

Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Purpose: We sought to investigate the association between Medicaid expansion under the Affordable Care Act and access to stage-appropriate definitive treatment for breast, colon, non-small-cell lung, and prostate cancer for underserved racial and ethnic minorities and at minority-serving hospitals (MSHs).

Methods: We conducted a retrospective, difference-in-differences study including minority patients with nonmetastatic breast, colon, non-small-cell lung, and prostate cancer and patients treated at MSHs between the age of 40 and 64, with tumors at stages eligible for definitive treatment from the National Cancer Database. We not only defined non-Hispanic Black and Hispanic cancer patients as racial and ethnic minorities but also report findings for non-Hispanic Black cancer patients separately. We examined the effect of Medicaid expansion on receipt of stage-appropriate definitive therapy, time to treatment initiation (TTI) within 30 days of diagnosis, and TTI within 90 days of diagnosis.

Results: Receipt of definitive treatment for minorities in expansion states did not change compared with minority patients in nonexpansion states. The proportion of racial and ethnic minorities in expansion states receiving treatment within 30 days increased (difference-in-differences: +3.62%; 95% CI, 1.63 to 5.61; < .001) compared with minority patients in nonexpansion states; there was no change for TTI within 90 days. Analysis focused on Black cancer patients yielded similar results. In analyses stratified by MSH status, there was no change in receipt of definitive therapy, TTI within 30 days, and TTI within 90 days when comparing MSHs in expansion states with MSHs in nonexpansion states.

Conclusion: In our cohort of cancer patients with treatment-eligible disease, we found no significant association between Medicaid expansion and changes in receipt of definitive treatment for breast, prostate, lung, and colon cancer for racial and ethnic minorities and at MSHs. Medicaid expansion was associated with improved TTI at the patient level for racial and ethnic minorities, but not at the facility level for MSHs. Targeted interventions addressing the needs of MSHs are still needed to continue mitigating national facility-level disparities in cancer outcomes.
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http://dx.doi.org/10.1200/OP.21.00010DOI Listing
May 2021

Limitations of using the National Cancer Database to examine the effect of policy change on stage at presentation at the population level.

J Am Acad Dermatol 2021 09 2;85(3):e195-e196. Epub 2021 May 2.

Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.04.086DOI Listing
September 2021

Limitations of using the National Cancer Database to examine the effect of policy change on stage at presentation at the population level.

J Am Acad Dermatol 2021 09 2;85(3):e195-e196. Epub 2021 May 2.

Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.04.086DOI Listing
September 2021

Comparison of comorbidity indices for prediction of morbidity and mortality after major surgical procedures.

Am J Surg 2021 Apr 14. Epub 2021 Apr 14.

Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Background: Assessing perioperative risk is essential for surgical decision-making. Our study compares the accuracy of comorbidity indices to predict morbidity and mortality.

Methods: Analyzing the National Surgical Quality Improvement Program, 16 major procedures were identified and American Society of Anesthesiologists (ASA), Charlson Comorbidity Index and modified Frailty Index were calculated. We fit models with each comorbidity index for prediction of morbidity, mortality, and prolonged length of stay (pLOS). Decision Curve Analysis determined the effectiveness of each model.

Results: Of 650,437 patients, 11.7%, 6.0%, 17.0% and 0.75% experienced any, major complication, pLOS, and mortality, respectively. Each index was an independent predictor of morbidity, mortality, and pLOS (p < 0.05). While the indices performed similarly for morbidity and pLOS, ASA demonstrated greater net benefit for threshold probabilities of 1-5% for mortality.

Conclusions: Models including readily available factors (age, sex) already provide a robust estimation of perioperative morbidity and mortality, even without considering comorbidity indices. All comorbidity indices show similar accuracy for prediction of morbidity and pLOS, while ASA, the score easiest to calculate, performs best in prediction of mortality.
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http://dx.doi.org/10.1016/j.amjsurg.2021.04.007DOI Listing
April 2021

Is Medicaid expansion associated with increases in palliative treatments for metastatic cancer?

J Comp Eff Res 2021 06 21;10(9):733-741. Epub 2021 Apr 21.

Division of Urological Surgery & Center for Surgery & Public Health, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Medicaid expansion following the 2010 Affordable Care Act has an unknown impact on palliative treatments. This registry-based study of individuals with metastatic cancer from 2010 to 2016 identified men and women with metastatic cancer in expansion and non-expansion states who received palliative treatments. A mixed effects logistic regression compared trends in expansion and non-expansion states and generated risk-adjusted probabilities or receiving palliative treatments each year. Despite lower baseline use of palliative treatments, the rate of change was more rapid in expansion states (odds ratio [OR]: 1.02; 95% CI: 1.01-1.03; p < 0.001). The adjusted probability of receiving palliative treatments rose from 21.3 to 26.0% in non-expansion states, and from 19.7 to 26.9% in expansion states. Use of palliative treatments among metastatic cancer patients increased from 2010 to 2016 with a significantly greater increase in Medicaid expansion states, even when adjusting for demographic differences between states.
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http://dx.doi.org/10.2217/cer-2020-0178DOI Listing
June 2021

Trends in mortality among Black and White men with prostate cancer in Massachusetts and Pennsylvania: Race and neighborhood socioeconomic position.

Cancer 2021 Jul 2;127(14):2525-2534. Epub 2021 Apr 2.

Division of Population Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts.

Background: Reducing disparities in men with prostate cancer (PCa) that may be caused by racial and socioeconomic differences is a major public health priority. Few reports have studied whether these disparities have changed over time.

Methods: Men diagnosed with PCa from January 1, 2000 to December 31, 2015 were identified from the Massachusetts and Pennsylvania cancer registries. All-cause mortality and PCa and cardiovascular cause-specific mortality were assessed. To estimate neighborhood socioeconomic position (nSEP), a summary score was generated using census tract-level measures of income, wealth, educational attainment, and racial and income segregation. Participants were grouped by diagnosis year (2000-2003, 2004-2007, 2008-2011, or 2012-2015), and changing trends in the mortality rate ratio by race and nSEP were estimated using covariate-adjusted Cox models with follow-up for up to 10 years, until death, or until censoring on January 1, 2018.

Results: There were 193,883 patients with PCa and 43,661 deaths over 1,404,131 person-years of follow-up. The Black-White adjusted hazard ratio (aHR) from 2000 to 2003 through 2012 to 2015 was stable for all-cause mortality (aHR, 1.14 to 0.97; P for heterogeneity = .42), decreased for PCa-specific mortality (aHR, 1.38 to 0.93; P for heterogeneity = .005), and increased for cardiovascular mortality (aHR, 1.09 to 1.28; P for heterogeneity = .034). The aHR comparing those in the lowest versus the highest nSEP quintile increased significantly for all-cause mortality (aHR, 1.54 to 1.79; P for heterogeneity = .008), but not for PCa-specific mortality (aHR, 1.60 to 1.72; P for heterogeneity = .40) or cardiovascular mortality (aHR, 1.72 to 1.89; P for heterogeneity = .085).

Conclusions: Although Black-White disparities in prostate mortality declined in Massachusetts and Pennsylvania over the study period, nSEP mortality disparity trends were stagnant or increased, warranting further attention.

Lay Summary: Few reports have examined whether racial and socioeconomic disparities in prostate cancer mortality have widened or narrowed in recent years. Using data from 2 state registries (Massachusetts and Pennsylvania) with differing intensities of government-mandated health insurance, trends in racial and neighborhood socioeconomic disparities were studied among Black and White men diagnosed from 2000 to 2015. Overall, trends in racial disparities were stagnant for all-cause mortality, shrank for prostate mortality, and widened for cardiovascular mortality. Disparities associated with neighborhood socioeconomic status either were stagnant or widened across all mortality end points. In general, disparities were more pronounced in Pennsylvania than in Massachusetts.
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http://dx.doi.org/10.1002/cncr.33506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249310PMC
July 2021

Impact of high-intensity local treatment on overall survival in stage IV upper tract urothelial carcinoma.

Urol Oncol 2021 07 16;39(7):436.e1-436.e10. Epub 2021 Mar 16.

Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Electronic address:

Objectives: To investigate the impact of high-intensity local treatment (LT) on overall survival (OS) in patients with stage IV upper tract urothelial carcinoma (UTUC).

Patients And Methods: Within the National Cancer Database, we identified 7,357 patients diagnosed with stage IV UTUC from 2004 to 2015. Patients who underwent high-intensity LT, defined as radical surgery of the primary tumor, were compared with those who did not. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Weighted survival analyses were used to test the association between high-intensity LT and OS. Multivariable Cox model was used to assess for independent predictors of OS. Sensitivity analysis was used to account for possible biases.

Results: Among stage IV patients, 10.6% (n = 779) had locally advanced disease (T4), 32.6% (n = 2,399) had node-positive disease (N+) and 56.8% (N = 4,179) had distant metastases (M+). Fewer than half of the patients underwent high-intensity LT (n = 2,908, 39.5%) while the remainder did not. On IPTW-adjusted survival analysis, high-intensity LT was associated with a prolonged OS (11.17 months [IQR, 5.19 to 24.28] months vs. 6.18 months [IQR, 2.27 to 14.49], P ≤ 0.001). A similar benefit was seen on adjusted survival analyses for each stage IV subgroup, defined according to TNM characteristics. The survival benefit was confirmed at sensitivity analysis.

Conclusion: High-intensity LT in balanced cohorts of patients with stage IV UTUC is associated with prolonged OS including those with locally advanced (T4), node-positive (N+) or distant metastases (M+).
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http://dx.doi.org/10.1016/j.urolonc.2021.01.031DOI Listing
July 2021

Temporal trends in the incidence of distant-stage bladder cancer among young individuals.

Int J Urol 2021 06 14;28(6):704-705. Epub 2021 Mar 14.

Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

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http://dx.doi.org/10.1111/iju.14550DOI Listing
June 2021

Reply by Authors.

J Urol 2021 05 11;205(5):1274. Epub 2021 Mar 11.

Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1097/JU.0000000000001601.02DOI Listing
May 2021

Results of a Randomized Phase II Trial of Intense Androgen Deprivation Therapy prior to Radical Prostatectomy in Men with High-Risk Localized Prostate Cancer.

J Urol 2021 07 8;206(1):80-87. Epub 2021 Mar 8.

Dana-Farber Cancer Institute, Boston, Massachusetts.

Purpose: This multicenter randomized phase 2 trial investigates the impact of intense androgen deprivation on radical prostatectomy pathologic response and radiographic and tissue biomarkers in localized prostate cancer (NCT02903368).

Materials And Methods: Eligible patients had a Gleason score ≥4+3=7, prostate specific antigen >20 ng/mL or T3 disease and lymph nodes <20 mm. In Part 1, patients were randomized 1:1 to apalutamide, abiraterone acetate, prednisone and leuprolide (AAPL) or abiraterone, prednisone, leuprolide (APL) for 6 cycles (1 cycle=28 days) followed by radical prostatectomy. Surgical specimens underwent central review. The primary end point was the rate of pathologic complete response or minimum residual disease (minimum residual disease, tumor ≤5 mm). Secondary end points included prostate specific antigen response, positive margin rate and safety. Magnetic resonance imaging and tissue biomarkers of pathologic outcomes were explored.

Results: The study enrolled 118 patients at 4 sites. Median age was 61 years and 94% of patients had high-risk disease. The combined pathologic complete response or minimum residual disease rate was 22% in the AAPL arm and 20% in the APL arm (difference: 1.5%; 1-sided 95% CI -11%, 14%; 1-sided p=0.4). No new safety signals were observed. There was low concordance and correlation between posttherapy magnetic resonance imaging assessed and pathologically assessed tumor volume. PTEN-loss, ERG positivity and presence of intraductal carcinoma were associated with extensive residual tumor.

Conclusions: Intense neoadjuvant hormone therapy in high-risk prostate cancer resulted in favorable pathologic responses (tumor 5 mm) in 21% of patients. Pathologic responses were similar between treatment arms. Part 2 of this study will investigate the impact of adjuvant hormone therapy on biochemical recurrence.
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http://dx.doi.org/10.1097/JU.0000000000001702DOI Listing
July 2021
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