PubTransformer

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Paul L Nguyen - Top 30 Publications

Prostate Cancer - Local Treatment after Radiorecurrence: Surgery - Back to the future?

Androgen Deprivation Therapy Is Associated With Prolongation of QTc Interval in Men With Prostate Cancer.

Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with increased cardiovascular mortality and sudden cardiac death, with some events occurring early after initiation of ADT. Testosterone levels are inversely associated with corrected QT (QTc) interval duration; therefore, prolongation of QTc duration could be responsible for some of these events during ADT.

Development and validation of a prostate cancer genomic signature that predicts early ADT treatment response following radical prostatectomy.

Currently no genomic signature exists to distinguish men most likely to progress on adjuvant androgen deprivation therapy (ADT) after radical prostatectomy (RP) for high risk prostate cancer. Here we develop and validate a gene expression signature to predict response to postoperative ADT.

Three-month posttreatment prostate-specific antigen level as a biomarker of treatment response in patients with intermediate-risk or high-risk prostate cancer treated with androgen deprivation therapy and radiotherapy.

Prostate-specific antigen (PSA) measurement after definitive radiotherapy (RT) and androgen deprivation therapy for localized prostate cancer has been proposed as an early prognostic biomarker. In the current study, the authors investigated the association between 3-month post-RT PSA level and biochemical progression-free survival (bPFS), prostate cancer-specific survival (PCSS), and overall survival (OS).

In Reply to Ong et al.

Liver Disease in Men Undergoing Androgen Deprivation Therapy for Prostate Cancer.

Androgen deprivation therapy is associated with development of diabetes and metabolic syndrome. Its effect on developing non-alcoholic fatty liver disease, a condition frequently co-occuring with metabolic syndrome, and other subsequent liver conditions (liver cirrhosis, hepatic necrosis, any liver disease) has not been investigated.
 MATERIALS & METHODS: We identified 82,938 men aged 66 and older diagnosed with localized prostate cancer within the Surveillance, Epidemiology and End Results- Medicare database, 1992-2009. Men with pre-existing non-alcoholic fatty liver disease, liver disease, diabetes, and metabolic syndrome were excluded. Propensity score adjusted Competing-risk regression models compared the risk of non-alcoholic fatty liver disease between men who received androgen deprivation with those who did not. We also explored the influence of cumulative exposure to androgen deprivation therapy, calculated as monthly equivalent doses of gonadotropin-releasing hormone agonists/antagonists (<7, 7- 11, >11 doses).
 RESULTS: Overall, 37.5% of men received androgen deprivation therapy. These were more likely to be diagnosed with non-alcoholic fatty liver disease (hazard ratio [HR] 1.54, 95 % confidence interval [CI] 1.40-1.68), liver cirrhosis (HR 1.35, 95 % CI 1.12 -1.60), liver necrosis (HR 1.41, 95% CI 1.15-1.72) and any liver disease (HR 1.47, 95% CI 1.35-1.60). A dose-response relationship was observed between the number of doses of androgen deprivation therapy, non-alcoholic fatty liver disease and any liver disease.

Increased Vulnerability to Poorer Cancer-Specific Outcomes Following Recent Divorce.

Prior studies have only considered the association between static marital status and cancer-specific outcomes. We aim to measure the effect of recent divorce on cancer-specific outcomes.

Impact of Health Insurance Status on Prostate Cancer Treatment Modality Selection in the United States.

A variety of treatment modalities are available for the management of clinically localized prostate cancer in the United States. In addition to clinical factors, treatment modality choice may be influenced by a patient's insurance status. Using a national data set, we investigated the relationship between insurance status and prostate cancer treatment modality selection among nonelderly men in the United States.

Radical Prostatectomy, External Beam Radiotherapy, or External Beam Radiotherapy With Brachytherapy Boost and Disease Progression and Mortality in Patients With Gleason Score 9-10 Prostate Cancer.

The optimal treatment for Gleason score 9-10 prostate cancer is unknown.

Patient-Reported Sexual Aid Utilization and Efficacy After Radiation Therapy for Localized Prostate Cancer.

To report sexual health-related quality of life outcomes and utilization and efficacy of sexual aids in a contemporary cohort of patients treated for localized prostate cancer.

Clinical and Genomic Characterization of Low-Prostate-specific Antigen, High-grade Prostate Cancer.

The consequences of low prostate-specific antigen (PSA) in high-grade (Gleason 8-10) prostate cancer are unknown.

Laboratory Eligibility Criteria as Potential Barriers to Participation by Black Men in Prostate Cancer Clinical Trials.

Reply to Christian D. Fankhauser, Nico C. Grossmann, Joerg Beyer, and Thomas Hermanns' Letter to the Editor re: Sophia C. Kamran, Thomas Seisen, Sarah C. Markt, et al. Contemporary Treatment Patterns and Outcomes for Clinical Stage IS Testicular Cancer. Eur Urol 2018;73:262-70.

Association of Androgen Deprivation Therapy and Thromboembolic Events: A Systematic Review and Meta-analysis.

To investigate the association of androgen deprivation therapy (ADT) for prostate cancer with thromboembolic events.

Focal MRI-Guided Salvage High-Dose-Rate Brachytherapy in Patients With Radiorecurrent Prostate Cancer.

Whole-gland salvage treatment of radiorecurrent prostate cancer has a high rate of severe toxicity. The standard of care in case of a biochemical recurrence is androgen deprivation treatment, which is associated with morbidity and negative effects on quality of life. A salvage treatment with acceptable toxicity might postpone the start of androgen deprivation treatment, might have a positive influence on the patients' quality of life, and might even be curative. Here, toxicity and biochemical outcome are described after magnetic resonance imaging-guided focal salvage high-dose-rate brachytherapy in patients with radiorecurrent prostate cancer.

The Development of Brain Metastases in Patients with Renal Cell Carcinoma: Epidemiologic Trends, Survival, and Clinical Risk Factors Using a Population-based Cohort.

The incidence of brain metastases (BM) in patients with renal cell carcinoma (RCC) is hypothesized to have increased in the last 2 decades.

Contemporary Incidence and Outcomes of Prostate Cancer Lymph Node Metastases.

The incidence of localized prostate cancer has decreased with shifts in prostate cancer screening. While recent population based studies demonstrated a stable incidence of locoregional prostate cancer, they categorized organ confined, extraprostatic and lymph node positive disease together. However, to our knowledge the contemporary incidence of prostate cancer with pelvic lymph node metastases remains unknown.

Brachytherapy monotherapy may be sufficient for a subset of patients with unfavorable intermediate risk prostate cancer.

Brachytherapy (BT) monotherapy is a well-established treatment modality for favorable intermediate risk (FIR) prostate cancer. However, patients with unfavorable intermediate risk (UIR) disease are often recommended trimodality therapy involving BT, androgen deprivation therapy (ADT), and external beam radiation therapy (EBRT). We sought to investigate the relative benefit of supplemental therapies (ADT and/or EBRT) for FIR and UIR prostate cancer in a large dataset.

Lack of Apparent Survival Benefit With Use of Androgen Deprivation Therapy in Patients With High-risk Prostate Cancer Receiving Combined External Beam Radiation Therapy and Brachytherapy.

Although level 1 evidence has demonstrated a survival benefit from the addition of androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) for patients with high-risk prostate cancer, the benefits of ADT with combined EBRT and brachytherapy for high-risk patients are unclear. We examined the association between ADT and overall survival in a national cohort of high-risk patients treated with EBRT with or without brachytherapy.

Optimizing androgen deprivation therapy with radiation therapy for aggressive localized and locally advanced prostate cancer.

Radiation therapy with androgen deprivation therapy (ADT) has historically been one of the mainstays of treatment for intermediate- and high-risk prostate cancer. The benefit of ADT likely derives from both enhancing local control and inhibiting micrometastatic disease. While level 1 evidence has demonstrated the benefits of 4-6 months of ADT for all men with intermediate-risk disease, further stratification of intermediate-risk prostate cancer into favorable and unfavorable subgroups indicates that ADT may not be necessary for favorable intermediate-risk disease but likely still provides a survival advantage for unfavorable intermediate-risk disease, even in the dose escalation era. Long-course ADT, consisting of 2-3 years of treatment, is the standard of care for high-risk prostate cancer managed with RT based on phase III trials. However, emerging data from a randomized trial raises the possibility that 18 months of ADT could be sufficient for select high-risk patients. The desire to minimize exposure to ADT lies in its many adverse effects, including the potential for cardiovascular harm in certain patients with significant coexisting comorbidity, possibly increased risk for neurocognitive and psychiatric events, and the well-documented metabolic changes. Providers need to carefully weigh these potential risks with the known survival benefits of ADT in aggressive localized and locally advanced prostate cancer.

Performance of a Prostate Cancer Genomic Classifier in Predicting Metastasis in Men with Prostate-specific Antigen Persistence Postprostatectomy.

Prostate cancer patients who have a detectable prostate-specific antigen (PSA) postprostatectomy may harbor pre-existing metastatic disease. To our knowledge, none of the commercially available genomic biomarkers have been investigated in such men.

Travel distance and stereotactic body radiotherapy for localized prostate cancer.

Definitive stereotactic body radiotherapy (SBRT) represents an emerging and debated treatment option for patients with prostate cancer, with potential economic savings and reports of short-term efficacy since 2006. The current study sought to define national trends in definitive prostate SBRT use and determine whether patterns vary by travel distance for treatment.

Pathologic Outcomes of Gleason 6 Favorable Intermediate-Risk Prostate Cancer Treated With Radical Prostatectomy: Implications for Active Surveillance.

The safety of active surveillance (AS) for Gleason 6 favorable intermediate-risk (FIR) prostate cancer is unknown. To provide guidance, we examined the incidence and predictors of upgrading or upstaging for Gleason 6 FIR patients treated with radical prostatectomy.

Development and Validation of a Novel Integrated Clinical-Genomic Risk Group Classification for Localized Prostate Cancer.

Purpose It is clinically challenging to integrate genomic-classifier results that report a numeric risk of recurrence into treatment recommendations for localized prostate cancer, which are founded in the framework of risk groups. We aimed to develop a novel clinical-genomic risk grouping system that can readily be incorporated into treatment guidelines for localized prostate cancer. Materials and Methods Two multicenter cohorts (n = 991) were used for training and validation of the clinical-genomic risk groups, and two additional cohorts (n = 5,937) were used for reclassification analyses. Competing risks analysis was used to estimate the risk of distant metastasis. Time-dependent c-indices were constructed to compare clinicopathologic risk models with the clinical-genomic risk groups. Results With a median follow-up of 8 years for patients in the training cohort, 10-year distant metastasis rates for National Comprehensive Cancer Network (NCCN) low, favorable-intermediate, unfavorable-intermediate, and high-risk were 7.3%, 9.2%, 38.0%, and 39.5%, respectively. In contrast, the three-tier clinical-genomic risk groups had 10-year distant metastasis rates of 3.5%, 29.4%, and 54.6%, for low-, intermediate-, and high-risk, respectively, which were consistent in the validation cohort (0%, 25.9%, and 55.2%, respectively). C-indices for the clinical-genomic risk grouping system (0.84; 95% CI, 0.61 to 0.93) were improved over NCCN (0.73; 95% CI, 0.60 to 0.86) and Cancer of the Prostate Risk Assessment (0.74; 95% CI, 0.65 to 0.84), and 30% of patients using NCCN low/intermediate/high would be reclassified by the new three-tier system and 67% of patients would be reclassified from NCCN six-tier (very-low- to very-high-risk) by the new six-tier system. Conclusion A commercially available genomic classifier in combination with standard clinicopathologic variables can generate a simple-to-use clinical-genomic risk grouping that more accurately identifies patients at low, intermediate, and high risk for metastasis and can be easily incorporated into current guidelines to better risk-stratify patients.

ACR Appropriateness Criteria for external beam radiation therapy treatment planning for clinically localized prostate cancer, part II of II.

To present the most updated American College of Radiology (ACR) Appropriateness Criteria formed by an expert panel on the appropriate delivery of external beam radiation to manage stage T1 and T2 prostate cancer (in the definitive setting and post-prostatectomy) and to provide clinical variants with expert recommendations based on accompanying Appropriateness Criteria for target volumes and treatment planning.

Reply to Aditya Bagrodia, Solomon Woldu, David F. Penson, Alexander Kutikov, and Samuel D. Kaffenberger's Letter to the Editor re: Sophia C. Kamran, Thomas Seisen, Sarah C. Markt, et al. Contemporary Treatment Patterns and Outcomes for Clinical Stage IS Testicular Cancer. Eur Urol 2018;73:262-70.

Approach to the Patient with High-Risk Prostate Cancer.

Men classified as having high-risk prostate cancer warrant treatment because durable outcomes can be achieved. Judicious use of imaging and considerations of risk factors are essential when caring for men with high-risk disease. Radical prostatectomy, radiation therapy, and androgen deprivation therapy all play pivotal roles in the management of men with high-risk disease, and potentially in men with metastatic disease. The optimal combinations of therapeutic regimens are an evolving area of study and future work looking into therapies for men with high-risk disease will remain critical.

Prostate cancer outcomes for men aged younger than 65 years with Medicaid versus private insurance.

In the current national debate regarding private insurance versus Medicaid expansion, understanding how insurance is associated with racial disparities in prostate cancer (CaP) outcomes has broad policy implications. In the current study, the authors examined the association between insurance status, race, and CaP outcomes.

Lack of Benefit From the Addition of External Beam Radiation Therapy to Brachytherapy for Intermediate- and High-risk Prostate Cancer.

A recent randomized controlled trial demonstrated that the addition of external beam radiation therapy (EBRT) to brachytherapy did not improve progression-free survival in select patients with intermediate-risk prostate cancer. We evaluated whether the addition of EBRT to brachytherapy improves prostate cancer-specific mortality (PCSM) for intermediate- and high-risk disease using a large national database.

Travel Distance as a Barrier to Receipt of Adjuvant Radiation Therapy After Radical Prostatectomy.

Following radical prostatectomy (RP), adjuvant radiation therapy (RT) decreases biochemical recurrence and potentially improves metastasis-free and overall survival for patients with high-risk pathologic features. Since adjuvant RT typically occurs daily over several weeks, the logistical challenges of extensive traveling may be a significant barrier to its use. We examined the association between distance to treatment facility and use of adjuvant RT.