Publications by authors named "Brent S Rose"

75 Publications

Racial and Ethnic Disparities in Prostate Cancer Outcomes in the Veterans Affairs Health Care System.

JAMA Netw Open 2022 Jan 4;5(1):e2144027. Epub 2022 Jan 4.

David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles.

Importance: Prostate cancer (PCa) disproportionately affects African American men, but research evaluating the extent of racial and ethnic disparities across the PCa continuum in equal-access settings remains limited at the national level. The US Department of Veterans Affairs (VA) Veterans Hospital Administration health care system offers a setting of relatively equal access to care in which to assess racial and ethnic disparities in self-identified African American (or Black) veterans and White veterans.

Objective: To determine the extent of racial and ethnic disparities in the incidence of PCa, clinical stage, and outcomes between African American patients and White patients who received a diagnosis or were treated at a VA hospital.

Design, Setting, And Participants: This retrospective cohort study included 7 889 984 veterans undergoing routine care in VA hospitals nationwide from 2005 through 2019 (incidence cohort). The age-adjusted incidence of localized and de novo metastatic PCa was estimated. Treatment response was evaluated, and PCa-specific outcomes were compared between African American veterans and White veterans. Residual disparity in PCa outcome, defined as the leftover racial and ethnic disparity in the outcomes despite equal response to treatment, was estimated.

Exposures: Self-identified African American (or Black) and White race and ethnicity.

Main Outcomes And Measures: Time to distant metastasis following PCa diagnosis was the primary outcome. Descriptive analyses were used to compare baseline demographics and clinic characteristics. Multivariable logistic regression was used to evaluate race and ethnicity association with pretreatment clinical variables. Multivariable Cox regression was used to estimate the risk of metastasis.

Results: Data from 7 889 984 veterans from the incidence cohort were used to estimate incidence, whereas data from 92 269 veterans with localized PCa were used to assess treatment response. Among 92 269 veterans, African American men (n = 28 802 [31%]) were younger (median [IQR], 63 [58-68] vs 65 [62-71] years) and had higher prostate-specific antigen levels (>20 ng/mL) at the time of diagnosis compared with White men (n = 63 467; [69%]). Consistent with US population-level data, African American veterans displayed a nearly 2-fold greater incidence of localized and de novo metastatic PCa compared with White men across VA centers nationwide. Among veterans screened for PCa, African American men had a 29% increased risk of PCa detection on a diagnostic prostate biopsy compared with White (hazard ratio, 1.29; 95% CI, 1.27-1.31; P < .001). African American men who received definitive primary treatment of PCa experienced a lower risk of metastasis (hazard ratio, 0.89; 95% CI, 0.83-0.95; P < .001). However, African American men who were classified as "other" race and received treatment were more likely to develop metastasis (adjusted hazard ratio, 1.29; 95% CI, 1.17-1.42; P < .001). Using the actual rate of metastasis from veterans who received definitive primary treatment, a persistent residual metastatic burden for African American men was observed across all National Comprehensive Cancer Network risk groups (low risk, 4 vs 2 per 100 000; intermediate risk, 13 vs 6 per 100 000; high risk, 19 vs 9 per 100 000).

Conclusions And Relevance: This cohort analysis found significant disparities in the incidence of localized and metastatic PCa between African American veterans and White veterans. This increased incidence is a major factor associated with the residual disparity in PCa metastasis observed in African American veterans compared with White veterans despite their nearly equal response to treatment.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.44027DOI Listing
January 2022

Association of Healthcare System and Survival in African American and Non-Hispanic White Patients with Bladder Cancer.

J Natl Cancer Inst 2021 Dec 16. Epub 2021 Dec 16.

Veterans Affairs San Diego Healthcare System, San Diego, 92161, CA, USA.

Background: African American patients with bladder cancer have inferior outcomes compared to non-Hispanic White (White) patients. We hypothesize that access to health care is a primary determinant of this disparity. We compared outcomes by race for patients with bladder cancer receiving care within the predominant hybrid-payer healthcare model of the United States captured in the Surveillance, Epidemiology, and End Results (SEER) database to those receiving care within the equal-access model of the Veterans' Health Administration (VHA).

Methods: African American and White patients diagnosed with bladder cancer were identified in SEER and VHA. Stage at presentation, bladder cancer-specific mortality (BCM), and overall survival (OS) were compared by race within each healthcare system.

Results: SEER cohort included 122,449 patients (93.7% White, 6.3% African American). VHA cohort included 36,322 patients (91.0% White, 9.0% African American). In both cohorts, African American patients were more likely to present with muscle-invasive disease and metastases but the differences between races were statistically significantly smaller in VHA. In SEER multivariable models, African American patients had worse BCM (hazard ratio [HR] = 1.22, 95% confidence interval [CI] = 1.15-1.29) and OS (HR = 1.26, 95% CI = 1.20-1.31). In contrast within VHA, African American patients had similar BCM (HR = 0.97, 95% CI = 0.88-1.07) and OS (HR = 0.99, 95% CI = 0.93-1.05).

Conclusion: In this study of contrasting healthcare models, receiving medical care in an equal-access system was associated with reduced differences in stage at presentation and eliminated disparities in survival outcomes for African American patients with bladder cancer. Our findings highlight the importance of reducing financial barriers to care to notably improve health equity and oncologic outcomes for African American patients.
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http://dx.doi.org/10.1093/jnci/djab219DOI Listing
December 2021

Evaluating Prostate-Specific Antigen Screening for Young African American Men with Cancer.

J Natl Cancer Inst 2021 Dec 10. Epub 2021 Dec 10.

VA San Diego Health Care System, La Jolla, CA, United States.

Background: Despite higher risks associated with prostate cancer, young African American men are poorly represented in prostate-specific antigen (PSA) trials, which limits proper evidence-based guidance. We evaluated the impact of PSA screening, alongside primary care provider utilization, on prostate cancer outcomes for these patients.

Methods: We identified African American men aged 40-55, diagnosed with prostate cancer between 2004-2017 within the Veterans Health Administration. Inverse probability of treatment weighted propensity scores were utilized in multivariable models to assess PSA screening on PSA > 20, Gleason score ≥ 8, and metastatic disease at diagnosis. Lead-time adjusted Fine-Gray regression evaluated PSA screening on PCSM, with non-cancer death as competing events. All statistical tests were 2-sided.

Results: The cohort included 4,726 patients. Mean age was 51.8 years, with 84-month median follow-up. There were 1,057 (22.4%) with no PSA screening prior to diagnosis. Compared to no screening, PSA screening was associated with statistically significantly reduced odds of PSA > 20 (odds ratio [OR] = 0.56, 95% confidence interval [CI] = 0.49-0.63, P < .001), Gleason score ≥ 8 (OR = 0.78, 95% CI = 0.69-0.88, P < .001), and metastatic disease at diagnosis (OR = 0.50, 95% CI = 0.39-0.64, P < .001), and decreased PCSM (subdistribution hazard ratio = 0.52, 95% CI = 0.36-0.76, P < .001). Primary care provider visits displayed similar effects.

Conclusions: Among young African American men diagnosed with prostate cancer, PSA screening was associated with statistically significantly lower risk of PSA > 20, Gleason score ≥ 8, and metastatic disease at diagnosis and statistically significantly reduced risk of PCSM. However, the retrospective design limits precise estimation of screening effects. Prospective studies are needed to validate these findings.
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http://dx.doi.org/10.1093/jnci/djab221DOI Listing
December 2021

Androgen deprivation therapy and acute kidney injury in patients with prostate cancer undergoing definitive radiotherapy.

Prostate Cancer Prostatic Dis 2021 Nov 22. Epub 2021 Nov 22.

Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA.

Background: Androgen deprivation therapy (ADT) is frequently utilized in conjunction with radiotherapy (RT) in the definitive management of prostate cancer. Prior studies have suggested an association between ADT use and acute kidney injury (AKI), however, these included heterogeneous populations undergoing a variety of treatments and relied on billing codes to ascertain the incidence of AKI.

Methods: We analyzed a cohort of 27,868 veterans undergoing definitive RT + /- ADT for prostate cancer between 2001 and 2015 using the Veterans Affairs Informatics and Computing Infrastructure (VINCI). Exposure was defined as use of ADT within one year of diagnosis. The primary outcome was AKI, defined by an increase in serum creatinine to at least 1.5 times the baseline value. AKIs were classified as mild, moderate, or severe in accordance with international guidelines. A multivariate competing risks model was used to account for demographic and oncologic factors as well as medications and procedures known to influence the risk of AKI.

Results: Most (n = 18,754) men received RT alone; 9,114 men received RT + ADT. The incidence of AKI at two years after diagnosis was 10.5% in the RT + ADT group and 7.9% in the RT group (Gray's test p < 0.01). Multivariate analysis confirmed ADT usage was associated with an increased risk for any AKI (SHR = 1.24, 95% CI = 1.14-1.36, p < 0.01). ADT was also associated with an increased risk of mild AKI (SHR = 1.13, 95% CI = 1.01-1.27, p = 0.04) and moderate AKI (SHR = 1.45, 95% CI = 1.20-1.76, p < 0.01), though not severe AKI (SHR = 1.33, 95% CI = 0.93-1.91, p = 0.11).

Conclusions: Our findings confirm that use of ADT is associated with an increased risk of AKI in patients undergoing definitive RT for prostate cancer. Clinicians should be alert to the potential for renal dysfunction in this population.
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http://dx.doi.org/10.1038/s41391-021-00415-3DOI Listing
November 2021

Disparities and trends in the participation of minorities, women, and the elderly in breast, colorectal, lung, and prostate cancer clinical trials.

Cancer 2021 Nov 22. Epub 2021 Nov 22.

Department of Urology, University of California San Diego School of Medicine, La Jolla, California.

Background: This study was done to determine the representation of minorities, women, and the elderly in National Cancer Institute (NCI) clinical trials.

Methods: This is an analysis in the NCI Clinical Data Update System. Patients were evaluated in breast, colorectal, lung, and prostate cancer trials from 2000 to 2019. Representation in a trial was determined by race/ethnicity, sex, and age. Secondarily, the change in trial participation by multivariable analysis by comparing years 2000 through 2004 to 2015 through 2019 was evaluated.

Results: The cohort included 242,720 participants: 197,320 Non-Hispanic White (81.3%), 21,190 Black (8.7%), 11,587 Hispanic (4.8%), and 6880 Asian/Pacific Islander (2.8%). Black and Hispanic patients were underrepresented for colorectal (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.50-0.67; P < .001 and OR, 0.74; 95% CI, 0.64-0.87; P < .001, respectively), lung (OR, 0.83; 95% CI, 0.76-0.91; P < .001 and 0.66; 95% CI, 0.57-0.77; P < .001, respectively), and prostate cancer trials (OR, 0.85; 95% CI, 0.79-0.92; P < .001 and OR, 0.58; 95% CI, 0.51-0.66; P < .001) between 2015 and 2019. The odds of participation in 2015 to 2019 increased among Black patients in breast (OR, 2.19; 95% CI, 2.07-%2.32; P < .001), lung (OR, 1.54; 95% CI, 1.38-1.73; P < .001), and prostate cancer trials (OR, 1.14; 95% CI, 1.04-1.26; P < .001). The odds of participation in a trial among Hispanic patients increased for breast (OR, 3.32; 95% CI, 3.09-3.56; P < .001), colorectal (OR, 2.46; 95% CI, 2.04-2.96; P < .001), lung (OR, 3.88; 95% CI, 3.20-4.69; P < .001), and prostate cancer (OR, 1.70; 95% CI, 1.42-2.04; P = .005).

Conclusions: This study identified that Black and Hispanic patients remain underrepresented in trials, but in recent years, participation has increased. These findings indicate that minority participation has increased over time, but further efforts are needed.
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http://dx.doi.org/10.1002/cncr.33991DOI Listing
November 2021

Prognostic Utility of Pretreatment Neutrophil-Lymphocyte Ratio in Advanced Larynx Cancer.

Biomark Insights 2021 11;16:11772719211049848. Epub 2021 Oct 11.

Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.

Purpose: Neutrophil-lymphocyte ratio has been explored as a prognosticator in several cancer types, but its association with larynx cancer outcomes is not well known. We aimed to identify an optimal NLR cutoff point and examine the prognostic utility of this biomarker in patients with locoregionally advanced larynx cancer treated with curative intent.

Methods: In the Veterans Affairs' (VA) national database, we identified patients with locoregionally advanced (T3-4N0-3M0) laryngeal squamous cell carcinoma diagnosed between 2000 and 2017 and treated with curative intent. NLR cutoff points were calculated using Contal/O'Quigley's method. Outcomes of larynx cancer-specific survival (CSS), overall survival (OS), and non-larynx cancer survival (NCS) were evaluated in multivariable Cox and Fine-Gray models.

Results: In 1047 patients, the optimal pretreatment NLR cutoff was identified as 4.17 - 722 patients with NLR ⩽ 4.17, 325 patients with NLR > 4.17. The elevated NLR cohort had a higher proportion of T4 disease (39.4% vs 28.4%), node positive disease (52.3% vs 43.1%), and surgical treatment (43.7% vs 35.2%). In multivariable analysis, NLR > 4.17 was independently associated with worse OS (HR 1.31, 95% CI 1.12-1.54,  = .001) and worse CSS (HR 1.46, 95% CI 1.17-1.83,  < .001), but not with NCS (HR 0.94, 95% CI 0.75-1.18,  = .58).

Conclusion: In locoregionally advanced larynx cancer treated with curative intent, we identified elevated NLR to be associated with inferior OS and CSS. Further prospective studies are needed to investigate pretreatment NLR and our identified 4.17 cutoff as a potential larynx cancer-specific marker for this high risk population.
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http://dx.doi.org/10.1177/11772719211049848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512256PMC
October 2021

Ascertainment of Veterans With Metastatic Prostate Cancer in Electronic Health Records: Demonstrating the Case for Natural Language Processing.

JCO Clin Cancer Inform 2021 09;5:1005-1014

VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT.

Purpose: Prostate cancer (PCa) is among the leading causes of cancer deaths. While localized PCa has a 5-year survival rate approaching 100%, this rate drops to 31% for metastatic prostate cancer (mPCa). Thus, timely identification of mPCa is a crucial step toward measuring and improving access to innovations that reduce PCa mortality. Yet, methods to identify patients diagnosed with mPCa remain elusive. Cancer registries provide detailed data at diagnosis but are not updated throughout treatment. This study reports on the development and validation of a natural language processing (NLP) algorithm deployed on oncology, urology, and radiology clinical notes to identify patients with a diagnosis or history of mPCa in the Department of Veterans Affairs.

Patients And Methods: Using a broad set of diagnosis and histology codes, the Veterans Affairs Corporate Data Warehouse was queried to identify all Veterans with PCa. An NLP algorithm was developed to identify patients with any history or progression of mPCa. The NLP algorithm was prototyped and developed iteratively using patient notes, grouped into development, training, and validation subsets.

Results: A total of 1,144,610 Veterans were diagnosed with PCa between January 2000 and October 2020, among which 76,082 (6.6%) were identified by NLP as having mPCa at some point during their care. The NLP system performed with a specificity of 0.979 and sensitivity of 0.919.

Conclusion: Clinical documentation of mPCa is highly reliable. NLP can be leveraged to improve PCa data. When compared to other methods, NLP identified a significantly greater number of patients. NLP can be used to augment cancer registry data, facilitate research inquiries, and identify patients who may benefit from innovations in mPCa treatment.
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http://dx.doi.org/10.1200/CCI.21.00030DOI Listing
September 2021

Evaluating the clinical trends and benefits of low-dose computed tomography in lung cancer patients.

Cancer Med 2021 10 16;10(20):7289-7297. Epub 2021 Sep 16.

Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California, USA.

Background: Despite guideline recommendations, utilization of low-dose computed tomography (LDCT) for lung cancer screening remains low. The driving factors behind these low rates and the real-world effect of LDCT utilization on lung cancer outcomes remain limited.

Methods: We identified patients diagnosed with non-small cell lung cancer (NSCLC) from 2015 to 2017 within the Veterans Health Administration. Multivariable logistic regression assessed the influence of LDCT screening on stage at diagnosis. Lead time correction using published LDCT lead times was performed. Cancer-specific mortality (CSM) was evaluated using Fine-Gray regression with non-cancer death as a competing risk. A lasso machine learning model identified important predictors for receiving LDCT screening.

Results: Among 4664 patients, mean age was 67.8 with 58-month median follow-up, 95% CI = [7-71], and 118 patients received ≥1 screening LDCT before NSCLC diagnosis. From 2015 to 2017, LDCT screening increased (0.1%-6.6%, mean = 1.3%). Compared with no screening, patients with ≥1 LDCT were more than twice as likely to present with stage I disease at diagnosis (odds ratio [OR] 2.16 [95% CI 1.46-3.20]) and less than half as likely to present with stage IV (OR 0.38 [CI 0.21-0.70]). Screened patients had lower risk of CSM even after adjusting for LDCT lead time (subdistribution hazard ratio 0.60 [CI 0.42-0.85]). The machine learning model achieved an area under curve of 0.87 and identified diagnosis year and region as the most important predictors for receiving LDCT. White, non-Hispanic patients were more likely to receive LDCT screening, whereas minority, older, female, and unemployed patients were less likely.

Conclusions: Utilization of LDCT screening is increasing, although remains low. Consistent with randomized data, LDCT-screened patients were diagnosed at earlier stages and had lower CSM. LDCT availability appeared to be the main predictor of utilization. Providing access to more patients, including those in diverse racial and socioeconomic groups, should be a priority.
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http://dx.doi.org/10.1002/cam4.4229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525167PMC
October 2021

Active surveillance for intermediate-risk prostate cancer in African American and non-Hispanic White men.

Cancer 2021 Dec 4;127(23):4403-4412. Epub 2021 Aug 4.

Veterans Health Administration San Diego Health Care System, La Jolla, California.

Background: The safety of active surveillance (AS) for African American men compared with non-Hispanic White (White) men with intermediate-risk prostate cancer is unclear.

Methods: The authors identified patients with modified National Comprehensive Cancer Network favorable ("low-intermediate") and unfavorable ("high-intermediate") intermediate-risk prostate cancer diagnosed between 2001 and 2015 and initially managed with AS in the Veterans Health Administration database. They analyzed definitive treatment, disease progression, metastases, prostate cancer-specific mortality (PCSM), and all-cause mortality by using cumulative incidences and multivariable competing-risks (disease progression, metastasis, and PCSM) or Cox (all-cause mortality) regression.

Results: The cohort included 1007 men (African Americans, 330 [32.8%]; Whites, 677 [67.2%]) followed for a median of 7.7 years; 773 (76.8%) had low-intermediate-risk disease, and 234 (23.2%) had high-intermediate-risk disease. The 10-year cumulative incidences of definitive treatment were not significantly different (African Americans, 83.5%; 95% confidence interval [CI], 78.5%-88.7%; Whites, 80.6%; 95% CI, 76.6%-84.4%; P = .17). Among those with low-intermediate-risk disease, there were no significant differences in the 10-year cumulative incidences of disease progression (African Americans, 46.8%; 95% CI, 40.0%-53.3%; Whites, 46.9%; 95% CI, 42.1%-51.5%; P = .91), metastasis (African Americans, 7.1%; 95% CI, 3.7%-11.8%; Whites, 10.8%; 95% CI, 7.6%-14.6%; P = .17), or PCSM (African Americans, 3.8%; 95% CI, 1.6%-7.5%; Whites, 3.8%; 95% CI, 2.0%-6.3%; P = .69). In a multivariable regression including the entire cohort, African American race was not associated with increased risks of definitive treatment, disease progression, metastasis, PCSM, or all-cause mortality (all P > .30).

Conclusions: Outcomes in the Veterans Affairs Health System were similar for African American and White men treated for low-intermediate-risk prostate cancer with AS.
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http://dx.doi.org/10.1002/cncr.33824DOI Listing
December 2021

Outcomes for Muscle-invasive Bladder Cancer with Radical Cystectomy or Trimodal Therapy in US Veterans.

Eur Urol Open Sci 2021 Aug 9;30:1-10. Epub 2021 Jun 9.

Division of Hematology-Oncology, Department of Internal Medicine, University of California San Diego, La Jolla, CA, USA.

Background: Muscle-invasive bladder cancer (MIBC) remains undertreated despite multiple potentially curative options. Both radical cystectomy (RC) with or without neoadjuvant chemotherapy and trimodal therapy (TMT), including transurethral resection of bladder tumor followed by chemoradiotherapy, are standard treatments.

Objective: To evaluate real-world clinical outcomes of RC with neoadjuvant chemotherapy (RC-NAC), RC without NAC, TMT with National Comprehensive Cancer Network guideline-preferred radiosensitizing chemotherapy including cisplatin or mitomycin-C and 5-fluorouracil (pTMT), and TMT with nonpreferred chemotherapy (npTMT).

Design Setting And Participants: US veterans with nonmetastatic MIBC (T2-4aN0-3M0) were studied.

Outcome Measurements And Statistical Analysis: Overall mortality (OM) was evaluated with multivariable Cox proportional hazard model. Bladder cancer-specific mortality (BCSM) was evaluated with multivariable Fine-Gray regression. Salvage cystectomy rates were obtained by chart review.

Results And Limitations: Overall 2306 patients were included: 1472 (64%) with RC without NAC, 506 (22%) with RC-NAC, 163 (7%) with pTMT, and 165 (7%) with npTMT. On multivariable analysis, pTMT was associated with similar OM (hazard ratio [HR] 1.19; 95% confidence interval [CI] 0.94-1.50;  = 0.15) and BCSM (HR 1.34; 95% CI 0.99-1.83;  = 0.06) to RC-NAC; npTMT was associated with worse OM (HR 1.30; 95% CI 1.04-1.61;  = 0.02) and BCSM (HR 1.45; 95% CI 1.09-1.94;  = 0.01). RC without NAC was associated with similar OM (HR 1.08; 95% CI 0.95-1.24;  = 0.24) and BCSM (HR 1.02; 95% CI 0.86-1.21;  = 0.79). When stratified by age, among patients ≥65 yr of age, treatment with pTMT was associated with similar OM (HR 1.14; 95% CI 0.87-1.50;  = 0.35) and BCSM (HR 1.11; 95% CI 0.76-1.62;  = 0.60). Among patients <65 yr of age, pTMT was associated with worse OM (HR 1.82; 95% CI 1.14-2.91;  = 0.01) and BCSM (HR 2.51; 95% CI 1.52-4.13;  < 0.01). The 5-yr cumulative incidence of salvage cystectomy in the TMT group was 3.6%.

Conclusions: In MIBC, patients receiving pTMT have comparable survival in RC-NAC patients ≥65 yr and inferior survival in RC-NAC patients <65 yr. Salvage cystectomy rates were low.

Patient Summary: Management of muscle-invasive bladder cancer is a multidisciplinary effort requiring thoughtful discussions with patients about treatment options, including trimodal therapy, which is an effective treatment option.
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http://dx.doi.org/10.1016/j.euros.2021.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317783PMC
August 2021

Performance of African-ancestry-specific polygenic hazard score varies according to local ancestry in 8q24.

Prostate Cancer Prostatic Dis 2021 Jun 14. Epub 2021 Jun 14.

School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, USA.

Background: We previously developed an African-ancestry-specific polygenic hazard score (PHS46+African) that substantially improved prostate cancer risk stratification in men with African ancestry. The model consists of 46 SNPs identified in Europeans and 3 SNPs from 8q24 shown to improve model performance in Africans. Herein, we used principal component (PC) analysis to uncover subpopulations of men with African ancestry for whom the utility of PHS46+African may differ.

Materials And Methods: Genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Genetic variation in a window spanning 3 African-specific 8q24 SNPs was estimated using 93 PCs. A Cox proportional hazards framework was used to identify the pair of PCs most strongly associated with the performance of PHS46+African. A calibration factor (CF) was formulated using Cox coefficients to quantify the extent to which the performance of PHS46+African varies with PC.

Results: CF of PHS46+African was strongly associated with the first and twentieth PCs. Predicted CF ranged from 0.41 to 2.94, suggesting that PHS46+African may be up to 7 times more beneficial to some African men than others. The explained relative risk for PHS46+African varied from 3.6% to 9.9% for individuals with low and high CF values, respectively. By cross-referencing our data set with 1000 Genomes, we identified significant associations between continental and calibration groupings.

Conclusion: We identified PCs within 8q24 that were strongly associated with the performance of PHS46+African. Further research to improve the clinical utility of polygenic risk scores (or models) is needed to improve health outcomes for men of African ancestry.
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http://dx.doi.org/10.1038/s41391-021-00403-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669040PMC
June 2021

Association of Prostate-Specific Antigen Velocity With Clinical Progression Among African American and Non-Hispanic White Men Treated for Low-Risk Prostate Cancer With Active Surveillance.

JAMA Netw Open 2021 05 3;4(5):e219452. Epub 2021 May 3.

Department of Radiation Medicine and Applied Science, University of California, San Diego, School of Medicine, La Jolla.

Importance: The association of prostate-specific antigen velocity (PSAV) with clinical progression in patients with localized prostate cancer managed with active surveillance remains unclear and, to our knowledge, has not been studied in African American patients.

Objectives: To test the hypothesis that PSAV is associated with clinical progression in patients with low-risk prostate cancer treated with active surveillance and to identify differences between African American and non-Hispanic White patients.

Design, Setting, And Participants: This was a retrospective population-based cohort study using patient records from the Veterans Heath Administration Informatics and Computing Infrastructure on 5296 patients with a diagnosis of localized prostate cancer from January 1, 2001, to December 31, 2015, who were managed with active surveillance. Follow-up extended through March 31, 2020. Low-risk prostate cancer was defined as International Society of Urologic Pathology grade group (GG) 1 clinical tumor stage 2A or lower, PSA level of 10 ng/dL or lower, active surveillance, and no definitive treatment within the first year after diagnosis with at least 1 additional staging biopsy after diagnostic biopsy.

Exposures: Prostate-specific antigen testing.

Main Outcomes And Measures: The primary outcome was GG progression detected after repeated biopsy or prostatectomy, defined as GG2 or higher or GG3 or higher. The secondary outcome was incident metastases. Cumulative incidence functions and multivariable Cox proportional hazards regression models were used to test associations between PSAV and outcomes.

Results: The final cohort (n = 5296) included 3919 non-Hispanic White men (74.0%; mean [SD] age, 65.7 [5.8] years) and 1377 African American men (26.0%; mean [SD] age, 62.8 [6.6] years). Compared with African American patients, non-Hispanic White patients were older (mean [SD] age, 65.7 [5.8] years vs 62.8 [6.6] years; P < .001), presented with higher cT stage (stage T2, 608 [15.5%] vs 111 [8.1%]; P < .001), had a higher Charlson Comorbidity Index score (1 and ≥2, 912 [23.3%] vs 273 [19.8%]; P = .002), had higher median income ($60 000 to ≥$100 000, 1223 [31.2%] vs 282 [20.5%]; P < .001), and had a higher median level of education (20% to ≥30% with college degree, 1192 [30.4%] vs 333 [24.2%]; P < .001). Progression to GG2 or higher occurred in 2062 patients (38.9%), with a cumulative incidence of 43.2%, and progression to GG3 or higher occurred in 728 patients (13.7%). Fifty-four patients (1.0%) developed metastases. On multivariable analysis, PSAV was significantly associated with progression to GG2 (hazard ratio, 1.32 [95% CI, 1.26-1.39]), GG3 (hazard ratio, 1.51 [95% CI, 1.41-1.62]), and metastases (hazard ratio, 1.38 [95% CI, 1.10-1.74]). Optimal PSAV thresholds that were associated with progression were significantly lower for African American patients (0.44 ng/mL/y) compared with non-Hispanic White patients (1.18 ng/mL/y).

Conclusions And Relevance: This study suggests that PSAV is significantly associated with grade progression among patients with low-risk prostate cancer managed with active surveillance, but at lower values for African American patients compared with non-Hispanic White patients. These data suggest that serial PSA measures may potentially substitute for multiple prostate biopsies and that African American patients may merit increased frequency of PSA testing.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.9452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129822PMC
May 2021

Prognostic utility of pretreatment neutrophil-lymphocyte ratio in survival outcomes in localized non-small cell lung cancer patients treated with stereotactic body radiotherapy: Selection of an ideal clinical cutoff point.

Clin Transl Radiat Oncol 2021 May 7;28:133-140. Epub 2021 Apr 7.

Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA 92037, USA.

Background And Purpose: Neutrophil-lymphocyte ratio (NLR) has been associated with overall survival (OS) in non-small cell lung cancer (NSCLC). We aimed to assess the utility of NLR as a predictor of lung cancer-specific survival (LCS) and identify an optimal, pretreatment cutoff point in patients with localized NSCLC treated with stereotactic body radiotherapy (SBRT) within the Veterans Affairs' (VA) national database.

Materials And Methods: In the VA database, we identified patients with biopsy-proven, clinical stage I NSCLC treated with SBRT between 2006 and 2015. Cutoff points for NLR were calculated using Contal/O'Quigley's and Cox Wald methods. Primary outcomes of OS, LCS, and non-lung cancer survival (NCS) were evaluated in Cox and Fine-Gray models.

Results: In 389 patients, optimal NLR cutoff was identified as 4.0. In multivariable models, NLR > 4.0 was associated with decreased OS (HR 1.44, p = 0.01) and NCS (HR 1.68, p = 0.01) but not with LCS (HR 1.32, p = 0.09). In a subset analysis of 229 patients with pulmonary function tests, NLR > 4.0 remained associated with worse OS (HR 1.51, p = 0.02) and NCS (HR 2.18, p = 0.01) while the association with LCS decreased further (HR 1.22, p = 0.39).

Conclusion: NLR was associated with worse OS in patients with localized NSCLC treated with SBRT; however, NLR was only associated with NCS and not with LCS. Pretreatment NLR, with a cutoff of 4.0, offers potential as a marker of competing mortality risk which can aid in risk stratification in this typically frail and comorbid population. Further studies are needed to validate pretreatment NLR as a clinical tool in this setting.
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http://dx.doi.org/10.1016/j.ctro.2021.03.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089768PMC
May 2021

Association of Health-Care System With Prostate Cancer-Specific Mortality in African American and Non-Hispanic White Men.

J Natl Cancer Inst 2021 Oct;113(10):1343-1351

Department of Radiation Medicine and Applied Sciences, University of California San Diego School of Medicine, La Jolla, CA, USA.

Background: Disparities in prostate cancer-specific mortality (PCSM) between African American and non-Hispanic White (White) patients have been attributed to biological and systemic factors. We evaluated drivers of these disparities in the Surveillance, Epidemiology, and End Results (SEER) national registry and an equal-access system, the Veterans Health Administration (VHA).

Methods: We identified African American and White patients diagnosed with prostate cancer between 2004 and 2015 in SEER (n = 311 691) and the VHA (n = 90 749). We analyzed the association between race and metastatic disease at presentation using multivariable logistic regression adjusting for sociodemographic factors and PCSM using sequential competing-risks regression adjusting for disease and sociodemographic factors.

Results: The median follow-up was 5.3 years in SEER and 4.7 years in the VHA. African American men were more likely than White men to present with metastatic disease in SEER (adjusted odds ratio = 1.23, 95% confidence interval [CI] = 1.17 to 1.30) but not in the VHA (adjusted odds ratio = 1.07, 95% CI = 0.98 to 1.17). African American vs White race was associated with an increased risk of PCSM in SEER (subdistribution hazard ratio [SHR] = 1.32, 95% CI = 1.10 to 1.60) but not in the VHA (SHR = 1.00, 95% CI = 0.93 to 1.08). Adjusting for disease extent, prostate-specific antigen, and Gleason score eliminated the association between race and PCSM in SEER (aSHR = 1.04, 95% CI = 0.93 to 1.16).

Conclusions: Racial disparities in PCSM were present in a nationally representative registry but not in an equal-access health-care system, because of differences in advanced disease at presentation. Strategies to increase health-care access may bridge the racial disparity in outcomes. Longer follow-up is needed to fully assess mortality outcomes.
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http://dx.doi.org/10.1093/jnci/djab062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486332PMC
October 2021

Association of race and health care system with disease stage and survival in veterans with larynx cancer.

Cancer 2021 Aug 2;127(15):2705-2713. Epub 2021 Apr 2.

Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California San Diego, San Diego, California.

Background: Black patients with laryngeal squamous cell carcinoma (LSCC) historically have inferior outcomes in comparison with White patients. The authors investigated these racial disparities within the Veterans Health Administration (VHA), an equal-access system, and within the Surveillance, Epidemiology, and End Results (SEER) program, which is representative of the US hybrid-payer system.

Methods: Patients with invasive (T1 or greater) LSCC were included from SEER (2004-2015) and the VHA (2000-2017). The primary outcomes of overall survival (OS) and larynx cancer-specific survival (LCS) were evaluated in Cox and Fine-Gray models.

Results: In the SEER cohort (7122 patients: 82.6% White and 17.4% Black), Black patients were more likely to present with advanced disease and had inferior OS (hazard ratio [HR], 1.37; 95% CI, 1.26-1.50; P < .0001) in a multivariable analysis. Black LCS was worse in a univariable analysis (HR, 1.42; 95% CI, 1.27-1.58; P < .0001), but this effect was attenuated by 83% when the authors controlled for the TNM category and was found to be insignificant in a multivariable analysis (HR, 1.05; 95% CI, 0.93-1.18; P = .42). In the VHA cohort (9248 patients: 79.7% White and 20.3% Black), the 2 racial cohorts presented with similar tumor characteristics and similar OS (HR, 0.95; 95% CI, 0.89-1.02; P = .14). Black LCS was similar in univariable (HR, 1.10; 95% CI, 1.00-1.22; P = .05) and multivariable analyses (HR, 1.02; 95% CI, 0.92-1.14; P = .67).

Conclusions: Black patients with LSCC had a tumor burden at diagnosis and survival outcomes comparable to those of White patients within the VHA; this was counter to what was observed in the SEER analysis and prior national trends. This study's findings point toward the notable role of health care access in contributing to racial health disparities in the realm of larynx cancer.
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http://dx.doi.org/10.1002/cncr.33557DOI Listing
August 2021

Impact of Radiation on Cardiovascular Outcomes in Older Resectable Esophageal Cancer Patients With Medicare.

Am J Clin Oncol 2021 06;44(6):275-282

University of California San Diego School of Medicine.

Objectives: Preoperative radiotherapy improves outcomes for operable esophageal cancer patients, though the proximity of the heart to the esophagus puts patients at risk of radiation-induced cardiovascular disease. This study characterizes the impact of radiotherapy and different radiation techniques on cardiovascular morbidity among a cohort of esophageal cancer patients.

Materials And Methods: We identified 1125 patients aged 65 and older diagnosed between 2000 and 2011 with esophageal cancer who received surgery alone, or surgery preceded by either preoperative chemotherapy or preoperative chemoradiation from the Surveillance Epidemiology and End Results (SEER)-Medicare database. We used Medicare claims to identify severe perioperative and late cardiovascular events. Multivariable logistic regression and Fine-Gray models were used to determine the effect of presurgery treatment on the risk of perioperative and late cardiovascular disease.

Results: Preoperative chemotherapy or chemoradiation did not significantly increase the risk of perioperative cardiovascular complications compared with surgery alone. Patients treated with preoperative chemoradiation had a 36% increased risk of having a late cardiovascular event compared with patients treated with surgery alone (subdistribution hazard ratio [SDHR]: 1.36; P=0.035). There was no significant increase in late cardiovascular events among patients treated with preoperative chemotherapy (SDHR: 1.18; P=0.40). Among patients treated with preoperative chemoradiation, those receiving intensity modulated radiotherapy had a 68% decreased risk of having a late cardiovascular event compared with patients receiving conventional radiation (SDHR: 0.32; P=0.007).

Conclusions: This study demonstrates an increased risk of cardiovascular complications among operative esophageal cancer patients treated with preoperative chemoradiation, though these risks might be reduced with more cardioprotective radiation techniques such as intensity modulated radiotherapy.
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http://dx.doi.org/10.1097/COC.0000000000000815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141011PMC
June 2021

Validation of an oncology-specific opioid risk calculator in cancer survivors.

Cancer 2021 05 30;127(9):1529-1535. Epub 2020 Dec 30.

Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California.

Background: Clinical guidelines recommend that providers risk-stratify patients with cancer before prescribing opioids. Prior research has demonstrated that a simple cancer opioid risk score might help identify to patients with cancer at the time of diagnosis with a high likelihood of long-term posttreatment opioid use. This current project validates this cancer opioid risk score in a generalizable, population-based cohort of elderly cancer survivors.

Methods: This study identified 44,932 Medicare beneficiaries with cancer who had received local therapy. Longitudinal opioid use was ascertained from Medicare Part D data. A risk score was calculated for each patient, and patients were categorized into low-, moderate-, and high-risk groups on the basis of the predicted probability of persistent opioid use. Model discrimination was assessed with receiver operating characteristic curves.

Results: In the study cohort, 5.2% of the patients were chronic opioid users 1 to 2 years after the initiation of cancer treatment. The majority of the patients (64%) were at low risk and had a 1.2% probability of long-term opioid use. Moderate-risk patients (33% of the cohort) had a 5.6% probability of long-term opioid use. High-risk patients (3.5% of the cohort) had a 75% probability of long-term opioid use. The opioid risk score had an area under the receiver operating characteristic curve of 0.869.

Conclusions: This study found that a cancer opioid risk score could accurately identify individuals with a high likelihood of long-term opioid use in a large, generalizable cohort of cancer survivors. Future research should focus on the implementation of these scores into clinical practice and how this could affect prescriber behavior and patient outcomes.

Lay Summary: A novel 5-question clinical decision tool allows physicians treating patients with cancer to accurately predict which patients will persistently be using opioid medications after completing therapy.
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http://dx.doi.org/10.1002/cncr.33410DOI Listing
May 2021

Association Between African American Race and Clinical Outcomes in Men Treated for Low-Risk Prostate Cancer With Active Surveillance.

JAMA 2020 11;324(17):1747-1754

VHA San Diego Health Care System, La Jolla, California.

Importance: There is concern that African American men with low-risk prostate cancer may harbor more aggressive disease than non-Hispanic White men. Therefore, it is unclear whether active surveillance is a safe option for African American men.

Objective: To compare clinical outcomes of African American and non-Hispanic White men with low-risk prostate cancer managed with active surveillance.

Design, Setting, And Participants: Retrospective cohort study in the US Veterans Health Administration Health Care System of African American and non-Hispanic White men diagnosed with low-risk prostate cancer between January 1, 2001, and December 31, 2015, and managed with active surveillance. The date of final follow-up was March 31, 2020.

Exposures: Active surveillance was defined as no definitive treatment within the first year of diagnosis and at least 1 additional surveillance biopsy.

Main Outcomes And Measures: Progression to at least intermediate-risk, definitive treatment, metastasis, prostate cancer-specific mortality, and all-cause mortality.

Results: The cohort included 8726 men, including 2280 African American men (26.1%) (median age, 63.2 years) and 6446 non-Hispanic White men (73.9%) (median age, 65.5 years), and the median follow-up was 7.6 years (interquartile range, 5.7-9.9; range, 0.2-19.2). Among African American men and non-Hispanic White men, respectively, the 10-year cumulative incidence of disease progression was 59.9% vs 48.3% (difference, 11.6% [95% CI, 9.2% to 13.9%); P < .001); of receipt of definitive treatment, 54.8% vs 41.4% (difference, 13.4% [95% CI, 11.0% to 15.7%]; P < .001); of metastasis, 1.5% vs 1.4% (difference, 0.1% [95% CI, -0.4% to 0.6%]; P = .49); of prostate cancer-specific mortality, 1.1% vs 1.0% (difference, 0.1% [95% CI, -0.4% to 0.6%]; P = .82); and of all-cause mortality, 22.4% vs 23.5% (difference, 1.1% [95% CI, -0.9% to 3.1%]; P = 0.09).

Conclusions And Relevance: In this retrospective cohort study of men with low-risk prostate cancer followed up for a median of 7.6 years, African American men, compared with non-Hispanic White men, had a statistically significant increased 10-year cumulative incidence of disease progression and definitive treatment, but not metastasis or prostate cancer-specific mortality. Longer-term follow-up is needed to better assess the mortality risk.
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http://dx.doi.org/10.1001/jama.2020.17020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610194PMC
November 2020

Outcomes of Black men with prostate cancer treated with radiation therapy in the Veterans Health Administration.

Cancer 2021 02 9;127(3):403-411. Epub 2020 Oct 9.

Department of Radiation Medicine and Applied Sciences, University of California San Diego School of Medicine, La Jolla, California.

Background: Population-based studies demonstrate that Black men in the United States have an increased risk of death from prostate cancer. Determinants of racial disparities are multifactorial, including socioeconomic and biologic factors.

Methods: The authors conducted a pooled analysis of patients derived from 152 centers within the Veterans Health Administration. The cohort included men who had nonmetastatic prostate diagnosed between 2001 and 2015 and received definitive radiation therapy. The primary endpoint was prostate cancer-specific mortality (PCSM). Secondary endpoints included all-cause mortality (ACM) and the time from a prostate-specific antigen level ≥4 ng/mL to biopsy and radiation therapy. A Cox regression model was performed to adjust for differences between clinical parameters.

Results: Among the 31,131 patients included in the cohort, 9584 (30.8%) were Black. The 10-year cumulative incidence of death from prostate cancer was lower in Black men compared with White men (4.0% vs 4.8%; P = .004). In a competing risk model, Black race was associated with a decreased risk of PCSM (subdistribution hazard ratio, 0.79; 95% CI, 0.69-0.92; P = .002). Similarly, the 10-year cumulative incidence of death from any cause was lower in Black men (27.6% vs 31.8%; P < .001). In multivariable analysis, Black men had a 10% decreased risk of ACM (hazard ratio, 0.90; 95% CI, 0.85-0.95; P < .001).

Conclusions: The current results indicate relatively lower PCSM and ACM among Black men who were included in a large Veterans Health Administration cohort and received radiation therapy as primary treatment for nonmetastatic prostate cancer. There is an ongoing need to continue to understand and mitigate the factors associated with disparities in health care outcomes.
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http://dx.doi.org/10.1002/cncr.33224DOI Listing
February 2021

Stereotactic body radiotherapy versus conventional/moderate fractionated radiation therapy with androgen deprivation therapy for unfavorable risk prostate cancer.

Radiat Oncol 2020 Sep 15;15(1):217. Epub 2020 Sep 15.

Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC, USA.

Background: Ultrahypofractionation using stereotactic body radiotherapy (SBRT) is an increasingly utilized technique for men with prostate cancer (PC). The comparative efficacy of SBRT plus androgen deprivation therapy (ADT) compared to fractionated radiotherapy (EBRT) plus ADT in higher-risk prostate cancer is unknown.

Methods: Men > 40 years old with localized PC treated with external beam radiation and concomitant ADT for curative intent between 2004 and 2016 were analyzed from the National Cancer Database. Patients who lacked ADT or risk stratification data were excluded. 558 men treated with SBRT versus 40,797 men treated with conventional or moderately hypofractionated EBRT were included. Patients were stratified by unfavorable intermediate (UIR) and high (HR) risk using NCCN criteria. Kaplan Meier and Cox proportional hazards were used to compare overall survival (OS) between RT modality, adjusting for age, race, and comorbidity index.

Results: With a median follow up of 74 months, there was no difference in estimated 6-year OS between men treated with SBRT versus EBRT regardless of risk group. On multivariable analysis, there was no difference in risk of death for men treated with SBRT compared to EBRT (UIR: adjusted HR 1.09, 95% CI 0.68-1.74, p = .72; HR: adjusted HR 0.93, 95% CI 0.76-1.14, p = .51). On sensitivity analyses, when confining the cohort to men treated with NCCN-preferred dose fractionations, with no comorbidities, or < 65 years old, there remained no survival difference between treatment groups for both UIR and HR.

Conclusion: Within study limitations, we found no difference in survival between SBRT+ADT and standard of care EBRT+ADT for UIR or HR PC. These results support recent NCCN guideline updates, which include SBRT as a non-preferred option for higher risk men. Prospective validation would further strengthen the evidence basis behind these recommendations.
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http://dx.doi.org/10.1186/s13014-020-01658-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493337PMC
September 2020

Evaluation of the Use of Cancer Registry Data for Comparative Effectiveness Research.

JAMA Netw Open 2020 07 1;3(7):e2011985. Epub 2020 Jul 1.

School of Medicine, University of California, San Diego, La Jolla.

Importance: Researchers often analyze cancer registry data to assess for differences in survival among cancer treatments. However, the retrospective, nonrandomized design of these analyses raises questions about study validity.

Objective: To examine the extent to which comparative effectiveness analyses using observational cancer registry data produce results concordant with those of randomized clinical trials.

Design, Setting, And Participants: In this comparative effectiveness study, a total of 141 randomized clinical trials referenced in the National Comprehensive Cancer Network Clinical Practice Guidelines for 8 common solid tumor types were identified. Data on participants within the National Cancer Database (NCDB) diagnosed between 2004 and 2014, matching the eligibility criteria of the randomized clinical trial, were obtained. The present study was conducted from August 1, 2017, to September 10, 2019. The trials included 85 118 patients, and the corresponding NCDB analyses included 1 344 536 patients. Three Cox proportional hazards regression models were used to determine hazard ratios (HRs) for overall survival, including univariable, multivariable, and propensity score-adjusted models. Multivariable and propensity score analyses controlled for potential confounders, including demographic, comorbidity, clinical, treatment, and tumor-related variables.

Main Outcomes And Measures: The main outcome was concordance between the results of randomized clinical trials and observational cancer registry data. Hazard ratios with an NCDB analysis were considered concordant if the NDCB HR fell within the 95% CI of the randomized clinical trial HR. An NCDB analysis was considered concordant if both the NCDB and clinical trial P values for survival were nonsignificant (P ≥ .05) or if they were both significant (P < .05) with survival favoring the same treatment arm in the NCDB and in the randomized clinical trial.

Results: Analyses using the NCDB-produced HRs for survival were concordant with those of 141 randomized clinical trials in 79 univariable analyses (56%), 98 multivariable analyses (70%), and 90 propensity score models (64%). The NCDB analyses produced P values concordant with randomized clinical trials in 58 univariable analyses (41%), 65 multivariable analyses (46%), and 63 propensity score models (45%). No clinical trial characteristics were associated with concordance between NCDB analyses and randomized clinical trials, including disease site, type of clinical intervention, or severity of cancer.

Conclusions And Relevance: The findings of this study suggest that comparative effectiveness research using cancer registry data often produces survival outcomes discordant with those of randomized clinical trial data. These findings may help provide context for clinicians and policy makers interpreting observational comparative effectiveness research in oncology.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.11985DOI Listing
July 2020

Testosterone therapy does not increase the risks of prostate cancer recurrence or death after definitive treatment for localized disease.

Prostate Cancer Prostatic Dis 2020 12 8;23(4):689-695. Epub 2020 Jun 8.

Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, 92093, USA.

Background: The safety of testosterone therapy (TT) after definitive treatment for localized prostate cancer remains undefined. We analyzed the risks of biochemical recurrence and mortality in men receiving TT after treatment for localized prostate cancer.

Methods: Cohort analysis using the national US Veterans Affairs Informatics and Computing Infrastructure. We identified 69,984 patients with localized prostate cancer diagnosed from 2001 to 2015 treated with surgery or radiation. We coded receipt of TT after treatment as a time-dependent covariate; used the National Death Index to identify cause of death; and defined biochemical recurrence as PSA > 0.2 ng/mL after surgery and nadir + 2 ng/mL after radiation. We analyzed recurrence and mortality using cumulative incidence curves, Fine-Gray competing risk regression, and Cox regression.

Results: This cohort included 28,651 surgery patients and 41,333 radiation patients, of whom 469 (1.64%) and 543 (1.31%), respectively, received TT with a median follow-up of 6.95 years. Comparing testosterone users to nonusers, there were no between-group differences in biochemical recurrence, prostate cancer-specific mortality, or overall mortality after surgery [hazard ratios (HR): 1.07; HR: 0.72 (p = 0.43); and HR: 1.11 (p = 0.43), respectively] or radiation [HR: 1.07; HR: 1.02 (p = 0.95); and HR: 1.02 (p = 0.86), respectively]. Limitations included lack of detailed data on TT duration and serum testosterone concentrations.

Conclusions: In this multi-ethnic national cohort, TT did not increase the risks of biochemical recurrence or prostate cancer-specific or overall mortality after surgery or radiation. These data suggest that TT is safe in appropriate men after definitive treatment of localized prostate cancer.
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http://dx.doi.org/10.1038/s41391-020-0241-3DOI Listing
December 2020

Palliative Radiotherapy Versus Esophageal Stent Placement in the Management of Patients With Metastatic Esophageal Cancer.

J Natl Compr Canc Netw 2020 05;18(5):569-574

Department of Radiation Medicine and Applied Sciences, University of California, San Diego, San Diego, California.

Background: Patients with advanced esophageal cancer often experience pain and dysphagia, yet the optimal palliative management remains unclear. This retrospective study evaluated outcomes and adverse effects of palliative radiotherapy (RT) compared with esophageal stenting among a cohort of U.S. veterans with metastatic esophageal cancer.

Patients And Methods: We identified 1,957 veterans in the United States with metastatic esophageal cancer who received palliative RT to the esophagus or esophageal stenting, and assessed the risks of severe adverse effects, including esophageal fistula formation, perforation, obstruction, hemorrhage, and esophagitis. We determined palliative efficacy by evaluating pain and dysphagia scores before and after intervention. Multivariable analyses were used to control for potential confounding factors.

Results: In our cohort, 1,593 patients underwent RT and 364 underwent esophageal stenting. The cumulative incidence of any severe adverse effect at 6 months was higher among patients who received stents compared with those who received RT (21.7% vs 12.4%; P<.0010). In multivariable analysis, patients who received stents had an increased risk of any severe adverse effect, including fistula, perforation, and hemorrhage (all P<.0500). Multivariable analysis also showed that, compared with stenting, RT was associated with more rapid and durable pain relief (P<.0010) with no difference in relief of dysphagia over time when accounting for pretreatment dysphagia scores (P=.1029).

Conclusions: Compared with esophageal stenting, RT was associated with a decreased risk of adverse effects, greater pain relief, and equivalent relief of moderate to severe dysphagia over time. Unmeasured patient- or tumor-related factors could have influenced the choice of intervention, thereby impacting our study outcomes. To our knowledge, this is the largest study to date analyzing the comparative risks and benefits of palliative RT and esophageal stenting among patients with metastatic esophageal cancer.
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http://dx.doi.org/10.6004/jnccn.2019.7524DOI Listing
May 2020

African-American men with low-risk prostate cancer treated with radical prostatectomy in an equal-access health care system: implications for active surveillance.

Prostate Cancer Prostatic Dis 2020 12 23;23(4):581-588. Epub 2020 Apr 23.

VA San Diego Health Care System, La Jolla, CA, USA.

Background: There is concern that African-American men (AA) with low-risk prostate cancer may present with more aggressive disease and thus may not be candidates for active surveillance (AS). However, it is uncertain if poorer outcomes are due to disparities in access to medical care rather than true biological differences.

Methods: Observational cohort study of patients diagnosed with low-risk PC-Gleason score ≤6, clinical tumor stage ≤2A, and prostate specific antigen (PSA) level ≤10-at US Department of Veterans Affairs between January 1, 2001 and October 31, 2015 and treated with radical prostatectomy. Outcomes included upgrading to Gleason Grade Group 2 (GG2), GG ≥ 3, PSA recurrence, pathologic tumor stage ≥3, positive surgical margins, and all-cause mortality.

Results: A total of 2857 men (AA: 835 White: 2022) with a median follow-up of 7.1 years. Overall, there was no significant difference between AA and White men in upgrading to GG ≥ 3 (RR = 1.18, p = 0.43), tumor stage ≥3 (RR = 0.95, p = 0.74), positive surgical margins (RR = 1.14, p = 0.20), PSA recurrence (SHR = 1.26, p = 0.06), and all-cause mortality (SHR = 1.26, p = 0.16). However, there was a significant increase in upgrading for AA to GG2 (RR = 1.49, p < 0.01).

Conclusions: There was no significant difference in most adverse pathologic outcomes between AA and White patients. However, GG2 upgrading was more common in AA men. The implication is that AA may need to undergo additional evaluation, such as a biopsy MRI, before initiating AS. Whether the increase in GG2 upgrading will lead to poorer long-term clinical outcomes such as metastasis and PCSM also requires further investigation.
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http://dx.doi.org/10.1038/s41391-020-0230-6DOI Listing
December 2020

Associations among statins, preventive care, and prostate cancer mortality.

Prostate Cancer Prostatic Dis 2020 09 6;23(3):475-485. Epub 2020 Feb 6.

Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA.

Background: Increasing evidence indicates an association between statins and reduced prostate cancer-specific mortality (PCSM). However, significant bias may exist in these studies. One particularly challenging bias to assess is the healthy user effect, which may be quantified by screening patterns. We aimed to evaluate the association between statin use, screening, and PCSM in a dataset with detailed longitudinal information.

Methods: We used the Veterans Affairs Informatics and Computing Infrastructure to assemble a cohort of patients diagnosed with prostate cancer (PC) between 2000 and 2015. We collected patient-level demographic, comorbidity, and tumor data. We also assessed markers of preventive care utilization including cholesterol and prostate specific antigen (PSA) screening rates. Patients were considered prediagnosis statin users if they had at least one prescription one or more years prior to PC diagnosis. We evaluated PCSM using hierarchical Fine-Gray regression models and all-cause mortality (ACM) using a cox regression model.

Results: The final cohort contained 68,432 men including 40,772 (59.6%) prediagnosis statin users and 27,660 (40.4%) nonusers. Prediagnosis statin users had higher screening rates than nonusers for cholesterol (90 vs. 69%, p < 0.001) and PSA (76 vs. 67%, p < 0.001). In the model which excluded screening, prediagnosis statin users had improved PCSM (SHR 0.90, 95% CI 0.84-0.97; p = 0.004) and ACM (HR 0.96, 95% CI 0.93-0.99; p = 0.02). However, after including cholesterol and PSA screening rates, prediagnosis statin users and nonusers showed no differences in PCSM (SHR 0.98, 95% CI 0.91-1.06; p = 0.59) or ACM (HR 1.02, 95% CI 0.98-1.05; p = 0.25).

Conclusion: We found that statin users tend to have more screening than nonusers. When we considered screening utilization, we observed no relationship between statin use before a prostate cancer diagnosis and prostate cancer mortality.
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http://dx.doi.org/10.1038/s41391-020-0207-5DOI Listing
September 2020

Survival of African American and non-Hispanic white men with prostate cancer in an equal-access health care system.

Cancer 2020 04 27;126(8):1683-1690. Epub 2020 Jan 27.

Department of Radiation Medicine and Applied Sciences, University of California at San Diego, La Jolla, California.

Background: African American (AA) men in the general US population are more than twice as likely to die of prostate cancer (PC) compared with non-Hispanic white (NHW) men. The authors hypothesized that receiving care through the Veterans Affairs (VA) health system, an equal-access medical system, would attenuate this disparity.

Methods: A longitudinal, centralized database of >20 million veterans was used to assemble a cohort of 60,035 men (18,201 AA men [30.3%] and 41,834 NHW men [69.7%]) who were diagnosed with PC between 2000 and 2015.

Results: AA men were more likely to live in regions with a lower median income ($40,871 for AA men vs $48,125 for NHW men; P < .001) and lower high school graduation rates (83% for AA men vs 88% for NHW men; P < .001). At the time of diagnosis, AA men were younger (median age, 63.0 years vs 66.0 years; P < .001) and had a higher prostate-specific antigen level (median, 6.7 ng/mL vs 6.2 ng/mL; P < .001), but were less likely to have Gleason score 8 to 10 disease (18.8% among AA men vs 19.7% among NHW men; P < .001), a clinical T classification ≥3 (2.2% vs 2.9%; P < .001), or distant metastatic disease (2.7% vs 3.1%; P = 0.01). The 10-year PC-specific mortality rate was slightly lower for AA men (4.4% vs 5.1%; P = .005), which was confirmed in multivariable competing-risk analysis (subdistribution hazard ratio, 0.85; 95% CI, 0.78-0.93; P < .001).

Conclusions: AA men diagnosed with PC in the VA health system do not appear to present with more advanced disease or experience worse outcomes compared with NHW men, in contrast to national trends, suggesting that access to care is an important determinant of racial equity.
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http://dx.doi.org/10.1002/cncr.32666DOI Listing
April 2020

Combined Androgen Blockade in Localized Prostate Cancer Treated With Definitive Radiation Therapy.

J Natl Compr Canc Netw 2019 12;17(12):1497-1504

aDepartment of Radiation Medicine and Applied Sciences.

Background: The addition of androgen deprivation therapy to radiation therapy (RT) improves survival in patients with intermediate- and high-risk prostate cancer (PCa), but it is not known whether combined androgen blockade (CAB) with a gonadotropin-releasing hormone agonist (GnRH-A) and a nonsteroidal antiandrogen improves survival over GnRH-A monotherapy.

Methods: This study evaluated patients with intermediate- and high-risk PCa diagnosed in 2001 through 2015 who underwent RT with either GnRH-A alone or CAB using the Veterans Affairs Informatics and Computing Infrastructure. Associations between CAB and prostate cancer-specific mortality (PCSM) and overall survival (OS) were determined using multivariable regression with Fine-Gray and multivariable Cox proportional hazards models, respectively. For a positive control, the effect of long-term versus short-term GnRH-A therapy was tested.

Results: The cohort included 8,423 men (GnRH-A, 4,529; CAB, 3,894) with a median follow-up of 5.9 years. There were 1,861 deaths, including 349 resulting from PCa. The unadjusted cumulative incidences of PCSM at 10 years were 5.9% and 6.9% for those receiving GnRH-A and CAB, respectively (P=.16). Compared with GnRH-A alone, CAB was not associated with a significant difference in covariate-adjusted PCSM (subdistribution hazard ratio [SHR], 1.05; 95% CI, 0.85-1.30) or OS (hazard ratio, 1.02; 95% CI, 0.93-1.12). For high-risk patients, long-term versus short-term GnRH-A therapy was associated with improved PCSM (SHR, 0.74; 95% CI, 0.57-0.95) and OS (SHR, 0.82; 95% CI, 0.73-0.93).

Conclusions: In men receiving definitive RT for intermediate- or high-risk PCa, CAB was not associated with improved PCSM or OS compared with GnRH alone.
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http://dx.doi.org/10.6004/jnccn.2019.7335DOI Listing
December 2019

Association of Treatment With 5α-Reductase Inhibitors and Prostate Cancer Mortality Among Older Adults.

JAMA Netw Open 2019 10 2;2(10):e1913612. Epub 2019 Oct 2.

Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla.

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http://dx.doi.org/10.1001/jamanetworkopen.2019.13612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813580PMC
October 2019

Tobacco smoking and death from prostate cancer in US veterans.

Prostate Cancer Prostatic Dis 2020 06 17;23(2):252-259. Epub 2019 Oct 17.

Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA.

Background: Cigarette smoking is a risk factor for mortality in several genitourinary cancers, likely due to accumulation of carcinogens in urine. However, in prostate cancer (PC) the link has been less studied. We evaluated differences in prostate cancer-specific mortality (PCSM) between current smokers, past smokers, and never smokers diagnosed with PC.

Methods: This was a retrospective cohort study of PCSM in men diagnosed with PC between 2000 and 2015 treated in the US Veterans Affairs health care system, using competing risk regression analyses.

Results: The cohort included 73,668 men (current smokers: 22,608 (30.7%), past smokers: 23,695 (32.1%), and never smokers: 27,365 (37.1%)). Median follow-up was 5.9 years. Current smoker patients were younger at presentation (median age current: 63, never: 66; p < 0.001), and had more advanced disease stage (stage IV disease current: 5.3%, never: 4.3%; p < 0.04). The 10-year incidence of PCSM was 5.2%, 4.8%, and 4.5% for current, past, and never smokers, respectively. On competing risk regression, current smoking was associated with increased PCSM (subdistribution hazard ratio: 1.14, 95% confidence interval: (1.05-1.24), p = 0.002), whereas past smoking was not. Hierarchical regression suggests that this increased risk was partially attributable to tumor characteristics.

Conclusions: Smoking at the time of diagnosis is associated with a higher risk of dying from PC as well as other causes of death. In contrast, past smoking was not associated with PCSM suggesting that smoking may be a modifiable risk factor. PC diagnosis may be an important opportunity to discuss smoking cessation.
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http://dx.doi.org/10.1038/s41391-019-0178-6DOI Listing
June 2020
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