Prostate Cancer Recurrence: Examining the Role of Salvage Radiotherapy Field and Risk Factors for Regional Disease Recurrence Captured on 18F-DCFPyL PET/CT.

PURPOSE: The role of elective pelvic nodal irradiation in salvage radiotherapy (sRT) remains controversial. Utilizing 18F-DCFPyL PET/CT, this study aimed to investigate differences in disease distribution after whole pelvic (WPRT) or prostate bed (PBRT) radiotherapy and to identify risk factors for pelvic lymph node (LN) relapse. METHODS: This retrospective study included patients with PSA > 0.1 ng/mL post-radical prostatectomy (RP) or post-RP and sRT who underwent 18F-DCFPyL PET/CT. Disease distribution on 18F-DCFPyL PET/CT after sRT was compared using Chi-square tests. Risk factors were tested for association with pelvic LN relapse after RP and salvage PBRT using logistic regression. RESULTS: 979 18F-DCFPyL PET/CTs performed at our institution between 1/1/2022 - 3/24/2023 were analyzed. There were 246 patients meeting criteria, of which 84 received salvage RT after RP (post-salvage RT group) and 162 received only RP (post-RP group). Salvage PBRT patients (n = 58) had frequent pelvic nodal (53.6%) and nodal-only (42.6%) relapse. Salvage WPRT patients (n = 26) had comparatively lower rates of pelvic nodal (16.7%, p = 0.002) and nodal-only (19.2%, p = 0.04) relapse. The proportion of distant metastases did not differ between the two groups. Multiple patient characteristics, including ISUP grade and seminal vesicle invasion, were associated with pelvic LN disease in the post-RP group. CONCLUSION: At PSA persistence or progression, salvage WPRT resulted in lower rates of nodal involvement than salvage PBRT, but did not reduce distant metastases. Certain risk factors increase the likelihood of pelvic LN relapse after RP and can help inform salvage RT field selection.

Validation of Biomechanical Computed Tomography for Fracture Risk Classification in Metastatic Hormone-sensitive Prostate Cancer.

BACKGROUND: Guidelines recommend dual-energy x-ray absorptiometry (DXA) screening to assess fracture risk and benefit from antiresorptive therapy in men with metastatic hormone-sensitive prostate cancer (mHSPC) on androgen deprivation therapy (ADT). However, <30% of eligible patients undergo DXA screening. Biomechanical computed tomography (BCT) is a radiomic technique that measures bone mineral density (BMD) and bone strength from computed tomography (CT) scans. OBJECTIVE: To evaluate the (1) correlations between BCT- and DXA-assessed BMD, and (2) associations between BCT-assessed metrics and subsequent fracture. DESIGN, SETTING, AND PARTICIPANTS: A multicenter retrospective cohort study was conducted among patients with mHSPC between 2013 and 2020 who received CT abdomen/pelvis or positron emission tomography/CT within 48 wk before ADT initiation and during follow-up (48-96 wk after ADT initiation). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used univariate logistic regression to assess the associations between BCT measurements and the primary outcomes of subsequent pathologic and nonpathologic fractures. RESULTS AND LIMITATIONS: Among 91 eligible patients, the median ([interquartile range) age was 67 yr (62-75), 44 (48.4%) were White, and 41 (45.1%) were Black. During the median follow-up of 82 wk, 17 men (18.6%) developed a pathologic and 15 (16.5%) a nonpathologic fracture. BCT- and DXA-assessed femoral-neck BMD T scores were strongly correlated (R2 = 0.93). On baseline CT, lower BCT-assessed BMD (odds ratio [OR] 1.80, 95% confidence interval or CI [1.10, 3.25], p = 0.03) was associated with an increased risk of a pathologic fracture. Lower femoral strength (OR 1.63, 95% CI [0.99, 2.71], p = 0.06) was marginally associated with an increased risk of a pathologic fracture. Neither BMD (OR 1.52, 95% CI [0.95, 2.63], p = 0.11) nor strength (OR 1.14, 95% CI [0.75, 1.80], p = 0.57) was associated with a nonpathologic fracture. BCT identified nine (9.9%) men eligible for antiresorptive therapy, of whom four (44%) were not treated. Limitations include low fracture numbers resulting in lower power to detect fracture associations. CONCLUSIONS: Among men diagnosed with mHSPC, BCT assessments were strongly correlated with DXA, predicted subsequent pathologic fracture, and identified additional men indicated for antiresorptive therapy. PATIENT SUMMARY: We assess whether biomechanical computer tomography (BCT) from routine computer tomography (CT) scans can identify fracture risk among patients recently diagnosed with metastatic prostate cancer. We find that BCT and dual-energy x-ray absorptiometry-derived bone mineral density are strongly correlated and that BCT accurately identifies the risk for future fracture. BCT may enable broader fracture risk assessment and facilitate timely interventions to reduce fracture risk in metastatic prostate cancer patients.

Development and Validation of a Tool to Identify Patients Diagnosed With Castration-Resistant Prostate Cancer.

PURPOSE: Several novel therapies for castration-resistant prostate cancer (CRPC) have been approved with randomized phase III studies with continuing observational research either planned or ongoing. Accurately identifying patients with CRPC in electronic health care data is critical for quality observational research, resource allocation, and quality improvement. Previous work in this area has relied on either structured laboratory results and medication data or natural language processing (NLP) methods. However, a computable phenotype using both structured data and NLP identifies these patients with more accuracy. METHODS: The Corporate Data Warehouse (CDW) of the Veterans Health Administration (VHA) was used to collect PCa diagnoses, prostate-specific antigen test results, and information regarding patient characteristics and medication use. The final system used for validation and subsequent analysis combined the NLP system and an algorithm of structured laboratory and medication data to identify patients as being diagnosed with CRPC. Patients with both a documented diagnosis of CRPC and a documented diagnosis of metastatic PCa were classified as having mCRPC by this system. RESULTS: Among 1.2 million veterans with PCa, the International Classification of Diseases (ICD)-10 diagnosis code for CRPC (Z19.2) identifies 3,791 patients from 2016 when the code was created until 2022, compared with the combined algorithm which identifies 14,103, 10,312 more than ICD-10 codes alone, from 2016 to 2022. The combined algorithm showed a sensitivity of 97.9% and a specificity of 99.2%. CONCLUSION: ICD-10 codes proved to be insufficient for capturing CRPC in the VHA CDW data. Using both structured and unstructured data identified more than double the number of patients compared with ICD-10 codes alone. Application of this combined approach drastically improved identification of real-world patients and enables high-quality observational research in mCRPC.

Flutamide With or Without PROSTVAC in Non-metastatic Castration Resistant (M0) Prostate Cancer.

BACKGROUND: Before 2018, there was no standard of care for non-metastatic (M0) castration resistant prostate cancer nmCRPC. Androgen receptor antagonists (ARAs) were commonly used sequentially nmCRPC. METHODS: This was a multicenter, randomized clinical trial comparing the ARA flutamide+/-PROSTVAC, a pox viral vaccine targeting PSA that includes T-cell co-stimulatory molecules. Eligible men had negative CT and Tc99 bone scans, and rising PSA on ADT. Previous treatment with ARA was a stratification factor. Patients were also evaluated for antigen-specific immune responses using intracellular cytokine staining. RESULTS: Thirty-three patients randomized to flutamide and 31 to flutamide+vaccine. The median age was 71.8 and 69.8 years, respectively. The median time to treatment failure after a median potential follow-up of 46.7 months was, 4.5 months (range 2-70) for flutamide alone vs. 6.9 months (2.5-40; P = .38) with flutamide+vaccine. Seven patients in each arm had a >50% PSA response. Antigen-specific responses were similar in both arms (58% of patients in flutamide alone and 56% in flutamide+vaccine). The treatments were well tolerated. The most common side effect > grade 2 was injection site reaction seen in 29/31 vaccine patients which were self-limiting. CONCLUSION: The combination of flutamide+PROSTVAC did not improve outcomes in men with nmCRPC compared with flutamide alone. (ClinicalTrials.gov Identifier: NCT00450463).

On-Site Nurse-Led Cancer Genetics Program Increases Cancer Genetic Testing Completion in Black Veterans.

PURPOSE: Telegenetics services can expand access to guideline-recommended cancer genetic testing. However, access is often not distributed equitably to all races and ethnicities. We evaluated the impact of an on-site nurse-led cancer genetics service in a diverse Veterans Affairs Medical Center (VAMC) oncology clinic on likelihood of germline testing (GT) completion. METHODS: We conducted an observational retrospective cohort study of patients who were referred for cancer genetics services at the Philadelphia VAMC between October 1, 2020, and February 28, 2022. We evaluated the association between genetics service (on-site v telegenetics) and likelihood of GT completion in a subcohort of new consults, excluding patients with prior consults and those referred for known history of germline mutations. RESULTS: A total of 238 Veterans, including 108 (45%) seen on site, were identified for cancer genetics services during the study period, with the majority referred for a personal (65%) or family (26%) history of cancer. In the subcohort of new consults, 121 Veterans (54% self-identified race/ethnicity [SIRE]-Black), including 60 (50%) seen on site, were included in the analysis of germline genetic testing completion. In a univariate analysis, patients who were seen by the on-site genetics service had 3.2-fold higher likelihood of completing GT (relative risk, 3.22; 95% CI, 1.89 to 5.48) compared with the telegenetics service. In multivariable regression analysis, the on-site genetics service was associated with higher likelihood of GT completion, but this association was only statistically significant in SIRE-Black compared with SIRE-White Veterans (adjusted RR, 4.78; 95% CI, 1.53 to 14.96; P < .001; P-interaction of race × genetics service = .016). CONCLUSION: An on-site nurse-led cancer genetics service embedded in a VAMC Oncology practice was associated with higher likelihood of germline genetic testing completion than a telegenetics service among self-identified Black Veterans.

Tumor testing and treatment patterns in veterans with metastatic castration-resistant prostate cancer.

INTRODUCTION: In 2016, the Department of Veterans Affairs (VA) and Prostate Cancer Foundation (PCF) began a partnership to improve access to testing. The primary objective of this analysis was to describe the use of tumor testing and treatment patterns in Veterans who progressed to metastatic castration-resistant prostate cancer (mCRPC) from 2016 to 2021. Secondary objectives including identifying factors associated with receipt of tumor testing, and reporting HRR mutation results among a subset who were tested. METHODS AND MATERIALS: Natural language processing algorithms were applied to VA electronic health record data to identify a nationwide cohort of veterans with mCRPC. Tumor testing over time and by region were reported, alongside first-, second-, and third-line treatment patterns. Factors associated with receipt of tumor testing were identified using generalized linear mixed models with binomial distributions and logit links to account for clustering by VA facility. RESULTS: Of the 9,852 veterans analyzed, 1,972 (20%) received tumor testing, with 73% of testing occurring in 2020-2021. Factors associated with tumor testing included younger age, later diagnosis year, being treated in the Midwest, or Puerto Rico or other compared to the South, and being treated at a PCF-VA Center of Excellence. Fifteen percent of tests were positive for a pathogenic HRR mutation. Seventy-six percent of the study cohort received first-line treatment, and among those, a subsequent 52% received second-line treatment. A subsequent 46% received third-line treatment. CONCLUSION: After the VA-PCF partnership, one-fifth of veterans with mCRPC received tumor testing, with most tests occurring in 2020-2021.

Effect of Androgen Suppression on Clinical Outcomes in Hospitalized Men With COVID-19: The HITCH Randomized Clinical Trial.

Importance: SARS-CoV-2 entry requires the TMPRSS2 cell surface protease. Antiandrogen therapies reduce expression of TMPRSS2. Objective: To determine if temporary androgen suppression induced by degarelix improves clinical outcomes of inpatients hospitalized with COVID-19. Design, Setting, and Participants: The Hormonal Intervention for the Treatment in Veterans With COVID-19 Requiring Hospitalization (HITCH) phase 2, placebo-controlled, double-blind, randomized clinical trial compared efficacy of degarelix plus standard care vs placebo plus standard care on clinical outcomes in men hospitalized with COVID-19 but not requiring invasive mechanical ventilation. Inpatients were enrolled at 14 Department of Veterans Affairs hospitals from July 22, 2020, to April 8, 2021. Data were analyzed from August 9 to October 15, 2021. Interventions: Patients stratified by age, history of hypertension, and disease severity were centrally randomized 2:1 to degarelix, (1-time subcutaneous dose of 240 mg) or a saline placebo. Standard care included but was not limited to supplemental oxygen, antibiotics, vasopressor support, peritoneal dialysis or hemodialysis, intravenous fluids, remdesivir, convalescent plasma, and dexamethasone. Main Outcomes and Measures: The composite primary end point was mortality, ongoing need for hospitalization, or requirement for mechanical ventilation at day 15 after randomization. Secondary end points were time to clinical improvement, inpatient mortality, length of hospitalization, duration of mechanical ventilation, time to achieve a temperature within reference range, maximum severity of COVID-19, and the composite end point at 30 days. Results: The trial was stopped for futility after the planned interim analysis, at which time there were 96 evaluable patients, including 62 patients randomized to the degarelix group and 34 patients in the placebo group, out of 198 initially planned. The median (range) age was 70.5 (48-85) years. Common comorbidities included chronic obstructive pulmonary disorder (15 patients [15.6%]), hypertension (75 patients [78.1%]), cardiovascular disease (27 patients [28.1%]), asthma (12 patients [12.5%]), diabetes (49 patients [51.0%]), and chronic respiratory failure requiring supplemental oxygen at baseline prior to COVID-19 (9 patients [9.4%]). For the primary end point, there was no significant difference between the degarelix and placebo groups (19 patients [30.6%] vs 9 patients [26.5%]; P = .67). Similarly, no differences were observed between degarelix and placebo groups in any secondary end points, including inpatient mortality (11 patients [17.7%] vs 6 patients [17.6%]) or all-cause mortality (11 patients [17.7%] vs 7 patents [20.6%]). There were no differences between degarelix and placebo groups in the overall rates of adverse events (13 patients [21.0%] vs 8 patients [23.5%) and serious adverse events (19 patients [30.6%] vs 13 patients [32.4%]), nor unexpected safety concerns. Conclusions and Relevance: In this randomized clinical trial of androgen suppression vs placebo and usual care for men hospitalized with COVID-19, degarelix did not result in amelioration of COVID-19 severity. Trial Registration: ClinicalTrials.gov Identifier: NCT04397718.

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

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 received nondefinitive treatment classified as "other" 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.

Long-term depression incidence and associated mortality among African American and White prostate cancer survivors.

BACKGROUND: Depression is common after a diagnosis of prostate cancer and may contribute to poor outcomes, particularly among African Americans. The authors assessed the incidence and management of depression and its impact on overall mortality among African American and White veterans with localized prostate cancer. METHODS: The authors used the Veterans Health Administration Corporate Data Warehouse to identify 40,412 African American and non-Hispanic White men diagnosed with localized prostate cancer from 2001 to 2013. Patients were followed through 2019. Multivariable logistic regression was used to measure associations between race and incident depression, which were ascertained from administrative and depression screening data. Cox proportional hazards models were used to measure associations between incident depression and all-cause mortality, with race-by-depression interactions used to assess disparities. RESULTS: Overall, 10,013 veterans (24.5%) were diagnosed with depression after a diagnosis of prostate cancer. Incident depression was associated with higher all-cause mortality (adjusted hazard ratio [aHR], 1.27; 95% confidence interval [CI], 1.23-1.32). African American veterans were more likely than White veterans to be diagnosed with depression (29.3% vs 23.2%; adjusted odds ratio [aOR], 1.15; 95% CI, 1.09-1.21). Among those with depression, African Americans were less likely to be prescribed an antidepressant (30.4% vs 31.7%; aOR, 0.85; 95% CI, 0.77-0.93). The hazard of all-cause mortality associated with depression was greater for African American veterans than White veterans (aHR, 1.32 [95% CI, 1.26-1.38] vs 1.15 [95% CI, 1.07-1.24]; race-by-depression interaction P < .001). CONCLUSIONS: Incident depression is common among prostate cancer survivors and is associated with higher mortality, particularly among African American men. Patient-centered strategies to manage incident depression may be critical to reducing disparities in prostate cancer outcomes.

Multiple myeloma treatment patterns and clinical outcomes in the Latin America Haemato-Oncology (HOLA) Observational Study, 2008-2016.

Limited data are available regarding contemporary multiple myeloma (MM) treatment practices in Latin America. In this retrospective cohort study, medical records were reviewed for a multinational cohort of 1103 Latin American MM patients (median age, 61 years) diagnosed in 2008-2015 who initiated first-line therapy (LOT1). Of these patients, 33·9% underwent autologous stem cell transplantation (ASCT). During follow-up, 501 (45·4%) and 129 (11·7%) patients initiated second- (LOT2) and third-line therapy (LOT3), respectively. In the LOT1 setting, from 2008 to 2015, there was a decrease in the use of thalidomide-based therapy, from 66·7% to 42·6%, and chemotherapy from, 20·2% to 5·9%, whereas use of bortezomib-based therapy or bortezomib + thalidomide increased from 10·7% to 45·5%. Bortezomib-based therapy and bortezomib + thalidomide were more commonly used in ASCT patients and in private clinics. In non-ASCT and ASCT patients, median progression-free survival (PFS) was 15·0 and 31·1 months following LOT1 and 10·9 and 9·5 months following LOT2, respectively. PFS was generally longer in patients treated with bortezomib-based or thalidomide-based therapy versus chemotherapy. These data shed light on recent trends in the management of MM in Latin America. Slower uptake of newer therapies in public clinics and poor PFS among patients with relapsed MM point to areas of unmet therapeutic need in Latin America.

Results of a Real-world Study of Enzalutamide and Abiraterone Acetate With Prednisone Tolerability (REAAcT).

BACKGROUND: The objective of this study was to evaluate differences in tolerability in patients with metastatic castration-resistant prostate cancer treated with enzalutamide (ENZA) or abiraterone acetate plus prednisone (AA+P). PATIENTS AND METHODS: This was a phase IV, prospective, open-label, multicenter, real-world study. Patients were prescribed ENZA or AA+P at the treating physician's discretion. Computerized tests of 4 cognitive domains (Cogstate), patient-reported outcomes (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [EORTC QLQ-30], Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue], Functional Assessment of Cancer Therapy-Cognitive Function [FACT-Cog]), and patient/caregiver surveys were assessed at baseline and 2 months. Safety data were collected. RESULTS: Of 100 treated patients, 92 were evaluable (46/arm). Baseline characteristics were similar, with mild cognitive impairment observed in ∼20% of patients. The FACIT-Fatigue demonstrated a statistically significant worsening from baseline of -4.00 (95% confidence interval, -6.61 to -1.39) for ENZA compared with AA+P, -0.01 (95% confidence interval, -2.40 to 2.38). Overall, more adverse events (AEs) and more AEs of fatigue were reported with ENZA versus AA+P (52% vs. 36% and 26% vs. 8%, respectively). Grade 3/4 AEs were similar (4% vs. 6%). Unique neuropsychiatric AEs reported with ENZA included amnesia, cognitive disorders, memory impairment, and confusional state; those for AA+P included cerebrovascular accident, presyncope, and spinal cord compression. Clinically meaningful cognitive decline was seen in 4 patients on ENZA versus 1 patient on AA+P. However, the overall mean changes from baseline for the Cogstate tests, the EORTC QLQ-C30, and the FACT-Cog assessment were similar and showed no meaningful change. Caregiver survey responses noted more fatigue with ENZA and more moodiness with AA+P compared with patient responses. CONCLUSIONS: Although baseline values were similar, more fatigue and neurocognitive differences were observed with ENZA compared with AA+P.

Comparative Survival Associated With Use of Targeted vs Nontargeted Therapy in Medicare Patients With Metastatic Renal Cell Carcinoma.

Importance: Targeted therapies for advanced renal cell carcinoma (RCC) have shown increased tolerability and survival advantages over older treatments in clinical trials, but understanding of real-world survival improvements is still emerging. Objective: To compare overall and RCC-specific survival associated with use of targeted vs nontargeted therapy for metastatic RCC. Design, Setting, and Participants: This retrospective cohort study used Surveillance, Epidemiology, and End Results-Medicare data from 2000 to 2013 to examine patients with stage IV (distant) clear cell RCC at the time of diagnosis who received any targeted or nontargeted therapy. A 2-stage residual inclusion model was fitted to estimate the survival advantages of targeted treatments using an instrumental variable approach to account for both measured and unmeasured group differences. Data analyses were conducted from July 24, 2017, to April 4, 2019. Exposures: Targeted therapy (study group) or nontargeted therapy (control group). Main Outcomes and Measures: Overall survival and RCC-specific survival, defined as the interval between the date of first drug treatment and date of death or end of the observation period. Results: The final sample included 1015 patients (mean [SD] age, 71.2 [8.1] years; 392 [39%] women); 374 (37%) received nontargeted therapy and 641 (63%) received targeted therapy. The targeted therapy group had a greater percentage of disabled patients (ie, those <65 years old who were eligible for Medicare because of disability) and older patients (ie, those ≥75 years old) and higher comorbidity index and disability scores compared with the nontargeted therapy group. Unadjusted Kaplan-Meier survival curves showed higher overall survival for targeted vs nontargeted therapy (log-rank test, χ21 = 5.79; P = .02); median survival was not statistically significantly different (8.7 months [95% CI, 7.3-10.2 months] vs 7.2 months [95% CI, 5.8-8.8 months]; P = .14). According to the instrumental variable analysis, the median overall survival advantage was 3.0 months (95% CI, 0.7-5.3 months), and overall survival improvements associated with targeted therapy vs nontargeted therapy were statistically significant: 8% at 1 year (44% [95% CI, 39%-50%] vs 36% [95% CI, 30%-42%]; P = .01), 7% at 2 years (25% [95% CI, 20%-30%] vs 18% [95% CI, 13%-23%]; P = .009), and 5% at 3 years (15% [95% CI, 11%-19%] vs 10% [95% CI, 6%-13%]; P = .01). Receipt of targeted therapy was associated with a lower hazard of death compared with nontargeted therapy (overall survival hazard ratio, 0.78 [95% CI, 0.65-0.94]; RCC-specific survival hazard ratio, 0.77 [95% CI, 0.62-0.96]). Conclusions and Relevance: Targeted therapies were associated with modest survival advantages despite a treatment group with more medical complexity, likely reflecting appropriateness for an expanded population of patients. As advances in cancer treatment continue, rigorous methods that account for unobserved confounders will be needed to evaluate their real-world impact on outcomes.

Patient-Centered Preference Assessment to Improve Satisfaction With Care Among Patients With Localized Prostate Cancer: A Randomized Controlled Trial.

PURPOSE: To study the effectiveness of the Patient Preferences for Prostate Cancer Care (PreProCare) intervention in improving the primary outcome of satisfaction with care and secondary outcomes of satisfaction with decision, decision regret, and treatment choice among patients with localized prostate cancer. METHODS: In this multicenter randomized controlled study, we randomly assigned patients with localized prostate cancer to the PreProCare intervention or usual care. Outcomes were satisfaction with care, satisfaction with decision, decision regret, and treatment choice. Assessments were performed at baseline and at 3, 6, 12, and 24 months, and were analyzed using repeated measures. We compared treatment choice across intervention groups by prostate cancer risk categories. RESULTS: Between January 2014 and March 2015, 743 patients with localized prostate cancer were recruited and randomly assigned to receive PreProCare (n = 372) or usual care (n = 371). For the general satisfaction subscale, improvement at 24 months from baseline was significantly different between groups (P < .001). For the intervention group, mean scores at 24 months improved by 0.44 (SE, 0.06; P < .001) from baseline. This improvement was 0.5 standard deviation, which was clinically significant. The proportion reporting satisfaction with decision and no regret increased over time and was higher for the intervention group, compared with the usual care group at 24 months (P < .05). Among low-risk patients, a higher proportion of the intervention group was receiving active surveillance, compared with the usual care group (P < .001). CONCLUSION: Our patient-centered PreProCare intervention improved satisfaction with care, satisfaction with decision, reduced regrets, and aligned treatment choice with risk category. The majority of our participants had a high income, with implications for generalizability. Additional studies can evaluate the effectiveness of PreProCare as a mechanism for improving clinical and patient-reported outcomes in different settings.

Lack of Effectiveness of Postchemotherapy Lymphadenectomy in Bladder Cancer Patients with Clinical Evidence of Metastatic Pelvic or Retroperitoneal Lymph Nodes Only: A Propensity Score-based Analysis.

BACKGROUND: Limited data is available on the role, and extent of, postchemotherapy lymphadenectomy (PC-LND) in patients with clinical evidence of pelvic (cN1-3) or retroperitoneal (RP) lymph node spread from urothelial bladder carcinoma. OBJECTIVE: To compare the outcomes of operated versus nonoperated patients after first-line chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: Data from 34 centers was collected, totaling 522 patients, treated between January 2000 and June 2015. Criteria for patient selection were the following: bladder primary tumor, lymph node metastases (pelvic±RP) only, first-line platinum-based chemotherapy given. INTERVENTION: LND (with cystectomy) versus observation after first-line chemotherapy for metastatic urothelial bladder carcinoma. OUTCOME MEASURES AND STATISTICAL ANALYSIS: Overall survival (OS) was the primary endpoint. Multiple propensity score techniques were adopted, including 1:1 propensity score matching and inverse probability of treatment weighting. Additionally, the inverse probability of treatment weighting analysis was performed with the inclusion of the covariates, that is, with doubly robust estimation. RESULTS AND LIMITATIONS: Overall, 242 (46.4%) patients received PC-LND and 280 (53.6%) observation after chemotherapy. There were 177 (33.9%) and 345 (66.1%) patients with either RP or pelvic LND only, respectively. Doubly robust estimation-adjusted comparison was not significant for improved OS for PC-LND (hazard ratio [HR]: 0.86, 95% confidence interval [CI]: 0.56-1.31, p=0.479), confirmed by matched analysis (HR: 0.91, 95% CI: 0.60-1.36, p=0.628). This was also observed in the RP subgroup (HR: 1.12, 95% CI: 0.68-1.84). The retrospective nature of the data and the heterogeneous patient population were the major limitations. CONCLUSIONS: Although there were substantial differences between the two groups, after accounting for major confounders we report a nonsignificant OS difference with PC-LND compared with observation only. These findings may be hypothesis-generating for future prospective trials. PATIENT SUMMARY: We found no differences in survival by adding postchemotherapy lymphadenectomy in patients with pelvic or retroperitoneal lymph node metastatic bladder cancer. The indication to perform postchemotherapy lymphadenectomy in the most suitable patients requires additional studies.

Neoadjuvant Dose-dense Gemcitabine and Cisplatin in Muscle-invasive Bladder Cancer: Results of a Phase 2 Trial.

BACKGROUND: Accelerated (also termed dose-dense, DD) chemotherapy regimens such as accelerated methotrexate, vinblastine, doxorubicin, and cisplatin have shown better efficacy and tolerability in the metastatic setting, and shortened the time to surgery in the neoadjuvant setting compared to standard-schedule regimens. We hypothesized that a DD schedule of gemcitabine and cisplatin (GC) would shorten the time to surgery and yield similar pathologic complete response rates (pT0) in patients with muscle-invasive bladder cancer (MIBC) compared with historical controls with standard GC. OBJECTIVE: To determine the safety and efficacy of neoadjuvant DDGC in MIBC. DESIGN SETTING AND PARTICIPANTS: Patients with cT2-4a, N0-1, M0 MIBC were eligible and received three 14-d cycles of DDGC with pegfilgrastim support followed by radical cystectomy with lymph node dissection. The primary end point was the pT0 rate. Molecular subtypes were assigned and correlated with survival. RESULTS AND LIMITATIONS: Thirty-one patients were evaluable for toxicity and response, of whom 58% had baseline clinical stage >T2N0M0; the median age was 69 yr. Ten patients (32%, 95% confidence interval [CI] 16-49%) achieved ypT0N0 status at cystectomy. Another four patients (13%, 95% CI 1-25%) were downstaged to non-muscle-invasive (

Temporal trends and characteristics of clinical trials for which only one racial or ethnic group is eligible.

BACKGROUND: Increasing diversity in clinical trials may be worthwhile. We examined clinical trials that restricted eligibility to a single race or ethnicity. METHODS: We reviewed 19,246 trials registered on ClinicalTrials.gov through January 2013. We mapped trial ZIP-codes to U.S. Census and American Community Survey data. The outcome was whether trials required participants to be from a single racial or ethnic group. RESULTS: In adjusted analyses, the odds of trials restricting eligibility to a single race/ethnicity increased by 4% per year (95% CI 1.01-1.08, p = .024). Behavioral (5.79% with single race/ethnicity requirements), skin-related (4.49%), and Vitamin D (6.14%) studies had higher rates of single race/ethnicity requirements. Many other trial-specific characteristics, such as funding agency and region of the U.S. in which the trial opened, were associated with eligibility restrictions. In terms of neighborhood characteristics, studies with single race eligibility requirements were more likely to be located in ZIP-codes with greater percentages of those self-reporting the characteristic. For example, 35.2% (SD = 24.9%) of the population self-reported themselves as Black or African American in ZIP-codes with trials requiring participants to be Black/African American, but only 5.9% (SD = 6.9%) self-reported themselves as Black/African American in ZIP-codes with trials that required Asian ethnicity. In ZIP-codes with trials requiring Asian ethnicity, 24.6% (SD = 16.2%) self-reported as Asian. In ZIP-codes with trials requiring Hispanic/Latino ethnicity, 33.3% (SD = 28.5%) self-reported as Hispanic/Latino. Neighborhood level poverty rates and reduced English language ability were also associated with more single race eligibility requirements. CONCLUSIONS: In selected fields, there has been a modest temporal increase in single race/ethnicity inclusion requirements. Some studies may not fall under regulatory purview and hence may be less likely to include diverse samples. Conversely, some eligibility requirements may be related to health disparities research. Future work should examine whether targeted enrollment criteria facilitates development of personalized medicine or reduces trial access.

Treating Second Breast Events After Breast-Conserving Surgery for Ductal Carcinoma in Situ.

Background: Because of screening mammography, the number of ductal carcinoma in situ (DCIS) survivors has increased dramatically. DCIS survivors may face excess risk of second breast events (SBEs). However, little is known about SBE treatment or its relationship to initial DCIS care. Methods: Among a prospective cohort of women who underwent breast-conserving surgery (BCS) for DCIS from 1997 to 2008 at institutions participating in the NCCN Outcomes Database, we identified SBEs, described patterns of care for SBEs, and examined the association between DCIS treatment choice and SBE care. Using multivariable regression, we identified features associated with use of mastectomy, radiation therapy (RT), or antiestrogen therapy (AET) for SBEs. Results: Of 2,939 women who underwent BCS for DCIS, 83% received RT and 40% received AET. During the median follow-up of 4.2 years, 200 women (6.8%) developed an SBE (55% ipsilateral, 45% invasive). SBEs occurred in 6% of women who underwent RT for their initial DCIS versus 11% who did not. Local treatment for these events included BCS (10%), BCS/RT (30%), mastectomy (53%), or none (6%); only 28% of patients received AET. Independent predictors of RT or mastectomy for SBEs included younger age, shorter time to SBE diagnosis, and RT or AET for the initial DCIS. Conclusions: A sizable proportion of patients with SBEs were treated with mastectomy, most especially those who previously received RT for their initial DCIS and those who developed an ipsilateral SBE. Despite the occurrence of an SBE, relatively few patients received AET. Future studies should investigate optimal treatment approaches for SBEs, including the benefit of mastectomy versus lumpectomy for an ipsilateral SBE and the benefit of AET for a hormone-receptor-positive SBE contingent on AET use for the initial DCIS diagnosis.

Provider and patient burdens of obtaining oral anticancer medications.

Oral anticancer medications (OAMs) are frequently used to treat patients with cancer. Unlike intravenous chemotherapy, OAMs are covered by prescription drug plans. We examined barriers to initiation of OAMs in 116 patients with prostate or kidney cancer (149 unique prescriptions). We found that the median time from initial prescription to prior authorization was 3 days and the median time from initial prescription to patient receipt of drug was 12 days. Seventy-three percent of all prescriptions required 2 or more phone calls by clinic staff and 40% required 5 or more calls. Of 107 prescriptions with data available, 54% utilized financial assistance; these required significantly more phone calls (P = .0001) and led to a longer median time to drug obtainment (P = .003) compared with those that did not require financial assistance. In those prescriptions with both initial and final co-pay information available, the initial out-of-pocket mean and median co-pays were $1226.03 and $329.73, respectively, but these dropped to $124.57 and $25.00 after utilization of co-pay assistance programs, excluding those with a $0 final co-pay. These early observations suggest that a more efficient process for initiation of OAMs is needed.

Patient-centered recruitment and retention for a randomized controlled study.

BACKGROUND: Recruitment and retention strategies for patient-centered outcomes research are evolving and research on the subject is limited. In this work, we present a conceptual model of patient-centered recruitment and retention, and describe the recruitment and retention activities and related challenges in a patient-centered comparative effectiveness trial. METHODS: This is a multicenter, longitudinal randomized controlled trial in localized prostate cancer patients. RESULTS: We recruited 743 participants from three sites over 15 months period (January 2014 to March 2015), and followed them for 24 months. At site 1, of the 773 eligible participants, 551 (72%) were enrolled. At site 2, 34 participants were eligible and 23 (68%) enrolled. Of the 434 eligible participants at site 3, 169 (39%) enrolled. We observed that strategies related to the concepts of trust (e.g., physician involvement, ensuring protection of information), communication (e.g., brochures and pamphlets in physicians' offices, continued contact during regular clinic visits and calling/emailing assessment), attitude (e.g., emphasizing the altruistic value of research, positive attitude of providers and research staff), and expectations (e.g., full disclosure of study requirements and time commitment, update letters) facilitated successful patient recruitment and retention. A stakeholders' advisory board provided important input for the recruitment and retention activities. Active engagement, reminders at the offices, and personalized update letters helped retention during follow-up. Usefulness of telephone recruitment was site specific and, at one site, the time requirement for telephone recruitment was a challenge. CONCLUSIONS: We have presented multilevel strategies for successful recruitment and retention in a clinical trial using a patient-centered approach. Our strategies were flexible to accommodate site-level requirements. These strategies as well as the challenges can aid recruitment and retention efforts of future large-scale, patient-centered research studies. TRIAL REGISTRATION: Clinicaltrials.gov , ID: NCT02032550 . Registered on 22 November 2013.