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Purpose: There is a need to increase palliative care access for hospitalized older adults with cancer discharged to a skilled nursing facility (SNF) at risk of poor outcomes. Assessing and Listening to Individual Goals and Needs (ALIGN) is a palliative care intervention developed to address this gap. This study gathered perspectives from clinicians across care settings to describe perceptions on serious illness communication and care coordination for patients with cancer after discharge to a SNF to guide ALIGN refinements., Methods: We conducted 37 semistructured interviews with clinicians and leaders in hospital medicine (n = 12), oncology (n = 9), palliative care (n = 12), home health care (n = 6), and hospice (n = 4). Some participants had experience working in more than one specialty. The Practical Robust Implementation and Sustainability Model framework was used to develop the interview guide that explored barriers to care, prognosis discussions, and hospice recommendations. Interviews were coded and analyzed using thematic content analysis., Results: Analysis identified four themes: (1) discharge to a SNF is recognized as a time of worsening prognosis; (2) care silos create communication and information barriers during a period of increasing palliative care need; (3) family caregiver distress escalates following care transitions; and (4) lack of clarity of roles and respect for the patient-oncologist relationship limits prognostic communication and changes in focus of treatment., Conclusion: These findings suggest that acute and postacute care clinicians defer serious illness conversations to the oncologist when patients are on a steep trajectory of decline, experiencing multiple care transitions, and may have limited contact with their oncologist. There is a need to clarify roles among nononcology and oncology clinicians in discussing prognosis and recommending hospice for older adults discharged to SNF.

Background: Approximately 20% of the United States' population lives in a state or jurisdiction where medical aid in dying (MAiD) is legal. It is unknown how physicians' own barriers are associated with their provision of the spectrum of MAiD services., Objective: To measure physicians' religious and/or ethical barriers to providing MAiD services and how such barriers relate to physicians' intentions and behaviors., Design: Three-wave cross-sectional survey fielded in Colorado in 2020-2021., Participants: Physicians providing care to patients likely clinically eligible for MAiD according to probabilistic sampling., Main Measures: Physicians self-reported barriers to their own participation in MAiD. We considered large ethical and/or religious barriers to be conscience-based barriers. We measured physicians' self-reported intention to participate and self-reported prior participation in MAiD since it was legalized in Colorado in 2017. We estimated differences in intention and behavior outcomes according to presence of conscience-based barriers, adjusting for physician gender, race/ethnicity, time in practice, and specialty., Key Results: Among 300 respondents, 26% reported "large" ethical and/or religious barriers to their involvement in MAiD. Physicians with longer time in practice and those identifying as non-White were more likely to report conscience-based barriers to MAiD. Comparing physicians with and without conscience-based barriers to MAiD, we found no difference in ancillary participation (discussing, referring) but significant differences in direct participation (serving as consultant [5% vs. 31%] or attending [0% vs. 22%])., Conclusions: Approximately one-quarter of physicians likely to care for MAiD-eligible patients in Colorado reported religious and/or ethical barriers to MAiD. Despite religious and/or ethical barriers, the vast majority of physicians were willing to discuss MAiD and/or refer patients seeking MAiD services. These data provide important empirical foundation for policy from hospitals and health systems as well as medical specialty groups with official positions on MAiD., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Background: Nivolumab plus cabozantinib (NIVO + CABO) was approved for first-line treatment of advanced renal cell carcinoma (aRCC) based on superiority versus sunitinib (SUN) in the phase III CheckMate 9ER trial (18.1 months median survival follow-up per database lock date); efficacy benefit was maintained with an extended 32.9 months of median survival follow-up. We report updated efficacy and safety after 44.0 months of median survival follow-up in intent-to-treat (ITT) patients and additional subgroup analyses, including outcomes by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic risk score., Patients and Methods: Patients with treatment-naïve aRCC received NIVO 240 mg every 2 weeks plus CABO 40 mg once daily or SUN 50 mg for 4 weeks (6-week cycles), until disease progression/unacceptable toxicity (maximum NIVO treatment, 2 years). Primary endpoint was progression-free survival (PFS) per blinded independent central review (BICR). Secondary endpoints were overall survival (OS), objective response rate (ORR) per BICR, and safety and tolerability., Results: Overall, 323 patients were randomised to NIVO + CABO and 328 to SUN. Median PFS was improved with NIVO + CABO versus SUN [16.6 versus 8.4 months; hazard ratio (HR) 0.59; 95% confidence interval (CI) 0.49-0.71]; median OS favoured NIVO + CABO versus SUN (49.5 versus 35.5 months; HR 0.70; 95% CI 0.56-0.87). ORR (95% CI) was higher with NIVO + CABO versus SUN [56% (50% to 62%) versus 28% (23% to 33%)]; 13% versus 5% of patients achieved complete response, and median duration of response was 22.1 months versus 16.1 months, respectively. PFS and OS favoured NIVO + CABO over SUN across intermediate, poor and intermediate/poor IMDC risk subgroups; higher ORR and complete response rates were seen with NIVO + CABO versus SUN regardless of IMDC risk subgroup. Any-grade (grade ≥3) treatment-related adverse events occurred in 97% (67%) versus 93% (55%) of patients treated with NIVO + CABO versus SUN., Conclusions: After extended follow-up, NIVO + CABO maintained survival and response benefits; safety remained consistent with previous follow-ups. These results continue to support NIVO + CABO as a first-line treatment for aRCC., Trial Registration: ClinicalTrials.gov, NCT03141177., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The incidence of severe immune-related adverse events (irAEs) in cancer subjects receiving immune checkpoint inhibitors (ICIs) following COVID-19 vaccination and the relationship between the incidence of severe irAE and the interval between COVID-19 vaccination and ICI dose have not been established. We performed a retrospective study evaluating the incidence of irAEs in solid tumor subjects receiving ICI therapy who received any COVID-19 vaccinations since FDA authorization. irAEs were defined as severe with one or more grade 3 or above events (CTCAE v5.0), multiple organ involvement, or requiring hospitalization for management. Two hundred and eighty-four subjects who received COVID vaccinations from December 2020 and February 2022 were included in this analysis [median age at vaccination 67 years (IQR 59.0-75.0); 67.3% male]. Twenty-nine subjects (10.2%) developed severe irAEs, of which 12 subjects (41.4%) received ICI monotherapy, 10 subjects (34.5%) received combination ICI therapy with nivolumab and ipilimumab, and 7 subjects (24.1%) received ICI plus VEGFR-TKI therapy. Hospitalization occurred in 62% of subjects with severe irAEs, with a median duration of 3 days (IQR: 3.0-7.5 days). Immunosuppressive therapy was required in 79.3%, with a median duration of 103 days (IQR: 42.0-179.0). ICI therapy was discontinued in 51.7% of subjects with severe irAE; dosing was held or interrupted in 34.5%. Among severe irAEs, the median interval between vaccination and ICI treatment closest to the occurrence of severe irAE was 15.5 days (IQR: 10.0-23.0). In solid tumor cancer subjects receiving ICIs, COVID-19 vaccination is not associated with an increased incidence of severe irAEs compared to historical data and may be safely administered during ICI cancer therapy in subjects who lack contraindications.

Objectives: Caregivers of adult phase 1 oncology trial patients experience high levels of distress and face barriers to in-person supportive care. The Phase 1 Caregiver LifeLine (P1CaLL) pilot study assessed the feasibility, acceptability, and general impact of an individual telephone-based cognitive behavioral stress-management (CBSM) intervention for caregivers of phase I oncology trial patients., Methods: The pilot study involved 4 weekly adapted CBSM sessions followed by participant randomization to 4 weekly cognitive behavioral therapy sessions or metta-meditation sessions. A mixed-methods design used quantitative data from 23 caregivers and qualitative data from 5 caregivers to examine the feasibility and acceptability outcomes. Feasibility was determined using recruitment, retention, and assessment completion rates. Acceptability was assessed with self-reported satisfaction with program content and participation barriers. Baseline to post-intervention changes in caregiver distress and other psychosocial outcomes were assessed for the 8-session intervention., Results: The enrollment rate was 45.3%, which demonstrated limited feasibility based on an a priori criterion enrollment rate of 50%. Participants completed an average of 4.9 sessions, with 9/25 (36%) completing all sessions and an 84% assessment completion rate. Intervention acceptability was high, and participants found the sessions helpful in managing stress related to the phase 1 oncology trial patient experience. Participants showed reductions in worry and isolation and stress., Significance of Results: The P1CaLL study demonstrated adequate acceptability and limited feasibility and provided data on the general impact of the intervention on caregiver distress and other psychosocial outcomes. Caregivers of phase 1 oncology trial patients would benefit from supportive care services; a telephone-based intervention may have more utilization and thus make a larger impact.

Background: Penile cancer accounts for less than 1% of male cancers in the United States. Localized disease, particularly T1 tumors are potentially curable with local therapy. We present the racial differences in survival outcomes for T1, penile cancer from the SEER database., Methods: From 2004 to 2016 all men with T1, N0, M0 penile cancer in the SEER-18 database were included. Kaplan-Meier analysis and multivariable Cox-Regression analysis were conducted to investigate prognostic variables for cancer specific survival (CSS)., Results: A total of 4,406 men were identified with penile cancer; 1,941 men had T1 disease. The Kaplan-Meier (KM) analysis showed those with primary site surgery had better 5-year CSS compared to those without primary site surgery (P <.0001) and a significant difference in CSS based on race (P= 0.0078). On multivariable analysis, Hispanic individuals had worse CSS (HR 1.92; P = 0.0057) compared to the White men. Black men were also found to have a poor CSS however this was not statistically significant (HR 1.53, P = 0.118). Men with penile cancer who had either penectomy (HR 0.45; P = 0.006) or penile preservation surgery (HR 0.25; P< 0.001) had improved CSS., Conclusion: Racial disparities in CSS exist among men with in early-stage penile cancer. KM analysis showed significant differences in CSS by race and in those receiving primary site surgery. On multivariable analysis, the CSS is worse in Hispanic compared to White men. There is a trend towards worse CSS in Black men however this was not statistically significant., Competing Interests: Declaration of Competing Interest Authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In Colorado, medical aid in dying (MAiD) is legal, allowing a terminally ill person to request a prescription and self-administer a medication to end their life. Such requests are granted under certain circumstances, including a malignant neoplasm diagnosis, with a goal of peaceful death. This study examined differences in attitudes and actual participation in MAiD between oncologists and non-oncologists, using data from a recent survey of physicians regarding MAiD., (© The Author(s) 2023. Published by Oxford University Press.)

Purpose: Immune checkpoint inhibitor and VEGFR inhibitor combinations are effective treatments for patients with metastatic renal cell carcinoma (mRCC). This phase I/II clinical trial evaluated the safety and efficacy of pembrolizumab and cabozantinib in patients with mRCC., Experimental Design: Eligible patients had mRCC with clear-cell or non-clear cell histology, adequate organ function, Eastern Cooperative Oncology Group 0-1 performance status, and no prior exposure to pembrolizumab or cabozantinib. The primary endpoint was objective response rate (ORR) at the recommended phase II dose (RP2D). Secondary endpoints included safety, disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS)., Results: Forty-five patients were enrolled. A total of 40 patients were treated at the RP2D of pembrolizumab 200 mg i.v. every 3 weeks and cabozantinib 60 mg orally once daily, 38 of which were evaluable for response. The ORR was 65.8% [95% confidence interval (CI), 49.9-78.8] for all evaluable patients [78.6% as first-line therapy, 58.3% as second-line therapy]. The DCR was 97.4% (95% CI, 86.5-99.9). Median DoR was 8.3 months (interquartile range, 4.6-15.1). At a median follow-up of 23.54 months, the median PFS was 10.45 months (95% CI, 6.25-14.63) and median OS was 30.81 months (95% CI, 24.2-not reached). The most common grade 1 and/or 2 treatment-related adverse events (TRAE) were diarrhea, anorexia, dysgeusia, weight loss, and nausea. The most common grade 3 and/or 4 TRAEs were hypertension, hypophosphatemia, alanine transaminase elevation, diarrhea, and fatigue. There was one grade 5 TRAE of reversible posterior encephalopathy syndrome related to cabozantinib., Conclusions: Pembrolizumab and cabozantinib treatment in patients with mRCC demonstrated encouraging preliminary efficacy and a manageable toxicity profile comparable with other available checkpoint inhibitor-tyrosine kinase inhibitor combinations., Trial Registration: ClinicalTrials.gov Identifier: NCT03149822 https://clinicaltrials.gov/ct2/show/NCT03149822., Significance: This study evaluated the safety and effectiveness of the combination of pembrolizumab and cabozantinib in patients with mRCC. The safety profile was manageable. The combination showed promising activity with an objective response rate of 65.8%, median PFS of 10.45 months, and median OS of 30.81 months., (© 2023 The Authors; Published by the American Association for Cancer Research.)

The majority of men with prostate cancer are diagnosed when they are older than 65 years; however, clinical trial participants are disproportionately younger and more fit than the real-world population treated in typical clinical practices. It is, therefore, unknown whether the optimal approach to prostate cancer treatment is the same for older men as it is for younger and/or more fit men. Short screening tools can be used to efficiently assess frailty, functional status, life expectancy, and treatment toxicity risk. These risk assessment tools allow for targeted interventions to increase a patient's reserve and improve treatment tolerance, potentially allowing more men to experience the benefit of the significant recent treatment advances in prostate cancer. Treatment plans should also take into consideration each patient's individual goals and values considered within their overall health and social context to reduce barriers to care. In this review, we will discuss evidence-based risk assessment and decision tools for older men with prostate cancer, highlight intervention strategies to improve treatment tolerance, and contextualize these tools within the current treatment landscape for prostate cancer.

Background: The involvement of Medical Aid in Dying (MAiD) experts to guide MAiD prescribers who may be unfamiliar with the process is unknown. Objective: To examine the involvement of consulting services on physician experiences participating in MAiD activities. Design: This is an anonymous survey. Participants: Colorado physicians ( n  = 583) likely to care for MAiD-eligible patients. Measures: Consulting services used in a recent MAiD case and perspectives on use of a MAiD service. Results: Of 300 physicians (response rate 55%), 49 physicians had served as a MAiD attending and/or consulting physician. In a recent MAiD case, commonly used services included palliative care (92%), hospice (81%), social work (78%), or a MAiD service (63%). When a MAiD service was not used vs. used, respondents felt the MAiD case was less professionally risky (28% vs. 7%, p  = 0.04). Conclusion: Along with palliative care, hospice, and social work, use of an experienced MAiD service was relatively common. The role and function of MAiD services warrant further exploration.

Medical aid in dying (MAiD), despite being legal in many jurisdictions, remains controversial ethically. Existing surveys of physicians' perceptions of MAiD tend to focus on the legal or moral permissibility of MAiD in general. Using a novel sampling strategy, we surveyed physicians likely to have engaged in MAiD-related activities in Colorado to assess their attitudes toward contemporary ethical issues in MAiD.

Background: Approximately 20% of the US population live in states where MAiD is a legal, though highly contentious, practice. Little generalizable data exists on the experiences of MAiD providers who comprise a small, and intentionally hidden, population., Objective: To examine the nature, extent, and consequences of physicians' participation in MAiD., Design: An anonymous, multi-wave, mailed survey (RR= 55%)., Participants: An enriched sample (n=583) of Colorado physicians caring for potential MAiD patients., Main Measures: Physician willingness, preparedness, and participation in a continuum of MAiD activities. Other outcomes include the effects of providing MAiD and the barriers physicians face related to MAiD., Key Results: Overall, 81.1% of respondents were willing to discuss MAiD with a patient, 88.3% to refer for MAiD, 46.3% to be a consultant, and 28.1% to be an attending. Fewer felt prepared to discuss MAiD (54.4%), provide a MAiD referral (62.8%), be a consultant (30.7%), or be an attending (18.0%). More than half of respondents (52.3%) had discussed MAiD with a patient, 27.3% provided a MAiD referral, 12.8% had been a MAiD consultant, and 8.5% had been a MAiD attending. Among MAiD consultants and attendings, 75% reported that their most recent MAiD case was emotionally fulfilling and professionally rewarding, though 75% also reported that it was time consuming and 46.9% reported that it was ethically challenging. Common barriers to physician participation in MAiD include lack of knowledge about MAiD (46.8%), the emotional (45.6%) and time (41.7%) investments, and ethical concerns (41.7%)., Conclusions: Many physicians in our sample are both willing and prepared to discuss MAiD with patients and to provide MAiD referrals. Fewer are prepared and willing to serve as an attending or consultant and fewer have provided these services. MAID consultants and attendings largely report the experience to be emotionally fulfilling and professionally rewarding, but all respondents reported multiple barriers to participation., (© 2021. The Author(s) under exclusive licence to Society of General Internal Medicine.)

Background: In the primary analysis of CheckMate 9ER, nivolumab plus cabozantinib showed superior progression-free survival, overall survival, and objective response over sunitinib in patients with previously untreated advanced renal cell carcinoma (median follow-up of 18·1 months). Here, we report extended follow-up of overall survival and updated efficacy and safety., Methods: This open-label, randomised, phase 3 trial was done in 125 hospitals and cancer centres across 18 countries. We included patients aged 18 years or older with previously untreated advanced or metastatic clear-cell renal cell carcinoma, a Karnofsky performance status of 70% or higher, measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 assessed by the investigator, any International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic risk category, and available tumour tissue for PD-L1 testing. Patients were randomly assigned (1:1) to nivolumab (240 mg) intravenously every 2 weeks plus cabozantinib (40 mg) orally once daily or sunitinib (50 mg orally) once daily (4 weeks per 6-week cycle). Randomisation, stratified by IMDC risk status, tumour PD-L1 expression, and geographical region, was done by permuted block within each stratum using a block size of four, via an interactive response system. The primary endpoint was progression-free survival by blinded independent central review. Overall survival was a secondary endpoint (reported here as the preplanned final analysis according to the protocol). Efficacy was assessed in all randomly assigned patients; safety was assessed in all patients who received at least one dose of any study drug. This ongoing study, closed to recruitment, is registered with ClinicalTrials.gov, NCT03141177., Findings: Between Sept 11, 2017, and May 14, 2019, 323 patients were randomly assigned to the nivolumab plus cabozantinib group and 328 to the sunitinib group. With an extended follow-up (data cutoff of June 24, 2021; median 32·9 months [IQR 30·4-35·9]), median overall survival was 37·7 months (95% CI 35·5-not estimable) in the nivolumab plus cabozantinib group and 34·3 months (29·0-not estimable) in the sunitinib group (hazard ratio [HR] 0·70 [95% CI 0·55-0·90], p=0·0043) and updated median progression-free survival was 16·6 months (12·8-19·8) versus 8·3 months (7·0-9·7; HR 0·56 [95% CI 0·46-0·68], p<0·0001). Grade 3-4 treatment-related adverse events occurred in 208 (65%) of 320 patients with nivolumab plus cabozantinib versus 172 (54%) of 320 with sunitinib. The most common grade 3-4 treatment-related adverse events were hypertension (40 [13%] of 320 patients in the nivolumab plus cabozantinib group vs 39 [12%] of 320 in the sunitinib group), palmar-plantar erythrodysaesthesia (25 [8%] vs 26 [8%]), and diarrhoea (22 [7%] vs 15 [5%]). Grade 3-4 treatment-related serious adverse events occurred in 70 (22%) of 320 patients in the nivolumab plus cabozantinib group and 31 (10%) of 320 in the cabozantinib group. One additional treatment-related death occurred with sunitinib (sudden death)., Interpretation: With extended follow-up and preplanned final overall survival analysis per protocol, nivolumab plus cabozantinib demonstrated improved efficacy versus sunitinib, further supporting the combination in the first-line treatment of advanced renal cell carcinoma., Funding: Bristol Myers Squibb and Ono Pharmaceutical., Competing Interests: Declaration of interests RJM reports advisory board fees from AstraZeneca, AVEO Pharmaceuticals, Eisai, EMD Serono, Exelixis, Genentech/Roche, Incyte, Lilly Oncology, Merck, Novartis, and Pfizer; and institutional funding from Bristol Myers Squibb (BMS), Eisai, Exelixis, Genentech/Roche, Merck, and Pfizer. TP reports grants from AstraZeneca, Roche, BMS, Exelixis, Ipsen, Merck, Merck Sharp & Dohme (MSD), Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas Pharma, Johnson & Johnson, and Eisai; consulting fees from BMS, Merck, AstraZeneca, Ipsen, Pfizer, Novartis, Incyte, Seattle Genetics, Roche, Exelixis, MSD, Merck Serono, Astellas Pharma, Johnson & Johnson, and Eisai; and travel support from Pfizer, MSD, AstraZeneca, Roche, and Ipsen. MB reports consulting fees from Roche/Genentech, BMS, MSD Oncology, Novartis, AstraZeneca; and speakers' bureau fees from Roche/Genentech, MSD Oncology, BMS, and AstraZeneca. BE reports an institutional research grant from BMS; consulting fees from Pfizer, BMS, Ipsen, AVEO, Oncorena, and Eisai; honoraria from Pfizer, BMS, Ipsen, Oncorena, and Eisai; and travel support from BMS, Ipsen, and MSD. MTB reports consulting fees from BMS, Asofarma, Eisai, MSD Oncology, Janssen Oncology, Novartis, Bayer, and Ferring; speakers' bureau fees from Asofarma, MSD Oncology, BMS, Bayer, Eisai, Janssen Oncology, Ipsen, Pfizer, Merck, Ferring, Tecnofarma, Medicamenta, AstraZeneca, and Astellas Pharma; honoraria from BMS and Tecnofarma; payment for expert testimony from Asofarma; travel support from Asofarma, Janssen-Cilag, MSD Oncology, BMS Mexico, Pfizer, Ipsen, and Sanofi; and steering committee honoraria from BMS. AYS reports research grants from BMS, Eisai, 4D Pharma, and EMD Serono; consulting fees from Exelixis, BMS, Pfizer, and EMD Serono; and honoraria from Eisai and Oncology Information Group. CSu reports research grants from AB Science, Aragon Pharmaceuticals, Astellas Pharma, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim España, BMS, Clovis Oncology, Exelixis, Genentech, GlaxoSmithKline, Hoffman-La Roche, Novartis Farmaceutica, Pfizer, and Sanofi-Aventis; speakers' bureau fees from Astellas Pharma, Bayer, BMS, EUSA Pharma, Hoffmann-La Roche, Ipsen, and Pfizer; and advisory board fees from Astellas Pharma, Bayer, BMS, EUSA Pharma, Hoffman-La Roche, Ipsen, MSD, Novartis, Pfizer, and Sanofi-Aventis. AH reports advisory board fees from MSD and Janssen. CP reports consulting fees from Angelini Pharma, AstraZeneca, BMS, Eisai, EUSA Pharma, Ipsen, Merck Serono, and MSD; speakers' bureau fees from BMS, EUSA Pharma, General Electric, Ipsen, and MSD; payment for expert testimony from EUSA Pharma and Pfizer; and travel support from Roche. CMH reports institutional research grant from BMS, and stock options from Telix Pharmaceuticals, Volpara Health Technologies, Alcidon, and Nanosonics. ERK reports a personal research grant from Medivation/Astellas; institutional research grant from BMS, Genentech/Roche, Pfizer, and Merck Serono; and stock options from Johnson & Johnson. HG reports advisory board fees from BMS, Ipsen, MSD, AstraZeneca, Janssen-Cilag, Pfizer, Roche, and Merck Serono; speakers' bureau fees from Merck Serono; and travel support from AstraZeneca. YT reports institutional research grants from Ono Pharmaceutical, Takeda, and Astellas; and honoraria from BMS, Pfizer, Ono Pharmaceutical, and Astellas. JB reports institutional research grants from BMS, Astellas Pharma, Ipsen, MSD Oncology, Novartis, Roche, Exelixis, Pfizer, and Seagen; consulting fees from BMS, Eisai, EUSA Pharma, Ipsen, MSD Oncology, AstraZeneca, Roche, Pfizer, and Merck; and speakers' bureau fees from MSD Oncology, BMS, Merck, Pfizer, Ipsen, and Roche. JZ and BS are employed by and have stock ownership in BMS. CSc is employed by and has stock ownership in Exelixis. TKC reports research grants, consulting fees, honoraria, and advisory board fees from AstraZeneca, Aravive, AVEO, Bayer, BMS, Calithera, Circle Pharma, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, IQVIA, Infinity, Ipsen, Janssen, Kanaph, Lilly, Merck, NiKang, Nuscan, Novartis, Pfizer, Roche, Sanofi-Aventis, Surface Oncology, Takeda, Tempest, UpToDate, and continuing medical education events (Peerview, OncLive, MJH, and others), outside the submitted work; institutional patents filed on molecular mutations and immunotherapy response, and circulating tumour DNA; leadership fees from the National Comprehensive Cancer Network, US NCI Genitourinary Steering Committee, American Society of Clinical Oncology, and European Society for Medical Oncology; stock ownership in Pionyr, Tempest, Osel, and NuscanDx; other financial or non-financial interests include medical writing and editorial assistance support that might in part have been funded by communications companies; potential funding (in part) from non-US sources or foreign institutions for mentoring of several non-US citizens on research projects; independent funding by drug companies or royalties potentially involved in research around the subject matter (institutional); and support in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE (2P50CA101942-16) and Program 5P30CA006516-56, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, and Loker Pinard Funds for Kidney Cancer Research at the Dana-Farber Cancer Institute. ABA declares no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Bladder cancer is one of the top 10 cancers diagnosed in Americans with a median age of 73. This is the patient population that tends to be older with multiple medical conditions, and previously described variability in treatment in the earlier stages of the disease. This study aimed to evaluate the first-line therapeutic choices for older adults newly diagnosed with advanced bladder cancer. In addition, this work evaluated predictors of response as well as the role of events of functional importance in relation to treatment assignment., Methods: A population-based cohort study was conducted using the SEER-Medicare database of patients with advanced stage bladder cancer not eligible for curative intent therapy between 2010 and 2013. Patient groups of interest were compared via univariate and multivariate associations. Additionally, a latent class analysis was applied to identify classes with similar features in reference to events of functional importance-events linked to the maintenance or improvement of physical function status., Results: Within the sample, we noted that a minority of patients received a standard cisplatin-containing regimen (14.77%) and a majority did not receive any chemotherapy (59.69%). Most patients were over age 75. The adjusted odds ratio of no chemo versus cisplatin in patients aged 76 and older compared to patients 66-75 was 6.61 (4.79-9.13; p < 0.0001). We applied latent class analysis methods to the dataset, and three classes demonstrated very low and moderate levels of functional events in the 12 months prior to a person's first outpatient visit for advanced bladder cancer care., Conclusions: Patients with new diagnosis of advanced bladder cancer largely do not receive the recommended first-line systemic therapy of cisplatin chemotherapy, and a significant majority does not receive any treatment. When evaluating the association between class assignment and predictors of chemotherapy use, such as comorbidity and age, patients with "low usage overall" were more likely to receive chemotherapy. Yet even patients who received chemotherapy had some events of functional importance., Competing Interests: CONFLICT OF INTEREST The authors have no conflicts of interest to report related to the data presented.

Objectives: Advanced bladder cancer (ABC) disproportionately affects older adults, and little is known about older patients' priorities for care planning in advanced cancer. Patient-centered communication remains crucial to shared decision-making between patients, families, and providers. Yet, older patients with cancer may not always know how to express their preferences, and oncologists do not always review patients' informational needs. This study aimed to understand preferences of older patients with ABC related to their communication with providers and navigation of care planning., Materials and Methods: This qualitative descriptive study involved in-depth interviews and focus groups with older patients with ABC and their care partners, which explored their priorities for care planning and communication with providers, decision-making processes, and valued traits in ABC care. Data were analyzed using thematic analysis., Results: Ten participants attended focus groups or interviews. Seven patients were male and three care partners were female. The mean age was 74. Time since ABC diagnosis ranged from three to seventeen months. Four key themes illustrate participants' priorities in their ABC care as older adults: 1. The significance of key phrasing in communication from oncologists, 2. The need for clear expectation-setting about prognosis and treatment, 3. The role of others in patient care decisions, and 4. Valued traits in care communication., Conclusion: Older patients with ABC and their care partners are active participants in their care. Oncologists should prioritize setting clear expectations for treatment, involving family in care planning, and communicating honestly about expected changes to quality of life and functional status., Competing Interests: Declaration of Competing Interest The Authors declare that there is no conflict of interest related to this current research., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Physicians who participate in medical-aid-in-dying (MAID) cannot be easily identified and studied due to cost and anonymity barriers. We developed and empirically tested a novel methodology to identify and survey physicians highly likely to participate in MAID activities. We used a state-level comprehensive administrative claims database to identify a cohort of patients with diagnoses and hospice enrollment similar to those known to have filled a prescription for MAID from 2017-2018. We then identified physicians who provided routine outpatient care to these patients using National Provider Identifier numbers. We surveyed these physicians in 3 waves (n = 583 total surveys), ranking physicians in order of their likelihood of being asked about MAID for each wave based on characteristics including specialty and the number of unique patients they had provided care to. We re-ranked physicians in waves 2 and 3 based on responses from prior waves. Physicians were surveyed only once and there was no follow-up to preserve anonymity. Surveys assessed the proportion of respondents who participated in MAID activities (discussions, referrals, and/or prescriptions). We identified 6369 physicians that provided care to 2960 patients. In survey waves one, two, and three respectively, response rates (55%, 52%, and 55%; p = 0.98) and the proportion of respondents that participated in MAID activities (58%, 56%, and 42%; p = 0.05) were similar. Small adjustments made to physician ranking criteria in waves two and three did not increase the proportion of physicians that participated in MAID activities. We used a novel methodology using administrative data to identify and survey physicians at high likelihood of participating in MAID activities. We achieved good overall response rates (52%), and a high proportion of respondents that participated in MAID activities (52%), demonstrating that it is possible to overcome cost and anonymity barriers to conducting quantitative research on MAID. This methodology could be used in larger scale studies of MAID or other bioethical issues with "hidden" physician populations., (© 2022. The Author(s).)

Background: Following a prostate cancer (PC) diagnosis, treatment-related symptoms may result in diminished quality of life (QoL). Improved diet and increased exercise may improve QoL in men with PC., Methods: We conducted a 4-arm pilot randomized trial to assess feasibility and acceptability of a 3-month web-based diet and exercise intervention, among men (>18 years of age) with PC (reported elsewhere). The purpose of this study is to describe the change in QoL measured by surveys (eg, QLQ-C30, PROMIS Fatigue) at enrollment and following the intervention. Men were randomized 1:1:1:1 to increasing levels of web-based behavioral support: Level 1: website; Level 2: Level 1 plus personalized diet and exercise prescription; Level 3: Levels 1-2 plus Fitbit and text messages; Level 4: Levels 1-3 plus 2 30-minute coaching calls. T -tests were used to compare pre-post change in mean QoL scores between each Level and Level 1., Results: Two hundred and two men consented and were randomized (n = 49, 51, 50, 52 for Levels 1-4, respectively). Men were predominantly white (93%), with a median age of 70 years (Intra-quartile Range [IQR]: 65,75) and 3 years (IQR: 1,9) post primary treatment for mostly localized disease (74% with T1-2). There were no meaningful changes in QoL, but there were notable trends. Level 3 participants had small improvements in QLQ-C30 Global Health (5.46; 95% CI: -0.02, 10.95) compared to Level 1. In contrast, Level 2 participants trended toward decreasing Global QoL (-2.31, 95% CI: -8.05, 3.42), which may reflect declines in function (eg, Cognitive: -6.94, 95% CI: -13.76, -0.13) and higher symptom burden (eg, Diarrhea: 4.63, 95% CI: -1.48, 10.74)., Conclusions: This short, web-based intervention did not appear to have an impact on PC survivors' QoL. Most men were several years past treatment for localized disease; the potential for this approach to reduce symptoms and improve QoL in men who have worse health may still be warranted.

Purpose of Review: Prostate cancer is the second most common cancer in men in the USA and several studies suggest more aggressive disease in older patients. However, screening remains controversial, especially in the older patient population., Recent Findings: Aggressive prostate cancers are more common in older men. Screening trial results are conflicting but data suggest an improvement in prostate cancer mortality and increased detection of metastatic disease with screening. When PSA is utilized with multiparametric MRI and biomarker assays, patients at significant risk of clinically meaningful prostate cancer can be appropriately selected for biopsy. A thoughtful and individualized approach is central when considering prostate cancer screening in older men. This approach includes life expectancy estimation, use of appropriate geriatric assessment tools, use of multiparametric MRI and biomarkers in addition to PSA, and most importantly shared decision-making with patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Central nervous system (CNS) metastasis from prostate cancer (PCA) is a rare event, but one with significant prognostic impact for those affected. There are limited data on its impact in contemporary cohorts treated with modern agents., Patients and Methods: A retrospective institutional review was performed to characterize the occurrence/outcome of PCA CNS metastasis on all cases of PCA from 2011 to 2017. A manual chart review was performed to confirm PCA CNS metastases in all cases identified through a diagnostic code screening of the health data., Results: A total of 6596 cases of PCA were identified, with 29 (20 dural and 9 intraparenchymal) confirmed cases of CNS metastases from PCA. The median survival from the time of diagnosis of CNS metastasis was 2.6 months (95% confidence interval, 2.04-10.78 months) and 5.41 months (95% confidence interval, 3.03 months to not reached) for dural and parenchymal metastases, respectively. Among those who developed CNS metastases, approximately 79% of patients had prior exposure to abiraterone and/or enzalutamide, of whom 50% had ≥ 6 months of exposure. Four (0.07%) of the 5841 patients developed CNS metastases prior to the initiation of therapy or on androgen deprivation therapy alone. In contrast, 24 (8.6%) of the 279 patients with 2 or more lines of medical therapy developed CNS metastases., Conclusions: Our analysis highlights the continued poor prognosis of parenchymal and dural CNS metastases from PCA. CNS metastases in PCA remain a rare event with a 0.4% incidence in this series, but this incidence is considerably increased in patients who receive medical therapy beyond first-line androgen deprivation therapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known., Methods: In this phase 3, randomized, open-label trial, we randomly assigned adults with previously untreated clear-cell, advanced renal-cell carcinoma to receive either nivolumab (240 mg every 2 weeks) plus cabozantinib (40 mg once daily) or sunitinib (50 mg once daily for 4 weeks of each 6-week cycle). The primary end point was progression-free survival, as determined by blinded independent central review. Secondary end points included overall survival, objective response as determined by independent review, and safety. Health-related quality of life was an exploratory end point., Results: Overall, 651 patients were assigned to receive nivolumab plus cabozantinib (323 patients) or sunitinib (328 patients). At a median follow-up of 18.1 months for overall survival, the median progression-free survival was 16.6 months (95% confidence interval [CI], 12.5 to 24.9) with nivolumab plus cabozantinib and 8.3 months (95% CI, 7.0 to 9.7) with sunitinib (hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.64; P<0.001). The probability of overall survival at 12 months was 85.7% (95% CI, 81.3 to 89.1) with nivolumab plus cabozantinib and 75.6% (95% CI, 70.5 to 80.0) with sunitinib (hazard ratio for death, 0.60; 98.89% CI, 0.40 to 0.89; P = 0.001). An objective response occurred in 55.7% of the patients receiving nivolumab plus cabozantinib and in 27.1% of those receiving sunitinib (P<0.001). Efficacy benefits with nivolumab plus cabozantinib were consistent across subgroups. Adverse events of any cause of grade 3 or higher occurred in 75.3% of the 320 patients receiving nivolumab plus cabozantinib and in 70.6% of the 320 patients receiving sunitinib. Overall, 19.7% of the patients in the combination group discontinued at least one of the trial drugs owing to adverse events, and 5.6% discontinued both. Patients reported better health-related quality of life with nivolumab plus cabozantinib than with sunitinib., Conclusions: Nivolumab plus cabozantinib had significant benefits over sunitinib with respect to progression-free survival, overall survival, and likelihood of response in patients with previously untreated advanced renal-cell carcinoma. (Funded by Bristol Myers Squibb and others; CheckMate 9ER ClinicalTrials.gov number, NCT03141177.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: Diet and exercise may be associated with quality of life and survival in men with prostate cancer., Objective: This study aimed to determine the feasibility and acceptability of a remotely delivered web-based behavioral intervention among men with prostate cancer., Methods: We conducted a multi-site 4-arm pilot randomized controlled trial of a 3-month intervention (TrueNTH Community of Wellness). Eligibility included self-reported prostate cancer diagnosis, having a personal device that connected to the internet, age ≥18 years, and ability to read English and receive text messages and emails. Men receiving chemotherapy or radiation, or those who reported contraindications to exercise, could participate with physician clearance. Participants were randomized (1:1:1:1) to additive intervention levels: website; website and personalized diet and exercise prescription; website, personalized prescription, Fitbit, and text messages; and website, personalized prescription, Fitbit, text messages, and 2 30-minute phone calls-one with an exercise trainer and one with a registered dietician. Primary outcomes were feasibility (accrual and attrition) and acceptability (survey data and website use). We described self-reported diet and exercise behavior at the time of enrollment, 3 months, and 6 months as secondary outcomes., Results: In total, 202 men consented and were randomized between August 2017 and September 2018 (level 1: 49, level 2: 51, level 3: 50, level 4: 52). A total of 160 men completed the onboarding process and were exposed to their randomly assigned intervention (38, 38, 42, and 42 in levels 1, 2, 3, and 4, respectively). The follow-up rate was 82.7% (167/202) at 3 months and 77.2% (156/202) at 6 months. Participants had a median age of 70 years and were primarily White and college educated. Website visit frequency over the 3-month intervention period increased across levels (median: 2, 9, 11, and 16 visits for levels 1, 2, 3, and 4, respectively). Most were satisfied or very satisfied with the intervention (20/39, 51%; 27/42, 64%; 23/44, 52%; and 27/42, 64% for levels 1, 2, 3, and 4, respectively). The percentage of men who reported being very satisfied was highest among level 4 participants (10/42, 24% vs 4/39, 10%; 5/42, 12%; and 5/44, 11% for levels 1, 2, and 3, respectively). Dissatisfaction was highest in level 1 (5/39, 13% vs 1/42, 2%; 3/44, 7%; and 2/42, 5% for levels 2, 3, and 4, respectively). We observed small improvements in diet and physical activity at 3 months among men in level 4 versus those in level 1., Conclusions: A web-based, remotely delivered, tailored behavioral intervention for men with prostate cancer is feasible. Future studies are warranted to increase the effect of the intervention on patient behavior while maintaining sustainability and scalability as well as to design and implement interventions for more diverse populations., Trial Registration: ClinicalTrials.gov NCT03406013; http://clinicaltrials.gov/ct2/show/NCT03406013., (©June M Chan, Erin L Van Blarigan, Crystal S Langlais, Shoujun Zhao, Justin W Ramsdill, Kimi Daniel, Greta Macaire, Elizabeth Wang, Kellie Paich, Elizabeth R Kessler, Tomasz M Beer, Karen S Lyons, Jeanette M Broering, Peter R Carroll, Stacey A Kenfield, Kerri M Winters-Stone. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 31.12.2020.)

Background: Exercise and a healthy diet can improve the quality of life and prognosis of prostate cancer survivors, but there have been limited studies on the feasibility of web-based lifestyle interventions in this population., Objective: This study aims to develop a data-driven grounded theory of web-based engagement by prostate cancer survivors based on their experience in the Community of Wellness, a 12-week randomized clinical trial designed to support healthy diet and exercise habits., Methods: TrueNTH's Community of Wellness was a four-arm pilot study of men with prostate cancer (N=202) who received progressive levels of behavioral support (level 1: website; level 2: website with individualized diet and exercise recommendations; level 3: website with individualized diet and exercise recommendations, Fitbit, and text messages; and level 4: website with individualized diet and exercise recommendations, Fitbit and text messages, and separate phone calls with an exercise trainer and a registered dietitian). The primary aim of the study is to determine the feasibility and estimate the effects on behaviors (results reported in a separate paper). Following the 12-week intervention, we invited participants to participate in 4 focus groups, one for each intervention level. In this report, we used grounded theory analyses including open, axial, and selective coding to generate codes and themes from the focus group transcripts. Categories were refined across levels using embodied categorization and constant comparative methods., Results: In total, 20 men with prostate cancer participated in the focus groups: 5, 4, 5, and 6 men in levels 1, 2, 3, and 4, respectively. Participants converged on 5 common factors influencing engagement with the intervention: environment (home environment, competing priorities, and other lifestyle programs), motivation (accountability and discordance experienced within the health care system), preparedness (technology literacy, health literacy, trust, and readiness to change), program design (communication, materials, and customization), and program support (education, ally, and community). Each of these factors influenced the survivors' long-term impressions and habits. We proposed a grounded theory associating these constructs to describe the components contributing to the intuitiveness of a web-based lifestyle intervention., Conclusions: These analyses suggest that web-based lifestyle interventions are more intuitive when we optimize participants' technology and health literacy; tailor interface design, content, and feedback; and leverage key motivators (ie, health care providers, family members, web-based coach) and environmental factors (ie, familiarity with other lifestyle programs). Together, these grounded theory-based efforts may improve engagement with web-based interventions designed to support prostate cancer survivorship., (©Elizabeth Y Wang, Rebecca E Graff, June M Chan, Crystal S Langlais, Jeanette M Broering, Justin W Ramsdill, Elizabeth R Kessler, Kerri M Winters-Stone, Erin L Van Blarigan, Stacey A Kenfield. Originally published in JMIR Cancer (http://cancer.jmir.org), 10.11.2020.)

Background: Most oncology trainees are not taught about the needs of older patients, who make up the majority of patients with cancer. Training of health care providers is critical to improve the care of older adults with cancer. There is no consensus about which geriatric oncology (GO) competencies are important for medical oncology trainees. Our objective was to identify GO competencies medical oncology trainees should acquire during training., Materials and Methods: A modified Delphi consensus of experts in oncology medical education and GO was conducted. Experts categorized at what training stage proposed competencies should be attained: internal medicine, oncology, or GO training. Consensus was obtained if two thirds of experts agreed on the training stage at which the competency should be attained., Results: A total of 78 potential competencies were identified, of which 35 (44.9%) proposed competencies were felt to be appropriate to be acquired during oncology training. The majority of the identified competencies pertained to prescribing of systemic therapy (n = 12) and psychosocial and supportive care (n = 13). No competencies related to geriatric assessment were identified for acquisition during oncology training., Conclusion: Experts in oncology education and geriatric oncology agreed upon a set of GO competencies appropriate for oncology trainees. These results provide the foundation for developing a GO curriculum for medical oncology trainees and will hopefully lead to better care of older adults with cancer., Implications for Practice: The aging population will drive the projected rise in cancer incidence. Although aging patients make up the majority of patients diagnosed with cancer, oncologists rarely receive training on how to care for them. Training of health care providers is critical to improving the care of older adults with cancer. The results of this study will help form the foundation of developing a geriatric oncology curriculum for medical oncology trainees., (© AlphaMed Press 2020.)

Bladder cancer is an extremely common cancer that primarily affects individuals aged >65 years. In caring for patients with bladder cancer, clinicians must also consider care of older persons in general. Management of muscle-invasive bladder cancer (MIBC) involves multidisciplinary treatment planning, because curative-intent therapy includes either surgery or radiation, with consideration of the role of systemic therapy. As clinicians develop a treatment plan, considering a geriatric oncology perspective may enhance patient care and influence outcomes for this large and growing population. Similarly, treatment plan development must also consider aspects unique to an older patient population, such as altered organ function, increased comorbidity, decreased functional reserve, and perhaps altered goals of treatment. Thus a thorough evaluation inclusive of disease assessment and geriatric assessment is essential to care planning. Population-based data show that as patients with MIBC age, use of standard therapies declines. Given the complexities of coordinating a multidisciplinary care plan, as well the complexities of treating a heterogeneous and potentially vulnerable older patient population, clinicians may benefit from upfront assessments to inform and guide the process. This review highlights the unique treatment planning considerations for elderly patients diagnosed with MIBC.

Purpose: Data supporting neoadjuvant chemotherapy of high grade upper tract urothelial carcinoma are scant. In this multi-institution, prospective, phase II trial we investigated pathological complete responses after neoadjuvant chemotherapy of high grade upper tract urothelial carcinoma., Materials and Methods: Patients with high grade upper tract urothelial carcinoma in whom nephroureterectomy was planned were assigned to 4 neoadjuvant chemotherapy cycles of accelerated methotrexate, vinblastine, doxorubicin and cisplatin in those with baseline creatinine clearance greater than 50 ml per minute or gemcitabine and carboplatin in those with creatinine clearance 30 to 50 ml per minute or less. The study primary end point was a pathological complete response (ypT0N0). The accrual goal was 30 patients per arm. An 18% pathological complete response was considered worth further study while a 4% pathological complete response would not have justified pursuing this regimen. With 28 eligible patients per arm success was defined as 3 or more pathological complete responses (10.7%) in a given arm. Secondary end points included safety, renal function and oncologic outcomes., Results: A total of 30 patients enrolled in the accelerated methotrexate, vinblastine, doxorubicin and cisplatin arm from 2015 to 2017. Six patients enrolled in the gemcitabine and carboplatin arm, which closed due to poor accrual. Of the 29 patients eligible for accelerated methotrexate, vinblastine, doxorubicin and cisplatin, including 23 men and 6 women with a median age of 65 years (range 40 to 84), 80% completed all planned treatments, 3 (10.3%) achieved ypT0N0 and 1 achieved ypT0Nx for a pathological complete response in 13.8% (90% CI 4.9-28.8). In 1 patient receiving accelerated methotrexate, vinblastine, doxorubicin and cisplatin nephroureterectomy was deferred due to grade 4 sepsis. The grade 3-4 toxicity rate was 23% in the accelerated methotrexate, vinblastine, doxorubicin and cisplatin arm with no grade 5 event., Conclusions: Accelerated methotrexate, vinblastine, doxorubicin and cisplatin neoadjuvant chemotherapy in patients with high grade upper tract urothelial carcinoma and creatinine clearance greater than 50 ml per minute was safe and demonstrated predefined activity with a 14% pathological complete response rate. Final pathological stage ypT1 or less in more than 60% of patients is encouraging. Together the results of this prospective trial support the use of neoadjuvant chemotherapy in eligible patients with high grade upper tract urothelial carcinoma.

Background: Malignant central airway obstruction (CAO) occurs in approximately 20-30% of patients with lung cancer and is associated with debilitating symptoms and poor prognosis. Multimodality therapeutic bronchoscopy can relieve malignant CAO, though carries risk. Evidence to guide clinicians regarding which patients may benefit from such interventions is sparse. We aimed to assess the clinical and radiographic predictors associated with therapeutic bronchoscopy success in relieving malignant CAO., Methods: We reviewed all cases of therapeutic bronchoscopy performed for malignant CAO at our institution from January 2010-February 2017. Therapeutic bronchoscopy success was defined as establishing airway patency of > 50%. Patient demographics and baseline characteristics, oncology history, degree of airway obstruction, procedural interventions, and complications were compared between successful and unsuccessful groups. Univariate and multivariate logistic regression identified the significant clinical and radiographic predictors for therapeutic success. The corresponding simple and conditional odds ratio were calculated. A time-to-event analysis with Kaplan-Meier plots was performed to estimate overall survival., Results: During the study period, 301 therapeutic bronchoscopies were performed; 44 (14.6%) were considered unsuccessful. Factors associated with success included never vs current smoking status (OR 5.36, 95% CI:1.45-19.74, p = 0.010), patent distal airway on CT imaging (OR 15.11, 95% CI:2.98-45.83, p < 0.0001) and patent distal airway visualized during bronchoscopy (OR 10.77, 95% CI:3.63-31.95, p < 0.001) in univariate analysis. Along with patent distal airway on CT imaging, increased time from radiographic finding to therapeutic bronchoscopy was associated with lower odds of success in multivariate analysis (OR 0.96, 95% CI:0.92-1.00, p = 0.048). Median survival was longer in the successful group (10.2 months, 95% CI:4.8-20.2) compared to the unsuccessful group (6.1 months, 95% CI:2.1-10.8, log rank p = 0.015)., Conclusions: Predictors associated with successful therapeutic bronchoscopy for malignant CAO include distal patent airway visualized on CT scan and during bronchoscopy. Odds of success are higher in non-smokers, and with decreased time from radiographic finding of CAO to intervention.

Adult Wilms tumor (WT) is a well-known, albeit rare entity and has historically been associated with worse overall clinical outcomes when compared to younger patients. Because WT is uncommon in adult patients, it is often misdiagnosed and treated off standardized pediatric protocols. WT associated with pregnancy is even more rare, and there is not a standardized approach to this small subset of patients. We present a case of an adult WT discovered and managed during the perinatal period and review prior published cases., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Contemporary treatment for metastatic hormone sensitive prostate cancer (mHSPC) includes androgen deprivation therapy (ADT) plus abiraterone or docetaxel. While these intensified regimens have improved efficacy, they are also associated with increased cost and toxicities. Not all men with mHSPC may be candidates for these intensified regimens, yet there are no clinical models or biomarkers used to optimize treatment selection. Herein, we hypothesized that longer time from prior definitive therapy (DT), either radical prostatectomy, definitive radiotherapy, or both, to onset of metastatic disease is associated with improved survival outcomes in men with newly diagnosed mHSPC., Methods: This multicenter retrospective study included men initiating systemic therapy with ADT for new mHSPC. Kaplan-Meier and COX proportional hazard models assessed time to metastatic castration-resistant prostate cancer (mCRPC) and overall survival (OS) by receipt of prior DT., Results: Of the 253 men with new mHSPC, 115 (45%) had received prior DT. In a multivariate analysis, increasing years from DT to the start of ADT was an independent predictor of time to mCRPC (per year: hazard ratio 0.91 95% confidence interval 0.84-0.99, P = 0.020) and improved OS (per year: hazard ratio 0.87, 95% confidence interval 0.74-0.99, P = 0.0025) in patients with new mHSPC, and may assist with risk stratification in these patients at time of mHSPC., Conclusion: Time from DT to start of ADT is an independent predictor of time to mCRPC and OS in men with new mHSPC, and may assist with risk stratification of these patients for systemic therapy selection., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Prostate cancer is one of the most common cancers in the United States, with an estimated incidence of 164,690 cases, accounting for 9.5% of all new cancer diagnoses. The mainstay of therapy for metastatic prostate cancer involves suppressing testosterone production through androgen deprivation therapy. However, nearly all patients on androgen deprivation therapy will develop resistance to hormone therapy. An improved understanding of the biology of castration resistance has allowed for the development of novel inhibitors of the androgen axis. Agents such as abiraterone acetate, which provides additional androgen suppression by inhibiting cytochrome P450 17A (CYP17A), have improved survival outcomes of patients with advanced prostate cancer. The longest experience with abiraterone acetate is in the metastatic castration-resistant setting. However, more recent trials have demonstrated that abiraterone acetate is an option for treatment earlier in the prostate cancer paradigm. This review will cover the current use of abiraterone acetate in combination with prednisone for the treatment of castration-resistant prostate cancer., (Copyright 2019 Clarivate Analytics.)

Background: Plant derivatives have been studied as therapies for prostate cancer based on their purported anti-inflammatory and antioxidant properties and low toxicities. The acai berry is an example of a plant rich in phytochemicals, which may slow the growth of prostate cancer., Methods: This was a phase II, Simon 2-stage clinical trial in patients with biochemically recurrent prostate cancer with a primary endpoint of prostate-specific antigen (PSA) response. Patients were asymptomatic, with a rising PSA of at least 0.2 ng/mL, and were treated with twice daily intake of Acai Juice Product until PSA progression, with a primary endpoint of PSA response., Results: Twenty-one patients were enrolled in the first stage of the trial. One of those patients had a PSA response within the study time period. The PSA doubling time was lengthened in 71% of patients (95% confidence interval = 48% to 89%) on the trial, and in a small number of responders, this was sustained over an extended time., Conclusions: This study did not meet its primary endpoint of 50% PSA response. Nevertheless, the overall tolerability and effects on PSA stabilization warrant further exploration in a biochemically recurrent population.

As the world population ages, we can expect to care for an increasing number of older cancer patients. Prostate cancer is inherently a condition that affects patients of advanced age. In caring for these patients who have advanced prostate cancer, it is important to first assess the health status of the patient and his goals of care. As this is established, likely through a geriatric assessment, this will inform how to modify or mold the treatment plan to fit a patient's needs and vulnerabilities. These vulnerabilities may surface as patients undergo treatment such as androgen deprivation therapy-the backbone of systemic therapy for advanced disease. Androgen deprivation therapy leads to long-term adverse effects; therefore, providers should carefully consider its use and proactively manage toxicity. It is important to assess patients before starting treatment and to adjust the choice of therapy, or supportive services, in order to maximize benefit and minimize potential harms.

Background: More than 3.1 million men in the United States are prostate cancer survivors. These men may improve their physical function, quality of life, and potentially their prognosis by adopting healthier lifestyle habits. The internet provides a scalable mechanism to deliver advice and support about improving physical activity and dietary habits, but the feasibility and acceptability of a Web-based lifestyle intervention and the dose of support necessary to improve health behaviors are not yet known., Objectives: The Community of Wellness is a Web-based intervention focused on supporting exercise and healthy dietary practices for men with prostate cancer. The objectives of this study were to determine the feasibility, acceptability, and preliminary efficacy of the Community of Wellness Web portal among prostate cancer survivors by conducting a randomized controlled trial (RCT) comparing 4 levels of additive Web-based content and interaction with participants: Level 1 (Teaching; Control), Level 2 (Teaching + Tailoring), Level 3 (Teaching + Tailoring + Technology), and Level 4 (Teaching + Tailoring + Technology + Touch)., Methods: This is a single-blinded RCT comparing 3 levels of behavioral support within the Community of Wellness Web portal intervention (Levels 2 to 4) with each other and with the control condition (Level 1). The control condition receives general static Web-based educational information only on physical activity and dietary habits, self-efficacy for behavior change, motivation for physical activity, and changes in anxiety and treatment-related side effects. We will enroll and randomize 200 men with prostate cancer equally to 4 levels of the Community of Wellness Web-based intervention for 3 months (50 men per level). Surveys will be completed by self-report at baseline, 3 months (immediately postintervention), and 6 months (3 months postintervention). Feasibility and acceptability will be assessed by enrollment statistics, Web-based usage metrics, and surveys at the 3-month time point. We will also conduct focus groups after the postintervention follow-up assessment in a sample of enrolled participants to evaluate elements of usability and acceptability that cannot be obtained via surveys., Results: Enrollment is ongoing, with 124 enrolled. Study completion (6-month follow-up) is expected by July 2019., Conclusions: The goal of the study is to identify the level of support that is feasible, acceptable, promotes behavior change, and improves health in men with prostate cancer to inform future efforts to scale the program for broader reach., Trial Registration: ClinicalTrials.gov NCT03406013; https://clinicaltrials.gov/ct2/show/NCT03406013 (Archived by WebCite at http://www.webcitation.org/73YpDIoTX)., International Registered Report Identifier (irrid): PRR1-10.2196/11257., (©Kerri M Winters-Stone, Stacey A Kenfield, Erin L Van Blarigan, Esther L Moe, Justin W Ramsdill, Kimi Daniel, Greta Macaire, Kellie Paich, Elizabeth R Kessler, Omer Kucuk, Theresa W Gillespie, Karen S Lyons, Tomasz M Beer, Jeanette M Broering, Peter R Carroll, June M Chan. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 15.11.2018.)

Context: Best supportive care (BSC) is often not standardized across sites, consistent with best evidence, or sufficiently described. We developed a consensus-based checklist to document BSC delivery, including symptom management, decision making, and care planning. We hypothesized that BSC can be feasibly documented with this checklist consistent with consolidated standards of reporting trials., Objective: To determine feasibility/acceptability of a BSC checklist among clinicians., Methods: To test feasibility of a BSC checklist in standard care, we enrolled a sample of clinicians treating patients with advanced cancer at four centers. Clinicians were asked to complete the checklist at eligible patient encounters. We surveyed enrollees regarding checklist use generating descriptive statistics and frequencies., Results: We surveyed 15 clinicians and 9 advanced practice providers. Mean age was 41 (SD = 7.9). Mean years since fellowship for physicians was 7.2 (SD = 4.5). Represented specialties are medical oncology (n = 8), gynecologic oncology (n = 4), palliative care (n = 2), and other (n = 1). For "overall impact on your delivery of supportive/palliative care," 40% noted improved impact with using BSC. For "overall impact on your documentation of supportive/palliative care," 46% noted improvement. Impact on "frequency of comprehensive symptom assessment" was noted to be "increased" by 33% of providers. None noted decreased frequency or worsening impact on any measure with use of BSC. Regarding feasibility of integrating the checklist into workflow, 73% agreed/strongly agreed that checklists could be easily integrated, 73% saw value in integration, and 80% found it easy to use., Conclusion: Clinicians viewed the BSC checklist favorably illustrating proof of concept, minor workflow impact, and potential of benefit to patients.

Urothelial carcinoma, or bladder cancer, is a malignancy that most commonly affects older patients. The median age at diagnosis is 73 years, and care of these patients requires consideration not just of the disease-related factors such as stage and histology, but also of patient-related factors. Many of these patients have concurrent medical morbidities and additional changes related to the aging process. Older patients with cancer are a unique population requiring additional considerations and assessment in treatment decision-making. It is important to look beyond chronologic age. The traditional treatment for advanced disease has relied on platinum-based chemotherapy. These multi-agent regimens require consideration of baseline organ function as well as competing conditions that may heighten toxicity. The advent of a new class of cancer therapeutics, the immune checkpoint inhibitors, has changed the care of patients with advanced disease considerably. These immunotherapeutics have been approved for treating patients with disease progression on chemotherapy, or those who are ineligible (or unfit) to receive cisplatin-based therapy. This expansion of the population of patients eligible for treatment has great applicability to the unique considerations in an older patient population. In general, these new immunotherapies are well tolerated and effective in this group of patients.

Over the past decade, our understanding of the biology and pathophysiology of renal cell carcinoma (RCC) has improved significantly. Insight into the disease process has helped us in developing newer therapeutic approaches toward RCC. In this article, we review the various genetic and immune-related mechanisms involved in the pathogenesis and development of this cancer and how that knowledge is being used to develop therapeutic targeted drugs for the treatment of RCC. The main emphasis of this review article is on the most common genetic alterations found in clear cell RCC and how various drugs are currently targeting such pathways. This article also looks at the role of the immune system in allowing the growth of RCC and how the immune system can be manipulated to reactivate cytotoxic immunity against RCC., Competing Interests: Competing interests: ETL receives kidney cancer clinical trial funding from Argos, Bristol-Myers Squibb, Calithera, Genentech, Merck, Peloton, Pfizer, and Roche; has served as a consultant for Bristol-Myers Squibb; and serves on the Independent Data Monitoring Board for Calithera. ERK receives kidney cancer clinical trial funding from Bristol-Myers Squibb. TWF receives clinical trial funding from Bristol-Myers Squibb, Novartis, Pfizer, Bavarian Nordic, Cougar Biotechnology, Dendreon, GTx, Janssen Oncology, Medivation, Sanofi, Genentech, Roche, Exelixis, Aragon Pharmaceuticals, Sotio, Tokai Pharmaceuticals, Astra-Zeneca/MedImmune, Lilly, Astellas, Agensys, and Seattle Genetics and has served as a consultant for GTx.No competing interests were disclosed.No competing interests were disclosed.

Introduction: Testicular germ cell tumors (GCTs) are the most common solid tumor among adolescent and young adult (AYA) males. AYA patients with GCTs most typically have non-seminoma compared with seminoma, and accordingly there are fewer data reported on the AYA experience with testicular seminoma., Objective: To evaluate national trends in postoperative treatment and overall survival (OS) outcomes in testicular seminoma by age group, specifically comparing AYAs with older adults., Study Design: The National Cancer Data Base (NCDB) was queried for patients with testicular seminoma diagnosed between 2004 and 2012, who underwent orchiectomy followed by observation or adjuvant therapy (chemotherapy, radiation (RT), or both). Patients were grouped by age: AYA (15-39 years), adults between 40 and 55 years, and adults >55 years. Overall survival (OS) was presented using Kaplan-Meier curves and groups compared via a log-rank test. Univariate (UVA) and multivariate (MVA) analyses were performed using Cox proportional hazards regression models. Binary multiple logistic regression identified differences in variables by age category., Results: Of the total 22,361 patients the majority were AYAs (12,880, 57.6%), followed by adults 40-55 years (8,022, 35.9%), and >55 years (1,459, 6.5%). Unadjusted 5-year OS was significantly better for AYAs versus adults 40-55 years and >55 years (98.0%, 96.4%, 87.7%; p < 0.001), as was 10-year OS (96.1%, 91.8%, 71.3% respectively; p < 0.001). The Table shows that on a MVA, OS was significantly better for AYAs versus adults 40-55 years and adults >55 years. AYA patients were also more commonly treated at centers with greater clinical volume. Additionally, AYA patients were less likely to present with metastatic disease. Accordingly, AYA patients were less likely to undergo retroperitoneal lymph node dissection (OR 0.81; p = 0.001) and were less often managed with adjuvant therapy including chemotherapy (OR 0.91; p = 0.027), RT (OR 0.93; p = 0.025), or both (OR 0.68; p = 0.020)., Discussion: AYA patients with testicular seminoma present with earlier stage disease and in the clinical Stage I setting are more often are managed with active surveillance following orchiectomy when compared with older adults in this population-based analysis. Among AYA patients, OS was modestly better when compared with adults 40-55 years and significantly better when compared with adults >55 years., Conclusion: Our objective to describe the patterns of care and survival outcomes for AYA patients with testicular seminoma in the USA was met by reviewing this large national dataset. These results may inform future guidelines for management of AYA seminoma., (Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate usage trends and identify factors associated with proton beam therapy (PBT) compared to alternative forms of external beam radiation therapy (RT) (EBRT) for localized prostate cancer., Patients and Methods: The National Cancer Database was queried for men with localized (N0, M0) prostate cancer diagnosed between 2004 and 2013, treated with EBRT, with available data on EBRT modality (photon vs. PBT). Binary multiple logistic regression identified variables associated with EBRT modality., Results: In total, 143,702 patients were evaluated with relatively few men receiving PBT (5,709 [4.0%]). Significant differences in patient and clinical characteristics were identified between those men treated with PBT compared to those treated with photon (odds ratio [OR]; 95% CI). Patients treated with PBT were generally younger (OR = 0.73; CI: 0.67-0.82), National Comprehensive Cancer Network low-risk compared to intermediate (0.71; 0.65-0.78) or high (0.44; 0.38-0.5) risk, white vs. black race (0.66; 0.58-0.77), with less comorbidity (Charlson-Deyo 0 vs. 2+; 0.70; 0.50-0.98), live in higher income counties (1.55; 1.36-1.78), and live in metropolitan areas compared to urban (0.21; 0.18-0.23) or rural (0.14; 0.10-0.19) areas. Most patients treated with PBT travelled more than 100 miles to the treatment facility. Annual PBT utilization significantly increased in both total number and percentage of EBRT over time (2.7%-5.6%; P<0.001). PBT utilization increased mostly in men classified as National Comprehensive Cancer Network low-risk (4%-10.2%)., Conclusion: PBT for men with localized prostate cancer significantly increased in the United States from 2004 to 2013. Significant demographic and prognostic differences between those men treated with photons and protons were identified., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In the last several years, many new drugs have been approved to treat metastatic renal cell carcinoma (RCC). Cabozantinib is a novel multikinase inhibitor with activity against vascular endothelial growth factor receptor (VEGFR), proto-oncogene tyrosine-protein kinase receptor Ret and other kinases that recently joined this impressive list of approved agents. Cabozantinib is an active agent in the preclinical and clinical setting, having recently demonstrated superiority over everolimus in a blinded, randomized phase III study of patients with progressive RCC after at least one prior line of antiangiogenic therapy. This agent's toxicity profile is similar to those of other multikinase inhibitors approved to treat RCC. This review will explore cabozantinib's pharmacologic and safety profile and its preclinical and clinical activity in RCC., (Copyright 2017 Clarivate Analytics.)

An immunotherapeutic strategy is discussed supporting anti-tumor activity toward malignancies overexpressing ganglioside D3. GD3 can be targeted by NKT cells when derived moieties are presented in the context of CD1d. NKT cells can support anti-tumor responses by secreting inflammatory cytokines and through cytotoxicity toward CD1d + GD3 + tumors. To overexpress GD3, we generated expression vector DNA and an adenoviral vector encoding the enzyme responsible for generating GD3 from its ubiquitous precursor GM3. We show that DNA encoding α-N-acetyl-neuraminide α-2,8-sialyltransferase 1 (SIAT8) introduced by gene gun vaccination in vivo leads to overexpression of GD3 and delays tumor growth. Delayed tumor growth is dependent on CD1d expression by host immune cells, as shown in experiments engaging CD1d knockout mice. A trend toward greater NKT cell populations among tumor-infiltrating lymphocytes is associated with SIAT8 vaccination. A single adenoviral vaccination introduces anti-tumor activity similarly to repeated vaccination with naked DNA. Here, greater NKT tumor infiltrates were accompanied by marked overexpression of IL-17 in the tumor, later switching to IL-4. Our results suggest that a single intramuscular adenoviral vaccination introduces overexpression of GD3 by antigen-presenting cells at the injection site, recruiting NKT cells that provide an inflammatory anti-tumor environment. We propose adenoviral SIAT8 (AdV-SIAT8) can slow the growth of GD3 expressing tumors in patients.

Background: In adolescents, approximately 90% of testicular germ cell tumors (T-GCTs) are non-seminomas (NS T-GCTs). Few studies have evaluated the impact of age, specifically in adolescence, on outcomes of NS T-GCTs., Objective: The purpose of this study was to review all patients diagnosed with NS T-GCTs in the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the association between age (adolescents vs. adults) and survival outcomes., Method: The SEER database was queried for individuals ≥13 years old diagnosed with NS T-GCTs from 1995 to 2012. Patients were categorized into adolescent (13-19 years) and adult (≥20 years) cohorts. A Cox proportional hazards model was used for multivariate analysis (MVA)., Results: A total of 13,963 patients (1496 adolescents, 12,467 adults) was included. Median follow-up was 71 months (range 1-215). Five-year overall survival (OS) for adolescent and adult patients was 94% and 92%, respectively (p = 0.007); 5-year cancer-specific survival (CSS) was 95% and 94%, respectively (p = 0.139). Under MVA, adolescent patients had improved OS (HR 0.61; 95% CI 0.50-0.75; p < 0.001) and CSS (HR 0.65; 95% CI 0.51-0.82; p < 0.001), when compared with adults (Table). In a logistic regression analysis adjusting for demographics, adolescent patients were more likely to present with regional or distant metastatic disease (OR 1.16; 95% CI 1.01-1.35; p = 0.039), undergo an orchiectomy (OR 2.44; 95% CI 1.50-4.00; p < 0.001) or tumor excision (OR 2.43; 95% CI 1.57-3.77; p < 0.001), and receive other adjuvant surgery (OR 5.87; 95% CI 2.25-15.30; p < 0.001)., Conclusions: To our knowledge, this is the largest population-based comparative analysis in NS T-GCTs comparing outcomes between these two age groups. Adolescent patients with NS T-GCTs had slightly improved survival compared with adults, despite presenting with more advanced disease. While adolescent patients present at more advanced stage, they achieve excellent survival outcomes possibly at the cost of a greater therapeutic burden., (Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Vandetanib is a multitargeted tyrosine kinase inhibitor that affects vascular endothelial growth factor receptor (VEGF), epidermal growth factor (EGF), and rearranged during transfection (RET) mediated receptors which are important for growth and invasion of biliary and pancreatic cancers. This phase I study evaluated the safety profile of vandetanib in combination with standard doses of gemcitabine and capecitabine in order to determine the maximum tolerated dose (MTD)., Methods: In this single center phase I trial, patients received gemcitabine intravenously (i.v.) at 1000 mg/m2 days 1, 8, 15 in a 28 day cycle, capecitabine orally at 850 mg/m2 twice daily on days 1-21, and escalating doses of vandetanib (200 or 300 mg orally daily). Once the MTD was defined, an expansion cohort of patients with advanced biliary cancers and locally advanced or metastatic pancreatic cancer was enrolled. Blood samples were also collected at predetermined time points for biomarker analysis., Results: Twenty-three patients were enrolled: 9 in the dose escalation and 14 in the dose expansion cohort. One dose limiting toxicity (DLT), of grade 4 neutropenia, occurred in the 200 mg vandetanib cohort. The most common adverse effects were diarrhea (39 %), nausea and vomiting (34%), and rash (33%). There were 3 partial responses and stable disease of >2 months (range 2-45, median 5) was observed in 15/23 patients. There was no association between changes in biomarker analytes and disease response., Conclusion: The combination of gemcitabine, capecitabine and vandetanib is well tolerated at the recommended phase II dose of gemcitabine 1000 mg/m2 weekly for three consecutive weeks, capecitabine 850 mg/m2 BID days 1-21, and vandetanib 300 mg daily, every 28 days. This combination demonstrated promising activity in pancreaticobiliary cancers and further evaluation is warranted in these diseases. NCT00551096.

Purpose: We report the radiographic and clinical response rate of stereotactic body radiation therapy (SBRT) compared with conventional fractionated external beam radiation therapy (CF-EBRT) for renal cell carcinoma (RCC) bone lesions treated at our institution., Methods and Materials: Forty-six consecutive patients were included in the study, with 95 total lesions treated (50 SBRT, 45 CF-EBRT). We included patients who had histologic confirmation of primary RCC and radiographic evidence of metastatic bone lesions. The most common SBRT regimen used was 27 Gy in 3 fractions., Results: Median follow-up was 10 months (range, 1-64 months). Median time to symptom control between SBRT and CF-EBRT were 2 (range, 0-6 weeks) and 4 weeks (range, 0-7 weeks), respectively. Symptom control rates with SBRT and CF-EBRT were significantly different (P = .020) with control rates at 10, 12, and 24 months of 74.9% versus 44.1%, 74.9% versus 39.9%, and 74.9% versus 35.7%, respectively. The median time to radiographic failure and unadjusted pain progression was 7 months in both groups. When controlling for gross tumor volume, dose per fraction, smoking, and the use of systemic therapy, biologically effective dose ≥80 Gy was significant for clinical response (hazard ratio [HR], 0.204; 95% confidence interval [CI], 0.043-0.963; P = .046) and radiographic (HR, 0.075; 95% CI, 0.013-0.430; P = .004). When controlling for gross tumor volume and total dose, biologically effective dose ≥80 Gy was again predictive of clinical local control (HR, 0.140; 95% CI, 0.025-0.787; P = .026). Toxicity rates were low and equivalent in both groups, with no grade 4 or 5 toxicity reported., Conclusions: SBRT is both safe and effective for treating RCC bone metastases, with rapid improvement in symptoms after treatment and more durable clinical and radiographic response rate. Future prospective trials are needed to further define efficacy and toxicity of treatment, especially in the setting of targeted agents., (Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)