PIK3/Akt/mTOR pathway alterations in metastatic castration-sensitive prostate cancer.

BACKGROUND: Alterations in the PIK3/Akt/mTOR pathway are commonly seen in metastatic castration-sensitive prostate cancer (mCSPC), however their role in outcomes is unknown. We aim to evaluate the prognostic significance as well as the genetic landscape of PIK3/Akt/mTOR pathway alteration in mCSPC. METHODS: Fourhundred and seventy-two patients with mCSPC were included who underwent next generation sequencing. PIK3/Akt/mTor pathway alterations were defined as mutations in Akt1, mTOR, PIK3CA, PIK3CB, PIK3R1, PTEN, TSC1, and TSC2. Endpoints of interests were radiographic progression-free survival (rPFS), time to development of castration resistant prostate cancer (tdCRPC), and overall survival (OS). Kaplan-Meier analysis was performed and Cox regression hazard ratios (HR) were calculated. RESULTS: One hundred and fifty-two (31.9%) patients harbored a PIK3/Akt/mTOR pathway alteration. Median rPFS and tdCRPC were 23.7 and 21.0 months in PIK3/Akt/mTOR altered compared to 32.8 (p = 0.08) and 32.1 months (p = 0.002) in wildtype tumors. On multivariable analysis PIK3/Akt/mTOR pathway alterations were associated with tdCRPC (HR 1.43, 95% CI, 1.05-1.94, p = 0.02), but not rPFS [Hazard ratio (HR) 1.20, 95% confidence interval (CI), 0.90-1.60, p = 0.21]. PIK3/Akt/mTOR pathway alterations were more likely to be associated with concurrent mutations in TP53 (40% vs. 28%, p = 0.01) and TMPRSS2-ERG (37% vs. 26%, p = 0.02) than tumors without PIK3/Akt/mTOR pathway alterations. Concurrent mutations were typically associated with shorter median times to rPFS and tdCRPC. DAVID analysis showed p53 signaling and angiogenesis pathways were enriched in PIK3/Akt/mTOR pathway altered tumors while beta-catenin binding and altered BRCA pathway were enriched in PIK3/Akt/mTOR pathway wildtype tumors. CONCLUSIONS: PIK3/Akt/mTOR pathway alterations were common in mCSPC and associated with poorer prognosis. The genetic landscape of PIK3/Akt/mTOR pathway altered tumors differed from wildtype tumors. Additional studies are needed to better understand and target the PIK3/Akt/mTOR pathway in mCSPC.

PROMISE Registry: A prostate cancer registry of outcomes and germline mutations for improved survival and treatment effectiveness.

BACKGROUND: Recently approved treatments and updates to genetic testing recommendations for prostate cancer have created a need for correlated analyses of patient outcomes data via germline genetic mutation status. Genetic registries address these gaps by identifying candidates for recently approved targeted treatments, expanding clinical trial data examining specific gene mutations, and understanding effects of targeted treatments in the real-world setting. METHODS: The PROMISE Registry is a 20-year (5-year recruitment, 15-year follow-up), US-wide, prospective genetic registry for prostate cancer patients. Five thousand patients will be screened through an online at-home germline testing to identify and enroll 500 patients with germline mutations, including: pathogenic or likely pathogenic variants and variants of uncertain significance in genes of interest. Patients will be followed for 15 years and clinical data with real time patient reported outcomes will be collected. Eligible patients will enter long-term follow-up (6-month PRO surveys and medical record retrieval). As a virtual study with patient self-enrollment, the PROMISE Registry may fill gaps in genetics services in underserved areas and for patients within sufficient insurance coverage. RESULTS: The PROMISE Registry opened in May 2021. 2114 patients have enrolled to date across 48 US states and 23 recruiting sites. 202 patients have met criteria for long-term follow-up. PROMISE is on target with the study's goal of 5000 patients screened and 500 patients eligible for long-term follow-up by 2026. CONCLUSIONS: The PROMISE Registry is a novel, prospective, germline registry that will collect long-term patient outcomes data to address current gaps in understanding resulting from recently FDA-approved treatments and updates to genetic testing recommendations for prostate cancer. Through inclusion of a broad nationwide sample, including underserved patients and those unaffiliated with major academic centers, the PROMISE Registry aims to provide access to germline genetic testing and to collect data to understand disease characteristics and treatment responses across the disease spectrum for prostate cancer with rare germline genetic variants.

Estimating oncologist variability in prescribing systemic cancer therapies to patients in the last 30 days of life.

INTRODUCTION: Clinical guidelines and quality improvement initiatives have identified reducing the use of end-of-life cancer therapies as an opportunity to improve care. We examined the extent to which oncologists differed in prescribing systemic therapies in the last 30 days of life. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data, we identified patients who died of cancer from 2012 to 2017 (N = 17,609), their treating oncologists (N = 960), and the corresponding physician practice (N = 388). We used multilevel models to estimate oncologists' rates of providing cancer therapy for patients in their last 30 days of life, adjusted for patient characteristics and practice variation. RESULTS: Patients' median age at the time of death was 74 years (interquartile range, 69-79); patients had lung (62%), colorectal (17%), breast (13%), and prostate (8%) cancers. We observed substantial variation across oncologists in their adjusted rate of treating patients in the last 30 days of life: oncologists in the 95th percentile exhibited a 45% adjusted rate of treatment, versus 17% among the 5th percentile. A patient treated by an oncologist with a high end-of-life prescribing behavior (top quartile), compared to an oncologist with a low prescribing behavior (bottom quartile), had more than four times greater odds of receiving end-of-life cancer therapy (OR, 4.42; 95% CI, 4.00-4.89). CONCLUSIONS: Oncologists show substantial variation in end-of-life prescribing behavior. Future research should examine why some oncologists more often continue systemic therapy at the end of life than others, the consequences of this for patient and care outcomes, and whether interventions shaping oncologist decision-making can reduce overuse of end-of-life cancer therapies.

Psychological Determinants of Physician Variation in End-of-Life Treatment Intensity: A Systematic Review and Meta-Synthesis.

BACKGROUND: Physicians treating similar patients in similar care-delivery contexts vary in the intensity of life-extending care provided to their patients at the end-of-life. Physician psychological propensities are an important potential determinant of this variability, but the pertinent literature has yet to be synthesized. OBJECTIVE: Conduct a review of qualitative studies to explicate whether and how psychological propensities could result in some physicians providing more intensive treatment than others. METHODS: Systematic searches were conducted in five major electronic databases-MEDLINE ALL (Ovid), Embase (Elsevier), CINAHL (EBSCO), PsycINFO (Ovid), and Cochrane CENTRAL (Wiley)-to identify eligible studies (earliest available date to August 2021). Eligibility criteria included examination of a physician psychological factor as relating to end-of-life care intensity in advanced life-limiting illness. Findings from individual studies were pooled and synthesized using thematic analysis, which identified common, prevalent themes across findings. RESULTS: The search identified 5623 references, of which 28 were included in the final synthesis. Seven psychological propensities were identified as influencing physician judgments regarding whether and when to withhold or de-escalate life-extending treatments resulting in higher treatment intensity: (1) professional identity as someone who extends lifespan, (2) mortality aversion, (3) communication avoidance, (4) conflict avoidance, (5) personal values favoring life extension, (6) decisional avoidance, and (7) over-optimism. CONCLUSIONS: Psychological propensities could influence physician judgments regarding whether and when to de-escalate life-extending treatments. Future work should examine how individual and environmental factors combine to create such propensities, and how addressing these propensities could reduce physician-attributed variation in end-of-life care intensity.

Functional impairment is associated with medical debt in male cancer survivors and credit card debt in female cancer survivors.

PURPOSE: To examine the associations of functional limitations with medical and credit card debt among cancer survivor families and explore sex differences in these associations. METHODS: This cross-sectional study used data from the 2019 wave of the Panel Study of Income Dynamics, a nationally representative, population-based survey of individuals and households in the US administered in both English and Spanish and includes all households where either the head of household or spouse/partner reported having been diagnosed with cancer. Participants reported on functional limitations in six instrumental activities of daily living (IADL) and seven activities of daily living (ADL). Functional impairment was categorized as 0, 1-2 and ≥ 3 limitations. Medical debt was defined as self-reported unpaid medical bills. Credit card debt was defined as revolving credit card debt. Multivariable logistic regression analyses were performed. RESULTS: Credit card debt was more common than medical debt (39.8% vs. 7.6% of cancer survivor families). Families of male cancer survivors were 7.3 percentage points more likely to have medical debt and 16.0 percentage points less likely to have credit card debt compared to families of female cancer survivors. Whereas male cancer survivors with increasing levels of impairment were 24.7 percentage point (p-value = 0.006) more likely to have medical debt, female survivors with more functional impairment were 13.6 percentage points (p-value = 0.010) more likely to have credit card debt. CONCLUSIONS: More research on medical and credit card debt burden among cancer survivors with functional limitations is needed.

Metastasis-Directed Therapy for Oligometastatic Castration-Sensitive Prostate Cancer: An Alternative to ADT?

PURPOSE OF REVIEW: The standard treatment of patients with metastatic prostate cancer is systemic treatment with androgen-deprivation therapy (ADT). The spectrum-based model of metastatic disease includes the presence of an oligometastatic state, an intermediary between localized and widespread metastatic disease, in which radical local treatment might improve systemic control. Our purpose is to review the literature on metastasis-directed therapy in the treatment of oligometastatic prostate cancer. RECENT FINDINGS: Several prospective clinical trials have reported improvements in ADT-free survival and progression-free survival with metastasis-directed therapy of oligometastatic prostate cancer. Retrospective studies have found improvements in oncologic outcomes for patients with oligometastatic prostate cancer undergoing metastasis-directed therapy, and several recent prospective clinical trials have confirmed these results. Advancements in imaging as well as an understanding of the genomics of oligometastatic prostate cancer may allow for better patient selection for metastasis-directed therapy and the potential for cure in selected patients.

Pilot Study Evaluating Cross-Disciplinary Educational Material to Improve Patients' Knowledge of Palliative Radiation Therapy.

Palliative radiation therapy (PRT) is underutilized, partially due to misconceptions about its risks, benefits, and indications. The objective of this pilot study was to determine if patients with metastatic cancer would gain knowledge from educational material describing PRT and perceive it as useful in their care. A one-page handout conveying information about the purpose, logistics, benefits, risks, and common indications for PRT was offered to patients undergoing treatment for incurable, metastatic solid tumors in one palliative care clinic and four medical oncology clinics. Participants read the handout, then completed a questionnaire assessing its perceived value. Seventy patients participated between June and December 2021. Sixty-five patients (93%) felt they learned from the handout (40% learned "lots"), and 69 (99%) felt the information was useful (53% "very useful"). Twenty-one patients (30%) were previously unaware that PRT can relieve symptoms, 55 (79%) were unaware that PRT can be delivered in five treatments or less, and 43 (61%) were unaware that PRT usually has few side effects. Sixteen patients (23%) felt they currently had symptoms not being treated well enough, and 34 (49%) felt they had symptoms that radiation might help with. Afterwards, most patients felt more comfortable bringing symptoms to a medical oncologist's (n = 57, 78%) or radiation oncologist's (n = 51, 70%) attention. Patient-directed educational material about PRT, provided outside of a radiation oncology department, was perceived by patients as improving their knowledge and adding value in their care, independent of prior exposure to a radiation oncologist.

Disease and debt: Findings from the 2019 Panel Study of Income Dynamics in the United States.

Medical debt has grown dramatically over the past few decades. While cancer and diabetes are known to be associated with medical debt, little is known about the impact of other medical conditions and health behaviors on medical debt. We analyzed cross-sectional data on 9174 households - spanning lower-income, middle-income, and higher-income based on the Census poverty threshold - participating in the 2019 wave of the nationally representative United States Panel Study of Income Dynamics (PSID). The outcomes were presence of any medical debt and presence of medical debt≥ $2000. Respondents reported on medical conditions (diabetes, cancer, heart disease, chronic lung disease, asthma, arthritis, anxiety disorders, mood disorders) and on health behaviors (smoking, heavy drinking). Medical debt was observed in lower-income households with heart disease (OR = 2.64, p-value = 0.006) and anxiety disorders (OR = 2.16, p-value = 0.02); middle-income households with chronic lung disease (OR = 1.73, p-value = 0.03) and mood disorders (OR = 1.53, p-value = 0.04); and higher-income households with a current smoker (OR = 2.99, p-value<0.001). Additionally, medical debt ≥$2000 was observed in lower-income households with asthma (OR = 2.16, p-value = 0.009) and a current smoker (OR = 1.62, p-value = 0.04); middle income households with hypertension (OR = 1.65, p-value = 0.05). These novel findings suggest that the harms of medical debt extend beyond cancer, diabetes and beyond lower-income households. There is an urgent need for policy and health services interventions to address medical debt in a wider range of disease contexts than heretofore envisioned. Intervention development would benefit from novel conceptual frameworks on the causal relationships between health behaviors, health conditions, and medical debt that center social-ecological influences on all three of these domains.

Financial hardship among cancer survivors in Southern New Jersey.

PURPOSE: To identify predictors of financial hardship, operationalized as foregoing health care, making financial sacrifices, and being concerned about having inadequate financial and insurance information. METHODS: Cancer survivors (n = 346) identified through the New Jersey State Cancer Registry were surveyed from August 2018 to September 2019. Multivariable logistic regression analyses were performed. RESULTS: Cancer survivors with household incomes less than $50,000 annually were more likely than those earning $50,0000-$90,000 to report foregoing health care (15.8 percentage points, p < 0.05). Compared to retirees, survivors who were currently unemployed, disabled, or were homemakers were more likely to forego doctor's visits (11.4 percentage points, p < 0.05), more likely to report borrowing money (16.1 percentage points, p < 0.01), and more likely to report wanting health insurance information (25.7 percentage points, p < 0.01). Employed survivors were more likely than retirees to forego health care (16.8 percentage points, p < 0.05) and make financial sacrifices (20.0 percentage points, p < 0.01). Survivors who never went to college were 9.8 percentage points (p < 0.05) more likely to borrow money compared to college graduates. Black survivors were more likely to want information about dealing with financial and insurance issues (p < 0.01); men were more likely to forego health care (p < 0.05). CONCLUSION: Findings highlight the role of employment status and suggest that education, income, race, and gender also shape cancer survivors' experience of financial hardship. There is a need to refine and extend financial navigation programs. For employed survivors, strengthening family leave policies would be desirable.

Impact of pathologic lymph node-positive renal cell carcinoma on survival in patients without metastasis: Evidence in support of expanding the definition of stage IV kidney cancer.

BACKGROUND: Stage III renal cell carcinoma (RCC) encompasses both lymph node-positive (pT1-3N1M0) and lymph node-negative (pT3N0M0) disease. However, prior institutional studies have indicated that among patients with stage III disease, those with lymph node disease have worse oncologic outcomes and experience survival that is similar to that of patients with American Joint Committee on Cancer (AJCC) stage IV disease. The objective of the current study was to validate these findings using a large, nationally representative sample of patients with kidney cancer. METHODS: Patients with AJCC stage III or stage IV RCC were identified using the National Cancer Data Base (NCDB). Patients were categorized as having lymph node-positive stage III (pT1-3N1M0), lymph node-negative stage III (pT3N0M0), or stage IV metastatic (pT1-3 N0M1) disease. Cox proportional hazards models compared outcomes while adjusting for comorbidities. Kaplan-Meier estimates illustrated relative survival when comparing staging groups. RESULTS: A total of 8988 patients met the inclusion criteria, with 6587 patients classified as having lymph node-negative stage III disease, 2218 as having lymph node-positive stage III disease, and 183 as having stage IV disease. Superior survival was noted among patients with lymph node-negative stage III disease, but similar survival was noted between patients with lymph node-positive stage III and stage IV RCC, with 5-year survival rates of 61.9% (95% confidence interval [95% CI], 60.3%-63.4%), 22.7% (95% CI, 20.6%-24.9%), and 15.6% (95% CI, 11.1%-23.8%), respectively. CONCLUSIONS: Current RCC staging systems group pT1-3N1M0 and pT3N0M0 disease as stage III disease. However, the results of the current validation study suggest the need for further stratification and even placement of patients with pT1-3N1M0 disease into the stage IV category. Staging that accurately reflects oncologic prognosis may help clinicians better counsel and select patients who might derive the most benefit from lymphadenectomy, adjuvant systemic therapy, more rigorous imaging surveillance, and clinical trial participation.

Similar incidence of DNA damage response pathway alterations between clinically localized and metastatic prostate cancer.

BACKGROUND: In this era of precision medicine, the DNA damage response (DDR) pathway has been shown to be a viable target of intervention in metastatic castration-resistant prostate cancer (CRPC) as approximately one-third of CRPC patients harbor DDR pathway mutations. To determine whether DDR pathway is a potential therapeutic target in localized disease, we analyzed The Cancer Genome Atlas (TCGA) in the present study. METHODS: TCGA is a publically available cancer genome database that is sponsored by the United States National Cancer Institute. Total of 455 cases were available in the database at the time of this analysis. RESULTS: DDR pathway gene mutations or copy number alterations were present in 136 (29.9%) of the 455 cases. On a univariate analysis, DDR pathway status did not correlate with serum prostate specific antigen, tumor stage or grade. However, among patients with high-risk features post-operatively (pathologic stage ≥ T3, Gleason score ≥ 8, or PSA > 20 ng/ml), DDR pathway alteration was associated with a lower overall survival (p = 0.0291). CONCLUSIONS: Collectively these results suggest that DDR pathway alterations may also be significant in localized prostate cancer and agents such as PARP inhibitors should be considered in patients with a high-risk disease.

The Role of Tumor and Host Microbiome on Immunotherapy Response in Urologic Cancers.

Introduction & Objective: The role of the microbiome in the development and treatment of genitourinary malignancies is just starting to be appreciated. Accumulating evidence suggests that the microbiome can modulate immunotherapy through signaling in the highly dynamic tumor microenvironment. Nevertheless, much is still unknown about the immuno-oncology-microbiome axis, especially in urologic oncology. The objective of this review is to synthesize our current understanding of the microbiome's role in modulating and predicting immunotherapy response to genitourinary malignancies. Methods: A literature search for peer-reviewed publications about the microbiome and immunotherapy response in bladder, kidney, and prostate cancer was conducted. All research available in PubMed, Google Scholar, clinicaltrials.gov, and bioRxiv up to September 2023 was analyzed. Results: Significant differences in urinary microbiota composition have been found in patients with genitourinary cancers compared to healthy controls. Lactic acid-producing bacteria, such as Bifidobacterium and Lactobacillus genera, may have value in augmenting BCG responsiveness to bladder cancer. BCG may also be a dynamic regulator of PD-L1. Thus, the combination of BCG and immune checkpoint inhibitors may be an effective strategy for bladder cancer management. In advanced renal cell carcinoma, studies show that recent antibiotic administration negatively impacts survival outcomes in patients undergoing immunotherapy, while administration of CBM588, a live bacterial product, is associated with improved progression-free survival. Specific bacterial taxa, such as Streptococcus salivarius, have been linked with response to pembrolizumab in metastatic castrate-resistant prostate cancer. Fecal microbiota transplant has been shown to overcome resistance and reduce toxicity to immunotherapy; it is currently being investigated for both kidney and prostate cancers. Conclusions: Although the exact mechanism is unclear, several studies identify a symbiotic relationship between microbiota-centered interventions and immunotherapy efficacy. It is possible to improve immunotherapy responsiveness in genitourinary malignancies using the microbiome, but further research with more standardized methodology is warranted.

Comparative Cardiovascular Safety of Gonadotropin-releasing Hormone Antagonists and Agonists Among Patients Diagnosed with Prostate Cancer: A Systematic Review and Meta-analysis of Real-world Evidence Studies.

BACKGROUND AND OBJECTIVE: Gonadotropin-releasing hormone (GnRH) antagonists and agonists are cornerstone treatments in prostate cancer. However, evidence regarding the comparative cardiovascular safety of these drugs from clinical trials is inconclusive. The objective of this study was to systematically assess the risk of adverse cardiovascular events of GnRH antagonists compared with GnRH agonists across real-world evidence studies. METHODS: We conducted a systematic search of PubMed, Embase, Cochrane Library, Scopus, and Web of Science (2008-2023). We included real-world evidence studies comparing the risk of cardiovascular outcomes of GnRH antagonists with those of GnRH agonists among patients with prostate cancer. We conducted a meta-analysis of effect estimates across studies at a low or moderate risk of bias, assessed via the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool, using random-effect models. KEY FINDINGS AND LIMITATIONS: Among ten included studies, four were classified as having a moderate and six as having a serious risk of bias. Across three studies at a moderate risk of bias in the primary analysis, degarelix was associated with an increased risk (pooled relative risk [RR]: 1.31, 95% confidence interval [CI]: 1.14-1.51) of major adverse cardiovascular events (MACEs). An augmented risk was observed in two studies among patients with a history of cardiovascular disease (pooled RR: 1.31, 95% CI: 1.11-1.56) compared with one study among patients without a history of cardiovascular disease (RR: 1.15, 95% CI: 0.83-1.59). CONCLUSIONS AND CLINICAL IMPLICATIONS: Real-world evidence studies indicate that degarelix, compared with GnRH agonists, is associated with a modest increased risk of MACEs, particularly among patients with a history of cardiovascular disease. However, residual confounding due to the treatment of high-risk patients with degarelix may account for these findings. Additional large studies with detailed data on tumor characteristics and cardiovascular risk factors are needed to confirm these findings. PATIENT SUMMARY: In this systematic evaluation of evidence among patients diagnosed with prostate cancer in routine care, degarelix was associated with higher cardiovascular adverse outcomes than gonadotropin-releasing hormone agonists.

Prostate-Specific Membrane Antigen PET Response Associates with Metastasis-Free Survival After Stereotactic Ablative Radiation in Oligometastatic Prostate Cancer.

Purpose: Emerging data suggest that metastasis-directed therapy (MDT) improves outcomes in patients with oligometastatic castration-sensitive prostate cancer (omCSPC). Prostate-specific membrane antigen positron emission tomography (PSMA-PET) can detect occult metastatic disease, and PSMA response has been proposed as a biomarker for treatment response. Herein, we identify and validate a PSMA-PET biomarker for metastasis-free survival (MFS) following MDT in omCSPC. Methods and Materials: We performed an international multi-institutional retrospective study of patients with omCSPC, defined as ≤3 lesions, treated with metastasis-directed stereotactic ablative radiation who underwent PSMA-PET/computed tomography (CT) before and after (median, 6.2 months; range, 2.4-10.9 months) treatment. Pre- and post-MDT PSMA-PET/CT maximum standardized uptake value (SUVmax) was measured for all lesions, and PSMA response was defined as the percent change in SUVmax of the least responsive lesion. PSMA response was both evaluated as a continuous variable and dichotomized into PSMA responders, with a complete/partial response (at least a 30% reduction in SUVmax), and PSMA nonresponders, with stable/progressive disease (less than a 30% reduction in SUVmax). PSMA response was correlated with conventional imaging-defined metastasis-free survival (MFS) via Kaplan-Meier and Cox regression analysis. Results: A total of 131 patients with 261 treated metastases were included in the analysis, with a median follow-up of 29 months (IQR, 18.5-41.3 months). After stereotactic ablative radiation, 70.2% of patients were classified as PSMA responders. Multivariable analysis demonstrated that PSMA response as a continuous variable was associated with a significantly worse MFS (hazard ratio = 1.003; 95% CI, 1.001-1.006; P = .016). Patients classified as PSMA responders were found to have a significantly improved median MFS of 39.9 versus 12 months (P = .001) compared with PSMA nonresponders. Our study is limited as it is a retrospective review of a heterogenous population. Conclusions: After stereotactic ablative radiation, PSMA-PET response appears to be a radiographic biomarker that correlates with MFS in omCSPC. This approach holds promise for guiding clinical management of omCSPC and should be validated in a prospective setting.

Final Results From a Phase I Trial and Expansion Cohorts of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced/Metastatic Genitourinary Tumors.

PURPOSE: Cabozantinib and nivolumab (CaboNivo) alone or with ipilimumab (CaboNivoIpi) have shown promising efficacy and safety in patients with metastatic urothelial carcinoma (mUC), metastatic renal cell carcinoma (mRCC), and rare genitourinary (GU) tumors in a dose-escalation phase I study. We report the final data analysis of the safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the phase I patients and seven expansion cohorts. METHODS: This is an investigator-initiated, multicenter, phase I trial. CaboNivo doublet expansion cohorts included (1) mUC, (2) mRCC, and (3) adenocarcinoma of the bladder/urachal; CaboNivoIpi triplet expansion cohorts included (1) mUC, (2) mRCC, (3) penile cancer, and (4) squamous cell carcinoma of the bladder and other rare GU tumors (ClinicalTrials.gov identifier: NCT02496208). RESULTS: The study enrolled 120 patients treated with CaboNivo (n = 64) or CaboNivoIpi (n = 56), with a median follow-up of 49.2 months. In 108 evaluable patients (CaboNivo n = 59; CaboNivoIpi n = 49), the ORR was 38% (complete response rate 11%) and the median duration of response was 20 months. The ORR was 42.4% for mUC, 62.5% for mRCC (n = 16), 85.7% for squamous cell carcinoma of the bladder (n = 7), 44.4% for penile cancer (n = 9), and 50.0% for renal medullary carcinoma (n = 2). Grade ≥ 3 treatment-related adverse events occurred in 84% of CaboNivo patients and 80% of CaboNivoIpi patients. CONCLUSION: CaboNivo and CaboNivoIpi demonstrated clinical activity and safety in patients with multiple GU malignancies, especially clear cell RCC, urothelial carcinoma, and rare GU tumors such as squamous cell carcinoma of the bladder, small cell carcinoma of the bladder, adenocarcinoma of the bladder, renal medullary carcinoma, and penile cancer.

Breaking bad news: during the holiday season.

Breaking bad news can be a difficult process. This can further be complicated when such news needs to be delivered around the holiday season. Here, we discuss such a case, and provide recommendations on breaking bad news around the holiday season.

Palliative Care Interventions Effects on Psychological Distress: A Systematic Review & Meta-Analysis.

BACKGROUND: Managing psychological distress is an objective of palliative care. No meta-analysis has evaluated whether palliative care reduces psychological distress. OBJECTIVES: Examine the effects of palliative care on depression, anxiety, and general psychological distress for adults with life-limiting illnesses and their caregivers. DESIGN: We searched PubMed, PsycInfo, Embase, and CINAHL for randomized clinical trials (RCTs) of palliative care interventions. RCTs were included if they enrolled adults with life-limiting illnesses or their caregivers, reported data on psychological distress at 3 months after study intake, and if authors had described the intervention as "palliative care." RESULTS: We identified 38 RCTs meeting our inclusion criteria. Many (14/38) included studies excluded participants with common mental health conditions. There were no statistically significant improvements in patient or caregiver anxiety (patient SMD: -0.008, P = 0.96; caregiver SMD: -0.21, P = 0.79), depression (patient SMD: -0.13, P = 0.25; caregiver SMD -0.27, P = 0.08), or psychological distress (patient SMD: 0.26, P = 0.59; caregiver SMD: 0.04, P = 0.78). CONCLUSIONS: Psychological distress is not likely to be reduced in the context of a typical palliative care intervention. The systemic exclusion of patients with common mental health conditions in more than 1/3 of the studies raises ethical questions about the goals of palliative care RCTS and could perpetuate inequalities.

Feasibility and Acceptability of an Online Oncologist Training to Optimize Oncologist-Patient Communication and Value-Concordant Care in Advanced Cancer.

Introduction: This pilot study tested the feasibility and acceptability of a low-resource-intensive scalable online communication training designed to improve oncologists' skills in prognostic and value-concordant care discussions with advanced cancer patients. Methods: The training consisted of on-demand videos on how to convey prognostic information, manage patient emotions, and elicit patient values and incorporate these values into treatment decision making. Post-intervention, oncologists reported on their perceptions of the training. Results: Fifteen oncologists were enrolled, of whom, 13 completed the training, and 14 completed post-intervention interviews. Most oncologists reported the intervention was acceptable: 92.9% indicated the intervention was "moderately" to "very helpful"; 78.6% rated it as "somewhat" to "very much" impactful on their communication with patients. Conclusions: The present self-paced online communication training was acceptable to oncologists, supporting additional research, including evaluating intervention efficacy for improving oncologists' communication skills and value-concordant care in advanced cancer.

Factors associated with clinical trial participation for patients with renal cell carcinoma.

OBJECTIVE: Recruitment of a diverse and representative study population is critical to the external validity of oncology clinical trials. The primary objective of this study was to characterize the factors associated with clinical trial participation for patients with renal cell carcinoma and the secondary objective was to examine differences in survival outcomes. MATERIALS AND METHODS: We used a matched case-control design by querying the National Cancer Database for patients with renal cell carcinoma who were coded as having enrolled in a clinical trial. Trial patients were matched in a 1:5 ratio to the control cohort based on clinical stage and then sociodemographic variables were compared between the 2 groups. Multivariable conditional logistic regression models evaluated factors associated with clinical trial participation. The trial patient cohort was then matched again in a 1:10 ratio based on age, clinical stage, and comorbidities. Log-rank test was used to compare overall survival (OS) between these groups. RESULTS: From 2004 to 2014, 681 patients enrolled in clinical trials were identified. Clinical trial patients were significantly younger and had a lower Charlson-Deyo comorbidity score. On multivariate analysis, male patients and white patients were more likely to participate compared to their Black counterparts. Having Medicaid or Medicare negatively associated with trial participation. Median OS was greater among clinical trial participants. CONCLUSION: Patient sociodemographic factors remain significantly associated with clinical trial participation and trial participants experienced superior OS to their matched counterparts.

Facilitating psychological adjustment for breast cancer patients through empathic communication and uncertainty reduction.

OBJECTIVES: This study examined the degree to which breast cancer patients' psychological well-being is facilitated through empathic provider communication. We explored symptom/prognostic uncertainty reduction as a mechanism through which provider communication influences patient psychological adjustment. Additionally, we tested if treatment status moderates this relationship. METHODS: Informed by uncertainty in illness theory, current (n = 121) and former (n = 187) breast cancer patients completed questionnaires about perceptions of their oncologists' empathy and their symptom burden, uncertainty, and adjustment to their diagnosis. Structural equation modeling (SEM) was conducted to test hypothesized relationships between perceived provider empathic communication, uncertainty, symptom burden, and psychological adjustment. RESULTS: SEM supported the following: (1) higher symptom burden was associated with increased uncertainty and reduced psychological adjustment, (2) lower uncertainty was associated with increased adjustment, and (3) increased empathic communication was associated with lower symptom burden and uncertainty for all patients (χ2(139) = 307.33, p < .001; RMSEA = .063 (CI .053, .072); CFI = .966; SRMR = .057). Treatment status moderated these relationships (Δχ2 = 264.07, Δdf = 138, p < .001) such that the strength of the relationship between uncertainty and psychological adjustment was stronger for former patients than for current patients. CONCLUSIONS: Results of this study reinforce the importance of perceptions of provider empathic communication as well as the potential benefits of eliciting and addressing patient uncertainty about treatment and prognosis throughout the cancer care continuum. PRACTICE IMPLICATIONS: Patient uncertainty should be a priority for cancer-care providers both throughout and post-treatment for breast cancer patients.