Phase II trial of palbociclib in patients with metastatic urothelial cancer after failure of first-line chemotherapy.

BACKGROUND: The majority of urothelial cancers (UC) harbor alterations in retinoblastoma (Rb) pathway genes that can lead to loss of Rb tumour suppressor function. Palbociclib is an oral, selective inhibitor of CDK 4/6 that restores Rb function and promotes cell cycle arrest. METHODS: In this phase II trial, patients with metastatic platinum-refractory UC molecularly selected for p16 loss and intact Rb by tumour immunohistochemistry received palbociclib 125 mg p.o. daily for 21 days of a 28-day cycle. Primary endpoint was progression-free survival at 4 months (PFS4) using a Simon's two-stage design. Next-generation sequencing including Rb pathway alterations was conducted. RESULTS: Twelve patients were enrolled and two patients (17%) achieved PFS4 with insufficient activity to advance to stage 2. No responses were seen. Median PFS was 1.9 months (95% CI 1.8-3.7 months) and median overall survival was 6.3 months (95% CI 2.2-12.6 months). Fifty-eight percent of patients had grade ≥3 hematologic toxicity. There were no CDKN2A alterations found and no correlation of Rb pathway alterations with clinical outcome. CONCLUSIONS: Palbociclib did not demonstrate meaningful activity in selected patients with platinum-refractory metastatic UC. Further development of palbociclib should only be considered with improved integral biomarker selection or in rational combination with other therapies.

Integrating Patient Preference into Treatment Decisions for Men with Prostate Cancer at the Point of Care.

PURPOSE: Men with clinically localized prostate cancer face an archetypal "preference sensitive" treatment decision. A shared decision making process incorporating patient values and preferences is paramount. We evaluated the benefit of a novel decision making application, and investigated associations between patient preferences and treatment choice. MATERIALS AND METHODS: We used a novel, web based application that provides education, preference measurement and personalized decision analysis for patients with newly diagnosed prostate cancer. Preferences are measured using conjoint analysis. The application ranks treatment options according to their "fit" (expected value) based on clinical factors and personal preferences, and serves as the basis for shared decision making during the consultation. We administered the decisional conflict scale before and after completion of the application. Additionally, we compared post-visit perceptions of shared decision making between a baseline "usual care" cohort and a cohort seen after the application was integrated into clinical practice. RESULTS: A total of 109 men completed the application before their consultation, and had decisional conflict measured before and after use. Overall decisional conflict decreased by 37% (p <0.0001). Analysis of the decisional conflict subscales revealed statistically significant improvements in all 5 domains. Patients completing the decision making application (33) felt more included in (88% vs 57%, p=0.01) and jointly responsible for (94% vs 52%, p <0.0001) the decision about further treatment compared to those receiving usual care (24). More patients who completed the application strongly agreed that different treatment options were discussed (94% vs 74%, p=0.02). CONCLUSIONS: Implementation of this web based intervention was associated with decreased decisional conflict and enhanced elements of shared decision making.

Collaboration Between Oncology Social Workers and Nurses: A Patient-Centered Interdisciplinary Model of Bladder Cancer Care.

OBJECTIVES: We propose a bladder cancer patient-centered, interdisciplinary collaboration model of care adapted from an earlier model by Black, Dornan, and Allegrante (1986). The Bladder Patient-Centered Interdisciplinary Team (BPIT) model provides a conceptual foundation for assembling interdisciplinary teams and emphasizes the patient as an active participant in treatment and member of the care team, along with oncology nurses, wound ostomy and continence nurses, and oncology social workers. DATA SOURCES: This model integrates scopes of practice and practice standards from nursing and social work professional organizations, findings from peer-reviewed articles, and expert clinical opinion in conceptualizing interdisciplinary bladder cancer care. CONCLUSION: BPIT is not meant to be an exhaustive or proscriptive catalog of roles and responsibilities. Future research is needed in this area to further refine and delineate the oncology social worker and nursing scopes of practice and standards for collaborative teamwork. IMPLICATIONS FOR NURSING PRACTICE: The unmet supportive care needs of patients with bladder cancer across all phases of the cancer continuum are well documented. Oncology and wound ostomy and continence nurses are of critical importance to holistically addressing these needs and enhancing the health-related quality of life. The BPIT model provides a broad overview of the discipline-specific and interdisciplinary team-specific roles and responsibilities for bladder cancer care.

A real-world evaluation of radium-223 in combination with abiraterone or enzalutamide for the treatment of metastatic castration-resistant prostate cancer.

INTRODUCTION: Radium-223, abiraterone, and enzalutamide have each been shown to significantly improve survival as monotherapy in patients with metastatic castration-resistant prostate cancer. However, effects of combination radium-223 plus abiraterone or enzalutamide on survival and safety remain unclear. PATIENTS AND METHODS: This single-center retrospective cohort study used electronic health record data of patients with metastatic castration-resistant prostate cancer and bone metastases who were treated with radium-223 between April 1, 2014 and February 19, 2019. Patients who received radium-223 monotherapy were compared to patients who received a combination of radium-223 plus either abiraterone or enzalutamide. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, time to symptomatic skeletal event, symptomatic skeletal event-free survival, and incidence of drug-related adverse events. Time-to-event analyses were estimated by log rank tests using Kaplan-Meier curves. Hazard ratios and 95% confidence intervals were derived from Cox proportional hazards models. Chi-square tests evaluated difference in serious adverse events between the two arms. RESULTS: A total of 60 patients met inclusion criteria (n = 41 in the monotherapy arm, n = 19 in the combination arm). Differences in median overall survival were not observed (12.7 vs. 12.8 months; HR 1.15, 95% CI 0.59-2.23; P = 0.68), but median progression-free survival was significantly longer in the combination arm (7.6 vs. 4.9 months; HR 1.94, 95% CI 1.11-3.40; P = 0.02). Significant differences were not observed in time to first SSE (P = 0.97), SSE-free survival (P = 0.16), or in the overall incidence of serious adverse events (P = 0.45). CONCLUSION: Combination radium-223 plus abiraterone or enzalutamide did not improve overall survival, but prolonged progression-free survival without increasing the incidence of serious adverse events in metastatic castration-resistant prostate cancer patients with bone metastases. However, these results are limited by small numbers and patient selection inherent in retrospective analysis.

Correction: A real-world evaluation of radium-223 in combination with abiraterone or enzalutamide for the treatment of metastatic castration-resistant prostate cancer.

[This corrects the article DOI: 10.1371/journal.pone.0253021.].

Improving couples' quality of life through a Web-based prostate cancer education intervention

PURPOSE/OBJECTIVES: To evaluate the feasibility and acceptability of a newly developed web-based, couple-oriented intervention called Prostate Cancer Education and Resources for Couples (PERC). DESIGN: Quantitative, qualitative, mixed-methods approach. SETTING: Oncology outpatient clinics at the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center at UNC­Chapel Hill. SAMPLE: 26 patients with localized prostate cancer (PCa) and their partners. METHODS: Pre- and postpilot quantitative assessments and a postpilot qualitative interview were conducted. MAIN RESEARCH VARIABLES: General and PCa-specific symptoms, quality of life, psychosocial factors, PERC's ease of use, and web activities. FINDINGS: Improvement was shown in some PCa-specific and general symptoms (small effect sizes for patients and small-to-medium effect sizes for partners), overall quality of life, and physical and social domains of quality of life for patients (small effect sizes). Web activity data indicated high PERC use. Qualitative and quantitative analyses indicated that participants found PERC easy to use and understand,as well as engaging, of high quality, and relevant. Overall, participants were satisfied with PERC and reported that PERC improved their knowledge about symptom management and communication as a couple. CONCLUSIONS: PERC was a feasible, acceptable method of reducing the side effects of PCa treatment­related symptoms and improving quality of life. IMPLICATIONS FOR NURSING: PERC has the potential to reduce the negative impacts of symptoms and enhance quality of life for patients with localized PCa and their partners, particularly for those who live in rural areas and have limited access to post-treatment supportive care.

Neoadjuvant chemotherapy administration and time to cystectomy for muscle-invasive bladder cancer: An evaluation of transitions between academic and community settings.

OBJECTIVES: Neoadjuvant chemotherapy (NAC) before radical cystectomy is the standard of care for muscle-invasive bladder cancer (MIBC). Many patients are referred to an academic medical center (AMC) for cystectomy but receive NAC in the community setting. This study examines if administration of NAC in the community is associated with differences in type of NAC received, pathologic response rate (pT0), and time to cystectomy as compared to NAC administered at an AMC. METHODS: We performed a retrospective study of patients with MIBC (cT2a-T4-Nx-M0) referred to a single AMC between 1/2012 and 1/2014 who received NAC. We analyzed chemotherapy received, time to cystectomy, pT0, and survival in patients who received NAC in our AMC compared to those treated in the community. RESULTS: In all, 47 patients were analyzed. A similar total dose of cisplatin (median: 280 mg/m(2) for both groups, P = 0.82) and pT0 rate (25% vs. 29%, P = 0.72) were seen in patients treated in our AMC and the community. However, administration of NAC in the community was associated with a prolonged time to cystectomy compared with that in our AMC (median number of days 162 vs. 128, P<0.01). This remained significant after adjusting for stage, comorbidity status, and distance to the AMC (P = 0.02). Disease-free survival and overall survival did not differ. CONCLUSION: Patients with MIBC treated with NAC in the community as compared to an AMC received similar chemotherapy and achieved comparable pT0 rates, indicating effective implementation of NAC in the community. However, NAC in the community was associated with longer time to cystectomy, suggesting a delay in the transition of care between settings.