Perceived barriers to the adoption of active surveillance in low-risk prostate cancer: a qualitative analysis of community and academic urologists.

BACKGROUND: Clinical practice guidelines recommend active surveillance as the preferred treatment option for low-risk prostate cancer, but only a minority of eligible men receive active surveillance, and practice variation is substantial. The aim of this study is to describe barriers to urologists' recommendation of active surveillance in low-risk prostate cancer and explore variation of barriers by setting. METHODS: We conducted semi-structured interviews among 22 practicing urologists, evenly distributed between academic and community practice. We coded barriers to active surveillance according to a conceptual model of determinants of treatment quality to identify potential opportunities for intervention. RESULTS: Community and academic urologists were generally in agreement on factors influencing active surveillance. Urologists perceived patient-level factors to have the greatest influence on recommendations, particularly tumor pathology, patient age, and judgements about the patient's ability to adhere to follow-up protocols. They also noted cross-cutting clinical barriers, including concerns about the adequacy of biopsy samples, inconsistent protocols to guide active surveillance, and side effects of biopsy procedures. Urologists had differing opinions on the impact of environmental factors, such as financial disincentives and fear of litigation. CONCLUSIONS: Despite national and international recommendations, both academic and community urologists note a variety of barriers to implementing active surveillance in low risk prostate cancer. These barriers will need to be specifically addressed in efforts to help urologists offer active surveillance more consistently.

Associations between self-reported physical activity, quality of life, and emotional well-being in men with prostate cancer on active surveillance.

OBJECTIVE: The relationship between physical activity (PA) and quality of life (QOL) relative to active treatment for prostate cancer (PCa) has been well-studied; however, little is known about this relationship during active surveillance (AS). Moreover, whether PA is associated with better emotional well-being (EWB) in men with low-risk PCa requires further investigation. Accordingly, we examined the association between self-reported PA and the average change in QOL and EWB over time during AS. METHODS: A total of 630 men on AS were included in this retrospective, longitudinal study from AS initiation until AS discontinuation. Generalized estimated equations were used to determine the association between self-reported PA (independent variable) and QOL and EWB (dependent variables) over time, adjusting for participants' age. RESULTS: QOL was higher over time in active ( ß^ (95%CI) = 1.14 (0.11, 2.16), P = .029) and highly active participants ( ß^ (95%CI) = 1.62 (0.58, 2.67), P = .002) compared to their inactive counterparts. Highly active participants had 55% greater odds of experiencing high EWB relative to inactive participants (OR (95%CI) = 1.55 (1.11, 2.16), P = .010). In men with low EWB at baseline (median = 3 months after diagnosis), the highest levels of PA (>1000 metabolic equivalent-minutes per week) were associated with high EWB over time (OR (95%CI) = 2.17 (1.06, 4.46), P = .034). CONCLUSIONS: These data further support the importance of PA as a supportive care strategy for men on AS. Our findings suggest that engaging in higher volumes of PA post-diagnosis may be beneficial particularly for men exhibiting low emotional well-being early on during AS.

Influence of physical activity on active surveillance discontinuation in men with low-risk prostate cancer.

PURPOSE: Epidemiologic data suggest that high levels of physical activity (PA) may reduce the risk of disease progression in men with prostate cancer (PCa), but it is unknown whether PA can delay the requirement for definitive treatment for those on active surveillance (AS). We investigated the influence of PA post-diagnosis on AS discontinuation in men with low-risk disease. METHODS: The effect of PA on the time to AS discontinuation was assessed in 421 patients, of whom 107 underwent additional PCa treatment over a median of 2.5 years. RESULTS: Using Cox regression models, we found that PA was not significantly associated with time to curative treatment initiation. Prostate-specific antigen (PSA) most proximal to AS initiation (HR, 1.11; 95% CI 1.03 to 1.21) and the number of positive cores (HR, 1.34; 95% CI 1.12 to 1.61) at diagnosis were associated with a significantly increased risk of discontinuing AS. CONCLUSION: Our findings suggest that PA during AS for PCa does not significantly influence time to curative treatment.

Setting Fire to ESA and EMA Resistance: New Targeted Treatment Options in Lower Risk Myelodysplastic Syndromes.

During the last decade, substantial advances have been made in the understanding of the complex molecular, immunological and cellular disturbances involved in the initiation as well as evolution of myelodysplastic syndromes (MDS). In 85% of the mainly frail and older patient population, anemia is present at the time of diagnosis and is thus a major therapeutic challenge. High rates of primary resistance to erythropoiesis-stimulating agents (ESAs), the currently only approved standard therapy to treat anemia in lower-risk MDS, demand the development of novel and efficient drugs with a good safety profile. Luspatercept, a ligand trap of activin receptor II, is able to promote late stage erythropoiesis even in patients failing prior ESA treatment. The presence of ring sideroblastic phenotype defines a subgroup of patients with higher response rates. Additionally, recent developments in clinical research using HIF-1 or telomerase modulation by roxadustat or imetelstat are promising. Other areas of translational research involve targeting the inflammasome by anti-inflammatory drugs in order to improve anemia. These efforts will hopefully pave the way for new targeted treatment options for anemic low-risk MDS patients.

Describing perspectives of health care professionals on active surveillance for the management of prostate cancer.

BACKGROUND: Over the last decade, active surveillance has proven to be a safe approach for patients with low-risk prostate cancer. Although active surveillance presents several advantages for both patients and the health care system, all eligible patients do not adopt this approach. Our goal was to evaluate the factors that influence physicians to recommend active surveillance and the barriers that impact adherence to this approach. METHODS: Focus groups (n = 5) were held with physicians who provided care for men with low-risk prostate cancer and had engaged in conversations with men and their families about active surveillance. The experience of health care professionals (HCPs) was captured to understand their decisions in proposing active surveillance and to reveal the barriers and facilitators that affect the adherence to this approach. A content analysis was performed on the verbatim transcripts from the sessions. RESULTS: Although physicians agreed that active surveillance is a suitable approach for low-risk prostate cancer patients, they were concerned about the rapidly evolving and non-standardized guidelines for patient follow-up. They pointed out the need for additional tools to appropriately identify proper patients for whom active surveillance is the best option. Urologists and radiation-oncologists were keen to collaborate with each other, but the role of general practitioner remained controversial once patients were referred to a specialist. CONCLUSIONS: Integration of more reliable tools and/or markers in addition to more specific guidelines for patient follow-up would increase the confidence of both patients and physicians in the choice of active surveillance.

Canadian Men's perspectives about active surveillance in prostate cancer: need for guidance and resources.

BACKGROUND: In prostate cancer, men diagnosed with low risk disease may be monitored through an active surveillance. This research explored the perspectives of men with prostate cancer regarding their decision-making process for active surveillance to identify factors that influence their decision and assist health professionals in having conversations about this option. METHODS: Focus group interviews (n = 7) were held in several Canadian cities with men (N = 52) diagnosed with prostate cancer and eligible for active surveillance. The men's viewpoints were captured regarding their understanding of active surveillance, the factors that influenced their decision, and their experience with the approach. A content and theme analysis was performed on the verbatim transcripts from the sessions. RESULTS: Patients described their concerns of living with their disease without intervention, but were reassured by the close monitoring under AS while avoiding harmful side effects associated with treatments. Conversations with their doctor and how AS was described were cited as key influences in their decision, in addition to availability of information on treatment options, distrust in the health system, personality, experiences and opinions of others, and personal perspectives on quality of life. CONCLUSIONS: Men require a thorough explanation on AS as a safe and valid option, as well as guidance towards supportive resources in their decision-making.

Disease and Clinical Characteristics of Patients With a Clinical Diagnosis of Myelofibrosis Enrolled in the MOST Study.

BACKGROUND: Clinical characteristics and treatment patterns of patients with lower-risk myelofibrosis (MF) are not well described. This analysis from the MOST (NCT02953704) assessed the demographic and clinical characteristics and treatment patterns of patients with the clinical diagnosis of lower-risk MF at enrollment. PATIENTS AND METHODS: MOST is an ongoing, prospective, observational study in patients with clinical diagnoses of MF or essential thrombocythemia enrolled at clinical practices throughout the United States. Patients included in the MF cohort (≥18 years of age) had low-risk MF by the Dynamic International Prognostic Scoring System or intermediate-1 (INT-1) risk MF (by age >65 years only) at enrollment. Patient data were entered into an electronic case report form during usual-care visits over a planned 36 month observation period. RESULTS: Two hundred five patients were eligible for this analysis (low risk, n = 85; INT-1 risk, n = 120; median age, 68 years [range, 35-88]); 166 patients (81.0%) had mutation testing results available. The median time from MF diagnosis to enrollment was 1.8 years. Hemoglobin and hematocrit levels were below the normal range in 50.5% and 48.7% of patients, respectively. Nearly all (98.0%) patients had comorbid conditions, most commonly hypertension (49.8%). Fatigue was the most common physician-reported MF symptom (30.7%). At enrollment, 55.6% of patients were receiving MF-directed monotherapy, most frequently hydroxyurea (46.5%) or ruxolitinib (40.4%). CONCLUSION: Future longitudinal analyses of data from MOST will help identify unmet needs and characterize how patients with lower-risk MF are managed throughout the disease course.

Active surveillance for low-risk prostate cancer in Austria: the online registry of the Qualitätspartnerschaft Urologie (QuapU).

BACKGROUND: Active surveillance (AS) is a well-recognized strategy to reduce the risk of overtreatment in men with low-risk prostate cancer. No data on this approach are available from Austria. METHODS: The Qualitätspartnerschaft Urologie (QuapU) developed an online database for patients managed with AS in Austria. Principal inclusion/exclusion criteria corresponded to those of the S3 prostate cancer guideline of German urologists: prostate-specific antigen (PSA) <10 ng/ml, Gleason score <7 (maximum 20% of biopsies being positive). Control visits were scheduled at 3­month intervals, control biopsies were scheduled at 12 and 36 months. RESULTS: To date 131 patients have been entered into this data base. Mean patient age is 64 years, 6% were younger than 50 years, two thirds of patients were aged 50-70 years and 25% were older than 70 years. Mean PSA value was 5.9 ng/ml (PSA 0-4 ng/ml: 15%; PSA >4-10 ng/ml: 85%). The prostate volume averaged 39 ml. The mean time under AS was 17.5 months (<12 months: 60%; >12 months: 40%). The AS adherence at 12 months was 85% and at 24 months 76%. To date, a total of 23 patients (17.6%) stopped AS. The most frequent reasons for discontinuing AS were patient wish for active treatment (43.5%) and PSA progression (30.4%). A histological progression was rarely seen (6.1%) and the control biopsy rate was low (19.8%). CONCLUSION: This study is the first description of AS in Austria and documents the feasibility of an online registry for AS. The data confirm the international experience with this approach with acceptable adherence rates.