Nutritional Status and Health-Related Quality of Life in Men with Advanced Castrate-Resistant Prostate Cancer.

Background Despite professional recommendations malnutrition is not adequately addressed in cancer patients. Here, we explored whether nutritional status (NS) is associated with HRQoL in men with metastatic castrate-resistant prostate cancer (mCRPC). Methods: Men with mCRPC enrolled into this prospective observational study were allocated to one of the four NS categories based on clinical, laboratory, and patient self-reported criteria: well-nourished (WN), nutritional risk without criteria for cachexia/sarcopenia (NR), sarcopenia, and cachexia. The HRQoL was evaluated by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. Association between NS and self-reported HRQoL was sought by the linear regression model, which was adjusted for known prognostic variables and body mass index. Results: Over the period of two years, 141 patients were enrolled. Their median age was 74.1 years (IQR 68.6-79.4 years) and majority of them were minimally symptomatic. Fifty-nine patients (41.8%) were WN, followed by 24 (17%), 42 (29.8%), and 16 (11.4%) patients with NR, sarcopenia, and cachexia, respectively. As compared to WN patients, all three other NS categories were significant negative predictors of HRQoL (P < 0.04). Conclusions: Abnormal NS is highly prevalent in men with mCRPC and is negatively associated with their HRQoL, which supports the recommendation for management of malnutrition in these patients.

Meta-Research on Oncology Trials: A Toolkit for Researchers with Limited Resources.

"Meta-research" is a discipline that investigates research practices. Meta-research on clinical trials is an attempt to summarize descriptive and methodological features of published or ongoing clinical trials, including aspects of their implementation, design, analysis, reporting, and interpretation. In this type of investigation, the unit of analysis is a primary source of information about a clinical trial (e.g., published reports, study protocols, or abstracts), with meta-research being a second layer of information that summarizes what is known from various primary sources. After the formulation of the primary research question, the methodology of meta-research resembles that of other research projects, with predefined eligibility criteria, exposure variables, primary and secondary outcomes of interest, and an analysis plan. This type of study usually provides a high-level picture of the literature on a specific topic, always accompanied by a critical evaluation of the methodology and/or the quality of reporting of the studies included. Because relatively few resources are consumed to produce meta-research, these studies offer a great opportunity for clinical scientists working in settings with limited resources. In this article, we present the principles of designing and conducting meta-research and use our experience to suggest recommendations on how to perform and how to report this type of potentially very creative study. IMPLICATIONS FOR PRACTICE: The term meta-research pertains to a type of study in which the unit of analysis is, in most cases, the publication of a clinical trial. This type of study usually provides a high-level picture of the literature on a specific topic, always accompanied by a critical evaluation of the methodology, design, and/or the quality of reporting of the studies included. Because relatively few resources are consumed to produce meta-research, these studies offer a great opportunity for clinical scientists who work in low-income countries. This article presents the principles of designing and conducting meta-research and proposes practical recommendations on how to perform and report this type of potentially very creative study.

Influence of control group therapy on the benefit from dose-dense chemotherapy in early breast cancer: a systemic review and meta-analysis.

PURPOSE: Results from clinical trials of adjuvant dose-dense chemotherapy in patients with breast cancer are inconsistent. METHODS: A systematic search of MEDLINE identified studies comparing the efficacy of dose-dense adjuvant chemotherapy to a standard treatment. The primary analysis included studies that used identical regimens in the experimental and control groups, but varied only dose density. A secondary analysis included studies that used either different drugs or doses in the experimental and the control groups. Hazard ratios (HRs) and 95% confidence intervals were computed for disease-free survival (DFS) and overall survival (OS) and pooled in a meta-analysis. Subgroup analyses and meta-regression explored drug schedules utilized in control groups and the influence of clinicopathologic variables on benefit from dose-dense therapy. RESULTS: The primary analysis included 5 studies comprising 9819 patients while the secondary analysis included 6 studies comprising 9679 patients. Dose-dense treatment significantly improved DFS (HR 0.85, p < 0.001) and OS (HR 0.86, p = 0.008) in the primary analysis. Similar results were observed in the secondary analysis. Dose-dense schedule was important primarily in studies utilizing paclitaxel every 3 weeks as the control group (interaction p = 0.04 for DFS interaction p = 0.001 for OS). A significantly greater relative magnitude of benefit was observed in pre-menopausal women and those with nodal involvement, but there was no influence of hormone receptor status on results. CONCLUSIONS: Adjuvant dose-dense regimens improve breast cancer outcomes. It remains uncertain whether the observed benefit reflects the impact of dose density or the inferiority of paclitaxel every 3 weeks as a control group.

Reporting of Randomized Trials in Common Cancers in the Lay Media.

BACKGROUND: Limited data exist about the role of the lay media in the dissemination of results of randomized controlled trials (RCTs) in common cancers. METHODS: Completed phase III RCTs evaluating new drugs in common cancers between January 2005 and October 2016 were identified from ClinicalTrials.gov. Lay media reporting was identified by searching LexisNexis Academic. Scientific reporting was defined as presentation at an academic conference or publication in full. Associations between reporting in the lay media before scientific reporting and study design and sponsorship were evaluated using logistic regression. RESULTS: Of 180 RCTs identified, 52% were reported in the lay media and in 27%, lay media reporting occurred before scientific reporting with an increasing trend over time (p = 0.009). Reporting in the lay media before scientific reporting was associated with positive results (OR: 2.10, p = 0.04), targeted therapy compared to chemotherapy (OR: 4.75, p = 0.006), immunotherapy compared to chemotherapy (OR: 7.60, p = 0.02), and prostate cancer compared to breast cancer (OR: 3.25, p = 0.02). CONCLUSIONS: Over a quarter of all RCTs in common cancers are reported in the lay media before they are reported scientifically with an increasing proportion over time. Positive trials, studies in prostate cancer, and trials of immunotherapy are associated with early reporting in the lay media.

Prognostic role of telomere length in malignancies: A meta-analysis and meta-regression.

Telomere length (TL) has been associated with several health conditions including cancer. To quantify the effect of TL on outcomes in malignancies and explore the role of type of TL measurement we conducted a librarian-led systematic search of electronic databases identified publications exploring the prognostic role of TL on cancer outcomes. Overall survival (OS) was the primary outcome measure while other time-to-event endpoints were secondary outcomes. Data from studies reporting a hazard ratio (HR) with 95% confidence interval (CI) and/or p-value were pooled in a meta-analysis. HRs were weighted by generic inverse variance and computed by random effects modeling. All statistical tests were two-sided. Sixty-one studies comprising a total of 14,720 patients were included of which 41 (67%) reported OS outcomes. Overall, the pooled HR for OS was 0.88 (95%CI=0.69-1.11, p=0.28). Long (versus short) telomeres were associated with improved outcomes in chronic lymphatic leukemia (CLL) and urothelial cancer (HR=0.45, 95%CI=0.29-0.71 and HR=0.68, 95%CI=0.46-1.00, respectively), conversely worse OS was seen with hepatocellular carcinoma (HR=1.90, 95%CI=1.51-2.38). Pooled HRs (95% CI) for progression-free survival, relapse/disease-free survival, cancer-specific survival, and treatment-free survival were 0.56 (0.41-0.76), 0.76 (0.53-1.10), 0.72 (0.48-1.10), and 0.48 (0.39-0.60), respectively. There was substantial heterogeneity of tissues and methods used for TL measurement and no clear association between TL and outcome was identified in subgroups. In conclusion, there is inconsistent effect of TL on cancer outcomes possibly due to variable methods of measurement. Standardization of measurement and reporting of TL is warranted before the prognostic value of TL can be accurately assessed.

Under-reporting of harm in clinical trials.

Appropriate safety evaluations of anticancer drugs are crucial to assess their benefit-risk ratio. Substantial evidence shows that clinicians under-report harm in clinical trials, and at least three factors contribute to this problem: assessment of harm by clinicians might not represent the experience of patients; harm might be detected within trials, but is not reported appropriately by investigators or reporting is influenced by sponsors; and short-term follow-up might not detect long-term and potentially serious toxicities. Additionally, because of the selection of patients with good functional status in clinical trials, study results might not apply to patients treated in everyday clinical practice. New approaches for the conduct, oversight, and reporting of clinical trials should include patient-reported assessment of side-effects. Effective pharmacovigilance programmes and large-scale observational studies are needed to improve understanding of the tolerability of anticancer drugs in a real world setting.

Relevance of randomised controlled trials in oncology.

Well-designed randomised controlled trials (RCTs) can prevent bias in the comparison of treatments and provide a sound basis for changes in clinical practice. However, the design and reporting of many RCTs can render their results of little relevance to clinical practice. In this Personal View, we discuss the limitations of RCT data and suggest some ways to improve the clinical relevance of RCTs in the everyday management of patients with cancer. RCTs should ask questions of clinical rather than commercial interest, avoid non-validated surrogate endpoints in registration trials, and have entry criteria that allow inclusion of all patients who are fit to receive treatment. Furthermore, RCTs should be reported with complete accounting of frequency and management of toxicities, and with strict guidelines to ensure freedom from bias. Premature reporting of results should be avoided. The bar for clinical benefit should be raised for drug registration, which should require publication and review of mature data from RCTs, post-marketing health outcome studies, and value-based pricing.

Transcriptomic analyses identify association between mitotic kinases, PDZ-binding kinase and BUB1, and clinical outcome in breast cancer.

Protein kinases are important components in oncogenic transformation of breast cancer. Evaluation of upregulated genes that codify for protein kinases could be used as biomarkers to predict clinical outcome. Gene expression and functional analyses using public datasets were performed to identify differential gene expression and functions in basal-like tumors compared with normal breast tissue. Overall survival (OS) associated with upregulated genes was explored using the KM Plotter online tool. The prognostic influence of these genes in luminal tumors and systemically untreated patients was also assessed. Of the 426 transcripts identified in basal-like tumors, 11 genes that coded for components of protein kinases were upregulated with more than a fourfold change. Regulation of cell cycle was an enriched function containing 10 of these 11 identified genes. Among them, expression of four genes, BUB1ß, CDC28, NIMA, and PDZ binding kinase, were all associated with improved OS when using at least one probe in the basal-like subtype. Two genes, BUB1ß and PDZ binding kinase, showed consistent association with improved OS irrespective of the gene probe used for the analysis. No association was observed for these genes with relapse-free survival. In contrast, both BUB1ß and PDZ binding kinase showed worse OS in luminal tumors and in a cohort of systemically untreated patients. BUB1ß and PDZ binding kinase are associated with improved OS in basal-like tumors and worse OS in luminal and untreated patients. The association with a better outcome in basal-like tumors could be due to a more favorable response to chemotherapy.

Pretreatment Differences in Intraindividual Variability in Reaction Time between Women Diagnosed with Breast Cancer and Healthy Controls.

OBJECTIVES: Chemotherapy has adverse effects on cognitive performance in women treated for breast cancer, but less is known about the period before chemotherapy. Studies have focused on mean level of performance, yet there is increasing recognition that variability in performance within an individual is also an important behavioral indicator of cognitive functioning and underlying neural integrity. METHODS: We examined intraindividual variability (IIV) before chemotherapy and surgery in women diagnosed with breast cancer (n=31), and a healthy control group matched on age and education (n=25). IIV was calculated across trials of a computerized Stroop task, including an examination of the slowest and fastest trials of reaction time (RT) responses. RESULTS: The groups were equivalent on overall accuracy and speed, and participants in both groups were less accurate and slower on incongruent trials compared with congruent trials. However, women with breast cancer became more variable with increased task difficulty relative to healthy controls. Among the slowest RT responses, women with breast cancer were significantly more variable than healthy controls on incongruent trials. This suggests that a specific variability-producing process (e.g., attentional lapses) occurs in task conditions that require executive control (e.g., incongruent trials). CONCLUSIONS: Results are consistent with other evidence of executive dysfunction among women treated for breast cancer. These findings highlight the importance of pretreatment assessment and show that variability in performance provides information about cognition that measures of central tendency do not.

Outcome of severe infections in afebrile neutropenic cancer patients.

BACKGROUND: In some neutropenic cancer patients fever may be absent despite microbiologically and/or clinically confirmed infection. We hypothesized that afebrile neutropenic cancer patients with severe infections have worse outcome as compared to cancer patients with febrile neutropenia. PATIENTS AND METHODS: We retrospectively analyzed all adult cancer patients with chemotherapy-induced neutropenia and severe infection, who were admitted to the Intensive Care Unit at our cancer center between 2000 and 2011. The outcome of interest was 30-day in-hospital mortality rate. Association between the febrile status and in-hospital mortality rate was evaluated by the Fisher's exact test. RESULTS: We identified 69 episodes of severe neutropenic infections in 65 cancer patients. Among these, 9 (13%) episodes were afebrile. Patients with afebrile neutropenic infection presented with hypotension, severe fatigue with inappetence, shaking chills, altered mental state or cough and all of them eventually deteriorated to severe sepsis or septic shock. Overall 30-day in-hospital mortality rate was 55.1%. Patients with afebrile neutropenic infection had a trend for a higher 30-day in-hospital mortality rate as compared to patients with febrile neutropenic infection (78% vs. 52%, p = 0.17). CONCLUSIONS: Afebrile cancer patients with chemotherapy-induced neutropenia and severe infections might have worse outcome as compared to cancer patients with febrile neutropenia. Patients should be informed that severe neutropenic infection without fever can occasionally occur during cancer treatment with chemotherapy.

Biological insights into effective and antagonistic combinations of targeted agents with chemotherapy in solid tumors.

The potential for synergistic interactions between anticancer drugs has been used to justify combinations of agents in clinical trials. However, most combinations of targeted agents and chemotherapies have been tested in the clinic without previous systematic evaluation of their potential benefit. Preclinical studies may help in the identification of synergistic or antagonistic interactions. For antineoplastic therapies, these studies may reveal synergy or antagonism of the drug combinations. Synergy occurs when two agents given together produce higher antitumoral activity than the sum of each individual drug. This represents the ideal setting for the development of combinations of targeted agents and chemotherapies. On the other side, certain drug combinations have shown adverse results, indicative of an antagonistic effect. In this article, we review the preclinical molecular bases that justify approved combinations of targeted agents with chemotherapy including examples of synergistic and antagonistic combinations. We also discuss scenarios for rational associations of targeted agents based on biological data and propose strategies that may improve the success of combinations of anticancer agents.

Impact of comorbidity on the outcome in men with advanced prostate cancer treated with docetaxel.

BACKGROUND: Men with metastatic castrate-resistant prostate cancer (mCRPC) may not receive docetaxel in everyday clinical practice due to comorbidities. Here we explore the impact of comorbidity on outcome in men with mCRPC treated with docetaxel in a population-based outcome study. METHODS: Men with mCRPC treated with docetaxel at the Institute of Oncology Ljubljana between 2005 and 2012 were eligible. Comorbidity was assessed by the age-adjusted Charlson comorbidity index (aa-CCI) and adult comorbidity evaluation (ACE-27) index. Hospital admissions due to the toxicity and deaths during treatment with docetaxel were used as a measure of tolerability. Association between comorbidity and overall survival (OS) was tested using the Cox proportional hazards analysis. RESULTS: Two hundred and eight men were treated with docetaxel. No, mild, moderate and severe comorbidity was present in 2%, 32%, 53% and 13% using aa-CCI and in 27%, 35%, 29% and 8% when assessed by ACE-27. A substantial dose reduction of docetaxel occurred more often in men with moderate or severe comorbidity as compared to those with no or mild comorbidity. At all comorbidity levels about one-third of men required hospitalization or died during treatment with docetaxel. In univariate analysis a higher level of comorbidity was not associated with worse OS (aa-CCI HR 0.99; [95% CI 0.87-1.13], p = 0.93; ACE-27: HR 0.96; [95% CI 0.79-1.17], p = 0.69). CONCLUSIONS: Men with mCRPC, who have comorbidities may benefit from treatment with docetaxel.

Barriers and challenges to global clinical cancer research.

BACKGROUND: There are concerns about growing barriers to cancer research. We explored the characteristics of and barriers to global clinical cancer research. METHODS: The American Society of Clinical Oncology International Affairs Committee invited 300 selected oncologists with research experience from 25 countries to complete a Web-based survey. Fisher's exact test was used to compare answers between participants from high-income countries (HICs) and low- and middle-income countries (LMICs). Barriers to clinical cancer research were ranked from 1 (most important) to 8 (least important). Mann-Whitney's nonparametric test was used to compare the ranks describing the importance of investigated obstacles. RESULTS: Eighty oncologists responded, 41 from HICs and 39 from LMICs. Most responders were medical oncologists (62%) at academic hospitals (90%). Researchers from HICs were more involved with academic and industry-driven research than were researchers from LMICs. Significantly higher proportions of those who considered their ability to conduct academic research and industry-driven research over the past 5 years more difficult were from HICs (73% vs. 27% and 70% vs. 30%, respectively). Concerning academic clinical cancer research, a lack of funding was ranked the most important (score: 3.16) barrier, without significant differences observed between HICs and LMICs. Lack of time or competing priorities and procedures from competent authorities were the second most important barriers to conducting academic clinical research in HICs and LMICs, respectively. CONCLUSION: Lack of funding, lack of time and competing priorities, and procedures from competent authorities might be the main global barriers to academic clinical cancer research.

Effect of multifocality and multicentricity on outcome in early stage breast cancer: a systematic review and meta-analysis.

Women with multifocal or multicentric breast tumors (multifocality henceforth) have been reported to have greater probability of nodal metastasis and relapse and worse survival than women with unifocal tumors. However, these associations have been inconsistent and multifocality is not taken into account by staging guidelines and prognostic models. A systematic review of electronic databases identified publications exploring the association between multifocality and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and loco-regional relapse (LRR). The hazard ratios (HRs) for OS and DFS for multifocal compared to unifocal tumors were extracted from multivariable analyses and included in a meta-analysis. For studies not reporting multivariable analyses, odds ratios (OR) were estimated from Kaplan-Meier curves for all endpoints at 5 and 10 years. Twenty-two studies comprising 67,557 women were included. Multifocality was reported in 9.5 % of patients. Classical prognostic factors were well balanced between unifocal and multifocal populations. In multivariable analyses, multifocality was associated with significantly worse OS (HR 1.65; P = 0.02), and a non-significant association with worse DFS (HR 1.96; P = 0.07). In univariable analyses, multifocality was associated with worse OS, DFS, DSS, and LRR at 5 years (OR 1.39, P = 0.02; OR 1.52, P = 0.02; OR 1.56, P = 0.03; and OR 3.23, P = 0.02, respectively). Similar estimates were observed at 10 years, but statistical significance was only reached for DSS and LRR. Mutifocality appears to be associated with a worse prognosis, however, substantial inter-study heterogeneity limits the precise determination of increased risk. Further validation of the independent prognostic impact of multifocality is warranted.

Osteoblastic bone metastases from renal cell carcinoma.

BACKGROUND: RCC accounts for only 2-3% of all cancers. Due to its' non-specific symptoms disease is often diagnosed in advanced stage. Disseminated RCC frequently produces bone metastases that are almost always highly destructive, hyper vascularized and purely osteolytic. CASE REPORT: In this article we describe a case of a 71-year old male patient with disseminated osteoblastic bone metastases from renal cell carcinoma (RCC), and present a short review of published literature reporting cases of osteoblastic bone metastases from RCC. Our patient presented with thoracic pain aggravated by movement. He was diagnosed with predominantly osteoblastic bone metastases in the skeleton of thoracic and lumbar vertebra along with metastases in iliac bones, ribs, humerus and clavicles. Initially, origin of bone metastases was unknown, but later a small tumor in patient's right kidney was identified. Microscopic evaluation of the open bone biopsy showed clear cell RCC with sarcomatoid differentiation. CONCLUSIONS: Although, due to its' rarity, RCC is not included in the primary differential diagnosis in patients with osteoblastic metastases, such rare cases suggest that RCC may be considered in the diagnosis when there no other primary tumor is found.

Potentially fatal complications of new systemic anticancer therapies: pearls and pitfalls in their initial management.

BACKGROUND: Various types of immunotherapy (i.e. immune checkpoint inhibitors [ICIs], chimeric antigen receptor [CAR] T-cells and bispecific T-cell engagers [BiTEs]) and antibody drug conjugates (ADCs) have been used increasingly to treat solid cancers, lymphomas and leukaemias. Patients with serious complications of these therapies can be presented to physicians of different specialties. In this narrative review we discuss potentially fatal complications of new systemic anticancer therapies and some practical considerations for their diagnosis and initial treatment. RESULTS: Clinical presentation of toxicities of new anticancer therapies may be unpredictable and nonspecific. They can mimic other more common medical conditions such as infection or stroke. If not recognized and properly treated these toxicities can progress rapidly into life-threatening conditions. ICIs can cause immune-related inflammatory disorders of various organ systems (e.g. pneumonitis or colitis), and a cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) may develop after treatment with CAR T-cells or BiTEs. The cornerstones of management of these hyper-inflammatory disorders are supportive care and systemic immunosuppressive therapy. The latter should start as soon as symptoms are mild-moderate. Similarly, some severe toxicities of ADCs also require immunosuppressive therapy. A multidisciplinary team including an oncologist/haematologist and a corresponding organ-site specialist (e.g. gastroenterologist in the case of colitis) should be involved in the diagnosis and treatment of these toxicities. CONCLUSIONS: Health professionals should be aware of potential serious complications of new systemic anticancer therapies. Early diagnosis and treatment with adequate supportive care and immunosuppressive therapy are crucial for the optimal outcome of patients with these complications.

Challenges in the management of operable triple-negative breast cancer in a survivor of the B-cell acute lymphoblastic leukemia: a case report.

Background: Operable triple-negative breast cancer (TNBC) is an unfavorable subtype of breast cancer, which usually requires an aggressive perioperative systemic treatment. When TNBC presents as a second primary cancer after cured acute leukemia, its management might be challenging. Case presentation: We present a case report of a young postmenopausal woman with an operable TNBC who had a history of the B-cell acute lymphoblastic leukemia (B-ALL) and graft versus host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT). A history of previous treatment with anthracyclines and radiotherapy and GVHD limited the use of doxorubicin for treatment of her TNBC. Due to the history of GVHD, perioperative treatment with pembrolizumab was omitted. Genetic testing was challenging due to the possible contamination of her tissues with the donor's cells after allo-SCT. In samples of our patient's buccal swab, peripheral blood, and tumor tissue, a pathogenic variant in the partner and localizer of BRCA2 (PALB2) gene was found. With neoadjuvant chemotherapy which included carboplatin, a pathologic complete response was achieved. Although our patient has a low risk for recurrence of TNBC, her risk for the development of new primary cancers remains substantial. Conclusion: This case highlights challenges in the systemic treatment, genetic testing, and follow-up of patients with operable TNBC and other solid cancers who have a history of acute leukemia.

Association of androgen receptor and tumour-infiltrating lymphocytes with bone recurrence in triple-negative breast cancer.

Background: As compared to endocrine responsive breast cancer bone is less frequent site of distant recurrence in triple-negative breast cancer (TNBC). A biomarker which predicts bone recurrence would allow a more personalized treatment approach with adjuvant bisphosphonates in TNBC. Here we hypothesised that tumour expression of androgen receptor (AR) is associated with bone recurrence in TNBC. Materials and methods: Patients with operable TNBC who were treated at the Institute of Oncology Ljubljana between 2005 and 2015 and developed distant recurrence were included into our study. Nuclear expression of AR in the tissue of primary tumours was determined immunohistochemically by using the Androgen Receptor (SP107) Rabbit Monoclonal Antibody. We applied a logistic regression model to test the association between expression of AR and development of bone metastases. The model was adjusted for selected known prognostic factors and possible confounders in TNBC, including the level of the stromal tumour-infiltrating lymphocytes (sTILs). Results: At recurrence 45 (45 %) out of 100 patients presented with bone metastases. Additionally, seven (7 %) developed bone metastases metachronously. AR was expressed in primary tumours of 35 (35 %) women and 19 (54.3 %) developed bone recurrence. In 25 (25 %) patients sTILs were absent. Neither the proportion of AR positive cancer cells (OR = 1.00; 95 % CI 0.96-1.03; p = 1.00) nor the intensity of AR positive reaction (OR = 0.71; 95 % CI 0.02-21.4; p = 1.00) were significantly associated with bone recurrence. However, women with at least mild level of the sTILs were at significantly lower risk for bone recurrence as compared to those without any sTILs (OR = 0.01; 95 % CI < 0.01-0.08; p = 0.01). Conclusions: Expression of AR is not significantly associated with the development of bone metastases in TNBC. However, patients with absent sTILs in their primary tumours are highly susceptible for recurrence in the bone and might particularly benefit from adjuvant bisphosphonates.

Prognostic Impact of Nutritional Status on Overall Survival and Health-Related Quality of Life in Men with Advanced Prostate Cancer.

PURPOSE: Prognostic role of nutritional status (NS) in patients with metastatic castrate-resistant prostate cancer (mCRPC) is unknown. We hypothesized that patients' NS at the presentation of mCRPC is prognostic for health-related quality of life (HRQoL) and overall survival (OS). METHODS: We conducted a prospective observational study in mCRPC patients. At enrollment, we allocated each patient into one of four NS categories: (i) well-nourished (WN), (ii) nutritional risk without sarcopenia/cachexia (NR), (iii) sarcopenia, or (iv) cachexia. We sought the prognostic role of the NS for OS and HRQoL by regression models. RESULTS: 141 patients were included into our study. When compared to WN patients, those with NR and cachexia had a higher chance of worse HRQoL (OR 3.45; 95% CI [1.28 to 9.09], and OR 4.17; 95% CI [1.28 to 12.5], respectively), as well as shorter OS (HR 2.04; 95% CI [1.19 to 3.39] and HR 2.9; 95% CI [1.56 to 5.41], respectively). However, when accounting for possible confounding factors, we could not prove the significant importance of NS for chosen outcomes. CONCLUSIONS: Suboptimal NS might be an unfavorable prognostic factor for HRQoL and OS. Further interventional studies focusing on therapy or prevention are warranted.

The trajectory of sarcopenia following diagnosis of prostate cancer: A systematic review and meta-analysis.

INTRODUCTION: Sarcopenia is a common skeletal muscle disorder in older people. Here we explore the prevalence of sarcopenia and its impact on men with prostate cancer. MATERIALS AND METHODS: We searched PubMed, Embase, and Web of Science databases for relevant studies with an explicit definition of sarcopenia in men with prostate cancer which were published between years 2000 and 2022. Prevalence of sarcopenia and its association with time to biochemical recurrence (BCR), progression-free survival (PFS), non-cancer mortality, overall survival (OS), and treatment-related complications in men with prostate cancer were explored. The summary prevalence, hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 24 studies comprising 3,616 patients with early and advanced prostate cancer were included. The prevalence of sarcopenia and sarcopenic obesity was 43.8% (95% CI 19.2%-68.5%) and 24.0% (95% CI 5.0%-43.1%), respectively. Sarcopenia was not associated with a shorter time to BCR (HR 0.89, 95% CI 0.64-1.23, p = 0.48), a shorter PFS (HR 1.20, 95% CI 0.73-1.97, p = 0.48), or a shorter OS (HR 1.29, 95% CI 0.90-1.85, p = 0.16). In contrast, sarcopenia was significantly associated with a higher non-cancer mortality (HR 1.85, 95% CI 1.23-2.80, p = 0.003). In four out of five studies eligible for assessment, sarcopenia was not associated with an increased risk of treatment-related complications. DISCUSSION: Sarcopenia increases the risk of death from other causes in men with prostate cancer. Patients with prostate cancer should be assessed and managed for sarcopenia in everyday clinical practice.