Prostate cancer clinical trials in low- and middle-income countries.

Background: Prostate cancer is the second most common form of cancer and a leading cause of cancer-related death in men. In an era of evidence-based medicine, clinical trials play a critical role, and adherence to best practices is crucial in managing complicated and non-communicable diseases, such as prostate cancer. For this reason, extrapolating research conducted in high-income countries (HICs) to low-middle-income countries (LMICs) may lead to incorrect findings or treatment plans for patients in these areas. Unfortunately, clinical trials in LMICs face several challenges in terms of design, funding and recruitment. This study aimed to examine clinical trials on prostate cancer in LMICs, including the scope of these trials, the type of interventions being tested and funding sources. Methods: A search of the Cochrane Library Controlled Trials Registry was conducted between January 2010 and June 2021 using keywords including: 'prostate cancer', 'prostate adenocarcinoma' and 'prostate tumour'). The trials were classified into either HICs or LMICs based on the World Bank Atlas classification. A descriptive analysis was performed to determine the characteristics of the trials. Results: A total of 3,455 clinical trials for prostate cancer have been conducted globally, with 542 (15.68%) conducted LMICs. Most of these trials (89%) were registered in upper-middle-income countries, with none being conducted in low-income countries. The majority of trials were prospective studies (98.1%), with 65.2% being randomised and 57% being phase III. Of the trials, 48.4% aimed to recruit fewer than 500 participants. The main source of funding was pharmaceutical companies in 78.1% of the cases, followed by institutional funds (16.1%) and public funds (5.8%). At the time of the search query, 74.6% of the trials were inactive, with 37% completed, 5% terminated due to insufficient funding and 75% terminated due to medical inefficacy or poor accrual. The majority of trials (88.2%) were interventional, with only 6% focusing on screening and prevention, and 2% designed for palliative care. Conclusion: This study sheds light on the challenges faced in conducting clinical trials for prostate cancer in LMICs. The findings underline the need for improved support from international organisations and pharmaceutical companies to bridge the gaps in prostate cancer research and facilitate collaboration between researchers in LMICs and other countries.

Swine Atrioventricular Node Ablation Using Stereotactic Radiosurgery: Methods and In Vivo Feasibility Investigation for Catheter-Free Ablation of Cardiac Arrhythmias.

BACKGROUND: Linear accelerator-based stereotactic radiosurgery delivered to cardiac arrhythmogenic foci could be a promising catheter-free ablation modality. We tested the feasibility of in vivo atrioventricular (AV) node ablation in swine using stereotactic radiosurgery. METHODS AND RESULTS: Five Large White breed swine (weight 40-75 kg; 4 females) were studied. Single-chamber St Jude pacemakers were implanted in each pig. The pigs were placed under general anesthesia, and coronary/cardiac computed tomography simulation scans were performed to localize the AV node. Cone beam computed tomography was used for target positioning. Stereotactic radiosurgery doses ranging from 35 to 40 Gy were delivered by a linear accelerator to the AV node, and the pigs were followed up with weekly pacemaker interrogations to observe for potential electrocardiographic changes. Once changes were observed, the pigs were euthanized, and pathology specimens of various tissues, including the AV node and tissues surrounding the AV node, were taken to study the effects of radiation. All 5 pigs had disturbances of AV conduction with progressive transition into complete heart block. Macroscopic inspection did not reveal damage to the myocardium, and pigs had preserved systolic function on echocardiography. Immunostaining revealed fibrosis in the target region of the AV node, whereas no fibrosis was detected in the nontargeted regions. CONCLUSIONS: Catheter-free radioablation using linear accelerator-based stereotactic radiosurgery is feasible in an intact swine model.

Nadir PSA is a strong predictor of treatment outcome in intermediate and high risk localized prostate cancer patients treated by definitive external beam radiotherapy and androgen deprivation.

BACKGROUND: The aim of this study is to investigate the effect of tumor characteristics and parameters of treatment response in predicting biochemical disease-free survival (BFS) for patients with intermediate or high risk prostate cancer treated by combined definitive external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT). METHODS: Between June 1995 and January 2015, 375 patients with localized prostate cancer and a National Comprehensive Cancer Network (NCCN) intermediate or high risk categories were treated by definitive EBRT and ADT. Median duration of androgen blockade was 10 months (range: 3-36 months); Median radiation dose was 72 Gy (Range: 70-78 Gy). Median follow-up time was 5.8 years (range: 0.8-16.39 years). The main study endpoint was biochemical disease free survival (BFS). RESULTS: Forty seven patients (12.5%) developed biochemical recurrence (BCR) during the observation period. Monovariate analysis identified baseline PSA (bPSA) (p = 0.024), T-stage (p = 0.001), Gleason's score (GS) (p = 0.042), radiation dose (p = 0.045), PSA pre-radiation therapy (p = 0.048), and nadir PSA (nPSA), (p < 0.001) as significant variables affecting BCR. The receiver operating characteristic (ROC) curve identified a nPSA of 0.06 ng/ml as optimal cut-off value significantly predicting the patients' risk of BCR (p < 0.001). Multivariate cox regression analysis revealed T-stage, GS, and nPSA as independent variable affecting BFS, while bPSA, age, and radiation dose were not. CONCLUSION: Nadir PSA at 0.06 is a strong independent predictor of BFS in patients with intermediate or high risk prostate cancer treated by definitive EBRT and ADT.

Preoperative lymphocyte-to-monocyte ratio predicts clinical outcome in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder: a retrospective analysis.

BACKGROUND: Inflammation is a critical component of tumorigenesis, and many cancers arise from sites of infection, chronic irritation, and inflammation. Inflammatory cytokines triggered by tumors alter hematologic components, including neutrophil, lymphocyte, and monocyte counts. The neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios have been shown to be valuable prognostic markers in various types of cancers, including bladder cancer. Risk stratification based on clinicopathologic data is insufficient to support treatment-related choices in patients with bladder cancer. Novel prognostic markers are therefore needed. An elevated pretreatment lymphocyte-to-monocyte ratio (LMR) is reportedly associated with improved overall survival (OS) and a longer time to treatment recurrence (TTR) in some types of cancers. However, these data are lacking in patients with bladder cancer. The aim of the present study was to investigate the effect of the preoperative LMR on OS and TTR in a cohort of patients with bladder cancer. METHODS: Sixty-eight patients with transitional cell carcinoma of the bladder were included in this retrospective analysis. The associations between a high and low LMR with OS and TTR were analyzed using Kaplan-Meier curves and compared by the log-rank test. RESULTS: In our study cohort, an elevated preoperative LMR was significantly associated with an increased TTR (P = 0.001) and OS (P = 0.020). Patients with an LMR of ≤2.87 showed a median TTR of 2.0 years (95% CI, 0.27-3.73), whereas patients with an LMR of >2.87 had a median TTR of 11.1 years (95% CI, 2.31-19.88) (P = 0.001). Patients with an LMR of ≤2.81 showed a median OS of 2.7 years (95% CI, 0.63-4.70), whereas patients with an LMR of >2.81 had a median OS of 6.0 years (95% CI, 3.60-8.40) (P = 0.020). The clinical stage at diagnosis was the only clinicopathologic feature associated with the LMR, while tumor invasion depth showed borderline significance. CONCLUSIONS: The LMR is an easily measured and inexpensive prognostic marker that was significantly correlated with OS and TTR in the present retrospective analysis. However, because of the small sample size in this study, larger multicenter, prospective studies are needed.