Androgen deprivation therapy for prostate cancer and neurocognitive disorders: a systematic review and meta-analysis.

BACKGROUND: Prostate cancer is a prevalent disease that urgently needs to address its treatment-related complications. By examining existing evidence on the association between Androgen Deprivation Therapy (ADT) and dementia, this study contributes to the understanding of potential risks. We sought to analyze the currently available evidence regarding the risk of dementia, Alzheimer's disease (AD), vascular dementia, and Parkinson's disease (PD) in patients undergoing ADT. METHODS: A systematic search of PubMed, EMBASE, Scopus, and Google Scholar was performed to identify studies published from the databases' inception to April 2023. Studies were identified through systematic review to facilitate comparisons between studies with and without some degree of controls for biases affecting distinctions between ADT receivers and non-ADT receivers. This review identified 305 studies, with 28 meeting the inclusion criteria. Heterogeneity was assessed using Higgins I2%. Variables with an I2 over 50% were considered heterogeneous and analyzed using a Random-Effects model. Otherwise, a Fixed-Effects model was employed. RESULTS: A total of 28 studies were included for analysis. Out of these, only 1 study did not report the number of patients. From the remaining 27 studies, there were a total of 2,543,483 patients, including 900,994 with prostate cancer who received ADT, 1,262,905 with prostate cancer who did not receive ADT, and 334,682 patients without prostate cancer who did not receive ADT. This analysis revealed significantly increased Hazard Ratios (HR) of 1.20 [1.11, 1.29], p < 0.00001 for dementia, HR 1.26 [1.10, 1.43], p = 0.0007 for Alzheimer's Disease, HR 1.66 [1.40, 1.97], p < 0.00001 for depression, and HR 1.57 [1.31, 1.88], p < 0.00001 for Parkinson's Disease. The risk of vascular dementia was HR 1.30 [0.97, 1.73], p < 0.00001. CONCLUSION: Based on the analysis of the currently available evidence, it suggests that ADT significantly increases the risk of dementia, AD, PD, and depression.

Sequential intravesical gemcitabine/docetaxel provides a durable remission in recurrent high-risk NMIBC following BCG therapy.

PURPOSE: Bacillus Calmette-Guerin (BCG) is the standard of care for high-risk nonmuscle invasive bladder cancer (NMIBC), but half of patients develop disease recurrence. Intravesical regimens for BCG unresponsive NMIBC are limited. We report the safety, efficacy, and differential response of sequential gemcitabine/docetaxel (gem/doce) depending on BCG failure classification. METHODS: Multi-institutional retrospective analysis of patients treated with induction intravesical gem/doce (≥5/6 instillations) for recurrent high-risk NMIBC after BCG therapy from May 2018 to December 2021. Maintenance therapy was provided to those without high-grade (HG) recurrence on surveillance cystoscopy. Kaplan-Meier curves and Cox regression analyses were utilized to assess survival and risk factors for disease recurrence. RESULTS: Our cohort included 102 patients with BCG-unresponsive NMIBC. Median age was 72 years and median follow-up was 18 months. Six-, 12-, and 24-month high-grade recurrence-free survival was 78%, 65%, and 49%, respectively. Twenty patients underwent radical cystectomy (median 15.5 months from induction). Six patients progressed to muscle invasive disease. Fifty-seven percent of patients experienced mild/moderate adverse effects (AE), but only 6.9% experienced a delay in treatment schedule. Most common AE were urinary frequency/urgency (41%) and dysuria (21%). Patients with BCG refractory disease were more likely to develop HG recurrence when compared to patients with BCG relapsing disease (HR 2.14; 95% CI 1.02-4.49). CONCLUSIONS: In patients with recurrence after BCG therapy, sequential intravesical gem/doce is an effective and well-tolerated alternative to early cystectomy. Patients with BCG relapsing disease are more likely to respond to additional intravesical gem/doce. Further investigation with a prospective trial is imperative.

Association of BCG Vaccine Treatment With Death and Dementia in Patients With Non-Muscle-Invasive Bladder Cancer.

Importance: The BCG vaccine-used worldwide to prevent tuberculosis-confers multiple nonspecific beneficial effects, and intravesical BCG vaccine is currently the recommended treatment for non-muscle-invasive bladder cancer (NMIBC). Moreover, BCG vaccine has been hypothesized to reduce the risk of Alzheimer disease and related dementias (ADRD), but previous studies have been limited by sample size, study design, or analyses. Objective: To evaluate whether intravesical BCG vaccine exposure is associated with a decreased incidence of ADRD in a cohort of patients with NMIBC while accounting for death as a competing event. Design, Setting, and Participants: This cohort study was performed in patients aged 50 years or older initially diagnosed with NMIBC between May 28, 1987, and May 6, 2021, treated within the Mass General Brigham health care system. The study included a 15-year follow-up of individuals (BCG vaccine treated or controls) whose condition did not clinically progress to muscle-invasive cancer within 8 weeks and did not have an ADRD diagnosis within the first year after the NMIBC diagnosis. Data analysis was conducted from April 18, 2021, to March 28, 2023. Main Outcomes and Measures: The main outcome was time to ADRD onset identified using diagnosis codes and medications. Cause-specific hazard ratios (HRs) were estimated using Cox proportional hazards regression after adjusting for confounders (age, sex, and Charlson Comorbidity Index) using inverse probability scores weighting. Results: In this cohort study including 6467 individuals initially diagnosed with NMIBC between 1987 and 2021, 3388 patients underwent BCG vaccine treatment (mean [SD] age, 69.89 [9.28] years; 2605 [76.9%] men) and 3079 served as controls (mean [SD] age, 70.73 [10.00] years; 2176 [70.7%] men). Treatment with BCG vaccine was associated with a lower rate of ADRD (HR, 0.80; 95% CI, 0.69-0.99), with an even lower rate of ADRD in patients aged 70 years or older at the time of BCG vaccine treatment (HR, 0.74; 95% CI, 0.60-0.91). In competing risks analysis, BCG vaccine was associated with a lower risk of ADRD (5-year risk difference, -0.011; 95% CI, -0.019 to -0.003) and a decreased risk of death in patients without an earlier diagnosis of ADRD (5-year risk difference, -0.056; 95% CI, -0.075 to -0.037). Conclusions and Relevance: In this study, BCG vaccine was associated with a significantly lower rate and risk of ADRD in a cohort of patients with bladder cancer when accounting for death as a competing event. However, the risk differences varied with time.

Breast Medical Oncologists' Perspectives of Telemedicine for Breast Cancer Care: A Survey Study.

PURPOSE: The COVID-19 pandemic forced rapid adoption of telemedicine (TM) for breast oncology visits in the United States, but the appropriate role of postpandemic TM is uncertain. We sought to understand physician and advance practice practitioner perspectives on the use of TM for outpatient breast cancer care through an electronically administered survey. METHODS: Breast medical oncology clinicians at two academic cancer centers and five satellite locations affiliated with the Dana Farber Cancer Institute and the Massachusetts General Cancer Center were invited to respond to a 21-question survey administered in September 2021 about clinicians' perceptions and attitudes toward TM during the previous 12 months. RESULTS: Of the 71 survey invitations, 51 clinicians (36 physicians and 15 advance practice practitioners) provided survey responses (response rate = 72%). Ninety-two percent of respondents (n = 47) agreed that TM visits enhance patient care. Ninety-two percent of respondents (n = 46) also agreed that TM is valuable for early-stage breast cancer follow-up visits. Most respondents felt that there was no difference between TM and face-to-face (F2F) visits when it came to patient adherence, ease of ordering tests, ease of accessing patient records, and workflow outside of the visit (82%, 82%, 78%, and 53%, respectively). Fifty-one percent of respondents (n = 26) said that TM was better for timely access to follow-up appointments. Most respondents said that F2F visits were better for seeing physical problems, personal connection with patients, overall quality of visits, and patient-physician communication (100%, 75%, 65%, and 63%, respectively). CONCLUSION: Breast clinicians believe that TM is a valuable tool to enhance outpatient breast cancer care. TM was felt to be appropriate for routine follow-up visits and second opinion consultations and is as good as or better than F2F visits for several routine aspects of breast cancer care.

Dual-frequency setting for urinary stone fragmentation during shock wave lithotripsy: an in vitro study.

Extracorporeal shock wave lithotripsy (SWL) is less invasive compared to the other invasive modalities of stone treatment that are gaining popularity. Hence, methods to improve the efficacy of SWL are desirable. We studied the effectiveness of dual frequency on the efficacy of stone fragmentation, but minimizing treatment time. A phantom 10 mm spherical BegoStone was fragmented in vitro in a kidney model using an electromagnetic lithotripter (Storz MODULITH®SLX-F2). A total of 78 stones were fragmented each with 3000 shocks at 60 Hz or 120 Hz or a dual frequency (DF) of 60-120 Hz. For the DF setting, the first 1000 shocks were delivered at 60 Hz and the next 2000 at 120 Hz. Total weight and number of significant fragments of > 3 mm (TWSF and TNSF, respectively) and also > 2 mm was measured. Results: The mean TWSF was 0.1, 0.16, and 0.08 g for 60 Hz, 120 Hz, and DF 60-120 Hz, respectively. The TWSF of DF 60-120 Hz was significantly lower than that of 120 Hz (p = 0.02), but same as the 60 Hz (p = 0.32). The mean TNSF of > 3 mm was 2.6, 3.0, and 2.0 for 60 Hz, 120 Hz, and DF 60-120 Hz, respectively, without significant differences between each setting. However, increasing trend of TWSF, TW2 mm and TN2 mm was seen in the order of DF, 60 Hz and 120 Hz (p = 0.019, p = 0.004 and 0.017, respectively). Treatment time for 60 Hz, 120 Hz, and DF 60-120 Hz was 50, 25, and 34 min, respectively. Dual-frequency setting produced effective stone fragmentation compared to the recommended 60 Hz, while decreasing treatment time. DF variation is one other factor that may be tailored for effective stone comminution and needs clinical evaluation.

Tuberculosis exposure, infection and disease among children with medical comorbidities.

Sixty-nine children with medical comorbidities were treated for tuberculosis (TB) exposure (7), infection (40) or disease (22). The most common comorbidities in children with TB disease were malignancy (23%), cyanotic heart disease (18%), hemoglobinopathies (18%) and autoimmune disease (14%). Ninety-six percent who received TB medications had no adverse events and 98% completed therapy. Two (9%) died of TB.