Current Status of Perioperative Therapy in Muscle-Invasive Bladder Cancer and Future Directions.

PURPOSE OF REVIEW: Cisplatin-based combination chemotherapy has been a standard of care in the perioperative management of muscle-invasive bladder cancer for years, but several novel therapies are under active investigation. This review aims to provide an update on recent relevant literature and a forward look at the future landscape of adjuvant and neoadjuvant therapy in muscle-invasive bladder cancer patients who opt for radical cystectomy. RECENT FINDINGS: The recent approval of nivolumab as adjuvant therapy established a new treatment option for high-risk patients with muscle-invasive bladder cancer after radical cystectomy. Several phase II studies of chemo-immunotherapy combinations and immunotherapy alone have reported pathological complete responses in the 26-46% range, including studies in cisplatin-ineligible patients. Randomized studies of perioperative chemo-immunotherapy, immunotherapy alone, and enfortumab vedotin are ongoing. Muscle-invasive bladder cancer remains a challenging disease associated with significant morbidity and mortality; however, increasing options in systemic therapy and an increasingly personalized approach to cancer treatment suggest continued future improvements in patient care.

Emergency department visits and hospitalizations in older women treated for early stage breast cancer.

INTRODUCTION: Older patients with cancer often require acute care treatment through emergency department (ED) visits and hospitalizations. This study investigates acute care utilization through ED visits and hospitalizations during treatment and in the two years following the completion of primary treatment for early stage breast cancer (EBC) in women aged 65 and older. MATERIALS AND METHODS: A retrospective analysis including descriptive statistics, univariate analysis, and relative risk analysis of 256 women with EBC was performed through medical record review of demographics, comorbidities, disease characteristics, treatment details, and causes of hospitalizations and ED visits. RESULTS: Both hospitalizations and ED visits were significantly more frequent for patients in the post-primary treatment period compared to during treatment (hospitalizations: 22% post-primary treatment vs 13% during treatment, 95% confidence interval [CI] of true difference = 2.5%-15.5; ED visits: 21% post-primary treatment vs 10% during treatment, 95% CI of true difference = 4.8%-17.2%). Both hospitalizations (79% versus 32%, 95% CI of true difference = 28.7%-65.3%) and ED visits (42% versus 12%, 95% CI of true difference = 9.1%-50.9%) were more often breast cancer related during primary treatment compared to following treatment. Following treatment, EBC related hospitalizations were most often for disease progression (42%) and EBC related ED visits were most often for post-systemic therapy complications (43%). Significant predictors for EBC related hospitalizations in the two years following treatment included stage III disease (relative risk [RR] = 8.77, 95% CI = 2.50-30.82), having underwent mastectomy (RR = 12.51, 95% CI = 2.91-53.78), and having received chemotherapy (RR = 3.95, 95% CI = 1.18-13.23). However, chemotherapy does not appear to be a significant predictor for hospitalization when controlling for stage III disease (RR = 2.22, 95% CI = 0.61-8.05), whereas stage III disease remains a significant risk factor when controlling for chemotherapy (RR = 6.09, 95% CI = 1.58-23.52). DISCUSSION: Our findings suggests that stage III disease, undergoing mastectomy, and chemotherapy treatment predict higher likelihood of EBC related hospitalization following primary treatment in older EBC patients, with stage III disease likely the strongest risk factor.

Secondary Immune Thrombocytopenia in Metastatic Renal Cell Carcinoma: A Case Report and Discussion of the Literature.

Immune thrombocytopenia (ITP) is a rare paraneoplastic syndrome of solid tumor malignancies. In previously described cases of renal cell carcinoma (RCC) associated with secondary ITP, treatment has consisted of nephrectomy, splenectomy, and corticosteroids. Here, we describe a case of metastatic RCC presenting with a right ventricular mass and subsequent development of secondary ITP. The clinical course was complicated by recurrent severe thrombocytopenia despite treatment with corticosteroids, rituximab, and thrombopoietin receptor agonists, precluding cancer-directed therapy and anticoagulation. Further study is needed to determine the optimal management strategy for malignancy-associated ITP.

Predicting Time From Metastasis to Overall Survival in Castration-Resistant Prostate Cancer: Results From SEARCH.

OBJECTIVE: To identify the predictors of time from initial diagnosis of metastatic castration-resistance prostate cancer (mCRPC) to all-cause death within the Shared Equal Access Regional Cancer Hospital cohort. PATIENTS AND METHODS: We performed a retrospective analysis of 205 mCRPC men. Overall survival was estimated and plotted using the Kaplan-Meier method. The uni- and multivariable overall survival predictors were evaluated with the Cox proportional hazards model. A nomogram was generated to predict overall survival at 1, 2, 3, and 5 years after mCRPC. Concordance index and calibration plot were obtained. RESULTS: A total of 170 men (83%) died over a median follow-up of 41 months. In univariable analysis, older age, more remote year of mCRPC, nonblack race, greater number of bone metastasis, higher prostate-specific antigen (PSA) levels, shorter PSA doubling time, and faster PSA velocity at mCRPC diagnosis were significantly associated with shorter overall survival (all P < .05). In multivariable analysis, older age, more remote year of mCRPC, greater number of bone metastasis, higher PSA levels, and shorter PSA doubling time at mCRPC diagnosis remained significantly associated with shorter overall survival (all P < .05). On the basis of these variables, a nomogram was generated yielding a concordance index of 0.67 and good calibration. CONCLUSION: The use of clinical parameter such as age, disease burden, and PSA levels and kinetics can be used to estimate overall survival in mCRPC patients.

Predictors of Time to Metastasis in Castration-resistant Prostate Cancer.

OBJECTIVE: To investigate predictors of time to metastasis among men treated with androgen deprivation therapy for nonmetastatic prostate cancer who developed castration-resistant prostate cancer (CRPC) within the Shared Equal Access Regional Cancer Hospital cohort. METHODS: This is a retrospective analysis of 458 nonmetastatic CRPC men. Metastases were detected in routine bone scans or other imaging tests. Predictors of time to metastasis were analyzed using proportional hazards model with CRPC as time zero. RESULTS: A total of 256 (56%) men were diagnosed with metastatic disease over a median follow-up of 36 months. Metastasis-free survival was 79%, 65%, 52%, 47%, and 41% at 1, 2, 3, 4, and 5 years after CRPC, respectively. In multivariable analysis, Gleason score 8-10 (hazard ratio [HR] = 1.61; P = .026), receiving primary localized treatment (HR = 1.38; P = .028), higher prostate-specific antigen (PSA) levels at CRPC diagnosis (logPSA HR = 1.64; P < .001), and PSA doubling time ≤6 months (HR = 1.42; P = .040) were independently associated with shorter time to metastasis. Race, year of CRPC, age, and time from androgen deprivation therapy to CRPC were not associated with metastasis. CONCLUSION: Among nonmetastatic CRPC men, nearly 60% developed metastatic disease during the first 5 years, with most of the metastasis occurring within the first 3 years. Higher Gleason score, receiving primary treatment, higher PSA, and shorter PSA doubling time were independently associated with shorter time to metastasis. Therefore, these variables can be used to stratify patients according to metastasis risk.

Neural mechanisms of negative reinforcement in children and adolescents with autism spectrum disorders.

BACKGROUND: Previous research has found accumulating evidence for atypical reward processing in autism spectrum disorders (ASD), particularly in the context of social rewards. Yet, this line of research has focused largely on positive social reinforcement, while little is known about the processing of negative reinforcement in individuals with ASD. METHODS: The present study examined neural responses to social negative reinforcement (a face displaying negative affect) and non-social negative reinforcement (monetary loss) in children with ASD relative to typically developing children, using functional magnetic resonance imaging (fMRI). RESULTS: We found that children with ASD demonstrated hypoactivation of the right caudate nucleus while anticipating non-social negative reinforcement and hypoactivation of a network of frontostriatal regions (including the nucleus accumbens, caudate nucleus, and putamen) while anticipating social negative reinforcement. In addition, activation of the right caudate nucleus during non-social negative reinforcement was associated with individual differences in social motivation. CONCLUSIONS: These results suggest that atypical responding to negative reinforcement in children with ASD may contribute to social motivational deficits in this population.

Practice patterns and predictors of followup imaging after a negative bone scan in men with castration resistant prostate cancer: results from the SEARCH database.

PURPOSE: We investigated imaging practice patterns in men with nonmetastatic (M0) castration resistant prostate cancer. MATERIALS AND METHODS: We analyzed data on 247 patients with documented M0 CRPC from the SEARCH database. Patients were selected regardless of primary treatment modality and all had a negative bone scan after a castration resistant prostate cancer diagnosis. Cox models were used to test associations of time to a second imaging test with several demographic and clinical factors. RESULTS: During a median followup of 29.0 months (IQR 12.9-43.5) after a post-castration resistant prostate cancer bone scan was negative, 190 patients (77%) underwent a second imaging test. On univariable analysis patients with higher prostate specific antigen (HR 1.13, p = 0.016), shorter prostate specific antigen doubling time (HR 0.79, p < 0.001) and faster prostate specific antigen velocity (HR 1.01, p < 0.001) were more likely to undergo a second imaging test. Treatment center was also a significant predictor of a second imaging test (p = 0.010). No other factor was a significant predictor. Results were similar on multivariable analysis. It was estimated that approximately 20% of men with a prostate specific antigen doubling time of less than 3 months did not undergo an imaging test in the first year after a post-castration resistant prostate cancer negative bone scan. However, 50% of patients with prostate specific antigen doubling time 15 months or greater underwent a second imaging test in the first year. CONCLUSIONS: Clinicians use some known predictors of positive imaging tests to determine which patients with M0 castration resistant prostate cancer undergo a second imaging test . However, there may be under imaging in those at high risk and over imaging in those at low risk. Further studies are needed to identify risk factors for metastasis and form clear imaging guidelines in patients with M0 castration resistant prostate cancer.