Cost-Effectiveness of Immune Checkpoint Inhibitors in Urothelial Carcinoma-A Review.

Over the last decade, an increasing number of immune checkpoint inhibitors (ICIs) have been assessed for therapeutic efficacy in urothelial carcinoma (UC). The high cost has prompted multiple cost-effectiveness analyses for the various disease stages, with no established consensus. We reviewed the literature to assess the available cost-effectiveness studies and summarize their findings. Studies were filtered for a calculated incremental cost-effectiveness ratio (ICER) to standardize comparison. Over 2600 articles were narrowed to eight primary investigations: one for BCG-refractory non-muscle invasive (NMI), one for neoadjuvant therapy in muscle-invasive (MI), and six for advanced disease. Cost-effectiveness was not achieved for NMI disease. Atezolizumab met the willingness-to-pay (WTP) threshold as neoadjuvant therapy for MI disease compared to chemotherapy, but with multiple limitations on the interpretation. Of the six studies on advanced disease, the results were mixed. This was at least partially attributable to varied methodologies including extrapolated time horizons, inconsistent cost inputs, and different WTP thresholds. Overall, the aggregate results were not compelling enough to establish ICIs as cost-effective compared to conventional chemotherapy. Value may improve with continued investigation into long-term outcomes, refined patient selection, and pricing discounts.

Association of Treatment With 5α-Reductase Inhibitors With Time to Diagnosis and Mortality in Prostate Cancer.

Importance: 5α-Reductase inhibitors (5-ARIs), commonly used to treat benign prostatic hyperplasia, reduce serum prostate-specific antigen (PSA) concentrations by 50%. The association of 5-ARIs with detection of prostate cancer in a PSA-screened population remains unclear. Objective: To test the hypothesis that prediagnostic 5-ARI use is associated with a delayed diagnosis, more advanced disease at diagnosis, and higher risk of prostate cancer-specific mortality and all-cause mortality than use of other or no PSA-decreasing drugs. Design, Setting, and Participants: This population-based cohort study linked the Veterans Affairs Informatics and Computing Infrastructure with the National Death Index to obtain patient records for 80 875 men with American Joint Committee on Cancer stage I-IV prostate cancer diagnosed from January 1, 2001, to December 31, 2015. Patients were followed up until death or December 31, 2017. Data analysis was performed from March 2018 to May 2018. Exposures: Prediagnostic 5-ARI use. Main Outcomes and Measures: The primary outcome was prostate cancer-specific mortality (PCSM). Secondary outcomes included time from first elevated PSA (defined as PSA≥4 ng/mL) to diagnostic prostate biopsy, cancer grade and stage at time of diagnosis, and all-cause mortality (ACM). Prostate-specific antigen levels for 5-ARI users were adjusted by doubling the value, consistent with previous clinical trials. Results: Median (interquartile range [IQR]) age at diagnosis was 66 (61-72) years; median [IQR] follow-up was 5.90 (3.50-8.80) years. Median time from first adjusted elevated PSA to diagnosis was significantly greater for 5-ARI users than 5-ARI nonusers (3.60 [95% CI, 1.79-6.09] years vs 1.40 [95% CI, 0.38-3.27] years; P < .001) among patients with known prostate biopsy date. Median adjusted PSA at time of biopsy was significantly higher for 5-ARI users than 5-ARI non-users (13.5 ng/mL vs 6.4 ng/mL; P < .001). Patients treated with 5-ARI were more likely to have Gleason grade 8 or higher (25.2% vs 17.0%; P < .001), clinical stage T3 or higher (4.7% vs 2.9%; P < .001), node-positive (3.0% vs 1.7%; P < .001), and metastatic (6.7% vs 2.9%; P < .001) disease than 5-ARI nonusers. In a multivariable regression, patients who took 5-ARI had higher prostate cancer-specific (subdistribution hazard ratio [SHR], 1.39; 95% CI, 1.27-1.52; P < .001) and all-cause (HR, 1.10; 95% CI, 1.05-1.15; P < .001) mortality. Conclusions and Relevance: Results of this study demonstrate that prediagnostic use of 5-ARIs was associated with delayed diagnosis and worse cancer-specific outcomes in men with prostate cancer. These data highlight a continued need to raise awareness of 5-ARI-induced PSA suppression, establish clear guidelines for early prostate cancer detection, and motivate systems-based practices to facilitate optimal care for men who use 5-ARIs.

Definitive Radiation Therapy and Survival in Clinically Node-Positive Prostate Cancer.

PURPOSE: The survival benefit of combined radiation therapy (RT) and androgen deprivation therapy (ADT) compared with ADT alone for clinically lymph node-positive prostate cancer remains controversial. METHODS AND MATERIALS: We identified patients with clinically node-positive, nonmetastatic prostate cancer diagnosed between 2000 and 2015 and treated with ADT (n = 450) or ADT-RT (n = 198) from a national Veterans Affairs database. We compared prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) between treatment groups using multivariable competing-risks regression and Cox regression, respectively. An interaction term between ADT-RT and prostate-specific antigen (PSA) level (dichotomized about the median) was included in the multivariable models. RESULTS: ADT-RT was associated with improved PCSM among patients with PSA levels less than the median of 26 ng/mL (sub-distribution hazard ratio, 0.50; 95% confidence interval [CI] 0.28-0.88; P = .02) but not greater than the median (hazard ratio [HR], 1.15; 95% CI 0.67-1.96; P = .62) (P = .038 for interaction). ADT-RT was also associated with improved ACM among patients with PSA levels less than the median (HR, 0.38; 95% CI 0.25-0.57; P < .001) but not greater than the median (HR, 0.91; 95% CI 0.60-1.38; P = .66) (P = .004 for interaction). CONCLUSIONS: Definitive treatment with ADT-RT is associated with improved PCSM and ACM among patients with clinically node-positive prostate cancer and lower baseline PSA levels. Patients with clinically node-positive disease appear to be a heterogeneous cohort, with a subset who may achieve long-term survival with combined RT and ADT.

Analysis of T1 Bladder Cancer on Biopsy and Transurethral Resection Specimens: Comparison and Ranking of T1 Quantification Approaches to Predict Progression to Muscularis Propria Invasion.

Urothelial carcinoma of the bladder invasive into lamina propria on biopsy or transurethral resection of bladder tumor, termed "T1" disease, progresses to muscularis propria invasion in a subset of patients. Prior studies have proposed histopathologic metrics to predict progression, although methods vary widely and it is unclear which method is most robust. This poses a challenge since recent World Health Organization and American Joint Commission on Cancer editions encourage some attempt to substratify T1 disease. To address this critical problem, we analyzed T1 specimens to test which T1 quantification method is best to predict progression and to then establish the optimal cut-off. Progression was analyzed for all patients or for patients with definitive muscularis propria only. Multivariate analysis and outcomes modeling controlled for additional histopathologic features. Our results suggest that aggregate linear length of invasive carcinoma (ALLICA) measured by optical micrometer is far superior to other methods (P=3.067×10) and could be applied to 100% of specimens. ALLICA retained significance in multivariate analysis and eliminated contribution of other histopathologic features to progression. The best cut-off for ALLICA using a 30% false-positive threshold was 2.3 mm and using a 10% false-positive threshold at 25 mm, although the latter severely limited patients who could achieve this threshold. After comparison of all proposed methods of T1 quantification, we recommend the adoption of the ALLICA measurement and a cut-off of ≥2.3 mm as the best predictor of progression, acknowledging that additional nonhistopathologic methods may be required to increase broad applicability and further reduce the false-positive threshold.

Robot-assisted triple neurectomy for iatrogenic inguinal pain: a technical note.

BACKGROUND: Painful neuromas are a relatively common complication of hernia and abdominal wall surgery. OBJECTIVE: Surgical neurectomy has the potential to to provide durable relief for chronic pain; however, current surgical approaches are not without morbidity or anatomical challenges.We sought a surgical alternative. METHODS: In the treatment of a case of incapacitating inguinal pain, we performed an anterior transperitoneal approach using a surgical robot. RESULTS: This approach was facile and provided elegant anatomical visualization. CONCLUSION: This case describes the first known robot-assisted laparoscopic triple neurectomy and details a simplified, transperitoneal approach.

Association of prostate cancer risk with SNPs in regions containing androgen receptor binding sites captured by ChIP-On-chip analyses.

BACKGROUND: Genome-wide association studies (GWAS) have identified approximately three dozen single nucleotide polymorphisms (SNPs) consistently associated with prostate cancer (PCa) risk. Despite the reproducibility of these associations, the molecular mechanism for most of these SNPs has not been well elaborated as most lie within non-coding regions of the genome. Androgens play a key role in prostate carcinogenesis. Recently, using ChIP-on-chip technology, 22,447 androgen receptor (AR) binding sites have been mapped throughout the genome, greatly expanding the genomic regions potentially involved in androgen-mediated activity. METHODOLOGY/PRINCIPAL FINDINGS: To test the hypothesis that sequence variants in AR binding sites are associated with PCa risk, we performed a systematic evaluation among two existing PCa GWAS cohorts; the Johns Hopkins Hospital and the Cancer Genetic Markers of Susceptibility (CGEMS) study population. We demonstrate that regions containing AR binding sites are significantly enriched for PCa risk-associated SNPs, that is, more than expected by chance alone. In addition, compared with the entire genome, these newly observed risk-associated SNPs in these regions are significantly more likely to overlap with established PCa risk-associated SNPs from previous GWAS. These results are consistent with our previous finding from a bioinformatics analysis that one-third of the 33 known PCa risk-associated SNPs discovered by GWAS are located in regions of the genome containing AR binding sites. CONCLUSIONS/SIGNIFICANCE: The results to date provide novel statistical evidence suggesting an androgen-mediated mechanism by which some PCa associated SNPs act to influence PCa risk. However, these results are hypothesis generating and ultimately warrant testing through in-depth molecular analyses.