IMPORTANCERecently, new drugs have been approved for the first-line treatment of metastatic renal cell carcinoma (mRCC). Nivolumab plus ipilimumab significantly increases overall survival for intermediate-and poor-risk patients with mRCC. However, considering the high cost of nivolumab plus ipilimumab, there is a need to assess its value by considering both efficacy and cost.OBJECTIVE To evaluate the cost-effectiveness of nivolumab plus ipilimumab vs sunitinib in the first-line setting for intermediate-and poor-risk patients with mRCC from the US payer perspective. DESIGN, SETTING, AND PARTICIPANTSA Markov model was developed to compare the lifetime cost and effectiveness of nivolumab plus ipilimumab vs sunitinib in the first-line treatment of mRCC using outcomes data from the CheckMate 214 phase 3 randomized clinical trial, which included 1096 patients with mRCC (median age, 62 years) and compared nivolumab plus ipilimumab vs sunitinib as first-line treatment of mRCC. In the analysis, patients were modeled to receive sunitinib or nivolumab plus ipilimumab for 4 doses followed by nivolumab monotherapy.MAIN OUTCOMES AND MEASURES Life-years, quality-adjusted life-years (QALYs), and lifetime costs were estimated, at a willingness-to-pay threshold of $100 000 to $150 000 per QALY. Univariable, 2-way, and probabilistic sensitivity analyses were performed to evaluate the model uncertainty. Additional subgroup analyses were performed. RESULTSNivolumab plus ipilimumab provided an additional 0.96 QALYs, at a cost of $108 363 per QALY. Sensitivity analyses found the results to be most sensitive to overall survival hazard ratio (0.63; 95% CI, 0.44-0.89) and mean patient weight (70 kg, range, 40-200 kg). Other variables, such as the cost of nivolumab plus ipilimumab (mean, $32 213.44; range, $25 770.75-$38 656.13), utility values for nivolumab plus ipilimumab (mean, 0.82; range, 0.65-0.98), and proportion receiving nivolumab in sunitinib arm (mean, 0.27; range, 0.22-0.32), had a moderate or minor influence on model results. Subgroup analyses demonstrated that nivolumab plus ipilimumab was most cost-effective for patients with programmed cell death 1 ligand 1 expression of at least 1% ($86 390 per QALY).

BACKGROUND:The IMpower150 trial found that adding atezolizumab to the combination of bevacizumab and chemotherapy improved survival for patients with metastatic, nonsquamous non-small cell lung cancer (NSCLC). However, considering the high cost of immunotherapy, there is a need to assess its value by considering both efficacy and cost. The current study evaluated the cost-effectiveness of atezolizumab in the first-line setting for the treatment of patients with metastatic NSCLC from the US payer perspective. METHODS: A Markov model was developed to compare the lifetime cost and effectiveness of the combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) with the combination of bevacizumab, carboplatin, and paclitaxel (BCP) and carboplatin and paclitaxel (CP) in the first-line treatment of patients with metastatic NSCLC. Life-years (LYs), qualityadjusted LYs (QALYs), and lifetime costs were estimated. One-way and probabilistic sensitivity analyses were performed to evaluate the model uncertainty. Additional subgroup analyses were performed. RESULTS: ABCP provided an additional 0.413 QALYs (0.460 LYs) and 0.738 QALYs (0.956 LYs), respectively, compared with BCP and CP. The corresponding incremental costs were $234,998 and $381,116, respectively. The incremental cost-effectiveness ratio for ABCP was $568,967 per QALY compared with BCP and $516,114 per QALY compared with CP. The subgroup analysis demonstrated that PD-L1 expression of ≥50% on tumor cells (TC3) or ≥10% on immune cells (IC3) decreased the incremental cost-effectiveness ratio to $464,703 per QALY. CONCLUSIONS: From the perspective of the US payer, ABCP is estimated to not be cost-effective compared with BCP or CP in the first-line setting for patients with metastatic, nonsquamous NSCLC at a willingness-to-pay threshold of $100,000 per QALY. Cancer 2019;125:3526-3534.

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Background : The programmed death 1 (PD1)/programmed death ligand 1 (PDL1) targeted therapies have gained positive outcomes in several tumors, but the evidence of the expression and prognosis value of PD1/PDL1 in high risk prostate cancer was rare. Methods : Immunohistochemical analysis of PDL1/PD1 expression by a validated antibody was performed in a retrospectively collected high risk prostate cancer cohort who received adjuvant hormonal therapy (AHT) after radical prostatectomy (RP). The association between PDL1/PD1 expression and prognosis was determined. Results : In total, 127 patients were enrolled. 49.6% patients were considered PDL1-high expression while the PD1-positive expression proportion was 24.4%. High PDL1 and negative PD1 expression were significantly associated with lower prostate specific antigen (PSA) density (p=0.010 and p=0.033, respectively). Compared with the PDL1-low expression patients, the PDL1-high expression patients had significantly shorter time to PSA nadir (TTN) (P=0.001) and biochemical recurrence (BCR) (P=0.004). In Kaplan-Meier analysis, the PDL1-high expression group (p<0.0001) and the PDL1-high/PD1-negative expression group (p<0.0001) showed markedly lower BCR-free survival in localized disease. Univariate cause-specific Cox proportional hazard regression model concluded total PSA (p=0.047), PDL1-high-expression (p<0.001), PDL1-high/PD1-negative expression (p<0.001) were significant risk factors of shorter progression time to BCR in localized disease. PDL1-high-expression was the independent predictor of time to BCR in multiple Cox regression of all patients (Hazard ratio [HR]: 3.901; 95% Confidence interval [CI]: 1.287-11.824; p=0.016). Conclusions : PDL1 expression is not only highly prevalent in high-risk prostate cancer, but is also an independent biomarker in the prognosis of high-risk prostate cancer received AHT after RP. PDL1/PD1 targeted therapy might be a potentially adjuvant treatment option for high-risk prostate cancer after RP.

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Histone lysine methyltransferases (HMT) comprise a subclass of epigenetic regulators; dysregulation of these enzymes affects gene expression, which may lead to tumorigenesis. Here, we performed an integrated analysis of 50 HMTs in bladder cancer and found intrinsic links between copy number alterations, mutations, gene expression levels, and clinical outcomes. Through integrative analysis, we identified six HMT genes (PRDM9, ASH1L, SETD3, SETD5, WHSC1L1, and KMT2D) that may play a key role in the development and progression of bladder cancer. Of these six HMTs, histone lysine N‐methyltransferase 2D (KMT2D) exhibited the highest mutation rate in bladder cancer. Our comparison of the mRNA and miRNA expression profiles of mutated and wild‐type KMT2D suggested that two signaling pathways (FOX1–miR‐1224‐5p–DLK1 and HIF/GATA5–miR‐133a‐3p–DRD5) may mediate the tumor suppressive effect of the KMT2D mutation. In summary, our findings indicate that mutations in HMT genes, especially KMT2D mutation, may play a role in the development of bladder cancer.

Aims Low‐intensity extracorporeal shock wave therapy (Li‐ESWT) has been applied in urolithiasis and some chronic diseases. We performed a systematic review and meta‐analysis to assess the efficacy of Li‐ESWT for the treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Methods A comprehensive search of MEDLINE, Web of Science, EMBASE, and the Cochrane Library to January 6, 2019 was performed for randomized controlled trials (RCTs) reporting on patients with CP/CPPS treated with Li‐ESWT compared with the sham group. Outcomes were evaluated based on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH‐CPSI). The quality assessment of included studies was performed by the Cochrane System. Results Six publications involving five RCTs with 280 patients were assessed in this review. NIH‐CPSI total score, pain domain and quality of life (QOL) were significantly better in the Li‐ESWT group than those in the control group at the endpoint (P < 0.00001, P = 0.003, and P < 0.00001), 4 weeks (P < 0.00001, P = 0.0002 and P < 0.00001) and 12 weeks (P < 0.00001, P < 0.00001, and P = 0.0002) after the treatment. For urinary score, significant difference existed at 12 weeks after the treatment (P = 0.006). At 24 weeks after treatment, there was no significant difference between the two groups in NIH‐CPSI total score (P = 0.26), pain domain (P = 0.32), urinary score (P = 0.07), and QOL (P = 0.29). Conclusions Li‐ESWT showed great efficacy for the treatment of CP/CPPS at the endpoint and during the follow‐up of 4 and 12 weeks, though the efficacy of 24‐week follow‐up was not significantly different due to insufficient data. Generally, Li‐ESWT is a promising minimal invasive method for the treatment of CP/CPPS.

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