Quality of Life and Health State Utilities in Bladder Cancer

BACKGROUND: Bladder cancer treatments may variably impact health-related quality of life (QOL). OBJECTIVE: To characterize the quality of life of patients with bladder cancer at various time points across the continuum of bladder cancer care from non-muscle-invasive disease to metastatic bladder cancer and develop utility scores to inform cost-effective analyses. METHODS: We performed a cross-sectional survey of bladder cancer patients in the Bladder Cancer Advocacy Network Patient Survey Network. Participants were classified into mutually exclusive health states based upon non-muscle invasive (NMIBC), muscle-invasive (MIBC), or metastatic bladder cancer and completed surveys of generic cancer and bladder cancer-specific quality of life, financial toxicity, and work impairment. We constructed generalized linear mixed models to identify patient, clinical, and treatment factors associated with quality of life over time and derived health state utilities. RESULTS: Among 911 self-identified patients with bladder cancer, overall QOL scores and function domains were worse among those with advanced cancer. Financial toxicity was similar among non-metastatic disease states. Work and activity impairment increased with advancing disease (13%and 12%among non-recurrent NMIBC to 63%and 31%for metastatic disease respectively; p < 0.01). On multivariable analysis, bowel-related QOL was diminished among patients with MIBC, with urinary symptoms and physical function most diminished among patients with metastatic disease. Patients with metastatic and MIBC experienced worse emotional functioning (p = 0.04; p = 0.048). Health state utilities were calculated, highest among those with non-recurrent NMIBC and lowest among those with metastatic disease. CONCLUSION: Generic and bladder cancer-specific QOL diminishes with advancing disease. Health state utility estimates derived from this study can inform shared decision making with patients and may be used to inform future cost-effective analyses.

Survival of patients with metastatic bladder cancer in the Russian Federation: results of a multicenter registry study URRU

Background. Data on the overall survival (OS) of patients with metastatic bladder cancer (BCa) is rarely published.The objective of the URRU register study is to assess OS and collect information on the administration of different treatments in patients with metastatic BCa in routine clinical practice in Russia.Materials and methods. Patients were retrospectively identified in 9 oncology centers in different regions of Russia and included in the study if they were diagnosed with metastatic BCa between January 2017 and January 2018. We collected anonymized data online, including demographic characteristics of patients, details of their therapy, and outcomes.Results. This study included 246 patients. Their mean age upon the diagnosis of metastatic BCa was 72 years with 60.6 % of patients over 70 years of age. The proportion of males was 74.8 %. The histological subtype of BCa (urothelial carcinoma, etc.) was identified in 70.3 % of cases. Ninety-two patients (37.4 %) received pharmacotherapy. The most common treatment option was chemotherapy (76 %); the most common drug combination was gemcitabine and cisplatin (41.3 %). Immunotherapy was used in 19.6 % of patients; 13.6 % of participants received more than two lines of therapy. Three-year OS rate was 10.6 %; median OS was 7 months (95 % confidence interval (CI) 5.4-8.6). Patients receiving systemic therapy demonstrated significantly longer survival than those receiving no therapy (21 months; 95 % CI 17.38-24.62 vs 3 months; 95 % CI 1.79-4.22; p <0.0001). Patients receiving immunotherapy had better survival than individuals receiving chemotherapy (median OS 34.5 months vs 18 months; p = 0.003).Conclusion. The survival rates in the URRU study were relatively low, which can be attributed to the fact that only one-third of patients received pharmacotherapy and very few patients received immunotherapy. Second and subsequent lines of therapy were rarely used in patients with progressive disease. The implementation of novel treatments, including immune checkpoint inhibitors, will increase the survival of BCa patients.

Primary Parotid Non-Hodgkin’s B-Cell Lymphoma in an Elderly Woman on Pembrolizumab for Metastatic Invasive Papillary Urothelial Cell Carcinoma of the Bladder

Primary lymphomas of the parotid are rare (4-5%) and seldom appear in patients with pre-existing metastatic cancer from other primary sources. We present a primary marginal zone B-cell lymphoma of the mucosaassociated lymphoid tissue (MALT) in an 84-year-old female with preexisting metastatic bladder cancer. A PET scan that identified positive pelvic/cervical lymphadenopathy and bilateral parotid masses. She underwent transurethral resection of a bladder tumor and started on pembrolizumab chemotherapy. After two years, the left parotid mass decreased in size but the right increased to 3.9cm. Right superficial parotidectomy diagnosed B-Cell Marginal zone lymphoma, staining positive for CD20, PAX5, and Bcl2. pembrolizumab was held and the patient was started on 4 weekly rituximab infusions. A PET scan done 3 months after completion of rituximab showed a good response to chemotherapy. This is the first reported case of a primary parotid gland lymphoma in a patient with active metastatic bladder cancer.

The association of access to systemic therapy and overall survival in metastatic bladder cancer in Russia: An analysis of URRU register.

88 Background: Social, economic and community disadvantages are well-described for metastatic bladder cancer (mBC) in different geographical regions. For the first time in Russian Federation we investigated treatment options and survival disparities for patients with mBC including urothelial cancer in URRU register. Methods: Patients were retrospectively identified at 9 cancer centers in southern, central, and eastern regions of Russia (Astrakhan, Ekaterinburg, Ivanovo, Khabarovsk, Krasnoyarsk, Moscow, Omsk, Rostov-on-Don, Vladivostok). Patients were included in the study if histologically confirmed mBC was diagnosed between January 2017 and January 2018 and they had at least one visit to the cancer center during the follow-up period. Anonymised data were collected by online registry. The outcomes of interest were overall survival (OS), patient characteristics and treatment patterns. Results: 246 adult patients were included in the study for analysis. Mean number of patients in one region per year was 31. All patients had metastatic disease. Median age at diagnosis of mBC was 72 (37-99) years (with 60.6% of patients aged ≥70 years). Patients were predominantly male (75%), histological subtype of BC (urothelial carcinoma, etc.) was determined in 70.32%. 92 (37.4%) patients received systemic therapy for mBC. Despite the approved checkpoint inhibitors for mBC in 2017-2018 in Russia the main treatment option was chemotherapy (n=70; 76%). Multivariate analysis by adjusting demographic and cancer variables showed that non-receipt of systemic therapy was independently associated with higher odds of death (Odds Ratio=3.1, confidence interval (CI)=1.89 to 5.18). Median OS (21 months; 95% CI 17.38-24.62) of patients who received systemic therapy was significantly longer than that of patients who did not received the therapy (3 months; 95% CI 1.79-4.22; p<0.0001). Patients receiving immunotherapy had better survival outcomes comparing to chemotherapy (median OS 34.5 vs. 18 months, p=0.003). Conclusions: In Russia only one third of patients with mBC received systemic therapy for metastatic disease which affected OS. Consistent with other studies these results indicate that patients should have access to novel therapies.

Survival Outcomes Associated with First and Second-Line Palliative Systemic Therapies in Patients with Metastatic Bladder Cancer

Background: Real-world data on palliative systemic therapies (PST) in treating metastatic bladder cancer (mBC) is limited. This study investigates current trends in treating mBC with first- (1L) and second-line (2L) chemotherapy (CT) and immunotherapy (IT). Methods: A chart review was conducted on patients diagnosed with stage II-IV bladder cancer in 2014–2016. Survival outcomes were compared between chemotherapy, immunotherapy, and supportive care. Results: out of 297 patients, 77% were male. 44% had stage IV disease at diagnosis. Median age at metastasis was 73 years. 40% of patients received 1L PST and 34% received 2L PST. Median overall survival (mOS) was longer in those receiving PST versus no treatment (p < 0.001). Patients receiving CT and IT sequentially had the longest mOS (18.99 months). First-line IT and CT mOS from treatment start dates were 5.03 and 9.13 months, respectively (p = 0.81). Gemcitabine with cisplatin (8.88 months) or carboplatin (9.13 months) were the most utilized 1L chemotherapy regimens (p = 0.85). 2L IT and CT mOS from treatment start dates were 6.72 and 3.78 months, respectively (p = 0.15). Conclusion: real-world mOS of >1.5 years in mBC is unprecedented and supports using multiple lines of PST. Furthermore, immunotherapy may be a comparable alternative to chemotherapy in both 1L and 2L settings.

PD-L1 (SP142) testing is concordant between Benchmark Ultra and Bond-III stainers

Background Atezolizumab is an inhibitor of programmed death-ligand 1 (PD-L1), used to treat advanced or metastatic bladder cancer, and in trials for non-invasive disease. In order to be eligible for treatment, patients require a PD-L1 immune cell score ≥ 5%, using the Ventana SP142 PD-L1 assay. Many laboratories do not have access to the required Ventana Benchmark Ultra stainer, and it is unclear if the assay performs similarly on other stainers. In this study, we compare SP142 assay results between Ventana Benchmark Ultra and Leica Bond-III stainers. Methods Serial sections of 90 samples of transurethral bladder resections (comprising 51 pTaHG, 8 pTis, 18 pT1, 10 pT2 tumors) were stained using the SP142 PD-L1 antibody on Ventana Benchmark Ultra and Leica Bond-III stainers, manually scored, and compared using accuracy and Cohen’s kappa measures. Results Both devices yielded highly concordant PD-L1 immune cell scores (accuracy 0.84, Cohen’s κ 0.732). Moreover, we found similar tumor cell (TC) PD-L1 scores using both stainers, and a trend towards greater TC scores in pT2 stage samples (p = 0.05). Conclusion This study is the first to compare the SP142 antibody in bladder cancer on two different stainers. Our results indicate that both Benchmark Ultra and Bond-III stainers yield highly concordant results using the SP142 PD-L1 antibody.