As major urothelial differentiation products, uroplakins are targeted to the apical surface of umbrella cells. Via the sequential actions of Rabs 11, 8, and 27b and their effectors, uroplakin vesicles are transported to a subapical zone above a K20 network and fuse, via a SNARE-mediated and MAL-facilitated step, with the urothelial apical membrane.

e13520 Background: Due to limited access to healthcare providers, lengthy travel times to clinics, and disadvantageous socioeconomic dynamics, patients in rural locations face significant challenges causing a low recruitment in clinical trials. However, there may be preconceived assumptions of a patient’s desire to participate in a trial leading to bias from healthcare organizations and thereby, decreased efforts in enrollment. Dartmouth Cancer Center is the smallest NCI designated comprehensive cancer center, serving rural New Hampshire and Vermont. In this study, we surveyed patients with cancer to assess their level of understanding of clinical trials, factors influencing patients’ willingness to enroll, and the difficulties faced after accrual in the trials. Methods: A 23 items anonymous questionnaire was distributed to the oncology patients at the outpatient clinic. The questions included demographics, socioeconomic status, time to travel, challenges faced in participating in the trials. Cox proportional regression analysis was done to identify factors influencing decision to participate in trials. Results: Among 93 respondents, 74% are within the age of 61 – 80 years, 64.45% are male and 74% are married, 51% are retired and 59.7% have household income of ≤$100,000. 32.2% of our respondents travelled over 1 hour to receive care. 73.3% of the respondents understood what it means to participate in a clinical trial. 91.8% are willing, yet only 40% were given an option to participate in a trial. Only 10.5% ever declined to participate. Additional cost, frequent travel, and possibility of receiving a placebo are the biggest factors in declining a participation. Up to 95% of the participants enrolled in a trial had positive experience and have the ultraistic motives. None of the socioeconomic or personal factors had any significant bearing on willingness to participate. Conclusions: Socioeconomic and regional factors have little bearing on a person's inclination to participate in clinical trials. There is a strong interest in understanding and enrolling in clinical studies. Cancer centers need to reduce the gap between patient interest in trials and actual trial participation.[Table: see text]

intravesical BCG immunotherapy. Interestingly, in a few studies, male patients have been shown to be less likely to respond to BCG therapy, compared with female patients. Meanwhile, emerging preclinical evidence suggests the involvement of androgen receptor (AR) signaling in urothelial tumorigenesis and cancer progression. This study aimed to investigate whether and how AR signals have an impact on the direct cytotoxic effects of BCG on bladder cancer cell growth. METHODS: We compared the inhibitory effects of BCG on bladder cancer cell viability or colony formation between AR-positive versus AR-knockdown lines or between AR-positive lines with versus without treatment with androgen (e.g. R1881) and/or anti-androgen (e.g. hydroxyflutamide). We also knocked down Rab27b, a GTPase known to mediate bacterial exocytosis (e.g. E. coli from urothelial cells), in bladder cancer cells to compare the cytotoxic effects and intracellular amounts of BCG. Immunohistochemistry of AR and Rab27b was then performed in bladder cancer specimens from patients undergoing BCG therapy. RESULTS: BCG treatment reduced the numbers of viable cells or colonies of AR-knockdown lines more significantly than those of ARpositive control lines. Similarly, R1881 and hydroxyflutamide lowered and enhanced, respectively, the BCG effects on cell proliferation of AR-positive lines. In addition, R1881 reduced BCG amount in ARpositive cells and up-regulated Rab27b expression. Rab27b knockdown cells contained larger amounts of BCG and were more sensitive to BCG treatment, compared with control cells. Meanwhile, the expression levels of both AR and Rab27b were considerably higher in BCG-resistant sublines than in respective control sublines. Using an orthotopic mouse xenograft model, Rab27b knockdown was also found to increase BCG amount in the tumors and its inhibitory effects on tumor growth. Finally, immunostaining showed positivity of AR and Rab27b in 4 (22%) of 18 responders versus 9 (64%) of 14 non-responders (P[0.016) and in 12 (67%) of 18 responders versus 14 (100%) of 14 non-responders (P[0.017), respectively. CONCLUSIONS: AR activity likely correlates with resistance to BCG treatment in bladder cancer, presumably via up-regulating Rab27b expression, leading to promotion of exocytosis of BCG from urothelial cells. Accordingly, anti-androgenic drugs may function as sensitizers of BCG therapy especially in male patients with AR-positive bladder cancer.

for FAM81A (P < 0.0001), and 1.06 and 1.80 for PCSK6 (P < 0.0001), respectively. Univariate Cox proportional hazards regression analysis showed that gender (P [ 0.0082), urinary cytology (P [ 0.0300), and tumor grade (P [ 0.0151) had a significant effect on recurrence-free survival. In multivariate analyses, gender was an independent prognostic factor for recurrence-free survival (P [ 0.0356, risk ratio 2.95, 95% confidence interval 1.08-7.34). Univariate Cox proportional hazards regression analysis showed that FAM81A (P [ 0.0022), and PCSK6 (P [ 0.0147) copy number had a significant effect on progression-free survival. In multivariate analyses, FAM81A copy number was an independent prognostic factor for progression-free survival (P [ 0.0419, risk ratio 7.59, 95% confidence interval 1.07-153.42).CONCLUSIONS: These data suggest that FAM81A CNP is potentially a new tumor marker for predicting the efficacy of BCG therapy for NMIBC.

e21563 Background: Circulating tumor DNA (ctDNA) is tumor-derived fragment of DNA circulating in plasma. ctDNA has been used to detect minimal residual disease (MRD) in early-stage cancers after curative intent therapy. However, ctDNA based MRD concept is not investigated in metastatic disease. There is a lack of clarity around optimal timing to stop immune checkpoint inhibitors (ICI) in melanoma and lung cancer patients who have achieved durable response (DR) and MRD may have a role here to select right patients to stop therapy at an optimal time. Methods: This is prospective study on metastatic lung cancer and melanoma patients with DR treated with ICI. DR is identified as objective response (CR/PR) by modified WHO criteria lasting ≥6 months continuously. We utilized Signatera assay by Natera. Signatera uses tissue from original biopsy of the patients and develop multiplex PCR based personalized assay to detect MRD. The level of ctDNA is reported in mean tumor molecules per mL. We obtained ctDNA assay at baseline, month 3 and month 6 at their routine follow up visits. If applicable, ctDNA assay was done at the time of progression, and 3 months after resuming treatment. Results: We identified 29 melanoma and 17 Lung cancer (both small cell and non-small cell) patients with metastases and DR. Median age was 69 years in both cohorts. Median duration of ICI was 14 months in melanoma and 24 months in lung cancer cohort. ctDNA assay was obtained in 26 melanoma and 13 lung cancer patients. One small cell lung cancer patient had detectable ctDNA at baseline, although radiographically, the patient had DR. The rest of the patients in both cohorts had undetectable ctDNA. 2 melanoma patients developed detectable ctDNA on subsequent assays and their therapies were changed. One small cell lung cancer patient has persistently detectable ctDNA on subsequent assays but remained in DR. A total of 10 patients in both cohorts decided to stop their therapy following several -ve ctDNA assay. Conclusions: The role of ctDNA needs to be investigated in advanced/metastatic settings as MRD may have a role to identify patients who may benefit from treatment break. MRD surveillance may also support radiographic assessment. [Table: see text]